MAPK Cancer Research Results

MAPK, mitogen-activated protein kinase: Click to Expand ⟱
Source: CGL-CS
Type:
Mitogen-activated protein kinases (MAPKs) are a group of proteins involved in transmitting signals from the cell surface to the nucleus, playing a crucial role in various cellular processes, including growth, differentiation, and apoptosis (programmed cell death).

MAPK Pathways: The MAPK family includes several pathways, the most notable being:
1.ERK (Extracellular signal-Regulated Kinase): Often associated with cell proliferation and survival.
2.JNK (c-Jun N-terminal Kinase): Typically involved in stress responses and apoptosis.
3.p38 MAPK: Associated with inflammatory responses and apoptosis.

Inhibitors: Targeting the MAPK pathway has become a strategy in cancer therapy. For example, BRAF inhibitors (like vemurafenib) are used in treating melanoma with BRAF mutations.
Altered Expression Levels:
Overexpression: Many cancers exhibit overexpression of MAPK pathway components, such as RAS, BRAF, and MEK. This overexpression can lead to increased signaling activity, promoting cell proliferation and survival.
Downregulation: In some cases, negative regulators of the MAPK pathway (e.g., MAPK phosphatases) may be downregulated, leading to enhanced MAPK signaling.
The expression levels of MAPK pathway components can serve as biomarkers for cancer diagnosis, prognosis, and treatment response. For example, high levels of phosphorylated ERK (p-ERK) may indicate active MAPK signaling and poor prognosis in certain cancers.

Numerous reports indicate that the MAPK pathway plays a major role in tumor progression and invasion, while inhibition of MAPK signaling reduces invasion.
Scientific Papers found: Click to Expand⟱
6462- 1,8-Cin,    Modes of Action of 1,8-Cineol in Infections and Inflammation
- Review, Var, NA - Review, AD, NA
*BioAv↑, become increasingly clear in the recent years that 1,8-Cineol spreads almost everywhere in the human body after its oral administration, from the gut to the blood to the brain.
*BBB↑,
*AntiViral↑, anti-viral effects have been observed to include numerous bacteria and fungi species.
*Bacteria↓,
*AntiFungal↑,
*Inflam↓, central mode of action of 1,8-Cineol is the inhibition of pro-inflammatory cytokine expression
*BioAv↑, 1,8-Cineol was detectable in nasal tissue samples after its oral administration for 14 days, which indicates the systemic distribution of 1,8-Cineol via the gut and the blood stream
*MUC2↓, significantly reduced expression levels of the mucin genes MUC2 and MUC19 in close association with a significantly attenuated activity of transcription factor NF-κB
*MUC19↓,
*NF-kB↓, reduced the expression levels of transcriptional activator nuclear factor (NF)-kB p65 and expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in lung tissues
*ICAM-1↓,
*VCAM-1↓,
DNAdam↑, colon cancer cells on the potential genotoxicity of 1,8-Cineol revealed a concentration-dependent increase in oxidative DNA damage, whereas it did not affect the cell viability due to DNA repair mechanisms
*lipid-P↓, suppressing the expression of lipid mediators and prostaglandin D2
*PGE2↓,
*IL4↓, decreased expression levels of different inflammatory cytokines such as interleukin (IL)-4, IL-6 and granulocyte macrophage colony stimulating factor (GM-CSF) in bronchial epithelial cells
*IL6↓,
*IL1β↓, 1,8-Cineol-containing leaf extracts significantly suppressed the expression of pro-inflammatory cytokines IL-1β and IL-6 [
*IL6↓,
eff↑, 1,8-Cineol in combination with ellagic acid has been shown to downregulate different cytokines such as transforming growth factor beta-1 (TGF-β1), Fascin-1 (FSCN1), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in p
TGF-β↓,
fascin↓,
VEGF↓,
MMP9↓,
*MAPK↓, 1,8-Cineol was shown to suppress the activation of the MAPK/ERK
*ERK↓,
JNK↓, decreased activities of transcription factor NFκB and the JNK (c-Jun N-terminal kinase)/AP-1 (activator protein-1) pathway in the human cancer cell lines U373 and HeLa in response to 1,8-Cineol, the active ingredient of the drug Soledum
Wnt↓, 1,8-Cineol acts as an inhibitor of the Wnt/β-catenin pathway in head and neck squamous cell carcinoma (HNSCC).
β-catenin/ZEB1↓,
GSK‐3β↑, decreased inhibition of glycogen synthase kinase 3 (GSK-3) and reduced levels of WNT11
*neuroP↑, 1,8-Cineol has been shown to have neuroprotective activity.
*GSK‐3β↓, decreased activity of GSK-3 in response to 1,8-Cineol could ameliorate advanced glycation end products,
*AGEs↓,
*BBB↑, eucalyptol reveals an opening effect on the blood–brain barrier
*NLRP3↓, controls inflammation by suppressing the NOD-like receptor pyrin domain-containing 3 (NLRP3) activation

5356- AL,    Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects
- Review, GC, NA
Apoptosis↑, induction of apoptosis, inhibition of proliferation, and disruption of cancer cell signaling pathways, including the MAPK, PI3K/AKT, and NF-κB pathways.
TumCP↓,
MAPK↓,
PI3K↓,
Akt↓,
NF-kB↓,
AntiCan↑, Allicin and its other derivatives, such as diallyl disulfide (DADS) and ajoene, have been found to have strong anticancer potential both in vitro and in vivo.
ChemoSen↑, effectiveness of allicin in augmenting conventional chemotherapy and retarding tumor growth proves that allicin is one of the most efficient complementary therapies.
TumCCA↑, In liver cancer, allicin has been shown to mediate cell cycle arrest and apoptosis
Apoptosis↑,
BioAv↑, Allicin (diallyl thiosulfinate) is a compound that is generated when a garlic clove is crushed
selectivity↑, Furthermore, it has no influence on the growth of healthy intestinal cells when it causes stomach cancer cells to undergo apoptosis
TGF-β↓, Allicin can reduce the production of TGF-β2 and its receptor after directly entering gastric cancer cells.
ROS↑, It induces oxidative stress by generating reactive oxygen species (ROS), leading to DNA damage and activation of key apoptotic mediators such as phospho-p53 and p21 [81].
DNAdam↑,
p‑P53↑,
P21↑,
cycD1/CCND1↓, Additionally, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs) can all be inhibited by allicin.
cycE/CCNE↓,
CDK4↓, suppressing the CDK-4/6/cyclin D complex
CDK6↓,
MMP↓, By lowering the outer mitochondrial membrane potential (MMP), allicin raises levels of nuclear factor kappa B (NF-κB), the proapoptotic protein Bax, while decreasing the antiapoptotic protein Bcl-2, which leads to apoptosis.
NF-kB↑,
BAX↑,
Bcl-2↓,
ER Stress↑, cellular effects of allicin, including its role in inducing ER stress
Casp↑, enhancing caspase activation and apoptosis-inducing factor (AIF)-mediated cell death.
AIF↑,
Fas↑, increasing Fas receptor expression and its binding to Fas ligand (FasL), leading to apoptosis through caspase-8 and cytochrome c activation.
Casp8↑,
Cyt‑c↑,
cl‑PARP↑, leading to poly (ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation.
Ca+2↑, allicin elevates intracellular free Ca2⁺ levels, causing endoplasmic reticulum (ER) stress, which plays a critical role in apoptosis induction
*NRF2↑, by activating the Nrf2 pathway via KLF9, allicin protects against arsenic trioxide-induced liver damage,
*chemoP↑, Additionally, allicin has shown promise in reducing hepatotoxicity caused by tamoxifen (TAM), a commonly used treatment for hormone-dependent breast cancer
*GutMicro↑, Shi et al. [85] found that allicin can ameliorate high-fat diet-induced obesity in mice by altering their gut microbiome.
CycB/CCNB1↑, DATS impaired cell survival in the G2 phase by significantly upregulating cyclins A2 and B1.
H2S↑, DATS can also react with the cellular thiol glutathione to create H2S gas, which can control several other cellular functions [79].
HIF-1↓, allicin treatment (40 µg/ml) for NSCLC lowers the expression of HIF-1 and HIF-2 in hypoxic cells [73]
RadioS↑, Allicin has been shown to increase the sensitivity of X-ray radiation therapy in colorectal cancer, presumably by suppressing the levels of NF-κB, IKKβ mRNA, p-NF-κB, and p-IKKβ protein expression in vitro and in vivo

299- ALA,  Cisplatin,  PacT,    Anti-cancer effects of alpha lipoic acid, cisplatin and paclitaxel combination in the OVCAR-3 ovarian adenocarcinoma cell line
- in-vitro, Ovarian, OVCAR-3
MMP9↓,
MMP11↓,
MAPK↓,

3450- ALA,    α-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-κB in H. pylori-Infected Gastric Epithelial AGS Cells
- in-vitro, NA, AGS
*IL8↓, α-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-κB in H. pylori-infected gastric epithelial cells
*MAPK↓,
*JAK↓,
*STAT↓,
*NF-kB↓,

6397- ANE,  Cisplatin,    Synergistic Effect of Anethole and Platinum Drug Cisplatin against Oral Cancer Cell Growth and Migration by Inhibiting MAPKase, Beta-Catenin, and NF-κB Pathways
- in-vitro, SCC, Ca9-22
AntiCan↑, anethole possesses an anti-oral cancer effect
ChemoSen↑, anethole (3 µM) potentiates cisplatin-induced inhibition of cell proliferation and decreases the ΔΨm on Ca9-22 cells.
TumCP↓,
MMP↓,
ROS↑, we also found anethole and cisplatin to enhance the cisplatin-induced generation of reactive oxygen species (ROS) and mitochondrial stress.
MAPK↓, inhibited by the combination of anethole and cisplatin such as MAPKase, beta-catenin, and NF-κB pathways.
β-catenin/ZEB1↓,
NF-kB↓,
EMT↓, anethole potentiates the effect of cisplatin against oral cell migration by blocking the epithelial-to-mesenchymal transition.
Casp↑, Anethole Synergy with Cisplatin in the Induction of Apoptosis via Caspase Activation

6401- ANE,    Anethole and Its Role in Chronic Diseases
- Review, Var, NA - Review, PSA, NA
*BioAv↝, Pure anethole is a colorless to faintly yellow liquid at above 23 °C [10]. It is poorly soluble in water, is highly soluble in alcohol, and is miscible with ether and chloroform.
*other↝, Trans-anethole has a sweet herbaceous smooth odor profile [7] and a sweet taste, being more than 10 times sweeter than common sugar
eff↓, Ultraviolet (UV) light and visible (VIS) light, temperature, atmospheric oxygen, the prolonged storage significantly influence the chemical stability of anethole.
TNF-α↓, Figure 3
IL10↑,
CXCR4↓,
MMP2↓,
MMP9↓,
TIMP1↑,
NF-kB↓,
AP-1↓,
STAT↓,
JNK↓,
ERK↓,
MAPK↓,
PI3K↓,
Akt↓,
JAK↓,
*AntiDiabetic↓,
*neuroP↑, Anethole dithiolethione (Fig. 4), a synthetic analogue of anethole, has an attractive potential in the development of neuroprotective agents in Parkinson’s disease due to its multifaceted antioxidant activity coupled with inhibition of monoamine oxid
*Imm↑, immunomodulatory profile of anethole may offer promising alternative therapy to counteract the effects of cytotoxic chemotherapeutic agents
chemoP↑,
*AntiThr↑, Anethole as well as fennel essential oil exhibit antithrombotic properties which are linked to a broad spectrum antiplatelet activity,
*AntiAg↑,
*antiOx↑, anticataract activity through the inhibition of lens aldose reductase (IC 50 = 3.8 lg/mL) and antioxidant activity. It increases SOD and catalase activities and restores GSH levels in the sugar induced lens opacification
*SOD↑,
*GSH↑,
*Wound Healing↑, administration of pharmaceutical formulation with 20 % anethole twice daily for 15 days accelerates wound closure of injured tissue
chemoPv↑, Cancer chemoprevention activity of anethole dithiolethione may be related to the increase of intracellular glutathione, up-regulation of phase II detoxification enzymes such as glutathione-S-transferase, and inhibition of NF-kB signaling activation
*GSTs↑,
*NF-kB↓,

4280- Api,    Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms
- Review, AD, NA - Review, Park, NA
*neuroP↑, Apigenin, a flavonoid found in various herbs and plants, has garnered significant attention for its neuroprotective properties
*antiOx↑, shown to possess potent antioxidant activity, which is thought to play a crucial role in its neuroprotective effects
*ROS↓, Apigenin has been demonstrated to scavenge ROS, thereby reducing oxidative stress and mitigating the damage to neurons
*Inflam↓, apigenin has been found to possess anti-inflammatory properties.
*TNF-α↓, inhibit the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, which are elevated in neurodegenerative diseases
*IL1β↓,
*PI3K↑, apigenin has been shown to activate the PI3K/Akt signaling pathway, which is involved in promoting neuronal survival and preventing apoptosis.
*Akt↑,
*BBB↑, Apigenin has additional neuroprotective properties due to its ability to cross the BBB and enter the brain
*NRF2↑, figure 1
*SOD↑, pigenin has also been shown to activate various antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)
*GPx↑,
*MAPK↓, Apigenin inhibits the MAPK signalling system, which significantly reduces oxidative stress-induced damage in the brain
*Catalase↑, , including SOD, catalase, GPx and heme oxygenase-1 (HO-1) [37].
*HO-1↑,
*COX2↓, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*PGE2↓,
*PPARγ↑, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*TLR4↓,
*GSK‐3β↓, Apigenin can inhibit the activity of GSK-3β,
*Aβ↓, Inhibiting GSK-3 can reduce Aβ production and prevent neurofibrillary disorders.
*NLRP3↓, Apigenin suppresses nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation by upregulating PPAR-γ
*BDNF↑, Apigenin causes upregulation of BDNF and TrkB expression in several animal models
*TrkB↑,
*GABA↑, Apigenin enhances GABAergic signaling by increasing the frequency of chloride channel opening, leading to increased inhibitory neurotransmission
*AChE↓, It blocks acetylcholinesterase and increases acetylcholine availability.
*Ach↑,
*5HT↑, Apigenin has been shown to increase 5-HT levels, decrease 5-HT turnover, and prevent dopamine changes.
*cognitive↑, Apigenin increases the availability of acetylcholine in the synapse after inhibiting AChE, thereby enhancing cholinergic neurotransmission and improving cognitive function and memory
*MAOA↓, apigenin acts as a monoamine oxidase (MAO) inhibitor and MAO inhibitors increase the levels of monoamines in the brain

2640- Api,    Apigenin: A Promising Molecule for Cancer Prevention
- Review, Var, NA
chemoPv↑, considerable potential for apigenin to be developed as a cancer chemopreventive agent.
ITGB4↓, apigenin inhibits hepatocyte growth factor-induced MDA-MB-231 cells invasiveness and metastasis by blocking Akt, ERK, and JNK phosphorylation and also inhibits clustering of β-4-integrin function at actin rich adhesive site
TumCI↓,
TumMeta↓,
Akt↓,
ERK↓,
p‑JNK↓,
*Inflam↓, The anti-inflammatory properties of apigenin are evident in studies that have shown suppression of LPS-induced cyclooxygenase-2 and nitric oxide synthase-2 activity and expression in mouse macrophages
*PKCδ↓, Apigenin has been reported to inhibit protein kinase C activity, mitogen activated protein kinase (MAPK), transformation of C3HI mouse embryonic fibroblasts and the downstream oncogenes in v-Ha-ras-transformed NIH3T3 cells (43, 44).
*MAPK↓,
EGFR↓, Apigenin treatment has been shown to decrease the levels of phosphorylated EGFR tyrosine kinase and of other MAPK and their nuclear substrate c-myc, which causes apoptosis in anaplastic thyroid cancer cells
CK2↓, apigenin has been shown to inhibit the expression of casein kinase (CK)-2 in both human prostate and breast cancer cells
TumCCA↑, apigenin induces a reversible G2/M and G0/G1 arrest by inhibiting p34 (cdc2) kinase activity, accompanied by increased p53 protein stability
CDK1↓, inhibiting p34 (cdc2) kinase activity
P53↓,
P21↑, Apigenin has also been shown to induce WAF1/p21 levels resulting in cell cycle arrest and apoptosis in androgen-responsive human prostate cancer
Bax:Bcl2↑, Apigenin treatment has been shown to alter the Bax/Bcl-2 ratio in favor of apoptosis, associated with release of cytochrome c and induction of Apaf-1, which leads to caspase activation and PARP-cleavage
Cyt‑c↑,
APAF1↑,
Casp↑,
cl‑PARP↑,
VEGF↓, xposure of endothelial cells to apigenin results in suppression of the expression of VEGF, an important factor in angiogenesis via degradation of HIF-1α protein
Hif1a↓,
IGF-1↓, oral administration of apigenin suppresses the levels of IGF-I in prostate tumor xenografts and increases levels of IGFBP-3, a binding protein that sequesters IGF-I in vascular circulation
IGFBP3↑,
E-cadherin↑, apigenin exposure to human prostate carcinoma DU145 cells caused increase in protein levels of E-cadherin and inhibited nuclear translocation of β-catenin and its retention to the cytoplasm
β-catenin/ZEB1↓,
HSPs↓, targets of apigenin include heat shock proteins (61), telomerase (68), fatty acid synthase (69), matrix metalloproteinases (70), and aryl hydrocarbon receptor activity (71) HER2/neu (72), casein kinase 2 alpha
Telomerase↓,
FASN↓,
MMPs↓,
HER2/EBBR2↓,
CK2↓,
eff↑, The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1
AntiAg↑, Apigenin inhibit platelet function through several mechanisms including blockade of TxA
eff↑, ex vivo anti-platelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and apigenin in patients in which aspirin fails to properly suppress the TxA
FAK↓, Apigenin inhibits expression of focal adhesion kinase (FAK), migration and invasion of human ovarian cancer A2780 cells.
ROS↑, Apigenin generates reactive oxygen species, causes loss of mitochondrial Bcl-2 expression, increases mitochondrial permeability, causes cytochrome C release, and induces cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor
Bcl-2↓,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp7↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑IAP2↑,
AR↓, significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. Apigenin treatment of LNCaP cells
PSA↓,
p‑pRB↓, apigenin inhibited hyperphosphorylation of the pRb protein
p‑GSK‐3β↓, Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta.
CDK4↓, both flavonoids exhibited cell growth inhibitory effects which were due to cell cycle arrest and downregulation of the expression of CDK4
ChemoSen↑, Combination therapy of gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer cells (MiaPaca-2, AsPC-1)
Ca+2↑, apigenin in neuroblastoma SH-SY5Y cells resulted in increased apoptosis, which was associated with increases in intracellular free [Ca(2+)] and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of caspase-9, calpain, caspase-3,12
cal2↑,

2584- Api,  Chemo,    The versatility of apigenin: Especially as a chemopreventive agent for cancer
- Review, Var, NA
ChemoSen↑, Apigenin has also been studied for its potential as a sensitizer in cancer therapy, improving the efficacy of traditional chemotherapeutic drugs and radiotherapy
RadioS↑, Apigenin enhances radiotherapy effects by sensitizing cancer cells to radiation-induced cell death
eff↝, It works by suppressing the expression of involucrin (hINV), a hallmark of keratinocyte development. Apigenin inhibits the rise in hINV expression caused by differentiating agents
DR5↑, Apigenin also greatly upregulates the expression of death receptor 5 (DR5
selectivity↑, Surprisingly, apigenin-mediated increase of DR5 expression is missing in normal mononuclear cells from human peripheral blood and doesn't subject these cells to TRAIL-induced death.
angioG↓, Apigenin has been found to prevent angiogenesis by targeting critical signaling pathways involved in blood vessel creation.
selectivity↑, Importantly, apigenin has been demonstrated to selectively kill cancer cells while sparing normal ones
chemoP↑, This selective cytotoxicity is beneficial in cancer therapy because it reduces the negative effects frequently associated with traditional treatments like chemotherapy
MAPK↓, Apigenin's ability to suppress MAPK signaling adds to its anticancer properties.
PI3K↓, Apigenin suppresses the PI3K/Akt/mTOR pathway, which is typically dysregulated in cancer.
Akt↓,
mTOR↓,
Wnt↓, Apigenin inhibits Wnt signaling by increasing β-catenin degradation
β-catenin/ZEB1↓,
GLUT1↓, fig 3
radioP↑, while reducing radiation-induced damage to healthy tissues
BioAv↓, obstacles associated with apigenin's low bioavailability and stability
chemoPv↑, Especially as a chemopreventive agent for cancer

4812- ASTX,    Astaxanthin suppresses the metastasis of colon cancer by inhibiting the MYC-mediated downregulation of microRNA-29a-3p and microRNA-200a
- in-vitro, CRC, HCT116
miR-29b↑, AXT increases miR-29a-3p and miR-200a expression, and thereby suppresses the expression of MMP2 and ZEB1, respectively.
miR-200b↑,
MMP2↓, Astaxanthin suppresses MMP2 activity through upregulation of miR-29a-3p
Zeb1↓,
EMT↓, As a result, AXT represses the epithelial-mesenchymal transition (EMT) of CRC cells.
Apoptosis↑, AXT suppresses oral carcinomas by inducing apoptosis through the inhibition of Erk/MAPK and PI3K/Akt signaling
ERK↓,
MAPK↓,
PI3K↓,
Akt↓,
MMPs↓, AXT reduces the metastasis of cancer cells by decreasing the expression of MMPs,
TumMeta↓, Astaxanthin suppresses the metastatic activity of colon cancer cell in in vivo model

5577- B-Gluc,    Lentinan progress in inflammatory diseases and tumor diseases
- Review, Var, NA - Review, IBD, NA
AntiTum↑, LNT are macromolecules with a β-1,3-D-glucan and its unique molecular structure is closely related to its pharmacological activity, and the glucan of the β-glycosidic bond is the key structure for its antitumor function [6, 7].
GutMicro↑, LNT could also improve the imbalance of gut microbial colonies [25].
*Inflam↓, LNT exerts its anti-inflammatory effect by downregulating cell surface TNFR1 to inhibit TNF-α-induced NF-κB activation
*TNF-α↓,
*NF-kB↓,
ChemoSen↑, LNT combined with cisplatin can not only reduce the dose of cisplatin, but also promote the activation of the intrinsic apoptosis pathway through the regulation of signals, leading to apoptosis of liver cancer cells
OS↑, LNT combined with pentafluorouracil improved survival time for advanced gastric cancer, which is consistent with the results of a meta-study of five randomized controlled trials [78, 79].
Imm↑, Although LNT has been approved in Japan as an immune agent for chemotherapy in gastric cancer
IL6↓, significantly enhance the immune function of CD4 cells, increase NK cells and reduce IL-6 levels
ERK↓, Studies have shown that LNT can inhibit the ERK/MAPK signaling pathway by regulating miR-340, thereby promoting apoptosis in osteosarcoma cells
MAPK↓,
*antiOx↑, LNT is an shiitake extract with anti-inflammatory, antioxidant, anti-tumor and other biological activities and functions.
eff↑, Furthermore,studies also found that LNT selenium nanoparticles can promote apoptosis by acting on specific signaling pathways [96, 97].

5580- B-Gluc,    Lentinan, a Shiitake Mushroom β-Glucan, Downregulates the Enhanced PD-L1 Expression Induced by Platinum Compounds in Gastric Cancer Cells
- in-vitro, GC, MKN45
PD-L1↓, lentinan treatment inhibited the platinum drug-stimulated expression of PD-L1 in gastric cancer cells mainly by suppressing MAPK signaling
MAPK↓,
OS↑, Lentinan has been reported to improve the overall survival of cancer patients receiving chemotherapy [23, 24] through its antitumor and immunomodulatory activitie
AntiTum↑,
Imm↑,

5251- Ba,    The Fascinating Effects of Baicalein on Cancer: A Review
- Review, Var, NA
AntiTum↑, The anti-tumor functions of baicalein are mainly due to its capacities to inhibit complexes of cyclins to regulate the cell cycle, to scavenge oxidative radicals, to attenuate mitogen activated protein kinase (MAPK), protein kinase B (Akt) or mammali
TumCCA↓,
ROS↓,
MAPK↓,
Akt↓,
mTOR↓,
Casp3↑, , to induce apoptosis by activating caspase-9/-3 and to inhibit tumorinvasion and metastasis by reducing the expression of matrix metalloproteinase-2/-9 (MMP-2/-9).
Casp9↑,
TumCI↓,
TumMeta↓,
MMP2↓,
MMP9↓,
Securin↓, Baicalein also induced cell death by reducing the expression of securin, while also inhibiting cancer cell death by affecting the expression of p-AKT and γ-H2AX [26].
γH2AX↝,
N-cadherin↓, Baicalein also decreased the expression of metastasis-associated molecules, including N-cadherin, vimentin, ZEB1, and ZEB2.
Vim↓,
Zeb1↓,
ZEB2↓,
TumCMig↓, researchers demonstrated that baiclalein inhibited cellular adhesion, migration, invasion, and growth of HCC cells both in vitro and in vivo.
TumCG↑,
12LOX↓, Baicalein is an inhibitor of 12-LOX and induced apoptosis, morphological changes, and carbonic anhydrase expression in PaCa cells.
DR5↑, Baicalein lessened this resistance to TRAIL by upregulating DR5 expression and promoting the expression of ROS, thus causing TRAIL sensitization in PC3 cells [85]
ROS↑,
RadioS↑, baicalein increased the sensitivity of prostate cancer cells to radiation without affecting this sensitivity in normal cells
ChemoSen↑, Combination therapy of baicalein with paclitaxel, which were assembled by nanoparticles, was demonstrated to have synergistic anticancer effects in A549 lung cancer cells and in mice bearing A549/PTX drug-resistant lung cancer xenografts [97].
BioAv↓, It is worth noting that the bioavailability of baicalein in vivo remains low.

2606- Ba,    Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular Carcinoma
- Review, HCC, NA
ChemoSen↑, In addition, the combination of baicalein and silymarin eradicates HepG2 cells efficiently superior to baicalein or silymarin alone
TumCP↓, Cell viability assays have demonstrated that baicalein is significantly cytotoxic against several HCC cell lines and can inhibit the proliferation of HCC cells through arresting the cell cycle.
TumCCA↑,
TumCMig↓, Baicalein has been proved to inhibit migration and invasion of human HCC cells by reducing the expression and their proteinase activity of matrix metalloproteinases (MMPs),
TumCI↓,
MMPs↓,
MAPK↓, A large number of studies found that baicalein could inhibit migration and invasion of cancer cells by targeting the MAPK, TGF-b/Smad4, GPR30 pathway and molecules such as, ezrin, zinc-finger protein X-linked (ZFX),
TGF-β↓,
ZFX↓,
p‑MEK↓, Baicalein could inhibited the phosphorylation of MEK1 and ERK1/2, leading to decreased expression and proteinase activity of MMP-2/9 and urokinase-type plasminogen activator (u-PA),
ERK↓,
MMP2↓,
MMP9↓,
uPA↓,
TIMP1↓, as well as increased expression of TIMP-1 and TIMP-2
TIMP2↓,
NF-kB↓, Additionally, the nuclear translocation of NF-kB/p50 and p65/RelA and the phosphorylation of I-kappa-B (IKB)-b could be down-regulated by baicalein
p65↓,
p‑IKKα↓,
Fas↑, Hep3 B cells via activating Fas, Caspase -2, -3, -8, -9, down-regulating Bcl-xL, and upregulating Bax [
Casp2↑,
Casp3↑,
Casp8↑,
Casp9↑,
Bcl-xL↓,
BAX↑,
ER Stress↑, baicalein could induced apoptosis via endoplasmic reticulum (ER) stress in SMMC-7721 and Bel-7402
Ca+2↑, increasing intracellular calcium(Ca2+ ), and activating JNK pathwa
JNK↑,
P53↑, selectively induce apoptosis in HCC J5 cells via upregulation of p53
ROS↑, baicalein could induced cell apoptosis through regulating ROS via increasing intracellular H2O 2 level [
H2O2↑,
cMyc↓, baicalein could promote apoptosis in HepG2 and Bel-7402 cells through inhibiting c-Myc and CD24 expression
CD24↓,
12LOX↓, baicalein could induced cell apoptosis in SMMC-7721 and HepG2 cells by specifically inhibiting expression of 12-lipoxygenase(12-LOX), a critical anti-apoptotic genes

2627- Ba,  Cisplatin,    Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways
RenoP↑, Pretreatment with baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and inflammation and improved kidney injury and function
*iNOS↑, Baicalein inhibited the cisplatin-induced expression of iNOS, TNF-α, IL-6 and mononuclear cell infiltration and concealed redox-sensitive transcription factor NF-κB activation via reduced DNA-binding activity, IκBα phosphorylation and p65 nuclear tra
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*MAPK↓, baicalein markedly attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys
*ERK↓,
*JNK↓,
*antiOx↑, Baicalein also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys.
*NRF2↓,
*HO-1↑,
*Cyt‑c∅, inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2 imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP
*Casp3∅,
*Casp9∅,
*PARP∅,

2613- Ba,    Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice
- in-vivo, Nor, NA
*hepatoP↑, baicalein significantly ameliorated APAP-exposed liver damage and histological hepatocyte changes
*MDA↓, baicalein (50 or 100 mg/kg) pretreatment significantly inhibited liver MDA level (p < 0.05; Figure 4), increased SOD, CAT and GSH activity.
*SOD↑,
*Catalase↑,
*GSH↑,
*MAPK↓, Baicalein Prevented the MAPK Pathway Activation
*p‑JAK2↓, BAI Suppressed the Expression of p-JAK2 and p-STAT3 Proteins in APAP Liver Injury
*p‑STAT3↓,
*ALAT↓, our experimental results suggested that serum ALT and AST levels were obviously alleviated by Baicalein in a dose-dependent manner
*AST↓,
*ROS↓, hepatoprotective role of BAI via attenuating oxidative stress
*antiOx↑, hepatoprotective activity of Baicalein might be associated with its antioxidative capacity.

1242- BBM,    Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways
- in-vivo, Nor, NA
*Macrophages↓,
*Neut↓,
*p‑NF-kB↓,
*p‑MAPK↓,
*p‑JNK↓,
*p‑ERK↓, ERK1/2

1395- BBR,    Analysis of the mechanism of berberine against stomach carcinoma based on network pharmacology and experimental validation
- in-vitro, GC, NA
Apoptosis↑,
ROS↑,
MMP↓,
ATP↓,
AMPK↑,
TP53↑,
p‑MAPK↓, decreased phosphorylated-MAPK3/1 expression
p‑ERK↓,

2690- BBR,    Berberine Differentially Modulates the Activities of ERK, p38 MAPK, and JNK to Suppress Th17 and Th1 T Cell Differentiation in Type 1 Diabetic Mice
- in-vivo, Diabetic, NA
*Inflam↓, Recent studies suggested that berberine has many beneficial biological effects, including anti-inflammation.
*Th17↓, Here we reported that 2 weeks of oral administration of berberine prevented the progression of type 1 diabetes in half of the NOD mice and decreased Th17 and Th1 cytokine secretion.
*Th1 response↓,
*ERK↑, berberine inhibited Th17 differentiation by activating ERK1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation.
*p38↓,
*JNK↓,
*STAT1↓, Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation,
*STAT4↓,
*MAPK↓,

2702- BBR,    The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1
- in-vitro, Lung, A549 - in-vitro, Lung, H1975
TumCG↓, BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a).
MAPK↓,
FOXO3↑,
TumCCA↑, BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells
TumCMig↓,
TumCI↓,
Sp1/3/4↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions.
PDK1↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1
DNMT1↓, BBR inhibited DNA methyltransferase 1 (DNMT1) gene expression and overexpressed DNMT1 resisted BBR-inhibited cell growth
eff↑, Finally, metformin enhanced the effects of BBR both in vitro and in vivo.

2670- BBR,    Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases
- Review, Var, NA
*Inflam↓, According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity
*antiOx↑,
*Ca+2↓, Impaired cerebral arterial vasodilation can be alleviated by berberine in a diabetic rat model via down-regulation of the intracellular Ca2+ processing of VSMCs
*BioAv↓, poor oral absorption and low bioavailability
*BioAv↑, Conversion of biological small molecules into salt compounds may be a method to improve its bioavailability in vivo.
*BioAv↑, Long-chain alkylation (C5-C9) may enhance hydrophobicity, which has been shown to improve bioavailability; for example, 9-O-benzylation further enhances lipophilicity and imparts neuroprotective effect
*angioG↑, figure 2
*MAPK↓,
*AMPK↓, 100 mg/kg berberine daily for 14 days attenuated ischemia–reperfusion injury via hemodynamic improvements and inhibition of AMPK activity in both non-ischemic and ischemic areas of rat heart tissue
*NF-kB↓,
VEGF↓,
PI3K↓,
Akt↓,
MMP2↓,
Bcl-2↓,
ERK↓,

2674- BBR,    Berberine: A novel therapeutic strategy for cancer
- Review, Var, NA - Review, IBD, NA
Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumMeta↓,
TumCI↓,
eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
TNF-α↓,
IL1↓,
BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
NF-kB↓,
IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
MCP1↓,
PGE2↓,
COX2↓,
*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
*GPx↑,
*Catalase↑,
AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
angioG↓,
Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
FasL↑,
ROS↑,
ATM↑,
P53↑,
RB1↑,
Casp9↑,
Casp8↑,
Casp3↓,
BAX↑,
Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
Bcl-xL↓,
IAP1↓,
XIAP↓,
survivin↓,
MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
MMP9↓,
CycB/CCNB1↓, Inhibition of cyclin B1, cdc2, cdc25c
CDC25↓,
CDC25↓,
Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
mTOR↓, U87 cell, Inhibition of m-TOR signaling
MDM2↓, Downregulation of MDM2
LC3II↑, Increase of LC3-II and beclin-1
ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
COX2↓,
MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
EMT↑,
ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
FAK↓,
RAS↓,
Rho↓,
NF-kB↓,
uPA↓,
MMP1↓,
MMP13↓,
ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents

3684- BBR,    Neuroprotective effects of berberine in animal models of Alzheimer’s disease: a systematic review of pre-clinical studies
- Review, AD, NA
*Inflam↓, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects.
*antiOx↓,
*AChE↓,
*BChE↓, berberine exerts inhibitory effects on the four key enzymes in the pathogenesis of AD: acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A, and monoamine oxidase B
*MAOA↓,
*MAOB↓,
*lipid-P↓, Fig3
*GSH↑,
*ROS↓,
*APP↓,
*BACE↓,
*p‑tau↓,
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*MAPK↓,
*PI3K↓,
*Akt↓,
*neuroP↑, neuroprotective effects of berberine have been extensively studied
*memory↑, berberine displayed significant effects in preventing memory impairment in these mechanistically different animal models, suggesting an over-all improvement of memory function by berberine

6503- BCP,    The Potential Therapeutic Role of Beta-Caryophyllene as a Chemosensitizer and an Inhibitor of Angiogenesis in Cancer
- Review, Var, NA
ChemoSen↑, Beta-Caryophyllene (BCP), was highlighted in several recent preclinical studies to enhance chemo-sensitization in chemo-resistant tumors and to efficiently inhibit angiogenesis and cancer cells’ ability to invade and metastasize.
angioG↓,
TumCI↓,
TumMeta↓,
ROS↑, BCP seems to work as a dual modulator of oxidative stress, increasing reactive oxygen species (ROS) in cancer cells, and thus enhancing apoptosis, but reducing ROS in normal cells to protect them from damage
*ROS↓,
chemoP↑,
CB2 / CNR2↑, important issue in BCP is its ability to bind to the body’s cannabinoid receptor 2 (CB2), where it binds selectively to the CB2 receptors and not the CB1 receptor, which makes it non-psychoactive and therapeutically appealing.
Inflam↓, activation of the CB2 receptor by BCP can suppress pro-inflammatory cytokines production, helping to create an anti-tumor immune environment
AntiTum↑,
*BioAv↑, Beta-Caryophyllene, a food additive approved by the Food and Drug Administration, is efficiently absorbed in the gastro-intestinal tract and can penetrate the blood–brain barrier and has a well-established safety profile, making it an attractive biom
*BBB↑,
Apoptosis↑, Induces apoptosis and suppresses proliferative activity of lung cancer cells
TumCP↑,
TumCCA↑, Induces G1 cell cycle arrest by dysregulating cyclins and other molecules
RadioS↑, GBM: Works as a potential radiosensitizer for improving RT outcomes by inhibiting DNA repair, inducing apoptosis, and suppressing anti-apoptotic and survival pathways
DNArepair↓,
ROS↑, BC: Enhances sensitization and promotes the cigarette smoke condensate (CSC)-induced apoptosis in MDA-MB-468 cells, mainly by triggering oxidative stress and inhibition of STAT3
STAT3↓,
*BioEnh↑, BCP is considered a key component in black pepper’s ability to enhance nutrient absorption, including compounds like curcumin.
Pain↓, BCP in cloves further supports their role in pain management and infection prevention.
AntiBio↓,
ROS↑, selectively induce apoptosis and oxidative stress in cancer cells while sparing normal cells at lower concentrations.
Dose↝, I50, for many cancer cell lines typically ranges from 19 to 64 μM
NF-kB↓, Beta-Caryophyllene was reported to inhibit the central to the regulators of inflammation, NF-κB and MAPK pathways, leading to a decrease in pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) production
MAPK↓,
TNF-α↓,
IL1β↓,
IL6↓,
cl‑PARP↑, through increasing the levels of cleaved PARP, caspases and Bax, and the downregulation of Bcl-2, directly by interaction with CB2.
Casp↑,
BAX↑,
Bcl-2↓,
VEGF↓, BCP blocks migration of endothelial cells by inhibiting the secretion of VEGF, and thus blocking the activity of the tyrosine kinase VEGFR2
VEGFR2↓,
MMP2↓, BCP can also prohibit the secretion of MMP-2, p-p38 and p-ERK
p‑p38↓,
p‑ERK↓,
EPR↑, BCP was suggested to accumulate in the cancer cell membrane, altering the cells’ permeability, leading to the accumulation of anticancer drugs, and consequently strengthening the drugs’ activity.
P-gp↓, direct inhibition of P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1), which are overexpressed in resistant tumors
MRP1/ABCC1↓,
*NRF2↑, Importantly, BCP’s selective antioxidant activity—activating Nrf2 in normal cells while increasing ROS in cancer cells—minimizes off-target toxicity,
*antiOx↑,

6507- BCP,    Exploring β-caryophyllene: a non-psychotropic cannabinoid's potential in mitigating cognitive impairment induced by sleep deprivation
- Review, AD, NA
*cognitive↑, highlights β-caryophyllene's ability to mitigate key contributors to sleep loss-induced cognitive impairment, such as inflammation, oxidative stress, neuronal death, and reduced neuroplasticity
*Inflam↓,
*ROS↓,
*TLR4↓, by modulating various signaling pathways, including TLR4/NF-κB/NLRP3, MAPK, Nrf2/HO-1, PI3K/Akt, and cAMP/PKA/CREB.
*NF-kB↓,
*NLRP3↓,
*MAPK↓,
*NRF2↑,
*HO-1↑,
*PI3K↑,
*Akt↑,
*cAMP↑,
*PKA↑,
*CREB↑,

2735- BetA,    Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications
- Review, Var, NA
mt-Apoptosis↑, BA and analogues (BAs) have been known to exhibit potential antitumor action via provoking the mitochondrial pathway of apoptosis
Casp↑, cytosolic caspase activation
p38↑, inhibition of pro-apoptotic p38, MAPK and SAP/JNK kinases [8],
MAPK↓,
JNK↓,
VEGF↓, decreased expression of pro-apoptotic proteins and vascular endothelial growth factor (VEGF)
AIF↑, BA was recognized to trigger the process of apoptosis in human metastatic melanoma cells (Me-45) by releasing apoptosis inducing factor (AIF) and cytochrome c (Cyt C) through mitochondrial membrane
Cyt‑c↑,
ROS↑, BA also stimulates the increased production of reactive oxygen species (ROS) that is considered a stress factor involved in initiating mitochondrial membrane permeabilization
Ca+2↑, Moreover, the calcium overload and thereby ATP depletion are other stress factors causing enhanced inner mitochondrial membrane permeability via nonspecific pores formation
ATP↓,
NF-kB↓, BA has also known to be involved in activation of nuclear factor kappa B (NF-κB) that is responsible for apoptosis induction in variety of cancer cells
ATF3↓, According to Zhang et al. [14], BA stimulates apoptosis through the suppression of cyclic AMP-dependent transcription factor ATF-3 and NF-κB pathways and downregulation of p53 gene.
TOP1↓, inhibition of topoisomerases
VEGF↓, ecreased expression of vascular endothelial growth (VEGF) and the anti-apoptotic protein surviving in LNCaP prostate cancer cells.
survivin↓,
Sp1/3/4↓, selective proteasome-dependent targeted degradation of transcription factors specificity proteins (Sp1, Sp3, and Sp4), which generally regulate VEGF and survivin expression and highly over-expressed in tumor conditions
MMP↓, perturbed mitochondrial membrane potential
ChemoSen↑, BA can support as sensitizer in combination therapy to enhance the anticancer effects with minimum side effects.
selectivity↑, Normal human fibroblasts [41], peripheral blood lymphoblasts [41], melanocytes [32] and astrocytes [30] were found to be resistant to BA in vitro
BioAv↓, The clinical use of BA is seriously challenging due to high hydrophobicity which subsequently causes poor bioavailability
BioAv↑, A BA-loaded oil-in-water nanoemulsion was developed using phospholipase-catalyzed modified phosphatidylcholine as emulsifier in an ultrasonicator [120].
BioAv↑, Aqueous solubility of BA may also be increased through grinding with hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, arabinogalactan) [121,122].
BioAv↑, Subsequently, for further improvement in biocompatibility, a technique of nanotube coating was employed with four biopolymers i.e. polyethylene glycol (PEG), chitosan, tween 20 and tween 80.
BioAv↑, Similarly, BA-coated silver nanoparticles displayed an improved antiproliferative and antimigratory activity, particularly against melanoma cells (A375: murine melanoma cells)

2758- BetA,    Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway
- in-vivo, Nor, NA
*ROS↓, protective effects and mechanisms of BA in blocking oxidative stress caused by acute exposure to T-2 toxin in the thymus of mice was studied.
*MDA↓, BA pretreatment reduced ROS production, decreased the MDA content, and increased the content of IgG in serum and the levels of SOD and GSH in the thymus.
*SOD↑,
*GSH↑,
*p‑p38↓, BA downregulated the phosphorylation of the p38, JNK, and ERK proteins, while it upregulated the expression of the Nrf2 and HO-1 proteins in thymus tissues.
*p‑JNK↓,
*p‑ERK↓,
*NRF2↑,
*HO-1↑,
*MAPK↓, suppressing the MAPK signaling pathway.
*heparanase↑, BA also showed protective activities against alcohol-induced liver damage and dexamethasone-induced spleen and thymus oxidative damage, and these protective effects were related to the antioxidant capacity of BA
*antiOx↑, BA Increased T-2 Toxin-Induced Thymus Antioxidative Capacity

2749- BetA,    Anti-Inflammatory Activities of Betulinic Acid: A Review
- Review, Nor, NA
Inflam↓, betulinic acid as a promissory lead compound with anti-inflammatory activity
*NO↓, BA can inhibit the production of NO, mainly in macrophages cultures stimulated with bacterial lipopolysaccharide (LPS) and/or interferon gamma (IFN-ɣ)
*IL10↑, (BA) has a broad-spectrum anti-inflammatory activity, significantly increasing IL-10 production, decreasing ICAM-1, VCAM-1, and E-selectin expression and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB),
*ICAM-1↓,
*VCAM-1↓,
*E-sel↓,
*NF-kB↓,
*IKKα↓, BA blocks the NF-κB signaling pathway by inhibiting IκB phosphorylation and d
*COX2↓, BA also inhibits cyclooxygenase-2 (COX-2) activity and, therefore, decrease prostaglandin E2 (PGE2) synthesis
*PGE2↓,
*IL1β↓, The production of critical pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8, IL-12, and TNF, is also decreased by BA treatment
*IL6↓,
*IL8↓,
*IL12↓,
*TNF-α↑,
*HO-1↑, induction of HO-1 enzyme activity is associated with the anti-inflammatory effect of BA, since SnPP, an inhibitor of HO-1, promoted a partial reversal of BA’s effect on NF-κB activity,
*IL10↑, BA also increased the amount of IL-10, a well-known anti-inflammatory cytokine
*IL2↓, decreasing the production of pro-inflammatory cytokines, such as IL-2, IL-6, IL-17, and IFN-γ
*IL17↓,
*IFN-γ↓,
*SOD↑, BA decreased the production of the inflammatory mediators described above at the inflammation site and increased enzyme activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver
*GPx↑,
*GSR↑,
*MDA↓, BA decreased malondialdehyde (MDA) levels, a key mediator of oxidative stress and widely used as a marker of free radical mediated lipid peroxidation injury, at the inflammation site
*MAPK↓, BA downregulates MAPK signaling pathways (ERK1/2, JNK, and p38) in the paw edema tissue, which, in part, explains the inhibition of cytokine production (IL-1β and TNF), COX-2 expression, and PGE2 production (Figure 3).

5680- BML,    Anticancer properties of bromelain: State-of-the-art and recent trends
- Review, Var, NA
*Inflam↓, anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair.
*Bacteria↓,
*Pain↓,
*Diar↓,
*Wound Healing↑,
ERK↓, Figure 1
JNK↓,
XIAP↓,
HSP27↓,
β-catenin/ZEB1↓,
HO-1↓,
lipid-P↓,
ACSL4↑,
ROS↑,
SOD↑,
Catalase↓,
GSH↓,
MDA↓,
Casp3↓,
Casp9↑,
DNAdam↑,
Apoptosis↑,
NF-kB↓,
P53↑,
MAPK↓,
APAF1↑,
Cyt‑c↓,
CD44↓,
Imm↑, Bromelain was also studied in the innate immune system, where it could enhance and sustain the process
ATG5↑,
LC3I↑,
Beclin-1↑,
IL2↓, bromelain in vitro experiments resulted in diminished amounts of IL-2, IL-6, IL-4, G-CSF, Gm-CSF, IFN-γ,
IL4↓,
IFN-γ↓,
COX2↓, proprietary bromelain extract could decrease IL-8, COX-2, iNOS, and TNF-α without affecting cell viability.
iNOS↓,
ChemoSen↑, Bromelain may increase the cytotoxicity of cisplatin in the treatment of breast cancer as reported in 2 studies with MDA-MB-231 and 4T1 Breast Tumor cell lines
RadioS↑, The size and weight of tumors in gamma-irradiated EST-bearing mice treated with bromelain decreased significantly with a significant amelioration in the histopathological examination
Dose↝, oral bromelain administration in breast cancer patients (daily up to a dose of 7800 mg)
other↓, The role of bromelain (in combination with papain, sodium selenite and Lens culinaris lectin) has been also tested as a complementary medicine on more than 600 breast cancer patients to reduce the side effects caused by the administration of the adju

5683- BML,    Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway
- in-vitro, NA, NA
COX2↓, Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway
MAPK↓,
NF-kB↓,
TumMeta↓, Pre-treatment of bromelain resulted in reduction in cumulative number of tumors (CNT) and average number of tumors per mouse.
P53↑, Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in Bcl-2.
BAX↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
MAPK↓, bromelain treatment curtailed extracellular signal regulated protein kinase (ERK1/2), p38 mitogen-activated protein kinase (MAPK) and Akt activity
ERK↓,
Akt↓,
TumVol↓, ~33% inhibition in tumor volume

709- Bor,    Cellular changes in boric acid-treated DU-145 prostate cancer cells
- in-vitro, Pca, DU145
Cyc↓, dose-dependent reduction in cyclins A–E
MAPK↓,
TumCMig↓,
LAMP2↓,
p‑ERK⇅, Phosphorylated ERK (P-ERK1/2) increased at intermediate exposures (100 and 250 μM), relative to control, but was reduced by higher concentrations of BA
TumCM/A↑, BA induces media acidosis

729- Bor,    Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies
- in-vitro, GBM, U87MG - in-vivo, Nor, HaCaT
TOS↑,
TumCG↓,
MDA↑,
SOD↑,
Catalase↑,
TAC↓,
GSH↓,
BRAF↑,
MAPK↓,
PTEN↓, BA application was found more favorable because of its inhibitory effect on PIK3CA, PIK3R1, PTEN and RAF1 genes
Raf↓, RAF1
*toxicity↓, We verified the selectivity of the compounds using a normal cell line, HaCaT and found an exact opposite condition after treating HaCaT cells with BA and BX

2775- Bos,    The journey of boswellic acids from synthesis to pharmacological activities
- Review, Var, NA - Review, AD, NA - Review, PSA, NA
ROS↑, modulation of reactive oxygen species (ROS) formation and the resulting endoplasmic reticulum stress is central to BA’s molecular and cellular anticancer activities
ER Stress↑,
TumCG↓, Cell cycle arrest, growth inhibition, apoptosis induction, and control of inflammation are all the effects of BA’s altered gene expression
Apoptosis↑,
Inflam↓,
ChemoSen↑, BA has additional synergistic effects, increasing both the sensitivity and cytotoxicity of doxorubicin and cisplatin
Casp↑, BA decreases viability and induces apoptosis by activat- ing the caspase-dependent pathway in human pancreatic cancer (PC) cell lines
ERK↓, BA might inhibit the activation of Ak strain transforming (Akt) and extracellular signal–regulated kinase (ERK)1/2,
cl‑PARP↑, initiation of cleavage of PARP were prompted by the treatment with AKBA
AR↓, AKBA affects the androgen receptor by reducing its expression,
cycD1/CCND1↓, decrease in cyclin D1, which inhibits cellular proliferation
VEGFR2↓, In prostate cancer, the downregulation of vascular endothelial growth factor receptor 2–mediated angiogenesis caused by BA
CXCR4↓, Figure 6
radioP↑,
NF-kB↓,
VEGF↓,
P21↑,
Wnt↓,
β-catenin/ZEB1↓,
Cyt‑c↑,
MMP2↓,
MMP1↓,
MMP9↓,
PI3K↓,
MAPK↓,
JNK↑,
*5LO↓, Table 1 (non cancer)
*NRF2↑,
*HO-1↑,
*MDA↓,
*SOD↑,
*hepatoP↑, Preclinical studies demonstrated hepatoprotective impact for BA against different models of hepatotoxicity via tackling oxidative stress, and inflammatory and apoptotic indices
*ALAT↓,
*AST↓,
*LDH↑,
*CRP↓,
*COX2↓,
*GSH↑,
*ROS↓,
*Imm↑, oral administration of biopolymeric fraction (BOS 200) from B. serrata in mice led to immunostimulatory effects
*Dose↝, BA at low concentration tend to stimulate an immune response, as those utilized in the study of Beghelli et al. (2017) however, utilizing higher concentration suppressed the immune response
*eff↑, Useful actions on skin and psoriasis
*neuroP↑, AKBA has substantially diminished the levels of inflammatory markers such as 5-LOX, TNF-, IL-6, and meliorated cognition in lipopolysaccharide-induced neuroinflammation rodent models
*cognitive↑,
*IL6↓,
*TNF-α↓,

5706- Brut,    Bergamot juice extract inhibits proliferation by inducing apoptosis in human colon cancer cells
- in-vitro, CRC, HT29
TumCG↓, we demonstrate that Citrus bergamia juice extracts (BJe) reduces CRC cell growth by multiple mechanisms.
MAPK↓, Low BJe concentrations inhibit MAPKs pathway and alter apoptosis-related proteins, that in turn induce cell cycle arrest and apoptosis in HT-29 cells.
TumCCA↑,
Apoptosis↑,
ROS↑, high concentrations of BJe induce oxidative stress causing DNA damage.
DNAdam↑,
AntiCan↑, strengthens our previous hypothesis that the flavonoid fraction of bergamot juice may play a role as anti-cancer drug.

5746- CA,    Caffeic acid hinders the proliferation and migration through inhibition of IL-6 mediated JAK-STAT-3 signaling axis in human prostate cancer
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP
tumCV↓, CA inhibits prostate cancer cells (PC-3 and LNCaP) proliferation and induces reactive oxygen species (ROS), cell cycle arrest, and apoptosis cell death in a concentration-dependent manner.
ROS↑,
TumCCA↑, CA induces ROS production, G2/M cell cycle arrest and apoptotic cell death in prostate cancer cells
Apoptosis↑,
p‑MAPK↓, CA treatment alleviates the expression phosphorylated form of MAPK families, i.e., extracellular signal-regulated kinase 1 (ERK1), c-Jun N-terminal kinase (JNK), and p38 in PC-3 cells.
ERK↓,
JNK↓,
p38↓,
IL6↓, CA inhibits the expression of IL-6, JAK1, and phosphorylated STAT-3 in both PC-3 and LNCaP cells.
JAK1↓,
p‑STAT3↓,
cycD1/CCND1↓, it resulted in decreased expression of cyclin-D1, cyclin-D2, and CDK1 in both PC-3 cells.
CDK1↓,
BAX↑, CA induces apoptosis by enhancing the expression of Bax and caspase-3; and decreased expression of Bcl-2 in prostate cancer cells.
Casp3↑,
Bcl-2↓,
TumCD↑, CA induces cell death and inhibits colony formation in prostate cancer cells

5869- CA,    Carnosic Acid Induces Antiproliferation and Anti-Metastatic Property of Esophageal Cancer Cells via MAPK Signaling Pathways
- in-vitro, ESCC, KYSE150
TumCP↓, CA dose-dependently inhibited cell proliferation, apoptosis, migration, and colony formation.
Apoptosis↓,
TumCMig↓,
TumCCA↑, CA arrested the cell cycle at G2/M phase, promoted cell apoptosis, induced DNA damage, and inhibited the MAPK signaling pathways.
DNAdam↑, CA Provokes Strong DNA Damage Response
MAPK↓,
γH2AX↑, CA dose-dependently increased the expression of γ-H2AX.
TumMeta↓, CA Inhibits Metastasis and Invasion of KYSE-150 Cells via Suppressed MAPK Signaling Pathway
TumCI↓,
P21↑, capabilities of CA to activate p21-mediated signaling pathway [25] and induced apoptosis and production of reactive oxygen species (ROS) [28],
ROS↑,
EMT↓, inhibited the EMT [29],
ChemoSen↑, enhanced the anticancer effects of other compounds [26],

1011- CA,    Dihydrocaffeic acid improves IL-1β-induced inflammation and cartilage degradation via inhibiting NF-κB and MAPK signalling pathways
- in-vivo, NA, NA
iNOS↓,
IL6↓,
SOX9↑,
NF-kB↓,
MAPK↓,

4263- CA,    Neuroprotective Effects of Carnosic Acid: Insight into Its Mechanisms of Action
- Review, AD, NA
*neuroP↑, neuroprotective effect of CA on neuronal cells subjected to ischemia/hypoxia injury via the scavenging or reduction of ROS (reactive oxygen species) and NO (nitric oxide) and inhibition of COX-2 and MAPK pathways
*ROS↓,
*NO↓,
*COX2↓,
*MAPK↓,
*NRF2↑, CA is known to activate the Keap1/Nrf2 pathway, thereby resulting in the production of cytoprotective proteins.
*GSH↑, activation of GSH metabolism
*HO-1↑, activation of Nrf2 target genes, including heme oxygenase 1 (HO-1) and thioredoxin reductase 1 (TXNRD1)
*5HT↑, Observations of increased serotonin and BDNF suggest that CA may represent a novel therapeutic avenue for depressive behaviors that should be further explored.
*BDNF↑, 10 μM CA results in a 1.5-fold increase in levels of BDNF
*PI3K↑, CA has been shown to mediate the activation of the PI3K/Akt/NF-κB pathway
*Akt↑,
*NF-kB↑,
*BBB↑, CA was shown to ameliorate brain edema and blood-brain barrier (BBB) disruption
*SIRT1↑, CA was also shown to increase SIRT1
*memory↑, CA was shown to significantly improve short-term and spatial memory attributes in rat models of AD
*Aβ↓, CA also delayed the deposition of Aβ and protected cells against Aβ-induced cholinergic and mitochondrial dysfunction in a Caenorhabditis elegans model of AD
*NLRP3↓, CA also inhibits the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome, which plays a critical role in the pathogenesis of neurodegenerative disorders, including AD and PD and COVID-19

5834- CAP,    Capsaicin and TRPV1: A Novel Therapeutic Approach to Mitigate Vascular Aging
- Study, Nor, NA
*AntiCan↑, capsaicin possesses anti-cancer, anti-inflammatory, and antioxidant properties and is used as a topical analgesic
*Inflam↓,
*antiOx↑,
*TRPV1↑, Studies demonstrate that capsaicin directly activates TRPV1 by binding to intracellular sites within the channel protein
*AMPK↑, Moreover, capsaicin and TRPV1 can activate the AMPK pathway [82, 83]
*SIRT1↑, elevating SIRT1 levels
*NADPH↓, suppressing NADPH oxidase and reducing reactive oxygen species
*ROS↓,
*MAPK↓, inhibiting MAPK pathways
*eNOS↑, activating eNOS
*Wnt/(β-catenin)↓, inhibiting the Wnt/β-catenin signaling pathway
RenoP↑, Furthermore, TRPV1 activation decreases renal perfusion pressure while increasing glomerular filtration rate and the excretion of sodium/water, thereby modulating renal hemodynamics and excretory functions

5887- CAR,  TV,    Antitumor Effects of Carvacrol and Thymol: A Systematic Review
- Review, Var, NA
Apoptosis↑, It was attested that carvacrol and thymol induced apoptosis, cytotoxicity, cell cycle arrest, antimetastatic activity,
TumCCA↑, accumulation of cells in the G1 phase, together with a reduction of cells in the S phase, slowing cell cycle/mitosis and provoking cell death.
TumMeta↓,
TumCP↓, antiproliferative effects and inhibition of signaling pathways (MAPKs and PI3K/AKT/mTOR).
MAPK↓,
PI3K↓,
Akt↓,
mTOR↓,
eff↑, carvacrol appears to be more potent than thymol
*Inflam↓, these compounds present anti-inflammatory (Li et al., 2018; Chamanara et al., 2019) and antioxidant
*antiOx↑,
AXL↓, These effects occurred mainly through the inhibition of tyrosine kinase receptor (AXL) expression and an increase in malondialdehyde (MDA
MDA↑,
Casp3↑, caspase-3 activation and Bcl-2 inhibition
Bcl-2↓,
MMP2↓, promoted a decrease in Bcl-2, metalloproteinase-2 and -9 (MMP-2 and MMP-9), p-ERK, p-Akt, cyclin B1 levels and an increase in p-JNK, Bax levels, resulting in cell cycle arrest at the G2/M phase
MMP9↓,
p‑JNK↑,
BAX↑,
MDA↓, In respect of breast cancer, treatment with carvacrol decreases MDA-MB231 (Jamali et al., 2018; Li et al., 2021) and MCF-7 cells line viability
TRPM7↓, TRPM7 pathway is one of the suggested pharmacological mechanisms of action
MMP↓, decreased mitochondrial membrane potential, cytochrome C release, caspase activation, PARP cleavage
Cyt‑c↑,
Casp↑,
cl‑PARP↑,
ROS↑, Carvacrol also induced cytotoxicity and apoptosis (via caspase-3 and reactive oxygen species—ROS) of human oral squamous cell carcinoma (OC2 cell line)
CDK4↓, In tongue cancer (Tca-8113, SCC-25 cell lines), Dai et al. (2016) reported that carvacrol effectively inhibited cell proliferation through the negative regulation of CCND1 and CDK4 expression, and the positive regulation of p21 expression,
P21↑,
F-actin↓, A blockade of TRPM7 channels, reduced expression of MMP-2 and F-actin, was also observed, together with the inhibition of PI3K/Akt and MAPK
GSH↓, by increasing ROS, Bax, Caspase-3, -9 levels and reducing Bcl-2 and GSH levels.
*SOD↑, Moreover, carvacrol was able to increase the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH), along with a reduction of lipid peroxides and the enzymes AST, ALT, AL
*Catalase↑,
*GPx↑,
*GSR↑,
*GSH↑,
*lipid-P↓,
*AST↓,
*ALAT↓,
*ALP↓,
*LDH↓,
DNAdam↑, hepatocellular carcinoma induced by diethylnitrosamine (DEN), carvacrol treatment promoted DNA fragmentation
AFP↓, carvacrol showed a reduction in serum levels of alpha-fetoprotein (AFP), alpha l-fucosidase (AFU), vascular endothelial growth factor (VEGF
VEGF↓,
Weight↑, Carvacrol supplementation significantly improved the weight gain and growth rate of animals with colon cancer
*chemoP↑, reduction in oxidative stress damage (higher levels of GSH, GPx, GR, SOD and CAT), suggesting that carvacrol presents chemopreventive effects
ROS↑, In vitro, carvacrol and thymol increased the generation of reactive oxygen species in 24.63% (n = 17) of the studies, a fact that is also observed in chemotherapeutics

5885- CAR,    Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation, migration and invasion
- in-vitro, GBM, U87MG - in-vitro, Nor, HEK293
TRPM7↓, investigated the effects of the TRPM7 inhibitor carvacrol on the viability, resistance to apoptosis, migration, and invasiveness of the human U87 glioblastoma cell line
tumCV↓, Carvacrol treatment reduced the viability, migration and invasion of U87 cells.
TumCMig↓, Carvacrol reduces U87 cell migration and invasion
TumCI↓, Carvacrol inhibited U87 cell migration, invasion and MMP-2 protein expression.
MMP2↓, Carvacrol also decreased MMP-2 protein expression and promoted the phosphorylation of cofilin.
toxicity↓, It's oral LD50 is 810 mg/kg in rats [26] and it is a “generally recognized as safe” food flavor additive according to the United States Food and Drug Administration.
*Inflam↓, carvacrol exhibits anti-inflammatory, antidiabetic, antinociceptive, cardioprotective, neuroprotective and anticarcinogenic properties [27]
AntiDiabetic↑,
cardioP↑,
neuroP↑,
selectivity↑, Carvacrol (CAR) blocked TRPM7 currents in HEK293 cells overexpressing TRPM7 and TRPM7-like currents in U87 cells.
Apoptosis↑, Carvacrol induces apoptosis in U87 cells
p‑Cofilin↑, Carvacrol upregulates phosphorylation of cofilin (p-cofilin) and reduces polymerization of F-actin
F-actin↓,
PI3K↓, Carvacrol suppresses PI3K/Akt and MEK/MAPK signaling pathways
Akt↓,
MEK↓,
MAPK↓,

5893- CAR,  TV,    Thymol and Carvacrol: Molecular Mechanisms, Therapeutic Potential, and Synergy With Conventional Therapies in Cancer Management
- Review, Var, NA
*Inflam↓, Monoterpenes like thymol and carvacrol are recognized for their anti‐inflammatory and anticancer properties,
AntiCan↑,
PI3K↓, Thymol derivatives, such as 1,2,3‐triazoles and carvacrol, effectively target breast cancer (BC) through PI3K/AKT/mTOR and NOTCH pathways and inhibit PIK3CA expression.
Akt↓,
mTOR↓,
NOTCH↓,
PIK3CA↓,
EGFR↓, thymol exhibits anti‐EGFR activity, while carvacrol modulates the HIF‐1α/VEGF pathway, making them potential candidates for colorectal cancer (CRC) management.
Hif1a↓,
VEGF↓,
ChemoSen↑, Their synergistic potential with chemotherapy, radiotherapy, and other bioactive compounds strengthens their therapeutic promise.
RadioS↑,
eff↝, challenges such as stability, bioavailability, and the need for clinical trials hinder their clinical application.
*cardioP↑, cardioprotective (Joshi et al. 2023), neuroprotective (Forqani et al. 2023) and hepato‐nephroprotective
*neuroP↑,
*hepatoP↑,
Apoptosis↑, Induction of Apoptosis
MMP↓, The apoptosis was due to ROS production, variations in the mitochondrial membrane, caspase‐3 activation, and DNA damage
Casp3↑,
ROS↑,
DNAdam↑,
eff↑, Thymol derivative, known as compound 10 (IC50 6.17 μM) exhibited 3.2‐fold more inhibition than 5‐fluorouracil (IC50 20.09 μM) against MCF‐7
BAX↑, Carvacrol (25, 50, 75, and 90 μM) enhanced the expression of Bax, Bad, Fas‐L, and cytochrome c, activated caspase‐9/3 and caspase‐8, induced cell cycle at G0/G1
BAD↑,
FasL↑,
Cyt‑c↑,
Casp9↑,
Casp8↑,
TumCCA↑,
P21↑, improved the expression of proteins (p21, cyclin D1, CDK4), and downregulated the SMO and GLI1 proteins expression in CC
Smo↓,
Gli1↓,
JNK↑, Moreover, thymol activated JNK and p38 MAPK while impeding the ERK pathway
ERK↓,
MAPK↓, Besides thymol, carvacrol has also been reported to inhibit MAPK or ERK pathways in previous studies.
TRPM7↓, inhibited TRPM7 expression in liver fibrotic C57BL/6J mice
Wnt/(β-catenin)↓, hymol inhibited HCT116 and LoVo cell line invasion via downregulating the Wnt/β‐catenin pathway and reducing c‐Myc and Cyclin D1 expression
BioAv↝, thymol and carvacrol are volatile, and their stability is influenced by these factors (temperature, light, oxygen, and pH)
BioAv↑, Ultrasonication is an effective technique to enhance the stability of thymol and other bioactive compounds. 400 watts of power elevated the performance of NC‐CH formulations, and NC‐CH‐400 displayed increased solubility.

5912- CAR,    Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation migration and invasion
- in-vitro, GBM, U87MG - in-vitro, Nor, HEK293
TRPM7↓, carvacrol may have therapeutic potential for the treatment of glioblastomas through its inhibition of TRPM7 channels.
tumCV↓, Carvacrol treatment reduced the viability, migration and invasion of U87 cells.
TumCMig↓,
TumCI↓,
MMP2↓, Carvacrol also decreased MMP-2 protein expression and promoted the phosphorylation of cofilin.
p‑Cofilin↑,
RAS↓, carvacrol inhibited the Ras/MEK/MAPK and PI3K/Akt signaling pathways.
MEK↓,
MAPK↓,
PI3K↓,
Akt↓,

5943- Cela,    Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases
- Review, Arthritis, NA - Review, IBD, NA - Review, AD, NA - Review, Park, NA
*other↝, The most abundant and promising bioactive compound derived from the root of this plant is celastrol, also called tripterine, which possess a broad range of biological activities
*other↝, TW is generally used in the treatment of Crohn’s disease (CD) in China.
*CRP↓, Inflammatory parameters, including c-reactive protein (CRP), also decreased
*eff↝, Etanercept plus TW had an equivalent therapeutic effect to that of Etanercept plus MTX and were both well tolerated
*other↑, TW in human kidney transplantation (26). Rejection occurred in 4.1% of patients treated with TW versus 24.5% of control patients, showing efficacy in the prevention of renal allograph rejection
*CXCR4↓, celastrol decreases hypoxia-induced FLS invasion by inhibiting HIF-1α-mediated CXCR4 transcription
*IL1β↓, Authors have shown that it decreases the production of IL-1β, IL-6, IL-17, IL-18, and TNF by SIC cells harvested from arthritic rats
*IL6↓,
*IL17↓,
*IL18↓,
*TNF-α↓,
*MMP9↓, celastrol reduces MMP-9 production, which limits bone damage
*PGE2↓, celastrol suppresses LPS-induced expression of PEG2 via the downregulation of COX-1 and COX-2 activation
*COX1↓,
*COX2↓,
*PI3K↓, associated with a decrease in PI3K/Akt pathway
*Akt↓,
*other↑, Remarkably, this bone-protective property of celastrol in arthritic models is further supported by studies performed in cancer models
TumCCA↑, celastrol induces cell cycle arrest, apoptosis, and autophagy by the activation of reactive oxygen species (ROS)/c-Jun N-terminal kinases (JNK) signaling pathway
Apoptosis↑,
ROS↑,
JNK↑,
TumAuto↑, celastrol is still able to induce autophagy through HIF/BNIP3 activation
Hif1a↓, The inhibitory effect of celastrol on angiogenesis is mediated by the suppression of HIF-1α,
BNIP3↝,
HSP90↓, The inhibition of HSP90 by celastrol
Fas↑, activation of Fas/Fas ligand pathway in non-small-cell lung cancer
FasL↑,
ETC↓, inhibition of mitochondrial respiratory chain (MRC) complex I
VEGF↓, This inhibition of HIF-1α leads to the decrease of its target genes, such as the VEGF
angioG↓, Angiogenesis Inhibition
RadioS↑, celastrol can overcome tumor resistance to radiotherapy in prostate (129) and lung cancer cells
*neuroP↑, celastrol is a promising neuroprotective agent in animal models of neurodegenerative diseases, such as Parkinson disease (149), Huntington disease (149–151), Alzheimer disease
*HSP70/HSPA5↑, his induction of HSP70 by celastrol explains its beneficial effects not only in neurodegenerative disorders but also in inflammatory diseases.
*ROS↓, celastrol protects human dopaminergic cells from injury and apoptosis and prevents ROS generation and mitochondrial membrane potential loss
*MMP↑,
*Cyt‑c↓, It inhibits cytochrome c release, Bax/Bcl-2 alterations, caspase-9/3 activation, and p38 MAPK activation
*Casp3↓,
*Casp9↓,
*MAPK↓,
*Dose⇅, Authors discuss that it seems to have a narrow therapeutic window, and suggest that it may have a biphasic effect with protective properties at low concentrations and toxic effects at higher concentrations.
*HSPs↑, induces a set of HSPs (HSP27, 32, and 70) in rat cerebral cortical cultures, which are selectively impacted during the progression of this disease
BioAv↓, Due to this poor water solubility, celastrol has low bioavailability. oral administration of celastrol in rats results in ineffective absorption into the systemic circulation, with an absolute bioavailability of 17.06%
Dose↝, narrow therapeutic window of dose together with the occurrence of adverse effects. Our own data showed in vivo that the doses of 2.5 and 5 μg/g/day are effective and non-toxic in the treatment of arthritis in rats;

6640- Cen,    Asiaticoside Antagonizes Proliferation and Chemotherapeutic Drug Resistance in Hepatocellular Carcinoma (HCC) Cells
- in-vitro, HCC, Bel-7402 - in-vitro, HCC, QGY-7703
TumCP↓, Our data indicated that asiaticoside significantly inhibited the proliferation of HCC cell lines QGY-7703 and Bel-7402 in a dose- and time-dependent manner.
Apoptosis↑, Moreover, asiaticoside significantly induced apoptosis in QGY-7703 and Bel-7402 cells.
TumCCA↑, Treatment with asiaticoside also caused G1 cell cycle arrest in QGY-7703 and Bel-7402 cells.
PI3K↓, mechanism underlying the effects of asiaticoside involves inhibiting the activity of the PI3K/Akt and MAPK/ERK pathways.
Akt↓,
MAPK↓,
ERK↓,
P-gp↓, We also found that asiaticoside reduces HCC cell drug resistance by downregulating the expression level of P-gp by decreasing the ROS level in chemotherapy-resistant HCC cells.
ROS↓,
p‑pRB↓, asiaticoside significantly downregulated the phosphorylation level of pRB and expression level of cyclin D1, and upregulated the p27 expression level, all in a dose-dependent manner
cycD1/CCND1↓,
p27↑,

6643- Cen,    Asiaticoside inhibits epithelial-mesenchymal transition and stem cell-like properties of pancreatic cancer PANC-1 cells by blocking the activation of p65 and p38MAPK
- vitro+vivo, PC, PANC1
tumCV↓, As the ATS concentration increased to 25 µmol/L, cell survival rate, levels of Ki67 and PCNA mRNA, expression of N-cadherin, vimentin, SOX2, OCT4, p-p65/p65, and p-p38MAPK/p38MAPK proteins, and the proportions of CD44+ and CD133+ positive cells signi
Ki-67↓,
PCNA↓,
N-cadherin↓,
Vim↓,
SOX2↓,
OCT4↓,
p65↓,
MAPK↓,
CD44↓,
CD133↓,
E-cadherin↑, while the expression of E-cadherin protein significantly increased
TumVol↓, 5 mg/kg the volume of the xenograft significantly decreased (P<0.05), the apoptosis rate significantly increased
TumCP↓, ATS may inhibit the proliferation, EMT, and stem cell-like properties of pancreatic cancer cells by blocking the phosphorylation of p38MAPK and nuclear factor-κB (NF-κB)/p65 in PANC-1 cells.
EMT↓,
CSCsMark↓,

6018- CGA,    Chlorogenic acid: a review on its mechanisms of anti-inflammation, disease treatment, and related delivery systems
- Review, Var, NA - Review, RCC, NA
*BioAv↓, Nevertheless, the inherent low bioavailability of chlorogenic acid poses challenges in practical deployments.
*Inflam↓, chlorogenic acid predominantly impedes the synthesis and secretion of inflammatory mediators such as TNF-α, NO, COX-2, and PGE2.
*TNF-α↓,
*NO↓,
*COX2↓,
*PGE2↓,
*NF-kB↓, Inhibition of NF-κB signaling pathway
*IL6↓, downregulates inflammatory mediators including IL-6, TNF-α, IL-1β, and TLR2 by hindering the phosphorylation of NF-κB pathway proteins,
*IL1β↓,
*TLR2↓,
*MAPK↓, Inhibition of MAPK signaling pathway
*NRF2↓, Activation of the Nrf2 signaling pathway
*HO-1↑, concomitant upregulation of HO-1 and NQO-1
*NQO1↑,
*cardioP↑, its cardioprotective attributes are further elucidated through modulating pertinent signaling pathways
*neuroP↑, This neuroprotection appears to correlate with an upregulation in SOD2 expression facilitated by chlorogenic acid
*SOD↑,
*GSH↑, compound bolsters SOD activity, elevates GSH concentrations, curtails ROS and LDH production, reduces MDA accumulation, and ameliorates cerebral ischemia-reperfusion (CI/R) injury sequels
*ROS↓,
*LDH↓,
*MDA↓,
*cognitive↑, Chlorogenic acid ameliorates such cognitive deficits, a process conceivably attributed to its inhibitory action on NF-κB and IL-6 within frontal brain structures (
*eff↑, One pivotal investigation showcased that bovine serum albumin (BSA)-facilitated chlorogenic acid silver nanoparticles (AgNPs-CGA-BSA) exude substantial antioxidant and anti-neoplastic properties across in vivo and in vitro matrices.

6010- CGA,    The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review
- Review, Nor, NA
*antiOx↑, mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system,
*hepatoP↑,
*RenoP↑,
AntiTum↑,
*glucose↝,
*Inflam↓,
*neuroP↑,
*ROS↓, ↓Active oxygen (ROS) , ↓Keap1,↑Nrf2, ↑SOD, ↑CAT, ↑Glutathione Peroxidase (GSH-Px), ↑Glutathione (GSH), ↓MDA
*Keap1↓,
*NRF2↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*MDA↓,
*p‑ERK↑, ↑ERK1/2 phosphorylation
*GRP78/BiP↑, ↑Glucose regulatory protein 78 (GRP78)
*CHOP↑, ↑C/EBP homologous protein (CHOP)
*GRP94↑, ↑Glucose Regulatory Protein 94 (GRP94)
*Casp3↓, ↓Caspase-9/Caspase-3
*Casp9↓,
*HGF/c-Met↑, ↑Hepatocyte Growth Factor (HGF)
*TNF-α↓, ↓Tumor Necrosis Factor-α (TNF-α)/Interferonγ (IFN-γ)
*TLR4↓, ↓TLR4
*MAPK↓, ↓MAPK signal pathway
*IL1β↓, ↓Interleukin 1β (IL-1β)/Interleukin 6 (IL-6)
*iNOS↓, ↓Inducible Nitric Oxide Synthase (iNOS)
TCA↓, ↓Tricarboxylic acid cycle (TCA) ↓Glycolysis
Glycolysis↓,
Bcl-2↓, ↓Anti-apoptotic gene Bcl-2/Bcl-XL
BAX↑, ↑Pro-apoptotic gene Bax/Bcl-XS/Bad
MAPK↑, ↑p38 mitogen-activated protein kinase (p38 MAPK)
JNK↑, ↑c-Jun N-terminal Kinase (JNK)
CSCs↓, ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4
Nanog↓,
SOX2↓,
CD44↓,
OCT4↓,
P53↑, ↑P53
P21↑, ↑p21
*SOD1↑, ↑CuZnSOD (SOD1)/MnSOD (SOD2)
*AGEs↓, ↓Glycosylation end products (AGEs)
*GLUT2↑, ↑Glucose Transporter 2 (GLUT2)
*HDL↑, ↑High-density lipoprotein (HDL)
*Fas↓, ↓Fatty acid synthase (FAS)
*HMG-CoA↓, ↓β-hydroxy-β-methylglutamyl-CoA (HMG-CoA) reductase
*NF-kB↓, ↑NF-κB signaling pathway
*HO-1↓, ↑Nrf2/HO-1 signaling pathway
*COX2↓, ↓Cyclooxygenase-2 (COX-2)
*TLR4↓, ↓Toll-like receptor 4 (TLR4)
*BioAv↑, One route may be immediate absorption in the stomach or upper gastrointestinal tract, and the other route may be slowly absorbed throughout the small intestine.
*BioAv↝, It indicates that the bioavailability of CGA is closely related to the metabolic capacity of the organism's gut flora
TumCP↓, CGA also inhibits the proliferation, migration, and invasion of cancer cells.
TumCMig↓,
TumCI↓,

6034- CGA,    Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation
- in-vivo, AD, NA
*cognitive↑, Chlorogenic acid can inhibit microglial polarization toward the M1 phenotype and improve neuroinflammation-induced cognitive dysfunction in mice by modulating these key targets in the TNF signaling pathway.
*TNF-α↓,
*antiOx↑, strong antioxidant and anti-inflammatory effects of CGA, many scholars have found that it has a good neuroprotective effect
*Inflam↓,
*neuroP↑,
*BBB↑, CGA is able to cross the blood-brain barrier (BBB) and can treat certain neurological disorders (
*eff↑, Several clinical and preclinical studies have shown that coffee extract (CGA, the main component) exhibits good therapeutic effects in Alzheimer’s disease and Parkinson’s disease
*memory↑, CGA improved memory loss and hippocampal cell death after transient total cerebral ischemia
*AKT1↓, Chlorogenic acid inhibited LPS-induced activation of Akt1, TNF, MMP9, PTGS2, MAPK1, MAPK14, and RELA targets in the TNF signaling pathway
*MMP9↓,
*MAPK↓,

6026- CGA,    Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression
- Review, Var, NA
ChemoSen↑, This article will elaborate the potency of CGA as a chemosensitizer in suppressing tumor growth through a metabolic pathway.
AMPK↑, AMPK pathway is the main cell metabolic pathway that is activated by CGA in some studies.
EGFR↓, Moreover, CGA inhibited EGFR/PI3K/mTOR, HIF, VEGF pathways and MAPK/ERK pathway that may suppress tumor cell growth.
PI3K↓,
mTOR↓,
Hif1a↓, CGA Inhibits HIF-1α/AKT Pathway
VEGF↓,
MAPK↓,
ERK↓,
DNAdam↑, CGA induced intracellular DNA damage and topoisomerase I- and II-DNA complexes formation that plays a key role in apoptosis.
TOP1↓, Topoisomerase inhibitor, known as cancer killer drug, works by inducing topoisomerase-mediated DNA damage
TOP2↓,
Apoptosis↑,
*BioAv↝, Around 70% of CGA is absorbed in small intestine and colon. CGA is relatively stable in saliva and gastric acid.
*Half-Life↓, most circulating CGA is eliminated quickly from the circulatory system with half-time of 0.3 to 1.9 hours and Tmax of 0.6 to 1 hour.


Showing Research Papers: 1 to 50 of 144
Page 1 of 3 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 144

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ATF3↓, 1,   Catalase↓, 1,   Catalase↑, 1,   GSH↓, 3,   H2O2↑, 1,   HO-1↓, 1,   lipid-P↓, 1,   MDA↓, 2,   MDA↑, 2,   ROS↓, 2,   ROS↑, 20,   SOD↑, 2,   TAC↓, 1,   TOS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 2,   ATP↓, 2,   CDC25↓, 2,   ETC↓, 1,   MEK↓, 2,   p‑MEK↓, 1,   MMP↓, 7,   Raf↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

12LOX↓, 2,   ACSL4↑, 1,   AMPK↑, 3,   cMyc↓, 1,   FASN↓, 1,   Glycolysis↓, 1,   H2S↑, 1,   PDK1↓, 1,   PIK3CA↓, 1,   TCA↓, 1,   TumCM/A↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 13,   APAF1↑, 2,   Apoptosis↓, 1,   Apoptosis↑, 16,   mt-Apoptosis↑, 1,   BAD↑, 1,   BAX↑, 9,   Bax:Bcl2↑, 1,   Bcl-2↓, 9,   Bcl-xL↓, 2,   Casp↑, 7,   Casp2↑, 1,   Casp3↓, 2,   Casp3↑, 6,   cl‑Casp3↑, 1,   cl‑Casp7↑, 1,   Casp8↑, 4,   cl‑Casp8↑, 1,   Casp9↑, 6,   cl‑Casp9↑, 1,   CK2↓, 2,   Cyt‑c↓, 1,   Cyt‑c↑, 8,   DR5↑, 2,   Fas↑, 4,   FasL↑, 3,   IAP1↓, 1,   cl‑IAP2↑, 1,   iNOS↓, 2,   JNK↓, 5,   JNK↑, 5,   p‑JNK↓, 1,   p‑JNK↑, 1,   MAPK↓, 30,   MAPK↑, 1,   p‑MAPK↓, 2,   MDM2↓, 1,   p27↑, 1,   p38↓, 1,   p38↑, 1,   p‑p38↓, 1,   survivin↓, 2,   Telomerase↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,   SOX9↑, 1,   Sp1/3/4↓, 2,  

Transcription & Epigenetics(tgid=7) ⓘ

other↓, 2,   p‑pRB↓, 2,   tumCV↓, 4,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↑, 3,   HSP27↓, 1,   HSP90↓, 1,   HSPs↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   BNIP3↝, 1,   LAMP2↓, 1,   LC3I↑, 1,   LC3II↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

ATM↑, 1,   DNAdam↑, 8,   DNArepair↓, 1,   DNMT1↓, 1,   P53↓, 1,   P53↑, 5,   p‑P53↑, 1,   cl‑PARP↑, 5,   PCNA↓, 1,   TP53↑, 1,   γH2AX↑, 1,   γH2AX↝, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 2,   CDK4↓, 3,   Cyc↓, 1,   CycB/CCNB1↓, 1,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 4,   cycE/CCNE↓, 1,   P21↑, 7,   RB1↑, 1,   Securin↓, 1,   TumCCA↓, 1,   TumCCA↑, 13,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

BRAF↑, 1,   CD133↓, 1,   CD24↓, 1,   CD44↓, 3,   CSCs↓, 1,   CSCsMark↓, 1,   EMT↓, 4,   EMT↑, 1,   ERK↓, 14,   p‑ERK↓, 2,   p‑ERK⇅, 1,   FOXO3↑, 1,   Gli1↓, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   IGF-1↓, 1,   IGFBP3↑, 1,   mTOR↓, 6,   Nanog↓, 1,   NOTCH↓, 1,   OCT4↓, 2,   PI3K↓, 12,   PTEN↓, 1,   RAS↓, 2,   Smo↓, 1,   SOX2↓, 2,   STAT↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TOP1↓, 2,   TOP2↓, 1,   TRPM7↓, 4,   TumCG↓, 4,   TumCG↑, 1,   Wnt↓, 3,   Wnt/(β-catenin)↓, 1,   ZFX↓, 1,  

Migration(tgid=13) ⓘ

AntiAg↑, 1,   AP-1↓, 1,   AXL↓, 1,   Ca+2↑, 4,   cal2↑, 1,   p‑Cofilin↑, 2,   E-cadherin↑, 2,   F-actin↓, 2,   FAK↓, 2,   fascin↓, 1,   ITGB4↓, 1,   Ki-67↓, 1,   miR-200b↑, 1,   miR-29b↑, 1,   MMP1↓, 2,   MMP11↓, 1,   MMP13↓, 1,   MMP2↓, 11,   MMP3↓, 1,   MMP9↓, 8,   MMPs↓, 3,   N-cadherin↓, 2,   Rho↓, 1,   ROCK1↓, 1,   TGF-β↓, 4,   TIMP1↓, 1,   TIMP1↑, 1,   TIMP2↓, 1,   TumCI↓, 10,   TumCMig↓, 8,   TumCP↓, 9,   TumCP↑, 1,   TumMeta↓, 8,   uPA↓, 2,   Vim↓, 2,   Zeb1↓, 2,   ZEB2↓, 1,   β-catenin/ZEB1↓, 6,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 4,   EGFR↓, 3,   EPR↑, 1,   HIF-1↓, 1,   Hif1a↓, 4,   VEGF↓, 11,   VEGFR2↓, 2,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 1,   P-gp↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CB2 / CNR2↑, 1,   CD4+↓, 1,   COX2↓, 4,   CXCR4↓, 2,   IFN-γ↓, 1,   p‑IKKα↓, 1,   IL1↓, 1,   IL10↑, 1,   IL1β↓, 1,   IL2↓, 1,   IL4↓, 1,   IL6↓, 5,   Imm↑, 3,   Inflam↓, 4,   JAK↓, 1,   JAK1↓, 1,   MCP1↓, 1,   NF-kB↓, 12,   NF-kB↑, 1,   p65↓, 2,   PD-L1↓, 1,   PGE2↓, 1,   PSA↓, 1,   TNF-α↓, 3,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 2,   CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 6,   BioAv↑, 6,   BioAv↝, 1,   ChemoSen↑, 15,   Dose↝, 3,   eff↓, 1,   eff↑, 9,   eff↝, 2,   MRP1/ABCC1↓, 1,   RadioS↑, 7,   selectivity↑, 5,  

Clinical Biomarkers(tgid=22) ⓘ

AFP↓, 1,   AR↓, 2,   BRAF↑, 1,   EGFR↓, 3,   GutMicro↑, 1,   HER2/EBBR2↓, 1,   IL6↓, 5,   Ki-67↓, 1,   PD-L1↓, 1,   PSA↓, 1,   TP53↑, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 5,   AntiDiabetic↑, 1,   AntiTum↑, 6,   cardioP↑, 1,   chemoP↑, 3,   chemoPv↑, 3,   neuroP↑, 1,   OS↑, 2,   Pain↓, 1,   radioP↑, 2,   RenoP↑, 3,   toxicity↓, 1,   TumVol↓, 2,   Weight↑, 1,  
Total Targets: 266

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1,   antiOx↑, 13,   Catalase↑, 5,   GPx↑, 5,   GSH↑, 9,   GSR↑, 2,   GSTs↑, 1,   HDL↑, 1,   HO-1↓, 1,   HO-1↑, 8,   Keap1↓, 1,   lipid-P↓, 3,   MDA↓, 6,   NQO1↑, 1,   NRF2↓, 2,   NRF2↑, 8,   ROS↓, 13,   SOD↑, 9,   SOD1↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AKT1↓, 1,   ALAT↓, 3,   AMPK↓, 1,   AMPK↑, 1,   cAMP↑, 1,   CREB↑, 1,   glucose↝, 1,   GLUT2↑, 1,   HMG-CoA↓, 1,   LDH↓, 2,   LDH↑, 1,   NADPH↓, 1,   PPARγ↑, 1,   SIRT1↑, 2,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   Akt↑, 3,   Casp3↓, 2,   Casp3∅, 1,   Casp9↓, 2,   Casp9∅, 1,   Cyt‑c↓, 1,   Cyt‑c∅, 1,   Fas↓, 1,   HGF/c-Met↑, 1,   iNOS↓, 1,   iNOS↑, 1,   JNK↓, 2,   p‑JNK↓, 2,   MAPK↓, 18,   p‑MAPK↓, 1,   p38↓, 1,   p‑p38↓, 1,   TRPV1↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

Ach↑, 1,   AntiThr↑, 1,   other↑, 2,   other↝, 3,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP↑, 1,   GRP78/BiP↑, 1,   GRP94↑, 1,   HSP70/HSPA5↑, 1,   HSPs↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

PARP∅, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 2,   ERK↑, 1,   p‑ERK↓, 2,   p‑ERK↑, 1,   GSK‐3β↓, 2,   PI3K↓, 2,   PI3K↑, 3,   STAT↓, 1,   STAT1↓, 1,   p‑STAT3↓, 1,   STAT4↓, 1,   Wnt/(β-catenin)↓, 1,  

Migration(tgid=13) ⓘ

5LO↓, 1,   AntiAg↑, 1,   APP↓, 1,   Ca+2↓, 1,   E-sel↓, 1,   heparanase↑, 1,   MMP9↓, 2,   PKA↑, 1,   PKCδ↓, 1,   VCAM-1↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↑, 1,   eNOS↑, 1,   NO↓, 3,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 6,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX1↓, 1,   COX2↓, 7,   CRP↓, 2,   CXCR4↓, 1,   ICAM-1↓, 2,   IFN-γ↓, 1,   IKKα↓, 1,   IL10↑, 2,   IL12↓, 1,   IL17↓, 2,   IL18↓, 1,   IL1β↓, 7,   IL2↓, 1,   IL4↓, 1,   IL6↓, 7,   IL8↓, 2,   Imm↑, 2,   Inflam↓, 16,   JAK↓, 1,   p‑JAK2↓, 1,   Macrophages↓, 1,   MUC2↓, 1,   Neut↓, 1,   NF-kB↓, 11,   NF-kB↑, 1,   p‑NF-kB↓, 1,   PGE2↓, 5,   Th1 response↓, 1,   Th17↓, 1,   TLR2↓, 1,   TLR4↓, 4,   TNF-α↓, 9,   TNF-α↑, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↑, 2,   AChE↓, 2,   BChE↓, 1,   BDNF↑, 2,   GABA↑, 1,   MAOA↓, 2,   p‑tau↓, 1,   TrkB↑, 1,  

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 2,   Aβ↓, 2,   BACE↓, 1,   MAOB↓, 1,   NLRP3↓, 4,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 6,   BioAv↝, 3,   BioEnh↑, 1,   Dose⇅, 1,   Dose↝, 1,   eff↑, 3,   eff↝, 1,   Half-Life↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 3,   ALP↓, 1,   AST↓, 3,   CRP↓, 2,   GutMicro↑, 1,   IL6↓, 7,   LDH↓, 2,   LDH↑, 1,   MUC19↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   AntiDiabetic↓, 1,   cardioP↑, 2,   chemoP↑, 2,   cognitive↑, 5,   hepatoP↑, 4,   memory↑, 3,   neuroP↑, 11,   Pain↓, 1,   RenoP↑, 1,   toxicity↓, 1,   Wound Healing↑, 2,  

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 1,   AntiViral↑, 1,   Bacteria↓, 2,   Diar↓, 1,  
Total Targets: 169

Scientific Paper Hit Count for: MAPK, mitogen-activated protein kinase
7 Quercetin
6 Berberine
6 Silymarin (Milk Thistle) silibinin
5 Curcumin
4 Baicalein
4 Carvacrol
4 Chlorogenic acid
4 EGCG (Epigallocatechin Gallate)
4 Emodin
4 Fisetin
4 Lycopene
4 Propolis -bee glue
3 Cisplatin
3 Apigenin (mainly Parsley)
3 Betulinic acid
3 Luteolin
3 Magnolol
3 Thymoquinone
3 Urolithin
2 Alpha-Lipoic-Acid
2 Anethole/trans-Anethole
2 Chemotherapy
2 beta-glucans
2 Beta-Caryophyllene
2 Bromelain
2 Boron
2 Caffeic acid
2 Carnosic acid
2 Thymol-Thymus vulgaris
2 Centella asiatica / Gotu kola → asiaticoside
2 Chrysin
2 Cichoric acid / Chicoric acid
2 Echinacea
2 diet FMD Fasting Mimicking Diet
2 Disulfiram
2 Ellagic acid
2 Piperine
2 Garcinol
2 Magnetic Fields
2 Nimbolide
2 Resveratrol
2 Vitamin K2
1 1,8-Cineole
1 Allicin (mainly Garlic)
1 Paclitaxel
1 Astaxanthin
1 Berbamine
1 Boswellia (frankincense)
1 Bruteridin(bergamot juice)
1 Capsaicin
1 Celastrol
1 Cinnamon
1 Cucurbitacin
1 Deguelin
1 immunotherapy
1 Copper and Cu NanoParticles
1 Eurycomanone
1 Eugenol
1 Ferulic acid
1 Gambogic Acid
1 Hydroxycinnamic-acid
1 Honokiol
1 Radiotherapy/Radiation
1 Magnetic Field Rotating
1 Myricetin
1 Naringin
1 Orlistat
1 Phenethyl isothiocyanate
1 Plumbagin
1 Pterostilbene
1 Rosmarinic acid
1 Salvia officinalis
1 salinomycin
1 Sanguinarine
1 Sulforaphane (mainly Broccoli)
1 Shikonin
1 Aflavin-3,3′-digallate
1 5-fluorouracil
1 Ursolic acid
1 Vitamin C (Ascorbic Acid)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:181  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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