Ginseng / Ca+2 Cancer Research Results

Gins, Ginseng: Click to Expand ⟱
Features:

Ginseng — a medicinal root from the genus Panax, principally Asian/Korean ginseng (Panax ginseng) and American ginseng (Panax quinquefolius). It is a botanical natural health product containing multiple pharmacologically active constituents, especially triterpenoid saponins called ginsenosides, including Rb1, Rb2, Rc, Rd, Re, Rg1 and, depending strongly on processing, Rg3, Rg5 and related compounds; intestinal metabolism also generates metabolites such as Compound K. Standard abbreviations include PG for Panax ginseng, KRG for Korean red ginseng and AG for American ginseng. White, red, fermented and heat-processed ginseng have substantially different ginsenoside profiles and should not be assumed mechanistically equivalent. Anticancer effects attributed to “ginseng” are predominantly derived from preclinical studies of specific ginsenosides such as Rg3 and Rh2 rather than conventional whole-root exposure.

Primary mechanisms (ranked):

  1. Suppression of oncogenic PI3K/Akt and related MAPK growth-survival signaling by selected ginsenosides, particularly Rg3 and Rh2.
  2. Induction of mitochondrial apoptosis through altered BCL-2/BAX balance, mitochondrial dysfunction and caspase activation.
  3. Suppression of tumor invasion, angiogenesis and metastatic signaling, including VEGF-related pathways, particularly by Rg3.
  4. Redox modulation: selected ginsenosides can increase mitochondrial ROS sufficiently to trigger apoptosis in cancer cells while ginseng/ginsenosides more commonly activate antioxidant defenses and reduce oxidative stress in nonmalignant tissues.
  5. Suppression of NF-κB-associated inflammatory and prosurvival signaling, with corresponding modulation of inflammatory cytokines.
  6. Chemo- and radiosensitization reported for selected ginsenosides, particularly Rg3, but predominantly at the preclinical level.
  7. Secondary NRF2/HO-1 antioxidant modulation, particularly relevant to normal-cell cytoprotection; its effect within tumors is context-dependent and may theoretically protect some malignant cells.

Bioavailability / PK relevance: Native ginsenosides generally have low and highly variable oral systemic exposure because of limited intestinal absorption and extensive gut-microbiota metabolism. Rb1 and related compounds can be converted sequentially to more readily absorbed metabolites including Compound K. Consequently, microbiome composition, ginseng species, processing and formulation strongly influence systemic exposure. Red or heat-processed ginseng contains substantially more Rg3/Rg5 than ordinary white ginseng.

In-vitro vs systemic exposure relevance: Many anticancer experiments with Rg3, Rh2 and related ginsenosides use approximately micromolar to tens-of-micromolar concentrations. Following conventional oral ginseng, circulating concentrations of many parent ginsenosides are substantially lower and exposure is frequently metabolite-driven. Therefore direct extrapolation of isolated-ginsenoside cancer-cell cytotoxicity to oral whole-root ginseng is weak. Pharmacologically enriched, fermented or purified ginsenoside products constitute materially different exposures.

Clinical evidence status: Direct anticancer efficacy of ordinary oral ginseng remains unestablished. A large phase III randomized trial supports American ginseng at 2 g/day for reduction of cancer-related fatigue, making supportive oncology its strongest cancer-related human evidence. Clinical literature on purified/enriched Rg3 combined with chemotherapy exists, particularly from China, but does not establish ordinary ginseng root as an anticancer therapy. Ginseng is marketed as a natural health/herbal product rather than an approved anticancer drug. Health Canada has specifically concluded that available evidence was insufficient to establish acceptable conditions for standardized Panax ginseng extract in supplemented foods when total ginsenoside intake would exceed 8 mg/day.

Ginseng (Panax ginseng) – This herb has been studied for its ability to enhance the immune system.
-Antioxidant Properties: Ginseng contains ginsenosides, which have antioxidant properties.
-Immune System Support
-Inhibition of Tumor Growth
-Chemopreventive Effects
-Synergistic Effects with Cancer Treatments: ginseng may enhance the effectiveness of certain cancer treatments, such as chemotherapy, and may help reduce side effect
Dose: Standardized Extract:
Dosage: extract containing 4-7% ginsenosides 200-400mg/d
Dried Root:1-2g/d
Tea: 1-2g dried root, 1-3x/d

Ginseng Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells Primary Effect Notes / Interpretation
1 PI3K/Akt survival signaling ↓ ↔ / ↑ (context-dependent) Reduced proliferation and survival One of the most reproducible anticancer axes for Rg3 and Rh2. Evidence largely concerns isolated ginsenosides rather than conventional whole-root ginseng.
2 Mitochondrial apoptosis ↑ ↔ / ↓ injury Apoptotic cell death Selected ginsenosides increase BAX/BCL-2 ratio, mitochondrial dysfunction and caspase-9/caspase-3 activation. Usually concentration-dependent.
3 Angiogenesis and VEGF signaling ↓ ↔ Reduced tumor vascularization Particularly associated with Rg3; inhibition of VEGF signaling and endothelial responses has been demonstrated preclinically.
4 NF-κB inflammatory and survival signaling ↓ ↓ excessive activation Reduced inflammation and prosurvival signaling May suppress inflammatory cytokines, invasion and treatment resistance. Magnitude varies substantially among individual ginsenosides and preparations.
5 Mitochondrial ROS increase ↑ (dose-dependent) ↓ oxidative stress Oxidative apoptosis in cancer cells Rh2 can induce mitochondrial ROS and apoptosis. This should not be generalized to all ginseng preparations because antioxidant effects predominate in many normal-tissue models.
6 Migration and invasion ↓ ↔ Reduced metastatic phenotype Selected ginsenosides suppress migration, invasion and associated signaling in multiple experimental cancer models.
7 Chemosensitization ↑ treatment response ↔ / ↓ toxicity (model-dependent) Enhanced chemotherapy response Rg3 has enhanced responses to agents including 5-FU, cisplatin and doxorubicin in experimental systems. Evidence for whole-root ginseng is substantially weaker.
8 Radiosensitization ↑ (model-dependent) ↔ / radioprotection reported Enhanced radiation response Rg3 can enhance radiation-induced tumor-cell killing through pathways including NF-κB suppression, while other ginsenosides may protect normal tissue from radiation injury.
9 NRF2 antioxidant defense ↔ / ↑ (context-dependent) ↑ Antioxidant cytoprotection Secondary mechanism. Potentially beneficial in normal tissue but mechanistically ambiguous in cancer because NRF2 activation can also support tumor antioxidant defenses.
10 Clinical Translation Constraint — — Predominantly adjunctive use Species, processing and ginsenoside composition vary markedly. Oral parent-ginsenoside exposure is low and microbiome-dependent, while many anticancer experiments use purified Rg3/Rh2 at substantially higher concentrations. Direct tumor-control efficacy of ordinary oral ginseng has not been established.


Ginseng and Alzheimer’s disease: Panax ginseng, Korean red ginseng and individual ginsenosides have substantial preclinical neuroprotective evidence involving amyloid processing, tau phosphorylation, neuroinflammation, oxidative stress, synaptic signaling and neurotrophic pathways. Small Korean clinical studies have reported improvements in cognitive scores, but these studies were generally small, open-label or otherwise at substantial risk of bias. Current evidence is insufficient to classify ginseng as a disease-modifying treatment for Alzheimer’s disease.

Primary mechanisms (ranked):

  1. Reduction of amyloidogenic processing and Aβ accumulation through modulation of APP-processing enzymes and Aβ clearance pathways.
  2. Reduction of tau phosphorylation and aggregation through multiple kinase/phosphatase pathways.
  3. Enhancement of synaptic plasticity and neurotrophic signaling including BDNF/TrkB-related pathways.
  4. Suppression of microglial activation, NF-κB signaling and neuroinflammatory cytokine production.
  5. Reduction of neuronal oxidative stress and mitochondrial dysfunction through antioxidant pathways including NRF2.
  6. Cholinergic support and modulation of neurotransmission.

Clinical evidence status: Small human studies of Korean red ginseng have reported improvements in MMSE, ADAS-cog and related cognitive measures, but adequately powered modern blinded placebo-controlled Alzheimer trials are lacking. The evidence remains preliminary and does not establish prevention of neurodegeneration or disease modification.


Ginseng Alzheimer-Relevant Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Amyloid processing and Aβ burden ↓ Reduced amyloidogenic pathology Ginsenosides and processed ginseng can influence APP processing, BACE activity and Aβ clearance in preclinical systems.
2 Tau phosphorylation and aggregation ↓ Reduced tau pathology Multiple ginseng constituents have reduced tau phosphorylation in experimental systems; red ginseng can also interfere with tau aggregation in vitro.
3 BDNF and TrkB neuroplasticity ↑ Synaptic and neurotrophic support Ginsenosides can increase neurotrophic signaling and support learning and memory in experimental models.
4 Neuroinflammation and NF-κB ↓ Reduced microglial inflammatory signaling Associated with reductions in inflammatory cytokines and activated microglial responses in preclinical models.
5 NRF2 antioxidant defense ↑ Reduced oxidative neuronal injury Activation of antioxidant-response pathways contributes to neuronal protection in several ginseng and ginsenoside models.
6 Oxidative stress and ROS ↓ Reduced neuronal oxidative damage Generally antioxidant in neuronal and other nonmalignant tissues, unlike the pro-oxidant response produced by some ginsenosides in cancer cells at high concentrations.
7 Cholinergic signaling ↑ Improved neurotransmission Modulation of acetylcholine synthesis, release and degradation has been reported, although this mechanism is less clinically established than standard cholinesterase inhibition.
8 Clinical Translation Constraint — Preliminary human evidence Human Alzheimer studies are small and methodologically limited. Different species, red-ginseng processing and purified ginsenosides cannot be considered interchangeable.


Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
Source:
Type:
In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.
Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.
In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).
Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.
Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.
Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.
High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.
Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.
Scientific Papers found: Click to Expand⟱
7283- Gins,    Ginsenoside-Rh2-induced mitochondrial depolarization and apoptosis are associated with reactive oxygen species- and Ca2+-mediated c-Jun NH2-terminal kinase 1 activation in HeLa cells
- in-vitro, Cerv, HeLa - in-vitro, BC, MCF-10AT - in-vitro, BC, MCF7
MMP↓, Casp↑, BAX↑, Ca+2↑, ROS↑, cJun↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,  

Cell Death(tgid=5) ⓘ

BAX↑, 1,   Casp↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cJun↑, 1,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,  
Total Targets: 6

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Ca+2, Calcium Ion Ca+2
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#:219  Target#:38  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page