Centella asiatica / Gotu kola → asiaticoside / cycD1/CCND1 Cancer Research Results

Cen, Centella asiatica / Gotu kola → asiaticoside: Click to Expand ⟱

Features:

Centella asiatica / Gotu kola → Asiaticoside

Centella asiatica, commonly known as Gotu kola, is a medicinal botanical used mainly for wound healing, skin repair, microcirculation support, anti-inflammatory effects, and possible neuroprotective activity.

Primary database product: Centella asiatica standardized extract
Common name / alias: Gotu kola
Other aliases: Indian pennywort, tiger grass, cica
Best form: Standardized Centella asiatica extract / titrated triterpenes
Main active marker: Asiaticoside
Other key actives: Madecassoside, asiatic acid, madecassic acid
Compound class: Pentacyclic triterpenoid saponins / triterpenes

Asiaticoside is one of the major active and marker compounds in Centella asiatica.

Asiaticoside role: Active constituent / quality marker
Source: Centella asiatica / Gotu kola
Main activities: Wound repair, collagen synthesis, fibroblast support, anti-inflammatory, antioxidant, skin barrier support
Relevant pathways: TGF-β/collagen, VEGF/angiogenesis, NF-κB, IL-1β, IL-6, TNF-α, COX-2/PGE2, oxidative stress pathways

Structure:

Centella asiatica / Gotu kola
  → Asiaticoside
  → Madecassoside
  → Asiatic acid
  → Madecassic acid

Centella asiatica / Gotu kola → asiaticoside — Centella asiatica is a medicinal botanical extract source, and asiaticoside is one of its major pentacyclic triterpenoid saponin marker constituents. The formal classification is botanical standardized extract / natural-product triterpenoid saponin modality, not an approved anticancer drug. The principal active family includes asiaticoside, madecassoside, asiatic acid, and madecassic acid; asiaticoside can also be metabolically linked to asiatic acid. Asiaticoside as the main active marker, with Centella asiatica standardized extract as the primary product.

Primary mechanisms (ranked):

NF-κB and inflammatory cytokine suppression, especially reduced TNF-α, IL-1β, IL-6, COX-2/PGE2, and downstream survival signaling in inflammatory and tumor models.
Mitochondrial apoptosis induction in cancer cells, with Bax:Bcl-2 shift, MMP loss, caspase-9 activation, caspase-3 activation, and p53/p21-associated cell-cycle arrest reported in preclinical models.
Anti-migration and anti-EMT effects, including suppression of p65/NF-κB-linked EMT, YAP1/VEGFA signaling, invasion, and radiation-induced migration in selected cancer-cell systems.
PI3K/Akt/mTOR/STAT3 modulation, more strongly supported for asiatic acid than for asiaticoside itself, with relevance to proliferation, survival, autophagy, and metastatic phenotype.
TGF-β/collagen/fibroblast and wound-repair axis activation in normal tissue contexts; beneficial for repair but mechanistically ambiguous in cancer because fibrosis and angiogenesis can be tumor-context dependent.
Oxidative-stress modulation, generally antioxidant and cytoprotective in normal cells; ROS/NRF2 effects are secondary and context-dependent rather than the core anticancer mechanism.

Bioavailability / PK relevance: Oral translation is constrained by variable extract composition, limited dissolution and bioavailability of triterpenes, metabolism of glycosides to aglycones, and formulation dependence. Standardized extracts such as ECa 233 and aqueous Centella asiatica products have human phase-1 PK data, but systemic exposure is still not equivalent to common high-concentration in-vitro cancer experiments.

In-vitro vs systemic exposure relevance: Cancer-cell studies commonly use micromolar asiaticoside or asiatic-acid exposures that may exceed or not cleanly map onto achievable plasma exposure after oral botanical dosing. Topical and local tissue uses are more plausible for skin/wound biology than systemic anticancer effects. For cancer translation, the entry should be treated as concentration- and formulation-dependent.

Clinical evidence status: Cancer relevance is weak / preclinical only, with no established oncology indication. Human evidence is stronger for wound healing, venous/skin-related uses, and early cognitive/AD-oriented safety or PK studies than for cancer treatment. AD relevance is possible / early clinical, with phase-1 target-engagement work in mild cognitive impairment or mild Alzheimer’s disease, but no proven disease-modifying efficacy.

Centella asiatica and Asiaticoside Mechanistic Profile

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	NF-κB inflammatory survival axis	NF-κB↓, p65↓, TNF-α↓, IL-1β↓	NF-κB↓, inflammatory cytokines↓	R,G	Anti-inflammatory and anti-survival signaling	Most central cross-context mechanism; supports anticancer, neuroinflammatory, and wound-healing interpretations but is not cancer-specific.
2	Mitochondrial apoptosis	MMP↓, Bax:Bcl-2↑, caspase-9↑, caspase-3↑	Apoptosis↔ or ↓ in injury models (context-dependent)	G	Intrinsic apoptotic priming in tumor models	Preclinical cancer-cell effect; selectivity depends strongly on dose, cell line, and compound form.
3	Cell-cycle checkpoint and p53 axis	p53↑, p21↑, cyclin D1↓, CDK4↓	Cell-cycle stress↔ (context-dependent)	G	Growth arrest and reduced proliferation	cytostatic activity; best treated as model-dependent rather than universal.
4	EMT migration invasion axis	Migration↓, invasion↓, EMT↓, YAP1/VEGFA↓, p65↓	Repair migration↑ in wound contexts (context-dependent)	G	Reduced metastatic phenotype in selected models	Important because Centella can promote normal wound repair while suppressing tumor-cell invasion in some systems; interpretation is tissue-context dependent.
5	PI3K Akt mTOR STAT3 survival axis	PI3K/Akt↓, mTOR↓, STAT3↓ (mainly asiatic acid)	Mixed cytoprotection or survival signaling↔	R,G	Reduced survival, proliferation, and metastatic signaling	Better supported for asiatic acid than asiaticoside; include as related triterpene-family mechanism rather than asiaticoside-only claim.
6	Autophagy axis	LC3-II↑, autophagy↑ (model-dependent)	Autophagy↔ or ↑ (context-dependent)	G	Stress adaptation or autophagic cell death	Direction and therapeutic meaning are model-dependent; can be pro-death or protective depending on tumor context.
7	ROS antioxidant NRF2 stress axis	ROS↔ or ↑ during apoptosis (context-dependent)	Oxidative stress↓, antioxidant defense↑, NRF2↔ or ↑	R,G	Normal-cell protection and redox modulation	Secondary mechanism.
8	TGF-β collagen fibroblast repair axis	TGF-β effects↔ (context-dependent)	Collagen synthesis↑, fibroblast activity↑, wound repair↑	G	Tissue repair and matrix remodeling	Core for Centella’s non-cancer use; potentially undesirable in some tumor-stroma or fibrosis contexts.
9	VEGF angiogenesis axis	VEGFA↓ in some breast cancer models	Angiogenesis↑ during wound repair (context-dependent)	G	Opposite effects depending on cancer versus repair context	Important interpretive caution: normal repair biology and cancer biology may diverge.
10	Radiosensitization migration constraint	Radiation-induced migration↓, invasion↓	Radioprotection↔ unknown	G	Anti-invasive adjunct signal after irradiation	Evidence is preclinical and more anti-migration than classic radiosensitization
11	Clinical Translation Constraint	High in-vitro exposure required (often)	Rare hepatotoxicity risk; product variability	G	Limits systemic anticancer translation	Bioavailability, formulation, extract standardization, dose limitation, and weak oncology trial evidence are the main constraints.

P: 0–30 min R: 30 min–3 hr G: >3 hr

AD relevance: Possible / preclinical. Interest is mainly through neuroinflammation, oxidative stress, mitochondrial protection, and general neuroprotective mechanisms.

Alzheimer’s disease relevance: Centella asiatica / Gotu kola has a plausible but unproven AD-oriented profile. The strongest rationale is not direct amyloid clearance as an established clinical effect, but combined modulation of neuroinflammation, oxidative stress, mitochondrial metabolism, synaptic or neuronal viability markers, and vascular/microcirculatory support. Human evidence is early: phase-1 PK/safety and target-engagement studies exist in older adults with mild cognitive impairment or mild Alzheimer’s disease, but efficacy remains unproven.

Clinical evidence status: AD / cognition evidence is preclinical plus small human and phase-1 clinical work. Early translational / investigational rather than established therapy.

Cancer relevance: Weak / preclinical.

AD-Oriented Mechanistic Profile

Rank	Pathway / Axis	Modulation	Primary Effect	Notes / Interpretation
1	Neuroinflammation NF-κB cytokine axis	NF-κB↓, TNF-α↓, IL-1β↓	Reduced inflammatory signaling	Most defensible AD-relevant mechanism; not disease-specific.
2	Mitochondrial metabolism neuronal viability	Mitochondrial function↑, metabolic stress↓	Neuronal bioenergetic support	Central to current target-engagement rationale in cognitive impairment studies.
3	Oxidative stress DNA oxidation axis	Oxidative stress↓, 8OHdG↓ (candidate marker)	Reduced oxidative injury	Relevant to trial biomarker strategy; clinical disease modification unproven.
4	Synaptic memory and neuronal morphology axis	Learning and memory markers↑ (model-dependent)	Cognitive-support signal in animals	Preclinical support is stronger than human efficacy evidence.
5	Amyloid-associated pathology	β-amyloid stress↓ (model-dependent)	Reduced amyloid-model metabolic disturbance	model-dependent, not as proven anti-amyloid clinical activity.
6	Clinical Translation Constraint	Bioavailability↔, extract variability↑, evidence limitation↑	Limits AD clinical interpretation	Current status is investigational; formulation, heavy-metal quality, dose, and trial endpoints matter.

cycD1/CCND1, cyclin D1 pathway: Click to Expand ⟱

Source:

Type:

Also called CCND1 Gatekeeper of Cell-Cycle Commitment
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.

Scientific Papers found: Click to Expand⟱

6652-

Cen,

AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells

in-vitro,

GC,

SGC-7901

in-vitro,

GC,

HGC27

TumCP↓, selectivity↑, TumCCA↑, cycD1/CCND1↓, CDK4↓, Apoptosis↑, Bcl-2↓, BAX↑, cMyc↓, Casp3↑, TumCMig↓, TumCI↓, MMP2↓, MMP9↓, tumCV↓,

6615-

Cen,

Asiaticoside suppresses cell proliferation by inhibiting the NF-κB signaling pathway in colorectal cancer

vitro+vivo,

CRC,

HCT116

mice

in-vitro,

CRC,

SW480

in-vitro,

CRC,

LoVo

Dose↝, TumCP↓, selectivity↑, MMP↓, Apoptosis↑, TumCCA↑, NF-kB↓, CDK4↓, cycD1/CCND1↓, Casp9↑, Casp3↑, Bax:Bcl2↑, TumCG↓, ChemoSen↑, TNF-α↓, IL1β↓, P53↑, P21↑,

6640-

Cen,

Asiaticoside Antagonizes Proliferation and Chemotherapeutic Drug Resistance in Hepatocellular Carcinoma (HCC) Cells

in-vitro,

HCC,

Bel-7402

6.807 μM

in-vitro,

HCC,

QGY-7703

6.724 μM

TumCP↓, Apoptosis↑, TumCCA↑, PI3K↓, Akt↓, MAPK↓, ERK↓, P-gp↓, ROS↓, p‑pRB↓, cycD1/CCND1↓, p27↑,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: cycD1/CCND1, cyclin D1 pathway

3 Centella asiatica / Gotu kola → asiaticoside

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#:417  Target#:73  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

Centella asiatica / Gotu kola → asiaticoside / cycD1/CCND1 Cancer Research Results