Rauwolfia serpentina/Indian Snakeroot / Mcl-1 Cancer Research Results

RS, Rauwolfia serpentina/Indian Snakeroot: Click to Expand ⟱
Features:

Rauwolfia serpentina - Indian Snakeroot, Sarpagandha

Type: Botanical extract / indole alkaloid-containing medicinal plant

Active Constituents: Reserpine, ajmaline, ajmalicine, serpentine, rescinnamine, and related indole alkaloids.

Function: Rauwolfia serpentina contains pharmacologically active indole alkaloids with effects on monoamine transport, adrenergic signaling, cardiovascular regulation, cell proliferation, apoptosis, and other signaling pathways.

Cancer: Experimental evidence suggests anticancer activity for Rauwolfia-derived alkaloids, particularly reserpine, including inhibition of proliferation, induction of apoptosis, and cell-cycle disruption. Evidence for whole Rauwolfia serpentina extract is more limited than for isolated constituents or other Rauwolfia species, so species-specific attribution should be maintained.

Rauwolfia serpentina — also called Indian snakeroot or Sarpagandha, is a medicinal plant in the Apocynaceae family whose roots contain pharmacologically active monoterpenoid indole alkaloids, most notably reserpine, along with ajmaline, ajmalicine, serpentine, rescinnamine, and related compounds. It is classified as a botanical medicinal product / indole-alkaloid source; Reserpine is the best-characterized constituent and acts primarily as an essentially irreversible vesicular monoamine transporter inhibitor, especially VMAT2, depleting norepinephrine, dopamine, and serotonin from neuronal and sympathetic storage vesicles. Historically, Rauwolfia preparations and reserpine were used as antihypertensive agents. Cancer evidence is substantially stronger for isolated reserpine than for standardized R. serpentina extracts, and results from other Rauvolfia species should not automatically be attributed to R. serpentina.

Primary mechanisms (ranked):

  1. Reserpine-mediated VMAT2 inhibition and depletion of vesicular monoamines, producing sustained sympatholytic and central monoaminergic effects; this is the principal established pharmacological mechanism but is not itself a validated anticancer mechanism.
  2. Mitochondrial apoptosis and loss of mitochondrial membrane potential in cancer cells, with BAX/BCL-2 and caspase-associated apoptotic signaling reported for reserpine.
  3. Cell-cycle arrest and inhibition of DNA synthesis/proliferation, including G2 arrest in androgen-independent prostate cancer cells and G0/G1 arrest in some breast-cancer models.
  4. Suppression of tumor invasion and DNA-repair-associated signaling through modulation of TGF-β-related pathways in experimental oral carcinogenesis.
  5. Hippo/YAP signaling modulation by reserpine, including ↓YAP and ↓BCL-2 with ↑MST1 and ↑BAX in a triple-negative breast-cancer model; this evidence derives from isolated reserpine studied alongside Rauvolfia tetraphylla rather than R. serpentina extract.
  6. ROS modulation is secondary and strongly context-dependent: reserpine increased oxidative stress in one triple-negative breast-cancer model but decreased measured ROS in PC3 prostate cancer cells despite mitochondrial depolarization.

Bioavailability / PK relevance: Reserpine is orally absorbed, widely distributed, crosses the blood-brain barrier and placenta, and accumulates substantially in tissues including adipose tissue. Human pharmacokinetic data indicate biphasic elimination, with an early half-life of approximately 4.5 hours and a terminal phase of approximately 11.3 days; pharmacodynamic effects can therefore persist well beyond plasma exposure. Whole-root preparations have variable alkaloid composition and cannot be assumed pharmacokinetically equivalent to purified reserpine.

In-vitro vs systemic exposure relevance: Anticancer findings are predominantly from cell-culture or animal experiments using purified reserpine or extracts whose achievable human tumor exposure is uncertain. Concentrations producing cancer-cell effects should therefore not be assumed achievable or safe with oral R. serpentina. Chronic pharmacological effects may occur at low systemic reserpine exposure because VMAT binding and monoamine depletion are prolonged, but this does not establish clinically relevant anticancer exposure.

Clinical evidence status: Hypertension: historical controlled human evidence and established pharmacology. Cancer: preclinical only; no established anticancer clinical efficacy. Human studies of Rauwolfia/re­serpine primarily concern hypertension rather than cancer. Major constraints include hypotension, bradycardia, CNS monoamine depletion, depression, Parkinsonian/extrapyramidal effects, gastrointestinal hypersecretion, drug interactions, and prolonged pharmacodynamic action. Reserpine-containing labeling also notes animal tumorigenicity and uncertain historical epidemiologic findings concerning breast cancer, making indiscriminate interpretation of reserpine as an anticancer compound inappropriate.

Rauwolfia serpentina Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial apoptosis ↑ apoptosis; ↓ mitochondrial membrane potential; ↑ BAX; ↓ BCL-2 Potential mitochondrial and CNS toxicity at pharmacologic exposure R/G Apoptotic cell death Best demonstrated for isolated reserpine. PC3 prostate-cancer cells show mitochondrial depolarization, DNA fragmentation, and apoptotic changes.
2 Cell cycle and DNA synthesis ↓ proliferation; ↓ DNA synthesis; ↑ cell-cycle arrest Potential ↓ proliferation in susceptible normal cells (context-dependent) G Growth suppression G2 arrest reported in PC3 cells; G0/G1 accumulation reported in reserpine-treated MDA-MB-231 cells. Phase depends on model.
3 TGF-β signaling and DNA repair ↓ tumor-promoting TGF-β-associated signaling; ↓ DNA repair; ↓ invasion Uncertain G Reduced survival and invasion Reported in experimental oral carcinogenesis with reserpine. Translation to whole R. serpentina preparations remains unestablished.
4 Hippo YAP signaling ↑ MST1; ↓ LATS1; ↓ YAP; ↓ YAP-TEAD activity; ↑ BAX; ↓ BCL-2 Uncertain G ↓ proliferation and ↑ apoptosis Observed with isolated reserpine in MDA-MB-231 cells in a Rauvolfia tetraphylla study. Constituent evidence is relevant to reserpine but should not be presented as direct R. serpentina extract evidence.
5 Migration and invasion ↓ migration; ↓ invasion Uncertain G Reduced metastatic phenotype Supported by breast-cancer and oral-carcinogenesis models using reserpine.
6 Reactive oxygen species ↑ or ↓ ROS (model-dependent) Potential oxidative and mitochondrial effects (context-dependent) R/G Secondary redox modulation Not suitable for a simple ROS↑ classification. ROS increased in reserpine-treated MDA-MB-231 cells but decreased in PC3 prostate-cancer cells despite mitochondrial depolarization.
7 VMAT2 and monoamine storage ↓ VMAT-dependent vesicular monoamine storage where expressed ↓ VMAT2 function; ↓ norepinephrine, dopamine and serotonin storage P/R Monoamine depletion Core established pharmacological action of reserpine. Highly relevant to systemic toxicity and pharmacology, but its contribution to most reported anticancer effects is not established.
8 Adrenergic and sympathetic signaling Potential ↓ adrenergic signaling (context-dependent) ↓ sympathetic tone; ↓ peripheral vascular resistance; ↓ heart rate R/G Sympatholytic effect Major clinically established effect resulting from catecholamine depletion. Anticancer significance remains indirect and unproven.
9 Prolactin signaling Potential ↑ prolactin-driven signaling in susceptible tumors ↑ prolactin (context-dependent) G Potential adverse proliferative signal Important safety counterpoint. Chronic reserpine increased mammary tumors in rodents, attributed partly to prolactin elevation; relevance to human breast-cancer risk remains uncertain.
10 Clinical Translation Constraint Preclinical anticancer exposure not clinically validated ↓ blood pressure; bradycardia; CNS monoamine depletion; depression risk; extrapyramidal effects G Limits anticancer translation Whole-root alkaloid composition is variable. Reserpine has prolonged tissue pharmacology and an approximately 11-day terminal elimination phase. No established cancer treatment regimen or human anticancer efficacy exists.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr
Mcl-1, myeloid cell leukemia 1: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
A member of the Bcl-2 family of proteins, which play a crucial role in regulating apoptosis, or programmed cell death. In cancer, Mcl-1 is often overexpressed, contributing to the development and progression of various types of tumors.
Mcl-1 is often overexpressed in several cancers, including hematological malignancies (like leukemia and lymphoma) and solid tumors (such as breast, lung, and prostate cancers).
Mcl-1 inhibits apoptosis by binding to pro-apoptotic proteins, preventing them from triggering the cell death pathway.


Scientific Papers found: Click to Expand⟱
7378- RS,    Reserpine inhibits DNA repair, cell proliferation, invasion and induces apoptosis in oral carcinogenesis via modulation of TGF-β signaling
*antiOx↑, *AntiBio↑, TGF-β↓, p‑SMAD3↓, p‑SMAD2↓, p‑SMAD4↓, SMAD3↓, Snail↓, ERCC1↓, ERCC4/XPF↓, Ku70/XRCC6↓, PCNA↓, cycD1/CCND1↓, Hif1a↓, IL6↓, Mcl-1↓, BAX↑, Cyt‑c↑, APAF1↑, Casp9↑, Casp3↑, PARP↑, DNArepair↓, TumCP↓, TumCI↓,

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:


NA, unassigned(tgid=0) ⓘ

ERCC4/XPF↓, 1,   Ku70/XRCC6↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ERCC1↓, 1,  

Cell Death(tgid=5) ⓘ

APAF1↑, 1,   BAX↑, 1,   Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   Mcl-1↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNArepair↓, 1,   PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

cycD1/CCND1↓, 1,  

Migration(tgid=13) ⓘ

p‑SMAD2↓, 1,   SMAD3↓, 1,   p‑SMAD3↓, 1,   p‑SMAD4↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL6↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 1,  
Total Targets: 24

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,  
Total Targets: 2

Scientific Paper Hit Count for: Mcl-1, myeloid cell leukemia 1
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#:441  Target#:182  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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