Betulinic acid

Clinical trial

Mechanism of Action

Anti-inflammatory and emerging antiviral properties; also found in birch bark

Anti-inflammatory via NF-kB inhibition; anti-tumor; neuroprotective through anti-apoptotic mechanisms

Enhanced NF-κB inhibition compared to betulin; pro-apoptotic in inflammatory cells; antitumor activity in preclinical models

Betulinic acid induces apoptosis selectively in cancer cells through the intrinsic (mitochondrial) pathway. It directly permeabilizes the outer mitochondrial membrane by interacting with voltage-dependent anion channels (VDAC), triggering cytochrome c release, apoptosome assembly, and executioner caspase-3/7 activation. This mechanism is largely independent of p53 status, making it effective against tumors with p53 mutations. Betulinic acid also inhibits topoisomerase I, blocks NF-kB activation, and downregulates Sp1 transcription factor target genes involved in angiogenesis (VEGF) and metastasis (MMP-2, MMP-9). Anti-HIV activity occurs through inhibition of viral maturation — betulinic acid derivatives (notably bevirimat/PA-457) block Gag polyprotein processing.

Betulinic acid is NOT synthesized by the Chaga fungus itself — it is derived from the bioconversion of betulin (a primary triterpene in birch bark) by fungal enzymatic activity. The fungus metabolizes birch betulin into the more bioavailable and pharmacologically active betulinic acid. Its anticancer mechanism involves selective induction of apoptosis in cancer cells via the mitochondrial pathway: it permeabilizes the outer mitochondrial membrane, triggers cytochrome c release, activates caspase-9 and caspase-3, and induces programmed cell death — critically, WITHOUT inducing apoptosis in normal cells at equivalent concentrations. It also inhibits topoisomerase I and modulates NF-κB inflammatory signaling.

Anti-inflammatory; anti-tumor via apoptosis induction; immunomodulatory

Anti-tumour (induces apoptosis via mitochondrial pathway); anti-inflammatory; anti-HIV; antiplatelet

Research Notes

AlderWestern

Extensively studied triterpene with anti-inflammatory, antiviral, and cytotoxic properties in preclinical research.

BacopaAyurvedic

Betulinic acid contributes anti-inflammatory and neuroprotective effects. In vitro studies demonstrate selective cytotoxicity and neuroprotection.

Birch BarkWestern

Betulinic acid is a naturally occurring oxidized derivative of betulin with enhanced anti-inflammatory and apoptotic properties. Preclinical evidence supports efficacy against inflammatory conditions and tumor cell lines, though human clinical data remains limited.

Birch PolyporeMushroom

Betulinic acid demonstrated selective cytotoxicity against melanoma, neuroblastoma, glioblastoma, and several other cancer cell lines in the NCI 60-cell panel screening, with minimal toxicity to normal cells. A 2001 study confirmed antiviral action against HIV by blocking viral reproduction. The derivative bevirimat (PA-457) advanced through Phase II clinical trials as a first-in-class HIV maturation inhibitor before development was discontinued for pharmacokinetic reasons. Animal toxicology showed no adverse effects up to 500 mg/kg body weight in mice.

ChagaMushroom

Betulinic acid demonstrated selective cytotoxicity against melanoma, neuroblastoma, and glioblastoma cell lines in vitro (Fulda et al., 1997, Journal of Biological Chemistry; Pisha et al., 1995, Nature Medicine). An NCI study confirmed activity against multiple cancer cell lines. Phase I/II clinical trials for betulinic acid (as an isolated compound, not Chaga extract) have been conducted for melanoma and other solid tumors. CRITICAL: betulinic acid is present ONLY in wild birch-grown Chaga sclerotia — cultivated Chaga grown on grain or artificial substrate does NOT contain betulinic acid because there is no birch host to provide the betulin precursor.

Jujube (Da Zao)TCM

Betulinic acid contributes anti-inflammatory and potential anti-tumor effects with selective cytotoxicity against cancer cell lines.

Red RootWestern

Anti-tumour activity against multiple cancer cell lines; anti-HIV activity (inhibits maturation); found in many plant species (birch bark is primary commercial source)

Found In 7 Herbs

3D Molecular Structure

Triterpene

Drag to rotate · Click atoms to explore

Betulinic acid

TriterpeneAromatic plant metabolites with anti-inflammatory properties

Representative pattern: C₁₀H₁₆O

Atoms

Carbon

Oxygen

Hydrogen

Related Compounds (Triterpene)

Asiatic acid(1)Myrrhanol A(1)Taraxasterol(3)

Live Research

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