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Gossypol
ModerateMechanism of Action
Gossypol acts as a BH3 mimetic, binding to the hydrophobic groove of anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-xL, Mcl-1), displacing pro-apoptotic BH3-only proteins and triggering mitochondrial outer membrane permeabilization, cytochrome c release, and caspase-mediated apoptosis. In spermatogenesis, it disrupts mitochondrial function in Sertoli and Leydig cells, causing energy depletion and impaired spermatogenesis. It inhibits 11-beta-hydroxysteroid dehydrogenase and lactate dehydrogenase C4 (LDH-C4), enzymes essential for testicular steroidogenesis and sperm metabolism.
Research Notes
Cotton Root BarkWestern
The R-(-) enantiomer of gossypol (AT-101) has been evaluated in Phase I/II clinical trials as an anti-cancer agent. A Phase II trial in castration-resistant prostate cancer (Liu et al., 2009, Clinical Cancer Research) showed modest single-agent activity. The male antifertility effect was documented in Chinese studies involving over 10,000 men, with effective contraception at 20 mg/day but unacceptable hypokalemia in 1–10% of subjects and irreversible azoospermia in approximately 20%.
Found In 1 Herb
3D Molecular Structure
Polyphenolic bisnaphthalene aldehyde
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Gossypol
Polyphenolic bisnaphthalene aldehydeSimple aromatic compounds with antimicrobial properties
Representative pattern: C₇H₆O₃
Atoms
Carbon
Oxygen
Hydrogen
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