Ginkgolide C

Pharmacology & Research

Ginkgolide C is one of the diterpene trilactones (the “ginkgolides”, A/B/C/J) that, with bilobalide, make up the terpene-lactone fraction of Ginkgo biloba leaf — see the ginkgolides class page. Within that series it is the minor, weakest congener: an extra 7β-hydroxyl makes it a substantially poorer platelet-activating-factor (PAF) antagonist than ginkgolide B, and it is also the poorest-absorbed of the group. The load-bearing point is that ginkgo’s human evidence rests on the standardised EGb 761 extract (and, for the class, an injectable ginkgolide mixture used in stroke), not on isolated ginkgolide C ^{6Reference 6DeFeudis FV · 2000Ginkgo biloba extract (EGb 761) and CNS functionsView study →}. Its own literature is thin and preclinical, with a single genuinely ginkgolide-C-specific efficacy signal: in-vitro anti-adipogenic activity via AMPK.

1. Anti-adipogenic / metabolic

The one genuinely ginkgolide-C-specific efficacy signal, and so the page’s distinctive hook. In differentiating 3T3-L1 adipocytes, ginkgolide C suppressed lipid accumulation, downregulated PPARγ and C/EBPα, raised the lipolytic enzymes ATGL/HSL, and increased AMPK phosphorylation (with SIRT1 implicated via compound-C blockade) ^{1Reference 1Liou CJ et al. · 2015Ginkgolide C suppresses adipogenesis in 3T3-L1 adipocytes via the AMPK signalling pathwayView study →}.

Gap: a single in-vitro cell-line study in a low-tier journal, with no animal or human confirmation — hypothesis-generating only ^{1Reference 1Liou CJ et al. · 2015Ginkgolide C suppresses adipogenesis in 3T3-L1 adipocytes via the AMPK signalling pathwayView study →}.

2. PAF antagonism (anti-platelet)

Ginkgolide C is a genuine but weak PAF antagonist — roughly 25× less potent than ginkgolide B, a difference attributed to its extra 7β-OH; SAR work on 7-substituted ginkgolides confirms the 7-position governs PAF potency ^{3Reference 3Strømgaard K et al. · 2003Preparation of 7-substituted ginkgolide derivatives: potent platelet-activating-factor receptor antagonistsView study →}. In human plasma its trilactone form (IC₅₀ ~8.7 µM) loses further activity on carboxylation (IC₅₀ → ~46 µM) ^{2Reference 2Chen F et al. · 2018Human pharmacokinetics of ginkgo terpene lactones and the impact of carboxylation in blood on their PAF-antagonistic activityView study →}.

Gap: this is the class mechanism, not an isolate indication — there is no isolated-ginkgolide-C anti-platelet outcome study, and its weak potency plus poor absorption make its contribution small ^{2,3Reference 2Chen F et al. · 2018Human pharmacokinetics of ginkgo terpene lactones and the impact of carboxylation in blood on their PAF-antagonistic activityView study →Reference 3Strømgaard K et al. · 2003Preparation of 7-substituted ginkgolide derivatives: potent platelet-activating-factor receptor antagonistsView study →}.

3. Glycinergic / CNS (mechanistic)

Ginkgolides are non-competitive glycine-receptor (and GABA-gated Cl⁻ channel) antagonists; ginkgolide C is roughly as potent as B at the glycine receptor (IC₅₀ ≈ 0.27 µM for both) ^{4Reference 4Chatterjee SS et al. · 2003Structure-activity studies with Ginkgo biloba extract constituents as receptor-gated chloride-channel blockers and modulatorsView study →}.

Gap: this is a receptor-blocking property, not a demonstrated therapeutic effect, and it is likely irrelevant at achievable brain levels given the ginkgolides’ limited, efflux-dominated BBB entry ^{4,5Reference 4Chatterjee SS et al. · 2003Structure-activity studies with Ginkgo biloba extract constituents as receptor-gated chloride-channel blockers and modulatorsView study →Reference 5Rangel-Ordóñez L et al. · 2011AnimalPlasma and brain levels of terpene trilactones in rats after an oral single dose of standardised Ginkgo biloba extract EGb 761View study →}.

Mechanisms

Target / pathway	Effect	Relevant to
PAF receptor (PAFR)	selective antagonist, ~25× weaker than ginkgolide B (7β-OH penalty); further attenuated by plasma carboxylation	anti-platelet, anti-inflammatory
AMPK → ACC / PPARγ / C-EBPα / SIRT1	↑ AMPK-P, ↓ lipogenic TFs, ↑ ATGL/HSL lipolysis (in-vitro 3T3-L1)	anti-adipogenic / metabolic
Glycine receptor (& GABA-A-gated Cl⁻ channel)	non-competitive pore antagonist (IC₅₀ ≈ 0.27 µM)	CNS/glycinergic (mechanistic only)

Pharmacokinetics

Ginkgolide C is a cage diterpene trilactone (C₂₀H₂₄O₁₁). It is the worst-absorbed of the ginkgolides: human data show apparent oral bioavailability of only 6–15% for ginkgolides C and J, versus >100% for A and B ^{2Reference 2Chen F et al. · 2018Human pharmacokinetics of ginkgo terpene lactones and the impact of carboxylation in blood on their PAF-antagonistic activityView study →}. Terminal half-life is ~4–7 h with predominantly renal (glomerular-filtration) excretion, and the lactone ring hydrolyses/carboxylates in blood — lowering both exposure and PAF activity ^{2Reference 2Chen F et al. · 2018Human pharmacokinetics of ginkgo terpene lactones and the impact of carboxylation in blood on their PAF-antagonistic activityView study →}. BBB penetration of the ginkgolides is limited and efflux-dominated, so the CNS relevance of its glycine/PAF activity is questionable ^{5Reference 5Rangel-Ordóñez L et al. · 2011AnimalPlasma and brain levels of terpene trilactones in rats after an oral single dose of standardised Ginkgo biloba extract EGb 761View study →}. Net: a minor, poorly-absorbed congener.

Clinical trials

There are no trials of isolated ginkgolide C. Ginkgo’s human evidence rests on the standardised EGb 761 extract; the ginkgolide-class human data (ischemic stroke) come from an injectable ginkgolide mixture, not this isolate. Human PK for ginkgolide C exists only as part of terpene-lactone profiling after extract dosing ^{2Reference 2Chen F et al. · 2018Human pharmacokinetics of ginkgo terpene lactones and the impact of carboxylation in blood on their PAF-antagonistic activityView study →}.

Last checked: July 2026.

Toxicity & Safety

Ginkgolide C carries a low flag: no isolate toxicology signals, and at the sub-percent levels present in standardised extracts the ginkgolides are well tolerated. The only practical caution is class-level and mechanism-based — PAF antagonism may add to antiplatelet/anticoagulant drugs (bleeding risk) — though ginkgolide C’s contribution is small given its weak PAF potency and poor absorption. It is not to be confused with the allergenic ginkgolic acids.

Pregnancy & lactation

Insufficient data — avoid the isolate. There are no reproductive-toxicity data on ginkgolide C, and the theoretical antiplatelet action plus the absence of safety data warrant avoidance in pregnancy and lactation (consistent with the ginkgo-extract precaution around bleeding and labour).

Dosage

There is no established human dose for isolated ginkgolide C, and none should be implied. It occurs only as a minor fraction of the ~5–7% terpene-trilactone content of standardised EGb 761 leaf extract (typically dosed 120–240 mg extract/day); all efficacy figures above are in-vitro concentrations, not doses.

References