Ginkgolide C

Evid Based Complement Alternat Med. 2015; 2015: 298635.

Ginkgolide C Suppresses Adipogenesis in 3T3-L1 Adipocytes via the AMPK Signaling Pathway[Pubmed: 26413119]

Ginkgolide C, isolated from Ginkgo biloba leaves, is a flavone reported to have multiple biological functions, from decreased platelet aggregation to ameliorating Alzheimer disease. The study aim was to evaluate the antiadipogenic effect of Ginkgolide C in 3T3-L1 adipocytes.
METHODS AND RESULTS:
Ginkgolide C was used to treat differentiated 3T3-L1 cells. Cell supernatant was collected to assay glycerol release, and cells were lysed to measure protein and gene expression related to adipogenesis and lipolysis by western blot and real-time PCR, respectively. Ginkgolide C significantly suppressed lipid accumulation in differentiated adipocytes. It also decreased adipogenesis-related transcription factor expression, including peroxisome proliferator-activated receptor and CCAAT/enhancer-binding protein. Furthermore, Ginkgolide C enhanced adipose triglyceride lipase and hormone-sensitive lipase production for lipolysis and increased phosphorylation of AMP-activated protein kinase (AMPK), resulting in decreased activity of acetyl-CoA carboxylase for fatty acid synthesis. In coculture with an AMPK inhibitor (compound C), Ginkgolide C also improved activation of sirtuin 1 and phosphorylation of AMPK in differentiated 3T3-L1 cells.
CONCLUSIONS:
The results suggest that Ginkgolide C is an effective flavone for increasing lipolysis and inhibiting adipogenesis in adipocytes through the activated AMPK pathway.

Proceeding of Clinical Medicine, 2013, 22(7):524-6.

Effect of Ginkgolide C in cardiac function of rats in the body.[Reference: WebLink]

To study the effect of Ginkgolide C(GC) in cardiac function of rats in the body.
METHODS AND RESULTS:
: Normal rats after anesthetized,inserted the intubate which connecting the pressure transducer into left ventricular from the right common carotid artery,then detected the cardiac function by the PowerLab biological signal acquisition system.Gave each of saline,1‰dimethyl sulfoxide(DMSO),100 μ mol / L GC,1 000 μ mol / L GC 1ml from the jugular vein,detected the cardiac function before and after administration by continuous recording the left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of pressure increase in systole phase(+dp / dtmax),maximal rate of pressure decrease in diastole phase(-dp / dtmax) and heart rate(HR).Compared with normal conditions,when given 100 μ mol / L GC,there are no significant effect on cardiac function;when given 1 000 μ mol / L GC,it showed inotropic activity by increasing △LVP,+dp / dtmax,-dp / dtmax significantly,but had no significant effect on HR.
CONCLUSIONS:
Ginkgolide C can increase△LVP significantly,enhances the myocardial systolic and diastolic function of rats,but has no significant effect on HR while it shows inotropic activity.

Biol Pharm Bull. 2007 Dec;30(12):2340-4.

Ginkgolide C inhibits platelet aggregation in cAMP- and cGMP-dependent manner by activating MMP-9.[Pubmed: 18057723 ]

METHODS AND RESULTS:
In this report, we investigated the effect of Ginkgolide C (GC) from Ginkgo biloba leaves in collagen (10 mug/ml)-stimulated platelet aggregation. It has been known that matrix metalloproteinase-9 (MMP-9) is released from human platelets, and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GC to form an activated MMP-9 (86-kDa) on gelatinolytic activities. And then, GC dose-dependently inhibited platelet aggregation, intracellular Ca(2+) mobilization, and thromboxane A(2) (TXA(2)) formation in collagen-stimulated platelets. In addition, GC significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have an anti-platelet function in both resting and collagen-stimulated platelets. Therefore, we demonstrate that the inhibitory effect of GC on platelet aggregation might be involved into the following pathways. GC may increase intracellular cAMP and cGMP production and MMP-9 activity, inhibit intracellular Ca(2+) mobilization and TXA(2) production, thereby leading to inhibition of platelet aggregation.
CONCLUSIONS:
These results strongly indicate that GC is a potent inhibitor of collagen-stimulated platelet aggregation. It may be a suitable tool for a negative regulator during platelet activation.

Acta Crystallogr C. 2002 Mar;58(Pt 3):o195-8.

Three ginkgolide hydrates from Ginkgo biloba L.: ginkgolide A monohydrate, ginkgolide C sesquihydrate and ginkgolide J dihydrate, all determined at 120 K.[Pubmed: 11870327]

A low-temperature structure of ginkgolide A monohydrate, (1R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)-3-(1,1-dimethylethyl)-hexahydro-4,7b-dihydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione monohydrate, C(20)H(24)O(9) x H(2)O, obtained from Mo K alpha data, is a factor of three more precise than the previous room-temperature determination.
METHODS AND RESULTS:
A refinement of the ginkgolide A monohydrate structure with Cu K alpha data has allowed the assignment of the absolute configuration of the series of compounds. Ginkgolide C sesquihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11S,11aR)-3-(1,1-dimethylethyl)-hexahydro-2,4,7b,11-tetrahydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione sesquihydrate, C(20)H(24)O(11) x 1.5H(2)O, has two independent diterpene molecules, both of which exhibit intramolecular hydrogen bonding between OH groups. Ginkgolide J dihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)-3-(1,1-dimethylethyl)-hexahydro-2,4,7b-trihydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione dihydrate, C(20)H(24)O(10) x 2H(2)O, has the same basic skeleton as the other ginkgolides, with its three OH groups having the same configurations as those in Ginkgolide C.
CONCLUSIONS:
The conformations of the six five-membered rings are quite similar across ginkgolides A-C and J, except for the A and F rings of ginkgolide A.