Sesquiterpenoid bilobalide inhibits gastric carcinoma cell growth and induces apoptosis both in vitro and in vivo models.

Gastric carcinoma is one of the most aggressive types of cancer that ranks fifth among all cancer incidences and third in cancer mortality. As it exhibits a prolonged asymptomatic condition and high recurrence rate, it is a great challenge to treat gastric cancer. Traditional medicine that utilizes herbal phytochemicals to treat various diseases is a potent alternative for current allopathic treatment. Hence, we evaluated the potency of a phytochemical bilobalide for treating gastric cancer in in vitro and in vivo models. Bilobalide, a sesquiterpenoid, is present in the Ginkgo biloba plant that belongs to the family of Ginkgoaceae. The cytotoxicity effect of bilobalide was evaluated in both gastric cancer (AGS) cells and normal gastric epithelial cells. Apoptosis-inducing property of bilobalide against the AGS cell line was analyzed with different fluorescent staining techniques and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and cell cycle analysis was carried out by flow cytometry. The in vivo studies were assessed with N-methyl-N-nitrosourea (MNU)-induced gastric cancer in rats. Serum-specific gastric markers were quantified and histopathological analysis of stomach tissue was performed. The expression of target-signaling molecules was analyzed by a reverse-transcription polymerase chain reaction. The in vitro results proved that bilobalide effectively suppressed the AGS cell growth and induced cell death by nuclear damage and apoptosis induction. The bilobalide treatment effectively arrested the cell cycle of AGS cells via inhibiting the PI3K-signaling pathway. Our in vivo results also confirmed that the bilobalide persuasively inhibited the MNU-induced gastric carcinoma via inhibiting the thioredoxin-fold family proteins and inflammatory markers' expression. Overall, our results authentically prove that bilobalide possesses therapeutic potency to cure gastric carcinoma.

A new bilobalide isomer and two cis-coumaroylated flavonol glycosides from Ginkgo biloba leaves.

A new bilobalide isomer (1), together with two flavonol glycosides (2, 3), have been isolated and elucidated from the extract of Ginkgo biloba leaves. Significantly, 1 was a new sesquiterpene lactone with two lactone ring groups, both 2 and 3 were two flavonol glycosides with a same cis-coumaroylated fragment. Their chemical structures were elucidated by NMR and MS spectroscopic date and the absolute configuration of 1 was specific established by Cu-Kα X-ray crystallographic analyses. However, 1-3 showed no obvious anti-platelet aggregation activity.

Bilobalide Suppresses Adipogenesis in 3T3-L1 Adipocytes via the AMPK Signaling Pathway.

Bilobalide, the only sesquiterpene compound from Ginkgo biloba leaf, exhibits various beneficial pharmaceutical activities, such as antioxidant, anti-inflammation, and protective effects for the central nervous system. Several bioactive components extracted from Ginkgo biloba extract reportedly have the potential to attenuate lipid metabolism. However, the effect of bilobalide on lipid metabolism remains unclear. In this study, we used 3T3-L1 cells as the cell model to investigate the effect of bilobalide on adipogenesis. The results showed that bilobalide inhibited 3T3-L1 preadipocyte differentiation and intracellular lipid accumulation. Quantitative real-time PCR and western blotting results indicated that several specific adipogenic transcription factors and a few important adipogenesis-related genes were significantly down regulated on both mRNA and protein levels in bilobalide treatment groups. By contrast, the expression of some lipolytic genes, such as adipose triglyceride lipase, hormone-sensitive lipase (HSL), and carnitine palmitoyltransferase-1α, were all up-regulated by bilobalide treatment, and the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase 1, and HSL were stimulated. Furthermore, bilobalide treatment partially restored AMPK activity following its blockade by compound C (dorsomorphin). These results suggested that bilobalide inhibited adipogenesis and promoted lipolysis in 3T3-L1 cells by activating the AMPK signaling pathway.