Ginkgetin, a biflavone from Ginkgo biloba leaves, prevents adipogenesis through STAT5-mediated PPARγ and C/EBPα regulation

Cho, Young‐Lai; Park, Jong‐Gil; Kang, Hyo Jin; Kim, Wooil; Cho, Min Ji; Jang, Ju-Hong; Kwon, Min‐Gi; Kim, Sungsik; Lee, Jangwook; Kim, Yeon‐Gu; Park, Young-Jun; Kim, Won Kon; Bae, Kwang‐Hee; Kwon, Byoung‐Mog; Chung, Sang J.; Min, Jeong‐Ki

doi:10.1016/j.phrs.2018.11.027

Cited by 31 publications

(17 citation statements)

References 65 publications

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“…Furthermore, 3T3-L1 cells subjected to hypoxia and incubated with bilobalide showed reduced pro-inflammatory biomarkers and improved insulin sensitivity (48). Similarly, ginkgetin, a biflavone from Ginkgo biloba , has been described as a STAT5 inhibitor, blocking the differentiation of pre-adipocytes into adipocytes harvested from high-fat diet-induced obese mice (49). Moreover, OP9 cells, which differentiate into adipocytes in vitro , showed reduced adipogenesis, increased HSL and decreased FAS expression upon treatment with quercetin (50).…”

Section: Discussionmentioning

confidence: 99%

Potential Anti-obesogenic Effects of Ginkgo biloba Observed in Epididymal White Adipose Tissue of Obese Rats

et al. 2019

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Exacerbated expansion of adipose tissue seen in diet-induced obesity leads to endocrine dysfunction and disturbance in adipokine secretion, with such abnormal profile positively associated with type 2 diabetes and other mild chronic inflammatory conditions. Ginkgo biloba extract (GbE), a mixture of polyphenols with antioxidant properties, has been recently investigated in a variety of experimental models of endocrine dysfunction, with several potentially beneficial effects identified, including improvement in insulin sensitivity in obese rats, and reduction of weight gain in ovariectomy-induced obesity and diet-induced obesity. The aim of this study was to investigate in high fat diet-induced obese male rats the effects of GbE supplementation for 2 weeks on adipocyte volume and adipose tissue lipid accumulation. GbE supplementation was effective in reducing energy intake in obese rats compared to the saline-treated placebo group. Epididymal adipocyte volume was reduced in GbE-supplemented rats, as were epididymal [1- 14 C]-acetate incorporation into fatty acids, perilipin ( Plin 1 ) and fatty acid synthase ( Fasn ) mRNA, and FAS protein levels. Adipocyte hypertrophy in obesity is associated with insulin resistance, and in the present study we observed a reduction in the adipocyte volume of GbE-supplemented obese rats to dimensions equivalent to adipocytes from non-obese rats. GbE supplementation significantly reduced acetate accumulation and tended to reduce [ 3 H]-oleate incorporation, into epididymal adipose tissue, suggesting a potentially anti-obesogenic effect in longer term therapies. Further studies that investigate the effects of GbE supplementation in other experimental models are required to fully elucidate its suggested beneficial effects on mild chronic inflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

Potential Anti-obesogenic Effects of Ginkgo biloba Observed in Epididymal White Adipose Tissue of Obese Rats

et al. 2019

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“…Both the ginkgolide C and bilobalides were described to modulate proteins involved in lipolysis and adipogenesis in the 3T3-L1 adipose cell line [37,38]. A similar anti-adipogenic effect was observed in the same cell line with the bi-flavone ginkgetin [39], while the improvement of brain metabolism was observed after the treatment with ginkgolide B [40].…”

Section: Discussionmentioning

confidence: 90%

A Single Dose of Ginkgo biloba Extract Induces Gene Expression of Hypothalamic Anorexigenic Effectors in Male Rats

et al. 2021

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Previous studies have shown that Ginkgo biloba extract (GbE) reduces food intake and body mass gain and regulates proteins related to lipid metabolism in obese rats. In ovariectomized rats, GbE restored the hippocampal and hypothalamic serotonergic system activity, favoring the spontaneous feeding decrement. Considering the promising hypophagic effect of GbE, this study aimed to investigate the effect of a single acute dose on hypothalamic pathways that regulate feeding behavior in male rats. Four-month-old Wistar male rats received either a single acute oral GbE dose (500 mg/kg) or vehicle. Food intake and body mass were measured after 1, 4, 12, and 24 h. Rats were euthanized, and hypothalami were removed for mRNA quantification of anorexigenic (POMC/CART) and orexigenic (AgRP/NPY) neuropeptides, leptin/serotonin receptors (5HT1A, 5HT1B, 5HT2C), and serotonin transporters. We also investigated POMC, 5-HT1B, and 5-HT2C protein levels. A single acute GbE dose induced the hypothalamic POMC, CART, and 5-HT2C gene expression but failed to modify orexigenic effectors. No alterations in food intake, body mass, and hypothalamic protein levels were observed. In summary, the present findings demonstrate the rapid stimulation of pivotal hypothalamic anorexigenic pathways in response to a single GbE administration, reinforcing the GbE hypophagic activity. However, more studies are necessary to evaluate its potential as an appetite modulator.

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“…GK-treated preadipocytes inhibited the expression of peroxisomal proliferation-activated receptor γ (PPARγ) and CCAAT/ enhancer binding protein α (C/EBPα) by inactivating STAT5. The above results indicate that GK can be used as anti-obesity drugs (Cho et al, 2019). GK mediates the dephosphorylation of STAT3 in Tyr705 and prevents it from entering the nucleus, thereby inhibiting STAT3-mediated gene expression, such as antiapoptotic Bcl-XL protein, thereby inhibiting the proliferation of prostate cancer DU-145 cells (Jeon et al, 2015).…”

Section: Biflavones Ginkgetinmentioning

confidence: 90%

Pharmacological Effects of Polyphenol Phytochemicals on the JAK-STAT Signaling Pathway

Yin

Wang

et al. 2021

Front. Pharmacol.

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The JAK-STAT signaling pathway is a common pathway of many cytokine signal transductions, closely related to cell proliferation, apoptosis, differentiation, and inflammatory response. It is essential for inhibiting the inflammatory response, initiating innate immunity, and coordinating adaptive immune mechanisms. Owing to the nature of this pathway and its potential cross-epitopes with multiple alternative pathways, the long-term efficacy of monotherapy-based adaptive targeting therapy is limited, and the majority of drugs targeting STATs are still in the preclinical phase. Meanwhile, curcumin, quercetin, and several kinds of plant polyphenol chemicals play roles in multiple sites of the JAK-STAT pathway to suppress abnormal activation. Polyphenol compounds have shown remarkable effects by acting on the JAK-STAT pathway in anti-inflammatory, antitumor, and cardiovascular disease control. This review summarizes the pharmacological effects of more than 20 kinds of phytochemicals on JAK-STAT signaling pathway according to the chemical structure of polyphenolic phytochemicals.

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Ginkgetin, a biflavone from Ginkgo biloba leaves, prevents adipogenesis through STAT5-mediated PPARγ and C/EBPα regulation

Cited by 31 publications

References 65 publications

Potential Anti-obesogenic Effects of Ginkgo biloba Observed in Epididymal White Adipose Tissue of Obese Rats

Potential Anti-obesogenic Effects of Ginkgo biloba Observed in Epididymal White Adipose Tissue of Obese Rats

A Single Dose of Ginkgo biloba Extract Induces Gene Expression of Hypothalamic Anorexigenic Effectors in Male Rats

Pharmacological Effects of Polyphenol Phytochemicals on the JAK-STAT Signaling Pathway

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