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Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway
Tang, D (Tang, Dan); Chen, QB (Chen, Qi-Bin); Xin, XL (Xin, Xue-Lei); Aisa, HA (Aisa, Haji-Akber); Xin, XL; Aisa, HA
2017
Source PublicationBIOMEDICINE & PHARMACOTHERAPY
Volume87Issue:3Pages:145-152
AbstractDiabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A-C (compounds A-C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A-C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A-C. The results suggested that compounds A-C improved glucose metabolism through promoting synthesis of glycogen. Expression of PTP1B protein was inhibited by compounds A-C in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by compounds A-C and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the insulin-mediated induction of insulin receptor substrate-1 (IRS-1) and glycogen synthase kinase-3 beta (GSK-3 beta) were also suppressed by wortmannin. Western blot results indicated that compounds A-C-induced IRS-1/ Akt activation was likely a consequence of PTP1B inhibition. Compounds A-C promoted glycogen synthesis through Akt-mediated GSK3 phosphorylation. Therefore, activation of PI3 K/Akt insulin signaling pathway and suppression of PTP1B is the molecular mechanism that contributes to the antidiabetic effect of compounds A-C in cellular models. The three alkaloids potentially serve as lead compounds for the development of antidiabetic drugs.
KeywordDiabetes Norditerpenoid Alkaloids Anti-diabetic Activity Glucose Metabolism Protein Tyrosine Phosphatase 1b Pi3k/akt Signaling Pathway
DOI10.1016/j.biopha.2016.12.058
Indexed BySCI
WOS IDWOS:000395525600016
Citation statistics
Cited Times:15[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/4747
Collection省部共建新疆特有药用资源利用重点实验室
Corresponding AuthorXin, XL; Aisa, HA
Affiliation1.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Key Lab Plant Resources & Chem Arid Zone, Urumqi 830011, Peoples R China
2.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, State Key Lab Basis Xinjiang Indigenous Med Plant, Urumqi 830011, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100039, Peoples R China
Recommended Citation
GB/T 7714
Tang, D ,Chen, QB ,Xin, XL ,et al. Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway[J]. BIOMEDICINE & PHARMACOTHERAPY,2017,87(3):145-152.
APA Tang, D ,Chen, QB ,Xin, XL ,Aisa, HA ,Xin, XL,&Aisa, HA.(2017).Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway.BIOMEDICINE & PHARMACOTHERAPY,87(3),145-152.
MLA Tang, D ,et al."Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway".BIOMEDICINE & PHARMACOTHERAPY 87.3(2017):145-152.
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