Phanginin A

Phanginin A is a potent and orally active SIK1 (salt-induced kinase 1) activator. Phanginin A inhibited gluconeogenesis. Phanginin A increases the expression of p-SIK1 and decreases the expression of p-CREB. Phanginin A reduces blood glucose levels and improves glucose tolerance and dyslipidemia. Phanginin A has the potential for the research of type 2 diabetes[1].

Research Areas >> Metabolic Disease

Signaling Pathways >> Immunology/Inflammation >> Salt-inducible Kinase (SIK)

SIK1

Phanginin A (2.5, 5, 10 µM) 以剂量依赖性方式抑制原代小鼠肝细胞中的糖异生[1]。 Phanginin A (5, 10 µM) 降低 G6P 和 PEPCK 的 mRNA 表达，并减少细胞内 cAMP 的积累[1]。 Phanginin A (5, 10 µM; 0-120 min) 以时间和剂量依赖的方式抑制原代小鼠肝细胞中 CREB 磷酸化的表达[1]。 Phanginin A (2.5, 5, 10 µM; 0-120 min) 以时间和剂量依赖的方式增加原代小鼠肝细胞中 p-SIK1 的表达[1]。 Phanginin A (5, 10 µM) 增加 PDE4 活性[1]。 RT-PCR[1] Cell Line: Primary mouse hepatocytes Concentration: 5, 10 µM Incubation Time: Result: Significantly decreased PEPCK mRNA expression by 25% and 43% under basal conditions and 45% and 67% under forskolin-stimulated conditions, The G6P mRNA expression was also significantly reduced, with 5 and 10 μM of phanginin A resulting in a decrease of 30% and 46% under basal conditions and 38% and 57% under forskolin-stimulated conditions, respectively. Western Blot Analysis[1] Cell Line: Primary mouse hepatocytes Concentration: 0-120 min Incubation Time: Result: Inhibited CREB phosphorylation in a time and dose-dependent manner.

Phanginin A (100 mg/kg; p.o.; once) 在 2 型糖尿病 ob/ob 小鼠中表现出抗糖异生活性[1]。 Phanginin A (100 mg/kg; p.o.; once daily for 26 days) 改善 ob/ob 小鼠的代谢紊乱[1]。 Animal Model: Type 2 diabetic ob/ob mice[1] Dosage: 100 mg/kg Administration: P.o.; once Result: Significantly reduced the blood glucose, increased the phosphorylation of SIK1 in the liver by 119%, PDE4 activity in the liver was elevated by 74%, decreased in the cAMP concentration along with a 46% decrease in the CREB phosphorylation level in the liver, decreased the mRNA levels of PEPCK and G6P. Animal Model: Male ob/ob mice[1] Dosage: 100 mg/kg Administration: P.o.; once daily for 26 days Result: Showed an average reduction rate of 29% and 32% in random and fast blood glucose, exhibited a marked improvement in glucose tolerance, significantly reduced by 20% in HbA1c level, showed no effect on food intake and body weight.

[1]. Liu S, et al. Activation of SIK1 by phanginin A inhibits hepatic gluconeogenesis by increasing PDE4 activity and suppressing the cAMP signaling pathway. Mol Metab. 2020 Nov;41:101045.