title: Timosaponin B-II Ameliorates Palmitate-Induced Insulin Resistance and Inflammation via IRS-1/PI3K/Akt and IKK/NF-[Formula: see text]B Pathways.
abstract: This study aimed to investigate the effect of timosaponin B-II (TB-II) on palmitate (PA)-induced insulin resistance and inflammation in HepG2 cells, and probe the potential mechanisms. TB-II, a main ingredient of the traditional Chinese medicine Anemarrhena asphodeloides Bunge, notably ameliorated PA-induced insulin resistance and inflammation, and significantly improved cell viability, decreased PA-induced production of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]) and interleukin-6 (IL-6) levels. Further, TB-II treatment notably decreased malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels, and improved superoxide dismutase (SOD) and nitric oxide (NO). TB-II also reduced HepG2 cells apoptosis. Insulin receptor substrate-1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/Akt and inhibitor of nuclear factor [Formula: see text]-B kinase (IKK)/NF-[Formula: see text]B pathways-related proteins, and IKK[Formula: see text], p65 phosphorylation, serine phosphorylation of insulin receptor substrate-1 (IRS-1) at S307, tyrosine phosphorylation of IRS-1, and Akt activation were determined by Western blot. Compared to model group, TB-II significantly downregulated the expression of p-NF-[Formula: see text]Bp65, p-IKK[Formula: see text], p-IRS-1, p-PI3K and p-Akt. TB-II is a promising potential agent for the management of palmitate-induced insulin resistance and inflammation, which might be via IR/IRS-1/PI3K/Akt and IKK/NF-[Formula: see text]B pathways.
authors.affiliation: * State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Yuan
authors.affiliation: † Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China.
authors.forename: Bao-Qin
authors.initials: BQ
authors.lastname: Lin
authors.affiliation: * State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: * State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Cui
authors.affiliation: * State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Shi-Xia
authors.initials: SX
authors.lastname: Ruan
authors.affiliation: * State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Zhong-Lin
authors.initials: ZL
authors.lastname: Yang
authors.affiliation: * State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: ‡ College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, P.R. China.
authors.forename: De
authors.initials: D
authors.lastname: Ji
mesh_terms: D056945:Hep G2 Cells; D006801:Humans; D051550:I-kappa B Kinase; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010168:Palmitates / Q000009:adverse effects*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013256:Steroids / Q000494:pharmacology*
chemical_list: D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D010168:Palmitates; D012503:Saponins; D013256:Steroids; C523027:timosaponin B-II; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase
keywords: IKK/NF-B; IR/IRS-1/PI3K/Akt; Inflammation; Insulin Resistance; Timosaponin B-II