Abstract
BackgroundObesity and its associated health conditions, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are worldwide health problems. It has been shown that insulin resistance is associated with increased hepatic lipid and causes hepatic steatosis through a myriad of mechanisms, including inflammatory signaling.MethodsHelminthostachys zeylanica (HZ) is used widely as a common herbal medicine to relieve fever symptoms and inflammatory diseases in Asia. In the present study, we evaluated whether HZ has therapeutic effects on obesity, NAFLD and insulin resistance. The protective effects of HZ extract were examined using free fatty acid-induced steatosis in human HuS-E/2 cells and a high-fat diet-induced NAFLD in mice.ResultsThe major components of the HZ extract are ugonins J and K, confirmed by HPLC. Incubation of human hepatocytes, HuS-E/2 cells, with palmitate markedly increased lipid accumulation and treatment with the HZ extract significantly decreased lipid deposition and facilitated AMPK and ACC activation. After 12 weeks of a high-fat diet with HZ extract treatment, the HFD mice were protected from hyperlipidemia and hyperglycemia. HZ extract prevented body weight gain, adipose tissue expansion and adipocyte hypertrophy in the HFD mice. In addition, fat accumulation was reduced in mice livers. Moreover, the insulin sensitivity-associated index, which evaluates insulin function, was also significantly restored.ConclusionsThese results suggest that HZ has a promising pharmacological effect on high-fat diet-induced obesity, hepatic steatosis and insulin resistance, which may have the potential for clinical application.
Highlights
Obesity and its associated health conditions, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are worldwide health problems
Because we found H. zeylanica (HZ) extract had an inhibitory effect on lipid deposition in human hepatocytes, possible molecular mechanisms were explored
To determine whether HZ extract increased levels of AMP-activated protein kinase (AMPK) and its activation, HuS-E/2 cells were incubated with 0.1 mM palmitate in the presence or absence of HZ extract and the expression of AMPK was assessed by western blotting
Summary
Obesity and its associated health conditions, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are worldwide health problems. It has been shown that insulin resistance is associated with increased hepatic lipid and causes hepatic steatosis through a myriad of mechanisms, including inflammatory signaling. HZ extract was considered to have neuroprotective activity because of its anti-inflammatory activity on human astrocytes, through bradykinin-induced MMP-9 signaling [13]. Another bioactive compound extracted from HZ, ugonin J, is considered to be a potential inhibitor of cell migration and neointima formation through MMP-2 and -9 pathways [14]. The therapeutic effect of HZ on abnormalities of lipid and glucose metabolism remains unclear
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