Herba Houttuyniae Extract Benefits Hyperlipidemic Mice via Activation of the AMPK/PGC-1α/Nrf2 Cascade.

Ke Cao,Weiqiang Lv,Zhihui Feng,Weijin Zang,Xuyun Liu,Kexin Wang,Yingying Fan,Lianxi Xing,Jianshu Liu,Jiankang Liu

doi:10.3390/nu12010164

Abstract

Hyperlipidemia is associated with metabolic disorders, but the detailed mechanisms and related interventions remain largely unclear. As a functional food in Asian diets, Herba houttuyniae has been reported to have beneficial effects on health. The present research was to investigate the protective effects of Herba houttuyniae aqueous extract (HAE) on hyperlipidemia-induced liver and heart impairments and its potential mechanisms. Male C57BL/6J mice were administered with 200 or 400 mg/kg/day HAE for 9 days, followed by intraperitoneal injection with 0.5 g/kg poloxamer 407 to induce acute hyperlipidemia. HAE treatment significantly attenuated excessive serum lipids and tissue damage markers, prevented hepatic lipid deposition, improved cardiac remodeling, and ameliorated hepatic and cardiac oxidative stress induced by hyperlipidemia. More importantly, NF-E2 related factor (Nrf2)-mediated antioxidant and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathways as well as mitochondrial complex activities were downregulated in the hyperlipidemic mouse livers and hearts, which may be attributable to the loss of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity: all of these changes were reversed by HAE supplementation. Our findings link the AMPK/PGC-1α/Nrf2 cascade to hyperlipidemia-induced liver and heart impairments and demonstrate the protective effect of HAE as an AMPK activator in the prevention of hyperlipidemia-related diseases.

Highlights

Metabolic syndrome (MS) has become one of the major diseases affecting human health.Hyperlipidemia, hyperglycemia, and hypertension are considered to be major symptoms and central risk factors of MS [1,2,3]
The levels of serum cholesterol low-density lipoprotein (c-LDL), free fatty acids (FFAs), and MDA and the activity of serum lactate dehydrogenase (LDH) were noticeably increased by poloxamer 407 (P407), and the houttuyniae aqueous extract (HAE) treatment significantly lowered c-LDL, FFA, and MDA content as well as LDH activity (Figure 1C–F)
We found that P407 induced significant increases in cardiac IVSd, interventricular septum thickness (IVSs), and LVPWd and decreases in LVIDd, LVIDs, left ventricle (LV)-Vol-d, and LV-Vol-s, indicating cardiac morphological changes caused by hyperlipidemia, and some of these changes were effectively attenuated by HAE

Summary

Introduction

Metabolic syndrome (MS) has become one of the major diseases affecting human health.Hyperlipidemia, hyperglycemia, and hypertension are considered to be major symptoms and central risk factors of MS [1,2,3]. The detailed mechanisms by which hyperlipidemia contributes to metabolic diseases remain unclear, evidence has suggested that, due to hyperlipidemia, excessive triglycerides (TG) and cholesterol (TC) are deposited in blood vessels and circulate to other organs, possibly leading to lipid metabolic disorders and tissue impairment and eventually increasing the risk of MS [7]. Apart from excessive lipid deposition, oxidative stress [8,9] and mitochondrial dysfunction [10,11] have been demonstrated to be closely linked to hyperlipidemia-related tissue impairment. Investigations have shown that excessive free fatty acids (FFAs) can amplify reactive oxygen species (ROS) generation, leading to increased oxidative stress and decreased mitochondrial oxidative capacity, which eventually causes morphological and functional changes in tissues [8,12]

Methods

Results

Discussion

Conclusion