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

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.

Puerarin Attenuates Oxidative Stress and Ferroptosis via AMPK/PGC1α/Nrf2 Pathway after Subarachnoid Hemorrhage in Rats

“…Huang et al [ 51 ] showed that promoting AMPK phosphorylation and upregulation of PGC1α expression had a neuroprotective role by attenuating oxidative stress and neuronal apoptosis in a hypoxic–ischemic encephalopathy rat model. As a master antioxidant regulator, Nrf2 was regulated by the AMPK/PGC1α-signaling pathway [ 52 , 53 ]. Recent studies have reported that activation of AMPK exerted a protective effect in ferroptosis-associated renal ischemia/reperfusion injury [ 20 ].…”

Hyperoside and Quercitrin in Houttuynia cordata Extract Attenuate UVB-Induced Human Keratinocyte Cell Damage and Oxidative Stress via Modulation of MAPKs and Akt Signaling Pathway

“…Furthermore, the extracts have been found to significantly reduce NO, PGE-2, TNF-α, and IL-6 levels [ 20 ]. In addition, H. cordata extract inhibited the generation of ROS in TNF-α stimulated human keratinocyte cells and activated Nrf2, along with the subsequent induction of antioxidative enzymes [ 21 , 22 ]. H. cordata contains a wide range of polyphenols, such as rutin, quercetin, hyperoside, quercitrin, and chlorogenic acid, which are known to be responsible for its pharmacological activity, including its anti-inflammatory and antioxidative properties [ 17 , 19 ].…”

The Role of NRF2 in Obesity-Associated Cardiovascular Risk Factors

“…Furthermore, NRF2 and PPARG were downregulated in hyperlipidemic mouse livers and hearts, which may be attributable to the loss of PRKAA2 activity. All of these changes were reversed by Herba houttuyniae supplementation [ 90 ]. Curcumin increases HO-1 via activation of NRF2, inducing to attenuation of HFD-induced elevations of malonedialdeyde (MDA) and ROS in skeletal muscle but not in adipose tissue or liver [ 91 , 92 ].…”

“…Several pieces of evidence showed that the main source of ROS is vascular wall, mainly through mitochondrial electron transport chain activity, NOX1, xanthine oxidase, and uncoupled nitric oxide synthase (NOS) (reviewed in [ 17 ]). Vascular cells produce ROS when stimulated by cytokines, ANG II, EDN1, aldosterone, and PDGF, favoring oxidative modifications of redox-sensitive proteins, such as calcium-calmodulin kinase, ryanodine receptor, and sarcoplasmic reticulum ATPase, thus altering their conformation, stability, activity, and ability to react with other proteins and modulate vascular function (reviewed in [ 90 ]). ROS generation is important to preserve endothelial and vascular smooth muscle cells function, vascular tone, responses related to inflammation process, cell growth, proliferation, apoptosis, and angiogenesis (reviewed in [ 112 ]).…”