Paeoniflorin alleviates liver injury in hypercholesterolemic rats through the ROCK/AMPK pathway

Abstract

Paeoniflorin (PF) is the main active component in Paeonia lactiflora Pall, and it has multiple effects. However, the precise mechanism of PF in hypercholesterolemia is unclear. In this study, rats were either fed a high-cholesterol diet (HCD) for 4 weeks to establish the hypercholesterolemic model or administered normal saline or PF (20 mg/kg/day). PF significantly reduced liver weight and the liver index. PF reduced hepatic lipid deposition and inflammation, improved serum lipid metabolism, and significantly inhibited serum and hepatic oxidative stress and the inflammatory response. PF treatment caused a marked decrease in the phosphorylated myosin phosphatase target subunit (p-MYPT)-1, nuclear sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS) levels, and an increase in the low-density lipoprotein receptor (LDLR) and phosphorylated-AMP-activated protein kinase (p-AMPK). Thus, PF could alleviate liver injury in hypercholesterolemic rats, and the specific mechanism may be related to the antioxidant, anti-inflammatory properties, and ROCK/AMPK/SREBP-1c signaling pathway.

Consequences of adiponectin deficiency: Can they be related to the pathophysiology of laminitis?

“…In the same model, treatment with pioglitazone, a drug that upregulates adiponectin production, improved survival and inhibited the increase in pro‐inflammatory cytokines and chemokines seen in this model 8 . Similarly, in rats undergoing caecal ligation and puncture to induce sepsis, exogenously administered adiponectin alleviated endothelial cell apoptosis and oxidative stress and inhibited the hypercoagulable state from being expressed in this model 9 and inhibited liver injury and hepatocyte apoptosis 10 . In human patients, higher pre‐septic plasma adiponectin concentration was associated with improved survival 11 as was a greater rate of increase in plasma adiponectin concentration in the first 7 days following hospitalisation 12 .…”

“…8 Similarly, in rats undergoing caecal ligation and puncture to induce sepsis, exogenously administered adiponectin alleviated endothelial cell apoptosis and oxidative stress and inhibited the hypercoagulable state from being expressed in this model 9 and inhibited liver injury and hepatocyte apoptosis. 10 In human patients, higher pre-septic plasma adiponectin concentration was associated with improved survival 11 as was a greater rate of increase in plasma adiponectin concentration in the first 7 days following hospitalisation. 12 Thus, it appears that further investigation of the protective role of adiponectin in equine SIRS is warranted.…”

Protective effect of omega-3 polyunsaturated fatty acids on sepsis via the AMPK/mTOR pathway

“… 2020 ; Liu, Xu, et al. 2020 ). Meanwhile, DHA, a component of ω-3 PUFAs, was found to regulate the AMPK/mTOR signaling pathway in cancer cells (Jing et al.…”

Protective effects of paeoniflorin on cardiovascular diseases: A pharmacological and mechanistic overview

“…Consequently, how to further develop paeoniflorin, improve its bioavailability and extend its medicinal applications is the next focus in pharmaceutics. In regards to safety, certain basic experiments have revealed hepatoprotective effects of paeoniflorin, such as its ability to interfere with bile acid metabolism and pivotal inflammation-related targets, as well as its capacity to ameliorate cholestatic liver injury ( Wei et al, 2020 ; Liu et al, 2022 ). Despite this, whether paeoniflorin could cause liver injury has not been declared yet.…”