Activation of AMPK Entails the Protective Effect of Royal Jelly against High-Fat-Diet-Induced Hyperglycemia, Hyperlipidemia, and Non-Alcoholic Fatty Liver Disease in Rats

Abstract

This study examined the mechanism underlying the protective effect of royal jelly (RJ) against high-fat-diet (HFD)-mediated non-alcoholic liver disease (NAFLD) in rats. Adult male rats were divided into five groups (n = 8 each): control fed a standard diet, control + RJ (300 mg/kg), HFD, HFD + RJ (300 mg/kg), and HFD + RJ + CC (0.2 mg/kg). The treatment with RJ reduced weight gain, increased fat pads, and attenuated fasting hyperglycemia, hyperinsulinemia, and glucose tolerance in the HFD-fed rats. It also reduced the serum levels of liver function enzymes, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin but significantly increased the serum levels of adiponectin. In addition, and with no effect on lipid excretion in stool, RJ significantly decreased the hepatic mRNA expression of SREBP1, serum, hepatic cholesterol, and triglycerides but increased hepatic mRNA levels of PPARα. Furthermore, RJ reduced the hepatic levels of TNF-α, IL-6, and malondialdehyde (MDA) in the livers of these rats. Of note, with no effect on the mRNA levels of AMPK, RJ stimulated the phosphorylation of AMPK and increased the levels of superoxide dismutase (SOD) and total glutathione (GSH) in the livers of the control and HFD-fed rats. In conclusion, RJ attenuates NAFLD via its antioxidant potential and adiponectin-independent activation of liver AMPK.

The Pharmacological Efficacy of Baicalin in Inflammatory Diseases

“…TNF-α is an important cytokine involved in metabolic diseases such as obesity, insulin resistance, hyperlipidemia, and NAFLD [59]. The production of TNF-α in the process of liver injury causes the release of IL-1β and IL-6, which mediates inflammatory response [60].…”

Spirulina platensis peptide-loaded nanoliposomes alleviate hepatic lipid accumulation in Male Wistar Rats by influencing redox homeostasis and lipid metabolism via the AMPK signaling pathway

“…Subsequently, an excess of endogenous reactive species such as reactive oxygen species (ROS) and in ammatory signaling cascade in the liver occurs, which leads to hepatocyte injury. A concurrent increase in the secretion of in ammatory cytokines, abnormal liver enzymes, and cellular death is also observed ( Signi cant evidence in animal and preclinical studies has indicated that 5′AMP-activated protein kinase (AMPK) is an effective treatment target for NAFLD (Felemban et al, 2023;Smith et al, 2016). AMPK activation levels are markedly decreased in animals and humans with NAFLD.…”

“…AMPK activation levels are markedly decreased in animals and humans with NAFLD. Similarly, activating AMPK through genetic modi cation, exercise, and mitochondria-inhibiting compounds (e.g., metformin) provided protective effects (Fang et al, 2022;Felemban et al, 2023;Strzyz, 2020). AMPK is the main regulator of metabolism, which may regulate food intake, whole-body expenditure, and glucose and lipid hemostasis by affecting various tissues including the hypothalamus, liver, pancreas, muscles, and adipose tissue.…”

“…AMPK is primarily triggered by energy depletion (low ATP) and glucose deprivation to enhance ATP generation by boosting catabolic pathways and inhibiting anabolic pathways (Zhao et al, 2020). AMPK provides protection by improving peripheral insulin sensitivity, suppressing de novo lipogenesis and lipogenic genes (e.g., SREBP-1c and acetyl-CoA carboxylase [ACC]), stimulating adipose tissue and liver fatty acid oxidation, as well as boosting mitochondrial function (Felemban et al, 2023;Garcia et al, 2019). Thus, developing safe and effective drugs that act on AMPK is critical in the treatment of NAFLD.…”

Natural Products and Health

“…Histological examination revealed improved liver structure with fewer fat vacuoles in RJ-treated rats. However, when RJ was co-administered with an AMPK inhibitor, compound C (CC), these beneficial effects were attenuated [26].…”