Non-alcoholic fatty liver disease (NAFLD) is prevalent in the elderly population, and has symptoms ranging from liver steatosis to advanced fibrosis. Citrus peel extracts (CPEs) contain compounds that potentially improve dyslipidemia; however, the mechanism of action and effects on hepatic steatosis regulation remains unclear. Current study was aimed to investigate the protective effect of CPEs extracted through hot-air drying (CPEW) and freeze-drying (CPEF) and the underlying mechanism in a rat model of high-fat diet-induced NAFLD. The high-fat diet (HFD)-fed rats showed significant increase in total cholesterol, alanine aminotransferase (ALT), triglycerides, aspartate aminotransferase (AST), and lipid peroxidation compared to the normal chow-diet (NCD) group rats; but CPEW and CPEF limited this effect. CPEW and CPEF supplementation reduced both hepatocyte steatosis and fat accumulation involving the regulatory effect of mTORC1. Collectively, CPEW and CPEF protected deterioration of liver steatosis with AMPK activation and regulating ROS accumulation associated with interstitial disorders, which are also associated with endoplasmic reticulum (ER) redox. Thus, the application of CPEW and CPEF may lead to the development of novel therapeutic or preventive agents against NAFLD.

The recent discovery that the impairment of autophagic flux in non-alcoholic fatty liver disease (NAFLD) might be a strong determining factor in steatosis suggests the potential of therapeutic control of autophagic flux with natural agents in restoring NAFLD. We investigated the potential of Eucommia ulmoides leaf extract (EUL) to control dyslipidemia in NAFLD. EUL supplementation (200 mg/kg) promoted recovery from high fat diet (HFD)-induced lipid dysmetabolism. This hepatoprotective efficacy was accompanied by suppression of endoplasmic reticulum (ER) stress, enhancing lysosomal functions, and thereby increasing autophagic flux. We found a strong indication that inhibition of the mTOR-ER stress pathway was related to the enhanced autophagic flux. However, the direct antioxidative effect of EUL on cytoprotection cannot be ruled out as a significant contributing factor in NAFLD. Our findings will aid in further elucidating the mechanism of the anti-steatosis activity of EUL and highlight the therapeutic potential of EUL in the treatment of NAFLD.

This study was carried out to elucidate the antidiabetic effects of Gryllus bimaculatus powder using a streptozotocin (STZ)‐induced rat model of type I diabetes. Administration of the insect powder significantly rescued representative diabetes markers (i.e., insulin and C‐peptide) in STZ‐treated rats. Improved glucose tolerance test (GTT) and insulin tolerance test (ITT) results were also observed, indicating that Gryllus bimaculatus powder exerts antidiabetic effects. Gryllus bimaculatus powder administration rescued STZ‐induced alterations in both islet morphology and insulin staining patterns. The extract increased antiapoptotic Bcl2 expression and decreased proapoptotic Bax and active caspase 3 expressions. In addition, the Gryllus bimaculatus powder supplementation enhanced AKT/mTOR pathway, a key marker of the state of anabolic metabolism, and its downstream effector, mTOR. Collectively, our results suggest that Gryllus bimaculatus contributes to the maintenance of pancreatic β‐cell function and morphology against a diabetic state through the regulations against apoptosis and anabolic metabolism.

Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic–pituitary–gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na⁺ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.

In this study, we investigated the hepatoprotective properties of 3,5-dicaffeoylquinic acid (DQA), a polyphenolic compound from green coffee beans, against dimethylnitrosamine (DMN)-induced hepatic fibrosis rat models. DQA, up to 10 μM concentration, did not exhibit any cytotoxic effect on Chang liver cells and Huh7 cells. DMN-treated rats showed typical biological symptoms of hepatic fibrosis, i.e., loss of body weight and pathological elevation of serum biomarkers for hepatic function. However, oral administration of DQA recovered body weight, and maintained serum biochemical markers such as albumin, bilirubin, ALP, ALT and AST in the normal range. Notably, histological and western assay proved DQA significantly alleviated collagen accumulation (α-smooth muscle actin, alpha 1 collagen type I) in liver tissue. The upregulated tissue expression of erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) suggested DQA upregulated the representative antioxidant enzymes and ameliorated the progression of hepatic fibrosis in DMN-treated rats.

Thi Quy Nguyen, Thi Quynh Nhu Tran, Seon Hui Jang, Seon Ah Park, and Seong Kyu Han. Korean J Physiol Pharmacol -0001;0:. https://doi.org/10.4196/kjpp.25.039