Chronic alcohol intake leads to alcoholic fatty liver. The pathogenesis of alcoholic fatty liver is related to abnormal lipid accumulation, oxidative stress, endotoxins, and cytokines. Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu island, Taiwan. Previous studies indicated that the aqueous extract of pepino was able to attenuate diabetic progression via its antioxidative and anti-inflammatory effects. However, the mechanisms of the antioxidative and anti-inflammatory effects of pepino leaf in preventing alcoholic fatty liver remain unknown. In this study, Lieber–DeCarli ethanol-containing liquid diet was used to induce alcoholic hepatic injury in C57BL/6 mice. The hepatoprotective effects and the related mechanisms of aqueous extract of pepino leaf (AEPL) were examined. Our results showed that 2% AEPL treatments protected the liver from ethanol-induced injury through reducing serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and triglyceride (TG) (all p < 0.05). AEPL had the effects in improving the ethanol-induced lipid accumulation in mice under histological examination. Molecular data indicated that the anti-lipid accumulation effect of AEPL might be mediated via inducing hepatic levels of phospho-adenosine monophosphate-activated kinase (p-AMPK) and peroxisome proliferator-activated receptor (PPAR)-α, and reducing the expressions of hepatic lipogenic enzymes, including sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) (all p < 0.05). AEPL also decreased hepatic levels of thiobarbituric acid relative substances (TBARS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, as well as the expression of nuclear factor kappa B (NF-κB) (all p < 0.05). Moreover, AEPL significantly elevated the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), and glutathione (GSH) content compared to the ethanol-fed group (all p < 0.05). Our present study suggests that AEPL could protect the liver against ethanol-induced oxidative injury and lipid accumulation.

Melanogenesis has many important physiological functions. However, abnormal melanin production causes various pigmentation disorders. Melanin synthesis is stimulated by α-melanocyte stimulating hormone (α-MSH) and ultraviolet (UV) irradiation. Lotus seedpod extract (LSE) has been reported as possessing antioxidative, anti-aging, and anticancer activities. The present study examined the effect of LSE on melanogenesis and the involved signaling pathways in vitro and in vivo. Results showed that non-cytotoxic doses of LSE and its main component epigallocatechin (EGC) reduced both tyrosinase activity and melanin production in the α-MSH-induced melanoma cells. Western blotting data revealed that LSE and EGC inhibited expressions of tyrosinase and tyrosinase-related protein 1 (TRP-1). Phosphorylation of p38 and protein kinase A (PKA) stimulated by α-MSH was efficiently blocked by LSE treatment. Furthermore, LSE suppressed the nuclear level of cAMP-response element binding protein (CREB) and disturbed the activation of melanocyte inducing transcription factor (MITF) in the α-MSH-stimulated B16F0 cells. The in vivo study revealed that LSE inhibited melanin production in the ear skin of C57BL/6 mice after exposure to UVB. These findings suggested that the anti-melanogenesis of LSE involved both PKA and p38 signaling pathways. LSE is a potent novo natural depigmenting agent for cosmetics or pharmaceutical applications.

Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the mechanism of AEPL on saturated long-chain fatty acid-induced lipotoxicity in HepG2 cells. Moreover, the phytochemical composition of AEPL was identified in the present study. HepG2 cells treated with palmitic acid (PA) were used for exploring the effect of AEPL on lipid accumulation, apoptosis, ER stress, and antioxidant response. The chemical composition of AEPL was analyzed by HPLC-ESI-MS/MS. AEPL treatment reduced PA-induced ROS production and lipid accumulation. Further molecular results revealed that AEPL restored cytochrome c in mitochondria and decreased caspase 3 activity to cease apoptosis. In addition, AEPL in PA-stressed HepG2 cells significantly reduced the ER stress and suppressed SREBP-1 activation for decreasing lipogenesis. For defending PA-induced oxidative stress, AEPL promoted Nrf2 expression and its target genes, SOD1 and GPX3, expressions. The present study suggested that AEPL protected from PA-induced lipotoxicity through reducing ER stress, increasing antioxidant ability, and inhibiting apoptosis. The efficacy of AEPL on lipotoxicity was probably concerned with kaempferol and isorhamnetin derived compounds.

The aim is to investigate the effect of lotus (Nelumbo nucifera Gaertn.) seedpod extract (LSE) on acetaminophen (APAP)-induced hepatotoxicity. LSE is rich in polyphenols and has potent antioxidant capacity. APAP is a commonly used analgesic, while APAP overdose is the main reason for drug toxicity in the liver. Until now, there has been no in vitro test of LSE in drug-induced hepatotoxicity responses. LSEs were used to evaluate the effect on APAP-induced cytotoxicity, ROS level, apoptotic rate, and molecule mechanisms. The co-treatment of APAP and LSEs elevated the survival rate and decreased intracellular ROS levels on HepG2 cells. LSEs treatment could significantly reduce APAP-induced HepG2 apoptosis assessed by DAPI and Annexin V/PI. The further molecule mechanisms indicated that LSEs decreased Fas/FasL binding and reduced Bax and tBid to restore mitochondrial structure and subsequently suppress downstream apoptosis cascade activation. These declines in COX-2, NF-κB, and iNOS levels were observed in co-treatment APAP and LSEs, which indicated that LSEs could ameliorate APAP-induced inflammation. LSE protected APAP-induced apoptosis by preventing extrinsic, intrinsic, and JNK-mediated pathways. In addition, the restoration of mitochondria and inflammatory suppression in LSEs treatments indicated that LSEs could decrease oxidative stress induced by toxic APAP. Therefore, LSE could be a novel therapeutic option for an antidote against overdose of APAP.

Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu Island, Taiwan. This present study aimed to investigate the protective effects of aqueous extract of Pepino leaves (AEPL) in mice with metabolic syndrome. Metabolic syndrome animal model was induced by continuous high‐fat diet feeding and low‐dose streptozotocin (40 mg/ml) for 5 days. A 1% AEPL or metformin were given for 6 weeks after streptozotocin injection. The results revealed that 1% AEPL effectively reduced fasting blood glucose, insulin resistance, and hyperlipidemia in metabolic syndrome mice. Histologic examination revealed lipid accumulation in liver decreased by 1% AEPL treatment. Further, western blot analysis revealed 1% AEPL treatment managed enzymes related to lipid synthesis and oxidation pathways and hepatic glucose production. Besides, 1% AEPL treatment increased liver antioxidant activities to against oxidative stress. These results concluded that AEPL treatment attenuated insulin resistance, hyperlipidemia, and hyperglycemia of metabolic syndrome. Practical applications Metabolic syndrome (MS) is a multifactorial chronic disease which is characterized by dyslipidemia, insulin resistance, and hyperglycemia. However, there is no single drug or defined medication for MS so far. The present study revealed that AEPL treatment was able to regulate lipid metabolism and glycemic control at the molecular level to alleviate MS. AEPL has the potential to be a novo complementary medication for metabolic syndrome.

A novel Ucp1-CreYH knock-in mouse exhibits improved efficiency and specificity of Cre recombinase activity in brown adipose tissue (BAT) compared with the widely used Ucp1-CreEvdr line, which showed nonspecific Cre activity in many organs. A BAT-deprived mouse model, generated with this Cre line, showed normal locomotion and body weight, but altered body weight and glucose homeostasis after high-fat feeding, validating its use for BAT-specific gene manipulation.