Methylglyoxal (MGO), a reactive carbonyl species, causes cellular damage and is closely related to kidney disease, particularly diabetic nephropathy. Although MGO has been reported to induce autophagy and apoptosis, the relationships between the two pathways are unclear. Here, we evaluated whether autophagy may be the underlying mechanism inhibiting MGO-induced apoptosis. MGO treatment induced concentration- and time-dependent apoptosis in HK-2 cells. Moreover, MGO upregulated the autophagy markers p62 and LC3-II. Apoptosis caused by MGO was increased in ATG5-knockdown cells compared to that in wild-type cells. In contrast, autophagy activation by 5-aminoimidazole-4-carboxamide ribonucleotide resulted in reduced apoptosis, suggesting that autophagy played a role in protecting against MGO-induced cell death. To examine the mechanisms through which autophagy occurred following MGO stimulation, we investigated changes in AKT/mammalian target of rapamycin (mTOR) signaling. Autophagy induction by MGO treatment was not related to AKT/mTOR signaling; however, it did involve autophagy-related gene expression promoted by AMP-activated protein kinase-mediated transcription factors, such as forkhead box 1. Overall, our findings indicate that MGO-induced cellular damage can be mitigated by autophagy, suggesting that autophagy may be a potential therapeutic target for diseases such as diabetic nephropathy.
Patrinia scabiosaefolia (PS) and Hippophae rhamnoides (HR) are traditionally used functional foods. Extracts from the root of PS are known for their anti-inflammatory effects, whereas those from the leaf of HR are effective at both preventing and treating obesity. This study investigated whether the extract combination of PS and HR (PHE) affected weight loss in obese mice. In vitro experiments demonstrated that PHE showed a synergistic effect on inhibiting adipocyte differentiation as compared with treatment with the single extracts. Additionally, PHE suppressed adipogenicrelated genes in a concentration-dependent manner. In vivo PHE supplementation suppressed body weight gain, inhibited hepatic lipid accumulation, decreased adipose size, serum triglycerides, and improved insulin resistance in obese mice. These results suggest that a treatment strategy using a combination of plant-derived extracts might be effective at ameliorating obesity. Practical applicationsCurrently, common methods for reducing obesity are diet and exercise. These can stimulate oxidative phosphorylation and metabolic activation so have significantly effects. However, these are largely due to individual compliance; there is no significant effect of reducing the worldwide obesity rate. Recently, herbal extracts has been reported as alternative medicine about inflammatory and obesity because diet with the herbal extracts can improve obesity with minimal side effects. Of particular, a mixture of herbal products was investigated for the treatment of obesity. Our reports demonstrated the synergistic effects of natural products and emphasizes the need for studies investigating other combinations of herbal extracts in the treatment of obesity. The results of our studies highlight the synergistic effects of combination phytochemical extracts and their role in ameliorating obesity.
The effects of a mixture of Hippophae rhamnoides (HR) and Zingiber mioga (ZM) extract (ZH) on intracellular lipid accumulation were investigated in vitro and the anti-obesity effects of ZH evaluated in mice with high-fat diet-induced obesity. The results revealed that ZH inhibited lipid accumulation in 3T3-L1 adipocytes and Huh-7 cells by suppressing adipogenic and lipogenic gene and protein expression. To evaluate the anti-obesity effects of ZH, mice fed a high-fat diet were orally administered low and high doses of ZH (low, ZM 400 mg/kg + HR 100 mg/kg; high, ZM 800 mg/kg + HR 200 mg/kg) for 9 weeks. ZH significantly reduced body weight gain and adipose tissue accumulation with no reduction in food intake when compared to control treatment. Furthermore, ZH reduced hepatic triglyceride and total cholesterol levels, as well as adipose cell size, in the liver and epididymal fat pads, respectively, through inhibition of adipogenesis and lipogenesis-related gene expression. These results suggested that ZH inhibits lipid accumulation, thereby indicating its potential for use as a new therapeutic strategy for obesity.
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