Background: The damage to intestinal barrier function plays an important role in the development of obesity and associated diseases. Soy isoflavones are effective natural active components for controlling obesity and reducing the level of blood lipid. Here, we explored whether these effects of soy isoflavones were associated with the intestinal barrier function. Methods and Results: The obese rat models were established by high fat diet feeding. Then, those obese rats were supplemented with soy isoflavones at different doses for 4 weeks. Our results showed that obesity induced the expressions of pro-inflammatory cytokines, decreased the anti-inflammatory cytokine (IL-10) expression, elevated intestinal permeability, altered gut microbiota and exacerbated oxidative damages in colon. The administration of soy isoflavones reversed these changes in obese rats, presenting as the improvement of intestinal immune function and permeability, attenuation of oxidative damage, increase in the fraction of beneficial bacteria producing short-chain fatty acids and short-chain fatty acid production, and reduction in harmful bacteria. Furthermore, soy isoflavones blocked the expressions of TLR4 and NF-κB in the colons of the obese rats. Conclusions: Soy isoflavones could improve obesity through the attenuation of intestinal oxidative stress, recovery of immune and mucosal barrier, as well as re-balance of intestinal gut microbiota.

The pandemic tendency of obesity and its strong association with serious co-morbidities have elicited interest in the underlying mechanisms of these pathologies. Lipid homeostasis, closely involved in obesity, has been reported to be regulated by multiple pathways. mTORC1 is emerging as a critical regulator of lipid metabolism. Here, we describe that the consumption of soy isoflavones, with a structural similarity to that of estradiol, could mitigate obesity through an AKT/mTORC1 pathway. Fed with soy isoflavones, the diet-induced obesity (DIO) male rats exhibited decreased body weight, accompanied with suppressed lipogenesis and adipogenesis, as well as enhanced lipolysis and β‑oxidation. The phosphorylation of AKT and S6 were decreased after soy isoflavone treatment in vivo and in vitro, suggesting an inhibition effect of soy isoflavones on mTORC1 activity. Our study reveals a potential mechanism of soy isoflavones regulating lipid homeostasis, which will be important for obesity treatment.

Soy isoflavones are natural active ingredients of soy plants that are beneficial to many metabolic diseases, especially obesity. Many studies have reported that obesity is closely related to visceral fatty acid metabolism, but the effect has not been well defined. In this study, we show that soy isoflavones improve visceral fatty acid metabolism in diet-induced obese male rats, which was indicated by reduced body weight and visceral fat cell area, as well as suppressed visceral fat synthesis and accelerated fat hydrolysis. We also found that common components of soy isoflavones, daidzein and genistein, were able to inhibit the lipid accumulation process in 3T3-L1 cells. Moreover, we showed that soy isoflavones can promote on AMP-activated protein kinase (AMPK) activity both in vivo and in vitro, which may be implicated in lipid metabolism regulation of soy isoflavones. Our study demonstrates the potential of soy isoflavones as a mechanism for regulating lipid homeostasis in visceral adipose tissue, proven to be beneficial for obesity treatment.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, thus treatments for it have attracted lots of interest. In this study, the Salviae miltiorrhizae Radix et Rhizoma (SMRR) polysaccharide was isolated by hot water extraction and ethanol precipitation, and then purified by DEAE anion exchange chromatography and gel filtration. With a high-fat-diet-induced obesity/NAFLD mouse model, we found that consumption of the SMRR polysaccharide could remarkably reverse obesity and its related progress of NAFLD, including attenuated hepatocellular steatosis, hepatic fibrosis and inflammation. In addition, we also reveal the potential mechanism behind these is that the SMRR polysaccharide could regulate the gut–liver axis by modulating the homeostasis of gut microbiota and thereby improving intestinal function.

Colon cancer is a common malignant tumor of the digestive tract, and it is considered among the biggest killers. Scientific and reasonable treatments can effectively improve the survival rate of patients if performed in the early stages. Polyphyllin I (PPI), a pennogenyl saponin isolated from Paris polyphylla var. yunnanensis, has exhibited strong anti-cancer activities in previous studies. Here, we report that PPI exhibits a cytotoxic effect on colon cancer cells. PPI suppressed cell viability and induced autophagic cell death in SW480 cells after 12 and 24 h, with the IC50 values 4.9 ± 0.1 μmol/L and 3.5 ± 0.2 μmol/L, respectively. Furthermore, we found PPI induced time-concentration-dependent autophagy and apoptosis in SW480 cells. In addition, down-regulated AKT/mTOR activity was found in PPI-treated SW480 cells. Increased levels of ROS might link to autophagy and apoptosis because reducing the level of ROS by antioxidant N-acetylcysteine (NAC) treatment mitigated PPI-induced autophagy and apoptosis. Although we did not know the molecular mechanism of how PPI induced ROS production, this is the first study to show that PPI induces ROS production and down-regulates the AKT/mTOR pathway, which subsequently promotes the autophagic cell death and apoptosis of colon cancer cells. This present study reports PPI as a potential therapeutic agent for colon cancer and reveals its underlying mechanisms of action.

Soy isoflavones (SIF) are biologically active compounds of non-steroidal and phenolic properties that are richly present in soybeans, which can reduce the body weight and blood lipids of obese animals. Recently, SIF have been reported to affect reproductive ability in obese male rats. However, the specific mechanism has not been well defined. The aim of the current study was to study the possible mechanisms for the effect of SIF administration on obesity induced spermatogenic defects. Obese rats model induced by high-fat diets were established and gavage treated with 0, 50,150 or 450 mg of SIF/kg body weight/day for 4 weeks. Here, our research shows that obesity resulted in spermatogenic degeneration, imbalance of reproductive hormone, testicular oxidative stress and germ cell apoptosis, whereas evidently recovery effects were observed at 150 and 450 mg/kg SIF. We also have discovered that 150 and 450 mg/kg SIF can activate Nrf2/HO-1 pathway in control of Bcl-2, BAX and cleaved caspase-3 expression with implications in antioxidant protection. Our study indicates the potential mechanism of SIF regulating spermatogenic function in obese rats, and provides a scientific experimental basis for the regulation of biological function of obese male reproductive system by SIF.