Protective effects of fermented Rosa roxburghii Tratt juice against ethanol­induced hepatocyte injury by regulating the NRF2­AMPK signaling pathway in AML­12 cells.

Alcohol­related liver disease (ALD) is a major health concern worldwide. In recent years, there has been growing interest in natural products and functional foods for preventing and treating ALD due to their potential antioxidant and hepatoprotective properties. Rosa roxburghii Tratt, known for its rich content of bioactive compounds, has demonstrated promising health benefits, including anti­inflammatory and antioxidant effects. Fermentation has been utilized as a strategy to enhance the bioavailability and efficacy of natural products. In the present study, using a mixture of Rosa roxburghii Tratt juice, lotus leaf extract and grape seed proanthocyanidins fermented by Lactobacillus plantarum HH­LP56, a novel fermented Rosa roxburghii Tratt (FRRT) juice was discovered that can prevent and regulate ethanol­induced liver cell damage. Following fermentation, the pH was significantly decreased, and the content of VC and superoxide dismutase (SOD) were significantly increased, along with a noticeable enhancement in hydroxyl and 2,2­diphenyl­1­picrylhydrazyl free radical scavenging abilities. Alpha Mouse liver 12 cells were exposed to ethanol for 24 h to establish an in vitro liver cell injury model. The present study evaluated the effects of FRRT on cell damage, lipid accumulation and oxidative stress markers. The results revealed that FRRT pretreatment (cells were pre­treated with 2.5 and 5 mg/ml FRRT for 2 h) significantly reduced lipid accumulation and oxidative stress in liver cells. Mechanistically, FRRT regulated lipid metabolism by influencing key genes and proteins, such as AMP­activated protein kinase, sterol regulatory element binding transcription factor 1 and Stearyl­CoA desaturase­1. Furthermore, FRRT enhanced antioxidant activity by increasing SOD activity, glutathione and catalase levels, while reducing reactive oxygen species and malondialdehyde levels. It also reversed the expression changes of ethanol­induced oxidative stress­related genes and proteins. In conclusion, a novel functional food ingredient may have been discovered with extensive potential applications. These findings indicated that FRRT has antioxidant properties and potential therapeutic benefits in addressing ethanol­induced liver cell damage through its effects on liver lipid metabolism and oxidative stress.

Effects and mechanisms of sciadonic acid on colonic transit function through regulating 5-HT4/cAMP/PKA/AQP4 signaling pathway in STC model mice.

Torreya grandis (T. grandis) oil has been reported to alleviate symptoms of slow transit constipation (STC). However, the impact of sciadonic acid (SA), a distinctive fatty acid found in T. grandis oil, on the pathological progression of STC remains unclear. This study aimed to evaluate the effect of SA on STC and uncover the underlying mechanisms. The STC model was established by feeding Balb/c mice with loperamide. After 2 weeks of intervention, SA significantly improved weight loss and intestinal motility decline induced by STC, along with enhancing plasma indices and reducing colon pathological damage. SA effectively reversed the STC-induced decrease in the 5-HT4/cAMP/PKA/AQP4 signaling pathway genes and expression. Furthermore, 16S rRNA analysis demonstrated that SA mitigated the imbalance of the intestinal microbiota induced by STC, by reducing the ratio of Firmicutes to Bacteroidetes (F/B) and increasing the abundance of beneficial bacteria such as Akkermansia. In conclusion, SA intervention alleviated colonic dysfunction in STC mice. The activation of the SA-mediated 5-HT4/cAMP/PKA/AQP4 signaling pathway may serve as a potential target for STC treatment. These findings suggest that SA holds promise as a treatment option for STC and could potentially be extended to other related gut diseases for further investigation.

Torreya grandis Kernel Oil Alleviates Loperamide-Induced Slow Transit Constipation via Up-Regulating the Colonic Expressions of Occludin/Claudin-1/ZO-1 and 5-HT3R/5-HT4R in BALB/c Mice.

SCOPE: Torreya grandis kernel has traditionally been used to remove intestinal parasites and increases intestinal motility. However, the effect of Torreya grandis kernel oil (TKO) on constipation has not yet been investigated. Therefore, mouse model is used to investigate the effect of TKO on slow transit constipation (STC) and its possible mechanism. METHODS AND RESULTS: The effects of TKO on intestinal motility of STC mice are evaluated by fecal weight, fecal water content, colon length, defecation test, and intestinal propulsion test. The mechanism of TKO alleviating STC is explored by detecting biochemical analysis, histological analysis, western blot, qRT-PCR, immunohistochemistry, and gut microbiota analysis. The results reveal that TKO effectively promotes defecation and intestinal motility, increases the level of endothelin-1, and restores the histopathological morphology of the colon under LOP pretreatment. The expression levels of occludin, claudin-1, and zonula occludens-1 (ZO-1) mRNA and protein are up-regulated in mice receiving TKO treatment. The colonic 5-hydroxytryptamine 3R/4R (5-HT3R/5-HT4R) expressions are also increased by TKO supplementation. Additionally, TKO rescues LOP-caused disorders of the gut microbiota. CONCLUSION: Consumption of TKO is beneficial to STC recovery, and it can alleviate LOP-induced STC by up-regulating the colonic expressions of Occludin/Claudin-1/ZO-1 and 5-HT3R/5-HT4R.

IL-6/Stat3 suppresses osteogenic differentiation in ossification of the posterior longitudinal ligament via miR-135b-mediated BMPER reduction.

Interleukin-6 (IL-6) has been reported to induce osteogenic differentiation of mesenchymal stem cells for increasing bone regeneration, while the role of IL-6 in osteogenic differentiation during ossification of the posterior longitudinal ligament (OPLL) remains to be determined. The current study aims to explore the downstream mechanism of IL-6 in cyclic tensile strain (CTS)-stimulated OPLL, which involves bioinformatically identified microRNA-135b (miR-135b). Initially, we clinically collected posterior longitudinal ligament (PLL) and ossified PLL tissues, from which ossified PLL cells were isolated, respectively. The obtained data revealed a greater osteogenic property of ossified PLL than non-ossified PLL cells. The effect of regulatory axis comprising IL-6, Stat3, miR-135b, and BMPER on osteogenic differentiation of CTS-stimulated ossified PLL cells was examined with gain- and loss-of-function experiments. BMPER was confirmed as a target gene to miR-135b. Knockdown of BMPER or overexpression of miR-135b inhibited the osteogenic differentiation of CTS-induced ossification in PLL cells. Besides, IL-6 promoted the post-transcriptional process to mature miR-135b via Stat3 phosphorylation. In conclusion, IL-6 inhibited CTS-induced osteogenic differentiation by inducing miR-135b-mediated inhibition of BMPER through Stat3 activation.