It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus, Streptococcus, Bacteroides and Lactobacillus genera, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and β-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.

Inflammatory bowel disease (IBD) is a serious disorder, and exploration of active compounds to treat it is necessary. An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata (Desv.) Spring, which contained galacturonic acid, galactose, xylose, arabinose, and rhamnose with the main chain structure of →4)-α-d-GalAp-(1→ and →6)-β-d-Galp-(1→ and the branched structure of →5)-α-l-Araf-(1→ . Animal experiments showed that compared with Model group, SUSP-4 significantly improved body weight status, disease activity index (DAI), colonic shortening, and histopathological damage, and elevated occludin and zonula occludens protein 1 (ZO-1) expression in mice induced by dextran sulfate sodium salt (DSS). 16S ribosomal RNA (rRNA) sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes. Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism, which was further confirmed by a targeted metabolism study. Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice. A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B (p-NF-κB) and cyclooxygenase-2 (COX-2) and elevating NF-E2-related factor 2 (Nrf2) levels compared with Model group. In conclusion, SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD. This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD, showing great potential for in-depth research and development applications.

Low-grade chronic inflammation without obvious infection is defined as “inflammageing” and a key driver of skin ageing. Although the importance of modulating inflammageing for treating skin diseases and restoring cutaneous homeostasis is increasingly being recognized. However, the mechanisms underlying skin inflammageing, particularly those associated with natural treatments, have not been systematically elucidated. This review explores the signaling pathways associated with skin inflammageing, as well as the natural plants and compounds that directly or indirectly target these pathways. Nine signaling pathways and 60 plants/constituents related to skin anti-inflammageing are discussed, exploring plant mechanisms to mitigate skin inflammageing. Common natural plants with anti-inflammageing activity are detailed by active ingredients, mechanisms, therapeutic potential, and quantitative effects on skin inflammageing modulation. This review strengthens our understanding of these botanical ingredients as natural interventions against skin inflammageing and provides directions for future research.

Photoaging is the main form of external skin aging, and ultraviolet radiation is the main cause. Long-term ultraviolet radiation can cause oxidative stress, inflammation, immune responses, and skin cell apoptosis. Therefore, it is necessary to explore active products from plants to treat skin photoaging. C57BL/6J mice were randomly divided into control, model, and purslane (Portulaca oleracea L.) extract-treated groups (150, 300, and 600 mg/kg). Ultraviolet (UV) radiation induces skin photoaging. Histopathological changes in the skin were observed by hematoxylin and eosin (H&E), Masson's trichrome, and toluidine staining. Levels of hydroxyproline (HYP), hyaluronic acid (HA), collagen I (COL1), catalase (CAT), malondialdehyde (MDA), and total superoxide dismutase (T-SOD) were measured. UVB-induced BJ and HaCaT cells were used to evaluate the effects of the crude extract. The effects of the purslane extract on miR-138-5p/Sirt1 signaling were then tested. The results showed that the purslane extract significantly increased cell viability in UVB-induced cells and decreased oxidative damage and inflammation. In addition, the extract affected the miR-138-5p levels in vivo and in vitro, and increased the levels of the target gene Sirt1. In UVB-induced cells, purslane extract significantly altered the expression levels of genes or proteins associated with miR-138-5p/Sirt1 signaling. Inflammation and oxidative damage were significantly enhanced when miR-138-5p was overexpressed, and the expression levels of the genes and proteins were reversed by the extract. Co-transfection with the miR-138-5p inhibitor and si-Sirt1 showed the same effects as the extract on the signal. Similar results have been observed in mice. In summary, purslane extract showed potent protective effects against skin photoaging by regulating the miR-138-5p/Sirt1 axis and should be used as a natural product for skin care.

Introduction: Atopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual’s appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.Methods: In this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.Results: The levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of Ruminococcaceae and Bifidobacteriaceae. The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.Discussion: These findings suggested that the metabolite linoleic acid negatively correlated with Ruminococcaceae and Bifidobacteriaceae may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.