Morus alba L. fruit, a medicinal and edible fruit in East Asia, showed potential health-promoting effects against metabolic syndrome (MetS). However, both the protective effects and mechanisms of different fractions extracted from Morus alba L. fruit against MetS remain unclear. Additionally, the gut microbiota and its metabolites are regarded as key factors in the development of MetS. This study aimed to investigate the potential role of polyphenols and polysaccharides derived from Morus alba L. fruit against MetS in high-fat diet (HFD)-fed mice, individually and in combination, focusing on remodeling effects on gut microbiota and metabolite profiles. In the study, polyphenols and polysaccharides derived from Morus alba L. fruit improved the traditional pharmacodynamic parameters of MetS, including reductions in body weight (BW) and fat accumulation, improvement in insulin resistance, regulation of dyslipidemia, prevention of pathological changes in liver, kidney and proximal colon tissue, and suppressive actions against oxidative stress. In particular, the group treated with polyphenols and polysaccharides in combination showed better efficacy. The relative abundance of beneficial bacterial genera Muribaculum and Lachnospiraceae_NK4A136_group were increased to various degrees, while opportunistic pathogens such as Prevotella_2, Bacteroides, Faecalibacterium and Fusobacterium were markedly decreased after treatments. Moreover, fecal metabolite profiles revealed 23 differential metabolites related to treatments with polyphenols and polysaccharides derived from Morus alba L. fruit, individually and in combination. Altogether, these results demonstrated that polyphenols and polysaccharides derived from Morus alba L. fruit attenuated MetS in HFD-fed mice, and improved the gut microbiota composition and fecal metabolite profiles.

Intraperitoneal injection of dihydromyricetin (DMY) has shown promising potential in the treatment of alcoholism. However, its therapeutic effect is limited due to its low solubility, poor stability, and high gut-liver first-pass metabolism, resulting in very low oral bioavailability. In this study, we developed a DMY-loaded self-emulsifying drug delivery system (DMY-SEDDS) to enhance the oral bioavailability and anti-alcoholism effect of DMY. DMY-SEDDS improved the oral absorption of DMY by facilitating lymphatic transport. The area under the concentration-time curve (AUC) of DMY in the DMY-SEDDS group was 4.13-fold higher than in the DMY suspension group. Furthermore, treatment with DMY-SEDDS significantly enhanced the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver of mice (p < 0.05). Interestingly, DMY-SEDDS also increased ADH activity in the stomach of mice with alcoholism (p < 0.01), thereby enhancing ethanol metabolism in the gastrointestinal tract and reducing ethanol absorption into the bloodstream. As a result, the blood alcohol concentration of mice with alcoholism was significantly decreased after DMY-SEDDS treatment (p < 0.01). In the acute alcoholism mice model, compared to saline treatment, DMY-SEDDS prolonged the onset of LORR (loss of righting reflex) (p < 0.05) and significantly shortened the duration of LORR (p < 0.01). Additionally, DMY-SEDDS treatment significantly reduced gastric injury in acute alcoholism mice. Collectively, these findings demonstrate the potential of DMY-SEDDS as a treatment in the treatment of alcoholism.