According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to glucose‒lipid metabolism. Our research indicates that the decrease in F. plautii and its product, phytosphingosine, contributes to gene expression changes related to metabolic disorders in PDC individuals and increases their susceptibility to metabolic disorders. These findings suggest that diagnosing PDC may be beneficial for identifying at-risk populations among apparently healthy individuals, thereby advancing the broader field of metabolic disorder prevention and TCM integration.

1. The global epidemic of metabolic diseases, such as obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated fatty liver disease (MAFLD), has emerged as a major public health challeng...

Oligoasthenozoospermia (OA) is one of the most common types of male infertility affecting sperm count and sperm motility. Unfortunately, it is difficult for existing drugs to fundamentally improve the sperm quality of OA patients, because the pathological mechanism of OA has not been fully elucidated yet.Morinda officinalis–Lycium barbarumcoupled-herbs (MOLBCH), as traditional Chinese Medicines, has been widely used for treating OA over thousands of years, but its molecular mechanism is still unclear. For this purpose, we adopted a comprehensive approach integrated network pharmacology and molecular docking to reveal the bioactive components and potential targets of MOLBCH against OA. The results showed that MOLBCH alleviated apoptosis, promoted male reproductive function, and reduced oxidant stress in the treatment of OA. Ohioensin-A, quercetin, beta-sitosterol and sitosterol were the key bioactive components. Androgen receptor (AR), Estrogen receptor (ESR1), Mitogen-activated protein kinase 3 (MAPK3), RAC-alpha serine/threonine-protein kinase (AKT1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were the core potential targets. PI3K/Akt signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications were the most representative pathways. Moreover, molecular docking was performed to validate the strong binding interactions between the obtained core components and targets. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic instructions to treat OA.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by the excessive accumulation of fat in hepatocytes. However, due to the complex pathogenesis of MAFLD, there are no officially approved drugs for treatment. Therefore, there is an urgent need to find safe and effective anti-MAFLD drugs. Recently, the relationship between the gut microbiota and MAFLD has been widely recognized, and treating MAFLD by regulating the gut microbiota may be a new therapeutic strategy. Natural products, especially plant natural products, have attracted much attention in the treatment of MAFLD due to their multiple targets and pathways and few side effects. Moreover, the structure and function of the gut microbiota can be influenced by exposure to plant natural products. However, the effects of plant natural products on MAFLD through targeting of the gut microbiota and the underlying mechanisms are poorly understood. Based on the above information and to address the potential therapeutic role of plant natural products in MAFLD, we systematically summarize the effects and mechanisms of action of plant natural products in the prevention and treatment of MAFLD through targeting of the gut microbiota. This narrative review provides feasible ideas for further exploration of safer and more effective natural drugs for the prevention and treatment of MAFLD.