Editorial: Prevention and treatment of metabolic diseases using bioactive metabolites of herbal medicines also used as foods

Liver disease is a general term for lesions that occur in the liver. Its pathogenesis is complex and mainly related to factors such as viral infection, metabolic abnormalities, drug effects, and alcohol intake (Zhong et al., 2025). These factors can lead to liver cell damage, inflammatory response, and fibrosis process (Bai et al., 2025). The main classifications of liver diseases include NAFLD, drug-induced liver injury, viral hepatitis, and liver cancer (Ma et al., 2025). The liver disease is extremely harmful, with hidden early symptoms and the possibility of developing into cirrhosis, liver failure, and even liver cancer in the later stages. This disease seriously endangers human health (Xiao et al., 2025). The current treatment of liver disease has made certain progress, and the combination of immunotherapy and targeted therapy for liver cancer significantly prolongs the survival of patients. The approval of the first MASH targeted drug marks a new stage in the treatment of metabolic liver disease, but there are still limitations (Ali and Lai, 2025). Antiviral drugs used to treat liver disease have a risk of drug resistance and a high recurrence rate after discontinuation. Some drugs used to treat liver diseases have high prices, drug resistance risks, and side effects (McNally and Carey, 2025). However, traditional Chinese medicine with the same origin of medicine and food has shown unique advantages in the treatment of liver disease (Ma et al., 2023). These natural medicines can regulate liver metabolism and reduce inflammatory reactions through multiple targets. It also has minimal side effects and is suitable for long-term regulation. It can effectively assist in improving liver function (Ma et al., 2024). In the future, the treatment of liver diseases will develop towards precision, intelligence, and minimally invasive methods (Ghosh et al., 2025). Gene editing, regenerative medicine, and other technologies are expected to break through existing treatment bottlenecks (Nair et al., 2025). Digitized liver resection technology and multidisciplinary integrated diagnosis and treatment models will further enhance treatment effectiveness, bringing new hope to liver disease patients.Xu et al. evaluated the effects of rhein on inflammation, renal function, and gut microbiota induced by high-fat diet in C57BL/6J mice. The mice were fed a 60% fat diet for 12 weeks to establish an obesity related glomerular model. After continuous feeding of rhein (300 mg/kg/day) for 12 weeks, serum cytokines (IL-6, TNF-α), renal tissue pathology, and 16S rRNA microbiome sequencing were measured and analyzed. The research results indicated that rhein significantly reduced body weight, serum triglycerides, proteinuria, and improved glomerular lesions in mice, and it also significantly reduced the levels of serum IL-6, TNF-α, and creatinine. It was found that rhein restored the diversity of gut microbiota (Chao1 index increased from 303.58 to 425.78) and reversed the imbalance between Firmicutes and Bacteroidetes through 16S rRNA sequencing. The study found that significant differences in microbial community structure (between the rhein group and the model group) were confirmed through similarity analysis (R=0.926, p=0.008). In a word, rhein occasionally alleviated the progression of obesity-related glomerulopathy, and confirmed that this was related to factors such as anti-inflammatory, lipid-lowering, and microbial community regulation mechanisms.Li et al. used LC-MS, computer simulation docking analysis, and molecular dynamics to study the inhibition of cytochrome P450 enzymes by triterpenoids of Ganoderma lucidum, and evaluated their interference with clinical drug metabolism processes. It was found that triterpenoids of Ganoderma lucidum inhibited multiple CYP450 subtypes and interfered with the pharmacokinetics of some drugs in rats.This study also evaluated the inhibitory effects of triterpenoids on CYP 1A2, 2D6, 3A4, 2A6, 2B6, 2C9, and 2C19. The results showed that lanostane triterpenoids significantly inhibited CYP 1A2, indicating a strong affinity for these compounds. It was also found that some triterpenoids of Ganoderma lucidum only showed extensive inhibitory effects on CYPs, except for CYP 3A4, 2D6, 2C9, and 2C19. In addition, LC-MS, computer simulation docking analysis, and molecular dynamics studies displayed that some triterpenoids of Ganoderma lucidum interfered with clinical metabolism by inhibiting CYPs in vitro, which probably induced potential drug interactions. The above research provides important reference value for the promotion of human health by triterpenoids of Ganoderma lucidum. Targeted serum metabolomics studies were conducted using UHPLC-LTQ Orbitrap MS in this work, and 16S rRNA analysis was employed to elucidate the mechanisms by regulating lipid and glucose metabolism. It was found that phenylpropanoids of Zea mays L. significantly reduced oral glucose tolerance test values, insulin, and blood glucose levels at a dose of 160 mg/kg/day (P < 0.001). The phenylpropanoids of Zea mays L. lowered the insulin resistance index, reversed the accumulation of glycogen in the liver, and reduced lipid deposition in the liver. The 16S rRNA sequencing results indicated that phenylpropanoids of Zea mays L. interacted with gut microbiota, exerting a positive regulatory effect on bifidobacteria, and lactobacilli.Therefore, phenylpropanoids of Zea mays L. have great potential as adjuvant therapy for complex metabolic diseases such as diabetes.Leonardo et al. found that Delites™ prevented metabolic syndrome in male SD rats induced by high cholesterol and high-fat diet, and regulated their gut microbiota in a randomized preclinical trial. Delites™ is a supplement closely related to traditional Chinese medicine, which holds potential development value in regulating intestinal microbiota and alleviating metabolic syndrome. In this study, SD rats were divided into 4 groups: control-normal, CFED, CFED+low-dose Delites™, and CFED+high-dose Delites™. Through analysis of lipid profile, enzyme activity, molecular biomarkers, and gut microbiota, it was found that Delites™ significantly improved the lipid profile, reduced TNF-α level, enhanced IL-10 expression, and increased PGC-1α level. Meanwhile, gut microbiota regulation showed an increase in bifidobacteria and lactobacilli, accompanied by a decrease in proteus. These studies have found that Delites™ has potential in precision medicine to combat metabolic disorders, and further research is needed to investigate its long-term effects and translational relevance for humans in the future.Xu et al. studied the therapeutic effect of "Gui-Zhi-Ge-Gen-Tang" on T2DM based on pharmacodynamics and pharmacokinetics. In this study, the decoction of "Gui-Zhi-Ge-Gen-Tang" was prepared using water extraction, and its chemical components were analyzed using UPLC-Q-TOF-MS and HPLC. This study established a T2DM model by intraperitoneal injection of streptozotocin, administered drugs by gavage for 6 consecutive weeks, and used ELISA to detect serum markers.In this study, the abundance of gut microbiota in rats was detected through 16S rDNA sequencing, the content of short-chain fatty acids in rat feces was measured using GC-MS, and the expression of GPR43 and GLP-1 proteins in rat colon tissue was assessed using Western Blot. Meanwhile, this study established a Caco-2/HT29 cell model to measure the TEER and ALP activity to evaluate the integrity and polarization of the cell model, and investigated the bidirectional transport mechanism of "Gui-Zhi-Ge-Gen-Tang" decoction. The research results indicated that the decoction of "Gui-Zhi-Ge-Gen-Tang" stimulated the intestinal flora, increased the content of short-chain fatty acids, activated GPR43 protein, and promoted the secretion of GLP-1 in intestinal L cells. This study demonstrated the scientificity and rationality of treating T2DM with the decoction of "Gui-Zhi-Ge-Gen-Tang" from the perspectives of pharmacodynamics and pharmacokinetics.Nan et al. revealed the mechanism of treating hyperlipidemia with Fagopyrum tataricum and kiwi juice co-fermentation products by utilizing transcriptomics and metabolomics. In this study, Fagopyrum tataricum was co-fermented with kiwi juice, and the flavonoids in the fermentation product were analyzed through non-targeted metabolomics. Transcriptomics and metabolomics were utilized to investigate the anti-hyperlipidemic effect of the fermentation product in zebrafish fed a high-fat diet.The research results revealed that the co-fermentation product was rich in quercetin, luteolin, rutin, and kaempferol, which significantly reduced lipid accumulation in zebrafish. Metabolomics revealed 24 core differentially expressed metabolites, including glycerophospholipids, sphingolipids, glycerides, and fatty acyls.Transcriptomic analysis showed that the co-fermentation product regulated genes such as PLTP, ApoC1, SOAT2, SCARB1, PLA2G12B, and HMGCRa, and these genes were related to cholesterol metabolism and pathways associated with fat digestion and absorption. Therefore, this study indicated that the co-fermentation product of MAFLD, can also be used to assess metabolism-related fat parameters. In this review analysis, researchers consulted relevant databases to obtain clinical randomized controlled trial data on the treatment of T2DM with MAFLD using traditional Chinese medicine preparations. Data analysis was conducted using RevMan 5.4 software, and the results were presented in the form of forest plots. A total of 599 papers were retrieved in this study, and 8 trials (involving 648 participants) were selected for inclusion. The analysis revealed that the traditional Chinese medicine preparation significantly reduced the CAP value in patients with T2DM complicated by MAFLD .85], P < 0.0001). Therefore, traditional Chinese medicine preparation effectively reduced the CAP value of T2DM combined with MAFLD, demonstrating significant therapeutic effects on glucose and lipid metabolism as well as liver function. This indicated that traditional Chinese medicine preparation reduced hepatic fat deposition, restored hepatocyte function, and exhibited a favorable therapeutic effect on T2DM combined with MAFLD.Cesar et al. found that citrus flavonoids enhanced the control of blood glucose and metabolism in patients with prediabetes treated with metformin. In a 12-week randomized and double-blind trial, participants received treatment with metformin combined with a citrus flavonoid supplement (250 mg/day). At the end of the intervention, it was found that the nutritional supplement group was able to improve postprandial glucose metabolism, reduce OGTT levels, and maintain GLP-1 levels. In contrast, the placebo group showed a decrease in GLP-1 level and an increase in insulin resistance. This flavonoid supplement reduced TNF-α level, enhanced plasma antioxidant capacity, and decreased indicators such as body weight, fat mass, and BMI (P ≤ 0.05). In summary, citrus flavonoids can improve postprandial blood glucose level, maintain GLP-1 level, reduce inflammation and oxidative stress, and improve blood pressure level, thus possessing potential research value in the treatment of early-stage T2DM.