Multi-omics analyses reveal a rhamnogalacturonan I (RG-I) from Polygonum aviculare ameliorates nephrolithiasis through regulation of the gut-kidney axis.

Thlaspi arvense (TA), commonly known as "Ximi" or "Subaijiang," is a traditional Chinese medicinal herb used to prevent and treat ulcerative colitis (UC). However, the precise mechanisms underlying its therapeutic effects remain unclear, necessitating further investigation to identify potential pharmaceutical applications for UC management. This study aims to elucidate the efficacy and mechanisms of TA and its active constituents in UC treatment. This study first evaluated the effects of varying TA doses on 3% dextran sulfate sodium (DSS)-induced UC. Gut microbiota alterations in UC mice were analyzed via 16S rRNA sequencing, with correlation analyses to reveal the relationship between gut microbiota and cytokines. Then, network pharmacology was utilized to identified potential TA targets for UC treatment. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed to explore TA's mechanisms. Molecular docking and dynamics simulations validated interactions between TA's active compounds and UC-related targets. Finally, TNF pathway modulation by TA and its active component, isovitexin, was verified in vitro and in vivo. TA alleviated DSS-induced weight loss in a dose-dependent manner, reduced disease activity indices, and preserved intestinal mucosal barrier integrity. Subsequently, fluorescence in situ hybridization (FISH) revealed TA suppressed microbial translocation in intestinal tissues. To further characterize inflammatory responses, ELISA demonstrated that TA modulated levels of key cytokines (TNF-α, IL-1β, IL-6, IL-10) and oxidative stress markers (SOD, MDA), indicating systemic anti-inflammatory effects. Building on these findings, 16S rRNA sequencing analyses showed that TA regulated gut microbiota alpha/beta diversity and inhibited infectious disease-related pathways. Notably, correlation heatmaps highlighted a strong association between TNF-α levels and Escherichia-Shigella abundance, with high-dose TA significantly reducing this pathogenic bacterial genus. To systematically explore molecular mechanisms, network pharmacology identified 220 potential TA targets for UC treatment. Consistent with experimental data, PPI and KEGG analyses implicated TNF-α, IL-6, and AKT as key targets, primarily through TNF signaling pathway modulation. To validate these predictions, molecular docking confirmed stable interactions between TA compounds and identified targets, while dynamics simulations specifically emphasized isovitexin's high affinity for TNF-α. Finally, experiments in vivo demonstrated TA's inhibition of TNF-α-mediated NF-κB pathway activation, and in vitro studies confirmed that isovitexin directly mitigated TNF-α-induced intestinal epithelial damage. Furthermore, TA demonstrated potent inhibition of TNF-α-mediated NF-κB inflammatory pathway activation in intestinal tissues, while its active constituent isovitexin effectively mitigated TNF-α-induced epithelial cell damage, collectively highlighting their complementary anti-inflammatory mechanisms. Collectively, Thlaspi arvense (TA) ameliorates ulcerative colitis through synergistic mechanisms involving gut microbiota modulation, inflammatory pathway suppression, and intestinal barrier preservation. By remodeling microbial communities to reduce Escherichia-Shigella colonization and microbial translocation. TA concurrently inhibits TNF-α/NF-κB-driven inflammation, and oxidative stress regulation. Furthermore, its active constituent isovitexin directly attenuates TNF-α-induced epithelial damage, demonstrating multi-scale therapeutic efficacy. These findings establish TA's multi-target pharmacology spanning host-microbe interactions and intracellular signaling, while providing a rationale for standardizing TA-based formulations and advancing isovitexin as a precision therapeutic agent for inflammatory bowel diseases.

Protein Molecular Markers for Herbal Natures of Six Traditional Chinese Medicinal Herbs

Gut microbial dysbiosis and the resultant metabolic disorder are intimately associated with calcium oxalate (CaOx) stone formation. Renal CaOx crystal deposition is one of the primary initiating factors of CaOx formation; however, the critical signaling metabolites communicating along the gut–kidney axis, and their regulation on renal CaOx crystal deposition remain unclear. Here, we investigate the role of gut microbiota-associated unconjugated bilirubin (UCB) metabolism in renal CaOx crystalline pathogenesis. The UCB was first distinguished as a significant risk factor of renal CaOx crystal deposition, by transplantation of fecal microbiota derived from healthy rat (healthy-FMT) to alleviate the renal CaOx crystal deposition in rat models, which was also testified in CaOx stone patients. Further experiments showed that UCB could increase renal CaOx crystal deposition significantly in both rat and Drosophila models. Mechanistically, UCB can promote apoptosis in renal tubular epithelial cells, enhance oxalate secretion by upregulating Slc26a6 expression, and facilitate CaOx crystal nucleation and aggregation, all of which contribute to renal CaOx crystalline pathogenesis. Furthermore, we identified significant gut microbiota dysbiosis in renal CaOx crystal deposition rats, particularly in β-glucuronidase (β-GD) and bilirubin reductase (BilR)-related dysbiosis, which modulate UCB levels and its enterohepatic circulation. These findings suggest that UCB is a novel regulator of renal CaOx crystal deposition, and targeting its metabolism via modulation of the gut microbiota may offer a promising therapeutic strategy for preventing renal CaOx crystal deposition-related nephropathy.

Hedyotis diffusa Willd. extract alleviates CCl4-induced liver fibrosis via modulation of the gut microbiota and FXR/SHP/CYP7A1-mediated bile acid metabolism.

The gut microbiota plays an important role in the human body, for example, they are responsible for the metabolism of some dietary factors. Many diseases are related to the imbalances in the gut microbiota. Accumulating evidence shows that traditional Chinese medicine herbs may prevent or treat some diseases through interacting with gut microbiota. Oral administration of Chinese herbs may change the composition of intestinal flora, and the ingredients in Chinese herbs can be catalyzed into bioactive metabolites by some intestinal microbes, resulting in their pharmacological effects. However, the interaction between Chinese herbs and gut microbiota remains unclear. One of the main challenges is the complexity and diversity of the components of Chinese herbs and intestinal flora. Recently, the correction among diseases, gut microbiota, and Chinese herbs through many methodologies are studied by using novel methods and techniques, such as high-throughput gene sequencing, real-time quantitative PCR, and metabolomics analysis as well as the multivariate data statistics. In the future, the clarified mechanism will open a new avenue for the prevention or treatment of diseases by taking Chinese herbs which regulate the composition of gut microbiota, which may achieve the goals of the personalized medicine.

Eucommia alleviates high fat diet-induced MASLD via the F. prausnitzii/butyrate/GPR43/GLP-1 signaling.

Total glycosides from stems of Cistanche tubulosa alleviate depression-like behaviors: bidirectional interaction of the phytochemicals and gut microbiota

Ginsenoside Ro alleviated cuproptosis induced by high oxalate via inhibiting zinc transporter ZnT1 in renal tubular epithelial cells

Oxidative stress and inflammatory response are closely related to nephrolithiasis. This study is aimed at exploring whether rosiglitazone (ROSI), a regulator of macrophage (Mp) polarization, could reduce renal calcium oxalate (CaOx) deposition by ameliorating oxidative stress and inflammatory response. Male C57 mice were equally and randomly divided into 7 groups. Kidney sections were collected on day 5 or day 8 after treatment. Pizzolato staining and polarized light optical microscopy were used to detect crystal deposition. PAS staining and TUNEL assay were performed to assess the tubular injury and cell apoptosis, respectively. Gene expression was assessed by immunohistochemistry, immunofluorescence, ELISA, qRT-PCR, and Western blot. The reactive oxygen species (ROS) level was assessed using a fluorescence microplate and fluorescence microscope. Hydrogen peroxide (H2O2), malonaldehyde (MDA), and glutathione (GSH) were evaluated to determine oxidative stress. Lactic dehydrogenase (LDH) activity was examined to detect cell injury. Adhesion of CaOx monohydrate (COM) crystals to HK-2 cells was detected by crystal adhesion assay. HK-2 cell death or renal macrophage polarization was assessed by flow cytometry. In vivo, renal crystal deposition, tubular injury, crystal adhesion, cell apoptosis, oxidative stress, and inflammatory response were significantly increased in the 7-day glyoxylic acid- (Gly-) treated group but were decreased in the ROSI-treated groups, especially in the groups pretreated with ROSI. Moreover, ROSI significantly reduced renal Mp aggregation and M1Mp polarization but significantly enhanced renal M2Mp polarization. In vitro, ROSI significantly suppressed renal injury, apoptosis, and crystal adhesion of HK-2 cells and markedly shifted COM-stimulated M1Mps to M2Mps, presenting an anti-inflammatory effect. Furthermore, ROSI significantly suppressed oxidative stress by promoting the Nrf2/HO-1 pathway in HK-2 cells. These findings indicate that ROSI could ameliorate renal tubular injury that resulted from oxidative stress and inflammatory response by suppressing M1Mp polarization and promoting M2Mp polarization. Therefore, ROSI is a potential therapeutic and preventive drug for CaOx nephrolithiasis.

Influenza is an acute respiratory communicable disease which can cause high morbidity and mortality in an epidemic. Traditional Chinese medicinal herbs following a particular theory may be a potential medicine of choice. The objective of this review was to assess the therapeutic effect and adverse reaction of Traditional Chinese medicinal herbs in treating uncomplicated influenza. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2004); MEDLINE (January 1966 to October 2004); EMBASE (January 1988 to October 2004); CBM (Chinese Biomedical Database) (January 1980 to December 2003); and the Chinese Cochrane Center's Controlled Trials Register (up to December 2003). We also searched Current Controlled Trials (www.controlled-trials.com) and the National Research Register (http://www.update-software.com/National/) for ongoing trials and reference lists of articles. We wrote to researchers in the field, or authors of studies evaluated in the review for more information. Randomised and quasi-randomised trials comparing traditional Chinese medicinal herbs with placebo, or various other Chinese medicinal herbs, or with other current regimes normally used in care or comparing drugs with herbal preparations to simple drugs in treating defined uncomplicated influenza patients. At least two reviewers extracted data and assessed trial quality. Eleven studies with the number of participants ranged from 52 to 479. In total 2,088 participants were included in the review. As the interventions of the included studies were different from each other and most of the studies were of low quality, we did not perform a summary meta-analysis. Some of the studies showed positive results favouring Traditional Chinese medicinal herb treatment compared to antiviral or antipyretic-analgesic drugs or the combination of them. Only three studies mentioned adverse reactions but no detailed data were acquired in the included studies. Eleven studies with the number of participants ranged from 52 to 479, 2,088 in total were included. As the interventions of the included studies were different from each other and most of the studies were of low quality, we failed to perform a summary meta-analysis. Some of the studies showed positive results favouring Traditional Chinese medicinal herb treatment compared to antiviral or antipyretic-analgesic drugs or the combination of them. Only three studies mentioned adverse reactions but no detailed data was acquired in the included studies. The small number of included studies and participants, as well as the low quality of most studies, made the evidence far from conclusive for clinical decision making, although traditional Chinese medicinal herbs as a whole seem to be comparatively or more effective compared to different chemical drugs. A certain herbal preparation could not be recommended for there was not enough evidence. More high quality randomised controlled trials (RCTs) with similar interventions are required to strengthen the evidence for the efficacy and safety of certain herbal preparation.

In this investigation, candidate traditional Chinese medicinal herbs for 3 neurodegenerative disorders, late-onset Alzheimer’s disease, late-onset Parkinson’s disease and Huntington disease were evaluated. The susceptibility genes were integrated to reconstruct traditional Chinese medicine-modern medicine network to discover the candidate herbs. For the 3 neurodegenerative disorders, the number of diseaserelated genes were increased from 2 to 16, which are directly associated with ingredients. Many traditional Chinese medicinal herbs associated with the 3 neurodegenerative disorders were identified (false discovery rate Benjamini-Hochberg<0.05). Four herbs for late-onset Alzheimer’s disease are related to β-amyloid 1-42 measurement-associated genes BCAM and APOE by ingredients resveratrol and kainic acid. There are 3 herbs correlated to late-onset Parkinson’s disease by both ingredient support and modern medicine symptom association evidence. Four traditional Chinese medicinal herbs are related to Huntington disease by ingredients. Available animal experiments in rats indicated that resveratrol could help to clean β-amyloid in brain to treat Alzheimer’s disease, probably through targeting LRP1 protein. This study provided a novel way to utilize genetic data to explore traditional Chinese medicinal herbs and a new insight into drug discovery of neurodegenerative disorders.

Context: Obesity has become a major health concern, and it places both personal and economic burdens on the world’s population. Traditional Chinese medicinal herbs are rich source of lead compounds and are possible drug candidates, which may be used to treat this condition.Objective: This study screened potent pancreatic lipase inhibitors found in traditional Chinese medicinal herbs for ability to treat obesity.Materials and methods: A porcine pancreatic lipase inhibition assay was established, and the inhibitory activity of 35 traditional Chinese medicinal herbs was evaluated at a concentration of 200 μg/mL. Two elutions of herbal extracts with strong lipase inhibitory activity were further fractionated by preparative high-performance liquid chromatography into 22 sub-fractions each, and these sub-fractions were tested for anti-lipase activity. Sub-fractions, which exhibited strong lipase inhibitory activity, were continuously fractionated into individual compounds. Two active compounds with potent anti-lipase activity were finally isolated and identified from two traditional Chinese medicinal herbs, respectively.Results: Among 35 traditional Chinese medicinal herbs, the 95% ethanol elutions of Panax notoginseng (Burk.) F.H. Chen (Araliaceae) and Magnolia officinalis Rehd. et Wils (Magnoliaceae) showed strong anti-lipase activity. Two compounds, including 20(S)-ginsenoside Rg3 and honokiol were identified using bioactivity-guided isolation with IC50 = 33.7 and 59.4 μg/mL, respectively.Conclusion: 20(S)-ginsenoside Rg3 and honokiol might be suitable candidates for the treatment of obesity.

Background: Metabolic-associated fatty liver disease (MAFLD) is prevalent in individuals with liver disease; however, it lacks effective therapeutic approaches. Smilax china L., a traditional Chinese medicinal herb, possesses excellent anti-inflammatory and antioxidant activity. This research aimed to explore the therapeutic effects of Smilax china L. extract (SCE) on MAFLD and to elucidate the pharmacological mechanisms. Methods: A rat model of MAFLD was induced through a high-fat diet (HFD), and the model rats subsequently received SCE as a therapeutic intervention for six weeks. The analysis involved 16S rDNA sequencing, untargeted fecal metabolomics, and targeted bile acid metabolomics to investigate the effects of SCE on the gut microbiota and bile acid metabolism. Results: Hepatic steatosis and lipid accumulation were significantly alleviated by the SCE treatment. SCE treatment modulated the gut microbiota disorder, by enhancing the relative abundance of the beneficial gut microbiota, including Clostridium, Oscillospira, and Romboutsia. Untargeted fecal metabolomics revealed a significant enrichment of the metabolites in secondary bile acid biosynthesis. Targeted bile acid metabolomics revealed that SCE reversed the abnormal fecal bile acid metabolic profile, such as HDCA, LCA, and T-β-MCA. These changes activated FXR and PPARα receptors to improve the lipid metabolism by regulating bile acid synthesis. Conclusions: Our study provides evidence that SCE alleviates MAFLD through regulation of the gut microbiota, bile acid metabolism, and activation of the FXR/PPARα pathway, illustrating the mechanism of action of SCE in MAFLD from a novel perspective, and further highlights its therapeutic potential.

Activity stimulating proliferation of osteoblast-like UMR106 cells was assayed in 97 traditional Chinese medicinal herbs and other plants. The cells were co-cultured with alcohol or aqueous extracts of plants, the cell proliferation was measured by the MTT method. Significant promotion of cell proliferation was observed in 11 of 24 alcohol extracts, and in 6 of 9 tested aqueous extracts, from “kidney-tonifying” traditional Chinese medicinal herbs. For those other than “kidney-tonifying” medicines, 2 of 20 alcohol extracts and 3 of 11 aqueous extracts markedly stimulated the proliferation of UMR106 cells. Only 2 alcohol extracts from 53 plants not yet being used as medication agents were found active. These active extracts may be a stimulator of bone formation and potential source of drugs for osteoporosis therapy or prevention. There is a promising possibility of using natural plants, paticularly “kidney-tonifying” traditional Chinese medicinal herbs, as an alternative intervention for osteoporosis.

Renal injury and calcium oxalate crystal deposition are the core pathological processes of kidney stone formation, and their molecular mechanisms have not been fully elucidated while the clinical intervention methods are limited. Many studies have shown that the intestinal microbiota can produce various metabolites that affect renal function through the gut-kidney axis and participate in the formation of kidney stones. This study aims to identify the microbial metabolites related to kidney stone patients and explore their mechanism of action in kidney stones. Microbiome and metabolome analyses are used to search for microbial-related metabolites in the intestines of kidney stone patients. Using COM crystal-treated TCMK-1 cells as a model, the functions of metabolites are evaluated by detecting cell viability, apoptosis rate, cell-crystal adhesion, reactive oxygen species and MDA levels in vitro. In vivo, a glyoxylate-based kidney stone mouse model is established, and the effects of metabolites on renal function are assessed by HE staining, PAS staining, creatinine and urea nitrogen levels. The effects of metabolites on renal injury and crystal deposition are evaluated by Tunel, Von-Kossa staining, CD44 and OPN level detection. Transcriptional sequencing combined with western blot is used to search and verify the related signaling pathways affected by metabolites. It is found that linoelaidic acid is significantly decreased in kidney stone patients. Supplementing linoelaidic acid in vitro can significantly reduce COM crystal-induced cell apoptosis, crystal adhesion, ROS and MDA levels, and increase cell viability. In kidney stone mice, supplementing linoelaidic acid reduces renal tubular damage, crystal deposition, and improves renal function. Mechanistically, linoelaidic acid upregulates the expression of PPARγ in kidney stones to inhibit the activation of the MAPK signaling pathway. Linoelaidic acid can alleviate renal injury, oxidative stress and crystal deposition by regulating the PPARγ/MAPK signaling pathway, and may be a useful strategy for the treatment of kidney stones.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00240-025-01848-4.