Jianpi-Qushi-Heluo formula (JQHF) has been used to treat idiopathic membranous nephropathy (IMN) in hospitals for many years. Elucidating the protective effect and exploring the potential mechanism of JQHF against IMN. Passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Then, the animals were treated with JQHF at 16.2 g/kg or 32.4 g/kg, with benzepril (10 mg/kg) as a positive control. Renal function was evaluated by biochemical measurements and pathological testing. Fecal samples were collected before and after treatment to analyze the gut microbiota composition by shotgun whole metagenome sequencing. JQHF exhibited potent efficacy in ameliorating PHN at both doses, as revealed by decreasing the deposition of IgG and C5b-9, relieving podocyte injury, and reducing glomerular and tubular cell apoptosis. The lower dose was corresponding to the clinical dosage and showed better therapeutic effects than the higher dose. Metagenomic analysis showed that gavage with 16.2 g/kg of JQHF shifted the structure of the gut microbiota in PHN rats and significantly increased the relative abundances of Prevotella copri, Lactobacillus vaginalis and Subdoligranulum variabile. Particularly, S. variabile was strongly negatively correlated with serum levels of TC and TG, the deposition of IgG and C5b-9, and apoptosis of glomerular cells. The JQHF is an effective agent for the treatment of experimental PHN. The PHN-allevating effect of JQHF is associated with specific alternation of gut microbiota.

Objectives: Global diabetes rates are rising sharply, driving a parallel increase in diabetic kidney disease (DKD) - a key diabetic complication. This trend poses mounting public health and economic burdens worldwide. Current therapies remain inadequate, making DKD progression a pressing unmet need. This review aims to assess the efficacy and molecular mechanisms of food-medicine homologous herbs for DKD treatment. Methods: A comprehensive literature search was conducted across multiple databases (PubMed, Web of Science, Cochrane Library, and Embase) from inception to March 2025, using keywords including “diabetic kidney disease”, and “traditional Chinese medicine”. The search was meticulously designed to cover relevant research extensively. Data extraction focused on herb names, bioactive compounds, experimental models, therapeutic effects, and molecular targets. Findings: This review highlights 29 food-medicine homologous herbs with proven safety and efficacy in DKD. These herbs alleviate immune-inflammatory responses by modulating NF-κB, interleukins, TNF-α, chemokines, and adhesion molecules. They also reduce mitochondrial and non-mitochondrial ROS production, improving oxidative stress via Keap1/Nrf2/ARE, AMPK/SIRT, and NF-κB pathways. Renal fibrosis is suppressed through targeting fibrosis markers and regulating TGF-β/Smad and Notch signaling. Additionally, these herbs inhibit the AGEs/RAGE axis, correct gut dysbiosis, reduce apoptosis, activate autophagy, inhibit ferroptosis, and modulate microRNAs, collectively exerting renoprotective effects in DKD. Conclusions: Food-medicine homologous herbs demonstrate properties that align well with medical nutrition therapy principles, offering novel adjunctive therapeutic options for DKD.

Background. Galactose‐deficient IgA1 (Gd‐IgA1) is a critical initiating factor in the pathogenesis of IgA nephropathy (IgAN), which plays an important role in the diagnosis and evaluation of this disease. Moreover, the whole pathogenesis process has an intimate association with the immune response of T and B lymphocytes and their inflammatory factors. There is no specific therapy for IgAN at present. Yiqi Yangyin Formula can significantly reduce urinary protein and hematuria in patients with IgAN. Yiqi Yangying Heluo Formula (YYHF) is optimized on the basis of the above prescription, but its specific mechanism remains to be further studied. Methods. The effect of YYHF on urinary protein and urinary red blood cell count in patients with IgAN was observed by a self‐controlled clinical study before and after treatment. On this basis, flow cytometry was used to detect the proportion of T lymphocyte subsets in peripheral blood of patients with IgAN before and after treatment and healthy controls. Meanwhile, the levels of Gd‐IgA1, B cell activation factor (BAFF), and their cytokines (IL‐4, IL‐6, and IL‐17) in peripheral blood were detected by enzyme‐linked immunosorbent assay. The changes in mechanism‐related indicators of the two groups were observed and subject to correlation analysis. Results. (1) Compared with the levels before treatment, 24‐hour urinary protein content decreased by 47.7% and urinary red blood cell number decreased by 67% in patients with IgAN intervened by YYHF after 48 weeks of follow‐up. (2) Compared with the healthy control group, patients with IgAN showed a significantly increased proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg, obviously reduced proportion of Th2 cells and Treg cells, and evidently elevated levels of Gd‐IgA1, BAFF, and their cytokines (IL‐4, IL‐6, and IL‐17) in the peripheral blood. (3) Following 48 weeks of follow‐up after intervention treatment with YYHF, the levels of Gd‐IgA1, BAFF, IL‐6, and IL‐17 were significantly lower, but the level of IL‐4 was higher in peripheral blood of patients with IgAN than those before treatment and after 24 weeks of treatment; simultaneously, the proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg decreased while that of Th2 cells and Treg cells increased after 48 weeks of follow‐up compared with that before treatment in peripheral blood of patients with IgAN. (4) The results of correlation analysis revealed that the level of Gd‐IgA1 in peripheral blood of patients with IgAN was positively correlated with the level of BAFF, as well as the proportion of Th1 cells, Th17 cells, Th1/Th2, IL‐6, and IL‐17 levels, and negatively correlated with the proportion of Treg cells. In addition, the level of Gd‐IgA1 in peripheral blood was positively correlated with proteinuria, yet without correlation with hematuria. Conclusion. YYHF can reduce the quantitative level of 24 h urinary protein and urinary red blood cell count in patients with IgAN. Patients with IgAN have obvious T cell immune imbalance. YYHF can significantly reduce the level of Gd‐IgA1 in patients with IgAN, and its mechanism may be explained by the reduced level of BAFF in peripheral blood and improved immune balance of T cells.

Autoimmune diseases (ADs) are a group of conditions characterized by an overactive immune response that damages one or more organs or tissues of the body. Emerging evidence highlights a critical association between reduced abundance of beneficial Clostridium and the pathogenesis of ADs. Studies show that certain Clostridium , such as Clostridium butyricum ( CB ) and Faecalibacterium prausnitzii ( FP ), are almost depleted in multiple ADs. This depletion is associated with impaired immune homeostasis, disrupted intestinal barrier integrity, and heightened inflammation. In diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and type 1 diabetes (T1D), restoration of Clostridium species or their metabolites may alleviate disease severity. Mechanistically, Clostridium probiotics may modulate ADs via multiple therapeutic mechanisms, including regulating gut microbiota composition, replenishing beneficial metabolites to restore intestinal barrier integrity, correcting dysregulated immune cell differentiation and homeostasis, and balancing pro- and anti-inflammatory cytokine levels. Our review synthesizes current evidence to delineate the immunomodulatory mechanisms by which Clostridium and its metabolites influence ADs. These findings underscore the therapeutic potential of Clostridium -based interventions in reestablishing immune-metabolic equilibrium in ADs.