Shen-yan-yi-hao oral solution ameliorates IgA nephropathy via intestinal IL-17/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world, it is one of the most common causes of kidney disease and can lead to end-stage kidney disease, however, its pathogenesis is still complicated. The Shen-yan-yi-hao oral solution (SOLI) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. AIM OF THE STUDY: This study investigates SOLI's effects on IgAN in rats, particularly on the intestinal mucosal barrier, and identifies potential therapeutic targets through network pharmacology and molecular docking, validated experimentally. MATERIALS AND METHODS: Target genes for SOLI in IgAN were identified and analysed through molecular docking and KEGG pathway enrichment. An IgAN rat model examined SOLI's effect on renal biomarkers and cytokines involved in specific pathways, ileum mucosal lesions, and the intestinal immune system. The IL-17 pathway's role was studied in IEC-6 cells with SOLI in vitro. RESULT: Rats developed increased proteinuria and kidney damage marked by IgA deposition and inflammation. SOLI treatment significantly ameliorated these symptoms, reduced galactose-deficient Ig A1 (Gd-IgA1), and decreased cytokines like IL-17, TNF-α, IL-6 and IL-1ß etc. SOLI also normalized intestinal tight junction protein expression, ameliorated intestinal damage, and regulated intestinal immune response (focused on IL-17/NF-κB signal pathway). SOLI moderated the abnormally activated IL-17 pathway, which damages intestinal epithelial cells, suggesting IgAN treatment potential. CONCLUSION: SOLI reduces proteinuria and enhances intestinal mucosal function in IgAN rats, kidney protection in the IgAN rat model may initiate from modulating the intestinal IL-17/NF-κB pathway and subsequent Gd-IgA1 accumulation.

[Treatment of chronic primary glomerulopathy patients of Shen deficiency and dampness heat syndrome by yishen qingli granule combined low-dose Tripterygium wilfordii multiglycoside tablet: a clinical efficacy observation].

OBJECTIVE: To evaluate the clinical efficacy and safety of treatment of chronic primary glomerulopathy (CPG) patients of Shen deficiency and dampness heat syndrome (SDDHS) by Yishen Qingli Granule (YQG) combined with low-dose Tripterygium Wilfordii multiglycoside Tablet (TWT). METHODS: Totally 231 CPG patients of SDDHS were enrolled in this study (including 60 patients from First Affiliated Hospital of Nanjing University of Chinese Medicine, 58 from First Affiliated Hospital of Nanjing Medical University, 46 from Xinqiao Hospital of Third Military Medical University, 35 from First Affiliated Hospital of Guangzhou University of Chinese Medicine, 14 from First Affiliated Hospital of Soochow University, and 18 from Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine). They were randomly assigned to the control group (116 cases) and the trial group (115 cases) according to block group method. There were 217 cases in the safety analysis set (109 cases in the trial group vs 108 cases in the control group), and 203 cases in the full analysis set (99 cases in the trial group vs 104 cases in the control group). All patients received basic treatment such as ACEI/ARB. Furthermore, YQG (consisting of raw astragalus 10 g, prepared Polygonum Multiflorum 10 g, Pyrrosia 10 g, 1.5 g each package, containing 10 g of crude drugs) was additionally given to patients in the trial group, each package, twice daily. The TWT (10 mg) was given, twice a day. The TWT dose was adjusted according to 24 h urinary total protein (UTP). The placebos of YQG and TWT were administered to those in the control group. The treatment course consisted of 24 weeks and the follow-up visit lasted for 24 weeks. The biochemical indices were observed before and after treatment including 24 h UTP, urine red cell count (U(RBC)), renal functions (BUN, SCr), blood routine test (WBC), and liver functions (SGPT, SGOT). Reverse reactions such as gastrointestinal discomfort, skin rash, and irregular menstruation were also observed. RESULTS: Compared with the control group, the total effective rate was better in the trial group (82.83% vs 61.54%, P < 0.01). Results of stratified comparison of UTP showed better efficacy in the trial group (0.8-3.0 g/24 h, P < 0.01). The UTP decline occurred in the trial group after 8 weeks of treatment, with stable action, showing statistical difference when compared with the control group (P < 0.01). In the trial group, U(RBC) level decreased after treatment but changed more significantly. But there was no statistical difference in the changes when compared with the control group (P > 0.05). After treatment, there were no statistical difference in safety indicators such as WBC, SGPT, and SGOT between the two groups after treatment (P > 0.05). CONCLUSION: On the basis of basic treatment such as ACEI/ARB, application of YQG combined with low-dose TWT had better effect in controlling proteinuria of CPG patients, and could help stabilizing their conditions with less adverse reactions.

Astragalus Total Saponins Ameliorate Peritoneal Fibrosis by Promoting Mitochondrial Synthesis and Inhibiting Apoptosis.

Peritoneal fibrosis (PF) is a disease caused by prolonged exposure of the peritoneum to high levels of dialysis fluid. Astragalus total saponins (ATS) is a phytochemical naturally occurring in Radix Astragali that has anti-inflammatory and anti-oxidant properties. In this study, we constructed an in vivo model of PF using 4.25% glucose-containing administered intraperitoneally to rats and incubated peritoneal mesothelial cells (PMCs) with 4.25% glucose-containing peritoneal dialysis fluid to construct an in vitro model of PF. Furthermore, siRNA of PGC-1[Formula: see text] was used to inhibit the expression of PGC-1[Formula: see text] to further investigate the mechanism of the protective effect of ATS on PF. In both in vivo and in vitro models, ATS treatment showed a protective effect against PF, with ATS reducing the thickness of peritoneal tissues in PF rats, increasing the viability of PMCs, increasing the mitochondrial membrane potential and reducing apoptosis ratio. ATS treatment also reduced the expressions of peritoneal fibrosis markers (Smad2, p-Smad2 and [Formula: see text]-SMA) and apoptosis markers (Caspase3, cleaved-Caspase3 and Bax) and restored the expressions of mitochondrial synthesis proteins (PGC-1[Formula: see text], NRF1 and TFAM) in ATS-treated peritoneal tissues or PMCs. Furthermore, in the presence of PGC-1[Formula: see text] inhibition, the protective effect of ATS on PF was blocked. In conclusion, ATS treatment may be an effective therapeutic agent to inhibit high glucose-induced in peritoneal fibrosis through PGC-1[Formula: see text]-mediated apoptosis.