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.

Baicalein improves renal interstitial fibrosis by inhibiting the ferroptosis in vivo and in vitro.

Evidence indicates that Baicalein can ameliorate renal interstitial fibrosis by inducing myofibroblast apoptosis and inhibit the RLS3-induced ferroptosis in melanocytes. However, the relationship between renal interstitial fibrosis and anti-ferroptosis affected by Baicalein remains unclear. In our study, the anti-fibrosis and anti-ferroptosis effects of Baicalein were assessed in a rat model induced by the UUO method in vivo, and the effects of Baicalein on Erastin-induced ferroptosis of renal MPC-5 cells were examined by Western blot of fibrosis-related and ferroptosis-related proteins in vitro. In the UUO-induced rat model, Baicalein decreased kidney weight loss, improved renal function assessed the biomarks of urinary albumin excretion, serum creatine, and BUN levels, and reduced renal tubular injury. Furthermore, Baicalein inhibited renal ferroptosis by reducing ROS and MDA levels and increasing SOD and GSH levels in the UUO rat model. In addition, Baicalein potently reduced the expression of fibrosis-related proteins such as TGF-ß1, a-SMA, and Smad-2 to prevent renal interstitial fibrosis, and increased the expression of ferroptosis-related proteins such as SLC7A11, GPX4, and FTH to inhibit ferroptosis both in vitro and in vivo. Taken together, Baicalein exerts anti-fibrosis activity by reducing the ferroptosis response on the UUO-induced rat model and renal MPC5 cells. Therefore, Baicalein, as a novel therapeutic method on kidney diseases with strong activity in suppressing ferroptosis, could be a potential alternative treatment for renal interstitial fibrosis.

[Jiawei Baitouweng Decoction affects intestinal mucosal tight junction proteins in rats with ulcerative colitis through p38 MAPK-MLCK signaling pathway].

The aim of this paper was to explore the effect and mechanism of Jiawei Baitouweng Decoction(JWBTW) against ulcerative colitis(UC) from the perspective of intestinal mucosal tight junction proteins. From 60 SPF-grade male SD rats, 10 were randomly selected as the blank control, and the remaining 50 were treated with 3% dextran sodium sulfate(DSS) solution to induce UC and then randomized into the model group, mesalazine group, and low-, medium-, and high-dose JWBTW( L-JWBTW, M-JWBTW and H-JWBTW) groups, with 10 rats in each group. After successive medication for 14 days, the rat general conditions like body weight and stool were observed and the disease activity index(DAI) was calculated. The pathological changes in colon tissue was observed under a microscope for injury severity scoring and histopathological scoring. The serum endotoxin content was determined by limulus assay, followed by the measurement of protein expression levels of ZO-1, occludin, claudin-1, p38 MAPK, MLCK, MLC2 and p-MLC in colon tissue by Western blot. The results showed that compared with the blank group, the model group exhibited significantly reduced body weight, elevated DAI, injury severity and histopathological scores and serum endotoxin content, up-regulated protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and down-regulated ZO-1, occludin and claudin-1. Compared with the model group,mesalazine and JWBTW at each dose obviously increased the body weight, lowered the DAI, injury severity and histopathological scores and serum endotoxin content, down-regulated the protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and up-regulated the ZO-1, occludin and claudin-1, with the most obvious changes noticed in the H-JWBTW group. All these have indicated that JWBTW exerts the therapeutic effect against UC by inhibiting the activation of p38 MAPK/MLCK pathway, reversing the protein expression levels of occludin, claudin-1 and ZO-1, decreasing the serum endotoxin content, promoting the repair of intestinal mucosal mechanical barrier, maintaining the integrity of tight junctions, and reducing the permeability of intestinal mucosa.

The antitumor effect of the combination of aconitine and crude monkshood polysaccharide on hepatocellular carcinoma.

Aconitine, the main component in Radix Aconiti Lateralis Preparata, not only exerts the anti-tumor effect on Hepatocellular Carcinoma (HCC) but also damages on immune system. In the present study, Crude Monkshood Polysaccharide (CMP), another one natural composition component originated from the same herbal with aconitine, combined with aconitine to investigate the effects on HCC and immunity in vitro and in vivo. The combination of CMP and aconitine enhanced the ability of the immunocyte to kill the tumor cell in vitro and had an additive effect on anti-HCC in vivo. Aconitine-CMP in combination improved the spleen weights, spleen index, thymus weights, thymus index. Elevated CD4+ T and CD8+ T cells and macrophages in spleen, decreased serum IL-6 level and increased serum IFN-γ and TNF-α levels were observed in mice treated with the combination of aconitine and CMP compare with control group (P<0.05). Our results showed that the combination of aconitine and CMP exerts anti-tumor effect by directly killing tumor cells and enhancing the anti-tumor immune responses, which further implies that chemotherapy drugs combined with Chinese medicine immunopotentiator maybe a feasible and effective strategy for HCC.

Pingkui Enema Alleviates TNBS-Induced Ulcerative Colitis by Regulation of Inflammatory Factors, Gut Bifidobacterium, and Intestinal Mucosal Barrier in Rats.

BACKGROUND: Ulcerative colitis (UC) is a chronic recurrent inflammation of the colon, and clinical outcome of UC is still unsatisfied. Pingkui enema, a traditional Chinese medicine prescription, has been safely applied for the treatment of diarrhea and dysentery in clinic for many years. However, its mechanism is still elusive. The present study is designed to investigate the effect of Pingkui enema on trinitrobenzene sulfonic acid- (TNBS-) induced ulcerative colitis (UC) and possible mechanism in rats. METHODS: UC was induced by intracolonic instillation of TNBS in male Sprague-Dawley rats, which were treated with different dosages of Pingkui enema (low, medium, and high) or sulfasalazine for ten days. Survival rate was calculated. A clinical disease activity score was evaluated. Histological colitis severity was analyzed by hematoxylin-eosin (HE) staining. Content of Bifidobacterium in intestinal tissue was analyzed by RT-PCR. Concentration of IL-8, IL-13, TNF-α, D-lactic acid (D-LA), and diamine oxidase (DAO) in serum and contents of adhesin and receptor of Bifidobacterium adhesion in rat intestinal mucus were measured by ELISA. RESULTS: The results showed that Pingkui enema treatment with high dosage markedly improved the survival rate compared with untreated and sulfasalazine treated groups. All dosages of Pingkui enema reduced pathological score. High dosage of Pingkui enema and sulfasalazine treatments significantly reduced the serum concentration of IL-8, TNF-α, D-LA, and DAO and markedly increased the serum concentration of IL-13. In addition, high-dose Pingkui enema and sulfasalazine treatments increased gut content of Bifidobacterium, gut mucus expressions of adhesin, and adhesin receptor of Bifidobacterium. CONCLUSIONS: Pingkui enema has therapeutic effect on TNBS-induced UC, and possible mechanism may be via regulation of gut probiotics (Bifidobacterium) and inflammatory factors and protection of intestinal mucosal barrier.

Therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer.

OBJECTIVE: To explore the therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer. METHODS: A total of 138 SD rats were selected to make rat models with gastric ulcer induced by acetic acid (24 rats with sham operation served as sham operation group), and were randomly divided into model group (n = 30), western medicine group (n = 30), traditional Chinese medicine (TCM) group (n = 24) and combination group (combined western medicine and TCM group, n = 30). Western medicine group was gavaged with omeprazole in the morning and with iso-volumetric distilled water in the afternoon; TCM group and TCM sham operation group were gavaged with iso-volumetric distilled water in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; combination group was gavaged with omeprazole in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; sham operation group and model group were gavaged with iso-volumetric distilled water both in the morning and afternoon. Ulcer indexes and degree of mucosal degree in rats at different time points after gavage were observed. Twenty-eight days after gavage, interleukin (IL)-1ß was given to induce ulcer recurrence so as to observe the recurrent severity and rate of ulcer in each group. RESULTS: Compared with model group and western medicine group, treatment in combination group could prominently reduce the ulcer index of rats with peptic ulcer, and increase the healing rate and inhibition rate of peptic ulcer. After IL-1ß-induced ulcer recurrence, combination group was significantly superior to model group and western medicine group in ulcer recurrent rate [50% (3/6) vs. 100% (6/6)] and severity. CONCLUSIONS: Basic acid-suppression therapy combined with Qi-Replenishing and Blood-Activating Formula can effectually improve the ulcer healing quality and reduce ulcer recurrence.

[Removal of Humic Acid from Water Using Pt/biochar Electrode Reactor].

A Pt/biochar electrode reactor was developed to remove humic acid in water. The removal efficiency and characteristics of the reactor were investigated. Experimental results showed that Pt/biochar electrode reactor obtained 74.58% removal rate after 300 min reaction under current density of 20 mA·cm-2. The removal rate was increased by 58.3% comparing with 47.10% removal rate achieved by Pt/graphite electrode reactor. Electrochemical oxidation and air floating played the main roles in removal of humic acid from water. The improved removal efficiency of humic acid in Pt/biochar electrode reactor was attributed to the fact that the biochar cathode could produce more H2O2 than graphite cathode. Three-dimensional excitation emission matrix fluorescence spectroscopy and Gel permeation chromatography measurement revealed that Pt/biochar electrode reactor had strong oxidation capability to mineralize the low molecular weight humic acid directly. It suggests that biochar could be use as an innovative cathode material of electrode reactor for organic pollutants treatment in water.