Effects of Periostracum Cicadae on Cytokines and Apoptosis Regulatory Proteins in IgA Nephropathy Rat Model

Abstract

Periostracum cicadae, the cast-off shell of the cicada Cryptotympana pustulata Fabricius, is used in traditional Chinese medicine for its diaphoretic, anticonvulsive, sedative, antipyretic, and antiallergic effects. However, the exact pathogenesis of immunoglobulin A nephropathy (IgAN) remains unclear, thereby hindering investigations to identify novel therapeutic agents. A rat IgAN model was established by administration of bovine serum albumin, lipopolysaccharide, and carbon tetrachloride, which simultaneously established blood stasis and a heat syndrome model. The animals were sacrificed to detect changes in protein levels in urine and blood. Immunofluorescence was performed to assess IgA deposition in the glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematology and eosin, periodic acid-Schiff, TUNEL, and immunohistochemical staining were performed to evaluate histopathological changes in kidney tissues. Additionally, target-related proteins were measured by western blotting. Periostracum cicadae resulted in a reduction in blood and urine protein levels. Serum TNF-α, IL-1β, and IL-6 levels significantly decreased in the periostracum cicadae-treated groups compared to the IgAN group. Furthermore, a reduction in MCP-1, TLR4, and IgA expression levels and a dose- dependent increase in caspace-3 expression were observed in response to periostracum cicadae treatment. TGF-β1 levels decreased, whereas that of Fas increased in the kidney tissues of the periostracum cicadae-treated groups. The findings of the present study indicate that periostracum cicadae induces apoptosis and improves kidney inflammation and fibrosis in IgA nephropathy rat models.

Traditional Chinese medicine in treating IgA nephropathy: from basic science to clinical research

“…In the last decades, several natural medicinal monomers have been widely used in the treatment of IgAN and are known to regain the balance of immune function, [55][56][57][58][59] regulate the expression of inflammatory factors, [61][62][63][64][65] and inhibit the proliferation of GMCs. [67][68][69] Among these, the Terpenoid lactones extracted from TwHF have been widely used as an alternative to immunosuppressive medications for the treatment of primary glomerular disease.…”

“…In IgAN rats, Periostracum cicadae could result in the reduction of the levels of TNF-α, IL-1β, and IL-6 in serum. [63] In addition, treated with hirudin, the expression of fibrosis indexes in IgAN rat kidney, included TGF-β1, collagen-IV, and fibronectin-1, was remarkably suppressed. [64] Schisandrin B therapy significantly increased the expression of cytoplasmic p65 and NF-κB in LPS-induced HK-2 cells.…”

BAFF is involved in the pathogenesis of IgA nephropathy by activating the TRAF6/NF‑κB signaling pathway in glomerular mesangial cells

“…a total of 2 weeks after the injection of BSA into the footpads, 6 mmol/l hydrochloric acid-acidified water containing 0.1% BSa was administered every other day. Blood was drawn after three immunization injections of BSA, and the serum anti-BSa antibody titer was measured using the double immunodiffusion method (28). When the antibody titer reached 1:16, 3 mg BSa was intraperitoneally injected daily.…”

“…l2880; Sigma-aldrich; Merck KGaa) was intraperitoneally injected. The model was established after 4 weeks (28). after fasting for 12 h, the rats were placed in a metabolic cage, urine was collected over 24 h, urine volume was recorded and the 24-h urine protein quantity was measured, as aforementioned.…”