Baicalin protects against renal interstitial fibrosis in mice by inhibiting the TGF-β/Smad signalling pathway

Abstract

Context Baicalin, a flavonoid extracted from radix scutellariae, possesses various pharmacological effects, including protective effects on renal interstitial fibrosis (RIF), but its possible role and mechanisms have not been fully elucidated. Objective This study explores the protective effects and mechanisms of baicalin on RIF. Materials and methods C57BL/6 male mice were divided into six groups: sham, model, low baicalin, middle baicalin, high baicalin and positive drug groups. The unilateral ureteral obstruction (UUO) model of RIF was constructed and treated with baicalin doses (10, 20 and 40 mg/kg) and a positive control drug (valsartan, 8 mg/kg). H&E staining was used to observe the pathological changes in renal tissues, Masson staining was performed to evaluate collagen deposition in renal tissues, and immunohistochemical examination was adopted to determine α-SMA and extracellular matrix (ECM) expression. Primary mouse fibroblasts were isolated, extracted and treated with baicalin and/or TGF-β. qRT-PCR and enzyme-linked immunosorbent assay (ELISA) were applied to detect the inflammatory responses. Moreover, ECM and TGF-β/Smad expression levels were evaluated by western blot assay. Results Baicalin ameliorated RIF in UUO mice by inhibiting fibrosis and inflammatory responses. The TGF-β/Smad pathway was significantly suppressed in the UUO mouse model. Additionally, baicalin significantly inhibited ECM expression and inflammatory factors in fibroblasts treated with TGF-β. TGF-β/Smad pathway activation was significantly decreased in fibroblasts. Discussion and conclusions These findings support the use of baicalin as a potential therapeutic option for the treatment of RIF by possibly inhibiting the TGF-β/Smad signalling pathway.

Simultaneous determination of multiple constituents, serum composition, and tissue distribution of Qingshen granule using ultra‐high performance liquid chromatography‐quadrupole‐orbitrap high‐resolution mass spectrometry

“…Meanwhile, KAE attenuates renal injury and reverses phenotypic transformation and collagen accumulation in renal tubular epithelial cells [22]. Baicalin, emodin, chrysophanol, and ferulic acid are potential therapeutic options for delaying renal fibrosis by inhibiting the TGF‐β/Smad signaling pathway [23–26]. Moreover, emodin and chlorogenic acid induce myofibroblast apoptosis by regulating the PI3K/Akt pathway, thereby improving renal tubular interstitial fibrosis [27, 28].…”

“…Baicalin, emodin, chrysophanol, and ferulic acid are potential therapeutic options for delaying renal fibrosis by inhibiting the TGF-β/Smad signaling pathway [23][24][25][26]. Moreover, emodin and chlorogenic acid induce myofibroblast apoptosis by regulating the PI3K/Akt pathway, F I G U R E 3 Continued thereby improving renal tubular interstitial fibrosis [27,28].…”

Antioxidant therapy against TGF‐β/SMAD pathway involved in organ fibrosis

“…Based on dosage, Baicalin activates TGF‐β/Smad signalling pathway and contributes to renal fibrosis 123 . Although it's not always the case, since a study conducted on mice models of RIF showed opposite results 124 . It was revealed that baicalin acts as an anti‐fibrotic agent in renal fibrosis via suppressing the mentioned pathway 124 …”

“…123 Although it's not always the case, since a study conducted on mice models of RIF showed opposite results. 124 It was revealed that baicalin acts as an anti-fibrotic agent in renal fibrosis via suppressing the mentioned pathway. 124 Table 4 summarizes treatment of renal fibrosis models and cell lines with different antioxidants and their subsequent impact on TGF-β/ SMAD pathway.…”

“… 124 It was revealed that baicalin acts as an anti‐fibrotic agent in renal fibrosis via suppressing the mentioned pathway. 124 …”