Lifei Gu1, Yange Wang1, Guolin Yang1, Akhtolkhyn Tilyek1, Chunlei Zhang1, Shaoheng Li1, Boyang Yu1, Chengzhi Chai2, Zhengyu Cao3. 1. Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. 2. Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. Electronic address: chaichengzhi@126.com. 3. Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. Electronic address: zycao1999@hotmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Ribes diacanthum Pall (RDP), a folk medicine, has been widely used in Mongolia to treat urinary system diseases. AIM OF THE STUDY: To investigate the effectiveness of RDP on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis and the underlying mechanisms. MATERIALS AND METHODS: A total of 60 mice were randomly divided into six groups: sham group, sham plus RDP (40 mg/kg) group, UUO model group, and UUO model plus RDP (10, 20 or 40 mg/kg) groups. After surgery, aqueous extract of RDP were administrated intragastrically (i.g) daily for a week and ipsilateral kidneys were collected seven days after surgery. Levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were detected to reflect the kidney injury. Hematoxylin & eosin and Masson's trichrome staining were used to evaluate the kidney morphological changes and fibrosis, respectively. ELISA was used to examine the levels of pro-inflammatory cytokines. Immunohistochemistry, western blot and PCR were used to examine the expression levels of key proteins involved in transforming growth factor (TGF-β)/Smad and mitogen-activated protein kinase (MAPK) signaling pathways. RESULTS: RDP treatment attenuates the level of BUN and kidney fibrosis in UUO mice, decreases the expressions of interleukin-6, tumor necrosis factor-α, Interleukin-1α, TGF-β1, monocyte chemotactic protein-1, α-smooth muscle actin, collagen I, fibronectin, and vimentin, while increases the expressions of E-cadherin and hepatocyte growth factor. Moreover, RDP administration significantly decreases the levels of p-Smad2/3, p-ERK1/2, p-p38 and p-JNK, while increases the expression level of Smad7 in UUO models. CONCLUSION: These data demonstrate that RDP ameliorates renal fibrosis through TGF-β/Smad and MAPK pathways in a UUO mouse model.
ETHNOPHARMACOLOGICAL RELEVANCE: Ribes diacanthum Pall (RDP), a folk medicine, has been widely used in Mongolia to treat urinary system diseases. AIM OF THE STUDY: To investigate the effectiveness of RDP on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis and the underlying mechanisms. MATERIALS AND METHODS: A total of 60 mice were randomly divided into six groups: sham group, sham plus RDP (40 mg/kg) group, UUO model group, and UUO model plus RDP (10, 20 or 40 mg/kg) groups. After surgery, aqueous extract of RDP were administrated intragastrically (i.g) daily for a week and ipsilateral kidneys were collected seven days after surgery. Levels of blood ureanitrogen (BUN) and serum creatinine (Scr) were detected to reflect the kidney injury. Hematoxylin & eosin and Masson's trichrome staining were used to evaluate the kidney morphological changes and fibrosis, respectively. ELISA was used to examine the levels of pro-inflammatory cytokines. Immunohistochemistry, western blot and PCR were used to examine the expression levels of key proteins involved in transforming growth factor (TGF-β)/Smad and mitogen-activated protein kinase (MAPK) signaling pathways. RESULTS:RDP treatment attenuates the level of BUN and kidney fibrosis in UUO mice, decreases the expressions of interleukin-6, tumor necrosis factor-α, Interleukin-1α, TGF-β1, monocyte chemotactic protein-1, α-smooth muscle actin, collagen I, fibronectin, and vimentin, while increases the expressions of E-cadherin and hepatocyte growth factor. Moreover, RDP administration significantly decreases the levels of p-Smad2/3, p-ERK1/2, p-p38 and p-JNK, while increases the expression level of Smad7 in UUO models. CONCLUSION: These data demonstrate that RDP ameliorates renal fibrosis through TGF-β/Smad and MAPK pathways in a UUO mouse model.