Tanshinone IIA attenuates renal fibrosis and inflammation via altering expression of TGF-β/Smad and NF-κB signaling pathway in 5/6 nephrectomized rats.
OBJECTIVE
In traditional Chinese medicine, Tanshinone IIA is used to treat chronic kidney disease (CKD). However, its biological activity and mechanism of action in renal fibrosis and inflammation are not fully identified. The current study was conducted to determine the effects of Tanshinone IIA treatment on CKD by assessing potential modulation of the TGF-β/Smad and NF-κB signaling pathway.


METHODS
CKD was produced in rats by 5/6 nephrectomy. They were then divided into the following groups: control (sham operation); CKD (5/6 nephrectomy); 5/6 nephrectomy+Tanshinone IIA (10mg/kg in average, once a day for 16 weeks). Serum and urine samples were obtained from animals in each group, and serum creatinine (Scr), blood urea nitrogen (BUN) levels and 24h urinary protein excretion were measured. Tissue samples from the kidney were used for morphometric studies (Masson's trichrome). The expression of fibronectin protein and collagen types I, III, IV, and TGF-β, TNF-α, CXCL-1, MCP-1, RANTES mRNA were evaluated using immunohistochemistry and RT-PCR analysis; the TGF-β/Smad and NF-κB signaling pathway was detected by immunohistochemistry and Western blot analysis.


RESULTS
The following effects were observed in CKD rats treated with Tanshinone IIA: (1) marked improvements in Scr, and 24h urine protein excretion; (2) significant reductions in protein and mRNA levels of fibronectin, collagen III, and collagen IV and TNF-α, MCP-1, and CXCL-1; (3) significantly inhibited the TGF-β/Smad and NF-κB signaling activation.


CONCLUSIONS
These results suggest that Tanshinone IIA suppresses renal fibrosis and inflammation via altering expression of TGF-β/Smad and NF-κB pathway in the remnant kidney, thus supporting the potential of Tanshinone IIA as a new therapeutic agent for slowing the progression of CKD.
Department of Nephrology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530011, China. Electronic address: 95401864@qq.com.
Dong-Tao
DT
Wang
Department of Nephrology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530011, China.
Ren-Hua
RH
Huang
Department of Nephrology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530011, China.
Xin
X
Cheng
Department of Traditional Chinese Medicine, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China.
Zhi-Hua
ZH
Zhang
Department of Pharmacology Guangdong Key Laboratory for R&D of Natural Drug, Guangdong Medical College, Zhanjiang 524023, China.
Ya-Jun
YJ
Yang
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510280, China.
Xin
X
Lin
D045784:Abietanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D008516:Medicine, Chinese Traditional; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D009392:Nephrectomy; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D051785:Smad Proteins / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C021751:tanshinone
Chronic kidney disease; Renal fibrosis; Tanshinone IIA