Effects and Mechanism of Combination of Rhein and Danshensu in the Treatment of Chronic Kidney Disease.
Traditional Chinese medicine (TCM) plays a systemic role in disease treatment, targeting multiple etiological factors simultaneously. Based on clinical experience, rhubarb and Salvia miltiorrhiza are commonly prescribed together for the treatment of chronic kidney disease (CKD) and have been proven to be very effective. However, the rationale of the combination remains unclear. The major active ingredients of these two herbs are rhein (RH) and danshensu (DSS), respectively. The aim of this paper is to investigate the renoprotective effects of RH and DSS in vitro and in vivo, and the underlying mechanism. A total of 5/6 nephrectomy rats and HK-2 cells were subjected to chronic renal injury. The combination of RH and DSS conferred a protective effect, as shown by a significant improvement in the renal function, blood supply, and fibrotic degree. Proinflammatory cytokines and adhesion molecules were suppressed by RH and DSS through NK-κB signaling. The combination also inhibited apoptosis by up-regulating Bcl-2 and down-regulating Bax. Inhibiting the TGF-β/Smad3 pathway was at least in part involved in the antifibrotic mechanism of the combination treatment of RH and DSS. This study demonstrates for the first time the renoprotective effect and the mechanism of RH and DSS combination on chronic renal injury. It could provide experimental evidence to support the rationality of the combinatorial use of TCM in clinical practices.
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Yue
Y
Guan
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Xiao-Xiao
XX
Wu
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Jia-Lin
JL
Duan
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Ying
Y
Yin
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Chao
C
Guo
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Guo
G
Wei
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Yan-Hua
YH
Wang
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Yan-Rong
YR
Zhu
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Yan
Y
Weng
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Miao-Miao
MM
Xi
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Ai-Dong
AD
Wen
D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007773:Lactates / Q000008:administration & dosage* / Q000494:pharmacology; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012250:Rheum / Q000737:chemistry; D027561:Salvia miltiorrhiza / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000880:Anthraquinones; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D007773:Lactates; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C035055:3,4-dihydroxyphenyllactic acid; C020491:rhein
Combination; Danshensu; Rhein