title: Timosaponin B-II ameliorates diabetic nephropathy via TXNIP, mTOR, and NF-κB signaling pathways in alloxan-induced mice.
abstract: BACKGROUND
  Many synthesized drugs with clinical severe side effects have been used for diabetic nephropathy (DN) treatment. Therefore, it is urgent and necessary to identify natural and safe agents to remedy DN. Timosaponin B-II (TB-II), a major steroidal saponin constituent in Anemarrhena asphodeloides Bunge, exhibits various activities, including anti-inflammatory and hypoglycemic functions. However, the anti-DN effects and potential mechanism(s) of TB-II have not been previously reported.
  
  
  OBJECTIVE
  To investigate the effect of TB-II on DN in alloxan-induced diabetic mice.
  
  
  METHODS
  TB-II was isolated and purified from A. asphodeloides Bunge using macroporous adsorption resin and preparative high-performance liquid chromatography. The effect of TB-II on DN was evaluated in alloxan-induced diabetic mice using an assay kit and immunohistochemical determination in vivo. The expression of mammalian target of rapamycin (mTOR), thioredoxin-interacting protein (TXNIP), and nuclear transcription factor-κB (NF-κB) signaling pathways was also measured using Western blot analysis.
  
  
  RESULTS
  TB-II significantly decreased the blood glucose levels and ameliorated renal histopathological injury in alloxan-induced diabetic mice. In addition, TB-II remarkably decreased the levels of renal function biochemical factors, such as kidney index, blood urea nitrogen, serum creatinine, urinary uric acid, urine creatinine, and urine protein, and it reduced lipid metabolism levels of total cholesterol and triglycerides and the levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-α in alloxan-induced mice. Furthermore, TB-II inhibited the expression of mTOR, TXNIP, and NF-κB.
  
  
  CONCLUSIONS
  The results revealed that TB-II plays an important role in DN via TXNIP, mTOR, and NF-κB signaling pathways. Overall, TB-II exhibited a prominently ameliorative effect on alloxan-induced DN.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Chang-Run
authors.initials: CR
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Shi-Xia
authors.initials: SX
authors.lastname: Ruan
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: De
authors.initials: D
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Zhong-Lin
authors.initials: ZL
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000496:Alloxan; D031403:Anemarrhena / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000378:metabolism*; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D013879:Thioredoxins / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D016328:NF-kappa B; D012503:Saponins; D013256:Steroids; C445672:Txnip protein, mouse; C523027:timosaponin B-II; D013879:Thioredoxins; D000496:Alloxan; D020123:Sirolimus
keywords: Anemarrhena asphodeloides Bunge; NF-κB; TXNIP; diabetic nephropathy; mTOR; timosaponin B-II