Huangkui capsule alleviates renal tubular epithelial–mesenchymal transition in diabetic nephropathy via inhibiting NLRP3 inflammasome activation and TLR4/NF-κB signaling

Autor: Yi-Gang Wan, Yan Long, Zi-Yue Wan, Yue Tu, Qian Ma, Ren-Mao Tang, Lu Huang, Wei Wu, Wen-Wen Wang, Wen-Bei Han, Hong-Yun Yee, Hai-Tao Tang, Ying-Lu Liu
Rok vydání: 2019
Předmět:
Male
Epithelial-Mesenchymal Transition
Inflammasomes
Serum albumin
Pharmaceutical Science
Pharmacology
Kidney
Nephrectomy
Rats
Sprague-Dawley
Diabetic nephropathy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
NLR Family
Pyrin Domain-Containing 3 Protein
Drug Discovery
medicine
Animals
Diabetic Nephropathies
Epithelial–mesenchymal transition
030304 developmental biology
Sirolimus
0303 health sciences
Creatinine
biology
business.industry
Anti-Inflammatory Agents
Non-Steroidal
NF-kappa B
Inflammasome
medicine.disease
Streptozotocin
Fibrosis
Toll-Like Receptor 4
Disease Models
Animal
Complementary and alternative medicine
chemistry
030220 oncology & carcinogenesis
biology.protein
TLR4
Molecular Medicine
business
Drugs
Chinese Herbal
Signal Transduction
medicine.drug
Zdroj: Phytomedicine. 57:203-214
ISSN: 0944-7113
DOI: 10.1016/j.phymed.2018.12.021
Popis: Background Huangkui capsule (HKC), an anti-inflammatory Chinese modern patent medicine, has been now widely applied to the clinical therapy of diabetic nephropathy (DN). However, the overall therapeutic mechanisms in vivo are still unclear. Renal tubular epithelial-to-mesenchymal transition (EMT) is one of the major pathogenesis of renal interstitial fibrosis in DN. Recently, the physiological roles of NLRP3 inflammasome activation and toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling are closely linked to EMT. But, it remains elusive whether HKC regulates renal tubular EMT in vivo through targeting NLRP3 inflammasome activation and TLR4/NF-κB signaling in the kidneys. Purpose This study thereby aimed to clarify the therapeutic effects of HKC on renal tubular EMT in DN and its underlying mechanisms in vivo, compared to rapamycin (RAP). Methods Thirty-two rats were randomly divided into 4 groups: the Sham group, the Vehicle group, the HKC group and the RAP group. The early DN rat models were induced by unilateral nephrectomy combined with intraperitoneal injection of streptozotocin, and administered with HKC suspension or RAP suspension or vehicle after modeling for 4 weeks. Changes in the incipient renal lesions-related parameters in urine and blood were analyzed, respectively. Renal interstitial tissues were isolated for histomorphometry, immunohistochemistry and Western blotting at sacrifice. Results For the early DN rat models, HKC at the suitable dose of 2 g/kg/day ameliorated the general condition and biochemical parameters partially including kidney weight (KW), urinary albumin (UAlb), serum creatinine (Scr) and serum albumin (Alb), attenuated renal tubular EMT significantly and inhibited the activation of NLRP3 inflammasome in the kidneys obviously, which was superior to RAP generally. In addition to these, HKC also suppressed TLR4/NF-κB signaling in the kidneys of the DN model rats accurately, which was different from RAP specifically. Conclusion The results of this study further indicated that HKC, different from RAP, can alleviate renal tubular EMT in the DN model rats, likely by inhibiting NLRP3 inflammasome activation and TLR4/NF-κB signaling in the kidneys. Our findings thus provide the more accurate information in vivo about a clinical value of HKC, a traditional anti-inflammatory phytomedicine, in the treatment of the early DN patients.
Databáze: OpenAIRE
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