PMID- 35855861 OWN - NLM STAT- MEDLINE DCOM- 20220721 LR - 20220728 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2022 DP - 2022 TI - Investigating the Mechanisms of Jieduquyuziyin Prescription Improves Lupus Nephritis and Fibrosis via FXR in MRL/lpr Mice. PG - 4301033 LID - 10.1155/2022/4301033 [doi] LID - 4301033 AB - Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) and one of the leading causes of death. An alternative effective treatment to ameliorate and relieve LN and delay the process of renal tissue fibrosis is urgently needed in the clinical setting. Jieduquyuziyin prescription (JP) has been successfully used to treat SLE, but its potential mechanisms are not sufficiently understood. In this study, we treated MRL/lpr mice with JP for 8 weeks and treated human renal tubular epithelial cells (human kidney 2 (HK-2)) with drug-containing serum to observe the antagonistic effects of JP on inflammation and fibrosis, as well as to investigate the possible mechanisms. Results demonstrated that JP significantly reduced urinary protein and significantly improved pathological abnormalities. Metabolomics combined with ingenuity pathway analysis illustrated that the process of kidney injury in lupus mice may be closely related to farnesoid X receptor (FXR) pathway abnormalities. Microarray biomimetic analysis and LN patients indicated that FXR may play a protective role as an effective therapeutic target for LN and renal fibrosis. JP significantly increased the expression of FXR and inhibited the expression of its downstream targets, namely, nuclear transcription factor kappaB (NF-kappaB) and alpha-smooth muscle actin (alpha-SMA), in the kidney of MRL/lpr mice and HK-2 cells, as confirmed by in vitro and in vivo experiments. In conclusion, JP may mediate the activation of renal FXR expression and inhibit NF-kappaB and alpha-SMA expression to exert anti-inflammatory and antifibrotic effects for LN prevention and treatment. CI - Copyright (c) 2022 Jingqun Liu et al. FAU - Liu, Jingqun AU - Liu J AUID- ORCID: 0000-0003-2524-1364 AD - The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Ma, Qing AU - Ma Q AUID- ORCID: 0000-0001-6453-6603 AD - The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Sun, Qice AU - Sun Q AUID- ORCID: 0000-0002-8963-6528 AD - The Second School of Zhejiang Chinese Medical University, 310053, China. FAU - Luo, Qihan AU - Luo Q AUID- ORCID: 0000-0002-2743-1332 AD - School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Wang, Yiheng AU - Wang Y AUID- ORCID: 0000-0002-5339-1979 AD - Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Wang, Cheng AU - Wang C AUID- ORCID: 0000-0002-1319-1438 AD - Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Zhu, Akao AU - Zhu A AUID- ORCID: 0000-0002-6394-5592 AD - The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. FAU - Zhao, Lisha AU - Zhao L AUID- ORCID: 0000-0001-6941-5253 AD - Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. FAU - Yin, Lu AU - Yin L AUID- ORCID: 0000-0001-7607-3351 AD - Department of Pathology, Affiliated Hangzhou First People's Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Lou, Jiang AU - Lou J AUID- ORCID: 0000-0002-2927-9709 AD - Department of Pharmacy, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. FAU - Dong, Yu AU - Dong Y AUID- ORCID: 0000-0003-0177-1678 AD - Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. FAU - Qiu, Ping AU - Qiu P AUID- ORCID: 0000-0003-0104-0082 AD - School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China. LA - eng PT - Journal Article DEP - 20220709 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Drugs, Chinese Herbal) RN - 0 (NF-kappa B) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (jieduquyuziyin) RN - 0C5V0MRU6P (farnesoid X-activated receptor) SB - IM MH - Animals MH - *Drugs, Chinese Herbal/administration & dosage MH - Humans MH - Kidney/metabolism/pathology MH - *Lupus Erythematosus, Systemic/drug therapy/metabolism/pathology MH - *Lupus Nephritis/drug therapy/metabolism/pathology MH - Mice MH - Mice, Inbred MRL lpr MH - NF-kappa B/metabolism MH - Prescriptions MH - *Receptors, Cytoplasmic and Nuclear/metabolism PMC - PMC9288302 COIS- The authors declare that there are no conflicts of interest. EDAT- 2022/07/21 06:00 MHDA- 2022/07/22 06:00 PMCR- 2022/07/09 CRDT- 2022/07/20 04:07 PHST- 2022/02/21 00:00 [received] PHST- 2022/05/30 00:00 [revised] PHST- 2022/06/19 00:00 [accepted] PHST- 2022/07/20 04:07 [entrez] PHST- 2022/07/21 06:00 [pubmed] PHST- 2022/07/22 06:00 [medline] PHST- 2022/07/09 00:00 [pmc-release] AID - 10.1155/2022/4301033 [doi] PST - epublish SO - Oxid Med Cell Longev. 2022 Jul 9;2022:4301033. doi: 10.1155/2022/4301033. eCollection 2022.