Fufang Zhenzhu Tiaozhi capsule attenuates renal damage by restoring Th17/Treg balance in diabetic db/db mice

Objective: To explore the renal protection effect and mechanism of Fufang Zhenzhu Tiaozhi capsule (FTZ) in diabetic db/db mice in vivo and in vitro. Methods: Male db/m mice were considered as control group, and male db/db mice were considered as diabetic kidney disease (DKD) group, which were admini...

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Main Authors: Yiqi YANG, Haibo TAN, Xiaoyu ZHANG, Minyi HUANG, Weijian BEI, Jiao GUO
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-03-01
Series:Journal of Holistic Integrative Pharmacy
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Online Access:http://www.sciencedirect.com/science/article/pii/S270736882300064X
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author Yiqi YANG
Haibo TAN
Xiaoyu ZHANG
Minyi HUANG
Weijian BEI
Jiao GUO
author_facet Yiqi YANG
Haibo TAN
Xiaoyu ZHANG
Minyi HUANG
Weijian BEI
Jiao GUO
author_sort Yiqi YANG
collection DOAJ
description Objective: To explore the renal protection effect and mechanism of Fufang Zhenzhu Tiaozhi capsule (FTZ) in diabetic db/db mice in vivo and in vitro. Methods: Male db/m mice were considered as control group, and male db/db mice were considered as diabetic kidney disease (DKD) group, which were administered with different doses of FTZ (FTZ-L, 1 g•kg-1•d-1; FTZ-H, 2 g•kg-1•d-1) and losartan (positive control, 30 mg•kg-1•d-1) treatment for 12 weeks respectively, and then all mice were sacrificed. The high glucose-induced Jurkat T cell was used to evaluate the immune regulatory effect of FTZ in vitro. The renal pathological change was evaluated by H&E method. The levels of serum creatinine (Scr), proteinuria, and urinary albumin-to-creatinine ratio (UACR) were detected by biochemical parameter test kits. The expression levels of fibronectin and collagen IV were detected by immunofluorescence (IF) and immunohistochemistry (IHC). The inflammation factors including TNF-α, TGF-β, IL-6, IL-8, and IL-10 were detected by ELISA kits. The protein expression levels of IL-17A, RORγt, Foxp3, p-NF-κB, p-IκB, NF-κB, and IκB were detected by western blot. The percentage of T helper 17 (Th17) cells and regulatory T (Treg) cells were measured by flow cytometry. Results: FTZ could significantly alleviate the renal pathological changes and decrease the levels of renal function parameters including Scr, proteinuria, UACR levels, and attenuate the renal inflammation injury by reducing the inflammatory cells infiltration and cytokines (TNF-α, TGF-β, IL-6, and IL-8) secretion, as well as inhibit NF-κB signaling pathway activation and restore the Th17/Treg balance in diabetic db/db mice. Furthermore, FTZ treatment could also decrease the protein levels of RORγt and IL-17A in high glucose-induced Jurkat T cells. Conclusion: FTZ exerted protective effects on the kidney in diabetic db/db mice, whose mechanism might be related to regulating the Th17/Treg balance and inhibiting NF-κB signaling pathway.
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spelling doaj-art-a86308df7f0e4d5e85d89a0ae33607fe2025-08-20T02:14:06ZengKeAi Communications Co., Ltd.Journal of Holistic Integrative Pharmacy2707-36882022-03-0131324410.1016/S2707-3688(23)00064-XFufang Zhenzhu Tiaozhi capsule attenuates renal damage by restoring Th17/Treg balance in diabetic db/db miceYiqi YANG0Haibo TAN1Xiaoyu ZHANG2Minyi HUANG3Weijian BEI4Jiao GUO5Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, ChinaGuangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, ChinaGuangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, ChinaGuangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, ChinaGuangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, ChinaCorresponding author; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, ChinaObjective: To explore the renal protection effect and mechanism of Fufang Zhenzhu Tiaozhi capsule (FTZ) in diabetic db/db mice in vivo and in vitro. Methods: Male db/m mice were considered as control group, and male db/db mice were considered as diabetic kidney disease (DKD) group, which were administered with different doses of FTZ (FTZ-L, 1 g•kg-1•d-1; FTZ-H, 2 g•kg-1•d-1) and losartan (positive control, 30 mg•kg-1•d-1) treatment for 12 weeks respectively, and then all mice were sacrificed. The high glucose-induced Jurkat T cell was used to evaluate the immune regulatory effect of FTZ in vitro. The renal pathological change was evaluated by H&E method. The levels of serum creatinine (Scr), proteinuria, and urinary albumin-to-creatinine ratio (UACR) were detected by biochemical parameter test kits. The expression levels of fibronectin and collagen IV were detected by immunofluorescence (IF) and immunohistochemistry (IHC). The inflammation factors including TNF-α, TGF-β, IL-6, IL-8, and IL-10 were detected by ELISA kits. The protein expression levels of IL-17A, RORγt, Foxp3, p-NF-κB, p-IκB, NF-κB, and IκB were detected by western blot. The percentage of T helper 17 (Th17) cells and regulatory T (Treg) cells were measured by flow cytometry. Results: FTZ could significantly alleviate the renal pathological changes and decrease the levels of renal function parameters including Scr, proteinuria, UACR levels, and attenuate the renal inflammation injury by reducing the inflammatory cells infiltration and cytokines (TNF-α, TGF-β, IL-6, and IL-8) secretion, as well as inhibit NF-κB signaling pathway activation and restore the Th17/Treg balance in diabetic db/db mice. Furthermore, FTZ treatment could also decrease the protein levels of RORγt and IL-17A in high glucose-induced Jurkat T cells. Conclusion: FTZ exerted protective effects on the kidney in diabetic db/db mice, whose mechanism might be related to regulating the Th17/Treg balance and inhibiting NF-κB signaling pathway.http://www.sciencedirect.com/science/article/pii/S270736882300064XFTZDiabetic kidney diseaseInflammationTh17/Tregdb/db mice
spellingShingle Yiqi YANG
Haibo TAN
Xiaoyu ZHANG
Minyi HUANG
Weijian BEI
Jiao GUO
Fufang Zhenzhu Tiaozhi capsule attenuates renal damage by restoring Th17/Treg balance in diabetic db/db mice
Journal of Holistic Integrative Pharmacy
FTZ
Diabetic kidney disease
Inflammation
Th17/Treg
db/db mice
title Fufang Zhenzhu Tiaozhi capsule attenuates renal damage by restoring Th17/Treg balance in diabetic db/db mice
title_full Fufang Zhenzhu Tiaozhi capsule attenuates renal damage by restoring Th17/Treg balance in diabetic db/db mice
title_fullStr Fufang Zhenzhu Tiaozhi capsule attenuates renal damage by restoring Th17/Treg balance in diabetic db/db mice
title_full_unstemmed Fufang Zhenzhu Tiaozhi capsule attenuates renal damage by restoring Th17/Treg balance in diabetic db/db mice
title_short Fufang Zhenzhu Tiaozhi capsule attenuates renal damage by restoring Th17/Treg balance in diabetic db/db mice
title_sort fufang zhenzhu tiaozhi capsule attenuates renal damage by restoring th17 treg balance in diabetic db db mice
topic FTZ
Diabetic kidney disease
Inflammation
Th17/Treg
db/db mice
url http://www.sciencedirect.com/science/article/pii/S270736882300064X
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