Integrating network analysis and experimental validation to reveal the mechanism of Cuscuta chinensis lam. Extract in the treatment of IgA nephropathy

Purpose/aim: IgA nephropathy represents a prevalent form of the common kidney disease globally, accounting for the majority of cases of chronic kidney disease and renal failure. Cuscuta chinensis Lam has been shown to nourish the liver and tonify the kidney, consolidate essence, and arrest polyuria,...

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Main Authors: Xianlong Zhang, Mingjie Liang, Ziyang Lin, Minyi Li, Tingting Duan, Yun Han, Lanqing Meng, Mengqiu Li, Guixuan Lin, Tao Xia, Ying Lai, Boen Liang, Bingqiong Li, Minhua Li, Fengxin Kang, Quan Zhu, Zhenghai Li, Junzheng Yang
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Journal of Functional Foods
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Online Access:http://www.sciencedirect.com/science/article/pii/S1756464624006613
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author Xianlong Zhang
Mingjie Liang
Ziyang Lin
Minyi Li
Tingting Duan
Yun Han
Lanqing Meng
Mengqiu Li
Guixuan Lin
Tao Xia
Ying Lai
Boen Liang
Bingqiong Li
Minhua Li
Fengxin Kang
Quan Zhu
Zhenghai Li
Junzheng Yang
author_facet Xianlong Zhang
Mingjie Liang
Ziyang Lin
Minyi Li
Tingting Duan
Yun Han
Lanqing Meng
Mengqiu Li
Guixuan Lin
Tao Xia
Ying Lai
Boen Liang
Bingqiong Li
Minhua Li
Fengxin Kang
Quan Zhu
Zhenghai Li
Junzheng Yang
author_sort Xianlong Zhang
collection DOAJ
description Purpose/aim: IgA nephropathy represents a prevalent form of the common kidney disease globally, accounting for the majority of cases of chronic kidney disease and renal failure. Cuscuta chinensis Lam has been shown to nourish the liver and tonify the kidney, consolidate essence, and arrest polyuria, However, whether Cuscuta chinensis Lam has the protective effects on IgA nephropathy and the underlying mechanisms remain unclear. Methods: A network pharmacology analysis was employed to examine the interactions between the active ingredients and core targets, with a view to elucidating the possible potential mechanisms in Cuscuta chinensis Lam. extract (CCLE) in the treatment of IgA nephropathy. Sprague-Dawley rats were administered with bovine serum albumin (BSA) with a dose of 800 mg/kg−1 every other day for a period of 12 weeks to obtain IgA nephropathy model. lipopolysaccharide (LPS) was injected through the tail vein at a dose of 0.05 mg at the 6th week, 8th week, and 10th week; 0.1 mL of CCl4 and 0.3 mL of castor oil were injected subcutaneously once a week for 12 weeks; the rats were gavaged with CCLE for 6 weeks from 13th week. Biochemical analysis, tGFR analysis, enzyme-linked immunosorbent assay (ELISA) analysis, periodic acid-Schiff (PAS) staining, Masson staining, and immunofluorescence staining were employed to evaluate the impact of CCLE on IgA nephropathy in rat. Western blotting was utilized to investigate the underlying mechanisms. Results: The results demonstrated that a significant decrease in the glomerular filtration rate, accompanied by a notable elevation in biochemical indexes in rats in model group, including the ratio of total protein to creatinine in urine, sCr, BUN, TG, AST, ALT, IL-1β and TNF-α; additionally, the rats in the model group exhibited substantial histopathological alterations, characterized by the presence of many IgA deposits; CCLE has been demonstrated to enhance the glomerular filtration rate, downregulate the levels of sCr, BUN, TG, AST, ALT, IL-1β and TNF-α, reduce the IgA deposition, and ameliorate the histopathological changes in IgA nephropathy rats; Western blotting demonstrated CCLE can suppress the expressions of p-PI3K, p-AKT, p-IKK, p-NF-κB, and p-IκB in IgA nephropathy rats. Conclusion: CCLE demonstrated superior protective effects on BSA + LPS + CCl4 + castor oil-induced IgA nephropathy in rats by regulating the PI3K-AKT and NF-κB signaling pathways. These findings suggest that CCLE has potential as a therapeutic agent for the treatment of IgA nephropathy.
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spelling doaj-art-e17c9368b13340159bb54c5619454ca32025-01-12T05:24:49ZengElsevierJournal of Functional Foods1756-46462025-01-01124106658Integrating network analysis and experimental validation to reveal the mechanism of Cuscuta chinensis lam. Extract in the treatment of IgA nephropathyXianlong Zhang0Mingjie Liang1Ziyang Lin2Minyi Li3Tingting Duan4Yun Han5Lanqing Meng6Mengqiu Li7Guixuan Lin8Tao Xia9Ying Lai10Boen Liang11Bingqiong Li12Minhua Li13Fengxin Kang14Quan Zhu15Zhenghai Li16Junzheng Yang17The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China; Guangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaThe Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China; Guangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, ChinaGuangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, China; Corresponding author.Guangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou 510530, China; Corresponding author.Purpose/aim: IgA nephropathy represents a prevalent form of the common kidney disease globally, accounting for the majority of cases of chronic kidney disease and renal failure. Cuscuta chinensis Lam has been shown to nourish the liver and tonify the kidney, consolidate essence, and arrest polyuria, However, whether Cuscuta chinensis Lam has the protective effects on IgA nephropathy and the underlying mechanisms remain unclear. Methods: A network pharmacology analysis was employed to examine the interactions between the active ingredients and core targets, with a view to elucidating the possible potential mechanisms in Cuscuta chinensis Lam. extract (CCLE) in the treatment of IgA nephropathy. Sprague-Dawley rats were administered with bovine serum albumin (BSA) with a dose of 800 mg/kg−1 every other day for a period of 12 weeks to obtain IgA nephropathy model. lipopolysaccharide (LPS) was injected through the tail vein at a dose of 0.05 mg at the 6th week, 8th week, and 10th week; 0.1 mL of CCl4 and 0.3 mL of castor oil were injected subcutaneously once a week for 12 weeks; the rats were gavaged with CCLE for 6 weeks from 13th week. Biochemical analysis, tGFR analysis, enzyme-linked immunosorbent assay (ELISA) analysis, periodic acid-Schiff (PAS) staining, Masson staining, and immunofluorescence staining were employed to evaluate the impact of CCLE on IgA nephropathy in rat. Western blotting was utilized to investigate the underlying mechanisms. Results: The results demonstrated that a significant decrease in the glomerular filtration rate, accompanied by a notable elevation in biochemical indexes in rats in model group, including the ratio of total protein to creatinine in urine, sCr, BUN, TG, AST, ALT, IL-1β and TNF-α; additionally, the rats in the model group exhibited substantial histopathological alterations, characterized by the presence of many IgA deposits; CCLE has been demonstrated to enhance the glomerular filtration rate, downregulate the levels of sCr, BUN, TG, AST, ALT, IL-1β and TNF-α, reduce the IgA deposition, and ameliorate the histopathological changes in IgA nephropathy rats; Western blotting demonstrated CCLE can suppress the expressions of p-PI3K, p-AKT, p-IKK, p-NF-κB, and p-IκB in IgA nephropathy rats. Conclusion: CCLE demonstrated superior protective effects on BSA + LPS + CCl4 + castor oil-induced IgA nephropathy in rats by regulating the PI3K-AKT and NF-κB signaling pathways. These findings suggest that CCLE has potential as a therapeutic agent for the treatment of IgA nephropathy.http://www.sciencedirect.com/science/article/pii/S1756464624006613CCLEIgA nephropathyPI3KAKTNF-κBRat
spellingShingle Xianlong Zhang
Mingjie Liang
Ziyang Lin
Minyi Li
Tingting Duan
Yun Han
Lanqing Meng
Mengqiu Li
Guixuan Lin
Tao Xia
Ying Lai
Boen Liang
Bingqiong Li
Minhua Li
Fengxin Kang
Quan Zhu
Zhenghai Li
Junzheng Yang
Integrating network analysis and experimental validation to reveal the mechanism of Cuscuta chinensis lam. Extract in the treatment of IgA nephropathy
Journal of Functional Foods
CCLE
IgA nephropathy
PI3K
AKT
NF-κB
Rat
title Integrating network analysis and experimental validation to reveal the mechanism of Cuscuta chinensis lam. Extract in the treatment of IgA nephropathy
title_full Integrating network analysis and experimental validation to reveal the mechanism of Cuscuta chinensis lam. Extract in the treatment of IgA nephropathy
title_fullStr Integrating network analysis and experimental validation to reveal the mechanism of Cuscuta chinensis lam. Extract in the treatment of IgA nephropathy
title_full_unstemmed Integrating network analysis and experimental validation to reveal the mechanism of Cuscuta chinensis lam. Extract in the treatment of IgA nephropathy
title_short Integrating network analysis and experimental validation to reveal the mechanism of Cuscuta chinensis lam. Extract in the treatment of IgA nephropathy
title_sort integrating network analysis and experimental validation to reveal the mechanism of cuscuta chinensis lam extract in the treatment of iga nephropathy
topic CCLE
IgA nephropathy
PI3K
AKT
NF-κB
Rat
url http://www.sciencedirect.com/science/article/pii/S1756464624006613
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