Investigation on therapeutic potential and molecular mechanisms of Kunxian capsule against diabetic kidney disease via reversing the imbalance of "immune-inflammation" network
10.16438/j.0513-4870.2021-1109
- VernacularTitle:昆仙胶囊通过矫正“免疫-炎症”失衡网络有效干预糖尿病肾病的潜能及其分子机制研究
- Author:
Yu-dong LIU
1
;
Zhao-chen MA
2
;
Cong-chong LI
1
;
Ya LIN
1
;
Yan-qiong ZHANG
3
;
Na LIN
2
Author Information
1. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
3. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
- Publication Type:Research Article
- Keywords:
iabetic nephropathy;
Kunxian capsule;
imbalance of immune-inflammation system;
network pharmacology;
PI3K/AKT/NF-кB
- From:
Acta Pharmaceutica Sinica
2022;57(2):375-384
- CountryChina
- Language:Chinese
-
Abstract:
Drug repositioning provides new clinical indications for existing drugs. The imbalance between body's "immune-inflammation" regulation is one of the important factors in the occurrence and development of diabetic nephropathy (DN). Chinese patent medicine Kunxian capsule is clinically used for treating rheumatoid arthritis with satisfying immune-modulatory and anti-inflammatory actions. Notably, accumulating clinical evidence based on small cohorts had shown that Kunxian capsule may be used to treat DN. But the underlying pharmacological mechanisms remain unclear. Therefore, this study integrated "drug target-disease gene-biological pathway-function module" multi-level associated network analysis, and in vivo and in vitro experiments, to verify the pharmacological effects of Kunxian capsules in DN and to elucidate its molecular mechanisms. The experimental protocol was reviewed by the Laboratory Animal Welfare and Ethics Committee of China Academy of Chinese Medical Sciences, and it complies with the relevant regulations on laboratory animal welfare and ethics. As a result, the network analysis showed that the candidate targets of Kunxian capsule against DN were significantly involved into various functional modules which were related to modulation of immune-inflammation system, basement membrane lesion, abnormal hemorheology, energy metabolism and hormone metabolism, and the number of targets enriched by PI3K/AKT/NF-κB pathway is the largest. In addition, both in vivo and in vitro experiments demonstrated that Kunxian capsule by gavage effectively reduced blood glucose, improved insulin resistance, reduced blood lipid, inhibited renal extracellular matrix protein production and renal inflammation, improved renal function and pathological damages, and inhibited the activity of PI3K/AKT/NF-κB/TNF-α/IL-1β pathway in diabetic nephropathy rats. Collectively, these findings suggest the therapeutic potentials of Kunxian capsule to alleviate DN by regulating the imbalance of immune-inflammation system.
