2. Academic Validation
  3. Integrating network pharmacology approach and experimental validation to reveal the alleviation of Shenkangning capsule on chronic nephritis

Integrating network pharmacology approach and experimental validation to reveal the alleviation of Shenkangning capsule on chronic nephritis

  • J Ethnopharmacol. 2022 Dec 5;299:115676. doi: 10.1016/j.jep.2022.115676.
Mengjuan Wei 1,  Zhimiao Qiu 1,  Han Li 1,  Bin Lu 1,  Changhong Wang 2,  Lili Ji 3
Affiliations

Affiliations

  • 1 The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 2 The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: wchcxm@shutcm.edu.cn.
  • 3 The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: lichenyue1307@126.com.
PMID: 36057408 DOI: 10.1016/j.jep.2022.115676
Abstract

Ethnopharmacological relevance: Shenkangning (SKN), a Chinese patent medicine composed by eight Chinese medicinal herbs, is commonly applied to treat chronic glomerulonephritis (CGN) in clinic. However, its mechanism is still not clear now.

Aim of the study: This study is designed to evaluate the SKN-provided alleviation on adriamycin (ADR)-induced nephropathy, to reveal its mechanism by integrating network pharmacology analysis and experimental evidences, and to further find the main drug that makes a major contribution to its efficacy.

Materials and methods: ADR was intravenously injected to mice to induce focal segmental glomerulosclerosis (FSGS). Renal histological evaluation was conducted. The level of urinary protein, and serum amounts of creatinine, urea nitrogen (BUN) and albumin were detected. The potential mechanisms were predicted by network pharmacology analysis and further validated by Real-time polymerase chain reaction (RT-PCR), Western-blot and enzyme-linked immunosorbent assay (ELISA).

Results: SKN (1, 10 g/kg) improved ADR-induced nephropathy in mice. Network pharmacology results predicted that inflammation and oxidative stress were crucially involved in the SKN-provided amelioration on nephropathy. SKN reduced the activation of nuclear factor-κB (NF-κB) and the expression of some pro-inflammatory cytokines, and increased the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of its downstream genes in ADR-induced nephropathy in mice. Furthermore, SKN also restored the reduced expression of both podocin and synaptopodin, which are podocyte-associated proteins. Further results showed that the toxic drug Danfupian (DFP) had no contribution to the SKN-provided alleviation on ADR-induced nephropathy in mice. After integrating the results from evaluating anti-inflammation, anti-oxidant and anti-injury of podocytes in vitro and from comparing the activity of the whole SKN and SKN without Astragali Radix (Huangqi, HQ) in vivo, we found that HQ played a crucial contribution to the SKN-provided amelioration on ADR-induced nephropathy in mice.

Conclusion: SKN improved ADR-induced nephropathy through suppressing renal inflammation and oxidative stress injury via abrogating NF-κB activation and activating Nrf2 signaling pathway. HQ played a main contribution to the SKN-provided amelioration on ADR-induced nephropathy.

Keywords

ADR; Nephropathy; Network pharmacology; SKN.

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