Therapeutic Effects of Saponins in Rheumatoid Arthritis: Network Pharmacology and Experimental Validation

Overview

Journal Bioengineered

Date 2023 Jan 25

PMID 36694450

Authors

Xinnan Ma

Xin Zhang

Yuanhang Kong

Bo Su

Leilei Wu

Daqian Liu

Xintao Wang

Affiliations

Soon will be listed here.

Abstract

saponins (PNS) have been reported to have good anti-inflammatory effects. However, the anti-inflammatory effect mechanism in rheumatoid arthritis (RA) remains unknown. The focus of this research was to investigate the molecular mechanism of PNS in the treatment of RA. The primary active components of PNS were tested utilizing the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform based on oral bioavailability and drug-likeness. The target databases for knee osteoarthritis were created using GeneCards and Online Mendelian Inheritance in Man (OMIM). The visual interactive network structure 'active component - action target - illness' was created using Cytoscape software. A protein interaction network was built, and associated protein interactions were analyzed using the STRING database. The key targets were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analyses. The effects of PNS on cell growth were studied in human umbilical vein endothelial cells (HUVECs) treated with various doses of PNS, and the optimum concentration of PNS was identified. PNS was studied for its implication on angiogenesis and migration. The active components of PNS had 114 common targets, including cell metabolism and apoptosis, according to the network analysis. The therapeutic effects of the PNS components were suggested to be mediated through apoptotic and cytokine signaling pathways. In vitro, PNS therapy boosted HUVEC proliferation. Wound healing, Boyden chamber and tube formation tests suggested that PNS may increase HUVEC activity and capillary-like tube branching. This study clarified that for the treatment of RA, PNS has multisystem, multicomponent, and multitargeted properties.

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References

Ghoreschi K, Laurence A, OShea J . Janus kinases in immune cell signaling. Immunol Rev. 2009; 228(1):273-87. PMC: 2782696. DOI: 10.1111/j.1600-065X.2008.00754.x. View

Zhang M, Yuan Y, Zhou W, Qin Y, Xu K, Men J . Network pharmacology analysis of Chaihu Lizhong Tang treating non-alcoholic fatty liver disease. Comput Biol Chem. 2020; 86:107248. DOI: 10.1016/j.compbiolchem.2020.107248. View

Ying J, Wang Q, Lu L, Liu J, Guo R, Hu H . Fermitin family homolog 2 (Kindlin-2) affects vascularization during the wound healing process by regulating the Wnt/β-catenin signaling pathway in vascular endothelial cells. Bioengineered. 2021; 12(1):4654-4665. PMC: 8806626. DOI: 10.1080/21655979.2021.1957526. View

Smolen J, Aletaha D, Koeller M, Weisman M, Emery P . New therapies for treatment of rheumatoid arthritis. Lancet. 2007; 370(9602):1861-74. DOI: 10.1016/S0140-6736(07)60784-3. View

Zhang C, Zhang S, Wang L, Kang S, Ma J, Liu S . The RIG-I Signal Pathway Mediated Saponin Anti-Inflammatory Effect in Ischemia Stroke. Evid Based Complement Alternat Med. 2021; 2021:8878428. PMC: 8403041. DOI: 10.1155/2021/8878428. View

Shen K, Ji L, Gong C, Ma Y, Yang L, Fan Y . Notoginsenoside Ft1 promotes angiogenesis via HIF-1α mediated VEGF secretion and the regulation of PI3K/AKT and Raf/MEK/ERK signaling pathways. Biochem Pharmacol. 2012; 84(6):784-92. DOI: 10.1016/j.bcp.2012.05.024. View

Khan M, Sarwar A, Rahat R, Ahmed R, Umar S . Stigmasterol protects rats from collagen induced arthritis by inhibiting proinflammatory cytokines. Int Immunopharmacol. 2020; 85:106642. DOI: 10.1016/j.intimp.2020.106642. View

Zhang H, Li Z, Zhou Z, Yang H, Zhong Z, Lou C . Antidepressant-like effects of ginsenosides: A comparison of ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K, and 20(S)-protopanaxadiol in mice models of despair. Pharmacol Biochem Behav. 2015; 140:17-26. DOI: 10.1016/j.pbb.2015.10.018. View

Wang D, Jie Q, Liu B, Li Y, Dai L, Luo J . Saponin extract from Panax notoginseng promotesangiogenesis through AMPK‑ and eNOS‑dependent pathways in HUVECs. Mol Med Rep. 2017; 16(4):5211-5218. PMC: 5647074. DOI: 10.3892/mmr.2017.7280. View

10.

Szklarczyk D, Gable A, Nastou K, Lyon D, Kirsch R, Pyysalo S . The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2020; 49(D1):D605-D612. PMC: 7779004. DOI: 10.1093/nar/gkaa1074. View

11.

Chu J, Wang X, Bi H, Li L, Ren M, Wang J . Dihydromyricetin relieves rheumatoid arthritis symptoms and suppresses expression of pro-inflammatory cytokines via the activation of Nrf2 pathway in rheumatoid arthritis model. Int Immunopharmacol. 2018; 59:174-180. DOI: 10.1016/j.intimp.2018.04.001. View

12.

Meyer S, Levine R . Molecular pathways: molecular basis for sensitivity and resistance to JAK kinase inhibitors. Clin Cancer Res. 2014; 20(8):2051-9. PMC: 3990645. DOI: 10.1158/1078-0432.CCR-13-0279. View

13.

Wang W, Hong G, Wang S, Gao W, Wang P . Tumor-derived exosomal miRNA-141 promote angiogenesis and malignant progression of lung cancer by targeting growth arrest-specific homeobox gene (GAX). Bioengineered. 2021; 12(1):821-831. PMC: 8291845. DOI: 10.1080/21655979.2021.1886771. View

14.

Hong S, Wan J, Zhang Y, Hu G, Lin H, Seto S . Angiogenic effect of saponin extract from Panax notoginseng on HUVECs in vitro and zebrafish in vivo. Phytother Res. 2008; 23(5):677-86. DOI: 10.1002/ptr.2705. View

15.

Pang H, Li M, Wang Y, Tang M, Ma C, Huang J . Effect of compatible herbs on the pharmacokinetics of effective components of Panax notoginseng in Fufang Xueshuantong Capsule. J Zhejiang Univ Sci B. 2017; 18(4):343-352. PMC: 5394099. DOI: 10.1631/jzus.B1600235. View

16.

McLornan D, Khan A, Harrison C . Immunological Consequences of JAK Inhibition: Friend or Foe?. Curr Hematol Malig Rep. 2015; 10(4):370-9. DOI: 10.1007/s11899-015-0284-z. View

17.

Ning K, Zhao X, Poetsch A, Chen W, Yang J . Computational Molecular Networks and Network Pharmacology. Biomed Res Int. 2017; 2017:7573904. PMC: 5698785. DOI: 10.1155/2017/7573904. View

18.

Bai L, Chen H, Zhou P, Yu J . Identification of Tumor Necrosis Factor-Alpha (TNF-α) Inhibitor in Rheumatoid Arthritis Using Network Pharmacology and Molecular Docking. Front Pharmacol. 2021; 12:690118. PMC: 8175775. DOI: 10.3389/fphar.2021.690118. View

19.

Yang Z, Zhu J, Zhang H, Fan X . Investigating chemical features of based on integrating HPLC fingerprinting and determination of multiconstituents by single reference standard. J Ginseng Res. 2018; 42(3):334-342. PMC: 6026368. DOI: 10.1016/j.jgr.2017.04.005. View

20.

Cao Y, Chen Y, Wang P, Lu J, Han X, She J . Network pharmacology and experimental validation to explore the molecular mechanisms of Bushen Huoxue for the treatment of premature ovarian insufficiency. Bioengineered. 2021; 12(2):10345-10362. PMC: 8810062. DOI: 10.1080/21655979.2021.1996317. View