Cayratia Albifolia C.L.Li Exerts Anti-rheumatoid Arthritis Effect by Inhibiting Macrophage Activation and Neutrophil Extracellular Traps (NETs)

Overview

Journal Chin Med

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2024 Mar 5

PMID 38444022

Authors

Wei Wang

Zai-Qi Zhang

Yi-Chi Zhang

Yi-Qiang Wu

Zhuo Yang

Yong-Zhe Zheng

Jia-Hong Lu

Peng-Fei Tu

Ke-Wu Zeng

Affiliations

Soon will be listed here.

Abstract

Background: Cayratia albifolia C.L.Li (CAC), commonly known as "Jiao-Mei-Gu" in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established.

Methods: Twenty-four Sprague-Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot.

Results: CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA.

Conclusions: We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation.

Citing Articles

The emerging role of neutrophil extracellular traps in the progression of rheumatoid arthritis.

Chen J, Cao Y, Xiao J, Hong Y, Zhu Y Front Immunol. 2024; 15:1438272.

PMID: 39221253 PMC: 11361965. DOI: 10.3389/fimmu.2024.1438272.

References

Xia T, Fu S, Yang R, Yang K, Lei W, Yang Y . Advances in the study of macrophage polarization in inflammatory immune skin diseases. J Inflamm (Lond). 2023; 20(1):33. PMC: 10568804. DOI: 10.1186/s12950-023-00360-z. View

van der Woude D, van der Helm-van Mil A . Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2018; 32(2):174-187. DOI: 10.1016/j.berh.2018.10.005. View

Wu D, Luo Y, Li T, Zhao X, Lv T, Fang G . Systemic complications of rheumatoid arthritis: Focus on pathogenesis and treatment. Front Immunol. 2023; 13:1051082. PMC: 9817137. DOI: 10.3389/fimmu.2022.1051082. View

Yao Y, Cai X, Ren F, Ye Y, Wang F, Zheng C . The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases. Front Immunol. 2021; 12:664871. PMC: 8044404. DOI: 10.3389/fimmu.2021.664871. View

Alfaro-Lara R, Espinosa-Ortega H, Arce-Salinas C . Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis. Reumatol Clin (Engl Ed). 2017; 15(3):133-139. DOI: 10.1016/j.reuma.2017.07.020. View

Jie S, Sun H, Liu J, Gao Y, Bai D, Zhu L . Simiao Yong'an decoction ameliorates murine collagen-induced arthritis by modulating neutrophil activities: An in vitro and in vivo study. J Ethnopharmacol. 2023; 305:116119. DOI: 10.1016/j.jep.2022.116119. View

Huang J, Hong W, Wan M, Zheng L . Molecular mechanisms and therapeutic target of NETosis in diseases. MedComm (2020). 2022; 3(3):e162. PMC: 9390875. DOI: 10.1002/mco2.162. View

Kumar L, Karthik R, Gayathri N, Sivasudha T . Advancement in contemporary diagnostic and therapeutic approaches for rheumatoid arthritis. Biomed Pharmacother. 2016; 79:52-61. DOI: 10.1016/j.biopha.2016.02.001. View

Osipova D, Janssen R, Martens H . [Rheumatoid arthritis: more than a joint disease]. Ned Tijdschr Geneeskd. 2020; 164. View

10.

Sharma D, Chaubey P, Suvarna V . Role of natural products in alleviation of rheumatoid arthritis-A review. J Food Biochem. 2021; 45(4):e13673. DOI: 10.1111/jfbc.13673. View

11.

Smolen J, Aletaha D . Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheumatol. 2015; 11(5):276-89. DOI: 10.1038/nrrheum.2015.8. View

12.

Patel J, Konanur Srinivasa N, Gande A, Anusha M, Dar H, Baji D . The Role of Biologics in Rheumatoid Arthritis: A Narrative Review. Cureus. 2023; 15(1):e33293. PMC: 9808655. DOI: 10.7759/cureus.33293. View

13.

Huang G, Yuan K, Zhu Q, Zhang S, Lu Q, Zhu M . Triptolide inhibits the inflammatory activities of neutrophils to ameliorate chronic arthritis. Mol Immunol. 2018; 101:210-220. DOI: 10.1016/j.molimm.2018.06.012. View

14.

Pan T, Cheng T, Jia Y, Li P, Li F . Anti-rheumatoid arthritis effects of traditional Chinese herb couple in adjuvant-induced arthritis in rats. J Ethnopharmacol. 2017; 205:1-7. DOI: 10.1016/j.jep.2017.04.020. View

15.

Cutolo M, Campitiello R, Gotelli E, Soldano S . The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis. Front Immunol. 2022; 13:867260. PMC: 9161083. DOI: 10.3389/fimmu.2022.867260. View

16.

Hirose J, Tanaka S . [Animal models for bone and joint disease. CIA, CAIA model]. Clin Calcium. 2011; 21(2):253-9. DOI: CliCa1102253259. View

17.

Choudhary N, Bhatt L, Prabhavalkar K . Experimental animal models for rheumatoid arthritis. Immunopharmacol Immunotoxicol. 2018; 40(3):193-200. DOI: 10.1080/08923973.2018.1434793. View

18.

Chan Y, Tan H, Lu Y, Zhang C, Cheng C, Wu J . Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis. Acta Pharm Sin B. 2023; 13(4):1554-1567. PMC: 10150138. DOI: 10.1016/j.apsb.2023.01.020. View

19.

An Z, Li J, Yu J, Wang X, Gao H, Zhang W . Neutrophil extracellular traps induced by IL-8 aggravate atherosclerosis via activation NF-κB signaling in macrophages. Cell Cycle. 2019; 18(21):2928-2938. PMC: 6791689. DOI: 10.1080/15384101.2019.1662678. View

20.

Vergadi E, Ieronymaki E, Lyroni K, Vaporidi K, Tsatsanis C . Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization. J Immunol. 2017; 198(3):1006-1014. DOI: 10.4049/jimmunol.1601515. View