Anti-inflammatory effects of Solanum procumbens on a low dose complete Freund's adjuvant-induced arthritis rat model

Abstract

Objective: To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund's adjuvant-induced arthritis rat models. Methods: We isolated and identified five compounds in the ethanol-soluble Solanum procumbens extract (SP) with anti-inflammatory effects, including ursolic acid, β-sitosterol, hexadecanoic acid, cis-vaccenic acid, and vanillic acid. Additionally, we investigated the anti-inflammatory effects of SP on rheumatoid arthritis symptoms, including paw volumes, local temperatures, withdrawal latency, and mechanical withdrawal threshold at the hind paw and white blood cell (WBC) number from complete Freund's adjuvant-induced arthritis rat models. Results: We have successfully established a complete Freund's adjuvant-induced arthritis rat model at a low dose (1 mg/mL). SP extract significantly reduced paw volumes (P<0.05), prolonged withdrawal latencies (P<0.05), decreased local temperature, and increased the mechanical withdrawal threshold (P<0.05), but only SP extract at the dose of 300 mg/kg significantly decreased WBC numbers. Conclusions: SP extract could be a potential medication candidate with anti-inflammatory effects for arthritis, but it requires further investigation into the mechanism of the SP and its effectiveness on other models as well as clinical trials.

Keywords

Solanum procumbens / Arthritis / Anti-inflammation / Complete Freund's adjuvant / Rats

Acknowledgments

This work is supported by Military Hospital 103 and Vietnam Military Medical University.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

The authors received no extramural funding for this study.

Authors’ contributions

XHD performed experiments, data acquisition, data analysis, and manuscript writing. TNN performed experiments, data acquisition, and data analysis. TCD collected experimental data and participated in revising the manuscript. TTMN, TNN, VNTD, HTL, XHN, GLN, DKH and HPD contributed to the experimental design, and data analysis, and participated in completing the relevant experiments. XHD, VMC, and VQL contributed to the design of the study and wrote the original manuscript. XHD, VMC, and VQL confirmed the authenticity of all raw data and agreed to be accountable for all aspects of the study in ensuring that questions related to the accuracy or integrity of any part of the study are appropriately investigated and resolved.

References

[1] Gibofsky A. Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A synopsis. Am J Manag Care 2014; 20(7 Suppl): S128-S135.

[2] Chatzidionysiou K, Emamikia S, Nam J, Ramiro S, Smolen J, Heijde D van der, et al. Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: A systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2017; 76(6): 1102-1107.

[3] Nandi P, Kingsley GH, Scott DL. Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis. Curr Opin Rheumatol 2008; 20(3): 251-256.

[4] Domper Arnal MJ, Hijos-Mallada G, Lanas A. Gastrointestinal and cardiovascular adverse events associated with NSAIDs. Expert Opin Drug Saf 2022; 21(3): 373-384.

[5] Magni A, Agostoni P, Bonezzi C, Massazza G, Menè P, Savarino V, et al. Management of osteoarthritis: Expert opinion on NSAIDs. Pain Ther 2021; 10(2): 783-808.

[6] Fine M. Quantifying the impact of NSAID-associated adverse events. Am J Manag Care 2013; 19(14 Suppl): s267-s272.

[7] Sepriano A, Kerschbaumer A, Smolen JS, van der Heijde D, Dougados M, van Vollenhoven R, et al. Safety of synthetic and biological DMARDs: A systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2020; 79(6): 760-770.

[8] Wang Y, Chen S, Du K, Liang C, Wang S, Owusu Boadi E, et al. Traditional herbal medicine: Therapeutic potential in rheumatoid arthritis. J Ethnopharmacol 2021; 279: 114368.

[9] Yang CLH, Or TCT, Ho MHK, Lau ASY. Scientific basis of botanical medicine as alternative remedies for rheumatoid arthritis. Clin Rev Allergy Immunol 2013; 44(3): 284-300.

[10] Senftleber NK, Nielsen SM, Andersen JR, Bliddal H, Tarp S, Lauritzen L, et al. Marine oil supplements for arthritis pain: A systematic review and meta-analysis of randomized trials. Nutrients 2017; 9(1): 42.

[11] Fletcher A, Lassere M, March L, Hill C, Carroll G, Barrett C, et al. Oral complementary medicine use among people with inflammatory arthritis: An australian rheumatology association database analysis. Int J Rheumatol 2020; 2020: 6542965.

[12] Ismail CAN, Noh ASM, Tan DC, Khir NAM, Shafin N. A review on complete Freund's adjuvant-induced arthritic rat model: Factors leading to its success. IIUM Med J Malay 2022; 21(4). doi: 10.31436/imjm.v21i4.2026.

[13] Noh ASM, Chuan TD, Khir NAM, Zin AAM, Ghazali AK, Long I, et al. Effects of different doses of complete Freund's adjuvant on nociceptive behaviour and inflammatory parameters in polyarthritic rat model mimicking rheumatoid arthritis. PLoS One 2021; 16(12): e0260423.

[14] Garrison SR, Stucky CL. Contribution of transient receptor potential ankyrin 1 to chronic pain in aged mice with complete Freund's adjuvant-induced arthritis. Arthritis Rheumatol 2014; 66(9): 2380-2390.

[15] Barrot M. Tests and models of nociception and pain in rodents. Neuroscience 2012; 211: 39-50.

[16] Rayiti RK, Munnangi SR, Bandarupalli R, Chakka V, Nimmagadda SL, Sk LS, et al. Effect of chrysin on mechanical hyperalgesia in chronic constriction injury-induced neuropathic pain in rat model. Int J Appl Basic Med Res 2020; 10(3): 189-193.

[17] Kang SY, Yoon SY, Roh DH, Jeon MJ, Seo HS, Uh DK, et al. The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models. J Pharm Pharmacol 2008; 60(10): 1347-1354.

[18] Baek SY, Lee J, Lee DG, Park MK, Lee J, Kwok SK, et al. Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation. Acta Pharmacol Sin 2014; 35(9): 1177-1187.

[19] Loizou S, Lekakis I, Chrousos GP, Moutsatsou P. Beta-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol Nutr Food Res 2010; 54(4): 551-558.

[20] Sun Y, Gao L, Hou W, Wu J. β-Sitosterol alleviates inflammatory response via inhibiting the activation of ERK/p38 and NF-κB pathways in LPS-exposed BV2 cells. Biomed Res Int 2020; 2020: 7532306.

[21] Aparna V, Dileep KV, Mandal PK, Karthe P, Sadasivan C, Haridas M. Anti-inflammatory property of n-hexadecanoic acid: Structural evidence and kinetic assessment. Chem Biol Drug Des 2012; 80(3): 434-439.

[22] Anyasor GN, Funmilayo O, Odutola O, Olugbenga A, Oboutor EM. Chemical constituents in n-butanol fractions of Castus afer ker Gawl leaf and stem. J Intercult Ethnopharmacol 2014; 3(2): 78-84.

[23] Ziadlou R, Barbero A, Martin I, Wang X, Qin L, Alini M, et al. Anti-inflammatory and chondroprotective effects of vanillic acid and epimedin C in human osteoarthritic chondrocytes. Biomolecules 2020; 10(6): 932.

[24] Poudel P, Goyal A, Lappin SL. Inflammatory arthritis. In: StatPearls. StatPearls Publishing: Treasure Island (FL); 2023. [Online] Available from: http://www.ncbi.nlm.nih.gov/books/NBK507704/ [Accessed on 4 Apr 2023].

[25] Gomes RP, Bressan E, Silva TM da, Gevaerd M da S, Tonussi CR, Domenech SC. Standardization of an experimental model suitable for studies on the effect of exercise on arthritis. Einstein (Sao Paulo) 2013; 11(1): 76-82.

[26] Mahdi HJ, Khan NAK, Asmawi MZB, Mahmud R, A/L Murugaiyah V. In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund's adjuvant (CFA)-induced arthritis in rats. Integr Med Res 2018; 7(1): 85-94.

[27] Zhang X, Dong Y, Dong H, Zhang W, Li F. Investigation of the effect of phlomisoside F on complete Freund's adjuvant-induced arthritis. Exp Ther Med 2017; 13(2): 710-716.

[28] Syed KM, Pinals RS. Leukocytosis in rheumatoid arthritis. J Clin Rheumatol 1996; 2(4): 197-202.

[29] Haqqi TM, Anthony DD, Gupta S, Ahmad N, Lee MS, Kumar GK, et al. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl Acad Sci USA 1999; 96(8): 4524-4529.

[30] Zheng Z, Sun Y, Liu Z, Zhang M, Li C, Cai H. The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats. Drug Des Devel Ther 2015; 9: 4931-4942.

[31] Gao XZ, Mousa KK, Bernard PL, Hwee SH, Charles M, Iain BM, et al. Resveratrol modulates murine collagen-induced arthritis by inhibiting Th17 and B-cell function. Ann Rheum Dis 2012; 71(1): 129-135.

[32] Kumar R, Singh S, Saksena AK, Pal R, Jaiswal R, Kumar R. Effect of Boswellia serrata extract on acute inflammatory parameters and tumor necrosis factor-α in complete Freund's adjuvant-induced animal model of rheumatoid arthritis. Int J Appl Basic Med Res 2019; 9(2): 100-106.

[33] Marstrand K, Campbell-Tofte J. The role of rose hip (Rosa canina L) powder in alleviating arthritis pain and inflammation - part II animal and human studies . Botanics 2016; 6: 59-73.

[34] Singh S, Singh TG, Mahajan K, Dhiman S. Medicinal plants used against various inflammatory biomarkers for the management of rheumatoid arthritis. J Pharm Pharmacol 2020; 72(10): 1306-1327.