Abstract
Tragia involucrata Linn. (T. involucrata) belongs to the family of Euphorbiaceae found in the subtropical regions. Traditionally, the plant parts are used to treat inflammation, wounds and skin infection by people of the Western Ghats, India. Few studies on the acute anti-inflammatory activity of T. involucrata extracts were reported earlier. The present study aims to identify the bioactive fraction of T. involucrata and to evaluate its mechanism in Complete Freund’s Adjuvant-induced arthritic rat model. The leaf extract was highly effective among the methanolic leaf and root extracts. The hexane (HF) and a methanolic fraction (MF) of the leaf extract of T involucrata were further identified as a bioactive fraction evaluated through protein denaturation assay. The HF and MF were further studied for their anti-inflammatory potential in a chronic inflammatory model, and their mechanism of action was explored further. Arthritis was induced by administering 0.1 ml of CFA intradermally. The treatment was started the next day with HF (100 and 250 mg/kg/day) and MF (100 and 250 mg/kg/day), while the HF and MF alone group served as the drug control, Indomethacin-treated group served as the positive control. On the 25th day, the animals were euthanized, and their body weight, paw thickness, arthritic score, spleen and thymus weight, haematological parameters, biochemical parameters, radiographs and histopathology were analyzed. Results showed that the MF-treated animals maintained dry weight, reduced paw thickness, arthritic scores, and haematological and biological parameters compared to the HF-treated and CFA-induced arthritic rats. Both radiological and histopathological analyses of the joints revealed that the MF-treated groups restored bone architecture without any erosion and normal tissue architecture with nil signs of active inflammation. Western blot analysis revealed that MF has effectively inhibited the protein expression levels of MMP-3, MMP-9, and NF-κB in the synovial tissues compared to that of CFA-induced arthritic rats. Besides, HPLC analysis revealed the presence of flavonoids, including gallic acid, rutin and Quercetin, in the MF of T. involucrata, which had shown to have potent anti-inflammatory potential. Thus, it can be emphasized that T. involucrata could be a potential therapeutic candidate for treating inflammatory diseases, which needs further experimental studies to confirm its safety and efficacy.
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References
Alagar Yadav S, Ramalingam S, Jabamalai Raj A, Subban R (2015) Antihistamine from Tragia involucrata L. leaves. J Complement Integr Medi 12:217–226. https://doi.org/10.1515/jcim-2015-0015
Alam P, Parvez MK, Arbab AH, Al-Dosari MS (2017) Quantitative analysis of rutin, quercetin, naringenin, and gallic acid by validated RP- and NP-HPTLC methods for quality control of anti-HBV active extract of Guiera senegalensis. Pharm Biol 55:1317–1323. https://doi.org/10.1080/13880209.2017.1300175
Appian S, Madhavachandran V, Appukuttannair G (2013) Medicinal plants in the treatment of arthritis. Ann Phytomedicine 2:3–36
Choudhary M, Kumar V, Gupta P, Singh S (2014) Investigation of antiarthritic potential of Plumeria alba L. leaves in acute and chronic models of arthritis. Biomed Res Int 2014:474616. https://doi.org/10.1155/2014/474616
Dhara AK, Suba V, Sen T et al (2000) Preliminary studies on the anti-inflammatory and analgesic activity of the methanolic fraction of the root extract of Tragia involucrata Linn. J Ethnopharmacol 72:265–268. https://doi.org/10.1016/S0378-8741(00)00166-5
Ekambaram SP, Perumal SS, Pavadai S (2017) Anti-inflammatory effect of Naravelia zeylanica DC via suppression of inflammatory mediators in carrageenan-induced abdominal oedema in zebrafish model. Inflammopharmacology 25:147–158. https://doi.org/10.1007/s10787-016-0303-2
Gohil P, Patel V, Deshpande S et al (2018) Anti-arthritic activity of cell wall content of Lactobacillus plantarum in freund’s adjuvant-induced arthritic rats: involvement of cellular inflammatory mediators and other biomarkers. Inflammopharmacology 26:171–181. https://doi.org/10.1007/s10787-017-0370-z
Kim K-W, Kim B-M, Moon H-W et al (2015) Role of C-reactive protein in osteoclastogenesis in rheumatoid arthritis. Arthritis Res Ther 17:41. https://doi.org/10.1186/s13075-015-0563-z
Kirtikar KR, Basu BD (1987) Indian medicinal plants, 2nd edn. International book distributors, Dehradun
Kumar BS, Suneetha P, Mohan A, Kumar DP, Sarma KVS (2017) Comparison of Disease Activity Score in 28 joints with ESR (DAS28), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) & Routine Assessment of Patient Index Data with 3 measures (RAPID3) for assessing disease activity in patients with rheumatoid arthritis at initial presentation. Indian J Med Res 146:S57–S62. https://doi.org/10.4103/ijmr.IJMR_701_15
Li Y, Kakkar R, Wang J (2018) In vivo and in vitro approach to anti-arthritic and anti-inflammatory effect of crocetin by alteration of nuclear factor-E2-related factor 2/hem oxygenase (HO)-1 and NF-κB expression. Front Pharmacol 9:1341
Liu T, Zhang L, Joo D, Sun S-C (2017) NF-κB signaling in inflammation. Signal Transduct Target Ther 2:17023. https://doi.org/10.1038/sigtrans.2017.23
Mallik BK, Panda T, Padhy RN (2012) Traditional herbal practices by the ethnic people of Kalahandi district of Odisha, India. Asian Pac J Trop Biomed 2:S988–S994. https://doi.org/10.1016/S2221-1691(12)60349-9
Mbiantcha M, Almas J, Shabana SU et al (2017) Anti-arthritic property of crude extracts of Piptadeniastrum africanum (Mimosaceae) in complete Freund’s adjuvant-induced arthritis in rats. BMC Complement Altern Med 17:111. https://doi.org/10.1186/s12906-017-1623-5
Mizushima Y, Kobayashi M (1968) Interaction of anti-inflammatory drugs with serum proteins, especially with some biologically active proteins. J Pharm Pharmacol 20:169–173. https://doi.org/10.1111/j.2042-7158.1968.tb09718.x
Naik S, Wala S (2014) Arthritis, a complex connective and synovial joint destructive autoimmune disease: animal models of arthritis with varied etiopathology and their significance. J Postgrad Med 60:309–317. https://doi.org/10.4103/0022-3859.138799
Nisar A, Mamat A, Mohamed Dzahir MIH et al (2017) Identification of flavonoids (quercetin, gallic acid and rutin) from Catharanthus Roseus plant parts using deep eutectic solvent. Recent Adv Biol Med 3:1–6. https://doi.org/10.18639/RABM.2016.02.347628
Panda D, Dash SK, Dash GK (2012) Phytochemical examination and antimicrobial activity of various solvent extracts and the selected isolated compounds from roots of Tragia involucrata Linn. Int J Pharm Sci Drug Res 4:44–48
Patel R, Kadri S, Gohil P et al (2021) Amelioration of complete Freund’s adjuvant-induced arthritis by Calotropis procera latex in rats. Futur J Pharm Sci 7:213. https://doi.org/10.1186/s43094-021-00361-w
Pope JE, Choy EH (2021) C-reactive protein and implications in rheumatoid arthritis and associated comorbidities. Semin Arthritis Rheum 51:219–229. https://doi.org/10.1016/j.semarthrit.2020.11.005
Rajendran R, Krishnakumar E (2010) Anti-arthritic activity of Premna serratifolia Linn., wood against adjuvant induced arthritis. Avicenna J Med Biotechnol 2:101–106
Rathinavel T, Ammashi S, Shanmugam G (2021) Analgesic and anti-inflammatory potential of lupeol isolated from Indian traditional medicinal plant Crateva adansonii screened through in vivo and in silico approaches. J Genet Eng Biotechnol 19:62. https://doi.org/10.1186/s43141-021-00167-6
Sakat S, Juvekar A, Gambhire M (2010) In vitro antioxidant and anti-inflammatory activity of methanol extract of Oxalis corniculata Linn. Int J Pharm Pharm Sci 2:146–155
Salehi B, Machin L, Monzote L et al (2020) Therapeutic potential of quercetin: new insights and perspectives for human health. ACS Omega 5:11849–11872. https://doi.org/10.1021/acsomega.0c01818
Samy RP, Gopalakrishnakone P, Houghton P et al (2006) Effect of aqueous extract of Tragia involucrata Linn. on acute and subacute inflammation. Phyther Res 20:310–312. https://doi.org/10.1002/ptr.1845
Samy PR, Sethi G, Chow TKV, Stiles GB (2013) Plant-based hydrocarbon esters from Tragia involucrata possess antimicrobial and anti-inflammatory activities. Infect Disord–drug Targets 13:141–153
Sen A (2020) Prophylactic and therapeutic roles of oleanolic acid and its derivatives in several diseases. World J Clin Cases 8:1767–1792. https://doi.org/10.12998/wjcc.v8.i10.1767
Sun S, Bay-Jensen A-C, Karsdal MA et al (2014) The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases. BMC Musculoskelet Disord 15:93. https://doi.org/10.1186/1471-2474-15-93
Uprety Y, Poudel RC, Gurung J et al (2016) Traditional use and management of NTFPs in Kangchenjunga landscape: implications for conservation and livelihoods. J Ethnobiol Ethnomed 12:19. https://doi.org/10.1186/s13002-016-0089-8
Velu V, Malipeddi H (2015) In vitro anti-arthritic and hemolytic activity of leaf extracts of Tragia involucrate. IntJ Pharm Tech Res 8:46–50
Xue M, McKelvey K, Shen K et al (2014) Endogenous MMP-9 and not MMP-2 promotes rheumatoid synovial fibroblast survival, inflammation and cartilage degradation. Rheumatology 53:2270–2279. https://doi.org/10.1093/rheumatology/keu254
Zhang X, Dong Y, Dong H et al (2017) Investigation of the effect of phlomisoside F on complete Freund’s adjuvant-induced arthritis. Exp Ther Med 13:710–716. https://doi.org/10.3892/etm.2016.3995
Zhang F, Liu Z, He X et al (2020) β-sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund’s adjuvant-induced arthritis in rats: involvement of NF-кB and HO-1/Nrf-2 pathway. Drug Deliv 27:1329–1341. https://doi.org/10.1080/10717544.2020.1818883
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Vigneshwaran, S., Maharani, K., Sivasakthi, P. et al. Bioactive fraction of Tragia involucrata Linn leaves attenuates inflammation in Freund’s complete adjuvant-induced arthritis in Wistar albino rats via inhibiting NF-κB. Inflammopharmacol 31, 967–981 (2023). https://doi.org/10.1007/s10787-023-01154-8
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DOI: https://doi.org/10.1007/s10787-023-01154-8