Abstract
Asphodelus tenuifolius is traditionally used in the management of rheumatic pain and inflamed body parts. The current study validated its traditional use as an anti-arthritic and anti-inflammatory agent using a series of in vivo models. Carrageenan and histamine-induced acute oedema models were employed to study the effects of n-hexane (n-HeAT) and ethanolic (EeAT) extracts on acute inflammatory mediators and were found to inhibit oedema formation in a dose-dependent manner. Formalin and complete Freund’s adjuvant (CFA) were injected into the hind paw of rats for the induction of arthritis. In the formalin model both n-HeAT and EeAT showed significantly better (p < 0.05) anti-oedema effects from day 6 onward. In CFA model rats were treated on 8th day of induction with extracts at the doses of 250, 500, and 750 mg/kg respectively. Piroxicam (10 mg/kg) and normal saline (10 mL/kg) were used as positive and negative controls respectively. Both n-HeAT and EeAT significantly (p < 0.05) decreased arthritis development in a time-dependent manner and at 28th day extent of inflammation was even less than that observed at day 8. The arthritic score was measured at day 12, 16, 20, 24, and 28 and was observed to be significantly less (p < 0.05) in animals treated with 750 mg/kg of n-HeAT and EeAT, respectively. Joint inflammation (p < 0.01), bone erosion (p < 0.001) and, pannus formation (p < 0.01) were significantly declined in A. tenuifolius treatment groups. Radiographic evaluations (X-ray) were conducted to check bone integrity and extent of inflammation and were observed to be diminished at day 28 in A. tenuifolius extracts treated groups. HPLC was performed to screen the phytochemical profile of n-HeAT and EeAT and were found to contain flavonoids and phenolic compounds. Quantitative real‐time polymerase chain reaction (qPCR) was performed to detect effects of n-HeAT and EeAT treatments on inflammatory markers i.e., IL-4, IL-6, IL-10, COX-2, NF-κB, and I-κB using blood samples. ELISA assays were performed for the detection of levels of C-reactive proteins, respectively. Significant downregulation of TNF-α, IL-4, IL-6, IL-1β, COX-2, NF-κB with simultaneous upregulation of IL-10 and I-κB was observed in n-HeAT and EeAT treatment groups. ELISA assays also showed significant (p < 0.05) down-modulation in the serum levels of CRP and TNF-α. Both extracts showed relatively weak antioxidant activities as compared with ascorbic acid in in vitro assay. Based on findings of the current study it is concluded that A. tenuifolius has anti-inflammatory and anti-arthritic effects and thus has potential to be used as an adjunct to standard NSAIDs therapy.
Graphic abstract
Similar content being viewed by others
References
Andreicut A-D et al (2018) Phytochemical analysis of anti-inflammatory and antioxidant effects of Mahonia aquifolium flower and fruit extracts. Oxid Med Cell Longev 2018
Anić B, Mayer MJR (2014) Pathogenesis of rheumatoid arthritis. Reumatizam 61:19–23
Asif M et al (2020) Evaluation of in vivo anti-inflammatory and anti-angiogenic attributes of methanolic extract of Launaea spinosa. Inflammopharmacology 1–16
Bancroft JD, Gamble M (2008) Theory and practice of histological techniques. Elsevier Health Sciences
Boddawar GD, Dhawale SC, Shaikh SS (2016) Assessment of anti-inflammatory potential of Sesbania bispinosa Linn. leaf extracts and fractions by acute and chronic models. Alex J Med 52:289–293
Brenner DR et al (2014) A review of the application of inflammatory biomarkers in epidemiologic cancer research. Cancer Epidemiol Prev Biomark 23:1729–1751
Crofford LJ (2013) Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther 15:S2
Dangi A, Aparna MS, Yadav J, Arora D, Chaudhary UJJ (2013) Antimicrobial potential of asphodelus tunifolius (CAV). J Evolut Med Dent Sci 12:5663–5667
Die JV, Roman B, Flores F, Rowland LJ (2016) Design and sampling plan optimization for RT-qPCR experiments in plants: a case study in blueberry. Front Plant Sci 7:271
Eddine LS, Segni L, Ridha OM (2015) In vitro assays of the antibacterial and antioxidant properties of extracts from Asphodelus tenuifolius Cav and its main constituents: a comparative study. Int J Pharm Clin Res 7:119–125
Finney A, Thwaites CJ (2010) Rheumatoid arthritis. 1: Background, symptoms and ensuring prompt diagnosis and treatment. Nurs Times 106:22–24
Fonseca LJS, Nunes-Souza V, Goulart MOF, Rabelo LA (2019) Oxidative stress in rheumatoid arthritis: what the future might hold regarding novel biomarkers and add-on therapies. Oxid Med Cell Longev
Foyet HS, Tsala DE, Bodo JZE, Carine AN, Heroyne LT, Oben EK (2015) Anti-inflammatory and anti-arthritic activity of a methanol extract from Vitellaria paradoxa stem bark. Pharmacogn Res 7:367
Hajja G, Bahlouli A (2018) Medicinal plants in the prevention and treatment of rheumatoid arthritis. MOJ Bioequiv Availab 5:00084
Huang Q-C, Wang M-J, Chen X-M, Yu W-L, Chu Y-L, He X-H, Huang R-Y (2016) Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis? Oncotarget 7:1193
Kadhim M, Kaizal A, Hameed I (2016) Medicinal plants used for treatment of rheumatoid arthritis: a review. Int J Pharm Clin Res 8:1685–1694
Kedare SB, Singh RP (2011) Genesis and development of DPPH method of antioxidant assay. J Food Sci Technol 48:412–422
Livshits G, Kalinkovich A (2018) Hierarchical, imbalanced pro-inflammatory cytokine networks govern the pathogenesis of chronic arthropathies. Osteoarthr Cartil 26:7–17
Lubberts E, van den Berg WB (2013) Cytokines in the pathogenesis of rheumatoid arthritis and collagen-induced arthritis. In: Madame Curie Bioscience Database [Internet]. Landes Bioscience
Madane A, Kamble S, Patil B, Aparadh V (2013) Assessment of solvent solubility by using phytochemical screen tests of some Euphorbiaceae members. Asian J Pharm Res 3:53–55
Makarov SS (2001) NF-κB in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction. Arthritis Res Ther 3:200
Malmir M, Serrano R, Caniça M, Silva-Lima B, Silva OJP (2018) A comprehensive review on the medicinal plants from the genus Asphodelus. Plants 7:20
Mateen S, Moin S, Shahzad S, Khan AQ (2017) Level of inflammatory cytokines in rheumatoid arthritis patients: correlation with 25-hydroxy vitamin D and reactive oxygen species. PLoS ONE 12:e0178879
Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20:1126–1167
Naqvi AA, Hassali MA, Aftab MT (2019) Epidemiology of rheumatoid arthritis, clinical aspects and socio-economic determinants in Pakistani patients: a systematic review and meta-analysis. JPMA 69:389–398
Olago-Rakuomi A, Oyoo G, Kamau E, Genga E, Okalebo F, Ogutu E (2017) Prevalence of abnormal liver function tests in rheumatoid arthritis. University of Nairobi
Ouyang L et al (2019) Effect of umbelliferone on adjuvant-induced arthritis in rats by MaPK/nF-κB pathway. Drug Des Dev Ther 13:1163
Owolabi OO, James DB, Sani I, Andongma BT, Fasanya OO, Kure B (2018) Phytochemical analysis, antioxidant and anti-inflammatory potential of Feretia apodanthera root bark extracts. BMC Complement Altern Med 18:12
Patil KR et al (2019) Animal models of inflammation for screening of anti-inflammatory drugs: implications for the discovery and development of phytopharmaceuticals. Int J Mol Sci 20:4367
Quinonez-Flores CM, Gonzalez-Chavez SA, Del Rio Najera D, Pacheco-Tena C (2016) Oxidative stress relevance in the pathogenesis of the rheumatoid arthritis: a systematic review. BioMed Res Int 2016
Rani HS, Madhavi G, Srikanth B, Jharna P, Rao U, Jyothy A (2006) Serum ADA and C-reactive protein in rheumatoid arthritis. Int J Hum Genet 6:195–198
Saeed SA, Ahmad AN, Sadiq M (1979) Density and frequency of weeds in wheat fields of the Punjab Province (Pakistan). Pak J Agric Sci 16:85–90
Saleem A, Saleem M, Akhtar MF, Shahzad M, Jahan S (2020a) Polystichum braunii extracts inhibit Complete Freund’s adjuvant-induced arthritis via upregulation of I-κB, IL-4, and IL-10, downregulation of COX-2, PGE2, IL-1β, IL-6, NF-κB, and TNF-α, and subsiding oxidative stress. Inflammopharmacology 1–16
Saleem M et al (2020b) Investigation of in vivo anti-inflammatory and anti-angiogenic attributes of coumarin-rich ethanolic extract of Melilotus indicus. Inflammopharmacology
Shabbir A et al (2018) Ziziphora clinopodioides ameliorated rheumatoid arthritis and inflammatory paw edema in different models of acute and chronic inflammation. Biomed Pharmacother 97:1710–1721
Sokka T et al (2009) Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study. Arthritis Res Ther 11:R7
Uttra AM (2017) Assessment of anti-arthritic potential of Ephedra gerardiana by in vitro and in vivo methods. Bangladesh J Pharmacol 12:403–409
Vasanthi P, Nalini G, Rajasekhar G (2007) Role of tumor necrosis factor-alpha in rheumatoid arthritis: a review. APLAR J Rheumatol 10:270–274
Yaseen H et al (2020) Methanolic extract of Ephedra ciliata promotes wound healing and arrests inflammatory cascade in vivo through downregulation of TNF-α. Inflammopharmacology
Yuan H, Ma Q, Ye L, Piao G (2016) The traditional medicine and modern medicine from natural products. Molecules 21:559
Author information
Authors and Affiliations
Corresponding authors
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Saleem, M., Iftikhar, A., Asif, M. et al. Asphodelus tenuifolius extracts arrested inflammation and arthritis through modulation of TNF-α, NF-κB, ILs, and COX-2 activities in in vivo models. Inflammopharmacol 29, 483–497 (2021). https://doi.org/10.1007/s10787-020-00761-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-020-00761-z