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Ethanol extract of Ziziphus nummularia ameliorates formaldehyde-induced arthritis in rats by regulating oxidative stress biomarkers and haematological profile

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Abstract

Background

Rheumatoid arthritis is an autoimmune inflammatory disorder that mainly affects bone and cartilage architecture. The continuous use of NSAIDs and DMARDs is associated with severe toxic effects. Therefore, the current study was designed to scrutinize herb-based therapy for the treatment of RA.

Aim

To evaluate the anti-arthritic activity of ethanol extract of Ziziphus nummularia using formaldehyde-induced arthritic model in rats and elucidate the possible mechanism for anti-arthritic activity.

Materials and methods

Anti-arthritic activity of ETZN was studied at three oral doses, i.e., 200, 400, and 600 mg/kg. Selected doses were studied using various clinical parameters viz. paw volume, inflammatory index, motility test, stair test, anti-nociceptive efficacy, walking track analysis, and motor activity) from day 1 to day 10. On the last day, the animals were killed for the evaluation of hematological parameters, oxidative stress biomarkers, and histological and radiographic studies of the hind paw.

Results

Treatment with ETZN 400 mg/kg and 600 mg/kg markedly elicited a significant reduction in paw volume, inflammatory index, and nociceptive action compared to diseased animals. Furthermore, the anti-inflammatory activity was confirmed by increased latency of pain threshold in thermal and mechanical algesia models. The anti-arthritic activity is mainly attributed to a reduction in oxidative stress biomarkers as well as restoration of haematological profile in treated animals when compared to diseased animals. Lastly, the anti-arthritic potential was confirmed by histological and radiological analysis which revealed a marked reduction in inflammatory cells and bone destruction as compared to diseased animals.

Conclusion

The study revealed that ETZN exhibits significant anti-arthritic activity via modulation of oxidative stress biomarkers, restoration of hematological profile, and reduction in bone erosion.

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References

  • Aletaha D, Kapral T, Smolen JS (2003) Toxicity profiles of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. Ann Rheum Dis 62:482–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ansari MM, Neha KHA (2015) Effect of cadmium chloride exposure during the induction of collagen induced arthritis. Chem Biol Interact 238:55–65

    Article  CAS  PubMed  Google Scholar 

  • Awasthi YC, Dao DD, Lal AK, Srivastava SK (1979) Purification and properties of glutathione peroxidase from human placenta. Biochem J 177:471–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bennett JC (1978) The infectious etiology of rheumatoid arthritis. Arthritis Rheumatol 21:531–538

    Article  CAS  Google Scholar 

  • Bihani GV, Rojatkar SR, Bodhankar SL (2014) Anti-arthritic activity of methanol extract of Cyathocline purpurea (whole plant) in Freund’s complete adjuvant-induced arthritis in rats. Biomed Aging Pathol 4:197–206

    Article  Google Scholar 

  • Bodroth RP, Das M (2012) Phytochemical screening and antimicrobial activity of ethanol and chloroform extract of Zizyphus nummularia Wt. & Arm. Afr J Biotechnol 11(21):4929–4933

    Google Scholar 

  • Brahn E, Banquerigo ML, Firestein GS, Boyle DL, Salzman AL, Szabo C (1998) Collagen induced arthritis: reversal by mercaptoethylguanidine, a novel antiinflammatory agent with a combined mechanism of action. J Rheumatol 25:1785–1793

    CAS  PubMed  Google Scholar 

  • Chance B, Herbert D (1950) The enzyme substrate compounds of bacterial catalase and peroxides. Biochem J 46:402–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dief AE, Mostafa DK, Sharara GM, Zeitoun TH (2015) Hydrogen sulfide releasing naproxen offers better anti-inflammatory and chondroprotective effect relative to naproxen in a rat model of zymosan induced arthritis. Eur Rev Med Pharmacol Sci 19(8):1537–1546

    CAS  PubMed  Google Scholar 

  • Fries JF, Williams CA, Ramey D, Bloch DA (1993) The relative toxicity of disease-modifying antirheumatic drugs. Arthritis Rheumatol 36:297–306

    Article  CAS  Google Scholar 

  • Goyal M, Sasmal D, Nagori BP (2011) Review on medicinal plants used by local community of Jodhpur district of Thar Desert. Int J Pharmacol 7:333–339

    Article  Google Scholar 

  • Haddad PS, Azar GA, Groom S, Boivin M (2005) Natural health products, modulation of immune function and prevention of chronic diseases, evidence-based complement. Altern Med 2:513–520

    Google Scholar 

  • Kotze M, Eloff JN (2002) Extraction of antibacterial compounds from Combretum microphyllum (Combretaceae), South African. J Bot 68:62–67

    CAS  Google Scholar 

  • Lawrence RC, Helmick CG (1998) Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 41:778–799

    Article  CAS  PubMed  Google Scholar 

  • Manish SG, Gautam K, Joshi VK, Goel RK (2013) Anti-inflammatory activity of two classical formulations of Laghupanchamula in rats. J Ayurveda Integr Med 4:23–27

    Article  Google Scholar 

  • Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  CAS  PubMed  Google Scholar 

  • McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219

    Article  CAS  PubMed  Google Scholar 

  • Mythilypriya R, Shanthi P, Sachdanandam P (2015) Therapeutic effect of Kalpaamruthaa, a herbal preparation on adjuvant induced arthritis in wistar rats. Inflammopharmacol 16:21–35

    Article  Google Scholar 

  • National Research Council. Guide for the care and use of laboratory animals (1996) (Washington DC, National Academy Press).

  • Paval J, Kaitheri SK, Potu BK, Govindan S, Kumar RS, Narayanan SN, Moorkoth S (2009) Anti-arthritic potential of the plant Justicia gendarussa Burm F. Clinics 64(4):357–362

    Article  PubMed  PubMed Central  Google Scholar 

  • Prajapati S, Singh S (2019) Phytoconstituents of Ziziphus nummularia (Burm. f.) Wight & Arn. Leaves Extracts Using GC-MS Spectroscopy. Res Rev J Life Sci 9:109–118

    Google Scholar 

  • Randall LO, Selitto JJ (1957) A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn 61:409–419

    Google Scholar 

  • Rathore M (2009) Nutrient content of important fruit trees from arid zone of Rajasthan. J Hortic for 1:103–108

    Google Scholar 

  • Scott DL, Wolfe F, Huizinga TWJ (2010) Rheumatoid arthritis. Lancet 376:1094–1108

    Article  PubMed  Google Scholar 

  • Shah A, Tariq M, Al-Yahya M (1990) Studies on the alkaloidal fraction from the stem bark of Ziziphus nummularia. Fitoterpia 61:452–469

    Google Scholar 

  • Soeken KL, Miller SA, Ernst E (2003) Herbal medicines for the treatment of rheumatoid arthritis: a systematic review. Rheumatol 42:652–659

    Article  CAS  Google Scholar 

  • Suksamrarn S, Suwannapoch N, Aunchai N, Kuno M, Ratananukul P, Haritakun R, Jansakul C, Ruchirawat S (2005) Ziziphine N, O, P and Q, new antiplasmodial cyclopeptide alkaloids from Ziziphus oenoplia var. brunoniana. Tetrahedron 61:1175–1180

    Article  CAS  Google Scholar 

  • Utley HG, Bernheim F, Hochstein P (1967) Effect of sulfhydryl reagents on peroxidation in microsomes. Arch Biochem Biophys 118:29–32

    Article  CAS  Google Scholar 

  • van Vollenhoven RF (2016) General treatment aspects, Biologics for the Treatment of Rheumatoid Arthritis. Springer International Publishing, Sweden

    Book  Google Scholar 

  • Wahane VD, Kumar VL (2010) Atorvastatin ameliorates inflammatory hyperalgesia in rat model of monoarticular arthritis. Pharmacol Res 61:329–333

    Article  CAS  PubMed  Google Scholar 

  • Winter CA, Risley EA, Nuss CW (1962) Carageenan induced edema in hind paw of the rats as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med 111:544–547

    Article  CAS  PubMed  Google Scholar 

  • Zuo J, Xia Y, Li X, Chen JW (2014) Therapeutic effects of dichloromethane fraction of Securidacain appendiculata on adjuvant induced arthritis in rat. J Ethnopharmacol 153(2):352–358

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The present study was supported by the Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak.

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Correspondence to Vandana Garg.

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Malhotra, H., Garg, V., Singh, G. et al. Ethanol extract of Ziziphus nummularia ameliorates formaldehyde-induced arthritis in rats by regulating oxidative stress biomarkers and haematological profile. Inflammopharmacol (2024). https://doi.org/10.1007/s10787-023-01377-9

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