Download PDF
Planta Med 2023; 89(01): 62-71
DOI: 10.1055/a-1906-1837
Biological and Pharmacological Activity
Original Papers

Pharmacological and Toxicological Study of Coumarinolignoids from Cleome viscosa in Small Animals for the Management of Rheumatoid Arthritis

Vineet Babu
1   Bioprospection and Product Development Division, Council of Scientific and Industrial Research (CSIR) – Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, Uttar Pradesh, India.
,
Rupali Singh
1   Bioprospection and Product Development Division, Council of Scientific and Industrial Research (CSIR) – Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, Uttar Pradesh, India.
,
Praveen K. Kashyap
2   Phytochemistry Division, CSIR-CIMAP, Lucknow, Uttar Pradesh, India.
,
Kaveri R. Washimkar
3   Department of Toxicology & Experimental Medicine, CSIR – Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh, India.
,
Madhav N. Mugale
3   Department of Toxicology & Experimental Medicine, CSIR – Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh, India.
,
Sudeep Tandon
2   Phytochemistry Division, CSIR-CIMAP, Lucknow, Uttar Pradesh, India.
,
Dnyaneshwar Umrao Bawankule
1   Bioprospection and Product Development Division, Council of Scientific and Industrial Research (CSIR) – Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, Uttar Pradesh, India.
4   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India.
› Author AffiliationsSupported by: CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow HCP-007
› Further Information
    Permissions and Reprints

Abstract

This study aims to explore the possible pharmacological potential of Cleome viscosa Linn (Cleomaceae), an annual weed, into therapeutic value-added products. In the present study, we have explored the pharmacological and toxicological profile of coumarinolignoids isolated from Cleome viscose for the management of rheumatoid arthritis and related complications in a small animal model. To avoid the biasness during experiments on animals, we have coded the isolated coumarinolignoids as CLIV-92 to perform the experimental pharmacological study. CLIV-92 was orally administrated (30,100, 300 mg/kg) to animal models of collagen-induced arthritis (CIA), carrageenan-induced acute inflammation, thermal and chemical-induced pain, and Brewerʼs yeast-induced pyrexia. Oral administration of CLIV-92 significantly decreases the arthritis index, arthritis score, and increases the limb withdrawal threshold in the CIA model in experimental rats. The anti-arthritis studies revealed that the anti-inflammatory effect of CLIV-92 was associated with inhibition of the production of inflammatory mediators like TNF-α, IL-6, IL-17A, MMP-1, MMP-9, Nitric oxide, and C-RP in CIA ratʼs serum, and also reduced the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue of CIA rats, in a dose-dependent manner. Further individual experiments related to arthritis-related complications in experimental animals demonstrated the analgesic, anti-inflammatory, and antipyretic potential of CLIV-92 in a dose-dependent manner. Further, an in-vivo acute oral toxicity study concluded that CLIV-92 is safe in experimental animals up to 2,000 mg/kg dose. The results of this study suggested that the oral administration of CLIV-92 may be a therapeutic candidate for further investigation in the management of rheumatoid arthritis and related complications.

Key words

Coumarinolignoid - Cleome viscosa - Cleomaceae - rheumatoid arthritis - experimental animals


Publication History

Received: 16 December 2021

Accepted after revision: 11 July 2022

Article published online:
27 September 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Mohanty S, Maurya AK, Jyotshna. Saxena A, Shanker K, Pal A, Bawankule DU. Flavonoids rich fraction of Citrus limetta fruit peels reduces proinflammatory cytokine production and attenuates malaria pathogenesis. Curr Pharm Biotechnol 2015; 16: 544-552
    CrossrefPubMedGoogle Scholar
  • 2 Randall JM. Defining Weeds of natural Areas. In: Luken JO, Thieret JW. eds. Assessment and Management of Plant Invasions. New York: Springer; 1997: 18-25
    Google Scholar
  • 3 Asolkar LV, Kakkar KK, Chakre OJ. Second supplement to glossary of Indian medicinal plants with active principles part-I (AK). New Delhi: Council of Scientific and Industrial Research; 1992: 217-218
    Google Scholar
  • 4 Mali RG. Cleome viscosa (wild mustard): A review on ethnobotany, phytochemistry, and pharmacology. Pharm Biol 2010; 48: 105-112
    CrossrefPubMedGoogle Scholar
  • 5 Yarrappagaari S, Gutha R, Narayanaswamy L, Thopireddy L, Benne L, Mohiyuddin SS, Vijayakumar V, Saddala RR. Eco-friendly synthesis of silver nanoparticles from the whole plant of Cleome viscosa and evaluation of their characterization, antibacterial, antioxidant and antidiabetic properties. Saudi J Biol Sci 2020; 27: 3601-3614
    CrossrefPubMedGoogle Scholar
  • 6 Krishnamoorthy R, Gassem MA, Athinarayanan J, Periyasamy VS, Prasad S, Alshatwi AA. Antifungal activity of nanoemulsion from Cleome viscosa essential oil against food-borne pathogenic Candida albicans . Saudi J Biol Sci 2020; 28: 286-293
    CrossrefPubMedGoogle Scholar
  • 7 Ray AB, Chattopadhyay SK, Kumar S, Konno C, Kiso YL, Hikino H. Structures of cleomiscosins, coumarinolignoids of Cleome viscosa seeds. Tetrahedron 1985; 41: 209-214
    CrossrefPubMedGoogle Scholar
  • 8 Ng JY, Azizudin AM. Rheumatoid arthritis and osteoarthritis clinical practice guidelines provide few complementary and alternative medicine therapy recommendations: a systematic review. Clin Rheumatol 2020; 9: 2861-2873
    CrossrefPubMedGoogle Scholar
  • 9 Giannini D, Antonucci M, Petrelli F, Bilia S, Alunno A, Puxeddu I. One year in review 2020: Pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol 2020; 38: 387-397
    PubMedGoogle Scholar
  • 10 Smolen JS, Breedveld FC, Eberl G, Jones I, Leeming M, Wylie GL, Kirkpatrick J. Validity and reliability of the twenty-eight-joint count for the assessment of rheumatoid arthritis activity. Arthritis Rheum 1995; 38: 38-43
    CrossrefPubMedGoogle Scholar
  • 11 Choy EHS, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001; 344: 907-916
    CrossrefPubMedGoogle Scholar
  • 12 Shen X, Li C, Zhao H, Li S, Chen J, Kobayashi Y, Shen W. Inhibitory effects of a traditional Chinese herbal formula TBL-II on type II collagen-induced arthritis in mice. J Ethnopharmacol 2011; 134: 399-405
    CrossrefPubMedGoogle Scholar
  • 13 Zhang RX, Fan AY, Zhou AN, Moudgil KD, Ma ZZ, Lee DY, Fong HH, Berman BM, Lao L. Extract of the Chinese herbal formula Huo Luo Xiao Ling Dan inhibited adjuvant arthritis in rats. J Ethnopharmacol 2009; 121: 366-371
    CrossrefPubMedGoogle Scholar
  • 14 Balkrishna A, Sakat SS, Joshi K, Paudel S, Joshi D, Joshi K, Ranjan R, Gupta A, Bhattacharya K, Varshney A. Anti-inflammatory and anti-arthritic efficacies of an Indian traditional herbo-mineral medicine ‘Divya Amvatari Ras’ in collagen antibody-induced arthritis (CAIA) mouse model through modulation of IL-6/IL-1β/TNF-α/NFκB signaling. Front Pharmacol 2019; 10: 659
    CrossrefPubMedGoogle Scholar
  • 15 Cameron M, Gagnier JJ, Chrubasik S. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev 2011; (02) CD002948
    PubMedGoogle Scholar
  • 16 Rathore B, Mahdi AA, Paul BN, Saxena PN, Das SK. Indian herbal medicines: Possible potent therapeutic agents for rheumatoid arthritis. J Clin Biochem Nutr 2007; 41: 12-17
    CrossrefPubMedGoogle Scholar
  • 17 Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA 2018; 320: 1360-1372
    CrossrefPubMedGoogle Scholar
  • 18 Barton NJ, Strickland IT, Bond SM, Brash HM, Bate ST, Wilson AW, Chessell IP, Reeve AJ, McQueen DS. Pressure application measurement (PAM): a novel behavioural technique for measuring hypersensitivity in a rat model of joint pain. J Neurosci Methods 2007; 163: 67-75
    CrossrefPubMedGoogle Scholar
  • 19 McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007; 7: 429-442
    CrossrefPubMedGoogle Scholar
  • 20 Huang Y, Wang Y, Xu J, Feng J, He X. Propacin, a coumarinolignoid isolated from durian, inhibits the lipopolysaccharide-induced inflammatory response in macrophages through the MAPK and NF-κB pathways. Food Funct 2020; 11: 596-605
    CrossrefPubMedGoogle Scholar
  • 21 Zhang GJ, Pan QM, Zhang YL, Liao HB, Yang YQ, Hou Y, Liang D. Coumarinolignoids and taraxerane triterpenoids from Sapium discolor and their inhibitory potential on microglial nitric oxide production. J Nat Prod 2018; 81: 2251-2258
    CrossrefPubMedGoogle Scholar
  • 22 Babu V, Binwal M, Ranjana. Kumari R, Sen S, Kumar A, Mugale MN, Shanker K, Kumar N, Bawankule DU. Hesperidin-rich ethanol extract from waste peels of Citrus limetta mitigates rheumatoid arthritis and related complications. Phytother Res 2021; 35: 3325-3336
    CrossrefPubMedGoogle Scholar
  • 23 Singh H, Mishra A, Mishra AK. The chemistry and pharmacology of Cleome genus: a review. Biomed Pharmacother 2018; 101: 37-48
    CrossrefPubMedGoogle Scholar
  • 24 Elufioye TO, Onoja JO. Anti-oxidant capacity and phenolic content of methanolic extract of Cleome viscosa L. Whole plant and its derived fractions. European J Med Plants 2016; DOI: 10.9734/EJMP/2016/21668.
    CrossrefPubMedGoogle Scholar
  • 25 Bawankule DU, Chattopadhyay SK, Pal A, Saxena K, Yadav S, Faridi U, Darokar MP, Gupta AK, Khanuja SP. Modulation of inflammatory mediators by coumarinolignoids from Cleome viscosa in female swiss albino mice. Inflammopharmacology 2008; 16: 272-277
    PubMedGoogle Scholar
  • 26 Yadav NP, Chanda D, Chattopadhyay SK, Gupta AK, Pal A. Hepatoprotective effects and safety evaluation of coumarinolignoids isolated from Cleome viscosa seeds. Indian J Pharm Sci 2010; 72: 759
    CrossrefPubMedGoogle Scholar
  • 27 Bawankule DU, Chattopadhyay SK, Pal A, Saxena KN, Yadav S, Yadav NP, Mani D, Tripathi AK, Beg SU, Srivastava A, Gupta A, Suman SK. An in-vivo study of the immunomodulatory activity of coumarinolignoids from Cleome viscosa . Nat Prod Commun 2007; 2: 923-926
    PubMedGoogle Scholar
  • 28 El-Shiekh RA, Abdelmohsen UR, Ashour HM, Ashour RM. Novel antiviral and antibacterial activities of Hibiscus schizopetalus. Antibiotics 2020; 9: 756
    CrossrefPubMedGoogle Scholar
  • 29 Bose U, Bala V, Ghosh TN, Gunasekaran K, Rahman AA. Antinociceptive, cytotoxic and antibacterial activities of Cleome viscosa leaves. Revista Brasileira de Farmacognosia 2011; 21: 165-169
    CrossrefPubMedGoogle Scholar
  • 30 Begum S, Saxena B, Goyal M, Ranjan R, Joshi VB, Rao ChV, Krishnamurthy S, Sahai M. Study of anti-inflammatory, analgesic and antipyretic activities of seeds of Hyoscyamus niger and isolation of a new coumarinolignan. Fitoterapia 2010; 81: 178-184
    CrossrefPubMedGoogle Scholar
  • 31 Murugesan D, Deviponnuswamy R. Potential anti-inflammatory medicinal plants – a review. Int J Pharm Pharm Sci 2014; 6: 43-49
    PubMedGoogle Scholar
  • 32 Tandon S, Chatterjee A, Chattopadhyay SK, Kaur R, Gupta AK. Pilot scale processing technology for extraction of Cliv-92: A combination of three coumarinolignoids cleomiscosins A, B and C from Cleome viscosa . Ind Crops Prod 2010; 31: 335-343
    CrossrefPubMedGoogle Scholar
  • 33 Chattopadhyay SK, Thakur RS, Patnaik GK, Srimal RC. A process for the preparation of coumarinolignoids having liver protective activity from Cleome viscosa . Indian Patent 1999; 182
    PubMedGoogle Scholar
  • 34 Sereika M, Urbanaviciute R, Tamasauskas A, Skiriute D, Vaitkiene P. GFAP expression is influenced by astrocytoma grade and rs2070935 polymorphism. J Cancer 2018; 9: 4496
    CrossrefPubMedGoogle Scholar
  • 35 Choy EH, Isenberg DA, Garrood T, Farrow S, Ioannou Y, Bird H, Cheung N, Williams B, Hazleman B, Price R, Yoshizaki K, Nishimoto N, Kishimoto T, Panayi GS. Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Arthritis Rheum 2002; 46: 3143-3150
    CrossrefPubMedGoogle Scholar