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BMC Complementary Medicine and Therapies

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Open Access 01-12-2021 | Diclofenac | Research

In vitro antioxidant activity of crude extracts of Harpagophytum zeyheri and their anti-inflammatory and cytotoxicity activity compared with diclofenac

Authors: Sibonokuhle F. Ncube, Lyndy J. McGaw, Emmanuel Mfotie Njoya, Hilton G. T. Ndagurwa, Peter J. Mundy, Samson Sibanda

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

This study evaluated the in vitro antioxidant activity and comparison of anti-inflammatory and cytotoxic activity of Harpagopytum zeyheri with diclofenac.

Methods

In vitro assays were conducted using water, ethanol, and ethyl acetate extracts of H.zeyheri. The antioxidant activity was evaluated using the 2,2′-diphenyl-1-picrylhydrazy (DPPH) and 2,2′- azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. The anti-inflammatory activity was determined by measuring the inhibition of nitric oxide (NO) on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages as well as cytokine (TNF-α and IL-10) expression on LPS-induced U937 human macrophages. For cytotoxicity, cell viability was determined using the 3-(4, 5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.

Results

The ethyl acetate extract had the lowest IC₅₀ values in the DPPH (5.91 μg/ml) and ABTS (20.5 μg/ml) assay compared to other extracts. Furthermore, the ethyl acetate extracts effectively inhibited NO and TNF-α and proved to be comparable to diclofenac at some concentrations. All extracts of H. zeyheri displayed dose-dependent activity and were associated with low levels of human-IL-10 expression compared to quercetin. Furthermore, all extracts displayed low toxicity relative to diclofenac.

Conclusions

These findings show that H. zeyheri has significant antioxidant activity. Additionally, similarities exist in the inflammatory activity of H. zeyheri to diclofenac at some concentrations as well as low toxicity in comparison to diclofenac.

Abdelouahab N, Heard CM. Effect of the major glycosides of Harpagophytum procumbens (Devil’s claw) on epidermal cyclooxygenase-2(COX-2) in vitro. J Nat Prod. 2008;71(5):746–9. https://doi.org/10.1021/np070204u.CrossRefPubMed

Al-Armin MM, Uddin MM, Rahman MM, et al. Effect of diclofenac and antidepressants on the inflammatory response in astrocyte cell culture. Inflammopharmacology. 2013;21(6):421–5. https://doi.org/10.1007/s10787-013-0181-9.CrossRef

Baghdikian B, Lanhers MC, Fleurentin J, Ollivier E, Maillard C, Balansard G, et al. An analytical study and anti-inflammatory and analgesic effects of Harpagophytum procumbens and Harpagophytum zeyheri. Planta Med. 1997;63(02):171–6. https://doi.org/10.1055/s-2006-957638.CrossRefPubMed

Beg S, Swain S, Hasan H, Barkat MA, Hussain MS. Systematic review of herbals as potential anti-inflammatory agents: recent advances, current clinical status and future perspectives. Pharmacogn Rev. 2011;5(10):120–37. https://doi.org/10.4103/0973-7847.91102.CrossRefPubMedPubMedCentral

Benito PB, Lanza AMD, Sen AMS, Galindez JDS, Matellano LF, Gómez AS, et al. Effects of some iridoids from plant origin on arachidonic acid metabolism in cellular systems. Planta Med. 2000;66(04):324–8. https://doi.org/10.1055/s-2000-8549.CrossRef

Betancor-Fernández A, Pérez-Gálvez A, Sies H, Stahl W. Screening pharmaceutical preparations containing extracts of turmeric rhizome, artichoke leaf, devil’s claw root and garlic or salmon oil for antioxidant capacity. J Pharm Pharmacol. 2003;55(7):981–6. https://doi.org/10.1211/0022357021468.CrossRefPubMed

Brendler T. From Bush Medicine to Modern Phytopharmaceutical: A Bibliographic Review of Devil’s Claw (Harpagophytum spp.). Pharmaceuticals. 2021;14(8):726. https://doi.org/10.3390/ph14080726.

Brendler T, Gruenwald J, Ulbricht C, Basch E. Devil’s claw (Harpagophytum procumbens DC) an evidence-based systematic review by the natural standard research collaboration. J Herb Pharmacother. 2006;6(1):89–126.PubMed

Chantre P, Cappelaere A, Leblan D, Guedon D, Vandermander J, Fournie B. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine. 2000;7(3):177–83. https://doi.org/10.1016/S0944-7113(00)80001-X.CrossRefPubMed

10.

Chrubasik S, Künzel O, Thanner J, Conradt C, Black A. A 1-year follow-up after a pilot study with Doloteffin® for low back pain. Phytomedicine. 2005;12(1-2):1–9. https://doi.org/10.1016/j.phymed.2004.01.005.CrossRefPubMed

11.

Chrubasik S, Conradt C, Black A. The quality of clinical trials with Harpagophytum procumbens. Phytomedicine. 2003;10(6-7):613–23. https://doi.org/10.1078/094471103322331647.CrossRefPubMed

12.

Chrubasik S, Thanner J, Kunzel O, Conradt C, Pollak ABS. Comparison of outcome measures during treatment with the proprietary Harpagophytum extract Doloteffin (registered) in patients with pain in the lower back, knee or hip. Phytomedicine. 2002;9(3):181–94. https://doi.org/10.1078/0944-7113-00140.CrossRefPubMed

13.

Do QD, Angkawijaya AE, Tran-Nguyen PL, Huynh LH, Soetaredjo FE, Ismadji S, et al. Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatic. J Food Drug Anal. 2014;22(3):296–302. https://doi.org/10.1016/j.jfda.2013.11.001.CrossRefPubMed

14.

Dzoyem JP, Tsamo AT, Melong R, Mkounga P, Nkengfack AE, McGaw LJ, et al. Cytotoxicity, nitric oxide and acetylcholinesterase inhibitory activity of three limonoids isolated from Trichilia welwitschii (Meliaceae). Biol Res. 2015;48(1):57. https://doi.org/10.1186/s40659-015-0049-0.CrossRefPubMedPubMedCentral

15.

European Union Herbal Monograph on Harpagophytum Procumbens DC. and/or Harpagophytum zeyheri Decne. Radix. Amsterdam: European Medicines Agency; 2016. p. 2–8.

16.

Fiebich BL, Heinrich M, Hiller KO, Kammerer N. Inhibition of TNF-α synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69. Phytomedicine. 2001;8(1):28–30. https://doi.org/10.1078/0944-7113-00002.CrossRefPubMed

17.

Frum Y, Viljoen AM. In vitro 5-lipoxygenase and anti-oxidant activities of South African medicinal plants commonly used topically for skin diseases. Skin Pharmacol Physiol. 2006;19(6):329-35. https://doi.org/10.1159/000095253. Epub 2006 Aug 23.

18.

Georgiev M, Alipieva K, Erdogan O, Ilkay. Cholinesterases inhibitory and antioxidant activities of Harpagophytum procumbens from in vitro systems. Phytother Res. 2012;26(2):313–6. https://doi.org/10.1002/ptr.3555.CrossRefPubMed

19.

Goci E, Shkeli R, Haloci E, Malaj L. Complementary and alternative medicine (CAM) for pain, herbal anti-inflammatory drugs. Eur Sci J. 2013;9:90–105.

20.

Grant L, McBean DE, Fyfe L, Warnock AM. A review of the biological and potential therapeutic actions of Harpagophytum procumbens. Phytother Res. 2007;21(3):199–209. https://doi.org/10.1002/ptr.2029.CrossRefPubMed

21.

Grote, K. The increased harvest and trade of Devil’s Claw (Harpagophytum procumbens) and its impacts on the people and environment of Namibia, Botswana and South Africa. Global Facilitation Unit for Underutilised Species, Italy. Available from: /http://www.underutilized-species.org/documents/publications/devils_claw.pdfS (Accessed 10.07.16). 2003.

22.

Handa SS, Khanuja S, Longo G, Rakesh DD. Extraction technologies for medicinal and aromatic plants, International centre for science and high technology; 2008. p. 21–5.

23.

Jang MH, Lim S, Han SM, Park HJ, Shin I, Kim JW, et al. Harpagophytum procumbens suppresses lipopolysaccharide- stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. J Pharmacol Sci. 2003;93(3):367–71. https://doi.org/10.1254/jphs.93.367.CrossRefPubMed

24.

Klein A, Eliakim R. Non-steroidal anti-inflammatory drugs and inflammatory bowel disease. Pharmaceuticals. 2010;3(4):1084–92. https://doi.org/10.3390/ph3041084.CrossRefPubMedPubMedCentral

25.

Lanas A, Sopeña F. Nonsteroidal anti-inflammatory drugs and lower gastrointestinal complications. Gastroenterol Clin N Am. 2009;38(2):333–52. https://doi.org/10.1016/j.gtc.2009.03.007.CrossRef

26.

Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44. https://doi.org/10.1038/nature07205.CrossRefPubMed

27.

McGregor G, Fiebich B, Wartenberg A, Brien S, Lewith G, Wegener T. Devil’s claw (Harpagophytum procumbens): an anti-inflammatory herb with therapeutic potential. Phytochem Rev. 2005;4(1):47–53. https://doi.org/10.1007/s11101-004-2374-8.CrossRef

28.

Mncwangi NP, Chen W, Vermaak I, Viljoen AM, Gericke N. Devil’s claw- a review of the ethnobotany, phytochemistry and biological activity of Harpagophytum procumbens. J Ethnopharmacol. 2012;143(3):755–71. https://doi.org/10.1016/j.jep.2012.08.013.CrossRefPubMed

29.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;16(1-2):55–63. https://doi.org/10.1016/0022-1759(83)90303-4.CrossRef

30.

Mundy PJ, Ncube SF. Devil’s claw – a natural substitute for diclofenac? Vulture News. 2014;67(2):43–7. https://doi.org/10.4314/vulnew.v67i2.CrossRef

31.

Muzila M. Genetic, morphological and chemical variation in the genus Harpagophytum. Uppsala: Doctoral Thesis, Swedish University of Agricultural Sciences; 2016.

32.

Passmore JS, Lukey PT, Ress SR. The human macrophage cell line U937 as an in vitro model for selective evaluation of mycobacterial antigen-specific cytotoxic T-cell function. Immunology. 2001;102(2):146–56. https://doi.org/10.1046/j.1365-2567.2001.01164.x.CrossRefPubMedPubMedCentral

33.

Pohanka M, Sobotka J, Svobodova H, Stetina R. Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model. Drug Chemical Toxicology. 2011;34(3):255–60. https://doi.org/10.3109/01480545.2010.542753.CrossRefPubMed

34.

Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999;26(9-10):1231–7. https://doi.org/10.1016/S0891-5849(98)00315-3.CrossRefPubMed

35.

Riciotti E, Fitzgerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986–1000. https://doi.org/10.1161/ATVBAHA.110.207449.CrossRef

36.

Sagnia B, Fedeli D, Casetti R, Montesano C, Falcioni G, Colizzi V. Antioxidant and anti-Inflammatory activities of extracts from Cassia alata, Eleusine indica, Eremomastax speciosa, Carica papaya and Polyscias fulva medicinal plants collected in Cameroon. PloS one. 2014;9:E103999.CrossRef

37.

Schneider E, Sanders J, von Willert D. Devil’s claw (Harpagophytum procumbens) from southern Africa. Sustainable use by cultivation combined with controlled harvesting in semiwild populations. In: Bogers RJ, Craker LE, Lange D, editors. Medicinal and aromatic plants. Berlin: Springer; 2006. p. 181–202. https://doi.org/10.1007/1-4020-5449-1_13.CrossRef

38.

Sharma JN, Mohammed LA. The role of leukotrienes in the pathophysiology of inflammatory disorders: is there a case for revisiting leukotrienes as therapeutic targets? Inflammopharmacology. 2006;14(1-2):10–6. https://doi.org/10.1007/s10787-006-1496-6.CrossRefPubMed

39.

Shimada K, Fujikawa K, Yahara K, Nakamura T. Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion. J Agric Food Chem. 1992;40:945–8.CrossRef

40.

Shultz S, Baral HS, Charman S, Cunningham AA, Das D, Ghalsasi GR, et al. Diclofenac poisoning is widespread in declining vulture populations across the Indian subcontinent. Proc Royal Soc London B. 2004;271(suppl_6):S458–60. https://doi.org/10.1098/rsbl.2004.0223.CrossRef

41.

Simon JE, Koroch AR, Acquaye D, Jefthas E, Juliani R, Govindasamy R. Medicinal crops of Africa. In: Janick J, Whipkey A, editors. Issues in new crops and new uses. Alexandria: ASHS Press; 2007.

42.

Stewart KM, Cole D. The commercial harvest of devil’s claw (Harpagophytum spp.) in southern Africa: the devil’s claw in the details. J Ethnopharmacol. 2005;100(3):225–36. https://doi.org/10.1016/j.jep.2005.07.004.

43.

Strohbach M, Cole D. Population dynamics and sustainable harvesting of the medicinal plant Harpagophytum procumbens in Namibia. BfN Skripten. 2007;203:59.

44.

Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines & Chemokines. At the crossroads of cell signalling and inflammatory disease. BBA-Molecular Cell Research. 2014;18643:2563–82.

45.

Van Wyk BE, Van Oudtshoorn B, Gericke N. Medicinal plants of South Africa. Briza: Publications, Pretoria; 1997.

46.

Wang Y, Feinstein SI, Manevich Y, Ho YS, Fisher AB. Lung injury and mortality with hyperoxia are increased in peroxiredoxin 6 gene-targeted mice. Free Radic Biol Med. 2004;37:1736–43.CrossRef

47.

Wolf AM, Wolf D, Rumpold H, Ludwiczek S, Enrich B, Gastl G, et al. The kinase inhibitor Imatinib Mesylate inhibits TNF-α; production invitro and prevents TNF-dependent acute hepatic inflammation. Proc Nat Acad Sci. 2005;102:13622–7.CrossRef

48.

Yang EJ, Yim EY, Song G, Kim GO, Hyun CG. Inhibition of nitric oxide production in lipopolysaccharide-activated RAW 264.7 macrophages by Jeju plant extracts. Interdiscip Toxicol. 2009;2:245–9.CrossRef

49.

Zhang JM, An J. Cytokines, inflammation, and pain. International anesthesiology clinics. 2007;45:27–37.CrossRef

50.

Zhang L, Feng L, Jia Q, Xu J, Wang R, Wang Z, et al. Effects of β glucosidase hydrolyzed products of harpagide and harpagoside on cyclooxygenase-2 (COX-2) in vitro. Bioorg Med Chem. 2011;19:4882–3886.CrossRef

Title: In vitro antioxidant activity of crude extracts of Harpagophytum zeyheri and their anti-inflammatory and cytotoxicity activity compared with diclofenac
Authors: Sibonokuhle F. Ncube
Lyndy J. McGaw
Emmanuel Mfotie Njoya
Hilton G. T. Ndagurwa
Peter J. Mundy
Samson Sibanda
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Diclofenac
Cytokines
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03407-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

In vitro antioxidant activity of crude extracts of Harpagophytum zeyheri and their anti-inflammatory and cytotoxicity activity compared with diclofenac

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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