In vitro and In silico Antigout arthritic activities of Ethanolic and Aqueous stem extracts of Cissus quadrangularis - A TLR2 and TLR4 Receptor approach

Tharini Palani; Krishnan Shobha; Thirunavukkarasu P; Rajeswary Hari

doi:10.7324/JAPS.2018.8904

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Abstract

The in vitro anti-gouty arthritic activity of ethanolic and aqueous extracts of Cissus quadrangularis stem was evaluated in terms of inhibition of xanthine oxidase, proteinase enzyme, protein denaturation and membrane stabilization. The Monosodium Urate (MSU) up-regulated expression patterns of toll-like receptors namely TLR-2 and TLR-4 were analyzed. The molecular docking was performed to select the antagonistic phyto ligand for receptors since their activation leads to the destructive immunological reactions occurring in gouty arthritis. The in vitro anti-gout arthritic activities were estimated using standard protocols. The MSU crystal-induced toll-like receptors gene expression was analyzed. Molecular docking and LIGPLOT analysis were performed with the GCMS-derived phytoconstituents in the ethanolic extract of Cissus quadrangularis with the receptors to find the interactions. Colchicine was used as a positive drug in the study. Among the two extracts, ethanolic extract revealed better in-vitro anti-arthritic activity in the present investigation. Out of the GCMS derived 13 phytocomponents, based on docking score three main components namely Pentadecanoic acid, 14-methyl,-methyl ester, 10-Octadecenoic acid, methyl ester, 4-one,2-(3,4- dihydroxyphenyl)-2,3-dihydro-3,5,7-trihydroxy showed better antagonistic action in the LIGPLOT analysis. It may be concluded these three ligands may further develop as a potential anti-gouty arthritic drug.

Keyword: Anti gout Monosodiumurate Toll-like receptor Xanthine oxidase.

Citation:

Palani T, Shobha K, Thirunavukkarasu P, Hari R. In vitro and In silico Antigout arthritic activities of Ethanolic and Aqueous stem extracts of Cissus quadrangularis – A TLR2 and TLR4 Receptor approach. J App Pharm Sci, 2018; 8(09): 015-022.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Chou CT. The anti–inflammatory effect of Tripterygium wilfordii Hook F on adjuvant induced paw edema in rats and inflammatory mediators release. Phytother Res, 1997; 11(2):152–54.https://doi.org/10.1002/(SICI)1099-1573(199703)11:2<152::AID-PTR45>3.0.CO;2-L
Corrado A, Onofrio FD, Santoro N, Melillo N, Cantatore FP. Pathogenesis, clinical findings and management of acute and chronic gout. Minerva Med, 2006; 97:495-509.
Dalbeth N, Haskard DO. Mechanism of inflammation in gout. Rheumatology, 2005; 44:1090-1096.https://doi.org/10.1093/rheumatology/keh640
Delapureta R, Martinez DE, Ruiz GV. Effect of minor components of virgin olive oil on topical anti-inflammatory assays. Zetschrift Fur Naturforschong, 2000; 55:814-19.
Getting SJ, Christian HC, Flower RJ, Perretti M. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis Rheum, 2002; 46:2765-2775.https://doi.org/10.1002/art.10526
Haskard DO, Landis RC. Interactions between leukocytes and endothelial cells in gout: lessons from a self-limiting inflammatory response. Arthritis Res., 2002; 3:91.https://doi.org/10.1186/ar562
Landis RC, Haskard DO. Pathogenesis of crystal-induced inflammation.Curr. Rheumatol. Rep, 2001; 3:36.https://doi.org/10.1007/s11926-001-0049-7
Liu-Bryan R, Pritzker K, Firestein GS, Terkeltaub R. TLR2 signaling in chondrocytes drives calcium pyrophosphate dehydrate and monosodium urate crystal-induced nitric oxide generation. J Immunol, 2005; 174:5016-5023.https://doi.org/10.4049/jimmunol.174.8.5016
Liu-Bryan R, Scott P, Sydlaske A, Rose DM, Terkeltaub R. Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum, 2005; 52:2936-2946.https://doi.org/10.1002/art.21238
Mehta M, Kaur N, Bhutani KK. Determination of marker constituents from Cissus quadrangularisLinn. and their quantitation by HPTLC and HPLC. Phytochem Anal, 2001; 12:91-5.https://doi.org/10.1002/pca.569
Mishra G, Srivastava S, Nagori BP. "Pharmacological and therapeutic activity of Cissus quadrangularis: An overview" International Journal of Pharm. Tech. Research, 2010; 2(2):1298-1310.
Mizushima Y, Kobayashi M. "Interaction of anti-inflammatory drugs with serum proteins especially with some biologically active proteins" J Pharm Pharmacol, 1968; 20:169-73.https://doi.org/10.1111/j.2042-7158.1968.tb09718.x
Owen P, Johns T. Xanthine oxidase inhibitory activity of north eastern North American plant remedies used for gout, J Ethnopharmacol, 1999; 64:149.https://doi.org/10.1016/S0378-8741(98)00119-6
Oyedapo, Famurewa AJ. "Anti-protease and membrane stabilizing activities of extracts of Fagra zanthoxiloides, Olax subscorpioides and Tetrapleura tetraptera". Int J. pharmacogn, 1995; 33:65-9.
Panthong A, Wanicha S, Kanjanapothi D, Tawat T, Vichai R. Analgesic, anti-inflammatory and venotonic effects of Cissus quadrangularis Linn. Journal of Ethnophramacology, 2007; 110:264-70.https://doi.org/10.1016/j.jep.2006.09.018
Sakat S, Juvekar AR, Gambhire MN. Inv itro antioxidant and anti-inflammatory activity of methanol extract of Oxalis corniculata Linn. Inter. J. Pharma Parmacol Sci, 2010; 2(1):146-55.
Seegmiller JE, Howel RR, Malaw ISTASE. The inflammatory reaction to urate. JAMA, 1962; 180:469-75.
Shirwaikar A, Khan S, Malini S. Antiosteoporotic effect of ethanol extract of Cissus quadrangularis Linn. on ovariectomized rat. J Ethnopharmacol, 2003; 89:245-50.https://doi.org/10.1016/j.jep.2003.08.004
Slinkard J, Singleton VL. Total phenol analysis: automation and comparison with manual methods. Am J Enol Vitic, 1977; 28:49.
Unno T, Sugimoto A, Kakuda T. Xanthine oxidase inhibitors from the leaves of Lagerstroemia speciosa (L.) Pers. J. Ethnopharmacol, 2004; 93:391-395.https://doi.org/10.1016/j.jep.2004.04.012
Yoganarsimhan SN. Medicinal plants of India. Cyber Media Bangalore 2, 2000; 2:136–137.
Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem, 1999; 64:555.https://doi.org/10.1016/S0308-8146(98)00102-2

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Albrecht E, Waldenberger M, Krumsiek J, Evans AM, Jeratsch U, Breier M, et al. Metabolite profiling reveals new insights into the regulation of serum urate in humans. Metabolomics, 2014; 10:141–151.https://doi.org/10.1007/s11306-013-0565-2

Chou CT. The anti–inflammatory effect of Tripterygium wilfordii Hook F on adjuvant induced paw edema in rats and inflammatory mediators release. Phytother Res, 1997; 11(2):152–54.https://doi.org/10.1002/(SICI)1099-1573(199703)11:2<152::AID-PTR45>3.0.CO;2-L

Corrado A, Onofrio FD, Santoro N, Melillo N, Cantatore FP. Pathogenesis, clinical findings and management of acute and chronic gout. Minerva Med, 2006; 97:495-509.

Dalbeth N, Haskard DO. Mechanism of inflammation in gout. Rheumatology, 2005; 44:1090-1096.https://doi.org/10.1093/rheumatology/keh640

Delapureta R, Martinez DE, Ruiz GV. Effect of minor components of virgin olive oil on topical anti-inflammatory assays. Zetschrift Fur Naturforschong, 2000; 55:814-19.

Getting SJ, Christian HC, Flower RJ, Perretti M. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis Rheum, 2002; 46:2765-2775.https://doi.org/10.1002/art.10526

Haskard DO, Landis RC. Interactions between leukocytes and endothelial cells in gout: lessons from a self-limiting inflammatory response. Arthritis Res., 2002; 3:91.https://doi.org/10.1186/ar562

Landis RC, Haskard DO. Pathogenesis of crystal-induced inflammation.Curr. Rheumatol. Rep, 2001; 3:36.https://doi.org/10.1007/s11926-001-0049-7

Liu-Bryan R, Pritzker K, Firestein GS, Terkeltaub R. TLR2 signaling in chondrocytes drives calcium pyrophosphate dehydrate and monosodium urate crystal-induced nitric oxide generation. J Immunol, 2005; 174:5016-5023.https://doi.org/10.4049/jimmunol.174.8.5016

Liu-Bryan R, Scott P, Sydlaske A, Rose DM, Terkeltaub R. Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum, 2005; 52:2936-2946.https://doi.org/10.1002/art.21238

Mehta M, Kaur N, Bhutani KK. Determination of marker constituents from Cissus quadrangularisLinn. and their quantitation by HPTLC and HPLC. Phytochem Anal, 2001; 12:91-5.https://doi.org/10.1002/pca.569

Mishra G, Srivastava S, Nagori BP. "Pharmacological and therapeutic activity of Cissus quadrangularis: An overview" International Journal of Pharm. Tech. Research, 2010; 2(2):1298-1310.

Mizushima Y, Kobayashi M. "Interaction of anti-inflammatory drugs with serum proteins especially with some biologically active proteins" J Pharm Pharmacol, 1968; 20:169-73.https://doi.org/10.1111/j.2042-7158.1968.tb09718.x

Owen P, Johns T. Xanthine oxidase inhibitory activity of north eastern North American plant remedies used for gout, J Ethnopharmacol, 1999; 64:149.https://doi.org/10.1016/S0378-8741(98)00119-6

Oyedapo, Famurewa AJ. "Anti-protease and membrane stabilizing activities of extracts of Fagra zanthoxiloides, Olax subscorpioides and Tetrapleura tetraptera". Int J. pharmacogn, 1995; 33:65-9.

Panthong A, Wanicha S, Kanjanapothi D, Tawat T, Vichai R. Analgesic, anti-inflammatory and venotonic effects of Cissus quadrangularis Linn. Journal of Ethnophramacology, 2007; 110:264-70.https://doi.org/10.1016/j.jep.2006.09.018

Sakat S, Juvekar AR, Gambhire MN. Inv itro antioxidant and anti-inflammatory activity of methanol extract of Oxalis corniculata Linn. Inter. J. Pharma Parmacol Sci, 2010; 2(1):146-55.

Seegmiller JE, Howel RR, Malaw ISTASE. The inflammatory reaction to urate. JAMA, 1962; 180:469-75.

Shirwaikar A, Khan S, Malini S. Antiosteoporotic effect of ethanol extract of Cissus quadrangularis Linn. on ovariectomized rat. J Ethnopharmacol, 2003; 89:245-50.https://doi.org/10.1016/j.jep.2003.08.004

Slinkard J, Singleton VL. Total phenol analysis: automation and comparison with manual methods. Am J Enol Vitic, 1977; 28:49.

Unno T, Sugimoto A, Kakuda T. Xanthine oxidase inhibitors from the leaves of Lagerstroemia speciosa (L.) Pers. J. Ethnopharmacol, 2004; 93:391-395.https://doi.org/10.1016/j.jep.2004.04.012

Yoganarsimhan SN. Medicinal plants of India. Cyber Media Bangalore 2, 2000; 2:136–137.

Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem, 1999; 64:555.https://doi.org/10.1016/S0308-8146(98)00102-2