Phytoconstituents of Cassia auriculata Linn inhibits the inflammatory enzymes (5-LOX, COX-1 and COX-2): An insilico study to identify anti-inflammatory drug candidates

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Research Paper 03/04/2024
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Phytoconstituents of Cassia auriculata Linn inhibits the inflammatory enzymes (5-LOX, COX-1 and COX-2): An insilico study to identify anti-inflammatory drug candidates

Tejaswini Hipparagi, Shivaleela Biradar, Babu R.L
Int. J. Biosci.24( 4), 24-36, April 2024.
Certificate: IJB 2024 [Generate Certificate]

Abstract

Inflammation is the most essential part of body’s immune system and responsible for diseases manifestation in asthma, rheumatoid arthritis, allergy, aging, autoimmune diseases and etc.  During of these conditions, many cytokines were regulated. The pro-inflammatory cytokines perform an essential function in development of an effective defense against disease infections and progression. Along with cytokines many enzymes play a critical role in regulation of inflammation. The enzymes such as 5-LOX, COX-1 and COX-2 are vital targets. Objective of study is to comprehensive screening of highly potential and precise phytoconstituents from ethnomedicinally important Cassia auriculata Linn which may have potential inhibitors for pro-inflammatory targets. Methanol extract of Cassia auriculata Linn leaf was subjected to HR-LCMS analysis. The phytochemical signature was analyzed and 85 phytochemicals are taken for the molecular docking studies with pro-inflammatory markers. After, through screening 10 compounds were showing good binding energy with hydrogen bond interaction with all three targets. Further, these compounds were subjected to ADME property prediction, wherein 6 compounds were showing the parameter values within acceptable range. Toxicity prediction reveals the 5 compounds are non-toxic. Insilico investigations revealed that 5 phytoconstituents namely Gallic acid; 2,6-Dihydroxybenzoic acid, Kaempferol; N-(3-Benzooxazol-2-yl-4- hydroxy-phenyl)-2-ptolyloxyacetamide; and Glycophymoline of Cassia auriculata Linn methanol leaf extract are potentially inhibiting the inflammatory enzymes. The study identified the precise phytoconstituents from Cassia auriculata Linn for anti-inflammatory activity.

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Bai J, Zhang Y, Tang C, Hou Y, Ai X, Chen X, Zhang Y, Wang X, Meng X. 2021. Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomedicine & Pharmacotherapy 133, 110985.

Banerjee P, Eckert AO, Schrey AK. Preissner R. 2018. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 46(W1), W257-w263.

Bangar SP, Chaudhary V, Sharma N, Bansal V, Ozogul F, Lorenzo JM. 2023. Kaempferol: A flavonoid with wider biological activities and its applications. Crit Rev Food Sci Nutr 63(28), 9580-9604.

Bharadwaj KK, Ahmad I, Pati S, Ghosh A, Rabha B, Sarkar T, Bhattacharjya D, Patel H, Baishya D. 2023. Screening of Phytocompounds for Identification of Prospective Histone Deacetylase 1 (HDAC1) Inhibitor: An In Silico Molecular Docking, Molecular Dynamics Simulation, and MM-GBSA Approach. Appl Biochem Biotechnol.

Boukhatem BS, Belhadj AE. 2023. In silico anti-inflammatory activity of lavender (Lavandula officinalis) essential oil bioactive compounds: Molecular docking analysis of COX-1 and COX-2, and ADMET prediction. AIMS Allergy and Immunology 7(2), 132-153.

Chanderraj P. 2023. In vitro antioxidant activities and molecular docking of Cassia auriculata medicinal plant 18, 107-111.

Chen CK, Leung SS, Guilbert C, Jacobson MP, McKerrow JH, Podust LM. 2010. Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole. PLoS Negl Trop Dis 4(4), e651.

Das K, Buchholz N. 2019. Benign prostate hyperplasia and nutrition. Clin Nutr ESPEN 33, 5-11.

Divya Rajaselvi N, Jida MD, Nair DB, Sujith S, Beegum N, Nisha AR. 2023. Toxicity prediction and analysis of flavonoid apigenin as a histone deacetylase inhibitor: an in-silico approach. In Silico Pharmacol 11(1), 34.

Düwel D, Metzger H. 1973. 2, 6-Dihydroxybenzoic acid anilides as fasciolicides. J Med Chem 16(5), 433-436.

Ge Y, Ganamet KJBJ. 2023. Using sitemap to aid in the identification of cryptic binding pockets.  122(3), 142a.

Guo H, Callaway JB. Ting JP. 2015. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nature Medicine 21(7), 677-687.

Gupta AK, Tandon N, Sharma M, saraswathy A, Kn SK, Shakila R, Amala K. 2008. Quality standards of Indian Medicinal Plants 7.

Hurley JV. 1964. Acute Inflammation: The Effect of Concurrent Leucocytic Emigration and Increased Permeability on Particle Retention by The Vascular Wall. British journal of experimental pathology 45(6), 627-633.

Kalirajan R, Pandiselvi A, Gowramma B, Balachandran P. 2019. In-silico Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Novel Isoxazole Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer. Current Drug Research Reviews 11(2), 118-128.

Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, Han L, He J, He S, Shoemaker BA, Wang J, Yu B, Zhang J, Bryant SH. 2016. PubChem Substance and Compound databases. Nucleic Acids Research 44(D1), D1202-1213.

Kondratov RV, Komarov PG, Becker Y, Ewenson A, Gudkov AV. 2001. Small molecules that dramatically alter multidrug resistance phenotype by modulating the substrate specificity of <i>P</i>-glycoprotein.  98(24), 14078-14083.

Mohd Amin SN, Md Idris MH, Selvaraj M,. Mohd Amin SN, Jamari H, Kek TL, Salleh MZJMS. 2020. Virtual screening, ADME study, and molecular dynamic simulation of chalcone and flavone derivatives as 5-Lipoxygenase (5-LO) inhibitor 46(6), 487-496.

Mukhopadhyay N, Shukla A, Makhal PN, Kaki VR. 2023. Natural product-driven dual COX-LOX inhibitors: Overview of recent studies on the development of novel anti-inflammatory agents. Heliyon 9(3), e14569.

Murad HAS, Alqurashi TMA, Hussien MA. 2022. Interactions of selected cardiovascular active natural compounds with CXCR4 and CXCR7 receptors: a molecular docking, molecular dynamics, and pharmacokinetic/toxicity prediction study. BMC Complement Med Ther 22(1), 35.

Ongaro A, Oselladore E, Memo M, Ribaudo G, Gianoncelli A. 2021. Insight into the LFA-1/SARS-CoV-2 Orf7a Complex by Protein–Protein Docking, Molecular Dynamics, and MM-GBSA Calculations. Journal of Chemical Information and Modeling 61(6), 2780-2787.

Manju SL, Ethiraj KR, Elias G. 2018. Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: A structure-based approach. European Journal of Pharmaceutical Sciences 121, 356-381.

Pandi S, Kulanthaivel L, Subbaraj GK, Rajaram S, Subramanian SJBRI. 2022. Screening of potential breast cancer inhibitors through molecular docking and molecular dynamics simulation.  2022.

Petrenko D, Timofeev V, Karlinsky D, Plashchinskaia D, Mikhailova A, Rakitina TJCR. 2022. Study of the Binding Free Energy of Peptide Substrates in the Active Site of Oligopeptidase B from Serratia proteamaculans by the MM-GBSA Method 67(3), 383-390.

Rabiu Z, Hamzah M, Hasham R, Zakaria ZA. 2021. Characterization and antiinflammatory properties of fractionated pyroligneous acid from palm kernel shell. Environmental Science and Pollution Research 28(30), 40535-40543.

Rafiq S, Wagay NA, Elansary HO, Malik MA,. Bhat IA, Kaloo ZA, Hadi A, Alataway A, Dewidar AZ, El-Sabrout AM, Yessoufou K, Mahmoud EA. 2022. Phytochemical Screening, Antioxidant and Antifungal Activities of Aconitum chasmanthum Stapf ex Holmes Wild Rhizome Extracts.  11(6), 1052.

Raja D, Jeganathan N, Manavalan R. 2013. In vitro antimicrobial activity and phytochemical analysis of Cassia auriculata Linn. International Current Pharmaceutical Journal 2.

Rajagopal A, Rajakannu S. 2022. Cassia auriculata and its role in infection / inflammation: A close look on future drug discovery. Chemosphere 287, 132345.

Ramakrishnan P, Kalakandan S, Pakkirisamy MJPJ. 2018. Studies on Positive and Negative ionization mode of ESI-LC-MS/MS for screening of Phytochemicals on Cassia auriculata (Aavaram Poo).  10(3).

Rose Y, Duarte JM, Lowe R, Segura J, Bi C, Bhikadiya C, Chen L, Rose AS, Bittrich S, Burley SK, Westbrook JD. 2021. RCSB Protein Data Bank: Architectural Advances Towards Integrated Searching and Efficient Access to Macromolecular Structure Data from the PDB Archive. Journal of Molecular Biology 433(11), 166704.

Rupeshkumar M, Kavitha K, Haldar PK. 2014. Role of herbal plants in the diabetes mellitus therapy: An overview. International Journal of Applied Pharmaceutics 6, 1-3.

Salma B, Janhavi P, Muthaiah S, Veeresh P, Santhepete Nanjundaiah M, Divyashree S, Serva Peddha M. 2021. Ameliorative Efficacy of the Cassia auriculata Root Against High-Fat-Diet + STZ-Induced Type-2 Diabetes in C57BL/6 Mice. ACS Omega 6(1), 492-504.

Sarkar M, Chakraborty DJP. 1979. Glycophymoline, a new minor quinazoline alkaloid from Glycosmis pentaphylla.  18(4), 694-695.

Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W. 2013. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design 27(3), 221-234.

Shelley JC, Cholleti A, Frye LL, Greenwood JR, Timlin MR, Uchimaya M. 2007. Epik: a software program for pK( a ) prediction and protonation state generation for drug-like molecules. Journal of Computer-Aided Molecular Design 21(12), 681-691.

Surana SJ, Gokhale SB, Jadhav RB., Sawant RL, Wadekar JB. 2008. Antihyperglycemic Activity of Various Fractions of Cassia auriculata Linn. in Alloxan Diabetic Rats. Indian Journal of Pharmaceutical Sciences 70(2), 227-229.

Yadav R, Imran M, Dhamija P, Suchal K, Handu S. 2021. Virtual screening and dynamics of potential inhibitors targeting RNA binding domain of nucleocapsid phosphoprotein from SARS-CoV-2. J Biomol Struct Dyn 39(12), 4433-4448.