Chemical and Pharmacological Potential of Adiantum philippense Linn and Further Molecular Simulation Study of Its Compounds Against COX-2: An Unexplored Medicinal Fern http://www.doi.org/10.26538/tjnpr/v7i9.1
Article Sidebar
Main Article Content
Abstract
Adiantum philippense Linn (Pteridiaceae), commonly known as “Goyalelata” which has been traditionally used to cure of different diseases including dysentery, ulcers, fevers, cooling and elephantiasis. This study aims to summarize the phytoconstituents reported for A. philippense and its pharmacological activities as well as further in-silico molecular dynamics studies to identify active compounds against COX-2 enzyme as potent analgesic. The data for this study were collected using online databases such as Google Scholar, PubMed, Scopus and Web of Science. Previous studies have established that a number of phytochemicals have been identified
from this plant including phenolic compounds (caffeic acid, chlorogenic acid, phloroglucino, esculetin), flavonoids (rutin, quercetin, luteolin), terpenoids (ursolic acid, botulin, carvone and glycyrrhetinic acid). Literature study demonstrated that A. philipense has the potential analgesic, antioxidant, antimicrobial, cytotoxic and hepatoprotective effects in both in-vivo and in-vitro test systems. The plant can act as suitable candidate for the biosynthesis of nanoparticles and application as a therapeutic purpose. The molecular docking analysis of its reported phytoconstituents with CoX-2 showed that quercetin, and luteolin exhibited the most favorablebinding affinity with a value of -8.1 and -8.0 kcal/mol, respectively. Further molecular dynamics study revealed that quercetin was the most promising anti-inflammatory compounds present in A. philippense confirmed by the RMSD, RMSF, Rg, SASA and hydrogen bond analysis. In summary, it is proved that A. philippense one of the potential traditional medicinal fern that possess bioactive compounds which could be useful in the prevention of pain and inflammation.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
Zahra F, Rahman AHM. Medicinal Uses of Angiosperm Weeds in and around Rajshahi Metropolitan City of Bangladesh. 2018;4.
Das D, B. P. Traditional pteridophytic herbal medicines and reproductive health disorders in women- A Review. J phytopharm. 2021;10(6):490-5.
Aulakh M, Kaur N, Saggoo M. Bioactive phytoconstituents of pteridophytes - a review. 2019.
Mazhani Muhammad, Zitty Sarah Ismail, Schneider H, Hawkins JA. Medicinal use of ferns: an ethnobotanical review. Sains Malaysiana,. 2020;49(3):1003-14.
Cao H, Chai TT, Wang X, Morais-Braga MFB, Yang JH, Wong FC, Wang R, Yao H, Cao J, Cornara L, Burlando B, Wang Y, Xiao J, Coutinho HDM. . Phytochemicals from fern species: potential for medicine applications. Phytochem Rev. 2017;16(3):379-440.
"Genus Adiantum". World Ferns. Synonymic Checklist and Distribution of Ferns and Lycophytes of the World. [Internet]. Dr. Michael Hassler. 2004–2023 [cited 17.08.2023]. Available from: www.worldplants.de/ferns/.
Heera Vinod A, Joseph E. A Study on the Phytochemical and Antibacterial Properties of Three Selected Ferns.
Adnan M, Patel M, Deshpande S, Alreshidi M, Siddiqui AJ, Reddy MN, Emira N, De Feo V. Effect of Adiantum philippense Extract on Biofilm Formation, Adhesion With Its Antibacterial Activities Against Foodborne Pathogens, and Characterization of Bioactive Metabolites: An in vitroin silico Approach. Front Microbiol. 2020;11:823.
Upreti K, Jalal JS, Tewari LM, Joshi G, Pangtey Y, Tewari G. Ethnomedicinal uses of Pteridophytes of Kumaun Himalaya, Uttarakhand, India. J Am Sci. 2009;5(4):167-70.
Ramesha KP, Mohana NC, Nuthan BR, Rakshith D, Satish S. Antimicrobial metabolite profiling of Nigrospora sphaerica from Adiantum philippense L. JGEB. 2020;18(1):1-9.
Paul T, Das B, Apte K, Banerjee S, Saxena R. Evaluation of anti-hyperglycemic activity of Adiantum philippense Linn, a pteridophyte in alloxan induced diabetic rats. J Diabetes Metab. 2012;3(9):1-8.
Ali MS, Amin MR, Kamal CMI, Hossain MA. In vitro antioxidant, cytotoxic, thrombolytic activities and phytochemical evaluation of methanol extract of the A. philippense L. leaves. Asian Pac J Trop Biomed. 2013;3(6):464-9.
Adnan M, Patel M, Deshpande S, Alreshidi M, Siddiqui AJ, Reddy MN, Emira N, De Feo V. . Effect of Adiantum philippense extract on biofilm formation, adhesion with its antibacterial activities against foodborne pathogens, and characterization of bioactive metabolites: An in vitro-in
silico approach. Front Microbiol. 2020;11:823.
McCurdy CR, Scully SS. Analgesic substances derived from natural products (natureceuticals). Life Sci. 2005;78(5):476-84.
Abdur R, Noor J, Zarka A, Mohammad SM. Analgesic Potential of Extracts and Derived Natural Products from Medicinal Plants. In: Cecilia M, editor. Pain Relief. Rijeka: IntechOpen; 2017. p. Ch. 17.
Dehdari S, Hajimehdipoor H. Medicinal Properties of Adiantum capillus-veneris Linn. in Traditional Medicine and Modern Phytotherapy: A Review Article. Iran J Public Health. 2018;47(2):188-97.
Carcuevas LAL, Garino RM, Monfero PMM, Narido KR, Soto MY, Rodriguez AA. Determination of the analgesic property of syrup from the crude leaves extract of Adiantum philippense (Kaikai).
Bekalo TH, Woodmatas SD, Woldemariam ZA. An ethnobotanical study of medicinal plants used by local people in the lowlands of Konta Special Woreda, southern nations, nationalities and peoples regional state, Ethiopia. J Ethnobiol Ethnomed. 2009;5(1):1-15.
Karplus M, McCammon JA. Molecular dynamics simulations of biomolecules. Nat Struct Biol. 2002;9(9):646-52.
Asiamah I, Obiri S, Tamekloe W, Armah F, Borquaye L. Applications of Molecular Docking in Natural ProductsBased Drug Discovery. Scientific African. 2023;20:e01593.
Chahal S, Rani P, Kiran, Sindhu J, Joshi G, Ganesan A, Kalyaanamoorthy S, Mayank, Kumar P, Singh R, Negi A. Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective. ACS Omega. 2023;8(20):17446-98.
Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol. 2015;1263:243- 50.
Wallace AC, Laskowski RA, Thornton JM. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 1995;8(2):127-34.
Berendsen HJC, van der Spoel D, van Drunen R. GROMACS: A message-passing parallel molecular dynamics implementation. Comput Phys Commun. 1995;91(1):43-56.
Vermaas JV, Hardy DJ, Stone JE, Tajkhorshid E, Kohlmeyer A. TopoGromacs: Automated Topology Conversion from CHARMM to GROMACS within VMD. J Chem Inf Model. 2016;56(6):1112-6.
Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I, Mackerell AD, Jr. CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem. 2010;31(4):671-90.
Pan C, Chen Y, Ma X, Jiang J, He F, Zhang Y. Phytochemical constituents and pharmacological activities of plants from the genus Adiantum: A review. Trop J Pharm Res. 2011;10(5):681-92.
Arora A, Byrem TM, Nair MG, Strasburg GM. Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids. Arch Biochem Biophys. 2000;373(1):102-9.
Marín L, Miguélez EM, Villar CJ, Lombó F. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. Biomed Res Int. 2015;2015.
Tsuchiya H, Iinuma M. Reduction of membrane fluidity by antibacterial sophoraflavanone G isolated from Sophora exigua. Phytomedicine. 2000;7(2):161-5.
Budzyńska A, Różalski M, Karolczak W, Szakiel MW, Sadowska B, Różalska B. Synthetic 3-Arylidenefl avanones as Inhibitors of the Initial Stages of Biofilm Formation by Staphylococcus aureus and Enterococcus faecalis. Zeitschrift für Naturforschung C. 2011;66(3-4):104-14.
Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288(5472):1765-9.
Raffa RB. Mechanism of action of analgesics used to treat osteoarthritis pain. Rheum Dis Clin North Am. 2003;29(4):733-45.
Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV, Woolf CJ. Interleukin-1betamediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature. 2001;410(6827):471-5.
Dray A. Inflammatory mediators of pain. Br J Anaesth. 1995;75(2):125-31.
Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol. 1983;32(7):1141-8.
Yang W, Chen X, Li Y, Guo S, Wang Z, Yu X. Advances in pharmacological activities of terpenoids. Nat Prod Commun. 2020;15(3):1934578X20903555.
Cushnie TT, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents. 2005;26(5):343-56.
Ramesha KP, Mohana NC, Nuthan BR, Rakshith D, Satish S. Antimicrobial metabolite profiling of Nigrospora sphaerica from Adiantum philippense L. Journal, genetic engineering & biotechnology. 2020;18(1):66.
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020;21(17).
Kakadia NP, Amin MA, Deshpande SS. Hepatoprotective and antioxidant effect of Adiantum lunulatum Burm. F. leaf in alcohol-induced rat model. Journal of Complementary and Integrative Medicine. 2020;17(3).
Shahidi F, Yeo J. Bioactivities of Phenolics by Focusing on Suppression of Chronic Diseases: A Review. Int J Mol Sci. 2018;19(6).
Araújo KCF, de M.B. Costa EM, Pazini F, Valadares MC, de Oliveira V. Bioconversion of quercetin and rutin and the cytotoxicity activities of the transformed products. FCT. 2013;51:93-6.
Gryglewski RJ, Korbut R, Robak J, Świȩs J. On the mechanism of antithrombotic action of flavonoids. Biochem Pharmacol. 1987;36(3):317-22.
Mathew L, Chandrasekaran N, Mukherjee A. Biomimetic synthesis of nanoparticles: science, technology & applicability. Biomimetics learning from nature. 2010.
Arvizo RR, Bhattacharyya S, Kudgus RA, Giri K, Bhattacharya R, Mukherjee P. Intrinsic therapeutic applications of noble metal nanoparticles: past, present and future. Chem Soc Rev. 2012;41(7):2943-70.
Daraee H, Eatemadi A, Abbasi E, Fekri Aval S, Kouhi M, Akbarzadeh A. Application of gold nanoparticles in biomedical and drug delivery. Artif Cells Nanomed Biotechnol. 2016;44(1):410-22.
Joy S, Gajendra NM, Somanjana K, Soumitra M, Krishnendu A. Polysaccharide capped antibacterial silver nanoparticles synthesis using green chemistry. Int J Nano Biomater. 2020;9(1/2):80-94.
Hayat MA. Colloidal gold: principles, methods, and applications: Elsevier; 2012.
Filipe V, Hawe A, Jiskoot W. Critical evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res. 2010;27(5):796-810.
Sarkar J, Chattopadhyay D, Patra S, Singh Deo S, Sinha S, Ghosh M, Mukherjee A, Acharya K. Alternaria alternata mediated synthesis of protein capped silver nanoparticles and their genotoxic activity. Dige J Nanomat Biostruct. 2011;6(2):563-573.
Maity D, Kanti Bain M, Bhowmick B, Sarkar J, Saha S, Acharya K, Chakraborty M, Chattopadhyay D. . In situ synthesis, characterization, and antimicrobial activity of silver nanoparticles using water soluble polymer. J Appl Polym Sci. 2011;122(4):2189-96.
Mollick MMR, Rana D, Dash SK, Chattopadhyay S, Bhowmick B, Maity D, Mondal D, Pattanayak S, Roy S, Chakraborty M. Studies on green synthesized silver nanoparticles using Abelmoschus esculentus (L.) pulp extract having anticancer (in vitro) and antimicrobial applications. Arab J Chem. 2019;12(8):2572-84.
Srikar SK, Giri DD, Pal DB, Mishra PK, Upadhyay SN. Green synthesis of silver nanoparticles: a review. CRGSC. 2016;6(1):34-56.
Mann S, Ozin GA. Synthesis of inorganic materials with complex form. Nature. 1996;382(6589):313-8.
Edison TJI, Sethuraman M. Instant green synthesis of silver nanoparticles using Terminalia chebula fruit extract and evaluation of their catalytic activity on reduction of methylene blue. Process Biochem. 2012;47(9):1351-7.
Lu R, Yang D, Cui D, Wang Z, Guo L. Egg white-mediated green synthesis of silver nanoparticles with excellent biocompatibility and enhanced radiation effects on cancer cells. Int J Nanomed. 2012;7:2101.
Shankar SS, Rai A, Ahmad A, Sastry M. Controlling the optical properties of lemongrass extract synthesized gold nanotriangles and potential application in infraredabsorbing optical coatings. Chem Mater. 2005;17(3):566- 72.
Mithraja MJ, Marimuthu J, Mahesh M, Paul ZM, Jeeva S. Inter–specific variation studies on the phyto–constituents of Christella and Adiantum using phytochemical methods. Asian Pac J Trop Biomed. 2012;2(1):S40-S5.
Sant DG, Gujarathi TR, Harne SR, Ghosh S, Kitture R, Kale S, Chopade BA, Pardesi KR. Adiantum philippense L. frond assisted rapid green synthesis of gold and silver nanoparticles. Journal of Nanoparticles. 2013;2013.
Chandra H, Kumari P, Bontempi E, Yadav S. Medicinal plants: Treasure trove for green synthesis of metallic nanoparticles and their biomedical applications. Biocatal Agric Biotechnol. 2020;24:101518.
Dubey SP, Lahtinen M, Sillanpää M. Tansy fruit mediated greener synthesis of silver and gold nanoparticles. Process Biochem. 2010;45(7):1065-71.
Garavito RM, DeWitt DL. The cyclooxygenase isoforms: structural insights into the conversion of arachidonic acid to prostaglandins. Biochim Biophys Acta. 1999;1441(2- 3):278-87.
Orlando BJ, Malkowski MG. Substrate-selective Inhibition of Cyclooxygeanse-2 by Fenamic Acid Derivatives Is Dependent on Peroxide Tone. J Biol Chem. 2016;291(29):15069-81.
Aier I, Varadwaj PK, Raj U. Structural insights into conformational stability of both wild-type and mutant EZH2 receptor. Sci Rep. 2016;6:34984.
Roccatano D, Colombo G, Fioroni M, Mark AE. Mechanism by which 2,2,2-trifluoroethanol/water mixtures stabilize secondary-structure formation in peptides: a molecular dynamics study. Proc Natl Acad Sci U S A. 2002;99(19):12179-84.
Lobanov M, Bogatyreva NS, Galzitskaia OV. [Radius of gyration is indicator of compactness of protein structure]. Mol Biol (Mosk). 2008;42(4):701-6.
Mazola Y, Guirola O, Palomares S, Chinea G, Menéndez C, Hernández L, Musacchio A. A comparative molecular dynamics study of thermophilic and mesophilic β- fructosidase enzymes. J Mol Model. 2015;21(9):228.
Antunes DA, Rigo MM, Sinigaglia M, de Medeiros RM, Junqueira DM, Almeida SE, Vieira GF. New insights into the in silico prediction of HIV protease resistance to nelfinavir. PLoS One. 2014;9(1):e87520.
Panigrahi SK. Strong and weak hydrogen bonds in proteinligand complexes of kinases: a comparative study. Amino Acids. 2008;34(4):617-33.
Maalik A, Bukhari SM, Zaidi A, Shah KH, Khan FA. Chlorogenic acid: A pharmacologically potent molecule. Acta Pol Pharm. 2016;73(4):851-4.
Lu H, Tian Z, Cui Y, Liu Z, Ma X. Chlorogenic acid: A comprehensive review of the dietary sources, processing effects, bioavailability, beneficial properties, mechanisms of action, and future directions. Compr Rev Food Sci Food Saf. 2020;19(6):3130-58.
Khan F, Bamunuarachchi NI, Tabassum N, Kim YM. Caffeic Acid and Its Derivatives: Antimicrobial Drugs toward Microbial Pathogens. J Agric Food Chem. 2021;69(10):2979-3004.
Lopes R, Costa M, Ferreira M, Gameiro P, Fernandes S, Catarino C, Santos-Silva A, Paiva-Martins F. Caffeic acid phenolipids in the protection of cell membranes from oxidative injuries. Interaction with the membrane phospholipid bilayer. Biochim Biophys Acta Biomembr. 2021;1863(12):183727.
Ajiboye TO, Ajala-Lawal RA, Adeyiga AB. Caffeic acid abrogates 1,3-dichloro-2-propanol-induced hepatotoxicity by upregulating nuclear erythroid-related factor 2 and downregulating nuclear factor-kappa B. Hum Exp Toxicol. 2019;38(9):1092-101.
Oboh G, Ojueromi OO, Ademosun AO, Omayone TP, Oyagbemi AA, Ajibade TO, Adedapo AA. Effects of caffeine and caffeic acid on selected biochemical parameters in L-NAME-induced hypertensive rats. J Food Biochem. 2021;45(3):e13384.
Liu M, Li Y, Pan J, Liu H, Wang S, Ju D, Wang R, Bai D, Wu J, Sun G, Miao Q, Liu L. Effect of esculetin on bone metabolism in ovariectomized rats. J Tradit Chin Med. 2018;38(6):896-903.
Witaicenis A, Seito LN, Di Stasi LC. Intestinal antiinflammatory activity of esculetin and 4-methylesculetin in the trinitrobenzenesulphonic acid model of rat colitis. Chem Biol Interact. 2010;186(2):211-8.
Huang SX, Mou JF, Luo Q, Mo QH, Zhou XL, Huang X, Xu Q, Tan XD, Chen X, Liang CQ. Anti-Hepatitis B Virus Activity of Esculetin from Microsorium fortunei In Vitro and In Vivo. Molecules. 2019;24(19):3475.
Pruccoli L, Breda C, Teti G, Falconi M, Giorgini F, Tarozzi A. Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington's Disease Models. Pharmaceuticals (Basel). 2021;14(10):1044.
Kang KS, Lee W, Jung Y, Lee JH, Lee S, Eom DW, Jeon Y, Yoo HH, Jin MJ, Song KI, Kim WJ, Ham J, Kim HJ, Kim SN. Protective effect of esculin on streptozotocininduced diabetic renal damage in mice. J Agric Food Chem. 2014;62(9):2069-76.
Wan Mohd Tajuddin WNB, Lajis NH, Abas F, Othman I, Naidu R. Mechanistic Understanding of Curcumin's Therapeutic Effects in Lung Cancer. Nutrients. 2019;11(12).
Tejada S, Manayi A, Daglia M, Nabavi SF, Sureda A, Hajheydari Z, Gortzi O, Pazoki-Toroudi H, Wound Healing Effects of Curcumin: A Short Review. Curr Pharm Biotechnol. 2016;17(11):1002-7.
Marton LT, Pescinini ESLM, Camargo MEC, Barbalho SM, Haber J, Sinatora RV, Detregiachi CRP, Girio RJS, Buchaim DV, Cincotto Dos Santos Bueno P. The Effects of Curcumin on Diabetes Mellitus: A Systematic Review. Front Endocrinol (Lausanne). 2021;12:669448.
Eghbaliferiz S, Farhadi F, Barreto GE, Majeed M, Sahebkar A. Effects of curcumin on neurological diseases: focus on astrocytes. Pharmacol Rep. 2020;72(4):769-82.
Peng Y, Ao M, Dong B, Jiang Y, Yu L, Chen Z, Hu C, Xu R. Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures. Drug Des Devel Ther. 2021;15:4503-25.
Vollono L, Falconi M, Gaziano R, Iacovelli F, Dika E, Terracciano C, Bianchi L, Campione E. Potential of Curcumin in Skin Disorders. Nutrients. 2019;11(9).
Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H,Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int. 2014;2014:186864.
Yavarpour-Bali H, Ghasemi-Kasman M, Pirzadeh M. Curcumin-loaded nanoparticles: a novel therapeutic strategy in treatment of central nervous system disorders. Int J Nanomedicine. 2019;14:4449-60.
Wong SK, Chin KY, Ima-Nirwana S. The Osteoprotective Effects Of Kaempferol: The Evidence From In Vivo And In Vitro Studies. Drug Des Devel Ther. 2019;13:3497-514.
Dabeek WM, Marra MV. Dietary Quercetin and Kaempferol: Bioavailability and Potential CardiovascularRelated Bioactivity in Humans. Nutrients. 2019;11(10).
Imran M, Salehi B, Sharifi-Rad J, Aslam Gondal T, Saeed F, Imran A, Shahbaz M, Tsouh Fokou PV, Umair Arshad M, Khan H, Guerreiro SG, Martins N, Estevinho LM. Kaempferol: A Key Emphasis to Its Anticancer Potential. Molecules. 2019;24(12):2277.
Devi KP, Malar DS, Nabavi SF, Sureda A, Xiao J, Nabavi SM, Daglia M. Kaempferol and inflammation: From chemistry to medicine. Pharmacol Res. 2015;99:1-10.
BinMowyna MN, AlFaris NA. Kaempferol suppresses acetaminophen-induced liver damage by upregulation/activation of SIRT1. Pharm Biol. 2021;59(1):146-56.
Cao J, Wang Y, Hu S, Ding Y, Jia Q, Zhu J, Kaempferol ameliorates secretagogue-induced pseudo-allergic reactions via inhibiting intracellular calcium fluctuation. J Pharm Pharmacol. 2020;72(9):1221-31.
Zhang YB, Li W, Jiang L, Yang L, Chen NH, Wu ZN, Li YL, Wang GC. Cytotoxic and anti-inflammatory active phloroglucinol derivatives from Rhodomyrtus tomentosa. Phytochemistry. 2018;153:111-9.
Zhang J, Yang YN, Jiang JS, Feng ZM, Yuan X, Zhang X, Zhang PC. New dimeric phloroglucinol derivatives from Agrimonia pilosa and their hepatoprotective activities. Bioorg Chem. 2021;116:105341.
Yang EJ, Kim H, Kim HS, Chang MJ. Phloroglucinol attenuates oligomeric amyloid beta peptide(1)(-)(42)- induced astrocytic activation by reducing oxidative stress. J Pharmacol Sci. 2021;145(4):308-12.
Song JG, Tang W, Wang X, Su JC, Huang XJ, Shi L, Ye WC, Wang Y. Phloroglucinol-derived lipids from the leaves of Syzygium cumini and their neuroprotective activities. Fitoterapia. 2021;153:104968.
Li W, Wang Y, Wang X, Zhang H, He Z, Zhi W, Liu F, Niu X. Gastroprotective effect of esculin on ethanol-induced gastric lesion in mice. Fundam Clin Pharmacol. 2017;31(2):174-84.
Niu X, Wang Y, Li W, Zhang H, Wang X, Mu Q, He Z, Yao H. Esculin exhibited anti-inflammatory activities in vivo and regulated TNF-α and IL-6 production in LPSstimulated mouse peritoneal macrophages in vitro through MAPK pathway. Int Immunopharmacol. 2015;29(2):779-
Song Y, Wang X, Qin S, Zhou S, Li J, Gao Y. Esculin ameliorates cognitive impairment in experimental diabetic nephropathy and induces anti-oxidative stress and antiinflammatory effects via the MAPK pathway. Mol Med Rep. 2018;17(5):7395-402.
Mokdad-Bzeouich I, Mustapha N, Chaabane F, Ghedira Z, Ghedira K, Ghoul M, Chebil L, Chekir-Ghedira L. Oligomerization of esculin improves its antibacterial activity and modulates antibiotic resistance. J Antibiot (Tokyo). 2015;68(3):148-52.
Shan LP, Zhang X, Hu Y, Liu L, Chen J. Antiviral activity of esculin against white spot syndrome virus: A new starting point for prevention and control of white spot disease outbreaks in shrimp seedling culture. J Fish Dis. 2022;45(1):59-68.
Zhao DL, Zou LB, Lin S, Shi JG, Zhu HB. Anti-apoptotic effect of esculin on dopamine-induced cytotoxicity in the human neuroblastoma SH-SY5Y cell line. Neuropharmacology. 2007;53(6):724-32.
Samsonowicz M, Kamińska I, Kalinowska M, Lewandowski W. Alkali metal salts of rutin–Synthesis, spectroscopic (FT-IR, FT-Raman, UV–VIS), antioxidant and antimicrobial studies. SAA. 2015;151:926-38.
Selloum L, Bouriche H, Tigrine C, Boudoukha C. Antiinflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation. Exp Toxicol Pathol. 2003;54(4):313-8.
Chen H, Miao Q, Geng M, Liu J, Hu Y, Tian L, et al. Antitumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis. Sci World J. 2013;2013.
Jung CH, Lee JY, Cho CH, Kim CJ. Anti-asthmatic action of quercetin and rutin in conscious guinea-pigs challenged with aerosolized ovalbumin. Arch Pharm Res. 2007;30(12):1599-607.
Liu Q, Pan R, Ding L, Zhang F, Hu L, Ding B, Zhu L, Xia Y, Dou X. Rutin exhibits hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipid-induced oxidative injuries. Int Immunopharmacol. 2017;49:132-41.
Chiow K, Phoon M, Putti T, Tan BK, Chow VT. Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection. Asian Pac J Trop Med. 2016;9(1):1-7.
Roman Junior WA, Piato AL, Conterato GM, Wildner SM, Marcon M, Mocelin R, Emanuelli MP, Emanuelli T, Nepel A, Barison A. Hypolipidemic effects of Solidago chilensis hydroalcoholic extract and its major isolated constituent quercetrin in cholesterol-fed rats. Pharm Biol. 2015;53(10):1488-95.
Zhang Y, Guo Y, Wang M, Dong H, Zhang J, Zhang L. Quercetrin from Toona sinensis leaves induces cell cycle arrest and apoptosis via enhancement of oxidative stress in human colorectal cancer SW620 cells. Oncol Rep. 2017;38(6):3319-26.
Kostić M, Ivanov M, Stojković D, Ćirić A, Soković M. Antibacterial and antibiofilm activity of selected polyphenolic compounds: An in vitro study on Staphylococcus aureus. Lekovite sirovine. 2020;40:57-61.
Ahn J, Lee H, Kim S, Park J, Ha T. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. BBRC. 2008;373(4):545-9.
Gatto MT, Falcocchio S, Grippa E, Mazzanti G, Battinelli L, Nicolosi G, Lambusta D, Saso L. Antimicrobial and anti-lipase activity of quercetin and its C2-C16 3-O-acylesters. Biorg Med Chem. 2002;10(2):269-72.
Baghel SS, Shrivastava N, Baghel RS, Agrawal P, Rajput S. A review of quercetin: antioxidant and anticancer properties. World J Pharm Pharmaceutical Sci. 2012;1(1):146-60.
Nègre-Salvayre A, Salvayre R. Quercetin prevents the cytotoxicity of oxidized LDL on lymphoid cell lines. Free Radic Biol Med. 1992;12(2):101-6.
Geng L, Liu Z, Zhang W, Li W, Wu Z, Wang W, Ren R, Su Y, Wang P, Sun L. Chemical screen identifies a geroprotective role of quercetin in premature aging. Protein & cell. 2019;10(6):417-35.
Ciocarlan A, Stroncea M, Aricu A, Lungu L, Vornicu N, Ambrosio M, editors. New antifungal and antibacterial activities of lagochilin and its derivatives. Phy Meth Coord Supram Chem. 2015; 8-9: 1-50.
Akramov DK, Bacher M, Zengin G, Bohmdorfer S, Rosenau T, Azimova SS, Mamadalieva N. Chemical composition and anticholinesterase activity of Lagochilus inebrians. Chem Nat Compd. 2019;55(3):575-7.
Belyaev EY. New medical materials based on modified polysaccharides. Pharm Chem J. 2000;34(11):607-12.
Wang X, He S, Yuan L, Deng H, Zhang Z. Synthesis, structure characterization, and antioxidant and antibacterial activity study of iso-orientin–zinc complex. J Agric Food Chem. 2021;69(13):3952-64.
Lee W, Bae J-S. Antithrombotic and antiplatelet activities of orientin in vitro and in vivo. J Funct Foods. 2015;17:388- 98.
Fu X-C, Wang M-W, Li S-P, Zhang Y, Wang H-L. Vasodilatation produced by orientin and its mechanism study. Biol Pharm Bull. 2005;28(1):37-41.
Ku S-K, Kwak S, Bae J-S. Orientin inhibits high glucoseinduced vascular inflammation in vitro and in vivo. Inflam. 2014;37(6):2164-73.
Aziz N, Kim M-Y, Cho JY. Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. J Ethnopharmacol. 2018;225:342-58.
Fan W, Qian S, Qian P, Li X. Antiviral activity of luteolin against Japanese encephalitis virus. Virus Res. 2016;220:112-6.
Ganai SA, Sheikh FA, Baba ZA, Mir MA, Mantoo MA, Yatoo MA. Anticancer activity of the plant flavonoid luteolin against preclinical models of various cancers and insights on different signalling mechanisms modulated. Phytother Res. 2021.
Ding L, Jin D, Chen X. Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes. J Nutr Biochem. 2010;21(10):941-7.
Hasan S, Khan R, Ali N, Khan A, Rehman M, Tahir M, Lateef A, Nafees S, Mehdi S, Rashid S. 18-β Glycyrrhetinic acid alleviates 2-acetylaminofluoreneinduced hepatotoxicity in Wistar rats: role in hyperproliferation, inflammation and oxidative stress. Hum Exp Toxicol. 2015;34(6):628-41.
Hardy ME, Hendricks JM, Paulson JM, Faunce NR. 18 β- glycyrrhetinic acid inhibits rotavirus replication in culture. Virol J. 2012;9(1):1-7.
Wang S, Shen Y, Qiu R, Chen Z, Chen Z, Chen W. 18 β- glycyrrhetinic acid exhibits potent antitumor effects against colorectal cancer via inhibition of cell proliferation and migration. Int J Oncol. 2017;51(2):615-24.
Novotný L, Vachalkova A, Biggs D. Ursolic acid: an antitumorigenic and chemopreventive activity. Minireview. Neoplasma. 2001;48(4):241-6.
Do Nascimento PG, Lemos TL, Bizerra AM, Arriaga ÂM, Ferreira DA, Santiago GM, Braz-Filho R, Costa JGM. Antibacterial and antioxidant activities of ursolic acid and derivatives. Molecules. 2014;19(1):1317-27.
Kanjoormana M, Kuttan G. Antiangiogenic activity of ursolic acid. Integr Cancer Ther. 2010;9(2):224-35.
Shukla B, Visen P, Patnaik G, Tripathi S, Srimal R, Dayal R, Dobhal P. Hepatoprotective activity in the rat of ursolic acid isolated from Eucalyptus hybrid. Phytother Res. 1992;6(2):74-9.
Tshilanda DD, Onyamboko DN, Babady-Bila P, Ngbolua K-t-N, Tshibangu DS, Mpiana PT. Anti-sickling activity of ursolic acid isolated from the leaves of Ocimum gratissimum L.(Lamiaceae). Nat Prod Bioprospect. 2015;5(4):215-21.
Shafik A, El-Sibai O. Botulin toxin in the treatment of nonrelaxing puborectalis syndrome. Dig Surg. 1998;15(4):347-51.
Jost WH. Ten years' experience with botulin toxin in anal fissure. Int J Colorectal Dis. 2002;17(5):298-302.
Raphael T, Kuttan* G. Immunomodulatory activity of naturally occurring monoterpenes carvone, limonene, and perillic acid. Immunopharmacol Immunotoxicol. 2003;25(2):285-94.
Morcia C, Malnati M, Terzi V. In vitro antifungal activity of terpinen-4-ol, eugenol, carvone, 1, 8-cineole (eucalyptol) and thymol against mycotoxigenic plant pathogens. Food Addit Contam. 2012;29(3):415-22.
Aydın E, Türkez H, Keleş MS. Potential anticancer activity of carvone in N2a neuroblastoma cell line. Toxicol Ind Health. 2015;31(8):764-72.
Elmastaş M, Dermirtas I, Isildak O, Aboul‐Enein HY. Antioxidant activity of S‐carvone isolated from spearmint (Mentha Spicata L. Fam Lamiaceae). J Liq Chromatogr Relat Technol. 2006;29(10):1465-75.
Moro IJ, Gondo GDGA, Pierri EG, Pietro RCLR, Soares CP, Sousa DPd, Santos AGd. Evaluation of antimicrobial, cytotoxic and chemopreventive activities of carvone and its derivatives. Braz J Pharm Sci. 2018;53.
Kubo I, Fujita Ki, Lee SH, Ha TJ. Antibacterial activity of polygodial. Phytother Res. 2005;19(12):1013-7.
Kubo I, Fujita Ki, Lee SH. Antifungal mechanism of polygodial. J Agric Food Chem. 2001;49(3):1607-11.
Moreno-Osorio L, Cortés M, Armstrong V, Bailén M, González-Coloma A. Antifeedant activity of some polygodial derivatives. ZNC. 2008;63(3-4):215-20.
Ban T, Singh IP, Etoh H. Polygodial, a potent attachmentinhibiting substance for the blue mussel, Mytilus edulis galloprovincialis from Tasmannia lanceolata. Biosci Biotechnol Biochem. 2000;64(12):2699-701.
Sikder MAA, Sharmin T, Rahman AM, Haque MR, Rahman MS, Rashid MA. Screenings of four medicinal plants of Bangladesh for bioactivities. Dhaka Univ J Pharm Sci. 2013;12(1):59-62.
Paul T, Apte KG, Parab PB, Das B. Role of Adiantum philippense L. on glucose uptake in isolated pancreatic cells and inhibition of adipocyte differentiation in 3T3-L1 cell line. Pharmacogn Mag. 2017;13(Suppl 2):S334.