Abstract
Plants are sources of many therapeutics used for the treatments of many complex diseases since ancient times. Plants can synthesize a plethora of natural compounds with diverse chemical structures. Despite many advances in the world, a large population of the world is still relying on the herbal system. Therefore, a holistic effort must be made for the conservation of herbal hot spots as well as also for the scientific documentation of active herbal ingredients present in a plant. A paradigm shift has taken from the herbal medicine system to modern approaches of drug design and therapy with the advancement of scientific research in the field of structural biology, genomics, proteomics, therapeutic biology, biochemistry, systems biology, and computer science. Rational approaches of drug development have made it possible to model the target, design various analogs, and dock them with the target, screen, analyze, and predict the pharmacokinetic and pharmacodynamic properties. Rational approaches have significantly reduced the cost, labor, and risk of failure in the process of drug discovery.
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Agnihotry S, Pathak RK, Srivastav A, Shukla PK, Gautam B (2020) Molecular docking and structure-based drug design. In: Singh DB (ed) Computer-aided drug design. Springer, Singapore, pp 115–131. https://doi.org/10.1007/978-981-15-6815-2_6
Alamgir ANM (2018) Molecular pharmacognosy. A new borderline discipline between molecular biology and pharmacognosy. In: Rainsford KD (ed) Therapeutic use of medicinal plants and their extracts: Volume 2. Phytochemistry and bioactive compounds, Progress in Drug Research, vol, vol 74. Springer, Cham, pp 665–720. https://doi.org/10.1007/978-3-319-92387-1_8
Allard PM, Bisson J, Azzollini A, Pauli GF, Cordell GA, Wolfender JL (2018) Pharmacognosy in the digital era: shifting to contextualized metabolomics. Curr Opin Biotechnol 54:57–64. https://doi.org/10.1016/j.copbio.2018.02.010
Anand U, Tudu CK, Nandy S, Sunita K, Tripathi V, Loake GJ, Dey A, Proćków J (2021) Ethnodermatological use of medicinal plants in India: from ayurvedic formulations to clinical perspectives–a review. J Ethnopharmacol 14:114744. https://doi.org/10.1016/j.jep.2021.114744
Batool M, Ahmad B, Choi S (2019) A structure-based drug discovery paradigm. Int J Mol Sci 20:2783. https://doi.org/10.3390/ijms20112783
Behl T, Rocchetti G, Chadha S, Zengin G, Bungau S, Kumar A, Mehta V, Uddin MS, Khullar G, Setia D, Arora S (2021) Phytochemicals from plant foods as potential source of antiviral agents: an overview. Pharmaceuticals 14:381. https://doi.org/10.3390/ph14040381
Borse SP, Singh DP, Nivsarkar M (2019) Understanding the relevance of herb–drug interaction studies with special focus on interplays: a prerequisite for integrative medicine. Porto Biomed J 4:e15. https://doi.org/10.1016/j.pbj.0000000000000015
Burley SK, Bhikadiya C, Bi C, Bittrich S, Chen L, Crichlow GV, Christie CH, Dalenberg K, Di Costanzo L, Duarte JM, Dutta S (2021) RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences. Nucleic Acids Res 49:D437–D451. https://doi.org/10.1093/nar/gkaa1038
Chandran H, Meena M, Barupal T, Sharma K (2020) Plant tissue culture as a perpetual source for production of industrially important bioactive compounds. Biotechnol Rep 26:e00450. https://doi.org/10.1016/j.btre.2020.e00450
Chen SL, Yu H, Luo HM, Wu Q, Li CF, Steinmetz A (2016) Conservation and sustainable use of medicinal plants: problems, progress, and prospects. Chin Med 11:37. https://doi.org/10.1186/s13020-016-0108-7
Chokheli VA, Dmitriev PA, Rajput VD, Bakulin SD, Azarov AS, Varduni TV, Stepanenko VV, Tarigholizadeh S, Singh RK, Verma KK, Minkina TM (2020) Recent development in micropropagation techniques for rare plant species. Plants 9:1733. https://doi.org/10.3390/plants9121733
Corns CM (2003) Herbal remedies and clinical biochemistry. Ann Clin Biochem 40:489–507. https://doi.org/10.1258/000456303322326407
Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2:303–336. https://doi.org/10.3390/metabo2020303
Ekor M (2014) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 4:77. https://doi.org/10.3389/fphar.2013.00177
El Khatabi K, El-Mernissi R, Aanouz I, Ajana MA, Lakhlifi T, Khan A, Wei DQ, Bouachrine M (2021) Identification of novel acetylcholinesterase inhibitors through 3D-QSAR, molecular docking, and molecular dynamics simulation targeting Alzheimer’s disease. J Mol Model 27:302. https://doi.org/10.1007/s00894-021-04928-5
Eren G, Bruno A, Guntekin-Ergun S, Cetin-Atalay R, Ozgencil F, Ozkan Y, Gozelle M, Kaya SG, Costantino G (2019) Pharmacophore modeling and virtual screening studies to identify novel selective SIRT2 inhibitors. J Mol Graph Model 89:60–73. https://doi.org/10.1016/j.jmgm.2019.02.014
Gao H, Li G, Lou HX (2018) Structural diversity and biological activities of novel secondary metabolites from endophytes. Molecules 23:646. https://doi.org/10.3390/molecules23030646
Gertsch J (2011) Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures. Planta Med 77:1086–1098. https://doi.org/10.1055/s-0030-1270904
Gervasini G, Vizcaino S, Carrillo JA, Caballero MJ, Benitez J (2006) The effect of CYP2J2, CYP3A4, CYP3A5 and the MDR1 polymorphisms and gender on the urinary excretion of the metabolites of the H-receptor antihistamine ebastine: a pilot study. Br J Clin Pharmacol 62:177–186. https://doi.org/10.1111/j.1365-2125.2006.02578.x
Gesto-Borroto R, Medina-Jiménez K, Lorence A, Villarreal ML (2021) Application of DNA barcoding for quality control of herbal drugs and their phytopharmaceuticals. Rev Bras Farmacogn 31:127–141. https://doi.org/10.1007/s43450-021-00128-7
Gupta PP, Bastikar VA, Bastikar A, Chhajed SS, Pathade PA (2020) Computational screening techniques for lead design and development. In: Singh DB (ed) Computer-aided drug design. Springer, Singapore, pp 187–222. https://doi.org/10.1007/978-981-15-6815-2_9
Gupta R, Srivastava D, Sahu M, Tiwari S, Ambasta RK, Kumar P (2021) Artificial intelligence to deep learning: machine intelligence approach for drug discovery. Mol Divers 25:1315–1360. https://doi.org/10.1007/s11030-021-10217-3
Hardy K (2021) Paleomedicine and the evolutionary context of medicinal plant use. Rev Bras Farmacogn 31:1–15. https://doi.org/10.1007/s43450-020-00107-4
Huang LQ, Yuan Y, Cui GH, Dai ZB, Xiao PG (2009) Molecular pharmacognosy: a new borderline discipline. Nat Prod Commun 4:1611–1613. https://doi.org/10.1177/1934578X0900401131
Huang L, Xiao P, Guo L, Gao W (2010) Molecular pharmacognosy. Sci China Life Sci 53:643–652. https://doi.org/10.1007/s11427-010-4006-4
Hussain MS, Fareed S, Ansari S, Rahman MA, Ahmad IZ, Saeed M (2012) Current approaches toward production of secondary plant metabolites. J Pharm Bioallied Sci 4:10–20. https://doi.org/10.4103/0975-7406.92725
Jaiswal Y, Liang Z, Zhao Z (2016) Botanical drugs in Ayurveda and traditional Chinese medicine. J Ethnopharmacol 194:245–259. https://doi.org/10.1016/j.jep.2016.06.052
Ji HF, Li XJ, Zhang HY (2009) Natural products and drug discovery: can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Rep 10:194–200. https://doi.org/10.1038/embor.2009.12
Karimi A, Majlesi M, Rafieian-Kopaei M (2015) Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol 4:27–30
Kayser O (2018) Ethnobotany and medicinal plant biotechnology: from tradition to modern aspects of drug development. Planta Med 84:834–838. https://doi.org/10.1055/a-0631-3876
Khashayar A, Bahari Z, Elliyeh M, Ghasemi M (2021) Therapeutic effects of berberine in metabolic diseases and diabetes mellitus. Rev Bras Farmacogn 31:272–281. https://doi.org/10.1007/s43450-021-00159-0
Kusonmano K, Vongsangnak W, Chumnanpuen P (2016) Informatics for metabolomics. Adv Exp Med Biol 939:91–115. https://doi.org/10.1007/10.1007/978-981-10-1503-8_5
Leonti M, Casu L, de Oliveira Martins DT, Rodrígues E, Benítez G (2020) Ecological theories and major hypotheses in ethnobotany: their relevance for ethnopharmacology and pharmacognosy in the context of historical data. Rev Bras Farmacogn 30:451–466. https://doi.org/10.1007/s43450-020-00074-w
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3–26. https://doi.org/10.1007/10.1016/s0169-409x(00)00129-0
Liu MZ, Zhang YL, Zeng MZ, He FZ, Luo ZY, Luo JQ, Wen JG, Chen XP, Zhou HH, Zhang W (2015) Pharmacogenomics and herb-drug interactions: merge of future and tradition. Evid-based Complement Altern 2015:321091. https://doi.org/10.1155/2015/321091
Mishra P, Kumar A, Nagireddy A, Mani DN, Shukla AK, Tiwari R, Sundaresan V (2016) DNA barcoding: an efficient tool to overcome authentication challenges in the herbal market. Plant Biotechnol J 14:8–21. https://doi.org/10.1111/pbi.12419
Moreira DDL, Teixeira SS, Monteiro MHD, De-Oliveira ACA, Paumgartten FJ (2014) Traditional use and safety of herbal medicines. Rev Bras Farmacogn 24:248–257. https://doi.org/10.1016/j.bjp.2014.03.006
Pang X, Shi L, Song J, Chen X, Chen S (2013) Use of the potential DNA barcode ITS2 to identify herbal materials. J Nat Med 67:571–575. https://doi.org/10.1007/s11418-012-0715-2
Pathak RK, Gupta A, Shukla R, Baunthiyal M (2018) Identification of new drug-like compounds from millets as xanthine oxidoreductase inhibitors for treatment of hyperuricemia: a molecular docking and simulation study. Comput Biol Chem 76:32–41. https://doi.org/10.1016/j.compbiolchem.2018.05.015
Pathak RK, Singh DB, Sagar M, Baunthiyal M, Kumar A (2020) Computational approaches in drug discovery and design. In: Singh DB (ed) Computer-aided drug design. Springer, Singapore, pp 1–21. https://doi.org/10.1007/978-981-15-6815-2_1
Patil VN, Shahnawaz M (2022) Tissue culture approaches to enhance plant secondary metabolites production. In: Shahnawaz M (ed) Biotechnological approaches to enhance plant secondary metabolites: recent trends and future prospects. CRC Press, Boca Raton, pp 89–97. https://doi.org/10.1201/9781003034957
Pereda-Miranda R, de Moraes Santos CA (2021) Trends in pharmacognosy: 35 years of research on therapeutical natural resources. Rev Bras Farmacogn 31:502–503. https://doi.org/10.1007/s43450-021-00208-8
Petrovska BB (2012) Historical review of medicinal plants’ usage. Pharmacogn Rev 6:1–5. https://doi.org/10.4103/0973-7847.95849
Prasad S, Aggarwal BB (2011) Turmeric, the golden spice: from traditional medicine to modern medicine. In: Benzie IFF, Wachtel-Galor S (eds) Herbal medicine: biomolecular and clinical aspects, 2nd edn. CRC Press, Boca Raton, pp 285–310
Rai SK, Pathak RK, Singh DB, Bhatt A, Baunthiyal M (2021) Chemo-informatics guided study of natural inhibitors targeting rho GTPase: a lead for treatment of glaucoma. In Silico Pharmacol 9:4. https://doi.org/10.1007/s40203-020-00061-y
Ramsay RR, Popovic-Nikolic MR, Nikolic K, Uliassi E, Bolognesi ML (2018) A perspective on multi-target drug discovery and design for complex diseases. Clin Trans Med 7:3. https://doi.org/10.1186/s40169-017-0181-2
Rifaioglu AS, Atas H, Martin MJ, Cetin-Atalay R, Atalay V, Doğan T (2019) Recent applications of deep learning and machine intelligence on in silico drug discovery: methods, tools, and databases. Brief Bioinform 20:1878–1912. https://doi.org/10.1093/bib/bby061
Rinschen MM, Ivanisevic J, Giera M, Siuzdak G (2019) Identification of bioactive metabolites using activity metabolomics. Nat Rev Mol Cell Biol 20:353–367. https://doi.org/10.1038/s41580-019-0108-4
Rosenkranz B, Fasinu P, Bouic P (2012) An overview of the evidence and mechanisms of herb–drug interactions. Front Pharmacol 3:69. https://doi.org/10.3389/fphar.2012.00069
Rubió L, Motilva MJ, Romero MP (2013) Recent advances in biologically active compounds in herbs and spices: a review of the most effective antioxidant and anti-inflammatory active principles. Crit Rev Food Sci Nutr 53:943–953. https://doi.org/10.1080/10408398.2011.574802
Salem MA, Perez de Souza L, Serag A, Fernie AR, Farag MA, Ezzat SM, Alseekh S (2020) Metabolomics in the context of plant natural products research: from sample preparation to metabolite analysis. Metabolites 10:37. https://doi.org/10.3390/metabo10010037
Sasidharan S, Chen Y, Saravanan D, Sundram KM, Latha LY (2011) Extraction, isolation, and characterization of bioactive compounds from plants extracts. Afr J Tradit Complement Altern Med 8:1–10
Schenone M, Dančík V, Wagner BK, Clemons PA (2013) Target identification and mechanism of action in chemical biology and drug discovery. Nat Chem Biol 9:232–240. https://doi.org/10.1038/nchembio.1199
Schmidt B, Ribnicky DM, Poulev A, Logendra S, Cefalu WT, Raskin I (2008) A natural history of botanical therapeutics. Metabol 57:S3–S9. https://doi.org/10.1016/j.metabol.2008.03.001
Selg E, Buccellati C, Andersson M, Rovati GE, Ezinga M, Sala A, Larsson AK, Ambrosio M, Låstbom L, Capra V, Dahlén B, Ryrfeldt A, Folco GC, Dahlén SE (2007) Antagonism of thromboxane receptors by diclofenac and lumiracoxib. Br. J Pharmacol 152:1185–1195. https://doi.org/10.1038/sj.bjp.0707518
Shukla R, Tripathi T (2020) Molecular dynamics simulation of protein and protein–ligand complexes. In: Singh DB (ed) Computer-aided drug design. Springer, Singapore, pp 133–161. https://doi.org/10.1007/978-981-15-6815-2_7
Singh DB, Pathak RK (2020) Computational approaches in drug designing and their applications. In: Gupta N, Gupta V (eds) Experimental protocols in biotechnology. Humana Press, New York, pp 95–117. https://doi.org/10.1007/978-1-0716-0607-0_6
Singh S, Singh VK (2020) Molecular dynamics simulation: methods and application. In: Singh DB, Tripathi T (eds) Frontiers in protein structure, function, and dynamics. Springer, Singapore, pp 213–238. https://doi.org/10.1007/978-981-15-5530-5_9
Singh PR, Singh LJ (2021) In vitro propagation for improvement of medicinal plants: a review. J Pharmacogn Phytochem 10:1484–1489
Sliwoski G, Kothiwale S, Meiler J, Lowe EW (2014) Computational methods in drug discovery. Pharmacol Rev 66:334–395. https://doi.org/10.1124/pr.112.007336
Sofowora A, Ogunbodede E, Onayade A (2013) The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med 10:210–229. https://doi.org/10.4314/ajtcam.v10i5.2
Stanzione F, Giangreco I, Cole JC (2021) Use of molecular docking computational tools in drug discovery. Prog Med Chem 60:273–343. https://doi.org/10.1016/bs.pmch.2021.01.004
Swaminathan P (2020) Advances in pharmacophore modeling and its role in drug designing. In: Singh DB (ed) Computer-aided drug design. Springer, Singapore, pp 223–243. https://doi.org/10.1007/978-981-15-6815-2_10
Thakur VV, Tripathi N, Tiwari S (2021) DNA barcoding of some medicinally important plant species of Lamiaceae family in India. Mol Biol Rep 48:3097–3106. https://doi.org/10.1007/s11033-021-06356-3
Thomford NE, Dzobo K, Chopera D, Wonkam A, Skelton M, Blackhurst D, Chirikure S, Dandara C (2015) Pharmacogenomics implications of using herbal medicinal plants on African populations in health transition. Pharmaceuticals 8:637–663. https://doi.org/10.3390/ph8030637
Thomford NE, Senthebane DA, Rowe A, Munro D, Seele P, Maroyi A, Dzobo K (2018) Natural products for drug discovery in the 21st century: innovations for novel drug discovery. Int J Mol Sci 19:1578. https://doi.org/10.3390/ijms19061578
Ventola CL (2010) Current issues regarding complementary and alternative medicine (CAM) in the United States. Part 1. The widespread use of CAM and the need for better-informed health care professionals to provide patient counseling. PT 35:461–468
Wang J, Wong YK, Liao F (2018) What has traditional Chinese medicine delivered for modern medicine? Expert Rev Mol Med 20(e4):1–9. https://doi.org/10.1017/erm.2018.3
Woodley CM, Amado PS, Cristiano ML, O’Neill PM (2021) Artemisinin inspired synthetic endoperoxide drug candidates: design, synthesis, and mechanism of action studies. Med Res Rev 41:3062–3095. https://doi.org/10.1002/med.21849
Xin T, Su C, Lin Y, Wang S, Xu Z, Song J (2018) Precise species detection of traditional Chinese patent medicine by shotgun metagenomic sequencing. Phytomedicine 47:40–47. https://doi.org/10.1016/j.phymed.2018.04.048
Yang J, Jia M, Guo J (2019a) Functional genome of medicinal plants. In: Huang L.-q. (ed) Molecular pharmacognosy. Springer, Singapore, pp 191–234. https://doi.org/10.1007/978-981-32-9034-1_7
Yang X, Wang Y, Byrne R, Schneider G, Yang S (2019b) Concepts of artificial intelligence for computer-assisted drug discovery. Chem Rev 119:10520–10594. https://doi.org/10.1021/acs.chemrev.8b00728
Zhang Z, Ge B, Zhou L, Lam TN, Zuo Z (2014) Induction of liver cytochrome P450s by Danshen-Gegen formula is the leading cause for its pharmacokinetic interactions with warfarin. J Ethnopharmacol 154:672–686. https://doi.org/10.1016/j.jep.2014.04.047
Zhang QW, Lin LG, Ye WC (2018) Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med 13:1–26. https://doi.org/10.1186/s13020-018-0177-x
Zhang K, Zhang Y, Li N, Xing F, Zhao J, Yang T, Liu C, Feng N (2019) An herbal-compound-based combination therapy that relieves cirrhotic ascites by affecting the L-arginine/nitric oxide pathway: a metabolomics-based systematic study. J Ethnopharmacol 241:112034. https://doi.org/10.1016/j.jep.2019.112034
Zhao L, Ciallella HL, Aleksunes LM, Zhu H (2020) Advancing computer-aided drug discovery (CADD) by big data and data-driven machine learning modeling. Drug Discov Today. 25:1624–1638. https://doi.org/10.1016/j.drudis.2020.07.005
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The authors are grateful to Professor Rogelio Pereda-Miranda, Editor-in-Chief of Revista Brasileira de Farmacognosia, for his help in improving the original manuscript.
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DBS developed the idea for this review article and its coverage. DBS and RKP drafted the article, and DR critically revised the work. All authors have read the final manuscript and approved the submission.
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Singh, D.B., Pathak, R.K. & Rai, D. From Traditional Herbal Medicine to Rational Drug Discovery: Strategies, Challenges, and Future Perspectives. Rev. Bras. Farmacogn. 32, 147–159 (2022). https://doi.org/10.1007/s43450-022-00235-z
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DOI: https://doi.org/10.1007/s43450-022-00235-z