*Article not assigned to an issue yet
Padmanabhan Deepthi, Manimekalai Ramaswamy, Senthil-Nathan Sengottayan, Suganthi Muthusamy, Palanisamy Senthilkumar
Keywords: Natural products, Novel drugs, Medicinal plants, Secondary metabolites
From the year 2016 to 2019, a total of 196 botanical drugs were registered for clinical trials, out of which 81 drugs were in phase II or III laid an environment for further trials and marketing of the drugs. Vasicine, a pyrroquinazoline alkaloidal compound found in some medicinal plants such as Justicia adhatoda and Sida cordifolia to name a few. Due to its broad range of health-promoting properties, the compound has piqued the attention of nutritionists and medicinal chemists. The compound’s recent pharmacological applications include antiviral activity against SARS-Co-V2, antimicrobial activity against E. aerogenes, S. epidermidis and P. aeruginosa, cytotoxic effect against lung adenocarcinoma and free radical scavenging activity, implying a potential role as an antioxidant. Vasicine was also discovered to have a possible anti-inflammatory property in carrageenan-induced inflammation, as well as neuroprotective efficacy in in vitro experiments on neuroblastoma cells by blocking cholinesterases in Alzheimer’s disease and improving memory and cognition. The integration of a multi-omics approach to elucidate the biosynthetic pathway and key regulatory enzymes laid the basis for metabolically engineering the entire pathway in microbial systems, as well as polyculture of microbes for robust biosynthesis strategies to overcome the limitations of traditional monoculture techniques for bioactive production. Genome editing with CRISPR Cas technologies plays a major role in the transformation of vasicine metabolite engineering to alter the process of biosynthesis and increase large-scale production in plants.
Abdulhafiz F, Mohammed A, Reduan MFH, Kari ZA, Wei LS, Goh KW (2022) Plant cell culture technologies: a promising alternatives to produce high-value secondary metabolites. Arab J Chem 15(11):104161. https://doi.org/10.1016/j.arabjc.2022.104161
Abdull Razis AF, Ibrahim MD, Kntayya SB (2014) Health benefits of Moringa oleifera. Asian Pac J Cancer Prev 15(20):8571–8576. https://doi.org/10.7314/APJCP.2014.15.20.8571
Ahmad M, Aga MA, Bhat JA, Kumar B, Rouf A, Capalash N, Mintoo MJ, Kumar A, Mahajan P, Mondhe DM, Nargotra A, Sharma PR, Zargar MA, Vishwakarma RA, Shah BA, Taneja SC, Hamid A (2017) Exploring derivatives of Quinazoline Alkaloid l-Vasicine as Cap groups in the design and biological mechanistic evaluation of novel antitumor histone deacetylase inhibitors. J Med Chem 60(8):3484–3497. https://doi.org/10.1021/acs.jmedchem.7b00322
Alagoz Y, Gurkok T, Zhang B, Unver T (2016) Manipulating the biosynthesis of bioactive compound alkaloids for next-generation metabolic engineering in opium poppy using CRISPR-Cas 9 genome editing technology. Sci Rep. https://doi.org/10.1038/srep30910
Ali SK, Hamed AR, Soltan MM, El-Halawany AM, Hegazy UM, Hussein AA (2016) Kinetics and molecular docking of vasicine from Adhatoda vasica: an acetylcholinesterase inhibitor for Alzheimer’s disease. South Afr J Bot 104:118–124. https://doi.org/10.1016/j.sajb.2015.09.021
Amala R, Sujatha S (2019) Presence of pyrroloquinazoline alkaloid in Adhatoda vasica attenuates inflammatory response through the downregulation of pro-inflammatory mediators in LPS stimulated RAW 264.7 macrophages. BioImpacts. https://doi.org/10.34172/bi.2021.03
Anand U, Jacobo-Herrera N, Altemimi A, Lakhssassi N (2019) A comprehensive review on medicinal plants as antimicrobial therapeutics: potential avenues of biocompatible drug discovery. Metabolites. https://doi.org/10.3390/metabo9110258
Arthi B, Chellathai D (2023) Effects of vasicine in neuroinflammatory zebrafish model. Bioinformation 19(5):595–604. https://doi.org/10.6026/97320630019595
Ayoola-Oresanya IO, Sonibare MA, Gueye B, Abberton MT, Morlock GE (2021) Elicitation of antioxidant metabolites in Musa species in vitro shoot culture using sucrose, temperature and jasmonic acid. Plant Cell Tissue Organ Cult (PCTOC) 146(2):225–236. https://doi.org/10.1007/s11240-021-02062-x
Baenas N, García-Viguera C, Moreno DA (2014) Elicitation: a tool for enriching the bioactive composition of foods. Molecules. https://doi.org/10.3390/molecules190913541
Bajpai VK, Agrawal P, Bang BH, Park YH (2015) Phytochemical analysis, antioxidant and antilipid peroxidation effects of a medicinal plant, Adhatoda vasica. Front Life Sci 8(3):305–312. https://doi.org/10.1080/21553769.2014.1002943
Bapat VA, Kavi Kishor PB, Jalaja N, Jain SM, Penna S (2023) Plant cell cultures: biofactories for the production of bioactive compounds. Agronomy. https://doi.org/10.3390/agronomy13030858
Batista R, De Jesus Silva Júnior A, De Oliveira AB (2009) Plant-derived antimalarial agents: new leads and efficient phytomedicines. Part II. Non-alkaloidal natural products. Molecules. https://doi.org/10.3390/molecules14083037
Bednarska K, Kuś P, Fecka I (2020) Investigation of the Phytochemical composition, antioxidant activity, and methylglyoxal trapping effect of Galega officinalis L. herb in vitro. Molecules. https://doi.org/10.3390/molecules25245810
Benson Muthee K, Maitho TE, Kanja LW, Onyancha JM (2022) Evaluation of uterotonic activity, acute oral toxicity, and phytochemical composition of Uvariodendron anisatum Verdc. Root extracts. Evid Based Complement Alternat Med. https://doi.org/10.1155/2022/7393537
Bhanukiran KTG, Krishnamurthy S, Singh SK, Hemalatha S (2023) Discovery of multi-target directed 3-OH pyrrolidine derivatives through a semisynthetic approach from alkaloid vasicine for the treatment of Alzheimer’s disease. Eur J Med Chem 249:115145. https://doi.org/10.1016/j.ejmech.2023.115145
Bhaskar R, Xavier LSE, Udayakumaran G, Kumar DS, Venkatesh R, Nagella P (2022) Biotic elicitors: a boon for the in-vitro production of plant secondary metabolites. Plant Cell Tissue Organ Cult (PCTOC) 149(1):7–24. https://doi.org/10.1007/s11240-021-02131-1
Broun P (2004) Transcription factors as tools for metabolic engineering in plants. Curr Opin Plant Biol 7(2):202–209. https://doi.org/10.1016/j.pbi.2004.01.013
Cao J, Shen HM, Wang Q, Qian Y, Guo HC, Li K, Qiao X, Guo DA, Luo XD, Ye M (2016) Characterization of chemical constituents and rats metabolites of an alkaloidal extract of Alstonia scholaris leaves by liquid chromatography coupled with mass spectrometry. J Chromatogr B 1026:43–55. https://doi.org/10.1016/j.jchromb.2015.07.044
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
Chattopadhyay S, Farkya S, Srivastava AK, Bisaria VS (2002) Bioprocess considerations for production of secondary metabolites by plant cell suspension cultures. Biotechnol Bioprocess Eng 7(3):138–149. https://doi.org/10.1007/BF02932911
Claeson UP, Malmfors T, Wikman G, Bruhn JG (2000) Adhatoda vasica: a critical review of ethnopharmacological and toxicological data. J Ethnopharmacol 72(1):1–20. https://doi.org/10.1016/S0378-8741(00)00225-7
Clemensen AK, Provenza FD, Hendrickson JR, Grusak MA (2020) Ecological implications of plant secondary metabolites—Phytochemical diversity can enhance agricultural sustainability. Front Sust Food Syst. https://doi.org/10.3389/fsufs.2020.547826
Dang TK, Hong SM, Dao VT, Tran PTT, Tran HT, Do GH, Hai TN, Nguyet Pham HT, Kim SY (2023) Anti-neuroinflammatory effects of alkaloid-enriched extract from Huperzia serrata on lipopolysaccharide-stimulated BV-2 microglial cells. Pharm Biol 61(1):135–143. https://doi.org/10.1080/13880209.2022.2159450
Dhyani P, Quispe C, Sharma E, Bahukhandi A, Sati P, Attri DC, Szopa A, Sharifi Rad J, Docea AO, Mardare I, Calina D, Cho WC (2022) Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer Cell Int 22(1):206. https://doi.org/10.1186/s12935-022-02624-9
DiCosmo F, Misawa M (1995) Plant cell and tissue culture: alternatives for metabolite production. Biotechnol Adv 13(3):425–453. https://doi.org/10.1016/0734-9750(95)02005-N
Dong Z, Wang Y, Tang Z, Li C, Jiang T, Yang Z, Zeng J (2022) Exploring the anti-inflammatory effects of protopine total alkaloids of Macleaya cordata (Willd.) R. Br. Front Vet Sci. https://doi.org/10.3389/fvets.2022.935201
Duggleby RG, Sneddon MK, Morrison JF (1978) Chorismate mutase-prephenate dehydratase from Escherichia coli: active sites of a bifunctional enzyme. Biochemistry 17(8):1548–1554. https://doi.org/10.1021/bi00601a030
Duraipandiyan V, Al-Dhabi NA, Balachandran C, Ignacimuthu S, Sankar C, Balakrishna K (2015) Antimicrobial, antioxidant, and cytotoxic properties of vasicine acetate synthesized from vasicine isolated from Adhatoda vasica L. Biomed Res Int. https://doi.org/10.1155/2015/727304
Efferth T (2019) Biotechnology applications of plant callus cultures. Engineering 5(1):50–59. https://doi.org/10.1016/j.eng.2018.11.006
Galal A, Raman V, Khan IA (2015) Sida cordifolia, a traditional herb in modern perspective—a review. Curr Tradit Med 1(1):5–17
Gantait S, Panigrahi J (2018) In vitro biotechnological advancements in Malabar nut (Adhatoda vasica Nees): achievements, status and prospects. J Genetic Eng Biotechnol 16(2):545–552. https://doi.org/10.1016/j.jgeb.2018.03.007
Gao H, Huang YN, Gao B, Li P, Inagaki C, Kawabata J (2008) Inhibitory effect on α-glucosidase by Adhatoda vasica Nees. Food Chem 108(3):965–972. https://doi.org/10.1016/j.foodchem.2007.12.002
Ghanta P, Doble M, Ramaiah B (2022) Alkaloids of Adhatoda vasica Nees. As potential inhibitors of cyclooxygenases—an in-silico study. J Biomol Struct Dynamics 40(16):7245–7255. https://doi.org/10.1080/07391102.2021.1895887
Gheware A, Dholakia D, Kannan S, Panda L, Rani R, Pattnaik BR, Jain V, Parekh Y, Enayathullah MG, Bokara KK, Subramanian V, Mukerji M, Agrawal A, Prasher B (2021) Adhatoda vasica attenuates inflammatory and hypoxic responses in preclinical mouse models: potential for repurposing in COVID-19-like conditions. Respir Res 22(1):99. https://doi.org/10.1186/s12931-021-01698-9
Ghosh R, Chakraborty A, Biswas A, Chowdhuri S (2021) Identification of alkaloids from Justicia adhatoda as potent SARS CoV-2 main protease inhibitors: an in silico perspective. J Mol Struct 1229:129489. https://doi.org/10.1016/j.molstruc.2020.129489
Giri CC, Zaheer M (2016) Chemical elicitors versus secondary metabolite production in vitro using plant cell, tissue and organ cultures: recent trends and a sky eye view appraisal. Plant Cell Tissue Organ Cult (PCTOC) 126(1):1–18. https://doi.org/10.1007/s11240-016-0985-6
Grange JM, Snell NJC (1996) Activity of bromhexine and ambroxol, semi-synthetic derivatives of vasicine from the Indian shrub Adhatoda vasica, against Mycobacterium tuberculosis in vitro. J Ethnopharmacol 50(1):49–53. https://doi.org/10.1016/0378-8741(95)01331-8
Guo M, Chen H, Dong S, Zhang Z, Luo H (2022) CRISPR-Cas gene editing technology and its application prospect in medicinal plants. Chin Med 17(1):33. https://doi.org/10.1186/s13020-022-00584-w
Gupta OP, Anand KK, Ghatak BJ, Atal CK (1978) Vasicine, alkaloid of Adhatoda vasica, a promising uterotonic abortifacient. Indian J Exp Biol 16(10):1075–1077
Gurung AB, Ali MA, Lee J, Farah MA, Al-Anazi KM (2020) Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 mpro enzyme through in silico approach. Life Sci 255:117831. https://doi.org/10.1016/j.lfs.2020.117831
Gyebi GA, Ogunro OB, Adegunloye AP, Ogunyemi OM, Afolabi SO (2020) Potential inhibitors of coronavirus 3-chymotrypsin-like protease (3CLpro): an in silico screening of alkaloids and terpenoids from African medicinal plants. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2020.1764868
Halder M, Sarkar S, Jha S (2019) Elicitation: a biotechnological tool for enhanced production of secondary metabolites in hairy root cultures. Eng Life Sci 19(12):880–895. https://doi.org/10.1002/elsc.201900058
Ho TT, Murthy HN, Park SY (2020) Methyl jasmonate induced oxidative stress and accumulation of secondary metabolites in plant cell and organ cultures. Int J Mol Sci. https://doi.org/10.3390/ijms21030716
Hua H, Cheng M, Li X, Pei Y (2002) A new pyrroloquinazoline alkaloid from Linaria vulgaris. Chem Pharm Bull 50(10):1393–1394. https://doi.org/10.1248/cpb.50.1393
Huccetogullari D, Luo ZW, Lee SY (2019) Metabolic engineering of microorganisms for production of aromatic compounds. Microb Cell Fact. https://doi.org/10.1186/s12934-019-1090-4
Isah T (2019) Stress and defense responses in plant secondary metabolites production. Biol Res 52(1):39. https://doi.org/10.1186/s40659-019-0246-3
Jahangir T, Khan TH, Prasad L et al (2006) Reversal of cadmium chloride-induced oxidative stress and genotoxicity by Adhatoda vasica extract in Swiss albino mice. Biol Trace Elem Res 111:217–228
Jalali A, Dabaghian F, Zarshenas MM (2021) Alkaloids of Peganum harmala: anticancer biomarkers with promising outcomes. Curr Pharm Des 27(2):185–196
Jiang T, Zhang L, Ding M, Li M (2019) Protective effect of vasicine against myocardial infarction in rats via modulation of oxidative stress, inflammation, and the PI3K/Akt pathway. Drug Des Devel Ther 13:3773–3784. https://doi.org/10.2147/DDDT.S220396
Jiang C, Lv G, Tu Y, Cheng X, Duan Y, Zeng B, He B (2021) Applications of CRISPR/Cas9 in the synthesis of secondary metabolites in filamentous Fungi. Front Microbiol 12:638096. https://doi.org/10.3389/fmicb.2021.638096
Jørgensen K, Rasmussen AV, Morant M, Nielsen AH, Bjarnholt N, Zagrobelny M, Bak S, Møller BL (2005) Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr Opin Plant Biol 8(3):280–291. https://doi.org/10.1016/j.pbi.2005.03.014
Kamińska M (2021) Role and activity of jasmonates in plants under in vitro conditions. Plant Cell Tissue Organ Cult (PCTOC) 146(3):425–447. https://doi.org/10.1007/s11240-021-02091-6
Kang SM, Min JY, Kim YD, Kang YM, Park DJ, Jung HN, Kim SW, Choi MS (2006) Effects of methyl jasmonate and salicylic acid on the production of bilobalide and ginkgolides in cell cultures of Ginkgo biloba. In Vitro Cell Dev Biol 42(1):44–49. https://doi.org/10.1079/IVP2005719
Kast P, Grisostomi C, Chen IA, Li S, Krengel U, Xue Y, Hilvert D (2000) A strategically positioned cation is crucial for efficient catalysis by chorismate mutase. J Biol Chem 275(47):36832–36838. https://doi.org/10.1074/jbc.M006351200
Kui L, Chen H, Zhang W, He S, Xiong Z, Zhang Y, Yan L, Zhong C, He F, Chen J, Zeng P, Zhang G, Yang S, Dong Y, Wang W, Cai J (2017) Building a genetic manipulation tool box for orchid biology: identification of constitutive promoters and application of CRISPR/Cas9 in the orchid, Dendrobium officinale. Front Plant Sci. https://doi.org/10.3389/fpls.2016.02036
Kumari N, Akhtar J, Ahmad M, Badruddeen, Khan MI (2021) An outline on vasicine, its ethnomedical and nanoformulation approach. J Biol Act Prod Nat 11(1):42–59. https://doi.org/10.1080/22311866.2021.1886990
Larkin PJ, Miller JAC, Allen RS, Chitty JA, Gerlach WL, Frick S, Kutchan TM, Fist AJ (2007) Increasing morphinan alkaloid production by over-expressing codeinone reductase in transgenic Papaver somniferum. Plant Biotechnol J 5(1):26–37. https://doi.org/10.1111/j.1467-7652.2006.00212.x
Li B, Li J, Chai Y, Huang Y, Li L, Wang D, Wang Z (2021) Targeted mutagenesis of CYP76AK2 and CYP76AK3 in Salvia miltiorrhiza reveals their roles in tanshinones biosynthetic pathway. Int J Biol Macromol 189:455–463. https://doi.org/10.1016/j.ijbiomac.2021.08.112
Liang C, Chen C, Zhou P, Xu L, Zhu J, Liang J, Zi J, Yu R (2018) Effect of Aspergillus flavus fungal elicitor on the production of terpenoid indole alkaloids in Catharanthus roseus cambial meristematic cells. Molecules. https://doi.org/10.3390/molecules23123276
Light SH, Anderson WF (2013) The diversity of allosteric controls at the gateway to aromatic amino acid biosynthesis. Protein Sci 22(4):395–404. https://doi.org/10.1002/pro.2233
Linh TM, Mai NC, Hoe PT, Ngoc NT, Thao PTH, Ban NK, Van NT (2021) Development of a cell suspension culture system for promoting alkaloid and vinca alkaloid biosynthesis using endophytic fungi isolated from local Catharanthus roseus. Plants. https://doi.org/10.3390/plants10040672
Liu X, Williams CE, Nemacheck JA, Wang H, Subramanyam S, Zheng C, Chen MS (2010) Reactive oxygen species are involved in plant defense against a gall midge. Plant Physiol 152(2):985–999. https://doi.org/10.1104/pp.109.150656
Liu W, Shi X, Yang Y, Cheng X, Liu Q, Han H, Yang B, He C, Wang Y, Jiang B, Wang Z, Wang C (2015a) In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent acetylcholinesterase and butyrylcholinesterase inhibitor. PLoS ONE 10(4):e0122366. https://doi.org/10.1371/journal.pone.0122366
Liu W, Wang Y, He D, Li S, Zhu Y, Jiang B, Cheng X, Wang Z, Wang C (2015b) Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids (±)-vasicine, deoxyvasicine, and (±)-vasicinone from aerial parts of Peganum harmala L. Phytomedicine 22(12):1088–1095. https://doi.org/10.1016/j.phymed.2015.08.005
Lu JJ, Bao JL, Chen XP, Huang M, Wang YT (2012) Alkaloids isolated from natural herbs as the anticancer agents. Evid Based Complement Alternat Med 2012:e485042. https://doi.org/10.1155/2012/485042
Ma ZZ, Hano Y, Nomura T, Chen YJ (2000) Alkaloids and phenylpropanoids from Peganum nigellastrum. Phytochemistry 53(8):1075–1078. https://doi.org/10.1016/S0031-9422(99)00440-9
Maeda H, Dudareva N (2012) The Shikimate pathway and aromatic amino acid biosynthesis in plants. Annu Rev Plant Biol 63(1):73–105. https://doi.org/10.1146/annurev-arplant-042811-105439
Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454(7203):Article7203. https://doi.org/10.1038/nature07201
Montecillo JAV, Chu LL, Bae H (2020) CRISPR-Cas9 system for plant genome editing: current approaches and emerging developments. Agronomy. https://doi.org/10.3390/agronomy10071033
Muthusamy SP, Jagadeeswaran A, Natarajan A (2024) Pharmacokinetics, dynamics, toxicology and molecular docking of bioactive alkaloid vasicine from Adhatoda vasica: a promising toxin binder against aflatoxin B1 and ochratoxin A. Poult Sci 103(2):103272. https://doi.org/10.1016/j.psj.2023.103272
Nepali K, Sharma S, Ojha R, Dhar KL (2013) Vasicine and structurally related quinazolines. Med Chem Res 22(1):1–15. https://doi.org/10.1007/s00044-012-0002-5
Ogita S, Uefuji H, Morimoto M, Sano H (2004) Application of RNAi to confirm theobromine as the major intermediate for caffeine biosynthesis in coffee plants with potential for construction of decaffeinated varieties. Plant Mol Biol 54(6):931–941. https://doi.org/10.1007/s11103-004-0393-x
Ozyigit II, Dogan I, Hocaoglu-Ozyigit A, Yalcin B, Erdogan A, Yalcin IE, Cabi E, Kaya Y (2023) Production of secondary metabolites using tissue culture-based biotechnological applications. Front Plant Sci. https://doi.org/10.3389/fpls.2023.1132555
Pa R, Mathew L (2012) Antimicrobial activity of leaf extracts of Justicia adhatoda L. in comparison with vasicine. Asian Pac J Trop Biomed 2(3):S1556–S1560. https://doi.org/10.1016/S2221-1691(12)60452-3
Pan Q, Wang Q, Yuan F, Xing S, Zhao J, Choi YH, Verpoorte R, Tian Y, Wang G, Tang K (2012) Overexpression of ORCA3 and G10H in Catharanthus roseus plants regulated alkaloid biosynthesis and metabolism revealed by NMR-metabolomics. PLoS ONE 7(8):e43038. https://doi.org/10.1371/journal.pone.0043038
Patra JK, Das G, Lee S, Kang SS, Shin HS (2018) Selected commercial plants: a review of extraction and isolation of bioactive compounds and their pharmacological market value. Trends Food Sci Technol 82:89–109. https://doi.org/10.1016/j.tifs.2018.10.001
Pence VC (2011) Evaluating costs for the in vitro propagation and preservation of endangered plants. In Vitro Cell Dev Biol Plant 47(1):176–187. https://doi.org/10.1007/s11627-010-9323-6
Qiu J, Chen Y, Zhuo J, Zhang L, Liu J, Wang B, Sun D, Yu S, Lou H (2022) Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson’s disease model. Neuropharmacology 207:108963. https://doi.org/10.1016/j.neuropharm.2022.108963
Rachana Sujata B, Mamta P, Priyanka KM, Sonam S (2011) Review & future perspectives of using vasicine, and related compounds. Indo Global J Pharm Sci 1(1):85–98
Ramirez-Estrada K, Vidal-Limon H, Hidalgo D, Moyano E, Golenioswki M, Cusidó RM, Palazon J (2016) Elicitation, an effective strategy for the biotechnological production of bioactive high-added value compounds in plant cell factories. Molecules. https://doi.org/10.3390/molecules21020182
Rudrapal M, Vallinayagam S, Aldosari S, Khan J, Albadrani H, Al-Shareeda A, Kamal M (2023) Valorization of Adhatoda vasica leaves: extraction, in vitro analyses and in silico approaches. Front Nutr. https://doi.org/10.3389/fnut.2023.1161471
Sabzehzari M, Zeinali M, Naghavi MR (2020) CRISPR-based metabolic editing: next-generation metabolic engineering in plants. Gene 759:144993. https://doi.org/10.1016/j.gene.2020.144993
Salmerón-Manzano E, Garrido-Cardenas JA, Manzano-Agugliaro F (2020) Worldwide research trends on medicinal plants. Int J Environ Res Public Health. https://doi.org/10.3390/ijerph17103376
Sasso S, Ramakrishnan C, Gamper M, Hilvert D, Kast P (2005) Characterization of the secreted chorismate mutase from the pathogen Mycobacterium tuberculosis. FEBS J 272(2):375–389. https://doi.org/10.1111/j.1742-4658.2004.04478.x
Sen S, Chakraborty R (2017) Revival, modernization and integration of Indian traditional herbal medicine in clinical practice: importance, challenges and future. J Traditional Complement Med 7(2):234–244. https://doi.org/10.1016/j.jtcme.2016.05.006
Senthil-Nathan S (2015) A Review of Biopesticides and Their Mode of Action Against Insect Pests. In P. Thangavel & G. Sridevi (Eds.), Environmental Sustainability: Role of Green Technologies. Springer India. https://doi.org/10.1007/978-81-322-2056-5_3
Shoaib A (2022) A systematic ethnobotanical review of Adhatoda vasica (L.), Nees. Cell Mol Biol (Noisy-le-grand) 67(4):248–263. https://doi.org/10.14715/cmb/2021.67.4.28
Shrivastava N, Srivastava A, Banerjee A, Nivsarkar M (2009) Anti-ulcer activity of Adhatoda vasica Nees. J Herbal Pharmacother. https://doi.org/10.1080/J157v06n02_04
Siddiqui ZH, Mujib A, Mahmooduzzafar Aslam J, Rehman Hakeem K, Parween T (2013) In vitro Production of Secondary Metabolites Using Elicitor in Catharanthus roseus: A Case Study. In K. R. Hakeem, P. Ahmad, & M. Ozturk (Eds.), Crop Improvement: New Approaches and Modern Techniques. Springer US. https://doi.org/10.1007/978-1-4614-7028-1_14
Singh R, Chandel S, Ghosh A, Dey D, Chakravarti R, Roy S, Ravichandiran V, Ghosh D (2021) Application of CRISPR/Cas system in the metabolic engineering of small molecules. Mol Biotechnol 63(6):459–476. https://doi.org/10.1007/s12033-021-00310-1
Sohn SI, Pandian S, Rakkammal K, Largia MJV, Thamilarasan SK, Balaji S, Zoclanclounon YAB, Shilpha J, Ramesh M (2022) Jasmonates in plant growth and development and elicitation of secondary metabolites: an updated overview. Front Plant Sci. https://doi.org/10.3389/fpls.2022.942789
Sträter N, Schnappauf G, Braus G, Lipscomb WN (1997) Mechanisms of catalysis and allosteric regulation of yeast chorismate mutase from crystal structures. Structure 5(11):1437–1452. https://doi.org/10.1016/S0969-2126(97)00294-3
Sun J, Peebles CAM (2016) Engineering overexpression of ORCA3 and strictosidine glucosidase in Catharanthus roseus hairy roots increases alkaloid production. Protoplasma 253(5):1255–1264. https://doi.org/10.1007/s00709-015-0881-7
Takeuchi C, Nagatani K, Sato Y (2013) Chitosan and a fungal elicitor inhibit tracheary element differentiation and promote accumulation of stress lignin-like substance in Zinnia elegans xylogenic culture. J Plant Res 126(6):811–821. https://doi.org/10.1007/s10265-013-0568-0
Takshak S, Agrawal SB (2019) Defense potential of secondary metabolites in medicinal plants under UV-B stress. J Photochem Photobiol B 193:51–88. https://doi.org/10.1016/j.jphotobiol.2019.02.002
Tamano K, Yoshimi A (2021) Metabolic engineering techniques to increase the productivity of primary and secondary metabolites within filamentous fungi. Front Fungal Biol. https://doi.org/10.3389/ffunb.2021.743070
Tehreem S, Rahman S, Bhatti MS, Uddin R, Khan MN, Tauseef S, El-Seedi HR, Bin Muhsinah A, Uddin J, Musharraf SG (2021) A UPLC-DAD-based bio-screening assay for the evaluation of the angiotensin converting enzyme inhibitory potential of plant extracts and compounds: pyrroquinazoline alkaloids from Adhatoda vasica as a case study. Molecules. https://doi.org/10.3390/molecules26226971
Tepe B, Sokmen A (2007) Production and optimisation of rosmarinic acid by Satureja hortensis L. callus cultures. Nat Prod Res 21(13):1133–1144. https://doi.org/10.1080/14786410601130737
Thangaraju P, Ty SS, Pasala PK, Ty SH, Venkatesan S, Thangaraju E (2021) The role of Justicia adhatoda as prophylaxis for COVID-19—analysis based on docking. Infect Disord Drug Targets 21(8):2–8
Thanigaivel A, Senthil-Nathan S, Vasantha Srinivasan P, Edwin ES, Ponsankar A, Selin Rani S, Pradeepa V, Chellappandian M, Kalaivani K, Abdel-Megeed A, Narayanan R, Murugan K (2017) Chemicals isolated from Justicia adhatoda Linn reduce fitness of the mosquito, Aedes aegypti L. Arch Insect Biochem Physiol 94(4):e21384. https://doi.org/10.1002/arch.21384
Wakhloo RL, Girija K, Gupta OP, Atal CK (1980) Safety of vasicine hydrochloride in human volunteers. Indian J Pharmacol 12(2):129
Weiss U (2008) Inflammation. Nature. https://doi.org/10.1038/454427a
Wink M (2015) Modes of action of herbal medicines and plant secondary metabolites. Medicines. https://doi.org/10.3390/medicines2030251
Winkel BSJ (2004) Metabolic channeling in plants. Annu Rev Plant Biol 55(1):85–107. https://doi.org/10.1146/annurev.arplant.55.031903.141714
Wu T, Kerbler SM, Fernie AR, Zhang Y (2021) Plant cell cultures as heterologous bio-factories for secondary metabolite production. Plant Commun 2(5):100235. https://doi.org/10.1016/j.xplc.2021.100235
Wu S, Chen W, Lu S, Zhang H, Yin L (2022) Metabolic engineering of shikimic acid biosynthesis pathway for the production of shikimic acid and its branched products in microorganisms: advances and prospects. Molecules. https://doi.org/10.3390/molecules27154779
Yeshi K, Crayn D, Ritmejerytė E, Wangchuk P (2022) Plant secondary metabolites produced in response to abiotic stresses has potential application in pharmaceutical product development. Molecules. https://doi.org/10.3390/molecules27010313
Zabalza A, Orcaray L, Fernández-Escalada M, Zulet-González A, Royuela M (2017) The pattern of shikimate pathway and phenylpropanoids after inhibition by glyphosate or quinate feeding in pea roots. Pestic Biochem Physiol 141:96–102. https://doi.org/10.1016/j.pestbp.2016.12.005
Zhang H, Abid S, Ahn JC, Mathiyalagan R, Kim YJ, Yang DC, Wang Y (2020) Characteristics of Panax ginseng Cultivars in Korea and China. Molecules. https://doi.org/10.3390/molecules25112635
Zhang X, Xu G, Cheng C, Lei L, Sun J, Xu Y, Deng C, Dai Z, Yang Z, Chen X, Liu C, Tang Q, Su J (2021) Establishment of an agrobacterium-mediated genetic transformation and CRISPR/Cas9-mediated targeted mutagenesis in hemp (Cannabis sativa L). Plant Biotechnol J 19(10):1979–1987. https://doi.org/10.1111/pbi.13611
Zhao L, Chang W, Xiao Y, Liu H, Liu P (2013) Methylerythritol phosphate pathway of isoprenoid biosynthesis. Annu Rev Biochem 82(1):497–530. https://doi.org/10.1146/annurev-biochem-052010-100934
Zhao YL, Yang ZF, Shang JH, Huang WY, Wang B, Wei X, Khan A, Yuan ZW, Liu YP, Wang YF, Wang XH, Luo XD (2018) Effects of indole alkaloids from leaf of Alstonia scholaris on post-infectious cough in mice. J Ethnopharmacol 218:69–75. https://doi.org/10.1016/j.jep.2018.02.040
Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, India