Iridoid glycosides from Picrorhiza genus endemic to the Himalayan region: phytochemistry, biosynthesis, pharmacological potential and biotechnological intercessions to boost production

References

• Joshi RK, Satyal P, Setzer WN. Himalayan aromatic medicinal plants: a review of their ethnopharmacology, volatile phytochemistry, and biological activities. Medicines. 2016;3(1):6.
   Google Scholar
• Ved DK, Mudappa A, Shanker D. Regulating export of endangered medicinal plant species-need for scientific vigour. Curr Sci. 1998;75:341–344.
   Web of Science ®Google Scholar
• Uniyal SK, Awasthi A, Rawat GS. (2002). current status and distribution of commercially exploited medicinal and aromatic plants in upper gori valley, Kumaon Himalaya, Uttaranchal. Curr Sci. 2002;82:1246–1252.
   Web of Science ®Google Scholar
• Kala CP. Status and conservation of rare and endangered medicinal plants in the Indian trans-Himalaya. Biol Conserv. 2000;93(3):371–379.
   Web of Science ®Google Scholar
• Dinda B, Debnath S, Harigaya Y. Naturally occurring iridoids. A review, part 1. Chem Pharm Bull. 2007;55(2):159–222.
   PubMed Web of Science ®Google Scholar
• Viljoen A, Mncwangi N, Vermaak I. Anti-inflammatory iridoids of botanical origin. Curr Med Chem. 2012;19(14):2104–2127.
   PubMed Web of Science ®Google Scholar
• Ghisalberti EL. Biological and pharmacological activity of naturally occurring iridoids and secoiridoids. Phytomedicine. 1998;5(2):147–163.
   PubMed Web of Science ®Google Scholar
• Wang C, Gong X, Bo A, et al. Iridoids: research advances in their phytochemistry, biological activities, and pharmacokinetics. Molecules. 2020;25(2):287.
   PubMed Web of Science ®Google Scholar
• Gonçalves GA, Eifler-Lima VL, von Poser GL. Revisiting nature: a review of iridoids as a potential antileishmanial class. Phytochem Rev. 2021;21:101–126.
   PubMed Web of Science ®Google Scholar
• Hussain H, Green IR, Saleem M, et al. Therapeutic potential of iridoid derivatives: patent review. Inventions. 2019;4(2):29.
   Google Scholar
• Kumar V, Chauhan RS, Tandon C. Biosynthesis and therapeutic implications of iridoid glycosides from Picrorhiza genus: the road ahead. J Plant Biochem Biotechnol. 2017;26(1):1–3.
   Web of Science ®Google Scholar
• Smit HF, Kroes BH, Van den Berg AJ, et al. Immunomodulatory and anti-inflammatory activity of Picrorhiza scrophulariiflora. J Ethnopharmacol. 2000;73(1–2):101–109.
   PubMed Web of Science ®Google Scholar
• Skinder BM, Ganai BA, Wani AH. Scientific study of Gentiana Kurroo Royle. Medicines. 2017;4(4):74.
   Google Scholar
• Kelayeh TP, Abedinzade M, Ghorbani A. A review on biological effects of Lamium album (white dead nettle) and its components. J Herbmed Pharmacol. 2019;8(3):185–193.
   Google Scholar
• Kumar N, Singh B, Kaul VK, et al. Chemical and biological aspects of iridoid bearing plants of temperate region. Stud Nat Prod Chem. 2005;32:247–302.
   Google Scholar
• Mulas M. Traditional uses of Labiatae in the Mediterranean area. Acta Hortic. 2006;723:25–32.
   Google Scholar
• Nickavar B, Mojab F, Bamasian S. Volatile components from aerial parts of Lamium amplexicaule from Iran. J Essent Oil-Bear Plants. 2008;11(1):36–40.
   Web of Science ®Google Scholar
• Panchal MA, Murti K, Lambole V. Pharmacological properties of Verbascum Thapsus—a review. Int J Pharm Sci Rev Res. 2010;5(2):73–77.
   Google Scholar
• Kubica P, Szopa A, Dominiak J, et al. Verbena officinalis (common vervain)–a review on the investigations of this medicinally important plant species. Planta Med. 2020;86(17):1241–1257.
   PubMed Web of Science ®Google Scholar
• Vishwanathan AS, Basavaraju RA, review on Vitex negundo L. A medicinally important plant. Eur J Biol Sci. 2010;3(1):30–42.
   Google Scholar
• Daniele C, Coon JT, Pittler MH, et al. Vitex agnus castus. Drug Saf. 2005;28(4):319–332.
   PubMed Web of Science ®Google Scholar
• Samuelsen AB. The traditional uses, chemical constituents and biological activities of Plantago major L. A review. J. Ethnopharmacol. 2000;71(1–2):1–21.
   PubMed Web of Science ®Google Scholar
• Wegener T, Kraft K. Plantain (Plantago lanceolata L.): anti-inflammatory action in upper respiratory tract infections. Wien Med Wochenschr Suppl. 1999;149(8–10):211–216.
   Google Scholar
• Zhao D, Hamilton JP, Pham GM, et al. De novo genome assembly of camptotheca acuminata, a natural source of the anti-cancer compound camptothecin. Gigascience. 2017;6(9):1–7.
   Web of Science ®Google Scholar
• Rafael M, Barros L, Carvalho AM, et al. Topical anti-inflammatory plant species: bioactivity of bryonia dioica, Tamus communis and lonicera periclymenum fruits. Ind Crops Prod. 2011;34(3):1447–1454.
   Web of Science ®Google Scholar
• Lamichhane J, Chhetri SB, Bhandari M, et al. Ethnopharmacological survey, phytochemical screening and antibacterial activity measurements of high altitude medicinal plants of Nepal: a bioprospecting approach. Indian J Traditional Knowledge. 2014;13(3):496–507.
   Web of Science ®Google Scholar
• Ghosal S, Singh AA, Biswas K. New 6-aryl-2-pyrones from Gentiana pedicellata. Planta Med. 1983;49(12):240–243.
   PubMedGoogle Scholar
• Prakash V, Kumari A, Kaur H, et al. Chemical constituents and biological activities of genus picrorhiza: an update. Indian J Pharm Sci. 2020;10(4):562–577.
   Google Scholar
• Nayar MP, Sastri ARK. 1990. Red data plants of India. New Delhi: CSIR Publication. p 271.
   Google Scholar
• Bantawa P, Saha-Roy O, Ghosh SK, et al. In vitro regeneration of an endangered medicinal plant picrorhiza scrophulariiflora. Biologia Plant. 2011;55(1):169–172.
   Web of Science ®Google Scholar
• Masood M, Arshad M, Qureshi R, et al. Picrorhiza kurroa: an ethnopharmacologically important plant species of himalayan region. PAB. 2015;4(3):407–417.
   Google Scholar
• Royle JF. Illustrations of the botany and other branches of the natural history of the Himalayan mountains, and of the flora of cashmere. Volume plates. Reprint 1970, New Delhi: Today & Tomorrow’s Printers & Publishers; 1970. 71:1835–1940a.
   Google Scholar
• Bentham G. 1927. Scrophularineae indicae. London: James Ridgway and Sons, p. 47.
   Google Scholar
• Pennell FW. 1943. The Scrophulariaceae of the Western Himalayas. In: The academy of natural sciences of philadelphia monographs, number 5. Lancaster, Pennsylvania: Wickersham Printing company
   Google Scholar
• Hong DY. Taxonomy and evolution of the veroniceae (Scrophulariaceae) with special reference to palynology. Opera Bot. 1984;75:1–60.
   Google Scholar
• Kumar R, Bhandari P, Singh B, et al. Evaluation of Picrorhiza kurroa accessions for growth and quality in North Western Himalayas. J Med Plants Res. 2020;6:2660–2665.
   Google Scholar
• Bantawa P, Ghosh SK, Bhandari P, et al. Micropropagation of an elite line of Picrorhiza Scrophulariiflora, Pennell, an endangered high valued medicinal plant of the Indo-China Himalayan region. Med Aromat Plant Sci Biotechnol. 2010;4:1–7.
   Google Scholar
• Sah JN, Varshney VK. Chemical constituents of picrorhiza genus. Am J Essent Oil. 2013;1(2):22–37.
   Google Scholar
• Win NN, Kodama T, Lae KZ, et al. Bis-iridoid and iridoid glycosides: viral protein R inhibitors from Picrorhiza kurroa collected in Myanmar. Fitoterapia. 2019;134:101–107.
   PubMed Web of Science ®Google Scholar
• Morikawa T, Nakanishi Y, Inoue N, et al. Acylated iridoid glycosides with hyaluronidase inhibitory activity from the rhizomes of picrorhiza kurroa royle ex benth. Phytochemistry. 2020;169:112185.
   PubMed Web of Science ®Google Scholar
• Singh H, Gahlan P, Dutt S, et al. Why uproot Picrorhiza kurrooa, an endangered medicinal herb? Curr Sci. 2011;100:1055–1059.
   Web of Science ®Google Scholar
• Rokaya MB, Parajuli B, Bhatta KP, et al. Neopicrorhiza scrophulariiflora (Pennell) Hong: a comprehensive review of its traditional uses, phytochemistry, pharmacology and safety. J Ethnopharmacol. 2020;247:112250.
   PubMed Web of Science ®Google Scholar
• Stuppner H, Wagner H. Minor iridoids and phenyl glycosides of Picrorhiza kurrooa. Planta Med. 1989;55(5):467–469.
   PubMedGoogle Scholar
• Stuppner H, Müller EP, Wagner H. Cucurbitacins from Picrorhiza kurrooa. Phytochemistry. 1991;30(1):305–310.
   Web of Science ®Google Scholar
• Gupta PP. Picroliv: hepatoprotectant, immunomodulator. Drugs Fut. 2001;26(1):25–31.
   Web of Science ®Google Scholar
• Wang DQ, Zheng HED, Feng BS, et al. Chemical constituents from Picrorhiza scrophulariiflora. Acta Bot Yunnanica. 1993;15:83–88.
   Google Scholar
• Weinges K, Kloss P, Henkels WD. Natural products from medicinal plants. XVII. Picroside-II, a new 6-Vanilloylcatapol from Picrorhiza kurrooa royle and benth. Justus Liebigs Ann Chem. 1972;759:173–182.
   PubMedGoogle Scholar
• Tiwari SS, Pandey MM, Srivastava S, et al. TLC densitometric quantification of picrosides (picroside-I and picroside-II) in picrorhiza kurroa and its substitute picrorhiza scrophulariiflora and their antioxidant studies. Biomed Chromatogr. 2012;26(1):61–68.
   PubMed Web of Science ®Google Scholar
• Rastogi R, Saksena S, Garg NK, et al. Effect of picroliv on antioxidant –system in liver of rats, after partial hepatectomy. Phytother Res. 1995;9(5):364–367.
   Web of Science ®Google Scholar
• Wang H, Wu FH, Xiong F, et al. Iridoids from neopicrorhiza scrophulariiflora and their hepatoprotective activities in vitro. Chem Pharm Bull. 2006;54(8):1144–1149.
   PubMed Web of Science ®Google Scholar
• Rastogi R, Srivastava AK, Rastogi K. Long term effect of vaflatoxin B1 on lipid peroxidation in rat liver and kidney: effect of picroliv and silymarin. Phytother Res. 2001;15(4):307–310.
   PubMed Web of Science ®Google Scholar
• Saraswat B, Visen PK, Patnaik GK, et al. Anticholestatic effect of picroliv, active hepatoprotective principle of Picrorhiza kurrooa, against carbon tetrachloride induced cholestasis. Indian J Exp Biol. 1993;31(4):316–318.
   PubMedGoogle Scholar
• Nandave M, Ojha SK, Kumari S, et al. Cardioprotective effect of Ropot extract of Picrorhiza kurroa (royle ex benth) against isoproterenol-induced cardiotoxicity in rats. Indian J Exp Biol. 2013;51:694–701.
   PubMed Web of Science ®Google Scholar
• Guo ZJ, Hou FF, Liu SX, et al. Picrorhiza scrophulariiflora improves accelerated atherosclerosis through inhibition of redox-sensitive inflammation. Int J Cardiol. 2009;136(3):315–324.
   PubMed Web of Science ®Google Scholar
• Husain GM, Singh PN, Kumar V. Antidiabetic activity of standardized extract of Picrorhiza kurroa in rat model of NIDDM. Drug Discov Ther. 2009;3:88–92.
   PubMedGoogle Scholar
• Manandhar N, Rokeya B, Amatya S. Antidiabetic effect of Neopicrorrhiza scrophulariflora on type 2 diabetes model rats. J Ints Med. 2012;33:53–57.
   Google Scholar
• Li P, Matsunaga K, Ohizumi Y. Enhancement of the nerve growth factor-mediated neurite outgrowth from PC12D cells by Chinese and Paraguayan medicinal plants. Biol Pharm Bull. 1999;22(7):752–755.
   PubMed Web of Science ®Google Scholar
• Li P, Matsunaga K, Yamakuni T, et al. Potentiation of nerve growth factor-action by picrosides I and II, natural iridoids, in PC12D cells. Eu J Pharmacol. 2000;406(2):203–208.
   PubMed Web of Science ®Google Scholar
• Najar IA, Sachin BS, Sharma SC, et al. Modulation of P-glycoprotein ATPase activity by some phytoconstituents. Phytother Res. 2010;24(3):454–458.
   PubMed Web of Science ®Google Scholar
• Rathee D, Rathee P, Rathee S, et al. Phytochemical screening and antimicro-bial activity of picrorhiza kurroa, an Indian traditional plant used to treat chronicdiarrhea. Arab. J. Chem. 2012;9:1307–1313.
   Google Scholar
• Van den Worm E, Beukelman CJ, Van den Berg AJ, et al. Effects of methoxylation of apocynin and analogs on the inhibition of reactive oxygen species production by stimulated human neutrophils. Eur J Pharmacol. 2001;433(2–3):225–230.
   PubMed Web of Science ®Google Scholar
• Simonyi A, Serfozo P, Lehmidi TM, et al. The neuroprotective effects of apocynin. Front Biosci. 2012;4(6):2183–2193.
   Google Scholar
• Stuppner H, Wagner H. New cucurbitacin glycosides from picrorhiza kurrooa. Planta Med. 1989;55(6):559–563.
   PubMedGoogle Scholar
• Wang H, Sun Y, Ye WC, et al. Antioxidative phenylethanoid and phenolic glycosides from Picrorhiza scrophulariiflora. Chem Pharm Bull. 2004;52(5):615–617.
   PubMed Web of Science ®Google Scholar
• Gahlan P, Singh H, Shankar R, et al. De novo sequencing and characterization of Picrorhiza kurrooa transcriptome at two temperatures showed major transcriptome adjustments. BMC Genom. 2012;13:126.
   PubMed Web of Science ®Google Scholar
• Shitiz K, Sharma N, Pal T, et al. NGS transcriptomes and enzyme inhibitors unravel complexity of picrosides biosynthesis in Picrorhiza kurroa Royle Ex. Benth. PLOS One. 2015;10(12):e0144546.
   PubMed Web of Science ®Google Scholar
• Wise ML, Croteau R. 1998. Monoterpene biosynthesis in comprehensive natural products chemistry. Volume 2. Edited by: Cane DE. Oxford: Pergamon Press
   Google Scholar
• Hampel D, Mosandl A, Wust M. Biosynthesis of Mono- and sesquiterpenes in strawberry fruits and foliage: 2H labeling studies. J Agric Food Chem. 2006;54(4):1473–1478.
   PubMed Web of Science ®Google Scholar
• Barsain BL, Purohit A, Kumar A, et al. PkGPPS.SSU interacts with two PkGGPPS to form heteromeric GPPS in picrorhiza kurrooa: molecular insights into the picroside biosynthetic pathway. Plant Physiol Biochem. 2020;154:115–128.
   PubMed Web of Science ®Google Scholar
• Kawoosa T, Singh H, Kumar A, et al. Light and temperature regulated terpene biosynthesis: hepatoprotective monoterpene picroside accumulation in Picrorhiza kurrooa. Funct Integr Genomics. 2010;10(3):393–404.
   PubMed Web of Science ®Google Scholar
• Kawoosa T, Gahlan P, Devi AS, et al. The GATA and SORLIP motifs in the 3-hydroxy-3-methyl-glutaryl-CoA reductase promoter of Picrorhiza kurrooa for the control of light mediated expression. Funct Integr Genomics. 2014;14(1):191–203.
   PubMed Web of Science ®Google Scholar
• Kumar V, Sood H, Sharma M, et al. A proposed biosynthetic pathway of picrosides linked through the detection of biochemical intermediates in the endangered medicinal herb Picrorhiza kurroa. Phytochem Anal. 2013;24(6):598–602.
   PubMed Web of Science ®Google Scholar
• Singh H, Gahlan P, Kumar S. Cloning and expression analysis of ten genes associated with picrosides biosynthesis in picrorhiza kurrooa. Gene. 2013;515(2):320–328.
   PubMed Web of Science ®Google Scholar
• Pandit S, Shitiz K, Sood H, et al. Expression pattern of fifteen genes of non-mevalonate (MEP) and mevalonate (MVA) pathways in different tissues of endangered medicinal herb Picrorhiza kurroa with respect to picrosides content. Mol Biol Rep. 2013;40(2):1053–1063.
   PubMed Web of Science ®Google Scholar
• Bhat WW, Dhar N, Razdan S, et al. (2013). molecular characterization of UGT94F2 and UGT86C4, two glycosyltransferases from Picrorhiza kurrooa: comparative structural insight and evaluation of substrate recognition. PLOS One. 2013;8(9):e73804.
   PubMed Web of Science ®Google Scholar
• Sharma T, Kawoosa T, Gahlan P, et al. Two light responsive WRKY genes exhibit positive and negative correlation with picroside content in Picrorhiza kurrooa royle ex benth, an endangered medicinal herb. 3 Biotech. 2020;10(6):255.
   PubMedGoogle Scholar
• Singh N, Gupta AP, Singh B, et al. Quantitation of picroside-I and picroside-II in Picrorhiza kurroa by HPTLC. J Liq Chromatogr Relat Technol. 2005;28(11):1679–1691.
   Web of Science ®Google Scholar
• Katoch M, Fazli IS, Suri KA, et al. Effect of altitude on picroside content in core collections of Picrorhiza kurrooa from the North Western Himalayas. J Nat Med. 2011;65(3-4):578–582.
   PubMed Web of Science ®Google Scholar
• Pandit S, Shitiz K, Sood H, et al. Differential biosynthesis and accumulation of picrosides in an endangered medicinal herb Picrorhiza kurroa. J Plant Biochem Biotechnol. 2013;22(3):335–342.
   Web of Science ®Google Scholar
• Yang CQ, Fang X, Wu XM, et al. Transcriptional regulation of plant secondary metabolism. J Integr Plant Biol. 2012;54(10):703–712.
   PubMed Web of Science ®Google Scholar
• Sood H, Chauhan R. Biosynthesis and accumulation of a medicinal compound, picroside-I, in cultures of Picrorhiza kurroa royle ex benth. Plant Cell Tiss Organ Cult. 2010;100(1):113–117.
   Web of Science ®Google Scholar
• Ghimire SK, McKey D, Aumeeruddy-Thomas Y. Conservation of Himalayan medicinal plants: harvesting patterns and ecology of two threatened species, Nardostachys grandiflora DC. and Neopicrorhiza scrophulariiflora (pennell) hong. Biol Conserv. 2005;124(4):463–475.
   Web of Science ®Google Scholar
• Vasil IK, Vasil V. 1980. Clonal propagation. In Perspectives in plant cell and tissue culture. (ed: Vasil, I.K.), pp. 145–173. Int. Rev. Cytol., Suppl. 11A. New York: Acad. Press.
   Google Scholar
• Lal N, Ahuja PS, Kukreja AK, et al. Clonal propagation of Picrorhiza kurroa royle ex benth. by shoot tip culture. Plant Cell Rep. 1988;7(3):202–205.
   PubMed Web of Science ®Google Scholar
• Sood H, Chauhan RS. High frequency callus induction and plantlet regeneration from different explants of Picrorhiza kurroa medicinal herb of Himalayas. Afr J Biotech. 2009;8:1965–1972.
   Web of Science ®Google Scholar
• Patial V, Devi K, Sharma M, et al. Propagation of Picrorhiza kurroa royle ex benth: an important medicinal plant of Western Himalaya. J Med Plant Res. 2014;6:4848–4860.
   Google Scholar
• Patial V, Bhattacharya A. TDZ plays key role in shoot regeneration from different explants of Picrorhiza kurroa: an endangered medicinal herb of Western Himalayas. CJAST. 2019;33:1–9.
   Google Scholar
• Jan A, Thomas G, Shawl AS, et al. Improved micropropagation protocol of an endangered medicinal plant- Picrorhiza kurrooa royle ex benth. promptly through auxin treatments. Chiang Mai J Sci. 2010;37:304–313.
   Web of Science ®Google Scholar
• Helena DS, Kannojia G, Gaur AK. In vitro regeneration of Picrorhiza kurroa royal ex benth for ex situ conservation and sustainable utilization. Ann Biol Res. 2015;6:7–14.
   Google Scholar
• Nyende AB, Schittenhelm S, Wagner GM, et al. Production, storability, and regeneration of shoot tips of potato (Solanum tuberosum L.) encapsulated in calcium alginate hollow beads. In Vitro Cell Dev Biol – Plant. 2003;39(5):540–544.
   Web of Science ®Google Scholar
• Mishra J, Singh M, Palni LMS, et al. Assessment of genetic fidelity of encapsulated microshoots of Picrorhiza kurrooa. Plant Cell Tiss Organ Cult. 2011;104(2):181–186.
   Web of Science ®Google Scholar
• Sharma N, Sharma B. Cryopreservation of shoot tips of Picrorhiza kurroa royle ex benth., an indigenous endangered medicinal plant through vitrification. Cryo-Lett. 2003;24:181–190.
   PubMed Web of Science ®Google Scholar
• Deavours BE, Dixon RA. Metabolic engineering of isoflavonoid biosynthesis in alfalfa. Plant Physiol. 2005;138(4):2245–2259.
   PubMed Web of Science ®Google Scholar
• Kirby J, Keasling JD. Biosynthesis of plant isoprenoids: perspectives for microbial engineering. Annu Rev Plant Biol. 2009;60:335–355.
   PubMed Web of Science ®Google Scholar
• Mishra J, Bhandari H, Singh M, et al. Hairy root culture of Picrorhiza kurrooa royle ex benth.: a promising approach for the production of picrotin and picrotoxinin. Acta Physiol Plant. 2011;33(5):1841–1846.
   Web of Science ®Google Scholar
• Verma PC, Rahman L, Negi AS, et al. Agrobacterium rhizogenes-mediated transformation of Picrorhiza kurroa royle ex benth: establishment and selection of superior hairy root clone. Plant Biotechnol Rep. 2007;1(3):169–174.
   Web of Science ®Google Scholar
• Bhat WW, Lattoo SK, Rana S, et al. Efficient plant regeneration via direct organogenesis and agrobacterium tumefaciens-mediated genetic transformation of Picrorhiza kurroa: an endangered medicinal herb of the alpine himalayas. In Vitro Cell Dev Biol-Plant. 2012;48:1–9.
   Web of Science ®Google Scholar
• Morozova O, Hirst M, Marra MA. Applications of new sequencing technologies for transcriptome analysis. Annu Rev Genomics Hum Genet. 2009;10:135–151.
   PubMed Web of Science ®Google Scholar
• Seki M, Narusaka M, Kamiya A, et al. Functional annotation of a full length arabidopsis cDNA collection. Science. 2002;296(5565):141–145.
   PubMed Web of Science ®Google Scholar
• Eveland AL, McCarty DR, Koch KE. Transcript profiling by 3’-untranslated region sequencing resolves expression of gene families. Plant Physiol. 2008;146(1):32–44.
   PubMed Web of Science ®Google Scholar
• Ruyter-Spira CP, de Koning DJ, van der Poel JJ, et al. Developing microsatellite markers from cDNA: a tool for adding expressed sequence tags to the genetic linkage map of the chicken. Anim Genet. 1998;29(2):85–90.
   PubMed Web of Science ®Google Scholar
• Vashisht I, Pal T, Sood H, et al. Comparative transcriptome analysis in different tissues of a medicinal herb, Picrorhiza kurroa pinpoints transcription factors regulating picrosides biosynthesis. Mol Biol Rep. 2016;43(12):1395–1409.
   PubMed Web of Science ®Google Scholar
• Kellner F, Kim J, Clavijo BJ, et al. Genome-guided investigation of plant natural product biosynthesis. Plant J. 2015;82(4):680–692.
   PubMed Web of Science ®Google Scholar
• Hoopes GM, Hamilton JP, Kim J, et al. Genome assembly and annotation of the medicinal plant Calotropis gigantea, a producer of anticancer and antimalarial cardenolides. G3. G3 (Bethesda). 2018;8(2):385–391.
   PubMedGoogle Scholar
• Liu Y, Tang Q, Cheng P, et al. Whole-genome sequencing and analysis of the Chinese herbal plant Gelsemium elegans. Acta Pharm Sin B. 2020;10(2):374–382.
   PubMed Web of Science ®Google Scholar
• Sharma T, Sharma NK, Kumar P, et al. The first draft genome of Picrorhiza kurrooa, an endangered medicinal herb from Himalayas. Sci Rep. 2021;11(1):14944.
   PubMed Web of Science ®Google Scholar
• Zhang G, Tian Y, Zhang J, et al. Hybrid de novo genome assembly of the Chinese herbal plant danshen (Salvia miltiorrhiza bunge). Gigascience. 2015;4:62.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zheng L, Zheng Y, et al. Assembly and annotation of a draft genome of the medicinal plant Polygonum cuspidatum. Front Plant Sci. 2019;10:1274.
   PubMed Web of Science ®Google Scholar
• Xia M, Han X, He H, et al. Improved de novo genome assembly and analysis of the Chinese cucurbit Siraitia grosvenorii, also known as monk fruit or Luo-Han-Guo. Gigascience. 2018;7(6):1–9.
   Web of Science ®Google Scholar
• Krishnan NM, Jain P, Gupta S, et al. An improved genome assembly of Azadirachta indica A. Juss. G3 (Bethesda). 2016;6(7):1835–1840.
   PubMedGoogle Scholar
• Upadhyay AK, Chacko AR, Gandhimathi A, et al. Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind its strong medicinal properties. BMC Plant Biol. 2015;15:212.
   PubMed Web of Science ®Google Scholar
• Chakraborty P. Herbal genomics as tools for dissecting new metabolic pathways of unexplored medicinal plants and drug discovery. Biochim Open. 2018;6:9–16.
   PubMedGoogle Scholar
• Jin D, Wang Y, Zhao Y, et al. Micro RNAs and their crosstalks in plant development. J Genet Genomics. 2013;40(4):161–170.
   PubMedGoogle Scholar
• Liu J, Yuan Y, Wang Y, et al. Regulation of fatty acid and flavonoid biosynthesis by miRNAs in lonicera japonica. RSC Adv. 2017;7(56):35426–35437.
   Web of Science ®Google Scholar
• Sunkar R, Li YF, Jagadeeswaran G. Functions of microRNAs in plant stress responses. Trends Plant Sci. 2012;17(4):196–203.
   PubMed Web of Science ®Google Scholar
• Pantaleo V, Szittya G, Moxon S, et al. Identification of grapevine microRNAs and their targets using high-throughput sequencing and degradome analysis. Plant J. 2010;62(6):960–976.
   PubMed Web of Science ®Google Scholar
• Pelaez P, Trejo MS, Iniguez LP, et al. Identification and characterization of microRNAs in Phaseolus vulgaris by high-throughput sequencing. BMC Genom. 2012;13:83.
   PubMed Web of Science ®Google Scholar
• Badola HK, Pal M. Endangered medicinal plants in Himachal Pradesh. Curr Sci. 2002;83:797–798.
   Google Scholar
• Ghosh D, Xu J. Abiotic stress responses in plant roots: a proteomics perspective. Front Plant Sci. 2014;5:6.
   PubMed Web of Science ®Google Scholar
• Bryant L, Flatley B, Patole C, et al. Proteomic analysis of Artemisia annua towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin. BMC Plant Biol. 2015;15:175.
   PubMed Web of Science ®Google Scholar
• Bhattacharyya D, Sinha R, Ghanta S, et al. Proteins differentially expressed in elicited cell suspension culture of podophyllum hexandrum with enhanced podophyllotoxin content. Proteome Sci. 2012;10(1):34.
   PubMedGoogle Scholar
• Kiirika LM, Schmitz U, Colditz F. The alternative Medicago truncatula defense proteome of ROS-defective transgenic roots during early microbial infection. Front Plant Sci. 2014;5:341.
   PubMed Web of Science ®Google Scholar
• Corchete P, Bru R. Proteome alterations monitored by DIGE analysis in silybum marianum cell cultures elicited with methyl jasmonate and methyl B cyclodextrin. J Proteomics. 2013;85:99–108.
   PubMed Web of Science ®Google Scholar
• Parkash J, Kashyap S, Kalita PJ, et al. Differential proteomics of picrorhiza kurrooa royle ex benth. in response to dark stress. Mol Biol Rep. 2014;41(9):6051–6062.
   PubMed Web of Science ®Google Scholar
• Kumar R, Joshi R, Kumari M, et al. Elevated CO2 and temperature influence key proteins and metabolites associated with photosynthesis, antioxidant and carbon metabolism in picrorhiza kurroa. J Proteomics. 2020;219:103755.
   PubMed Web of Science ®Google Scholar
• Gong F, Hu X, Wang W. Proteomic analysis of crop plants under abiotic stress conditions: where to focus our research? Front Plant Sci. 2015;6:418.
   PubMed Web of Science ®Google Scholar
• DellaPenna D. Plant metabolic engineering. Plant Physiol. 2001;125(1):160–163.
   PubMed Web of Science ®Google Scholar
• Lewinsohn E, Schalechet F, Wilkinson J, et al. Enhanced levels of the aroma and flavor compound S-linalool by metabolic engineering of the terpenoid pathway in tomato fruits. Plant Physiol. 2001;127(3):1256–1265.
   PubMed Web of Science ®Google Scholar
• Chun JH, Adhikari PB, Park SB, et al. Production of the dammarene sapogenin (protopanaxadiol) in transgenic tobacco plants and cultured cells by heterologous expression of PgDDS and CYP716A47. Plant Cell Rep. 2015;34(9):1551–1560.
   PubMed Web of Science ®Google Scholar
• Kumar V, Sharma N, Sood H, et al. Exogenous feeding of immediate precursors reveals synergistic effect on picroside-I biosynthesis in shoot cultures of picrorhiza kurroa royle ex benth. Sci Rep. 2016;6:29750.
   PubMed Web of Science ®Google Scholar