Secondary Metabolites of Medicinal Plants. Bharat Singh

acuminata hairy roots. Plant Cell Rep. 22: 437–441.

      39 Lu, A.J., Zhang, Z.S., Zheng, M.Y. et al. (2007). 3D-QSAR study of 20(S)-camptothecin analogs. Acta Pharmacol. Sin. 28: 307–314.

      40 Ni, X., Wen, S., Wang, W. et al. (2011). Enhancement of camptothecin production in Camptotheca acuminata hairy roots by overexpressing ORCA3 gene. J. Appl. Pharm. Sci. 1: 85–88.

      41 Pan, X.-W., Shi, Y.-Y., Liu, X. et al. (2004). Influence of inorganic microelements on the production of camptothecin with suspension cultures of Camptotheca acuminata. Plant Growth Regul. 44: 59–63.

      42 Pi, Y., Jiang, K., Hou, R. et al. (2010). Examination of camptothecin and 10-hydroxycamptothecin in Camptotheca acuminata plant and cell culture, and the affected yields under several cell culture treatments. Biocell 34: 139–143.

      43 Pi, Y., Jiang, K., Lin, J. et al. (2012). Effects of over-expression of allene oxide cyclase on camptothecin production by cell cultures of Camptotheca acuminata. Afr. J. Biotechnol. 11: 6535–6541.

      44 Roja, G. (2008). Micropropagation and production of Camptothecin from in vitro plants of Ophiorrhiza rugosa var. decumbens. Nat. Prod. Res. 22: 1017–1023.

      45 Sakato, K. and Misawa, M. (1974). Effects of chemical and physical conditions on growth of Camptotheca acuminata cell cultures. Agric. Biol. Chem. 38: 491–497.

      46 Song, H.X. and Hu, H.H. (2012). Hydroxycamptothecin inhibits proliferation of human lung carcinoma cell line A549 and down-regulates its Bcl-2 gene expression in vitro. J. South Med. Univ. 9: 1341–1345.

      47 Sun, H.Z., Fan, J., and Tang, X.D. (2001). Effect of 10-hydroxycamptothecim on autocrine expression of T24 minary bladder cancer cells. Chin. J. Exp. Surg. 18: 17–18.

      48 Tien, H.J., Tien, J.M., Yeh, M.Y. et al. (1977). Studies on the constituents of Camptotheca acuminata Decne. I. Constituents of leaves. Chemistry 2: 51–54.

      49 Tu, S.-P., Zhong, J., Tan, J.-H. et al. (2000). Induction of apoptosis by arsenic trioxide and hydroxy camptothecin in gastriccancer cells in vitro. World J. Gastroenterol. 6: 532–539.

      50 Valletta, A., Santamaria, A.R., and Pasqua, G. (2007). CPT accumulation in the fruit and during early phases of plant development in Camptotheca acuminata Decaisne (Nyssaceae). Nat. Prod. Res. 21: 1248–1255.

      51 Wall, M.E., Wani, M.C., Cook, C.E. et al. (1966). Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J. Am. Chem. Soc. 88: 3888–3890.

      52 Wang, H.M., Liu, X.M., and Bao, Y.M. (2004). Inhibition of proliferation and induction of apoptosis in human tongue cancer cells by camptothecin. Chin. J. Dermatovenereol Integr. Tradit. West. Med. 3: 3–6.

      53 Wang, P., Luo, J., Wang, X.-B. et al. (2015). New indole glucosides as biosynthetic intermediates of camptothecin from the fruits of Camptotheca acuminata. Fitoterapia 103: 1–8.

      54 Wani, M.C. and Wall, M.E. (1969). Plant antitumor agents. II. Structure of two new alkaloids from Camptotheca acuminata. J. Organomet. Chem. 34: 1364–1367.

      55 Wiedenfeld, H., Furmanowa, M., Roeder, E. et al. (1997). Camptothecin and 10-hydroxycamptothecin in callus and plantlets of Camptotheca acuminata. Plant Cell Tissue Organ Cult. 49: 213–218.

      56 Wu, T.S., Tien, H.J., and Yeh, M.Y. (1980). Studies on the constituents of Formosan folk medicine. VII. Constituents of the flowers of Vanilla somai Hayata and the roots of Camptotheca acuminata Decne. Chenggong Daxue Xuebao 15: 65–67.

      57 Wu, T.S., Chen, M.T., Kuoh, C.S. et al. (1985). Studies on the constituents of Camptotheca acuminata Decne, II. The constituents of fresh fruits. J. Chin. Chem. Soc. 32: 173–175.

      58 Wu, Y., Zeng, F.Q., and Xia, W. (2007). The systematic evaluation of the postoperative recurrence of cystectomy for the prevention of bladder tumor. J. Clin. Urol. 22: 345–347.

      59 Xu, E.S., Xu, Q., and Wang, J.J. (2003). The effects of hydroxycampyxine on the proliferation and apoptosis of human hepatocellular carcinoma. J. Clin. Hepatol. 6: 138–140.

      60 Yamazaki, Y., Urano, A., Sudo, H. et al. (2003). Metabolite profiling of alkaloids and strictosidine synthase activity in camptothecin producing plants. Phytochemistry 62: 461–470.

      61 Yamazaki, M., Asano, T., and Saito, K. (2013). Camptothecin production and biosynthesis in plant cell cultures. Recent Adv. Phytochem. 43: 43–54.

      62 Yang, C.X., Huang, H.X., and Li, G.S. (2002). The clinical analysis of oxaliplatin combined with hydroxycampyline for advanced gastric cancer. Cancer 21: 885–887.

      63 Ye, M., Lin, L., Fang, Y. et al. (2007). 10-Hydroxycamptothecin induces apoptosis via activating nuclear factor NF-κB in a Bcap-37 cell line. Chin. J. Pathophysiol. 23: 146–150.

      64 Yin, F. and Hu, L.H. (2005). Two DNA topoisomerase I inhibitors from Camptotheca acuminata Decne. (Nyssaceae). Zhongguo Tianran Yaowu 3: 21–24.

      65 Zeng, Q., Jiang, L., Wang, D. et al. (2012). Camptothecin and 10-hydroxycamptothecin accumulation in tender leaves of Camptotheca acuminata saplings after treatment with plant growth regulators. Plant Growth Regul. 68: 467–473.

      66 Zhang, Z.Z., Li, S.Y., Zhang, S.M. et al. (2004). New camptothecin and ellagic acid analogues from the root bark of Camptotheca acuminata. Planta Med. 70: 1216–1221.

      67 Zhang, J., Yu, Y., Liu, D., and Liu, Z. (2007). Extraction and composition of three naturally occurring anti-cancer alkaloids in Camptotheca acuminata seed and leaf extracts. Phytomedicine 14: 50–56.

2.19 Cannabis Species

      2.19.1 Ethnopharmacological Properties and Phytochemistry

      Cannabis sativa L. (Fam. – Cannabaceae) is an annual herbaceous plant and indigenous to Central Asia and India subcontinent. The phytochemicals in this plant species are secreted by the glandular trichomes found on the calyx and bracts of flowers. The Cannabis plant is used in the treatment of nausea and vomiting during chemotherapy; it also recommended to treat chronic pain and muscle spasms and central nervous system (CNS) and as anti-inflammatory (Li 1973; Gubellini et al. 2002; Brotchie 2003; Johnson et al. 2009; Radwan et al. 2009; Styrczewska et al. 2012; Tabrez et al. 2012; Borgelt et al. 2013; Whiting et al. 2015), as well as Parkinson's disease (Pisani et al. 2005, 2010, 2011). Based on the 2500-year-old ancient reports unearthed in the Turpan district in Xinjiang, China, it was concluded that Cannabis plant was used for ancient customs/rituals and in medicines (Jiang et al. 2006; Manduca et al. 2012; Radwan et al. 2015). Cannabigerol and olivetol are bound into tetrahydrocannabinol and other neutral cannabinoids (Kajima and Piraux 1982; Elzinga et al. 2015).

      The toxicity levels of glutamate were reduced significantly by cannabidiol and by antioxidant compounds because several cannabinoids demonstrated antioxidant effects. Cannabidiol and tetrahydrocannabidiol also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in neuron cell cultures (Hampson et al. 1998; Radwan et al. 2008, 2015; Aizpurua-Olaizola et al. 2014). Due to differences in terpenoid composition, the cultivars of the two drug biotypes may exhibit distinctive medicinal properties (Hillig 2004). A cell suspension culture of C. sativa L. can convert cannabidiol to bound cannabielsoin and Δ-9-tetrahydrocannabinol to cannabicoumaronon (Braemer and Paris 1987; Choi et al. 2004; Fischedick et al. 2010b). Geranyl diphosphate and olivetolic acid are considered as specific intermediates in the cannabinoid biosynthesis (Fellermeier et al. 2001).

The cannabichromenic acid synthase enzyme catalyzes the oxidocyclization of cannabigerolic acid and cannabinerolic acid to cannabichromenic acid. It was interpreted that cannabichromenic acid is synthesized from cannabigerolic acid rather than cannabinerolic acid. In this reaction, the enzyme did not require any molecular oxygen or hydrogen peroxide; this indicates that cannabichromenic acid synthase reaction was completed by dehydrogenation without hydroxylation (Shoyama et al. 1968; Morimoto et al. 1998; Giacoppo et al. 2014; Nascimento et al. 2015). The cannabinoids isolated from the resin of these sessile glands induced cell death in leaves