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An Introduction to the Ethnopharmacology of Wild Plants
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Shandesh Bhattarai, Christiane Mendes Feitosa, Mahendra Rai
Terrestrial plants, Licorice (Glycyrrhiza glabra), Myrrh (Commiphora species), and Poppy capsule latex (Papaver somniferum), were recorded from Mesopotamia in 2600 BC, and are still in use today (Newman et al. 2000). A semisynthetic derivative of glycyrrhizic acid found in licorice (i.e., Hemisuccinate carbenoxolone sodium) is recommended for gastric and duodenal ulcers (Dewick 2002). Furthermore, morphine, codeine, noscapine (narcotine), and papaverine isolated from P. somniferum were developed as single chemical drugs and are still used clinically (Dewick 2002). Codeine is an alkaloid prepared from Opium or morphine by methylation. Opium is an isoquinolone alkaloid obtained from poppy plant [Papaver somniferum]. Codeine is used as a pain reliever, and for cough suppression (Online Medical Dictionary 2007, Bhandari et al. 2011).
Nutraceutical’s Role in Proliferation and Prevention of Gynecological Cancers
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Aaishwarya B. Deshmukh, Jayvadan K. Patel, Bharat Mishra
Majority of nutraceuticals with antioxidant activity inhibit NF-κB-regulated anti-apoptotic proteins target by inhibiting NF-κB activation. Garcinol causes apoptosis in human breast carcinoma, MDA-MB-231 and MCF-7, cells through the activation of caspase and NF-κB-regulated genes down regulation [63]. γ-Tocotrienol, acetoxychavicol acetate, evodiamine, thymoquinone, noscapine have shown inhibiting plumbagin-induced apoptosis with related inactivation of DNA binding activity of NF-κB and Bcl-2 in breast tumor cells [64]. Isodeoxyelephantopin, anacardic acid, indirubin, coronarin D, β-escin, and withanolides, are some of the most popular among nutraceuticals reported to have antioxidant activities for cancer treatment [4].
Drug therapy problems in pediatric and geriatric patients at Farmasi Airlangga Pharmacy
Published in Elida Zairina, Junaidi Khotib, Chrismawan Ardianto, Syed Azhar Syed Sulaiman, Charles D. Sands, Timothy E. Welty, Unity in Diversity and the Standardisation of Clinical Pharmacy Services, 2017
Mufarrihah, D.M. Machfud, V.D.A. Purworini, A. Yuda, Y. Priyandani, Y. Nita
Drugs obtained in low doses included acetaminophen, mefenamic acid, cefadroxil, chlortrimeton, guaifenesin, dextromethorphan, noskapin, pseudoephedrine, and Rovamycin®. A 2-year-old patient weighing 23 kg was prescribed 16.67 mg of guaifenesin three times a day. In other words, this patient received 50 mg guaifenesin/day. Meanwhile, the normal dose of guaifenesin for a 2-year-old is 12 mg/kg body weight/day, which means that this patient should receive guaifenesin at a dose of 276 mg/day (Taketomo et al. 2010). Therefore, we can conclude that the patient took a too low dose of the prescribed guaifenesin. Ingredients in drugs administered for a very long interval were chlortrimeton, acetaminophen, codeine, guaifenesin, and pseudoephedrine. Meanwhile, the reason for the too low dosage is that drug interactions potentially lead to the reduction in the amount of the active drug as in the interaction between phenobarbital and acetaminophen, for example. Phenobarbital lowers the level of acetaminophen by increasing its metabolism, so that the level of acetaminophen is reduced and its effectiveness is decreased (Drug Interaction Checker 2013).
Inhibition of CYP2C9 by natural products: insight into the potential risk of herb-drug interactions
Published in Drug Metabolism Reviews, 2020
Kai Wang, Qing Gao, Tingting Zhang, Jinqiu Rao, Liqin Ding, Feng Qiu
Noscapine, a naturally occurring phthalide isoquinoline alkaloid obtained from Papaver somniferum L., has been broadly accepted as a safe and promising oral antitussive for a long time (Chen et al. 2015). Nevertheless, several clinical DDI reports related to noscapine showed that serious adverse drug response (bleeding or increased INR (international normalized ratio)) occurred when warfarin was coadministered (Ohlsson et al. 2008; Scordo et al. 2008). Noscapine also markedly increased the losartan phenotypic index after multiple dosing of twelve healthy subjects, which was indicative of CYP2C9 enzyme inhibition (Rosenborg et al. 2010). The human liver microsome (HLM) incubation study showed that noscapine exhibited time-dependent inhibition (TDI) of CYP2C9, and kinetic analysis demonstrated that the inhibition mode showed the best fit for noncompetitive type with a Ki value of 8.9 μM (Fang et al. 2010). Interestingly, further research demonstrated that noscapine inhibited (S)-warfarin metabolism in both an NADPH- and time-dependent manner, and CYP2C9 activity was not recovered by ultrafiltration analysis, suggesting that noscapine was a mechanism-based inactivator of CYP2C9. The mechanism related to the MBI of CYP2C9 by noscapine was likely to be correlated with the metabolic activation of the methylenedioxyphenyl group that was incorporated into the noscapine structure (Zhang et al. 2013). Specifically, its bioactivation is possibly initiated by O-dealkylation, by which the methylenedioxyphenyl group is metabolized to the corresponding catechol, and sequential oxidation of the catechol produces an ortho-quinone. The resulting quinone may be responsible for enzyme inhibition (Mao et al. 2015).
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Another clinically relevant herb-drug interactions involve the opioid alkaloid noscapine and warfarin (Rosenborg et al. 2010). Noscapine (Figure 9(b)), a close structural analog of hydrastine containing the MDP moiety, is a nonaddictive phthalideisoquinoline alkaloid obtained from opium poppy latex and has been widely used as an antitussive drug (Empey et al. 1979). In recent years, noscapine has drawn much attention for its excellent anticancer activity and low toxicity (Tomar et al. 2017). Despite the therapeutic benefits, studies suggested that noscapine is potentially carcinogenic (Porter et al. 1992). Oral administration of noscapine in rats led to decreased GSH levels and enhanced lipid peroxidation (Aneja et al. 2004). Of significant concern was the clinical drug interactions between noscapine and warfarin (Scordo et al. 2008). Noscapine was found to be both a competitive and a mechanism-based inhibitor of CYP2C9 with estimated kinact/KI = 6.0 ml/min/μmol, indicating high inactivation efficiency (Zhang et al. 2013). Noscapine is a 2- to 3-fold more efficient inactivator of CYP2C9.2 and CYP2C9.3 variants than the wild type. In vitro GSH trapping suggested that noscapine formed a reactive o-quinone via initial CYP2C9-mediated O-demethylenation of the MDP moiety to a catechol followed by two-electron oxidation (Fang et al. 2012) (Figure 9(b)). Spectral scanning of the reaction between CYP2C9 and noscapine revealed the formation of an absorption spectrum at 458 nm, indicating formation of the MDP carbene complexes with ferrous heme iron of CYP2C9 (Zhang et al. 2013). It’s estimated that co-administration of noscapine and warfarin could lead to up to 7-fold increases in AUC of (S)-warfarin mainly due to mechanism-based inactivation of CYP2C9 by noscapine, which would warrant reduction of warfarin dose (Fang et al. 2010; Zhang et al. 2013).