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Terpenoids in Treatment of Liver Disease
Published in Dijendra Nath Roy, Terpenoids Against Human Diseases, 2019
Sujan Chatterjee, Debajyoti Patra, Pujita Ghosh, Akash Prasad, Kaustav Dutta Chowdhury
In vitro analysis with Andrographolide, isolated from Andrographis paniculata, suggests it has a role in the reduction of HSC activation and decrease in collagen deposition. It also reduces cellular formation of ROS, enhances Nrf2 nuclear translocation and increases the expression of Nrf2 downstream anti-oxidant genes in HSCs (Yan et al. 2018). Liver microsomal inhibitory effects of andrographolide were estimated by using morphine as an in vitro UGT2B7 probe substrate. Results suggest marked inhibition of morphine 3- and 6-glucuronidation in liver microsomes occurs after andrographolide treatment (Uchaipichat and Verawan 2017). A cytoprotective role against carbon tetrachloride (CCl4) toxicity in a liver cell line indicates that andrographolide is a potent inhibitor of CCl4-mediated lipid peroxidation (Krithika et al. 2013). Moreover, it has potent anti-inflammatory activity due to its ability to inhibit NF-κB. The drug effectively inhibits LPS-induced interleukin (IL)-1β expression via NF-κB inhibition in fat-laden cells. Inflammasome modulation by an NF-κB–dependent mechanistic pathway may be involved in the therapeutic effects of andrographolide (Cabrera et al. 2017). Derivatives of andrographolide such as isoandrographolide (IAN) and 3,19-acetonylidene andrographolide can ameliorate hepatic steatosis and lipotoxicity as assessed in palmitate-oleate–induced steatotic cell lines. Treatment with IAN has significantly reduced the lipid accumulation and the leakage of lactate dehydrogenase (LDH) and transaminase (Toppo et al. 2017). Andrographolide and 14-deoxy-11,12-didehydroandrographolide have been shown to inhibit cytochrome P450s. Effective suppression of CYP1A2 and CYP2D6 expressions were reported in an in vitro experiment, and the inhibition on CYP3A4 after andrographolide and 14-deoxy-11,12-didehydroandrographolide treatment warrants further validation (Ooi et al. 2011).
Environmental impact and biological removal processes of pharmaceutically active compounds: The particular case of sulfonamides, anticonvulsants and steroid estrogens
Published in Critical Reviews in Environmental Science and Technology, 2020
Cristiano S. Leal, Daniela P. Mesquita, António Luís Amaral, Almerinda M. Amaral, Eugénio C. Ferreira
The metabolism of CBZ in the human body leads to the formation of 10,11-epoxycarbamazepine (EP-CBZ) and 10,11-dihydro-10,11-trans-dihydroxycarbamazepine (DiOH-CBZ). The CBZ is transformed by the cytochrome P450 3A4 (CYP3A4) in the liver and possibly undergoes glucuronidation by UDP-glucuronosyltransferase-2B7 (UGT2B7) isoenzyme. Only 3% of CBZ remains unchanged when excreted, and is mainly found in the urine, whereas their (mono)hydroxylated and conjugated metabolites can be found in the feces (RxList, 2016a; INCHEM, 2016; Toxnet, 2016).