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Ethnomedicinal and Pharmacological Importance of Glycyrrhiza glabra L
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Wild Plants, 2020
Ashish K. Bhattarai, Sanjaya M. Dixit
Glycyrrhetinic acid (GA) and some of its derivatives may offer a role in combating cancer types having bad prognosis. Some GA derivatives are indeed able to target both the proteasome and Peroxisome Proliferator-Activated Receptors (PPARs), two proteins that play major roles in cancer cell biology, but are not related to Multi-Drug Resistant (MDR) and/or apoptosis-related resistance phenotypes (Lallemand et al. 2011).
Manufacture of Ayurvedic Medicines – Regulatory Aspects
Published in D. Suresh Kumar, Ayurveda in the New Millennium, 2020
V. Remya, Alex Thomas, D. Induchoodan
The common ayurvedic herb licorice (Glycyrrhiza glabra) contains glycyrrhizin and glycyrrhetinic acid. These phytocompounds are potent inhibitors of 11-β hydroxy steroid dehydrogenase, causing raised cortisol and increased mineralocorticoid activity, leading to hypertension and suppression of the renin-angiotensin aldosterone system. Licorice also interacts with some antihypertensives and antiarrhythmics (Serra et al. 2002). Therefore, manufacturers of ayurvedic medicines should also provide some information about the safety of the formulations (including dosage schedule and drug storage conditions) on the drug labels. The drug control department should enforce the laws pertaining to the marketing of ayurvedic medicines. These measures will prevent the irrational use of ayurvedic medicines.
Carboxylesterase Inhibitors: Relevance for Pharmaceutical Applications
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Other natural pentacyclic triterpenoids, such as β-boswellic acid with carboxyl group at the C-23 site, demonstrated strong inhibitory effects on CES2 and high selectivity over CES1 (Zou et al., 2017). Glycyrrhetinic acid (GA), the major bioactive ingredient of the roots and rhizomes of licorice (Glycyrrhiza species), which displays satisfying safety during long history of medicinal use, was selected as a reference compound for the development of potent and specific inhibitors against CES2 (Zou et al., 2016). Guided by the structure-CES2 inhibition relationships of a series of GA derivatives, Ge et al. designed and developed a more potent compound 3-O-(β-carboxypropionyl)-11-deoxo- glycyrrhetinic acid-30-ethyl ester as a novel and highly selective inhibitor against CES2, with the IC50 value of 20 nM and very high selectivity over CES1 (1000-fold), which was 3463-fold more potent than the parent compound GA. The SARs of these pentacyclic triterpenoids as CES1 or CES2 inhibitors were summarized in Fig. 9.6, which are very helpful for medical chemists to design and develop more potent and highly selective CES1 or CES2 inhibitors for biomedical applications.
Influence of glycyrrhetinic acid on the pharmacokinetics of warfarin in rats
Published in Xenobiotica, 2020
Jiaying Song, Huizhen Dai, Huan Zhang, Yanchao Liu, Wenjing Zhang
Glycyrrhetinic acid (GA) is isolated from the dried roots of Chines herbal medicine licorice, such as Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., and Glycyrrhiza glabra L. (Hussain et al., 2018). Numerous studies have revealed many pharmacological activities of GA, such as anti-inflammatory (Cao et al., 2017; Ge et al., 2018), antiviral (Wang et al., 2015), antiallergic (Chen et al., 2017), and antitumor proliferative effects (Cai et al., 2016; Xu et al. 2017). Moreover, GA could inhibit CYP3A4 activity competitively, and inhibit CYP2C9 and CYP2C19 significantly in human liver microsomes (HLMs), as well as in mice (Liu et al., 2011; Lv et al., 2015; Zhao et al., 2012), which may inhibit the effect of warfarin. With the wide application of GA, it might be co-administered with warfarin in clinical, the interaction between them is the main factor that effect their bioavailability. Previous investigations have shown that many drugs that inhibit CYP3A4 and CYP2C9 could augment the anticoagulant effect of warfarin (Yamaori et al., 2015; Zhang et al., 2018). Therefore, the DDI between warfarin and GA should be investigated. To the best of our knowledge, there is little available data for the effect of GA on the oral pharmacokinetics of warfarin.
Hepatic targeting of glycyrrhetinic acid via nanomicelles based on stearic acid-modified fenugreek gum
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Minghui Zhou, Shuang Li, Sheng Shi, Shaolong He, Yanni Ma, Wenping Wang
Glycyrrhetinic acid (≥98%) was supplied by Nanjing Jingzhu Biotechnology Co. Ltd. (Nanjing, China). Tween 20 was from Shanghai Chemical Reagent Co., Ltd. (Shanghai, China). Pancreatic enzyme was purchased from Sigma-Aldrich (St. Louis, MO, USA). 1, 1′-Dioctadecyl-3, 3, 3′ 3′-tetramethylindotricarbocyanine iodide (DiR) was bought from Amyjet Scientific Inc. (Wuhan, China). Phosphoric acid was obtained from Tianjin Chemical Company (Tianjin, China). Dialysis tubing (molecular weight cut-off 3.4 kDa) was supplied by Greenbird Biological Technology Co., Ltd. (Shanghai, China). Dulbecco’s Modified Eagle’s Medium (DMEM) and foetal calf serum (FCS) were obtained from Thermo Fisher Scientific, Inc. (Waltham, MA, USA). The methyl thiazolyl tetrazolium (MTT) kit was purchased from KeyGEN BioTECH Co., Ltd (Nanjing, China). Both HPLC grade Methanol and Methyl tertiary butyl ether (MTBE) were supplied by Chemical Company (Tianjin, China). Triton x-100 was from HiTo Co., Ltd. (Guangzhou, China). Phosphate-buffered saline (PBS; 0.01 M, pH 7.2–7.6) and other reagents were analytical grade and used as received. Ultrapurified water (Milli-Q, Millipore, USA) was used throughout the experiment.
Preparation and in vitro and in vivo evaluations of 10-hydroxycamptothecin liposomes modified with stearyl glycyrrhetinate
Published in Drug Delivery, 2019
Ting Zhou, Xin Tang, Wei Zhang, Jianfang Feng, Wei Wu
Liposomes, which are composed of two layers, are widely accepted as a drug delivery system (Liu et al., 2016a). Compared to free drugs, liposomal formulations achieve more drug accumulation in the tumor region through an enhanced permeability and retention (EPR) effect, prolonged blood circulation time, reduced drug toxicity and increased therapeutic efficacy (Maruyama, 2011; Corvo et al., 2016). Nevertheless, the passive targeting effect of liposomes cannot guarantee increased cellular uptake of the drug (Li et al., 2015; Liu et al., 2016b). In recent years, aiming to improve the targeting and stability of liposomes, many scholars have studied surface modification of liposome membranes (Qi et al., 2015; Xie et al., 2015; Yang et al., 2015; Zhu et al., 2015; Xie et al., 2016; Liu et al., 2017). Glycyrrhetinic acid (GA) is one of the main bioactive compounds extracted from licorice, which has been used to treat hepatic disease (Tian et al., 2012; Zhang et al., 2012; Darvishi et al., 2015; Jing et al., 2017a). Stearyl glycyrrhetinate (SG), the stearyl ester of 18-β-glycyrrhetinic acid, is a derivative of GA. It has been demonstrated that GA and its derivatives may be used as ligands targeting the liver (Radwan et al., 2016; Zhu et al., 2018). Because it has been shown that abundant receptors for GA exist on liver cell membranes, several recent research efforts have attempted to utilize GA as a targeting ligand for hepatocyte-targeting (He et al., 2010; Huang et al., 2011; Shi et al., 2012; He et al., 2014; Zhang et al., 2015; Chen et al., 2015b).