Manufacture of Ayurvedic Medicines – Regulatory Aspects
D. Suresh Kumar in Ayurveda in the New Millennium, 2020
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
Peter Grunwald in 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.
Ethnomedicinal and Pharmacological Importance of Glycyrrhiza glabra L
Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa in Wild Plants, 2020
The main constituents with pharmacological value of licorice are glycyrrhizin and its aglycone, namely 18β-glycyrrhetinic acid. These two compounds were found to show wide biological activities. They exhibit anti-ulceric, anti-inflammatory, anti-allergic, antioxidative, antiviral, anticarcinogenic, antithrombotic, hepatoprotective, neuroprotective, and antidiabetic activities (Zhang and Ye 2009). The glycyrrhizin has also been used as a potential therapeutic agent for different viral diseases such as chronic hepatitis B and C, human immune deficiency virus (Zhang and Ye 2009). It has traditional applications in stimulating digestive system functions, eliminating phlegm, relieving coughing, nourishing qi, and alleviating pain (Yang et al. 2017). Other studies have elaborated its other effects, such as nootropic action (Dhingra et al. 2004), anticariogenic action (Ajagannanavar et al. 2014), anti-tussive action (Kuang et al. 2018), and hair growth (Roy et al. 2014).
Preparation, evaluation, and in vitro cytotoxicity studies of artesunate-loaded glycyrrhetinic acid decorated PEG-PLGA nanoparticles
Published in Drug Development and Industrial Pharmacy, 2020
Xuwang Pan, Shourong Liu, Liping Ju, Jianjun Xi, Ruoyu He, Yanmei Zhao, Rangxiao Zhuang, Jinsong Huang
Surface functionalization with biologically active ligands facilitates the targeting of specific cells [12,13]. Suitable targeting ligand for drug delivery is determined by the specificity required, the cost and market supply of the ligand. Glycyrrhetinic acid (GA), a pentacyclic triterpenoid compounds, is mainly isolated from licorice, the root of Glycyrrhiza glabra L. abundant GA receptors has been confirmed on the cellular membrane of hepatocytes. Protein kinase C-α was reported as the target binding protein of GA, which had 1.5- to 5-fold more expression in HCC cells than in the adjacent nontumor liver cells [14,15]. Additionally, a great deal of studies have found that GA increases apoptosis in hepatoma cells and possesses the anti-tumor property [8,16]. Recently, some GA-modified active TDDS have been developed and can effectively deliver drugs to the lesion of the liver, improve the therapeutic index of the drug, reduce the drug dosage and the adverse reaction [14,17–19]. Therefore, it could be expected that GA-modified NPs could target selectively to HCC cells and tissues.
Therapeutic potential of glycyrrhetinic acids: a patent review (2010-2017)
Published in Expert Opinion on Therapeutic Patents, 2018
Hidayat Hussain, Ivan R. Green, Umair Shamraiz, Muhammad Saleem, Amin Badshah, Ghulam Abbas, Najeeb Ur Rehman, Muhammad Irshad
Current bioscientific research on licorice showed that on the one hand it can be used as a flavoring and sweetening agent, while on the other hand it has various clinical applications [7,15]. For instance, it has been documented that licorice is capable of having ulcer-healing properties [7,16] and is also to treat spasmodic pains of chronic gastritis [7,17,18]. In addition, its possess laxative effects [7,19], antineoplastic activity toward melanoma and gastric cancer cells [7,20–22], antiatherogenic activity [7], antioxidant effects, hypolipidemic effects [23,24], well able to treat atopic dermatitis [7,25]. It is worth mentioning that licorice possess in vitro antiviral activities toward various viruses viz., the Hepatitis B virus, Epstein Barr virus, severe acute respiratory syndrome (SARS) corona virus, Japanese encephalitis virus, human immunodeficiency virus (HIV), and herpes simplex virus [7,26–31]. Two stereoisomers of glycyrrhetinic acid viz., 18β-glycyrrhetinic acid (enoxolone; β-GA, 1) and 18α-glycyrrhetinic acid (α-GA, 2) (Figure 1), were isolated from licorice. Glycyrrhetinic acid, as illustrated, is an oleanane-type triterpenoid having carboxylic acid at C-30 in place of the usual methyl group [32]. Moreover, the amount of β-GA in liquorice root is between 0.1% and 1.6% whereas α-GA is normally lower than 0.7% [33,34].
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.
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