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Herbs with Antidepressant Effects
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
Mitochondrial abnormalities play a role in MDD. Glycyrrhizin and licochalcone A extracted from Glycyrrhiza inflata upregulate proliferator-activated receptor γ coactivator 1α (PGC-1a), a critical factor in mitochondrial biogenesis.14 PGC-1 also inhibits proinflammatory cytokine production.15 It is suspected that increases in PGC-1 activity is what in part mediates the beneficial effects of exercise on MDD.16
Recent Perspectives Of Chalcone-Based Molecules As Protein Tyrosine Phosphatase 1b (Ptp1b) Inhibitors
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Vivek Asati
A large number of chalcones were isolated from nature which has been reported to exhibit potential PTP1B inhibition activity (Figure 6.3). Hoang et al. isolated three methylcyclohexene substituted chalcones derived Diels-Alder type compounds from Morus bombycis namely, kuwanon J (1), kuwanon R (2), and kuwanon V (3). All these derivatives showed remarkable inhibition of PTP1B with IC50 in range of 2.7–13.8 μM in mixed–type manner. The number of hydroxyl moieties play essential role on activity. The hydroxyl groups not only provided the needed penetration into the active site but also likely to produce an effective hydrogen bonding interaction with the amide backbone of the active-site loop. These facts suggest that with an increase in number of OH groups in chalcone-derived Diels–Alder-type compounds, the potential inhibitory effects against PTP1B increases tremendously. The compound (2), having seven OH groups demonstrate strong dose-independent inhibition, compared to (3), which contains six OH groups. Compound (1) has an additional OH group at C-2, which increases the potency of (1) upto 3 times with respect to (3). The order of inhibitory activity of chalcone-derived Diels–Alder-type compounds can be summarize as 1>2>3. [52]. Broussochalcone (4), isolated from Broussonetia papyrifa was reported to effectively inhibit PTP1B with IC50 of 21.5 µM. The two-hydroxyl groups at both the rings are assumed to be responsible for effective inhibition. As the number of hydroxyl groups increases, the inhibitory activity increases concurrently [53]. A novel chalcone, abyssinone-VI-4-O-methyl ether (5) was isolated from ethyl acetate-soluble extract of the root bark of Erythrina mildbraediiexhibited in vitro PTP1B inhibitory activity with IC50 value 14.8 µM [54]. Licochalcone A, isolated from Glycyrrhiza inflata and its semi-synthetic derivatives have been reported to be inhibitor of PTP1B. The isolated chalcones isoliquiritigenin (6), echinatin (7), licochalcone A (8), licochalcone C (9), licochalcone E (10), licochalcone B (11), and licochalcone D (12). The semi-synthetic derivatives (13) and (14) were fabricated by methylation and compounds (15) and (16) were formed by acetylating the licochalcone A. Compounds (17) and (18) were prepared by THP-protection of the 4-hydroxy group in the A ring followed by methylation or acetylation of the 4′-hydroxyl group in the B ring and subsequent cleavage of the THP-ether under acidic conditions. Acetylation of compound (13) and compound (17) affords compounds (19) and (20). The semi-synthetic derivative (13) presented the highest activity [55–56]. Isoliquiritigenin (ISL) restores PTP1B activity by inhibiting PTP1B oxidation and IR/PI3K/AKT phosphorylation during the early stages of insulin-induced adipogenesis. The antioxidant capacity of ISL attenuated insulin IR/PI3K/AKT signaling through inhibition of PTP1B oxidation, and ultimately attenuated insulin-induced adipocyte differentiation of 3T3-L1 cells [58].
Discovery of orally active chalcones as histone lysine specific demethylase 1 inhibitors for the treatment of leukaemia
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Yang Li, Ying Sun, Yang Zhou, Xinyang Li, Huan Zhang, Guojun Zhang
Chalcones as 1,3-diaryl-2-propene-1-ones with the enone system between two aromatic rings possess a wide range of biological activities such as antibacterial, antioxidative, anticancer, antileishmanial, antiulcer, antiangiogenic, antiviral, immunosuppressive and anti-inflammatory activities9–11. More particularly, a number of synthetic and natural chalcones exhibited the potent anticancer activity against many cancer cell lines12,13. Chalcone 1 (Figure 2), a natural product isolated from the root of Glycyrrhiza inflata, could inhibit the drug transport function of ABCG2 and reverse ABCG2-mediated multidrug resistance in human multidrug-resistant cancer cell lines14. Chalcone 2 exhibited the reduction of tumour cell growth combined with inhibition of Notch1 intracellular domain15. Naphthalene-chalcone derivative 3 was found to induce significant cell cycle arrest at the G2/M phase and cell apoptosis against MCF-7 cell line16. Chalcone 4 displayed the potent antiproliferative activity against cancer cells by up-regulating the expression of P53 protein17.
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.
Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide-induced hepatotoxicity via up-regulation of the Nrf2 pathway
Published in Drug Delivery, 2018
Qin-You Tan, Qian Hu, Sheng-Nan Zhu, Lu-Lu Jia, Juan Xiao, Hua-Zhen Su, Shao-Yuan Huang, Jing Zhang, Junfei Jin
Traditional medicinal licorice (Glycyrrhiza glabra L.) is obtained from the roots of Glycyrrhiza uralensis Fischer, Glycyrrhiza glabra L. or Glycyrrhiza inflata Batalin (Fabaceae), and the extract can enhance the effectiveness of other ingredients or reduce their toxicities (Gong et al., 2015; Chirumbolo, 2016). When treating rheumatoid arthritis, licorice can be combined with TWHF to mitigate the hepatotoxicity associated with TWHF (Cao et al., 2015); however, the hepatoprotective effect of licorice is not fully understood. Magnesium isoglycyrrhizinate (MIG), also known as tetrahydrate magnesium 18α, 20β-hydroxy-11-oxonorolean-12-en-3β-yl-2-O-β-D-glucopyranurosyl-α-D glucopyranosiduronate, is a magnesium salt of the 18-α glycyrrhizic acid stereoisomer in licorice root extract (LE) (Wang et al., 2017). MIG is an agent that protects hepatocytes. It is anti-inflammatory (He et al., 2010), protects liver cell membranes (Jiang et al., 2017), and improves liver function (Huang et al., 2014), and has been shown clinically to have hepatoprotective effects in cases of drug-induced liver injury, immune-mediated liver injury, and fatty liver (Tang et al., 2015). MIG has become a better candidate for treating inflammation and for hepatic protection than glycyrrhizin and β-glycyrrhizic acid due to its dramatic curative benefits and smaller number of adverse effects (Tang et al., 2015). It was recently reported that isoliquiritigenin and glycyrrhetinic acid are anti-oxidative and defend against TP-induced hepatotoxicity by activating Nrf2-associated HO-1 and NQO1 in HepG2 cells (Cao et al., 2016b); however, the hepatoprotective mechanisms of MIG remain to be elucidated.