Modification, Antitumor Activity, and Targeted PPARγ Study of 18β-Glycyrrhetinic Acid, an Important Active Ingredient of Licorice

Abstract

Licorice is a traditional Chinese medicine, which is often used as sweetener and cosmetic ingredients in food and pharmaceutical industries. Among them, glycyrrhetic acid is one of the most important agents. Studies have shown that glycyrrhetic acid exhibited antitumor activities as PPARγ agonist. However, the limited number of PPARγ glycyrrhetinic agonists and their high toxicity greatly limit the design based on the structure. Therefore, clarifying the binding mode between PPARγ and small molecules, we focused on the introduction of a natural active piperazine skeleton in the position of glycyrrhetinic acid C-3. According to the Combination Principle and the Structure-Based Drug Design, 19 glycyrrhetic acid derivatives were designed and synthesized as potential PPARγ agonists. Compounds 4c and 4q were screened as high-efficiency and low-toxicity lead compounds.

<p>ISL Induces Apoptosis and Autophagy in Hepatocellular Carcinoma via Downregulation of PI3K/AKT/mTOR Pathway in vivo and in vitro</p>

“…[32][33][34][35] Among the bioactive ingredients isolated from licorice, ISL has been reported to possess considerable biological activities. 15,[35][36][37][38] However, the specific antitumor effect of ISL in hepatoma cells and its mechanism is still not well understood. At present, various cancer therapies, such as chemotherapy, immunotherapy, and gene therapy, focus on the apoptosis signal transduction pathway.…”

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx

“…Licorice products are also most often consumed as avoring and sweetening agents in food products in Western countries [8]. Licorice is promoted as an herb that can be used to treat peptic ulcers, eczema, skin infections, cold sores, menopausal symptoms, liver disease, respiratory ailments, in ammatory problems, chronic fatigue syndrome, acquired immune de ciency syndrome, and even cancer [9,10]. However, there are few studies on anti-pseudo-allergic effect of licorice.…”

Dual Strategy for Improving the Oral Bioavailability of Resveratrol: Enhancing Water Solubility and Inhibiting Glucuronidation

“…But the surface active agent will be harmful to humans. However, GA possesses many pharmacological activities as RES, such as anticancer, antioxidant, anti-inflammatory, and liver protection activities . Thus, with GA as an inhibitor of UGTs, RES/GA-PC can not only enhance the bioavailability of RES by inhibiting its glucuronidation but might also be helpful to human health.…”