18β-Glycyrrhetinic Acid for Anti-inflammation Skin Soothing Redness Relief and Barrier Repair

1. Description

18β-glycyrrhetinic acid is a naturally occurring pentacyclic triterpenoid compound and the primary active metabolite of glycyrrhizic acid in the body. It is widely derived from the rootstock of the leguminous plant Glycyrrhiza. It appears as a white crystalline powder, is soluble in dimethyl sulfoxide (DMSO; solubility approximately 252.5 mg/mL), and is practically insoluble in water and ethanol. Its melting point is 292–295°C, with the molecular formula C₃₀H₄₆O₄ and a molecular weight of approximately 470.69 Da. It should be stored in a light-protected, sealed container at room temperature or 2–8°C in a dry environment; prolonged exposure to air may result in a decrease in content. This compound exhibits various biological activities, including anti-inflammatory, antioxidant, antitumor, hepatoprotective, anti-ulcer, antiviral, and antibacterial properties.

2. Application

(1) Hepatoprotective Studies: Used in studies of liver injury models induced by carbon tetrachloride, acetaminophen, and triptolepine. Research indicates that 18β-glycyrrhetinic acid exerts hepatoprotective effects by activating the SIRT1/FXR signaling pathway, upregulating PPARγ and Nrf2 expression, and alleviating oxidative stress and inflammatory responses. In a rat model of Tripterygium glycoside-induced liver injury, pretreatment with a 50 mg/kg dose significantly reduced serum transaminase levels and inhibited the release of inflammatory cytokines.

(2) Oncology Studies: Used to investigate the mechanisms of antiproliferation and apoptosis induction in various cancer cell lines, including hepatocellular carcinoma, colorectal cancer, gastric cancer, breast cancer, and prostate cancer. In HepG2 liver cancer cells, 18β-glycyrrhetinic acid increases the production of reactive oxygen species (ROS) and nitric oxide (NO), leading to a loss of mitochondrial membrane potential, activation of caspase-3 and caspase-9, upregulation of the Bax/Bcl-2 ratio, and induction of apoptosis. It exhibits no significant toxic effects on normal liver cells.

(3) Anti-inflammatory and Skin Disease Research: Used in studies of inflammatory skin diseases such as atopic dermatitis, psoriasis, and UV-induced photoaging. It reduces the production of pro-inflammatory cytokines by inhibiting the NF-κB signaling pathway and downregulating iNOS and COX-2 expression. Modern delivery systems (such as liposomes and nanoemulsions) can enhance its skin permeability and bioavailability.

(4) Anti-ulcer and Gastrointestinal Protection Research: Used in studies on gastric ulcers and digestive system diseases. It exerts a protective effect on the gastric mucosa by inhibiting 15-hydroxyprostaglandin dehydrogenase activity and increasing prostaglandin concentrations in the digestive system.

(5) Antimicrobial and antiviral research: Used in studies on pathogenic bacteria such as Staphylococcus aureus (including methicillin-resistant strains) and Helicobacter pylori, as well as in studies on antiviral activity. Research indicates that 18β-glycyrrhetinic acid can enhance the activity of antibiotics against drug-resistant strains.

(6) Renal Protection Studies: Used in studies on drug-induced kidney injury, such as that caused by cisplatin, exerting a renal protective effect through antioxidant and anti-inflammatory mechanisms.

(7) Neuroprotection Studies: Used in studies on neurological disorders such as cerebral ischemia, exerting a neuroprotective effect through anti-inflammatory and antioxidant mechanisms.

3. Main Efficacy

(1) Anti-inflammatory effects: By inhibiting the activation of the NF-κB signaling pathway, it downregulates the expression of iNOS and COX-2 and reduces the production of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. It has demonstrated significant anti-inflammatory effects in various inflammatory models.

(2) Antioxidant Effects: By activating the Nrf2/ARE pathway, it enhances the activity of endogenous antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, reduces the formation of malondialdehyde (a lipid peroxidation product), and protects cells from oxidative stress damage.

(3) Hepatoprotective effects: By activating the SIRT1/FXR signaling pathway, it regulates bile acid metabolism; it also activates autophagy inhibition mediated by the pregnane X receptor, thereby alleviating hepatocyte damage. It has demonstrated protective effects in various models of liver injury, including those induced by carbon tetrachloride, acetaminophen, and triptolepine.

(4) Antitumor activity: Inhibits tumor cell proliferation through multiple mechanisms, including inducing apoptosis (by regulating Bax/Bcl-2 and activating caspase-3/9), increasing reactive oxygen species (ROS) production, and causing loss of mitochondrial membrane potential. It exhibits inhibitory effects on various tumor cell lines, including hepatocellular carcinoma, colorectal cancer, gastric cancer, and breast cancer.

(5) Anti-ulcer and Gastric Mucosal Protection: It exerts anti-ulcer effects by inhibiting 15-hydroxyprostaglandin dehydrogenase, increasing the concentration of prostaglandin E2 in the gastric mucosa, and enhancing the defensive capacity of the gastric mucosa.

(6) Antimicrobial Activity: It inhibits Staphylococcus aureus (including methicillin-resistant strains) and can enhance the antimicrobial activity of conventional antibiotics. It also inhibits Helicobacter pylori infection.

(7) Renal Protective Effects: Through antioxidant and anti-inflammatory mechanisms, it alleviates drug-induced renal tubular damage and renal dysfunction caused by agents such as cisplatin.

(8) Skin protection: Through anti-inflammatory and antioxidant mechanisms, it provides protective effects against atopic dermatitis, psoriasis, and UV-induced photoaging of the skin. Delivery systems such as liposomes and nanoemulsions can significantly improve its transdermal permeability and bioavailability.