Product name: 18α,20β-Glycyrrhizic acid
Synonym name: 18α-Glycyrrhizin; 18α-Glycyrrhizinic acid; 18αH-Glycyrrhizic acid
Catalogue No.: BP2279
Cas No.: 83896-44-0
Formula: C42H62O16
Mol Weight: 822.942
Botanical Source:
Type of Compound: Triterpenoids
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
For Reference Standard and R&D, Not for Human Use Directly.
HPLC of 18α,20β-Glycyrrhizic acid
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
18α-Glycyrrhizic acid (CAS No.: 83896-44-0) is a natural triterpene saponin derived from licorice (Glycyrrhiza spp.). As one of the isomers of glycyrrhizic acid, 18α-glycyrrhizic acid exhibits structural differences from the more common 18β-glycyrrhizic acid, giving it unique biological activity and pharmacological characteristics. In recent years, with the deepening development of natural product pharmacology, 18α-glycyrrhizic acid has gradually become a research hotspot in the field of antiviral drug development due to its remarkable antiviral activity and relatively good safety.
This review will systematically summarize the chemical structure and physicochemical properties of 18α-glycyrrhizic acid, its plant origins and extraction methods, focusing on its pharmacological activity and mechanism of action, exploring its pharmacokinetic characteristics in conjunction with druggability evaluation, and finally looking forward to its clinical application potential and future research directions, aiming to provide comprehensive and authoritative reference materials for researchers in related fields.
The molecular formula of 18α-glycyrrhizic acid is C42H62O16, with a molecular weight of 822.9420. Its structural core is a tricyclopentaene-type triterpene backbone, connecting two glucose molecules to form a typical saponin structure. Compared with 18β-glycyrrhizic acid, 18α-glycyrrhizic acid has a α configuration at C-18 and a β at position 20. These differences affect its binding to biological targets and pharmacological activity.
In terms of physicochemical properties, the LogP value of 18α-glycyrrhizic acid is 2.3483, indicating moderate lipid solubility that facilitates cell membrane penetration. The topological pole surface area (TPSA) reaches as high as 267.0400, reflecting its strong molecular polarity, which may limit its passive ability to pass through the blood-brain barrier, which aligns with its low permeability. Water solubility is 0.1287 mg/mL, indicating poor water solubility, but its bioavailability can be improved with appropriate formulation techniques. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test result was 0.0, indicating extremely low genotoxicity risk and high safety.
18α-Glycyrrhizic acid is mainly found in the roots and rhizomes of licorice, with plants of the genus Licorice (such as Glycyrrhiza glabra and Glycyrrhiza uralensis) as its primary natural sources. Licorice, as a traditional Chinese medicinal herb, is widely distributed in China, Russia, and the Mediterranean region, and its roots contain abundant glycyrrhizic acid isomers.
The extraction method typically uses water extraction and alcohol precipitation, combined with column chromatography for separation and purification. The specific steps include: crushing the dried licorice roots, refluxing extraction with water or 70%-80% ethanol, concentrating the extract and adding ethanol precipitate impurities, then separating them using a silica gel column or a C18 reversed phase column, monitoring purity by high-performance liquid chromatography (HPLC), and finally obtaining high-purity 18α-glycyrrhizic acid. In recent years, the application of ultrasound-assisted extraction, microwave-assisted extraction, and membrane separation technologies has significantly improved extraction efficiency and purity, while reducing production costs.
18α-Glycyrrhizic acid exhibits broad-spectrum antiviral activity, covering both DNA and RNA viruses, with significant inhibitory effects especially against herpes virus (HSV), human immunodeficiency virus (HIV), and human papillomavirus (HPV). In vitro experiments showed that 18α-glycyrrhizic acid effectively inhibited the replication of HSV-1 and HSV-2, reduced viral load, and alleviated virus-induced cellular lesions.
In HIV infection models, 18α-glycyrrhizic acid exhibits potential antiretroviral activity by interfering with key viral enzymes (such as HIV-1 protease HIV1-PR) and co-receptors CCR5 and CXCR4, blocking viral entry and replication. Additionally, it has certain inhibitory effects on viral integrase (INT) and various virus-specific proteins (UL42, UL54, ICP27, TK, gD), suggesting its multi-target antiviral mechanism.
Research shows that 18α-glycyrrhizic acid can regulate host immune responses, enhance macrophage activity, promote balanced secretion of cytokines (such as TNF-α, IL-6), and reduce inflammatory responses triggered by viral infections. Its regulatory effect on myeloperoxidase (MPO) helps suppress oxidative stress and tissue damage, further exerting protective effects.
In addition to antiviral effects, 18α-glycyrrhizic acid has also been reported for anti-tumor, antioxidant, and liver protection. By regulating cell apoptosis signaling pathways and inhibiting free radical production, it demonstrates multiple biological activities and holds potential for development into multifunctional drugs.
The antiviral effects of 18α-glycyrrhizic acid involve multi-target and multi-pathway mechanisms:
Viral enzyme inhibition: Directly binds to and suppresses key enzyme activities such as viral DNA polymerase (UL42, UL54), protease (HIV1-PR), and kinase (TK), blocking the viral replication cycle.
Viral protein function interference: Inhibits the function of viral transcriptional regulatory protein ICP27 and the viral surface glycoprotein gD, hindering viral assembly and release.
Receptor blockade: By competitively binding to CCR5 and CXCR4 co-receptors, it blocks HIV virus invasion into host cells.
Immune regulation: regulates host immune cell activity, suppresses excessive inflammatory responses, and reduces tissue damage caused by viral infection.
Molecular docking and kinetic simulation studies further revealed that 18α-glycyrrhizic acid binds to various viral target proteins with strong binding energy and stable binding sites, supporting its multi-target inhibitory properties.
The druggability parameters of 18α-glycyrrhizic acid indicate that it has good potential for drug development. The LogP is moderate, indicating some membrane permeability, but high TPSA and low water solubility limit oral bioavailability. The blood-brain barrier has low permeability, reducing the risk of toxic side effects in the central nervous system.
Pharmacokinetic studies show that 18α-glycyrrhizic acid is absorbed slowly orally and has a long plasma half-life, mainly metabolized by the liver, with bile excretion predominantly. Its metabolites are mostly hydrolysates of glycyrrhizic acid monosaccharides, which have certain biological activity. In vivo distribution shows high concentrations in the liver, lungs, and kidneys, meeting the targeted requirements for its antiviral and hepatoprotective effects.
In terms of safety evaluation, 18α-glycyrrhizic acid showed no significant hERG channel inhibitory effect, and the Ames test was negative, indicating low cardiotoxicity and genotoxicity risks, making it suitable for long-term use.
Given the significant antiviral activity and good safety profile of 18α-glycyrrhizic acid, it has broad application prospects in clinical antiviral therapy. Especially in adjuvant therapy against HSV, HIV, and emerging viral infections, 18α-glycyrrhizic acid acts as a naturally derived multi-target antiviral agent, which can compensate for the shortcomings of existing single-target drugs and reduce the risk of resistance.
Future research should focus on:
Additionally, combining nanocarriers with targeted delivery technology is expected to overcome pharmacokinetic limitations and enable precise treatment.
18α-Glycyrrhizic acid, as a natural triterpene saponin with a unique three-dimensional configuration, demonstrates significant potential as a novel antiviral drug due to its broad-spectrum antiviral activity, multi-target mechanism, and good safety. Although current research mostly focuses on in vitro and animal models, future interdisciplinary collaborations combined with modern medicinal chemistry and formulation technologies are expected to promote clinical application and provide new natural drug candidates for antiviral therapy.
In summary, 18α-glycyrrhizic acid not only enriches the pharmacological connotations of glycyrrhizic acid compounds but also provides valuable scientific basis and practical pathways for the development of naturally derived antiviral drugs. We look forward to more in-depth and systematic research in the future to help realize its clinical value.
