Exploring the Pharmacological Potential of Glycyrrhizic Acid: From Therapeutic Applications to Trends in Nanomedicine
Abstract
:1. Introduction
2. GA: Molecular Mechanisms of Action and Pharmacological Applications
2.1. Anti-Inflammatory and Hepatoprotective Activity
2.2. Antiviral and Anti-Parasitic Activity
2.3. Antibacterial Activity
2.4. Antitumor and Antioxidant Activities
2.5. Some Evidence for GA Efficacy: Clinical Trials
Pharmacological Activities | Main Results | References |
---|---|---|
Anti-inflammatory | GA exhibits antiinflammatory effects through inhibition of MIP-1 in a mouse model of acute P. acnes-induced inflammatory liver injury. | [18] |
Anti-inflammatory | GA interrupted JNK/c-Jun and IκB/NF-κB signaling pathways, which decrease activator protein-1 (AP-1) and NF-κB mediated ICAM-1 expressions. | [19] |
Anti-inflammatory | GA inhibits the expression of TNF-α, IL-6, IL-1β and RANTES in LPS-stimulated macrophages. | [20] |
Anti-inflammatory | GA inhibits IL-1β induced inflammation by blocking PI3K/Akt phosphorylation and NF-κB activation and alleviated OA progression in surgical-induced DMM mouse model. | [22] |
Anti-inflammatory | GA inhibits the LPS/D-galactosamine-induced liver injury through preventing inflammatory responses and IL-18 production. | [23] |
Anti-inflammatory | GA may prevent tissue injury in chronic hepatitis and in many autoimmune diseases by suppressing the lytic pathway of the complement system. | [24] |
Anti-inflammatory | GA was effective and reduced atopic dermatitis in a human and children double-blind clinical trial. | [56,57,58] |
Anti-inflammatory | GA promoted ulcer healing in patiets with peptic ulcer. | [6,63,64] |
Antiviral | GA augmented IFN-induced reduction of virus in the HCVcc system (cell culture produced HCV). | [15] |
Antioxidant | GA were able to increase the intracellular reduced glutathione concentration, in AFB1-treated cells. | [25] |
Anti-apoptotic | GA has inhibitory effects on hepatocyte apoptosis and liver fibrosis. | [26] |
Antiviral | GA increased the number of OKT4 lymphocytes, and demonstrated a suitable treatment for preventing the development of asymptomatic carrier (AC) in hemophilia patients into AIDS. | [27] |
Antiviral | GA attenuated inflammatory responses in HSV by inhibition of adhesion between CCEC and PMN. | [28] |
Antiviral | Water Extract of GA has inhibitory Inhibited Enterovirus 71 in a Human Foreskin Fibroblast Cell Line. | [29] |
Antiviral | Inhibitory effect of GA on HIV replication in patients with AIDS. | [31] |
Antiviral | GA has inhibitory effect on a chemoattractant (RANTES) released by influenza A virus (H1N1)-infected human bronchial epithelial cells. | [32] |
Antiviral | GA inhibits replication, adsorption, and penetration of the virus during the early steps of the replica-tive cycle in Vero cells. GA inhibits replication of the SARS-associated virus. | [33] |
Antiviral | GA inhibits replication of the SARS-associated virus. | [34] |
Anti-parasitic | GA suppressed inflammation in Leishmania donovani infection by inhibiting COX-2-mediated PGE2 release. | [38] |
Anti-parasitic | GA adecreased hepatic and splenic parasite burden and increased T cell proliferation in Leishmania-infected BALB/c mice. | [39] |
Anti-parasitic | GA has anthelmintic activity against gastrointestinal nematodes of small ruminants. | [40] |
Anti-parasitic | GA has a potential antileishmanial chemotherapeutic agent by killing the parasite affecting sterol biosynthetic pathway. | [41] |
Antibacterial | GA inhibited Arylamine N-acetyltransferase (NAT) activities in a strain of H. pylori. | [42] |
Antibacterial | GA promoted antibacterial resistance of severely burned mice to P. aeruginosa burn wound infection. | [43] |
Antibacterial | GA reduced skin lesion size and attenuates expression of key virulence genes in a mouse model of S. aureus. | [44] |
Antibacterial | GA showed a significant antibacterial activity against S. aureus, E. coli, P. fluorescens, and Bacillus cereus. | [45] |
Antibacterial | GA increased the eradication rate of H. pylori in patients with gastrointestinal disorders. | [60,61,62] |
Antioxidant | GA were able to increase the intracellular reduced glutathione concentration, in AFB1-treated cells. | [25] |
Anti-apoptotic | GA has inhibitory effects on hepatocyte apoptosis and liver fibrosis. | [26] |
Antitumor | GA exhibited anti-tumor property in astric ancer cells partly by inducing apoptosis and cell cycle arrest. | [47] |
Antitumor and Antioxidat | GA induces apoptotic cell death in SiHa cells and exhibits a synergistic effect against antibiotic, anti-cancer and drug toxicity. | [48] |
Antitumor | GA has chemopreventive effect via modulation of inflammatory markers and induction of apoptosis in human hepatoma cell line (HepG2). | [50] |
Antibacterial | GA suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of wistar rats. | [52] |
Antitumor and Antioxidat | GA induced apoptosis and was found to modulate critical end points of oxidative stress in c.ultured primary rat hepatocytes. | [54] |
Antitumor and Antioxidat | GA induces programmed cell death, probably inhibiting the liver enzyme 11-hydroxysteroid dehydrogenase type. | [55] |
Antitumor and Antiviral | GA reduced the increased risk of hepatocellular carcinoma in patients with HCC. | [6,59] |
2.6. Glycyrrhizic Acid and Their Therapeutic Associations—The Role of Nanomedicine
3. Final Considerations
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nanomaterial | Composition | Main Results | References |
---|---|---|---|
Nanoparticles | Glycyrrhizic acid-based nanoparticle suspension | GA nanoparticle inhibited the activity of LPS-induced inflammatory cytokine (NO, PGE2, TNF-α, and IL-6) production in macrophage cells. | [71] |
Nanoparticles | 10-hydroxycamptothecin (HCPT)-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles | GA-BSA-HCPT nanoparticles can target liver tumor cells. | [72] |
Nanoparticles | pDNA-polyethylenimine-glycyrrhizic acid | pDNA/PEI/GL showed high gene expressions in the liver, especially in parenchymal cells after intravenous administration. | [66] |
Nanoparticles | Chitosan-katira gum nanoparticles | GA encapsulated in chitosan-katira gum nanoparticles enhanced its anti-inflammatory activity. | [75] |
Nanoparticles | Hyaluronic acid-glycyrrhizic acid succinate copolymers | Enhanced liver-targeting, and all the copolymers presented no significant cytotoxicity to HepG2 cells. | [21] |
Nanoparticles | Glycyrrhizic acid-functionalized graphene oxide | GA-GO@DOX induced mitochondria-mediated apoptosis (MMA) of cancer cells. | [70] |
Nanoparticles | Glycyrrhizic acid-loaded pH-sensitive poly-(lactic-co-glycolic acid) | GA-loaded nanoparticles release GA to the colon and treat bowel mucosal inflammation. | [74] |
Nanoparticles | Glycyrrhizic acid | GANPs had antiviral, anti-inflammatory, and antioxidant effects in vitro and in vivo. | [30] |
Micelles | Paclitaxel-loaded glycyrrhizic acid micelles | PTX-loaded GA micelles demonstrated a significant improvement in the pharmacokinetic parameters of PTX after oral administration. | [73] |
Micelles | Podophyllotoxin-loaded glycyrrhizic acid micelles | The POD-loaded GA micelles caused less skin inflammation than traditional POD tincture. | [77] |
Liposomes | Pegylatedliposomes | Nano-liposome encapsulation of silibinin with glycyrrhizic acid increased the biological activity of the free drugs. | [65] |
Micelles | Glycyrrhizic acid-nafamostat mesilate | A computational method for screening candidates for drug delivery systems selected GA and nafamostat mesilate (NM), which were converted into micelle nanoparticles to improve drug stability and to effectively treat COVID-19. | [78] |
Carbon dots | Glycyrrhizic acid-based carbon dots | Biological experiments demonstrated that Gly-CDs have excellent antiviral activity against the porcine reproductive and respiratory syndrome virus (PRRSV). | [76] |
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Nascimento, M.H.M.d.; de Araújo, D.R. Exploring the Pharmacological Potential of Glycyrrhizic Acid: From Therapeutic Applications to Trends in Nanomedicine. Future Pharmacol. 2022, 2, 1-15. https://doi.org/10.3390/futurepharmacol2010001
Nascimento MHMd, de Araújo DR. Exploring the Pharmacological Potential of Glycyrrhizic Acid: From Therapeutic Applications to Trends in Nanomedicine. Future Pharmacology. 2022; 2(1):1-15. https://doi.org/10.3390/futurepharmacol2010001
Chicago/Turabian StyleNascimento, Mônica Helena Monteiro do, and Daniele Ribeiro de Araújo. 2022. "Exploring the Pharmacological Potential of Glycyrrhizic Acid: From Therapeutic Applications to Trends in Nanomedicine" Future Pharmacology 2, no. 1: 1-15. https://doi.org/10.3390/futurepharmacol2010001
APA StyleNascimento, M. H. M. d., & de Araújo, D. R. (2022). Exploring the Pharmacological Potential of Glycyrrhizic Acid: From Therapeutic Applications to Trends in Nanomedicine. Future Pharmacology, 2(1), 1-15. https://doi.org/10.3390/futurepharmacol2010001