Glycyrrhizic acid ameliorates submandibular gland oxidative stress, autophagy and vascular dysfunction in rat model of type 1 diabetes

The burden of diabetes mellitus (DM) and associated complications is increasing worldwide, affecting many organ functionalities including submandibular glands (SMG). The present study aims to investigate the potential ameliorative effect of glycyrrhizic acid (GA) on diabetes-induced SMG damage. Experimental evaluation of GA treatment was conducted on a rat model of type I diabetes. Animals were assigned to three groups; control, diabetic and GA treated diabetic groups. After 8 weeks, the SMG was processed for assessment of oxidative stress markers, autophagy related proteins; LC3, Beclin-1 and P62, vascular regulator ET-1, aquaporins (AQPs 1.4 and 5), SIRT1 protein expressions in addition to LC3 and AQP5 mRNA expressions. Also, parenchymal structures of the SMG were examined. GA alleviated the diabetes-induced SMG damage via restoring the SMG levels of oxidative stress markers and ET-1 almost near to the normal levels most probably via regulation of SIRT1, AQPs and accordingly LC-3, P62 and Beclin-1levels. GA could be a promising candidate for the treatment of diabetes-induced SMG damage via regulating oxidative stress, autophagy and angiogenesis.

Nanoformulation of Glycyrrhizic acid as a potent antiviral agent against Covid-19

In many previous studies, it has been found that liquorice plant (Glycyrrhiza glabra) extracts contain more than 300 natural compounds, most of which are triterpenoids and flavonoids, and had shown promising results in clinical studies for treating many microbial and viral infections. Triterpenoids like glycyrrhizic acid have shown anti-SARS-CoV activity in- vitro. Experimentally, certain glycyrrhizic acid derivatives have shown increased activity by many folds against SARS-associated viruses. These compounds can potentially inhibit the replication cycle of SARS-associated viruses by interfering with the viral gene expression or by inhibiting the spike protein expression, which in turn inhibits the adhesion and entry of the virus. Although the therapeutic has shown great antiviral activity in vitro, but in vivo its efficiency deteriorates till it reaches the liver for metabolism. In the current review, we analyze the unique replication strategy of SARS-CoV-2 and glycyrrhizic acid as a potential drug against SARS-CoV-2. We also discuss possible nano-formulations of glycyrrhizic acid for efficient drug delivery in humans, as a potent therapeutic strategy for COVID-19.

PROSPECTS FOR THE CREATION OF MEDICINES BASED ON A NATURAL ADAPTOGEN IN THE COMPLEX THERAPY OF VIRAL INFECTIONS

В статье описано современное состояние распространения, переработки и использования солодки в Казахстане. Представлены литературные данные использования компонентов корня солодки в создании лекарственных средств для профилактики и лечения иммунодефицитного состояния при вирусных инфекциях. Обобщены литературные данные о комбинированных препаратах, содержащих экстракт корня солодки, глицирризиновую кислоту. The article describes the current state of distribution, processing and use of licorice in Kazakhstan. The literature data on the use of licorice root components in the creation of medicines for the prevention and treatment of immunodeficiency in viral infections are presented. The literature data on combined preparations containing licorice root extract and glycyrrhizic acid are summarized.

Solvent Effect in Glycyrrhizic Acid Spectra (Absorption and Fluorescence)

In this research paper, a method built on UV/VIS spectrofluorophotometer and spectrophotometer by finding the fluorescence of glycyrrhizic acid in licorice root. Glycyrrhizic acid is an imperative active component present in licorice (Glycyrrhiza uralensis Fisch). Solvent effect had been studied in different solvents like deionized water and methanol. The differences between them were explored by the glycyrrhizic acid absorption and emission spectra. Under work conditions, i.e. 100% methanol solvent, a liquid ratio concentration 10−2 to 10−5 g /mL and second solvent with same conditions 100% deionized water in the same concentrations ,was done. The effect of the solvent was significant by change the value for λmax. The result was validated for parameters confines for Ex (λ Excitation) in different solvents. The results of absorption spectra obey Beer-Lambert's law. Because of the same property of these solvents (protic), the absence of a significant difference in the absorption spectra are shown. From florescence spectra, the spectrum at concentration 10−4 is the best for both solvents..

Exploring the Pharmacological Potential of Glycyrrhizic Acid: From Therapeutic Applications to Trends in Nanomedicine

Glycyrrhizic acid (GA) is the main active component of the licorice root, which has been known in traditional medicine since the ancient times. It is a molecule composed of a hydrophilic part, two glucuronic acid molecules, and a hydrophobic part, glycyrrhetinic acid. GA, when subjected to acid hydrolysis, releases 18β- and 18α-glycyrrhetinic acids. Glycyrrhetinic acid is most responsible for the pharmacological activities of licorice. GA has been reported to have multiple therapeutic properties: anti-viral, anti-inflammatory, antitumor, antimicrobial and hepatoprotective. Different approaches have revealed similar anti-inflammatory mechanisms of action of GA, such as the inhibition of translocation of nuclear factor-κB (NF-κB) and suppression of Tumour Necrosis Factor alpha (TNF-α) and interleukins. In this sense, several in vitro and in vivo studies have described the use of GA in the prevention and treatment of several complications, especially microbial/viral infection, and as a novel chemo-preventive agent for liver injury. Recent studies postulated that GA nanoparticles (GANPs) can be a promising strategy for the treatment of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infections. This mini-review summarizes the pharmacological activities of GA and its beneficial effects against various health problems and provides perspectives on the development of versatile nanoplatforms to overcome some limiting physicochemical properties and for enhancing the therapeutic benefits of GA.

Preparation and Characterization of a Glycyrrhizic Acid-Based Drug Delivery System for Allergen-Specific Immunotherapy

The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. It is also known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, meaning that it could potentially enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of the supramolecular complexes (micelles) of GA with extracts of allergens holds promise for the development of new drugs for AIT.

Revealing the Toxicity-Enhancing Essence of Glycyrrhiza on Genkwa Flos Based on Ultra-high-performance Liquid Chromatography Coupled With Quadrupole-Orbitrap High-Resolution Mass Spectrometry and Self-Assembled Supramolecular Technology

Researchers often focus on the mechanisms of synergistic agents, a few explore drug combinations that enhance toxicity, while few have studied the internal mechanism of compatibility enhancement in chemical level. Herein, we present a comprehensive analysis based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) and a self-assembled supramolecular strategy, which reveals the toxicity-enhancing essence of glycyrrhizic acid originated in licorice when combined with Genkwa Flos. Through this method, we discovered the toxicity was enhanced through the formation of a supramolecular complex from Genkwa Flos/glycyrrhizic acid. The morphology and size distribution of the self-assembled nanoparticles were characterized by scanning electron microscopy and dynamic light scattering Furthermore, a total of 58 constituents (eight diterpenoids, 35 flavonoids, five phenylpropanoids, four nucleosides, two amino acids, and four other compounds) consisted from the supramolecular complex were identified through accurate-mass measurements in full-scan MS/data-dependent MS/MS mode. Based on the hydrophobic interaction of glycyrrhizic acid with yuanhuacine (one of main ingredients from Genkwa Flos), the supramolecular self-assembly mechanism was revealed with proton nuclear magnetic resonance (1H-NMR) and NOESY 2D NMR. The toxicity of Genkwa Flos and Genkwa Flos/glycyrrhizic acid supramolecular complex were compared through in vitro studies on L-02 cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; and 4′,6-diamidino-2-phenylindole (DAPI) staining was performed to further confirm the enhancement inhibition of Genkwa Flos/glycyrrhizic acid supramolecular complex than Genkwa Flos. This study provides fundamental scientific evidence of the formation of a self-assembled phytochemical supramolecular when Genkwa Flos and glycyrrhizic acid are combined, enabling to understand their clinical incompatibility and contraindication.