A Dual-Targeted, Long-Circulating, and Intelligent-Responsive Antiviral Agent Suppresses SARS-CoV-2 by Blocking Viral Entry and Replication.

High-affinity, broad-spectrum, "centipede-like" multi-branched drug conjugates, anchored to the S protein, for blocking coronavirus infection.

The therapeutic potential of glycyrrhizic acid (GA) with various pharmacological properties is extremely limited owing to its poor water solubility. To solve this problem, nanocarrier-nontoxic Glycyrrhizae Radix et Rhizoma-derived carbon dots (GRR-CDs) with a narrow particle distribution of (1.90 ±0.44) nm were developed by an ecofriendly, simple and low-cost calcination method using GRR as the sole precursor. Then, the solubility of GA was shown to be prominently improved up to 27 times by GRR-CDs via a convenient and cost-effective ultrasonic dispersion method without needing to add any organic reagent. Various technologies were further used to demonstrate the interaction between GA and GRR-CDs. In addition, a release study in vitro exhibited a sustained release of GA for 24 h with a higher release ratio of up to 92.87% compared with that of pure GA. A significantly higher antinociceptive activity of the GRR-CDs-GA complexes compared to unprocessed GRR-CDs and GA was further demonstrated in both hot-plate model and acetic acid-induced writhing model. These results support the promising application of GRR-CDs as a potential tool for improving the solubility and antinociceptive activity of poorly water-soluble drugs, such as GA.

The case for a limited distribution model

Glycyrrhetinic acid (GA) is a commonly used drug for the chemotherapy of Chronic Hepatitis B, allergic dermatitis, inflammation, etc. But some problems such as poor water-solubility, low bioavailability and short plasma halflife, have limited its use. In the present study, PEGylation derivatives of GA derivatives were synthesized and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, etc. The PEG-GA conjugates having a critical micelle concentration of 0.081-0.73 mg/mL were used to form nano-sized micelles, with mean diameters of 120.86 ± 31.74 nm. The physico-chemical properties of the PEG – GA conjugate were evaluated including stability, cellular toxicity, and drug release profile. All the conjugates synthesized showed good stabilities in acidic and neutral solutions, while the stability in alkaline solution and the enzymatic hydrolysis rate, were significantly affected by the linkage between the GA and PEG chain. The results demonstrate that, by PEGylation of GA derivatives, the greatly increased water solubility and desirable self-assembly abilities of PEG-GA were obtained. The novel conjugates have potential medical applications for intravenously delivery of insoluble drug delivery. Keywords: Glycyrrhetinic acid, in vitro evaluation, micelles, poly(etylene glycol), self assembly, antitumor activities, glycyrrhizic acid, drug delivery, nontoxic, biocompatible

Glycyrrhizic acid ameliorates hepatic fibrosis by inhibiting oxidative stress via AKR7A2

Glycyrrhizin micellar nanocarriers for topical delivery of baicalin to the hair follicles: A targeted approach tailored for alopecia treatment

Artemisinin is a natural compound that is extracted from the plant Artemisia annua. While it was used to treat fever and pain in the past, it is currently approved by World Health Organization (WHO) to be used in combating malaria. It is an effective anti-malarial drug because of its high efficacy even towards multi-drug resistant Plasmodium strains and exhibits no significant side effects in humans. However, artemisinin has poor solubility in water or oil, poor bioavailability and a short half-life in vivo . Therefore, derivatives of artemisinin consisting of semi-synthetic and fully synthetic compounds with improved properties have been synthesized. Semi-synthetic derivatives include artesunate, artemether and dihydroartemisinin. Artemisinin and its derivatives are sesquiterpene lactones that contain a unique endoperoxide bond in its trioxane ring, which is essential for their anti-malarial activity. The importance of this bond is shown by the findings of studies that the abrogation of the endoperoxide bond led to a significant reduction in toxicity of the drugs. For example, the removal of one O-atom in the endoperoxide moiety was associated with a complete loss of anti-malarial activity. The activation mechanism of artemisinin is hypothesized to involve the reduction of the endoperoxide bond by Fe2+, which is a catalyst that can generate free radicals from peroxidic structures. The selective toxicity of the drug towards parasite-infected cells as compared to non-infected cells is attributed to the higher heme level in parasite-infected cells. In malarial parasite-infected red blood cells, the parasites break down hemoglobin in the food vacuole to gain amino acids for synthesis of their parasite-specific proteins. As a result, heme is released, which can be further degraded into iron in the vacuole. Therefore, hemoglobin degradation gives rise in an increase in both heme and free iron level in infected erythrocytes. As a result, whether heme or iron is the crucial activator of the drug is yet to be elucidated. One of the pleiotropic effects of the drug is that the reduced endoperoxide bond forms cytotoxic carbon-centered radicals that can alkylate target proteins and affect their functions. Other effects include the alkylation of heme, generation of reactive oxygen species (ROS) and inhibition of PfATP6, which is the P. falciparum ortholog of the endoplasmic reticulum Ca2+ pump. Some studies have also found that artemisinin builds up within neutral lipids and damage the parasite membrane. The combination of these toxic effects of artemisinin and its derivatives result in parasitic death. Artemisinin is used to relieve pain and fever in the older days. Today, artemisinin is widely used as an anti-malarial drug as our first line of defense to combat the emergence of drug resistance malaria parasite. Besides its anti-malarial properties, artemisinin is being investigated in other diseases. It is found to possess a wide spectrum of pharmacological activities, including anticancer, anti-asthma etc. However, its mechanism of action (MOA) is still not fully understood. Recently, “omics” approach has been used in identify the targets and unravel the mechanism of action of artemisinin. This review will summarize the recent progress in artemisinin target and mechanism study.

Development of a self-assembled micelles based on cryptotanshinone and glycyrrhizic acid: An efficient strategy for acne treatment.

Fabrication and in vitro/vivo evaluation of quercetin nanocrystals stabilized by glycyrrhizic acid for liver targeted drug delivery

Exploring the binding effect and mechanism of glycyrrhizin to ovomucin by combining spectroscopic analysis and molecular docking

Neutrophils are a type of granulocyte important in the "first line of defense" of the innate immune system. Upon activation, they facilitate the destruction of invading microorganisms by the production of superoxide radicals, as well as the release of the enzymatic contents of their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, as well as the recently discovered neutrophil serine protease 4 (NSP4). Under normal conditions, the proteolytic activity of neutrophil proteases is tightly regulated by endogenous serpins; however, this mechanism can be subverted during tissue stress, thereby resulting in the uncontrolled activity of serine proteases, which induce chronic inflammation and subsequent pathology. Herein, we describe the development of low-molecular-weight activity-based probes that specifically target the active sites of neutrophil proteases.

Comparative analysis of the humoral immunity of skin mucus from several marine teleost fish

Evaluation on the antibacterial activity of glycyrrhizin against Pseudomonas plecoglossicida in ayu fish (Plecoglossus altivelis)

Glycyrrhizinic acid (also known as glycyrrhizin) (GA) and its derivative 18-β-Glycyrrhetinic acid (18b-GA), which are isolated from the plant Glycyrryza glabra, show several therapeutic properties, including antioxidant, anti-inflammatory, and antiviral activity. These are therefore being evaluated for several medical proposes, among them the treatment of respiratory infections induced by viruses. The current review aimed to highlight the potential of GA and 18b-GA as efficient drugs. Both molecules have demonstrated antiviral activity against SARS-CoV-2, due to different mechanisms; for instance, blocking key enzymes for virus entry to the cell or by limiting virus replication. Those properties are well known from in vitro and animal assay research, however, reports of their effects on humans are scarce. One of the main challenges of using GA and 18b-GA as a drug is improving their solubility and permeability, as well as using therapeutic doses without toxic effects. Due to the biological properties of GA and 18b-GA, the dose and administration type are crucial to achieving a high local concentration and therefore a therapeutic effect.

Abstract: Background: Glycyrrhizin (GZ) is a bioactive ingredient of Glycyrrhiza glabra, reported for various therapeutic effects including gastro-protection. It has been associated with low absorption, early elimination, short half-life and poor bioavailability. Objectives: Aim of the current study was to formulate GZ loaded mucoadhesive microspheres by using mucopolymers like sodium alginate and guar gum for the management of peptic ulcer. Methods: Various GZ loaded microspheres (GZ-MS1-3) were prepared by an emulsification-crosslinking technique. These formulations were developed with different proportions of guar gum and sodium alginate. The formulations were characterized and evaluated by various parameters including particle size, zeta potential, entrapment efficiency (% EE), % yield, SEM, FTIR, swelling index, mucoadhesive efficiency, in vitro drug release and in vivo antioxidant activities. Results: Result stated that suitable particle size (50.18 ± 1.15 μm), zeta potential (-31.12 ± 2.16 mV), %EE (92.67 ± 1.91) and % yield (97.45 ± 1.83) was achieved with optimized formulation, GZ-MS1. Significant (***P<0.001) swelling index (0.94 ± 0.04) and mucoadhesive efficiency (95.98 ± 3.62%) was obtained with GZ-MS1. GZ-MS1 showed maximum drug release profile (94.57 ± 4.03 %) in simulated gastric fluid (SGF, pH 1.2) at 37 ± 0.5°C for 24 h. FTIR study confirmed that there was no interaction observed between GZ and excipients. Conclusion: Sustained release profile of the optimized formulation was achieved due to significant mucoadhesive efficiency of the sodium alginate and guar gum. Thus, the mucoadhesive microspheres of GZ would be an effective strategy for the management of peptic ulcer. Key words: Mucoadhesive microspheres, Glycyrrhizin, Mucopolymers, Sodium alginate, Guar gum, Sustained release, Peptic ulcer.