Licorice Research Articles

Modern Treatment of Dry Post-viral Cough. Focus on Efficiency and Safety

Cough is the most common symptom of bronchopulmonary diseases, about which patients consult the doctors of both primary and secondary care. Cough can be caused by diseases of the respiratory tract, digestive tract, and cardiovascular diseases. However, cough most often develops during acute respiratory viral infections (ARVI), which disrupts the patient’s normal activities and limits his work capacity. Since most respiratory infections are viral in nature, the use of antibacterial drugs will not only be of no benefit, but will also significantly worsen the patient’s condition. The objective: to analyze the effectiveness and tolerability of a combined antitussive agent, which includes codeine, thermopsis extract, licorice root and sodium bicarbonate, in the treatment of dry post-viral cough. Materials and methods. The study included 60 patients with a dry cough that caused by ARVI, namely: 49 (82%) men and 11 (18%) women. The average age of the patients was 46±4.7 years. Most of the subjects (90%) had smoking experience of more than 20 years. The research participants were divided into two groups of 30 people each. The groups were comparable by age, duration and severity of symptoms, as well as clinical manifestations of respiratory disease. The patients of the first group took a combined antitussive drug containing codeine, thermopsis extract, licorice root, and sodium bicarbonate for 5 days. Patients of the second group received alternative antitussive drugs. At the beginning and at the end of treatment, the severity of cough was determined on a visual analog scale and the physical, psychological and social conditions of patients in both groups were assessed using the Leicester Acute Cough Questionnaire. Results. As a result of the research, it was found that the patients of the first group, who received the combined antitussive drug, have achieved the desired treatment result much earlier and more effectively than the patients of the second group. The intensity of their cough decreased by 2.5 times during the treatment period. The patients of the first group also had better results of treatment, comparing indicators of physical, psychological and social conditions. In the control group, positive results of treatment were determined, although a less significant effect was found. Conclusions. The conducted study confirmed the high efficiency of the combined antitussive agent, which includes codeine, thermopsis extract, licorice root and sodium bicarbonate, in the treatment of dry debilitating cough caused by ARVI. Thanks to the use of this drug, the severity of cough significantly decreased, which led to a significant improvement in the general condition and quality of life of patients.

PHARMACOGNOSTIC AND PHARMACEUTICAL EVALUATION OF YASHTIMADHU (GLYCYRRHIZA GLABRA LINN.)

Background: Yashtimadhu, botanically identified as Glycyrrhiza glabra L., is a well-known herb in Ayurveda. It is cultivated in India, mainly in Punjab and sub-Himalayan tracts. Root and stolon have been widely used in different formulations. Pancha Vidha Kashaya Kalpanas (Pharmaceutics) are mentioned primarily to achieve the maximum efficacy of the drug and to upgrade its palatability. Some kalpanas are also made to increase the shelf-life of a drug. In the conventional system, dosage forms are mainly preferred based on the solubility of a drug to enhance its bioavailability. Yashtimadhu, as per the literature, have been used in 22 dosage forms. Churna (powder), Kashaya (decoction), Phanta (infusion), Ksheerapaka (milk-based preparation), Taila (Oil-based preparation) and Gritha (ghee-based preparation) are mainly used to enhance its therapeutic utility. Aim: To analyse the pharmacognostic changes; this study evaluated Yashtimadhu and its pharmaceutics for its characteristic features. Method: The formulations were prepared using the classical methods and analysed based on the standard parameters. Result: The evaluation showed that the parameters were comparable to the standard references. Conclusion: The genuine authenticity and shelf-life of a drug remain an essential criterion for a drug to be fit for therapeutic consumption. Evaluation of Yashtimadhu in its different forms for various parameters revealed its significance.

Synthesis and Characterization of Nano-Composites of Polypropylene / Cr2O3 Nanoparticles Using Licorice Extract

In this work, biosynthesized nanoparticles (Cr2O3) NPs were extracted by licorice root and proven by AFM technique to have a particle diameter of 14.99 nm. These particles were superimposed on polypropylene, and nanocomposites were synthesizes and diagnosed using different techniques, such as FT-IR, SEM, EDS, XRD, TG, DTA, and DSC. To identify the shapes, sizes, and nature of the particles of nanocomposites synthesized in an environmentally friendly way using the mentioned techniques, inhibitory actions of microorganisms were studied using several types of bacteria and fungi. To identify the protective role of environmentally friendly nanoparticles, the antimicrobial activity of the synthesized nanoparticles was characterized by green methods. Antioxidant activity was calculated by DPPH, and acceptable results were obtained for scavenging free radicals.

The King of Chinese Medicine——Glycyrrhiza glabra (Licorice): All-round Inquiry in its Chemical Composition, Pharmacodynamics, Traditional and Medicinal Value

Licorice, a perennial herb of Leguminosa, is one of the oldest and most widely used herbal medicines worldwide. Its distinct sweet flavor and rich medicinal value make it an integral component of traditional Chinese medicine (TCM) formulations, which continue to be widely employed. The main chemical constituents of licorice include triterpenoid saponins, flavonoids, and polysaccharides. Experimental and clinical studies have demonstrated that various extracts and pure compounds derived from licorice exhibit a wide range of pharmacological properties including anti-inflammatory, antioxidant, antimicrobial, antiviral, antitumor, immune-regulatory, and neuroprotective activities. The bioactive constituents of licorice offer therapeutic benefits for cardiovascular and cerebrovascular diseases, diabetes mellitus, and liver disorders. This comprehensive review discusses the primary chemical constituents of licorice and their pharmacological activities, describes in vivo and in vitro models employed for studying licorice, and its potential targets and mechanisms of action. Furthermore, we discuss the toxicological profile, side effects, dosage recommendations, and clinical applications of licorice. This review aims to establish a foundation for further research on the safe and effective utilization of licorice while facilitating an in-depth exploration of its properties and fostering the development of novel therapeutic agents. Graphical abstract: http://links.lww.com/AHM/A102

18β-glycyrrhetinic acid suppresses Lewis lung cancer growth through protecting immune cells from ferroptosis.

18β-glycyrrhetinic acid (GA), the main metabolite of glycyrrhizic acid extracted from the root of licorice, has been reported to possess anti-cancer and immunomodulatory activity, but the mechanisms are not well understood. Recent studies have shown that ferroptosis of immune cells is involved in tumor-associated immune suppression. The purpose of this study was to investigate whether the enhanced immune response via inhibiting immune cell ferroptosis contributed to the anticancer effect of 18β-GA. Lewis Lung carcinoma mouse model and Murine CD8+T cell culture model were used to examine the changes of immune response and ferroptosis of immune cells. We found that 18β-GA was effective against lung cancer accompanied by enhanced activation of tumor-infiltrating CD8+ T cells in Lewis Lung carcinoma mouse model. Furthermore, we demonstrated that the boosted immune response by GA was attributed to its ability to inhibit arachidonic acid (AA)-mediated CD8+ T ferroptosis via suppressing CD36 expression. The findings of the present study unraveled a novel mechanism underlying the anti-cancer and immunomodulatory activity of 18β-GA and support that 18β-GA holds potential to be used as an immune enhancer for lung cancer prevention or treatment.

Comparative Teratogenic and Skin whitening effect of Herbal extract Glycyrrhiza glabra and Citrus sineus on Zebrafish (Danio rerio)

Objective: To determine acute toxicity and Synergistic effect of the anti-melanogenic activity of methanolic extract Glycyrrhiza glabra and Citrus sineus on zebrafish. Materials and method: Fish embryo toxicity (FET) was studied as per OECD guidelines 236. The LC50 and maximum non-lethal concentration of both the extracts were calculated. The images of zebrafish larvae exposed to different concentrations of methanolic extracts and their combination were taken by using labomed digital microscope. The skin whitening effect of extract was studied by measuring integrated density of images by using imageJ software Result: LC50 Value and maximum non-lethal concentration of methanolic extracts of Glycyrrhiza glabra and Citrus sineus were found to be 56.23ppm and 34.7ppm respectively. The result revealed significant reduction in percentage hatchability (p < 0.0014 for glycyrrhiza glabra and p<0.0011 for Citrus sinenus), dose dependant increased in percentage mortality and different developmental morphological abnormalities in zebrafish embryos exposed to the methanolic extracts Glycyrrhiza glabra and Citrus sineus. The synergistic effect of herbal extracts was found to be more effective in reducing the melanin content. Conclusion: Very High concentration of Glycyrrhiza glabra and Citrus Sineus showed teratogenic effect in zebrafish embryoes. However, based on OECD aquatic toxicity classification, both the extracts were found to be safe. Our study also revealed synergestic skin whitening effect of both the extracts in zebrafish larvae which might be due to reduction of melatonin content by these extracts.

Ammonium Glycyrrhizate: A natural biosurfactant for the design of innovative nanocarriers

In this paper, the surfactant properties of Ammonium Glycyrrhizate, a bioactive compound present in Licorice root were studied. Considering the ability of this bioactive molecule to form micelles, we investigated for the first time the self-assemble of Ammonium Glycyrrhizate in vesicle structures. The organization of Ammonium Glycyrrhizate in vesicles allows to increase its bioavailability and, so, efficacy but also to use them as carrier of other drugs for potential combination therapy. Niosomes made up of Ammonium Glycyrrhizate were prepared using thin layer evaporation technique without the use of additional excipients and characterized in term of size, polydispersion index, Zeta potential and colloidal stability. Moreover, the performance of these innovative vesicles as carriers of hydrophilic drug (Fluorescein sodium) or a lipophilic molecule (Curcumin), was evaluated. Nanocarriers showed nanometric sizes, hexagonal shape, high colloidal stability and ability to encapsulate both hydrophilic and hydrophobic molecules. These vesicles did not showed cytotoxicity nor antimicrobial activityMoreover, it was found that these niosomes enhanced skin permeation and diffusion in several media and an important ability to interact with mucin. Considering its antinflammatory nature, in vitro inhibition of albumin denaturation assay was also carried out to test if the drug maintains these properties also when organized in colloidal structures. The obtained results highlighted an important antinflammatory activity suggesting the potential role of these nanodevices alone or loaded with other therapeutic molecules for the treatment of inflammatory-based diseases.

Synthesis and Accumulation of Phytocompounds in Field-, Tissue-Culture Grown (Stress) Root Tissues and Simultaneous Defense Response Activity in Glycyrrhiza glabra L.

Harsh climates, i.e., drought, extreme temperatures, and toxic gases, pose issues to agriculture by altering plants’ growth and yield. Biotechnology with biochemical defense approaches is beneficial for generating new plants/varieties with extra resilience to adverse conditions. In response to stress, cultures show an enriched level of secondary metabolite synthesis. Here, an efficient in vitro propagation method using axillary shoot proliferation, along with callus formation, was established in Glycyrrhiza glabra L. The phytochemical composition of in vitro and in vivo grown tissues was analyzed using a gas chromatography–mass spectrometry (GC–MS) technique, and the biochemical attributes were measured and compared in different investigated tissues. Callus formation from root explants was achieved with a frequency of 88.89% on MS medium containing 2.0 mg/L BAP and 0.5 mg/L 2,4-D. Axillary shoot proliferation was obtained from dormant buds when cultured onto MS supplemented with BAP alone, or in combination with, IAA. The maximum shoot proliferation (94.44%) was recorded on MS with 1.0 mg/L BAP with an average shoot length of 10.5 cm. The regenerated shoots were subcultured and transferred to the root induction medium, supplemented with various concentrations of IAA/IBA, wherein 2.0 mg/L IBA resulted in the best rooting frequency (88.89%). The GC–MS-based phytocompounds analysis of the methanolic extracts of root-derived callus and in vivo- and in vitro- grown root tissues was conducted. These samples revealed the presence of more than 35 therapeutically important bioactive compounds, such as methylglabridin, sitosterol, lupeol, squalene, stearic acid, linoleic acid, etc. The biochemical parameters, like total phenolic content, flavonoid content, DPPH scavenging activity, superoxide dismutase, and peroxidase activity were also measured. All the biochemical attributes were found to be higher in in vitro derived roots than the callus and in vivo grown root (donor) samples. These findings demonstrated that callus (root derived) and in vitro roots are a stable and potent source of multiple phytocompounds, encompassing medical significance with wide applications. This study may serve as an alternative opportunity in the sustained and continuous synthesis of important compounds without harming natural vegetation and normal environment.

Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum

IntroductionMalaria control is hindered by drug-resistant parasites, leading to a shortage of effective drugs. There is a need to find new, better antimalarial drug. Traditional Chinese Medicine (TCM) are more accessible and cheaper alternative for combating resistance in the treatment of malaria, therefore the anti-malarial efficacy of root extracts and isolated phytomolecules from Glycyrrhiza glabra L was assessed. MethodsThe anti-plasmodial potential of root extracts and isolated phytomolecules from Glycyrrhiza glabra L. was assessed using the Giemsa staining method. In- vivo, antimalarial efficacy was evaluated by conducting a four-day suppression test in a mouse model. The mechanistic studies of ISL were carried out using caspase-like activity, mitochondrial membrane potential, and reactive oxygen species (ROS) assay. Further, proteomics analysis was carried out by LC-MS/MS. The interaction of the combinations was evaluated using the fixed ratio method by calculating the fractional inhibitory concentration (FIC). ResultsExtracts of G. glabra contain Phytomolecule(s) with moderate anti-plasmodial activity against multidrug-resistant strain (K1) of P. falciparum. Isoliquiritigenin (ISL) exhibited a significant reduction in parasitemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis infected mice. ISL showed potent activity with no cytotoxic effect and increased caspase-3 activity, leading increasing reactive oxygen species (ROS) and loss of mitochondrial potential. ISL also displayed synergy with chloroquine, glabridin and liquiritigenin against multi-drug-resistant P. falciparum. DiscussionThe present study found ISL to be a potential phytomolecule of G. glabra. The study explored the mechanism of action of ISL and suggested its suitability for further study in managing drug-resistant malaria.

Treatment with Glycyrrhiza glabra Extract Induces Anxiolytic Effects Associated with Reduced Salt Preference and Changes in Barrier Protein Gene Expression.

We have previously identified that low responsiveness to antidepressive therapy is associated with higher aldosterone/cortisol ratio, lower systolic blood pressure, and higher salt preference. Glycyrrhiza glabra (GG) contains glycyrrhizin, an inhibitor of 11β-hydroxysteroid-dehydrogenase type-2 and antagonist of toll-like receptor 4. The primary hypothesis of this study is that food enrichment with GG extract results in decreased anxiety behavior and reduced salt preference under stress and non-stress conditions. The secondary hypothesis is that the mentioned changes are associated with altered gene expression of barrier proteins in the prefrontal cortex. Male Sprague-Dawley rats were exposed to chronic mild stress for five weeks. Both stressed and unstressed rats were fed a diet with or without an extract of GG roots for the last two weeks. GG induced anxiolytic effects in animals independent of stress exposure, as measured in elevated plus maze test. Salt preference and intake were significantly reduced by GG under control, but not stress conditions. The gene expression of the barrier protein claudin-11 in the prefrontal cortex was increased in control rats exposed to GG, whereas stress-induced rise was prevented. Exposure to GG-enriched diet resulted in reduced ZO-1 expression irrespective of stress conditions. In conclusion, the observed effects of GG are in line with a reduction in the activity of central mineralocorticoid receptors. The treatment with GG extract or its active components may, therefore, be a useful adjunct therapy for patients with subtypes of depression and anxiety disorders with heightened renin-angiotensin-aldosterone system and/or inflammatory activity.

Neuroprotective aftermath of Monodora myristica and Glycyrrhiza glabra against cassava diet containing vacuum gas oil induced brain injury in Wistar rats

Vacuum gas oil (VGO) is a hydrocarbon combination formed during crude oil extraction, and its consumption may have neurological repercussions. This study investigated the neuroprotective properties of Monodora myristica and Glycyrrhiza glabra in rats given cassava flour diet containing vacuum gas oil (CFD-VGO). Thirty rats were separated into six groups and treated as follows: Group 1 severed as normal control. Group 2 were fed CFD-VGO only. After a normal diet was given to groups 3, 4, and 5, M. myristica, G. glabra, and M. myristica plus G. glabra extracts were administered. Group 6, 7, 8 and 9 were given CFD-VGO and then treated with M. myristica extract, G. glabra extract, M. myristica plus G. glabra extracts and 2-methyl cellulose respectively. The rats were euthanized using carbon dioxide after experimental period of 28 days. The brain was excised for biochemical assays. The results showed that the concentration of the assessed 16 PAHs in CFD-VGO using GC-MS was 53.38 ppm. Significant (p < 0.05) increase were observed in malondialdehyde (MDA), total cholesterol (T.Chl), triacylglycerol (TAG), low density lipoprotein-cholesterol (LDL-C), and decrease in high density lipoprotein-cholesterol (HDL-C), acetylcholinesterase (AChE) and ATPases in the brain rats fed with CFD-VGO. On the other hand, administration of M. myristica and G. glabra extract effectively restored altered antioxidants, ATPases, and lipids in brain of rats fed with cassava diet containing VGO.

Effect, main targets and molecular mechanisms of glycyrrhiza-derived flavonoids on malignant tumor in comprehensive cancer treatment

Glycyrrhiza flavonoids (GF) are essential antitumor components of Glycyrrhiza uralensis, Glycyrrhiza glabra, and Glycyrrhiza inflata roots and tubers, with antioxidant, anti-inflammatory, antibacterial, immune-enhancing amongst other properties. In recent years, significant progress has been made in understanding the mechanisms and targets of GF in various pharmacological settings. This review summarizes the clinical value, targets and research progress of the molecular mechanisms underlying GF in the treatment of malignant tumors. This will provide as a theoretical foundation for further studies into GF as a therapeutic option in the management of cancerous tumors.

Glycyrrhizic acid restores the downregulated hepatic ACE2 signaling in the attenuation of mouse steatohepatitis

Glycyrrhizic acid (GA), one of the major active components derived from licorice root, exerts liver-protecting activity. Its molecular mechanisms of action, however, remain not completely understood. The angiotensin (Ang) converting enzyme (ACE) 2/Ang-(1–7)/Mas axis, regulated by ACE2 through converting Ang II into Ang-(1–7) to activate Mas receptor, counteracts the pro-inflammatory and pro-steatotic effects of the ACE/Ang II/Ang II receptor type 1 (AT1) axis. Here, it was found that pretreatment with GA suppressed LPS/D-galactosamine-induced serum hyperactivities of alanine aminotransferase and aspartate aminotransferase, hepatomegaly, pathological changes, and over-accumulation of triglycerides and fatty droplets in the liver of mice. GA also diminished LPS/free fatty acid-induced inflammation and steatosis in cultured hepatocytes. Mechanistically, GA restored hepatic protein hypoexpression of ACE2 and Mas receptor, and the decrease in hepatic Ang-(1–7) content. Hepatic overexpression of angiotensin II and AT1 was also suppressed. However, GA did not alter hepatic protein expression of renin and ACE. In addition, GA inhibited hepatic protein over-phosphorylation of the p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and nuclear factor κB at Ser536. Hepatic overexpression of tumor necrosis factor α, interleukin 6, interleukin 1β, sterol regulatory element-binding protein 1c, and fatty acid synthase was also inhibited. GA-elicited recovery of ACE2 and Mas protein hypoexpression was further confirmed in the hepatocyte. Thus, the present results demonstrate that GA restores the downregulated hepatic ACE2-mediated anti-inflammatory and anti-steatotic signaling in the amelioration of steatohepatitis. We suggest that GA may protect the liver from injury by regulating the hepatic ACE2-mediated signaling.

In Silico Analysis of Selected Glycyrrhiza glabra (Licorice) Constituents: Exploring Their Modulatory Effects on Human Superoxide Dismutase, Human Phosphodiesterase-9 and Human Dipeptidyl Peptidase-4.

Background Glycyrrhiza glabra (Licorice) has been known for its various biological activities. In the current investigation, we aimed to evaluate 11 (10 natural and one synthetic) selected constituents of G. glabra as potent modulatory agents of human superoxide dismutase (hSOD), human phosphodiesterase-9 (hPDE 9) and human dipeptidyl peptidase-4 (hDPP 4) using in silico method. Methodology The 11 selected constituents of G. glabra (Licorice) were investigated on the docking behaviour of hSOD, hPDE 9 and hDPP 4 by using the PatchDock method. In addition to docking, toxicity analysis was also carried out using the pkCSM free online server (University of Melbourne,Melbourne,AUS). Results Toxicity analysis has shown that four ligands (36%) of G. glabra (Licorice) are predicted to have human ether-a-go-go-related gene-2 (hERG 2) inhibition activity. The docking analysis showed that glabridin (-224.13 kcal/mol) has shown the highest atomic contact binding energy with the hSOD enzyme, whereas carbenoxolone has shown the maximum atomic contact binding energy with both the hPDE 9 and hDPP 4 enzymes(-239.57 and -173.50 kcal/mol) respectively. Conclusion Thus the present finding provides new information about 11 selected ligands of G. glabra (Licorice) as potent modulatory agents of hSOD, hPDE 9and hDPP 4.

Licochalcone A induces endoplasmic reticulum stress-mediated apoptosis of endometrial cancer cells via upregulation of GRP78 expression.

Licochalcone A (LicA), a natural compound extracted from licorice root, has been shown to exert a variety of anticancer activities. Whether LicA has such effects on endometrial cancer (EMC) is unclear. This study aims to investigate the antitumor effects of LicA on EMC. Our results show that LicA significantly reduced the viability and induced apoptosis of EMC cells and EMC-7 cells from EMC patients. LicA was also found to induce endoplasmic reticulum (ER) stress, leading to increased expression of ER-related proteins (GRP78/PERK/IRE1α/CHOP) in EMC cell lines. Suppression of GRP78 expression in human EMC cells treated with LicA significantly attenuated the effects of LicA, resulting in reduced ER-stress mediated cell apoptosis and decreased expression of ER- and apoptosis-related proteins. Our findings demonstrate that LicA induces apoptosis in EMC cells through the GRP78-mediated ER-stress pathway, emphasizing the potential of LicA as an anticancer therapy for EMC.

New Insights into the Anti-Oomycete Mechanisms of a Leaf Extract from Glycyrrhiza glabra Against Pseudoperonospora cubensis.

Cucurbit downy mildew, caused by Pseudoperonospora cubensis, is responsible for high economic losses worldwide in cucumber production. Synthetic pesticides or copper-based products are still important tools to manage the disease. However, the pathogen has developed resistance against common fungicides rather quickly, and there is a need for alternative plant-protecting agents. Glycyrrhiza glabra leaf extract is known for its antifungal activity and was highly effective in former bioassays and semi-commercial trials against downy mildew of cucumber. To elucidate the active ingredients and the mode of action, licorice leaf extract was here fractionated into five fractions (F1 to F5) with a newly developed and optimized separation process via flash chromatography. The crude extract (P1) and fraction F1 inhibited the zoospore release from sporangia, the zoospore germination, and germ tube development of P. cubensis almost completely on two cucumber cultivars, one tolerant and one susceptible to the pathogen. Infestation rates were reduced between 73 and 96%. F1 contained three previously reported antifungal polyphenols: glabranin, pinocembrin, and licoflavanon. Here, we report an additional new compound, naringenin. Furthermore, F5 is found here to show some protective effects against P. cubensis, based on either direct fungicidal or indirect effects via the host plant. The presented results show that licorice leaf extract can serve as an alternative plant protection agent, able to manage P. cubensis infestation on cucumber cultivars with differing levels of susceptibility by interfering with important early stages in the pathogen development.

The Role of Different Medicinal Herbs in Treatment of Polycystic Ovary Syndrome: A Review

Abstract: Polycystic ovary syndrome (PCOS/PCOD) indicates a common, multifactorial endocrine condition marked by polycystic ovaries, chronic anovulation, and hyperandrogenism, resulting in asymmetric menstrual periods, hirsutism, acne, and infertility. Standard treatment for PCOS is often accompanied by adverse effects, and is ineffective in certain situations, refutation-based medical guidance accented an integrative progress. Furthermore, women suffering from PCOS may benefit from alternative treatments. Herbal treatment includes herbs that have a phytoestrogenic and non-estrogenic nature, including Mentha spicata, Panax ginseng, Glycyrrhiza glabra, Aloe barbadensis, Cinnamomum zeylanicum, Matricaria chamomilla, Trigonella foenum-graecum, Linum usitatissimum, and Zingiber officinale, which are effective and safe. This review focuses on the reproductive endocrine effects of phytomedicine as a choice treatment so as to PCOD and accompanying oligo/amenorrhoea, acne, hirsutism, and infertility.

The Efficient Activity of Glabridin and its Derivatives Against EGFRmediated Inhibition of Breast Cancer.

Breast cancer (BC) is one of the most typical causes of cancer death in women worldwide. Activated epidermal growth factor receptor (EGFR) signaling has been increasingly associated with BC development and resistance to cytotoxic drugs. Due to its significant association with tumour metastasis and poor prognosis, EGFR-mediated signaling has emerged as an attractive therapeutic target in BC. Mainly in all BC cases, mutant cells over-expresses EGFR. Certain synthetic drugs are already used to inhibit the EGFR-mediated pathway to cease metastasis, with several phytocompounds also revealing great chemopreventive activities. This study used chemo-informatics to predict an effective drug from some selected phytocompounds. The synthetic drugs and the organic compounds were individually screened for their binding affinities, with EGFR being the target protein using molecular docking techniques. The binding energies were compared to those of synthetic drugs. Among phytocompounds, Glabridin (phytocompound of Glycyrrhiza glabra</i>) manifested the best dock value of -7.63 Kcal/mol, comparable to that of the highly effective anti-cancer drug Afatinib. The glabridin derivatives also exhibited comparable dock values. The AMES properties deciphered the non-toxic features of the predicted compound. Pharmacophore modeling and in silico</i> cytotoxicity predictions also exhibited a superior result assuring their drug likeliness. Therefore, Glabridin can be conceived as a promising therapeutic method to inhibit EGFR-mediated BC.

Licorice flavonoid ameliorates ethanol-induced gastric ulcer in rats by suppressing apoptosis via PI3K/AKT signaling pathway

Ethnopharmacological relevanceLicorice is the dry roots and rhizomes of Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L. and Glycyrrhiza inflata Bat., which was first recorded in Shengnong's herbal classic. Licorice flavonoid (LF) is the main compound isolated from licorice with an indispensable action in treating gastric ulcer (GU). However, the underlying mechanisms need to be further explored. Aim of the studyThis study aimed to investigate and further elucidate the mechanisms of LF against ethanol-induced GU using an integrated approach. Materials and methodsThe anti-GU effects of LF were evaluated in an ethanol-induced gastric injury rat model. Then, the metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Next, the network pharmacology combined with metabolomics strategy was employed to predict the targets and pathways of LF for GU. Finally, these predictions were validated by molecular docking, RT-qPCR, and western blotting. ResultsLF had a positive impact on gastric injury and regulated the expression of GU-related factors. Upon serum metabolomics analysis, 25 metabolic biomarkers of LF in GU treatment were identified, which were primarily involved in amino acid metabolism, carbohydrate metabolism, and other related processes. Subsequently, a “components-targets-metabolites” network was constructed, revealing six key targets (HSP90AA1, AKT1, MAPK1, EGFR, ESR1, PIK3CA) that may be associated with GU treatment. More importantly, KEGG analysis highlighted the importance of the PI3K/AKT pathway including key targets, as a critical route through which LF exerted its anti-GU effects. Molecular docking analyses confirmed that the core components of LF exhibited a strong affinity for key targets. Furthermore, RT-qPCR and western blotting results indicated that LF could reverse the expression of these targets, activate the PI3K/AKT pathway, and ultimately reduce apoptosis. ConclusionLF exerted a gastroprotective effect against gastric ulcer induced by ethanol, and the therapeutic mechanism may involve improving metabolism and suppressing apoptosis through the PI3K-AKT pathway.

Anti-inflammatory ability of licorice (Glycyrrhiza glabra) root extract in cyclooxygenase-2 enzyme inhibition: In silico study

Background: Inflammation represents the body's natural response to injury, which can be induced by chemical, physical, or biological agents. Current approaches to managing inflammatory conditions involve addressing the primary etiological factors and administering anti-inflammatory medications like Nonsteroid Anti Inflammatory Drugs (NSAIDs) in inhibiting cyclooxygenase 2 (COX-2). However, data from 2021 reveals that 78.8% of patients experience gastritis as a side effect of such treatment. Licorice root extract (LRE)-an ayurvedic plants emerges as a promising alternative due to its potent anti-inflammatory properties attributed to the presence of glycyrrhizin, constituting between 2% to 25% of its dry weight. Objectives: To find out and determine the molecular inhibition of compound in LRE against COX-2 enzyme. Method: The process involves isolating the active constituents of LRE using pubchem and BioVia application, isolation active site of COX-2 by exploring RCSB PDB and isolate it using PyMol and engaging in molecular docking simulations using PyRx. Results and discussions: Cyclooxygenase-2 (COX-2) emerges as a pivotal enzymatic orchestrator intricately woven into the fabric of the inflammatory cascade. Licorice root extract stands at the forefront of prospective candidates in the realm of anti-inflammatory drug development, buoyed by its remarkable anti-inflammatory attributes. Regarding to ∆Gbind value, molecular docking tests show LRE compounds inhibit COX-2 better than arachidonic acid and mefenamic acid. Six LRE compounds outperform reference compounds, indicating potential anti-inflammatory capabilities. Other compounds show anti-inflammatory activity, and RMSD values affirm the accuracy of in silico predictions. Conclusion: LRE had potential as oral topical anti-inflammatory drugs through COX-2 inhibition with the best anti-inflammation ability is 18β‐glycyrrhetic acid.