Rhizomes Of Glycyrrhiza Uralensis Research Articles

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.

Chemical analysis of the Chinese herbal medicine licorice (Gan-Cao): An update review

Ethnopharmacological relevanceLicorice, called Gan-Cao in China, is one of the most popular traditional herbal medicines. It is derived from the dried roots and rhizomes of Glycyrrhiza uralensis, G. glabra, and G. inflata. Licorice is recorded in the pharmacopoeias of China, Japan, US, and Europe. AimThis review updates research progress of licorice from the perspectives of chemical analysis, quality evaluation, drug metabolism, and pharmacokinetic studies from 2009 to April 2022. Materials and methodsBoth English and Chinese literatures were collected from databases including PubMed, Elsevier, Web of Science, and CNKI (Chinese). Licorice, extraction, structural characterization/identification, quality control, metabolism, and pharmacokinetics were used as keywords. ResultsNewly developed analytical methods, including LC/UV, 2DLC, LC/MS, GC/MS, and mass spectrometry imaging (MSI) for chemical analysis of licorice were summarized. ConclusionThis review provides a comprehensive summary on chemical analysis of licorice.

Glycoside Compounds From Glycyrrhiza uralensis and Their Neuroprotective Activities

This paper concerns the study of the roots and rhizomes of Glycyrrhiza uralensis where one new alkaloid glycoside, 3,4-dihydroxyquinoline 4- O-β-d-glucopyranoside, along with 13 known compounds (12 phenolic glycosides and one triterpene glycoside) were isolated and identified. The structure of the new compound and the known ones were identified on the basis of nuclear magnetic resonance (NMR) and mass spectrometric (MS) analysis. All the glycosides were tested for their anti-neuroinflammatory activities by inhibiting nitric oxide (NO) release in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells. Several compounds were tested for their antioxidant activities in rat adrenal pheochromocytoma PC12 cells. A structure–activity relationship (SAR) analysis was carried out and revealed that the position and amount of sugar moieties have significant impact on antioxidant activities.

Pharmacokinetic Change of Glycyrrhetinic Acid from the Roots and Rhizomes of Glycyrrhiza uralensis by Coadministration with the Rhizomes of Atractylodes japonica, A. macrocephala, or A. chinensis in an Animal Model

Atractylodes rhizomes (Atractylodes japonica Koidz. ex Kitam., A. macrocephala Koidz., and A. chinensis), Asteraceae, are widely used to treat digestive disorders and these rhizomes are commonly paired with the roots and rhizomes of Glycyrrhiza uralensis Fisch., Fabaceae, in herbal formulae, which may lead to mutual interaction in vivo. To assess the influence of three species of Atractylodes rhizomes on the pharmacokinetic features of G. uralensis, the levels of glycyrrhetinic acid in rat plasma samples were quantified using ultra-performance liquid chromatography/ion-trap mass spectrometry after intragastric coadministration. The results demonstrated that simultaneous administration of the extracts of the three Atractylodes rhizomes reduced the mean residence time and last measured concentration of glycyrrhetinic acid in plasma samples. Among the Atractylodes rhizomes, the combination of A. japonica shortened the elimination half-life and time to the maximum concentration of glycyrrhetinic acid. In conclusion, Atractylodes rhizomes, especially A. japonica, might alter the pharmacokinetic characteristics (mostly the duration in vivo) of glycyrrhetinic acid from G. uralensis when these herbs are coadministered. This study provides an understanding for species-specific influences on pharmacokinetic features in herbal combinations.

Phenolic compounds from cultivated Glycyrrhiza uralensis and their PD-1/PD-L1 inhibitory activities

One new compound (1) and fifteen known phenolic compounds (2–16) were isolated and identified from the roots and rhizomes of Glycyrrhiza uralensis, including ten flavonoids, four coumarins, and two benzofurans compounds. Their structures were identified by NMR and MS analysis. Most of these compounds showed weak PD-1/PD-L1 inhibitory activities with the inhibition ratios from 30 to 65% at 100 uM. To our knowledge, it is the first time that their PD-1/PD-L1 inhibition activities were reported.

Chemical influences of the rhizomes of Atractylodes japonica, A. macrocephala, or A. chinensis on the extraction efficiencies of chemical compounds in the roots and rhizomes of Glycyrrhiza uralensis during hot-water extraction

Chemical influences of the rhizomes of Atractylodes japonica, A. macrocephala, or A. chinensis on the extraction efficiencies of chemical compounds in the roots and rhizomes of Glycyrrhiza uralensis during hot-water extraction

Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models.

The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process. The low levels of acetylcholine and dopamine are major neuropathological feature of NDDs in addition to oxidative stress, intracellular calcium ion imbalance, mitochondrial dysfunction, ubiquitin-proteasome system impairment and endoplasmic reticulum stress. Current treatments minimally influence these diseases and are ineffective in curing the multifunctional pathological mechanisms. Synthetic neuroprotective agents sometimes have negative reactions as an adverse effect in humans. Recently, numerous ethnobotanical studies have reported that herbal medicines for the treatment or prevention of NDDs are significantly better than synthetic drug treatment. Medicinal herbs have traditionally been used around the world for centuries. Radix Glycyrrhizae (RG) is the dried roots and rhizomes of Glycyrrhiza uralensis or G. glabra or G. inflata from the Leguminosae/Fabaceae family. It has been used for centuries in traditional medicine as a life enhancer, for the treatment of coughs and influenza, and for detoxification. Diverse chemical constituents from RG have reported including flavanones, chalcones, triterpenoid saponins, coumarines, and other glycosides. Among them, flavanone liquiritigenin (LG) and its precursor and isomer chalcone isoliquiritigenin (ILG) are the main bioactive constituents of RG. In the present review, we summarize evidence in the literature on the structure and phytochemical properties and pharmacological applications of LG and ILG in age-related diseases to establish new therapeutics to improve human health and lifespan.

Bioactive Constituents of Glycyrrhiza uralensis (Licorice): Discovery of the Effective Components of a Traditional Herbal Medicine.

Traditional herbal medicines have been reported to possess significant bioactivities. In this investigation, a combined strategy using both phytochemical and biological approaches was conducted to discern the effective components of licorice, a widely used herbal medicine. Altogether, 122 compounds (1-122), including six new structures (1-6), were isolated and identified from the roots and rhizomes of Glycyrrhiza uralensis (licorice). These compounds were then screened using 11 cell- and enzyme-based bioassay methods, including Nrf2 activation, NO inhibition, NF-κB inhibition, H1N1 virus inhibition, cytotoxicity for cancer cells (HepG2, SW480, A549, MCF7), PTP1B inhibition, tyrosinase inhibition, and AChE inhibition. A number of bioactive compounds, particularly isoprenylated phenolics, were found for the first time. Echinatin (7), a potent Nrf2 activator, was selected as an example for further biological work. It attenuated CCl4-induced liver damage in mice (5 or 10 mg/kg, ip) and thus is responsible, at least in part, for the hepatoprotective activity of licorice.

Determination of the Plant Origin of Licorice Oil Extract, a Natural Food Additive, by Principal Component Analysis Based on Chemical Components

"Licorice oil extract" (LOE) (antioxidant agent) is described in the notice of Japanese food additive regulations as a material obtained from the roots and/or rhizomes of Glycyrrhiza uralensis, G. inflata or G. glabra. In this study, we aimed to identify the original Glycyrrhiza species of eight food additive products using LC/MS. Glabridin, a characteristic compound in G. glabra, was specifically detected in seven products, and licochalcone A, a characteristic compound in G. inflata, was detected in one product. In addition, Principal Component Analysis (PCA) (a kind of multivariate analysis) using the data of LC/MS or (1)H-NMR analysis was performed. The data of thirty-one samples, including LOE products used as food additives, ethanol extracts of various Glycyrrhiza species and commercially available Glycyrrhiza species-derived products were assessed. Based on the PCA results, the majority of LOE products was confirmed to be derived from G. glabra. This study suggests that PCA using (1)H-NMR analysis data is a simple and useful method to identify the plant species of origin of natural food additive products.

Antithrombotic phenolic compounds from Glycyrrhiza uralensis

A new coumestan, named glycyrurol, and nine phenolic compounds were isolated from the ethyl acetate extract of the roots and rhizomes of Glycyrrhiza uralensis. Their structures were elucidated based on spectroscopic analysis and literature data, and anticoagulative assay found significant antithrombotic activity of compounds 4, 8 and 10.

Beta-glucuronidase inhibitory activity and hepatoprotective effect of 18 beta-glycyrrhetinic acid from the rhizomes of Glycyrrhiza uralensis.

An inhibitor of beta-glucuronidase from the rhizomes of Glycyrrhiza uralensis was isolated and its hepatoprotective activity on CCI4-induced hepatotoxicity of rats was investigated. From the water-soluble extract of G. uralensis, glycyrrhizin was isolated as a potent inhibitor of beta-glucuronidase. When glycyrrhizin was orally administered, it had a hepatoprotective activity. However, when glycyrrhizin was intraperitoneally administered, it did not have a hepatoprotective activity. 18 beta-Glycyrrhetinic acid, which is a major metabolite of glycyrrhizin by human intestinal bacteria, was also a potent inhibitor of beta-glucuronidase. When 18 beta-glycyrrhetinic acid was intraperitoneally administered, it also had some hepatoprotective activity. These results suggest that glycyrrhizin may be a natural prodrug for the observed hepatoprotective effect in rats and that serum beta-glucuronidase levels have implications for the liver injury, as reductions of its activity by administration of inhibitors such as G. uralensis or its derived products and silymarin correlate with reductions in biochemical indices of liver injury.