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ABSTRACT Background Aim Methods Results Conclusions The dermal extracellular matrix (ECM) is a dynamic scaffold composed mainly of proteins, with collagen as the key structural component providing resilience and support to the skin. Post‐menopause, declining estrogen levels lead to a significant reduction in skin health, notably a 30% decrease in collagen types I and III within 5 years.To discover natural extracts that stimulate collagen production.We utilized PathwayStudio to analyze protein–protein interactions and identify regulators of essential collagen types. Our study assessed Glycyrrhiza uralensis extract's ability to boost collagen production and enhance dermal density both in vitro and in vivo.PathwayStudio analysis highlighted phytoestrogens including glycyrrhizin, isoliquiritigenin, liquiritigenin, liquiritin, and glabrol, as potential candidates. Liquorice rhizome (G. uralensis), used in traditional Chinese medicine, is rich in phytoestrogens like liquiritigenin. The G. uralensis extract increased collagen I and III gene expression and pro‐collagen I protein levels in human dermal fibroblasts and inhibited UVB and pollution‐induced matrix metalloproteinase‐1 (MMP1) production. In an in vivo study, a topical formulation containing the extract significantly improved dermal density after 56 days, measured by the DUB SkinScanner.These findings suggest G. uralensis extract as a promising agent for enhancing collagen production and skin health, particularly in postmenopausal women. Further research is needed to explore its mechanisms and long‐term effects. [ABSTRACT FROM AUTHOR]

SUMMARY: Licorice is one of the most extensively studied medicinal plants in the world, whose roots and rhizomes have long been used as both a sweetener and an essential component in numerous herbal preparations. However, the genus Glycyrrhiza has a complex composition, and the interspecies chromosomal relationships, origin, and evolution are still largely unclear. Here, we develop a set of whole‐chromosome painting probes that allowed identification of all eight chromosomes of licorice on same metaphase chromosomes. Comparative chromosome painting analyses in seven different Glycyrrhiza species revealed that the genus Glycyrrhiza maintained extraordinarily conserved chromosomal synteny after about 3–12 million years of divergence. No cytologically visible inter‐chromosomal rearrangements were identified in any species. By comparative chromosomal karyotype analyses, we revealed interspecific chromosome evolutionary relationships and dramatic variable chromosomal karyotype after independent divergence and demonstrated that G. prostrate was the most closely related to the ancestral type among the seven Glycyrrhiza species. Furthermore, we also discovered a G. glandulosa seed with distinct triploid‐genome for the first time in China, suggesting the existence of a polyploid evolutionary pathway in the genus Glycyrrhiza, which challenges the previous notion that only diploids of licorice existed in nature. This study expands our knowledge of the chromosome evolution of licorice and will lay an important foundation for the genome origin and evolution studies in the genus Glycyrrhiza. Significance Statement: Whole‐chromosome oligo‐painting in licorice reveals interspecific chromosome evolutionary features, phylogenetic relationships, karyotype variation, and polyploid evolution. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted in order to determine the effect on halitosis and the antibacterial effect against halitosis‐causing bacteria of the mouthwash made of the natural material, Glycyrrhiza uralensis (G. uralensis) extract. Materials and Methods: A randomized, double‐blind, placebo‐controlled study was conducted on 60 patients who visited M dental clinic located in Busan, South Korea, excluding those with systemic disease that may induce halitosis. There were 30 patients classified to the saline gargle group and the remaining 30 patients were classified to the G. uralensis extract gargle group. In addition, their level of halitosis and halitosis‐causing bacteria were measured. They visited the dental clinic on a fasted state at baseline before gargle application (Baseline), immediately after gargle application (Treatment) and 5 days after gargle application (After 5 Days). For clinical indicators, participants were tested for halitosis and bacteria immediately after waking up without brushing their teeth and without hydration. Results: The prevalence of halitosis decreased in the G. uralensis extract gargle group compared to the saline gargle group at Treatment and After 5 Days. In cases with pseudo halitosis, there was a significant decrease in halitosis‐causing bacteria when G. uralensis extract gargle was applied (p < 0.05). Conclusions: It was identified that using a mouthwash made with G. uralensis extract is effective for halitosis improvement and reduction of halitosis‐causing bacteria. Therefore, using a mouthwash containing G. uralensis extract, it will be effective in improving bad breath and oral hygiene will be possible. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy can be a suitable cancer treatment option in certain instances. Here we investigated the potential immunomodulatory effect of oral glycyrrhiza polysaccharides (GCP) on the antitumor function of γδT cells in intestinal epithelial cells in mice. We found that GCP can inhibit tumor growth and was involved in the regulation of systemic immunosuppression. GCP administration also promoted the differentiation of gut epithelia γδT cells into IFN‐γ‐producing subtype through regulation of local cytokines in gut mucosa. GCP administration increased local cytokine levels through gut microbiota and the gut mucosa Toll‐like receptors / nuclear factor kappa‐B pathway. Taken together, our results suggest that GCP might be a suitable candidate for tumor immunotherapy, although further clinical research, including clinical trials, are required to validate these results. [ABSTRACT FROM AUTHOR]

Background. Preeclampsia (PE) is a common obstetric disorder hallmarked by impaired trophoblast invasion and a skew toward an inflammatory immune response. Echinatin, a flavonoid with established anti-inflammatory, antioxidant, and anticancer activities, may offer therapeutic benefits in PE. Our study aimed to investigate the effect of echinatin on preeclampsia in vitro and in vivo and to reveal the potential molecular mechanism of its action. Methods. Eighteen adult female Sprague Dawley rats were randomized into three experimental groups: a PE model group, a PE + echinatin treatment group, and a PE + echinatin treatment group with TLR4 overexpression. Placental tissue CK7 expression was assessed by immunohistochemistry. TUNEL immunofluorescence staining quantified placental cell apoptosis. Cell viability, proliferation, and migration were evaluated using cell counting kit-8, EdU incorporation, and Transwell assays, respectively. Oxidative stress parameters of malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. Flow cytometry determined cell apoptosis and intracellular reactive oxygen species (ROS) levels. Western blotting evaluated the expression of proteins related to the TLR4-MyD88-NF-κB signaling pathway, and the concentrations of TNF-α, IL-6, and IL-18 were measured with ELISA kits. Results. Echinatin mitigated placental damage, reduced apoptosis, and increased CK7 expression. It significantly enhanced HTR-8/SVneo cell viability and migration. Echinatin also counteracted H2O2-induced ROS production and cell death in HTR-8/SVneo cells. Moreover, it inhibited the expression of proteins within the TLR4-MyD88-NF-κB signaling cascade. Overexpression of TLR4 negated echinatin's protective effects. Conclusion. Echinatin exerts protective effects against oxidative stress and inflammation in PE by targeting the TLR4-MyD88-NF-κB pathway, suggesting its therapeutic potential for the management of preeclampsia. [ABSTRACT FROM AUTHOR]

A well‐established mechanism of action for managing pneumonia using Glycyrrhiza is unknown. Using network pharmacology and molecular docking simulations, we investigated the mechanism of action of Glycyrrhiza against pneumonia. To identify the targets of the active components of Glycyrrhiza from the Traditional Chinese Medicine Systems Pharmacology database, oral bioavailability and drug likeness were utilized as indicators. Pneumonia‐associated genes were identified and screened from the databases. Integrated analysis was conducted to elucidate the relationship between the active components of Glycyrrhiza and intersecting genes; a comprehensive Glycyrrhiza active component‐target gene relationship map was constructed. Intersecting genes underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to examine their biological functions. A protein–protein interaction network map was constructed to identify hub genes. Molecular docking simulations were performed to investigate binding interactions between hub genes and their corresponding active components. Of the 96 overlapping genes, topological analysis revealed 10 hub genes. Glycyrrhiza exerts therapeutic effects through a multi‐target and multipathway approach, suggesting a synergistic treatment for pneumonia. MAPK14 showed a favorable binding affinity with most of the active compounds, indicating that MAPK14 and related compounds in Glycyrrhiza have development potential. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA), a major health and economic problem facing older adults worldwide, is a degenerative joint disease. Glycyrrhiza uralensis Fisch. (GC) plays an integral role in many classic Chinese medicine prescriptions for treating knee osteoarthritis. Still, the role of GC in treating KOA is unclear. To explore the pharmacological mechanism of GC against KOA, UPLC‐Q‐TOF/MS was conducted to detect the main compounds in GC. The therapeutic effect of GC on DMM‐induced osteoarthritic mice was assessed by histomorphology, μCT, behavioural tests, and immunohistochemical staining. Network pharmacology and molecular docking were used to predict the potential targets of GC against KOA. The predicted results were verified by immunohistochemical staining Animal experiments showed that GC had a protective effect on DMM‐induced KOA, mainly in the improvement of movement disorders, subchondral bone sclerosis and cartilage damage. A variety of flavonoids and triterpenoids were detected in GC via UPLC‐Q‐TOF/MS, such as Naringenin. Seven core targets (JUN, MAPK3, MAPK1, AKT1, TP53, RELA and STAT3) and three main pathways (IL‐17, NF‐κB and TNF signalling pathways) were discovered through network pharmacology analysis that closely related to inflammatory response. Interestingly, molecular docking results showed that the active ingredient Naringenin had a good binding effect on anti‐inflammatory‐related proteins. In the verification experiment, after the intervention of GC, the expression levels of pp65 and F4/80 inflammatory indicators in the knee joint of KOA model mice were significantly downregulated. GC could improve the inflammatory environment in DMM‐induced osteoarthritic mice thus alleviating the physiological structure and dysfunction of the knee joint. GC might play an important role in the treatment of knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Cervical cancer significantly impacts women's health due to its high mortality rate and increasing prevalence among younger individuals, thereby posing a severe threat. Echinatin is the primary active component of licorice in traditional Chinese medicine. However, studies on its use in cervical cancer treatment are limited. In our study, 198 targets of Echinatin were identified by some databases. Among these, 40 core targets related to cervical cancer were selected. Enrichment analyses revealed that Echinatin operated through genes associated with cell cycle, apoptosis, senescence, and various cancer-related signaling pathways. Differential expression of intersecting targets was verified in the GEO database, and molecular docking also indicated a strong binding capacity between active compounds and identified targets. Moreover, the results of western blot provided further evidence at the protein level. Echinatin hindered the proliferation, migration, and invasion of HeLa and SiHa cells while increasing their apoptosis. This study predicted the potential targets and beneficial effects of Echinatin in cervical cancer treatment, which provides a new avenue for further research into the molecular mechanisms underlying the role of Echinatin in cervical cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Licorice‐induced pseudoaldosteronism has been identified as a side effect of excessive licorice consumption. This condition is often characterized by hypertension, hypokalemia, and hyporeninemic hypoaldosteronism. If left untreated, this condition can lead to severe complications, such as arrhythmia and rhabdomyolysis, which can be life‐threatening. Thus, it is critical to recognize the early symptoms of pseudoaldosteronism to facilitate prompt intervention and effective management. Here, we investigated the frequency of various accompanying symptoms by systematically reviewing case reports of licorice‐induced pseudoaldosteronism not covered in similar studies and comparing findings with the manual on pseudoaldosteronism published by the Ministry of Health, Labour and Welfare (MHLW). Methods: A comprehensive search was conducted using MEDLINE/PubMed to gather relevant human studies published between 1960 and July 2023 and written in English; data focusing on accompanying symptoms were summarized. Results: Thirty‐seven pertinent articles, encompassing 48 case reports (26 females and 1 unreported sex, mean age 64.6 ± 14.6), were identified and scrutinized. The analysis revealed that hypertension was the most prevalent followed by weakness and edema. None of the researched cases reported instances of spasticity or rigidity. Discussion: The study findings identified hypertension and weakness followed by edema as the predominant symptoms associated with pseudoaldosteronism which is in agreement with the MHLW manual. However, we doubt that spasticity, rigidity, and possibly numbness could be noticed by patients and their families as common initial symptoms outlined in the manual. [ABSTRACT FROM AUTHOR]

The aim of this review is to enumerate medicinal plants and their bioactive compounds that may become potential leads in the mitigation of oral submucous fibrosis (OSMF) in the forthcoming future. It is focused on pathophysiology, risk factors, current treatment regimen, potential plant leads, and future therapies for OSMF. Data were extracted from a vast literature survey by using SciFinder, Web of Science, Google Scholar, and PubMed search engines with relevant keywords. Upon literature survey, we found that the phytochemical 'arecoline' present in the areca nut is the main causative agent of OSMF condition. Currently, OSMF is treated by immunomodulatory and anti‐inflammatory agents such as corticosteroids, enzymes (hyaluronidase, chymotrypsin, and collagenase), anti‐inflammatory mediators (isoxsuprine and pentoxifylline), dietary supplements (vitamins, antioxidants, and micronutrients), and anti‐fibrotic cytokines like interferon‐gamma that provides short‐term symptomatic relief to OSMF patients. However, some plant leads have been proven effective in alleviating symptoms and mitigating OSMF, which ultimately improves the quality of OSMF patients' life. We concluded that plant drugs like lycopene, curcumin, Aloe vera, colchicine, and Glycyrrhiza glabra are effective against OSMF in various in vitro and/or clinical studies and are being used by modern and traditional practitioners. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hippodamia variegata (Goeze) (Coleoptera: Coccinellidae), a dominant predatory natural enemy species in cotton‐planting, is a key biological control agent for aphids in China. Our previous study showed that herbivore‐induced plant volatiles (HIPVs) from Glycyrrhiza uralensis (Fisch.) (Fabales: Fabaceae) and Alhagi sparsifolia (Desv.) (Fabales: Fabaceae) plants infested with Aphis atrata (Zhang) (Homoptera: Aphididae), were important semiochemicals for Hippodamia variegata to locate aphids. However, little was known about the varieties and function of active volatiles from HIPVs of the two plant species. RESULTS: In this study, results from gas chromatography‐electroantennography detection (GC‐EAD) demonstrated that seven HIPVs (butyl acrylate, α‐pinene, butyl isobutyrate, β‐pinene, butyl butyrate, 1,3‐diethylbenzene and 1,4‐diethylbenzene) identified from the two damaged plant species elicited antennal responses from Hippodamia variegata. Also, results from gas chromatograph–mass spectrometry (GC–MS) analysis showed that the concentrations of the seven active volatiles were significantly higher than those from corresponding healthy plants. Hippodamia variegata exhibited varying degrees of response to each active volatile in electroantennography (EAG) trials, however, only α‐pinene, butyl isobutyrate, β‐pinene and butyl butyrate significantly attracted Hippodamia variegata in behavioral trials conducted in the laboratory. They also had a better trapping effect on Hippodamia variegata in cotton fields. CONCLUSION: Four active compounds (α‐pinene, butyl isobutyrate, β‐pinene and butyl butyrate) identified from two damaged plant species were considered the most effective HIPVs that attract Hippodamia variegata. These findings provide possibilities for the development of Hippodamia variegata attractants. They also provide a theoretical basis for the biological prevention and control of aphids using Hippodamia variegata. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Licorice (Glycyrrhiza spp.) is a versatile industrial and fodder crop with important medicinal, economic, and forage values. However, little is known about their salt tolerance mechanisms. Here, to investigate the osmotic adjustment mechanism of Glycyrrhiza inflata, a licorice species with excellent adaptation to the severe saline habitat, we compared the growth, the contributions of major osmolytes to osmotic potential, and the expression of genes associated with the accumulation of major osmolytes under salt stress between G. inflata and Glycyrrhiza uralensis, another licorice species mainly grown in mild salinized regions. The results showed that G. inflata displayed stronger salt tolerance than G. uralensis. Compared with G. uralensis, G. inflata accumulated higher contents of proline, betaine, and soluble sugars, as well as Na+ and NO3− in roots, and meanwhile, accumulated higher concentrations of K+ and Cl− in leaves for osmotic adjustment under salt stress. Analysis combining transcriptome and quantitative reverse transcription polymerase chain reaction indicated that compared with that in G. uralensis, the expression of key genes responsible for the biosynthesis of above organic osmolytes, the uptake of NO3−, and the xylem unloading and vacuolar compartmentation of Na+ and NO3− were upregulated in roots of G. inflata under salt stress; meanwhile, higher expression levels of key genes function in xylem loading of K+ and Cl− in roots and vacuolar K+ and Cl− compartmentation in leaves were observed in G. inflata under salt stress. The identified key genes associated with the strong osmotic adjustment capacity of G. inflata could facilitate the genetic improvement of stress tolerance in crops. Core Ideas: Glycyrrhiza inflata possesses a stronger salt tolerance than Glycyrrhiza uralensis.G. inflata accumulates higher contents of proline, betaine, and soluble sugar for osmotic adjustment in roots.G. inflata accumulates higher contents of Na+, NO3− in roots, and K+, Cl− in leaves for osmotic adjustment.G. inflata shows induced expression pattern of key genes related to above solute accumulation under salt stress. [ABSTRACT FROM AUTHOR]

Quality consistency of Glycyrrhiza formula granules is essential for guaranteeing clinical efficacy. However, a suitable method to accurately and conveniently evaluate the consistency of the clinical efficacy of Glycyrrhiza formula granules is currently not available. This study established a method for the simultaneous determination of 12 active components in Glycyrrhiza formula granules using ultra‐high‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight tandem mass spectrometry. The rate of inhibition of cyclooxygenase‐2 by different batches of Glycyrrhiza formula granules was determined. Near‐infrared spectra were collected for different batches of Glycyrrhiza formula granules to detect their biological activity in the inhibition of cyclooxygenase‐2. The quality consistency of the 11 batches of Glycyrrhiza formula granules was evaluated using principal component and correlation analyses. The results showed significant differences in the formula granules of Glycyrrhiza uralensis produced by the different manufacturers. Some differences were also observed among batches of formula granules produced by the same manufacturer. Correlation analysis of the chemical components and cyclooxygenase‐2 activity showed that glycyrrhizic acid, liquiritin, and isoliquiritin were the main active components of Glycyrrhiza. Correlation analysis of the near‐infrared spectra and cyclooxygenase‐2 inhibition activity showed a high correlation between the active components and three characteristic bands: 3383–3995, 4227–4651, and 5315–5878 cm−1. In this study, the main active anti‐inflammatory components of Glycyrrhiza granules were screened. Thus, the near‐infrared spectrum and characteristic active band of multi‐index active components can be used to quickly detect the quality consistency of Glycyrrhiza formula granules, thereby improving the ability to control the quality and consistency of these granules. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effects of dietary Glycyrrhiza polysaccharide (GCP) on growth performance, blood parameters and immunity in weaned piglets. A total of 240 (10.33 ± 0.62 kg body weight) 35‐day‐old (Duroc × Landrace × White) weaned piglets were randomly assigned to four dietary treatments, with six replicate pens per treatment and 10 piglets per pen (five males and five females). The dietary treatments continued for 21 days and comprised a basal diet supplemented with 0 (control group), 500, 1000 and 2000 mg/kg GCP. The results showed that the inclusion of 1000 and 2000 mg/kg GCP increased the average daily gain and decreased the feed conversion rate compared with the control group (p < 0.05). The piglets treated with 500 and 1000 mg/kg GCP had a lower diarrhoeal incidence than the control group (p < 0.05). Moreover, supplementation with 1000 mg/kg GCP increased the counts of white blood cells, neutrophils, red blood cells, and platelets, and elevated alkaline phosphatase, total protein, globulin, glucose, triglyceride, immunoglobulin A, immunoglobulin G, and total antioxidant capacity levels (p < 0.05), and decreased malondialdehyde content compare with the control group (p < 0.05). In addition, relative to the control group, piglets fed 500 and 1000 mg/kg GCP had significantly lower expression of interleukin‐6 mRNA in spleen (p < 0.05). Our results indicate that dietary supplementation with GCP can improve growth performance, blood parameters and immunity in weaned piglets. Our study suggests that adding 1000 mg/kg GCP to the diet had the most beneficial effect. [ABSTRACT FROM AUTHOR]

The liquorice tribe Glycyrrhizeae is a leguminous herbaceous group of plants comprised of the genera Glycyrrhiza and Glycyrrhizopsis. Some Glycyrrhiza taxa contain glycyrrhizin, a pharmacologically significant sweet substance that also has applications in crafting industrial materials. Here, we utilized an expanded taxon sampling of Glycyrrhizeae to reconstruct the phylogenetic relationships in the tribe based on genome skimming data, including whole chloroplast genomes, nuclear ribosomal DNA, and low‐copy nuclear DNA. We also launched machine learning analysis (MLA) for one species pair with controversial taxonomic boundary. The integrated results indicated Glycyrrhizopsis should be split from Glycyrrhiza, while the former genus Meristotropis should be treated as part of Glycyrrhiza. Glycyrrhizopsis includes two species, Glycyrrhizopsis asymmetrica and Glycyrrhizopsis flavescens, and we recognize 13 species in Glycyrrhiza: Glycyrrhiza acanthocarpa, Glycyrrhiza astragalina, Glycyrrhiza bucharica, Glycyrrhiza echinata, Glycyrrhiza foetida, Glycyrrhiza glabra, Glycyrrhiza gontscharovii, Glycyrrhiza lepidota, Glycyrrhiza macedonica, Glycyrrhiza pallidiflora, Glycyrrhiza squamulosa, Glycyrrhiza triphylla, and Glycyrrhiza yunnanensis. We propose a broader G. glabra that includes former Glycyrrhiza aspera, G. glabra s.s., Glycyrrhiza inflata, and Glycyrrhiza uralensis, and represents the glycyrrhizin‐contained medicinal group. Our ancestral state inferences show the ancestor of Glycyrrhiza lacked glycyrrhizin, and the presence of glycyrrhizin evolved twice within Glycyrrhiza during the last one million years. Our integrative phylogenomics‐MLA study not only provides new insights into long‐standing taxonomic controversies of Glycyrrhizeae, but also represents a useful approach for future taxonomic studies on other plant taxa. [ABSTRACT FROM AUTHOR]

Introduction: During the ongoing COVID‐19 outbreak, face mask use has increased and became a part of our daily lives. While wearing, prolonged contact time and microenvironmental change profoundly lead to an acne flare‐up, defined as "maskne." Aims: We aimed to assess the efficacy and safety of snail secretion filtrate, Calendula officinalis, and Glycyrrhiza glaba root extract combination serum (SCGS) in treating the maskne. Methods: This was a randomized, double‐blind, placebo‐controlled trial study. This study enrolled 66 participants with mild‐to‐moderate maskne. The SCGS and placebo were randomly assigned for participants to use twice daily for 12 weeks. Percentage change of acne lesion count, acne severity by Investigator Global Evaluation Acne (IGEA), sebum levels, corneometry levels, transepidermal water loss (TEWL), erythema score by Visia®, and adverse events were evaluated 4‐weekly at baseline to Week 12. At Week 12, all participants evaluated their satisfaction scores using a 10‐point visual analog scale (VAS). Results: In the mask‐covered area, the percent reduction in inflammatory acne lesions from the treatment group was significantly greater than the placebo group at all time points (coefficient of percentage change of inflammatory lesions = −33.89 [95% CI −65.24, −2.53]; p = 0.03). Also, a subgroup analysis with participants using concurrent acne treatments revealed similar results (12 participants, coefficient = −50.30 [95% −88.65, −11.95]; p = 0.01). However, there were no significant differences in non‐inflammatory lesions, all skin biophysics, and VAS between groups. Adverse events were mild and occurred in a few cases in both groups. Conclusions: The SCGS could significantly improve inflammatory acne lesions and had a favorable tolerability profile, suggesting its role as an adjunctive treatment in maskne. [ABSTRACT FROM AUTHOR]

Summary: Glycyrrhiza uralensis Fisch is a medicinal plant widely used to treat multiple diseases in Europe and Asia, and its efficacy largely depends on liquiritin and glycyrrhizic acid. The regulatory pattern responsible for the difference in efficacy between wild and cultivated G. uralensis remains largely undetermined. Here, we collected roots and rhizosphere soils from wild (WT) G. uralensis as well as those farmed for 1 year (C1) and 3 years (C3), generated metabolite and transcript data for roots, microbiota data for rhizospheres and conducted comprehensive multi‐omics analyses. We updated gene structures for all 40 091 genes in G. uralensis, and based on 52 differentially expressed genes, we charted the route‐map of both liquiritin and glycyrrhizic acid biosynthesis, with genes BAS, CYP72A154 and CYP88D6 critical for glycyrrhizic acid biosynthesis being significantly expressed higher in wild G. uralensis than in cultivated G. uralensis. Additionally, multi‐omics network analysis identified that Lysobacter was strongly associated with CYP72A154, which was required for glycyrrhizic acid biosynthesis. Finally, we developed a holistic multi‐omics regulation model that confirmed the importance of rhizosphere microbial community structure in liquiritin accumulation. This study thoroughly decoded the key regulatory mechanisms of liquiritin and glycyrrhizic acid, and provided new insights into the interactions of the plant's key metabolites with its transcriptome, rhizosphere microbes and environment, which would guide future cultivation of G. uralensis. [ABSTRACT FROM AUTHOR]

Bread is one of the highest-selling food products throughout the world. Lots of demand arose from the bread producers by the consumers to convert the traditional bread into functional food. In this study, normal bread was converted to functional herbal bread by infusing it with extracts of Glycyrrhiza glabra. The functional components of the Glycyrrhiza glabra were analyzed by liquid chromatography-mass spectroscopy (LCMS). The antioxidant study revealed that the extract has high antioxidant potency. The present study also investigated the antidiabetic potency of the extract. Bread is fortified with various percentages of Glycyrrhiza glabra, such as 2, 4, and 6. The fortified bread was analyzed for various sensory and taste parameters. Biochemical assays such as the in vitro digestibility test and glycaemic index suggest that fortified bread reduces the glycaemic index. From the study, it was inferred that 6% of infused bread was found to have high potency as a functional food when compared to 2 and 4%. From the above study, it was suggested that fortified bread reduces the glycaemic index and is best suited for diabetic people and diet watchers. [ABSTRACT FROM AUTHOR]

A method based on elemental fingerprint, stable isotopic analysis and combined with chemometrics was proposed to trace the geographical origins of Licorice (Glycyrrhiza uralensis Fisch) from 37 producing areas. For elemental fingerprint, the levels of 15 elements, including Ca, Cu, Mg, Pb, Zn, Sr, Mn, Se, Cd, Fe, Na, Al, Cr, Co, and K, were analyzed by inductively coupled plasma atomic emission spectrometry (ICP-AES). Three stable isotopes, including δ13C, δ15N, and δ18O, were measured using an isotope-ratio mass spectrometer (IRMS). For fine classification, three multiclass strategies, including the traditional one-versus-rest (OVR) and one-versus-one (OVO) strategies and a new ensemble strategy (ES), were combined with two binary classifiers, partial least squares discriminant analysis (PLSDA) and least squares support vector machines (LS-SVM). As a result, ES-PLSDA and ES-LS-SVM achieved 0.929 and 0.921 classification accuracy of GUF samples from the 37 origins. The results show that element fingerprint and stable isotope combined with chemometrics is an effective method for GUF traceability and provides a new idea for the geographical traceability of Chinese herbal medicine. [ABSTRACT FROM AUTHOR]

Introduction. The importance of women's health and the quality of life after menopause is a critical issue. To prevent disability and menopause complications as well as avoid the side effects of hormone replacement therapy (HRT), in this study, licorice hydroalcoholic extract (Glycyrrhiza uralensis roots) was evaluated as a natural remedy. Methods. Seventy-two female Sprague-Dawley rats were divided into six groups: control group, Sham-operated group, Glycyrrhiza (Gly) 30% group, and ovariectomized group as well as two ovariectomized groups treated with Gly 10% and Gly 30%. Normal saline and different treatments were administered orally for 8 weeks. At the end of the study, calcium, alkaline phosphatase, estrogen, and progesterone levels in the ovariectomized rats were determined. Moreover, the stereological and histopathological changes in uterine tissue in all groups were determined. Phytochemical analyses were also performed to determine the total phenolic content and antioxidant potential of the extract. Result. The hydroalcoholic extract of licorice root exhibited considerable effect to improve calcium, estrogen, and progesterone levels in the ovariectomized rats. Also, hydroalcoholic extract of licorice root successfully decreases the amount of alkaline phosphatase (ALP) level. The stereological and histopathological findings confirmed the therapeutic potential of this extract. The considerable effects of hydroalcoholic extract of licorice root could be due to high amounts of phytoestrogens with similar estrogen-like structures. Considerable total phenolic content and antioxidant activity were also seen in licorice root extract. Conclusion. Hydroalcoholic extract of licorice root due to containing high amounts of phytoestrogens with similar chemical structures to estradiol notably improves biochemical parameters as well as stereological and histopathological markers of uterine tissues in ovariectomy rats, so it could be a potential agent for prevention and/or treatment as hormone replacement therapy in healthy middle-aged and/or older women. [ABSTRACT FROM AUTHOR]

Singapore grouper iridovirus (SGIV) is a serious pathogen that negatively impacts grouper aquaculture. Because of its 90% fatality rate, effective medications that control SGIV infection are urgently needed. Glycyrrhiza uralensis is a well‐known medicinal plant that contains active ingredients with antiviral, antibacterial, and other biological activities. In this study, we evaluated the application of G. uralensis components against SGIV infection. The safe working concentrations of G. uralensis components, which were identified by light microscope observation and CCK‐8 detection, were as follows: aqueous extract (GUF) ≤ 10 mg/ml, glycyrrhizin ≤ 100 μg/ml, glycyrrhetinic acid ≤ 50 μg/ml, liquiritin ≤ 25 μg/ml, isoliquiritigenin ≤ 10 μg/ml, and liquiritigenin ≤ 10 μg/ml. The ingredients did not have significant effects against SGIV infection, whereas GUF showed significant anti‐SGIV infection activity in a concentration‐dependent manner, and it also destroyed the structure of virus particles. Therefore, GUF might impact the binding of virus particles to cell receptors and the stage of virus replication in host cells. These results show that G. uralensis aqueous extracts have good anti‐SGIV effects and great potential for treating SGIV infection. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy (TCM) causes QT interval prolongation, potentially leading to a fatal arrhythmia. We report the first case of TCM associated with licorice‐induced pseudoaldosteronism causing fatal arrhythmia in an older patient on polypharmacy including yokukansan (TJ‐54) and galantamine. Polypharmacy should be resolved to prevent unexpected adverse events in older patients. [ABSTRACT FROM AUTHOR]

Growing evidences indicate that high glucose toxicity‐associated fibrotic effects play a pivotal role in diabetic nephropathy (DN). Tubular epithelial‐myofibroblast transdifferentiation is a major hallmark of renal fibrosis event under diabetic stress. Roots of Glycyrrhiza uralensis (Radix glycyrrhizae) used as a sweetener and traditional Chinese medicine possess high potential for renal protection. In this study, a cell model for high glucose (HG) injury with HK‐2 renal proximal tubular epithelial cell line and a type‐II‐diabetes model with Apoeem1/Narl/Narl mice was established and the beneficial effects of aqueous R. glycyrrhizae extract (RGE) was investigated. RGE‐induced regulation on the high glucose‐induced excessive production of TGF‐β1 and the Smad/Stat3 mechanisms of renal fibrosis were determined. HK‐2 cells were challenged with 45 mM of high glucose for 48 hr. Following high glucose challenge, the cells were treated with 0.5, 1, and 1.5 mg/ml concentrations of RGE. The effect of RGE on DN was determined using high fructose diet‐induced type‐II‐diabetes in Apoeem1/Narl/Narl mice models. Our results showed that RGE suppressed the expression of HG‐induced TGFβ signaling and associated fibrosis mechanism better than the pharmacological drug acarbose. These data suggest that RGE as a potential herbal supplement in attenuating fibrosis‐associated diabetic nephropathy and a potential agent in diabetes treatments. [ABSTRACT FROM AUTHOR]

Aim: The incidence of adverse events associated with Kampo prescriptions is still unclear. We retrospectively studied the adverse events in 1104 patients prescribed jidabokuippo (JDI) to examine the safety of JDI based on adverse event rate. Methods: Adverse events to JDI treatment were observed in 14 patients (adverse event group) while 1090 had none (non‐adverse event group). We compared age, sex, comorbidity, dose, dosing period, concomitant use of Kampo prescription, and concomitant use of analgesics between these two groups. Results: The adverse event rate was 1.3%. The most common adverse event was diarrhea caused by rhubarb rhizome (0.6%). The adverse event rate of Glycyrrhiza‐induced pseudoaldosteronism was 0.3%. All symptoms improved on JDI withdrawal or taking JDI after meals. Median duration of JDI was significantly shorter in the adverse event group than in the non‐adverse event group (P = 0.0141). Conclusion: The adverse event rate associated with JDI use was low and onset was relatively rapid. We can further reduce this adverse event rate by paying attention to the pharmacological action of rhubarb rhizome and Glycyrrhiza root. [ABSTRACT FROM AUTHOR]

This study was conducted to explore the effects of ethanolic extracts of leaves of Glycyrrhiza uralensis on the growth and nutritional quality of Chinese flowering cabbage (Brassica rapa subsp. parachinensis) under field conditions. Preliminary greenhouse experiments were carried out with different concentrations of G. uralensis extracts to select the suitable dose for field studies. An extract concentration of 12.5 g/L was selected based on relative growth rate analysis and increase in photosynthetic pigment biosynthesis. Shoot length, shoot fresh weight and dry weight, number of leaves, and marketable value of Chinese flowering cabbage plants were significantly increased in the field trials with foliar application of G. uralensis leaves extracts at a concentration of 12.5 g/L. This biotic elicitor also enhanced the total phenolic and flavonoid contents, with optimal values increasing by 18.76% and 22.43%, respectively, compared with the control under field conditions. The total glucosinolate content was effectively increased (from 11.21 to 15.37 μmol·g−1 DW sinigrin equivalents), particularly 4-methoxyglucobrassicin (from 4.31 to 6.72 μmol·g−1 DW sinigrin equivalents) and glucoalyssin (from 0.14 to 0.19 μmol·g−1 DW sinigrin equivalents) compared with the control plants in field trials. Overall, foliar application of leaf extracts of G. uralensis can markedly increase the growth of Chinese flowering cabbage and enhance its medicinal and nutritional quality in the fields. [ABSTRACT FROM AUTHOR]

Licorice is the dried roots and rhizomes of various species of the genus Glycyrrhiza (Fabaceae) that have been used in folk medicine from ancient times. Many important research projects have established several beneficial effects for this medicinal herb, including antiinflammatory, antimicrobial, antiviral, antiprotozoal, antioxidant, antihyperglycemic, antihyperlipidemic, hepatoprotective, and neuroprotective. Licorice contains important bioactive components, such as glycyrrhizin (glycyrrhizic, glycyrrhizinic acid), liquiritigenin, liquiritin, and glycyrrhetinic acid. The protective effects of licorice and its main chemical components against toxins and toxicants in several organs including the brain, heart, liver, kidney, and lung have been shown. In this comprehensive review article, the protective effects of these constituents against natural, industrial, environmental, and chemical toxicities with attention on the cellular and molecular mechanism are introduced. Also, it has been revealed that this plant and its main compounds can inhibit the toxicity of different toxins by the antioxidant, antiinflammatory, and anti‐apoptotic properties as well as the modulation of Inhibitor of kappaB kinase (IKK), Extracellular signal‑regulated protein kinase1/2 (ERK1/2), p38, inducible nitric oxide synthase, and nuclear factor‐κB (NF‐κB) signaling pathways. More high‐quality investigations in both experimental and clinical studies need to firmly establish the efficacy of licorice and its main constituents against toxic agents. [ABSTRACT FROM AUTHOR]

Objective: To test the effectiveness of a dentifrice containing the turmeric and licorice extract compared to a control for preventing plaque and gingivitis over a four‐month period. Material and methods: Ninety (non‐dental) participants with moderate gingival inflammation (≥ 40%) were selected. The triple blind study consisted of two phases, namely at first a 3‐week pre‐experimental phase of using an oxygenating and chlorhexidine (CHX) mouthrinse. Secondly, a 4‐month experimental period in which participants were randomly assigned to a test or control group. All were instructed to brush their teeth twice daily for 2 minutes with their assigned dentifrice. Gingival bleeding (BI), plaque (PI) and gingivitis (GI) were assessed. Results: Eighty participants completed the protocol. At the first assessment in the pre‐experimental phase, the mean scores of all indices showed no differences for the two groups. At the second session, the values of all three parameters had decreased significantly (p < 0.001). At the last session, the BI values were 0.52(0.25) for the test group and 0.56(0.25) for the control, the mean GI was 0.27(0.17) for the test group and 0.31(0.16) for the control, and for PI the scores were 1.89(0.46) for the test group and 1.98(0.43) for the control group. Statistical comparison of the scores for the two groups at each stage of the study showed no significant difference for any of the parameters. Conclusion: Within the limits of the current study design, dentifrice formulation and concentration of turmeric/licorice extracts, the results show that the adjuvant effect of the natural ingredients in the test dentifrice was not evident on clinical parameters of gingivitis and plaque. [ABSTRACT FROM AUTHOR]

Viral hemorrhagic septicemia causes significant economic losses for olive flounder (Paralichthys olivaceus) farms in Korea. The purpose of this study was to optimize extraction conditions for licorice (Glycyrrhiza uralensis roots) extract using the 23 full factorial design and thereby optimizing the antiviral activity against viral hemorrhagic septicemia virus (VHSV). The optimum conditions were ethanol concentration 100%, extraction temperature 40˚C and extraction time 5 h. Optimized extract (OE) prepared under these conditions showed potent antiviral activity against VHSV with a 95.2% CPE reduction at 75 µg/ml of OE, and a predictive capacity of 94%. Fish that received 250 and 500 mg/kg body weight/day of OE as either preventive or therapeutic administration had higher relative survival rates of 25 to 62.5% (p < 0.05) compared with VHSV‐infected control group. Active components of licorice, glycyrrhizin (GL) and glycyrrhetinic acid (GLA) showed antiviral activity against VHSV with 50% effective concentration values of 100.6 and 26.0 µM respectively. Besides, time course studies by plaque reduction assay showed that GLA exhibited a direct virucidal effect on VHSV or may inhibit the penetration and internalization of the virus to cells. These results suggest that OE may be used as an anti‐VHSV agent in aquaculture. [ABSTRACT FROM AUTHOR]

In times of health crisis, including the current COVID‐19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday self‐care and health care, but, since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical, and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well‐being. Newly emerging viral infections, specifically COVID‐19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, especially regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and antiinflammatory effects include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate‐yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections. [ABSTRACT FROM AUTHOR]

Licorice is a traditional Chinese medicine that has been used for a long time in China and still in great use today. The effect of licorice on tonifying spleen and invigorating qi has been proved for thousands of years, but the material basis of its effect is not clear. In this paper, we established the fingerprints of 21 batches of licorice collected from different origins in China with High-Performance Liquid Chromatography (HPLC) to identify the common peaks. Its effect of tonifying spleen and invigorating qi was confirmed through a series of praxiology experiments. The spectrum-effect relationship between HPLC fingerprints and its effect of tonifying spleen and invigorating qi of licorice was examined by gray relational analysis and partial least squares regression analysis. Results showed that the effect of licorice on tonifying spleen and invigorating qi resulted from various compounds and peaks. X2–X6 is presumed to be the main pharmacological substance base. This research successfully identified the spectrum-effect relationship between HPLC fingerprints and the effect of licorice on tonifying spleen and invigorating qi. The research method based on the spectrum-effect relationship helps provide new research ideas and strategies for the study of the basis of the medicinal materials and quality control of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

It has been reported that drought stress adversely affects the growth and yield of Glycyrrhiza uralensis, Chinese liquorice, in agricultural production. Bacillus pumilus, an important plant growth‐promoting bacterium, play a significant role in improving plant tolerance to abiotic stress. However, the role of Bacillus pumilus G5 in resisting drought stress is largely unknown. In the present study, we found that drought stress significantly inhibited the growth and reduced the biomass of G. uralensis seedlings by restraining C‐ and N‐metabolism, while this could be effectively reversed by B. pumilus G5 inoculation. Specifically, B. pumilus G5 significantly increased the content of primary metabolites such as soluble sugar, soluble protein, and free amino acids by regulating the C and N metabolic processes in G. uralensis seedlings. Moreover, B. pumilus G5 increased the content of glycyrrhizic acid, one of the important secondary metabolites, likely mediated through the increased content of primary metabolites and by recovering the expression of three key enzymes, HMGR, SQS, and β‐AS, in the biosynthesis of glycyrrhizic acid. Interestingly, the regulating effect of B. pumilus G5 inoculation on promoting the accumulation of glycyrrhizic acid and increasing the expression of synthesis‐related genes is spatially selective. In summary, our findings suggest that B. pumilus G5 could alleviate adverse effects induced by drought stress on the growth of G. uralensis seedlings by regulating C‐ and N‐metabolisms that further triggered the accumulation of secondary metabolites, and this finally improved the drought tolerance of cultivated G. uralensis seedlings. [ABSTRACT FROM AUTHOR]

Objective. To establish a method for simultaneous determination of liquiritin, liquiritigenin, and isoliquiritinin glycyrrhizin using hydrogen nuclear magnetic resonance quantitative technology (1H-qNMR). Methodology. Deuterated dimethyl sulfoxide was used as the solvent, and dichloromethane was used as the internal standard. The probe temperature was 298.0 K, the pulse sequence was Zg30, the number of scans was 16, and relaxation delay (D1) was 10 s. Quantitative characteristic signal peaks were δ 4.891∼4.878 ppm, δ 8.187∼8.172 ppm, and δ 6.790∼6.776 ppm for liquiritin, isoliquiritin, and liquiritigenin, respectively. Results. The experimental result showed that the content of flavonoids in Licorice, from Chifeng, Inner Mongolia, was the highest. Conclusion. In this study, a new method for determination of three flavonoids in Licorice using 1H-qNMR was established. This experimental method has the advantages of accuracy, efficiency, and economy. It lays a foundation for the study on the determination of flavonoids content in licorice by proton nuclear magnetic resonance spectroscopy. [ABSTRACT FROM AUTHOR]

Glycyrrhiza uralensis Fisch. is used in large quantities in traditional Chinese medicine. It contains flavonoids, saponins, and polysaccharides, with flavonoids being the main active ingredients. In this study, flavonoids were isolated from the roots of Glycyrrhiza uralensis Fisch. grown in 21 areas in China by water extraction, alcohol precipitation, polyamide resin separation, and other methods. Fingerprints were established by high performance liquid chromatography (HPLC). There were 15 common peaks in the fingerprints by similarity evaluations of the chromatographic fingerprints. The spectrum-effect relationships between the HPLC fingerprints and pharmacological activities of flavonoids in G. uralensis Fisch., including the heat clearing, detoxifying effects, cough relief, and phlegm elimination effects, were assessed by gray relational analysis and partial least squares regression. After HPLC-quadrupole time-of-flight mass spectrometry and standard comparison, these five identified compounds (liquiritin apioside, neoisoliquiritin, licochalcone A, licochalcone B, and licochalcone C) could be used to evaluate licorice quality with regard to its efficacy. This research provides a scientific basis for improving licorice quality and also establishes a model for modernization of traditional Chinese medicines. [ABSTRACT FROM AUTHOR]

Radix Aconiti Lateralis Preparata (Fuzi) is a traditional Chinese medicine. Its alkaloids are both cardiotonic and cardiotoxic; however, the underlying mechanisms are unclear. Compatibility testing and processing are the primary approaches used to reduce the toxicity of aconite preparations. The purpose of this study was to compare the effects of crude Fuzi (CFZ), CFZ combined with Glycyrrhiza (Gancao) (CFZ+GC), and prepared materials of CFZ (PFZ) on heart failure (HF) in C57BL/6J mice and explore the potential mechanisms of action of CFZ. Transverse aortic constriction (TAC) was used to generate the HF state, and CFZ (1.5 g·mL−1), PFZ (1.5 g·mL−1), or CFZ+GC (1.8 g·mL−1) was orally administered to the HF-induced mice daily. For the subsequent 8 weeks, hemodynamic indicators, ventricular pressure indices, and mass indices were evaluated, and histopathological imaging was performed. CFZ, CFZ+GC, and PFZ significantly improved left ventricular function and structure and reduced myocardial damage. CFZ+GC was more effective than CFZ and PFZ, whereas CFZ had higher toxicity than CFZ+GC and PFZ. CFZ and CFZ+GC attenuated ischemia-induced inflammatory responses and also inhibited Toll-like receptor-4 (TLR4) and nuclear factor kappa beta (NF-κB) action in the heart. Moreover, mass spectrometry analysis revealed a decrease in the levels of toxic components of CFZ+GC, whereas those of the protective components were increased. This study suggested that GC reduces the toxicity and increases the efficacy of CFZ on HF induced by TAC. Furthermore, GC+CFZ reduces the risk of HF by ameliorating the inflammation response, which might be partially related to the inhibition of the TLR4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

We successfully extracted isoliquiritigenin from Glycyrrhiza uralensis through the utilization of an ionic liquid-based ultrasonic-assisted extraction (ILUAE) approach. Briefly, we utilized the solution of 1-butyl-3-methylimidazolium bromide ([BMIM]Br) as solvent and optimized key ILUAE parameters such as solid-liquid ratios, concentrations of ionic liquids, and the times of ultrasonication. Based on a single-factor experiment, we utilized the response surface method (RSM) approach to optimize the extraction procedure. The approach revealed that the optimal energy consumption time was 120 min, with the ultrasonic extraction temperature of 60°C. Using these optimized parameters together with the solid-liquid ratio (dried G. uralensis powder: [BMIM]Br of 0.3 mol/L) of 1 : 16.163 and the [BMIM]Br of 0.3 mol/L, we achieved a 0.665 mg/g extraction yield. Overall, these findings thus indicate that we were able to effectively use ILUAE as an efficient approach to reliably extract isoliquiritigenin in a reproducible and environmentally friendly manner. [ABSTRACT FROM AUTHOR]

Glycyrrhiza uralensis Fisch., known as licorice, is one of the most famous traditional Chinese medicines. In this study, we perform a metabolome analysis using liquid chromatography–tandem mass spectrometry to assign bioactive components in different parts of licorice from different geographical origins in Gansu province of China. Sixteen potential biomarkers of taproots from different geographical origins were annotated, such as glycycoumarin, gancaonin Z, licoricone, and dihydroxy kanzonol H mainly exist in the sample of Jiuquan; neoliquiritin, 6′‐acetylliquiritin, licochalcone B, isolicoflavonol, glycyrol, and methylated uralenin mainly exist in Glycyrrhiza uralensis from Lanzhou; gancaonin L, uralenin, and glycybridin I mainly exist in licorice from Wuwei for the first time. [ABSTRACT FROM AUTHOR]

Patients with non-small-cell lung cancer (NSCLC) containing epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to tyrosine kinase inhibitor gefitinib; however, the treatment is less effective over time. Gefitinib resistance mechanisms include MET gene amplification. A therapeutic strategy targeting MET as well as EGFR can overcome resistance to gefitinib. In the present study we identified Echinatin (Ecn), a characteristic chalcone in licorice, which inhibited both EGFR and MET and strongly altered NSCLC cell growth. The antitumor efficacy of Ecn against gefitinib-sensitive or -resistant NSCLC cells with EGFR mutations and MET amplification was confirmed by suppressing cell proliferation and anchorage-independent colony growth. During the targeting of EGFR and MET, Ecn significantly blocked the kinase activity, which was validated with competitive ATP binding. Inhibition of EGFR and MET by Ecn decreases the phosphorylation of downstream target proteins ERBB3, AKT and ERK compared with total protein expression or control. Ecn induced the G2/M cell cycle arrest, and apoptosis via the intrinsic pathway of caspase-dependent activation. Ecn induced ROS production and GRP78, CHOP, DR5 and DR4 expression as well as depolarized the mitochondria membrane potential. Therefore, our results suggest that Ecn is a promising therapeutic agent in NSCLC therapy. [ABSTRACT FROM AUTHOR]

Pacific white shrimp is the major farmed shrimp species in the world. It is known to be very sensitive to the environmental and management changes such as intensification, which is one of the primary necessities to increase shrimp production, but represents a stressful condition, and needs to be managed properly to diminish its negative effects in aquaculture. In this study, juvenile Pacific white shrimp were fed diets supplementing with equal quantities of Astragalus membranaceus, Codonopsis pilosula and Glycyrrhiza uralensis extracts in different concentrations (0, 1.0, 2.0 and 3.0 g/kg) for 8 weeks. We subsequently estimated the effects of supplemented diets on growth performance, haematological parameters, and histological changes of hepatopancreas. Results revealed that the supplemented mixture had no benefits on growth and survival rate, but had favourable effects on haemocyte count, number of granulocytes, and hemocyanin concentration in the haemolymph (p > 0.05). We observed that R cells and B cells were increased in hepatopancreatic tubules of shrimps fed on supplemented diets. Besides, a diet containing 2.0 g/kg of extract mixture maintained the decreased levels of alanine aminotransferase (p < 0.05) and aspartate aminotransferase (p > 0.05). Among the used concentrations, 2.0 g/kg seemed to be the most suitable concentration. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA), a mycotoxin constituent of a range of food commodities, including coffee, wine, beer, grains, and spices, exerts toxicological and pathological effects in vivo, such as nephrotoxicity, hepatotoxicity, and immunotoxicity. In a previous report, we highlighted the potential of OTA to induce apoptosis via reactive oxygen species (ROS) generation in mouse blastocysts that led to impaired preimplantation and postimplantation embryo development in vitro and in vivo. Here, we have shown that liquiritigenin (LQ), a type of flavonoid isolated from Glycyrrhiza radix, effectively protects against OTA‐mediated apoptosis and inhibition of cell proliferation in mouse blastocysts. Preincubation of blastocysts with LQ clearly prevented OTA‐triggered impairment of preimplantation and postimplantation embryonic development and fetal weight loss, both in vitro and in vivo. Detailed investigation of regulatory mechanisms revealed that OTA mediated apoptosis and embryotoxicity through ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase‐9 and caspase‐3, which were effectively prevented by LQ. The embryotoxic effects of OTA were further validated in an animal model in vivo. Intravenous injection of dams with OTA (3 mg/kg/day) led to apoptosis of blastocysts, impairment of embryonic development from zygote to blastocyst stage and decrease in day 18 fetal weight. Notably, preinjection of dams with LQ (5 mg/kg/day) effectively prevented OTA‐induced apoptosis and toxic effects on embryo development. Our collective results clearly demonstrate that OTA exposure via injection has the potential to damage preimplantation and postimplantation embryonic development against which LQ has a protective effect. [ABSTRACT FROM AUTHOR]

Background and Purpose: Liquorice is the root of Glycyrrhiza glabra, which is a popular food in Europe and China that has previously shown benefits for skeletal fatigue and nutrient metabolism. However, the mechanism and active ingredients remain largely unclear. The aim of this study was to investigate the active ingredients of liquorice for muscle wasting and elucidate the underlying mechanisms.Experimental Approach: RNA-Seq and bioinformatics analysis were applied to predict the main target of liquorice. A machine learning model and a docking tool were used to predict active ingredients. Isotope labelling experiments, immunostaining, Western blots, qRT-PCR, ChIP-PCR and luciferase reporters were utilized to test the pharmacological effects in vitro and in vivo. The reverse effects were verified through recombination-based overexpression.Key Results: The liposoluble constituents of liquorice improved muscle wasting by inhibiting protein catabolism and fibre atrophy. We further identified FoxO1 as the target of liposoluble constituents of liquorice. In addition, hispaglabridin B (HB) was predicted as an inhibitor of FoxO1. Further studies determined that HB improved muscle wasting by inhibiting catabolism in vivo and in vitro. HB also markedly suppressed the transcriptional activity of FoxO1, with decreased expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1.Conclusions and Implications: HB can serve as a novel natural food extract for preventing muscle wasting in chronic kidney disease and possibly other catabolic conditions. [ABSTRACT FROM AUTHOR]

Objectives: Colon cancer is the major health disease related with high mortality. Glycyrrhizic acid (GA) is an active constituent of licorice with anti‐inflammatory and anticarcinogenesis effects. We investigated the chemopreventive potential of GA against 1,2‐dimethylhydrazine (DMH)‐induced colon tumorigenesis in Wistar rats. Methods: Glycyrrhizic acid was administered orally at the dose of 15 mg/kg b.wt. and DMH was administered at the dose of 20 mg/kg b.wt. once a week for first 15 weeks. All the rats were euthanized after 30 weeks. GA supplementation significantly inhibited the tumor incidence and multiplicity. Results: Glycyrrhizic acid treatment reduced the expression of Ki‐67, proliferating cell nuclear antigen (PCNA), nuclear factor‐kappa B (NF‐kB), cyclooxygenase‐2 (COX‐2), induced nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) while enhanced the expression of p53, connexin‐43, b‐cell lymphoma‐2 (Bcl‐2), survivin, and cleaved caspase‐3. Glycyrrhizic acid also significantly ameliorated DMH‐induced decreased activities of caspase‐9 and caspase‐3. Furthermore, GA treatment reduced mast cells infiltration, attenuated the shifting of sialomucin to sulphomucin as well the levels of pro‐inflammatory cytokines. Conclusion: The findings of the study suggest that GA has chemopreventive potential against DMH‐induced colon tumorigenesis plausibly through the attenuation of hyperproliferative responses, pro‐inflammatory cytokines level, inflammatory and angiogenic markers, and apoptotic responses. [ABSTRACT FROM AUTHOR]

In the last years, consumers are paying much more attention to natural medicines and principles, mainly due to the general sense that natural compounds are safe. On the other hand, there is a growing demand by industry for plants used in traditional medicine that could be incorporated in foods, nutraceuticals, cosmetics, or even pharmaceuticals. Glycyrrhiza glabra Linn. belongs to the Fabaceae family and has been recognized since ancient times for its ethnopharmacological values. This plant contains different phytocompounds, such as glycyrrhizin, 18β-glycyrrhetinic acid, glabrin A and B, and isoflavones, that have demonstrated various pharmacological activities. Pharmacological experiments have demonstrated that different extracts and pure compounds from this species exhibit a broad range of biological properties, including antibacterial, anti-inflammatory, antiviral, antioxidant, and antidiabetic activities. A few toxicological studies have reported some concerns. This review addresses all those issues and focuses on the pharmacological activities reported for G. glabra. Therefore, an updated, critical, and extensive overview on the current knowledge of G. glabra composition and biological activities is provided here in order to explore its therapeutic potential and future challenges to be utilized for the formulation of new products that will contribute to human well-being. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: The laxative action of daiokanzoto (a compound containing rhubarb and glycyrrhiza) is thought to be due to sennoside A, an ingredient in rhubarb. Glycyrrhizin, which has anti‐inflammatory effects, is the main ingredient in glycyrrhiza, and it alleviates adverse reactions, such as abdominal pain and painful defecation, due to rhubarb. No consensus has been reached, however, on why daiokanzoto contains glycyrrhiza. We found that sennoside A exerts a laxative action by decreasing aquaporin‐3 (AQP3) expression through the activation of macrophages in the colon. This study analyzed the effect of glycyrrhizin on the laxative action of sennoside A focusing on AQP3 expression. Methods: Sennoside A, glycyrrhizin, or a combination of both were given orally to rats, and diarrhea severity was assessed. The expression of AQP3, inflammatory cytokines, and cyclo‐oxygenase (COX) was analyzed. Results: Although diarrhea occurred when sennoside A and glycyrrhizin were given together orally, it was less severe than when sennoside A was used alone, and, correspondingly, only sennoside A inhibited AQP3 expression to a greater extent than the combination of both drugs. When glycyrrhizin was given concomitantly, the sennoside A‐induced increased expression of pro‐inflammatory cytokines and COX‐2 was suppressed. Conclusions: The laxative action of sennoside A and the decreased expression of AQP3 were suppressed when sennoside A and glycyrrhizin were given concomitantly, likely due to the anti‐inflammatory effects of glycyrrhizin. This indicates that glycyrrhizin both attenuates the adverse reactions caused by sennoside A and plays a role in its laxative action. [ABSTRACT FROM AUTHOR]

Lung cancer has very high mortality and glycyrrhizin was found to significantly inhibit the growth of lung cancer cells in vitro and tissues in mice. However, the detailed inhibitory role of glycyrrhizin in the growth of lung cancer is still unclear. In this study, we first found that glycyrrhizin inhibited the growth of lung tumor in PDX mice. And high level of HMGB1 promoted the migration and invasion of lung cancer cells, which was suppressed by glycyrrhizin. Moreover, glycyrrhizin reduced the activity of JAK/STAT signaling pathway, which is the upstream regulator of HMGB1. Therefore, this study revealed a potential mechanism by which glycyrrhizin can inhibit the progression of lung cancer. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Glycyrrhizic acid (GA) is an effective inhibitor of reactive oxygen species (ROS) production. We investigated the role of GA in the progression of renal injury in DN. Albumin (Alb)/creatinine (crea) levels were significantly lower, and renal histopathology was attenuated in the diabetic db/db mice that were treated with GA (15 mg/kg via intraperitoneal injection) once per day for eight weeks. These changes were associated with significantly lower levels of α-smooth muscle actin (α-SMA) and transforming growth factor β1 (TGF-β1) expression. Additionally, diabetic db/db mice displayed more terminal deoxynucleotidyl transferase-mediated nick-end labeling- (TUNEL-) positive nuclei and diabetes-induced ROS production in the kidneys, and these effects were attenuated by the treatment with GA, which activated adenosine monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling in the kidneys. In summary, in diabetic db/db mice, the effect of GA on DN involved, in part, the inhibition of ROS and the activation of AMPK/SIRT1/PGC-1α signaling in the kidneys. GA, therefore, shows therapeutic potential for preventing and treating DN. [ABSTRACT FROM AUTHOR]

Licorice (Glycyrrhiza glabra) has been considered as an herbal drug since ancient time. Nowadays, it is a well-known spice that possesses worth pharmacological effects. However, some relevant articles have revealed negative impacts of licorice in health. By considering the great wishes in using herbal medicine, it is important to show adverse effects of herbal medicine in health. At present, there are misunderstandings toward the safety of herbal medicines. Herein, we gathered scientific research projects on the toxicity effects of licorice and glycyrrhizin to highlight their safety. In this regards, we categorized our findings about the toxicity effects of licorice and glycyrrhizin in acute, sub-acute, sub-chronic, and chronic states. Besides, we discussed on the cytotoxicity, genotoxicity, mutagenicity, and carcinogenicity of licorice and glycyrrhizin as well as their developmental toxicity. This review disclosed that G. glabra and glycyrrhizin salts are moderately toxic. They need to be used with caution during pregnancy. G. glabra and glycyrrhizin possess selective cytotoxic effects on cancerous cells. The most important side effects of licorice and glycyrrhizin are hypertension and hypokalemic-induced secondary disorders. Licorice side effects are increased by hypokalemia, prolonged gastrointestinal transient time, decreased type 2 11-beta-hydroxysteroid dehydrogenase activities, hypertension, anorexia nervosa, old age, and female sex. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background. HMGB1 acts as an important inflammatory mediator and is a potential therapeutic target for sepsis. Glycyrrhizin (GL), a natural triterpene glycoside derived from licorice, has been demonstrated to inhibit HMGB1 activity. The aim of this study is to explore how GL affects the HMGB1 signaling in sepsis. Methods. We used a CLP model of sepsis and in vitro LPS or HMGB1-treated NR8383 cells to examine the effects of GL on expression of HMGB1 and proinflammatory cytokines. Furthermore, we explored the effect of GL on interactions between HMGB1 and RAGE or TLR4 and the activations of NF-κB and MAPKs. Results. GL significantly decreased mortality and reduced serum levels of HMGB1 in vivo. GL also attenuated the release and expression of HMGB1 and proinflammatory cytokines. Direct stimulation by HMGB1 elevated the release of proinflammatory cytokines faster than LPS did and it was also inhibited by GL. Furthermore, GL blocked the interaction of HMGB1 with RAGE and TLR4 and suppressed the downstream MAPKs/NF-κB signaling pathway. Conclusion. GL may protect rats against sepsis by blocking the interaction of HMGB1 with cell surface receptors and HMGB1-mediated inflammatory responses. [ABSTRACT FROM AUTHOR]

This article has been retracted by Hindawi following an investigation undertaken by the publisher [[1]]. We wish to credit our own Research Integrity and Research Publishing teams and anonymous and named external researchers and research integrity experts for contributing to this investigation. [Extracted from the article]

Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4'-dihydroxyflavone (7,4'-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition. Human lung fibroblast-1 cells were used to identify the potency of 7,4'-DHF compared with other compounds from G. uralensis, to compare 7,4'-DHF with Dex on eotaxin production following 24-h short-time culture and 72-h longer-time (LT) culture, and to determine the effects of the 7,4'-DHF on Dex LT culture augmented eotaxin production and molecule mechanisms. 7,4'-DHF was the most potent eotaxin/CCL-11 inhibitor among the ten compounds and provided continued suppression. In contrast to short-time culture, Dex LT culture increased constitutively, and IL-4/TNF-α stimulated eotaxin/CCL11 production by human lung fibroblast-1 cells. This adverse effect was abrogated by 7,4'-DHF co-culture. 7,4'-DHF significantly inhibited Dex LT culture augmentation of p-STAT6 and impaired HDAC2 expression. This study demonstrated that 7,4'-DHF has the ability to consistently suppress eotaxin production and prevent Dex-paradoxical adverse effects on eotaxin production. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Chinese liquorice/licorice ( Glycyrrhiza uralensis) is a leguminous plant species whose roots and rhizomes have been widely used as a herbal medicine and natural sweetener. Whole-genome sequencing is essential for gene discovery studies and molecular breeding in liquorice. Here, we report a draft assembly of the approximately 379-Mb whole-genome sequence of strain 308-19 of G. uralensis; this assembly contains 34 445 predicted protein-coding genes. Comparative analyses suggested well-conserved genomic components and collinearity of gene loci (synteny) between the genome of liquorice and those of other legumes such as Medicago and chickpea. We observed that three genes involved in isoflavonoid biosynthesis, namely, 2-hydroxyisoflavanone synthase ( CYP93C), 2,7,4′-trihydroxyisoflavanone 4′- O-methyltransferase/isoflavone 4′- O-methyltransferase ( HI4 OMT) and isoflavone-7- O-methyltransferase ( 7- IOMT) formed a cluster on the scaffold of the liquorice genome and showed conserved microsynteny with Medicago and chickpea. Based on the liquorice genome annotation, we predicted genes in the P450 and UDP-dependent glycosyltransferase ( UGT) superfamilies, some of which are involved in triterpenoid saponin biosynthesis, and characterised their gene expression with the reference genome sequence. The genome sequencing and its annotations provide an essential resource for liquorice improvement through molecular breeding and the discovery of useful genes for engineering bioactive components through synthetic biology approaches. [ABSTRACT FROM AUTHOR]