Glycyrrhiza Species Research Articles

Whole-chromosome oligo-painting in licorice unveils interspecific chromosomal evolutionary relationships and possible origin of triploid genome species.

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.

Licochalcone A Ameliorates Cognitive Dysfunction in an Alzheimer's Disease Model by Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis.

Endoplasmic reticulum (ER) stress-induced neurodegeneration has been considered an underlying cause of Alzheimer disease (AD). Here, we investigated the beneficial effects of licochalcone A (Lico A), a valuable flavonoid of the root of the Glycyrrhiza species, against cognitive impairment in AD by regulating ER stress. The triple transgenic mouse AD models were used and were administrated 5 or 15mg/kg Lico A. Cognitive deficits, Aβ deposition, ER stress, and neuronal apoptosis were determined using Morris Water Maze test, probe trial, immunofluorescence staining, western blotting, and TUNEL staining. To investigate the mechanisms of how Lico A exerts anti-AD effects, primary hippocampal neurons were isolated from the AD model mice and treated with Lico A, salubrinal, an eIF2α phosphatase inhibitor, ML385, a Nrf2 inhibitor, or LY294002, an inhibitor of PI3K. Pharmacokinetics and toxicity of Lico A (15mg/kg) in AD mice were evaluated. We found that Lico A improved cognitive impairment, decreased Aβ plaques, inhibited ER stress, and reduced neuronal apoptosis in the hippocampus and cortex of AD mice. Treatment with Lico A in primary hippocampal neurons exerted the same effects as it did in vivo. Additionally, cotreatment with ML385 or LY294002 significantly impeded the effects of Lico A against ER stress. Moreover, 15mg/kg Lico A had a good bioavailability and low toxicity in AD mice. Our results demonstrated that Lico A ameliorates ER stress-induced neuronal apoptosis by inhibiting PERK/eIF2α/ATF4/CHOP signaling, suggesting the therapeutic potential of Lico A in AD treatment.

The Anticancer Journey of Liquiritin: Insights into Its Mechanisms and Therapeutic Prospects.

Liquiritin (LIQ), a bioactive flavonoid from Glycyrrhiza species, has shown significant potential in cancer therapy. LIQ exhibits potent inhibitory effects on various cancer cell types, including breast, lung, liver, and colon cancers, while demonstrating low toxicity towards healthy cells. Its anticancer mechanisms include inducing cell cycle arrest, promoting apoptosis, and modulating inflammation-related pathways. Additionally, LIQ impedes angiogenesis and enhances the efficacy of conventional chemotherapies through sensitization and synergistic effects with other natural compounds and targeted therapies. These multifaceted actions highlight LIQ as a promising candidate for further development as an anticancer agent. This abstract provides an overview of LIQ's chemistry, biological effects, and underlying mechanisms.

An insight into the therapeutic effects of isoliquiritigenin in breast cancer.

Breast cancer ranks as the most widespread malignant condition in women, emerging as a primary contributor to mortality. The primary challenges in cancer treatments involve undesirable side effects. Therefore, exploring natural compounds as additional therapy could provide valuable insights. Isoliquiritigenin (ILN), an isoflavonoid featuring a chalcone moiety primarily sourced from Glycyrrhiza species, has garnered increasing interest in breast cancer research. This review aims to provide a comprehensive understanding of ILN's mechanisms of action in breast cancer, drawing from a range of in vitro and in vivo studies. ILN primarily acts by inhibiting angiogenesis, aromatase, inflammation, and cell proliferation, and preventing invasion and metastasis. Mechanistically, it downregulates miR-374a, phosphoinositide-3-kinase-protein kinase B/Akt, maternal embryonic leucine zipper kinase, vascular endothelial growth factor, and estrogen receptor protein levels, and causes enhancement of Wnt inhibitory factor-1, and Unc-51-like kinase 1 expression to treat breast cancer. ILN emerges as a promising natural option, offering therapeutic advantages with minimal side effects. However, it is important to note that current research on ILN is primarily limited to preclinical models, underscoring the need for further investigation to validate its potential efficacy.

An efficient method for rapid screening of triterpenoid saponins in three Glycyrrhiza species using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry combined with mass defect filtering

Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF). Firstly, comprehensive date acquisition was achieved using RRLC-Q-TOF-MS. Secondly, a polygonal MDF method was established by summarizing known and speculated substituents and modifications based on the core structure to rapidly screen potential triterpenoid saponins. Thirdly, based on the fragmentation patterns of reference compounds, an identification strategy for characterisation of triterpenoid saponins was proposed. The strategy divided triterpenoid saponins into three distinct classes. By this strategy, 98 triterpenoid saponins including 10 potential new ones were tentatively characterised. Finally, triterpenoid saponins of three Glycyrrhiza species were further analysed using principle component analysis (PCA) and orthogonality partial least squares discriminant analysis (OPLS-DA). Among these, 18 compounds with variable importance in projections (VIP) > 1.0 and P values < 0.05 were selected to distinguish three Glycyrrhiza species. Overall, our study provided a reference for quality control and rational use of the three species.

Phytochemical Profiling and In Vitro Antioxidant, Antimicrobial, Cytotoxicity Effects of Some Glycyrrhiza Species from Turkey

Phytochemical Profiling and In Vitro Antioxidant, Antimicrobial, Cytotoxicity Effects of Some Glycyrrhiza Species from Turkey

Comparative genomics and phylogenomics of the genus Glycyrrhiza (Fabaceae) based on chloroplast genomes.

Glycyrrhiza (Fabaceae) species are rich in metabolites and widely used in medicine. Research on the chloroplast genome of Glycyrrhiza is important for understanding its phylogenetics, biogeography, genetic diversity, species identification, and medicinal properties. In this study, comparative genomics and phylogenomics of Glycyrrhiza were analyzed based on the chloroplast genome. The chloroplast genomes of six Glycyrrhiza species were obtained using various assembly and annotation tools. The final assembled chloroplast genome sizes for the six Glycyrrhiza species ranged from 126,380 bp to 129,115 bp, with a total of 109-110 genes annotated. Comparative genomics results showed that the chloroplast genomes of Glycyrrhiza showed typically lacking inverted repeat regions, and the genome length, structure, GC content, codon usage, and gene distribution were highly similar. Bioinformatics analysis revealed the presence of 69-96 simple sequence repeats and 61-138 long repeats in the chloroplast genomes. Combining the results of mVISTA and nucleotide diversity, four highly variable regions were screened for species identification and relationship studies. Selection pressure analysis indicated overall purifying selection in the chloroplast genomes of Glycyrrhiza, with a few positively selected genes potentially linked to environmental adaptation. Phylogenetic analyses involving all tribes of Fabaceae with published chloroplast genomes elucidated the evolutionary relationships, and divergence time estimation estimated the chronological order of species differentiations within the Fabaceae family. The results of phylogenetic analysis indicated that species from the six subfamilies formed distinct clusters, consistent with the classification scheme of the six subfamilies. In addition, the inverted repeat-lacking clade in the subfamily Papilionoideae clustered together, and it was the last to differentiate. Co-linear analysis confirmed the conserved nature of Glycyrrhiza chloroplast genomes, and instances of gene rearrangements and inversions were observed in the subfamily Papilionoideae.

Two Multidimensional Chromatography/High-Resolution Mass Spectrometry Approaches Enabling the In-Depth Metabolite Characterization Simultaneously from Three Glycyrrhiza Species: Method Development, Comparison, and Integration.

Two offline multidimensional chromatography/high-resolution mass spectrometry systems (method 1: fractionation and online two-dimensional liquid chromatography, 2D-LC; method 2: fractionation and offline 2D-LC) were established to characterize the metabolites simultaneously from three Glycyrrhiza species. Ion exchange chromatography in the first-dimensional (1D) separation was well fractionated between the acidic (mainly triterpenoids) and weakly acidic components (flavonoids). These obtained subsamples got sophisticated separation by the second (2D) and third dimension (3D) of chromatography either by online reversed-phase chromatography × reversed-phase chromatography (RPC × RPC) or offline hydrophilic interaction chromatography × RPC (HILIC × RPC). Orthogonality for the 2D/3D separations reached 0.73 for method 1 and 0.81 for method 2, respectively. We could characterize 1097 compounds from three Glycyrrhiza species based on an in-house library and 33 reference standards, involving 618 by method 1 and 668 by method 2, respectively. They exhibited a differentiated performance and complementarity in identifying the multiple subclasses of Glycyrrhiza components.

Integrated metabolomic and transcriptomic analysis provides insights into the flavonoid formation in different Glycyrrhiza species

Medicinal licorice is obtained from the roots and rhizomes of three species, Glycyrrhiza inflata, G. glabra, and G. urelensis. Previous studies have reported chemical differences among these species, but the detailed composition of specialized metabolites and the underlying molecular basis for the formation of characteristic compounds remain unclear. Here, we performed integrated metabolic and transcriptomic analysis to identify the characteristic flavonoids (CFs) of these three licorice species as well as the key regulators of their biosynthesis. A total of 866 metabolites including 251 flavonoids were identified. Among them, 71 flavonoids were differentially accumulated in three licorice species. Transcriptome analysis showed that a set of the structural genes involved in CF biosynthesis were differentially expressed among the three licorice species. In addition, weighted gene co-expression network analysis (WGCNA) was used to construct a regulatory network for CF biosynthesis. A candidate transcription factor GibHLH69 was proved to promote GiCHS20 expression and contribute to the accumulation of multiple CFs in G. inflata. These results provide valuable information for further understanding the biosynthesis of CFs and future breeding of Glycyrrhiza varieties.

Licochalcone A: A Potential Multitarget Drug for Alzheimer's Disease Treatment.

Licochalcone A (Lico-A) is a flavonoid compound derived from the root of the Glycyrrhiza species, a plant commonly used in traditional Chinese medicine. While the Glycyrrhiza species has shown promise in treating various diseases such as cancer, obesity, and skin diseases due to its active compounds, the investigation of Licochalcone A's effects on the central nervous system and its potential application in Alzheimer's disease (AD) treatment have garnered significant interest. Studies have reported the neuroprotective effects of Lico-A, suggesting its potential as a multitarget compound. Lico-A acts as a PTP1B inhibitor, enhancing cognitive activity through the BDNF-TrkB pathway and exhibiting inhibitory effects on microglia activation, which enables mitigation of neuroinflammation. Moreover, Lico-A inhibits c-Jun N-terminal kinase 1, a key enzyme involved in tau phosphorylation, and modulates the brain insulin receptor, which plays a role in cognitive processes. Lico-A also acts as an acetylcholinesterase inhibitor, leading to increased levels of the neurotransmitter acetylcholine (Ach) in the brain. This mechanism enhances cognitive capacity in individuals with AD. Finally, Lico-A has shown the ability to reduce amyloid plaques, a hallmark of AD, and exhibits antioxidant properties by activating the nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant defense mechanisms. In the present review, we discuss the available findings analyzing the potential of Lico-A as a neuroprotective agent. Continued research on Lico-A holds promise for the development of novel treatments for cognitive disorders and neurodegenerative diseases, including AD. Further investigations into its multitarget action and elucidation of underlying mechanisms will contribute to our understanding of its therapeutic potential.

Exploring the effect and mechanism of Haizao Yuhu decoction containing three variants of glycyrrhiza on goiter using an integrated strategy of network pharmacology and RNA sequencing

Ethnopharmacological relevanceHaizao Yuhu decoction (HYD) is a classic Chinese herbal formula described in the surgical monographs of the Ming Dynasty “Waikezhengzong.” It has been widely used to treat goiter for approximately 500 years and found to be particularly effective. HYD contains glycyrrhiza and sargassum. This pair of herbs belongs to “18 incompatible medicaments” of traditional Chinese medicine theory. Although these two herbs are opposite, our preliminary study proved that they have superior effect when added into HYD at 2 times the dose of Chinese Pharmacopoeia. However, the species of glycyrrhiza in HYD that are the most effective have not been recorded in ancient Chinese medical texts. According to the Chinese Pharmacopoeia, glycyrrhiza is divided into the following three species: Glycyrrhiza uralensis Fish., G. glabra L., and G. inflata Bat. The effect of HYD containing different species of glycyrrhiza and their mechanisms remain to be further explored. Aim of the studyTo investigate the effect of HYD containing three species of glycyrrhiza on goiter, and to elucidate the molecular mechanism using network pharmacology combined with RNA sequencing (RNA-seq). Materials and methodsA rat model of goiter was established by 14 days of intragastric gavage of propylthiouracil (PTU), and the rats were treated for 4 weeks with HYD containing three different species of glycyrrhiza. The body weight and rectal temperature of rats were tested weekly. At the end of the experiment, the serum and thyroid tissues of rats were collected. The effect of the three HYDs was assessed based on general observations (including body weight, rectal temperature, and living status of rats), absolute/relative thyroid weight, thyroid function (including triiodothyronine, thyroxine, free triiodothyronine, free thyroxine, and thyroid-stimulating hormone levels), and thyroid tissue pathology. Next, we explored their pharmacological mechanisms using network pharmacology combined with RNA-seq and validated key targets using real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR), western blotting (WB), and immunofluorescence (IF) assays. ResultsThe three HYDs reduced the absolute/relative weights of thyroid tissues and improved the pathological structure, thyroid function, and general findings of rats with goiter. Overall, the effect of HYD-G. uralensis Fish. (HYD-U) was better. Results from network pharmacology and RNA-seq jointly suggested that both the pathogenesis of goiter and the mechanism of action of HYD for goiter were related to the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway. We validated the key targets in the pathway, namely, vascular endothelial growth factor (VEGF) A, VEGF receptor 2, phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and its encoded protein PI3K (p85), AKT serine/threonine kinase 1 (AKT1), phospho-AKT and cyclin D1 using RT-qPCR, WB, and IF assays. The PI3K-Akt pathway was hyperactivated in rats with PTU-induced goiter, whereas the three HYDs could inhibit the pathway. ConclusionThis study confirmed the definite effect of the three HYDs in the treatment of goiter, and HYD-U was found to be more effective. The three HYDs inhibited angiogenesis and cell proliferation in goiter tissue by inhibiting the PI3K-Akt signaling pathway.

Breast cancer prevention with liquiritigenin from licorice through the inhibition of aromatase and protein biosynthesis in high-risk women’s breast tissue

Breast cancer risk continues to increase post menopause. Anti-estrogen therapies are available to prevent postmenopausal breast cancer in high-risk women. However, their adverse effects have reduced acceptability and overall success in cancer prevention. Natural products such as hops (Humulus lupulus) and three pharmacopeial licorice (Glycyrrhiza) species have demonstrated estrogenic and chemopreventive properties, but little is known regarding their effects on aromatase expression and activity as well as pro-proliferation pathways in human breast tissue. We show that Gycyrrhiza inflata (GI) has the highest aromatase inhibition potency among these plant extracts. Moreover, phytoestrogens such as liquiritigenin which is common in all licorice species have potent aromatase inhibitory activity, which is further supported by computational docking of their structures in the binding pocket of aromatase. In addition, GI extract and liquiritigenin suppress aromatase expression in the breast tissue of high-risk postmenopausal women. Although liquiritigenin has estrogenic effects in vitro, with preferential activity through estrogen receptor (ER)-β, it reduces estradiol-induced uterine growth in vivo. It downregulates RNA translation, protein biosynthesis, and metabolism in high-risk women’s breast tissue. Finally, it reduces the rate of MCF-7 cell proliferation, with repeated dosing. Collectively, these data suggest that liquiritigenin has breast cancer prevention potential for high-risk postmenopausal women.

A Review of the Antiviral Activities of Glycyrrhizic Acid, Glycyrrhetinic Acid and Glycyrrhetinic Acid Monoglucuronide.

Licorice, a natural medicine derived from the roots and rhizomes of Glycyrrhiza species, possesses a wide range of therapeutic applications, including antiviral properties. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG) is the active metabolite of GL. GL and its metabolites have a wide range of antiviral activities against viruses, such as, the hepatitis virus, herpes virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and so on. Although their antiviral activity has been widely reported, the specific mechanism of action involving multiple links such as the virus itself, cells, and immunity are not clearly established. In this review, we will give an update on the role of GL and its metabolites as antiviral agents, and detail relevant evidence on the potential use and mechanisms of actions. Analyzing antivirals, their signaling, and the impacts of tissue and autoimmune protection may provide promising new therapeutic strategies.

Geographic distribution and impacts of climate change on the suitable habitats of Glycyrrhiza species in China

Climate change has a major impact on the growth and distribution of plants. Glycyrrhiza is widely used in the treatment of many diseases in China. However, with the overexploitation and the growing demand for medicinal uses in of Glycyrrhiza plants. The investigation of the geographical distribution of Glycyrrhiza plants and the analysis of future climate change are of great significance for the conservation of Glycyrrhiza. In this study, combined with administrative maps of Chinese provinces, the present and future of geographical distribution and richness of six Glycyrrhiza plants in China were studied by using DIVA-GIS and MaxEnt software. A total of 981 herbarium records of these six species of Glycyrrhiza were collected to research. Results show that the change of climate in the future will lead to an increase in habitat suitability for some Glycyrrhiza species as follows: Glycyrrhiza inflata by 61.6%, Glycyrrhiza squamulosa by 47.5%, Glycyrrhiza pallidiflora by 34.0%, Glycyrrhiza yunnanensis by 49.0%, Glycyrrhiza glabra by 51.7%, and Glycyrrhiza aspera by 65.9%. Glycyrrhiza plants have considerable medicinal and economic value, so it is necessary to adopt targeted development and rational management strategies for it.

Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling.

Oral squamous cell carcinoma (OSCC) is the sixth most common type of cancer worldwide. Despite advancement in treatment, advanced-stage OSCC is associated with poor prognosis and high mortality. The present study aimed to investigate the anticancer activities of semilicoisoflavone B (SFB), which is a natural phenolic compound isolated from Glycyrrhiza species. The results revealed that SFB reduces OSCC cell viability by targeting cell cycle and apoptosis. The compound caused cell cycle arrest at the G2/M phase and downregulated the expressions of cell cycle regulators including cyclin A and cyclin-dependent kinase (CDK) 2, 6, and 4. Moreover, SFB induced apoptosis by activating poly-ADP-ribose polymerase (PARP) and caspases 3, 8, and 9. It increased the expressions of pro-apoptotic proteins Bax and Bak, reduced the expressions of anti-apoptotic proteins Bcl-2 and Bcl-xL, and increased the expressions of the death receptor pathway protein Fas cell surface death receptor (FAS), Fas-associated death domain protein (FADD), and TNFR1-associated death domain protein (TRADD). SFB was found to mediate oral cancer cell apoptosis by increasing reactive oxygen species (ROS) production. The treatment of the cells with N-acetyl cysteine (NAC) caused a reduction in pro-apoptotic potential of SFB. Regarding upstream signaling, SFB reduced the phosphorylation of AKT, ERK1/2, p38, and JNK1/2 and suppressed the activation of Ras, Raf, and MEK. The human apoptosis array conducted in the study identified that SFB downregulated survivin expression to induce oral cancer cell apoptosis. Taken together, the study identifies SFB as a potent anticancer agent that might be used clinically to manage human OSCC.

Determination and Comparison of Bioactive Compounds in Different Parts of Glycyrrhiza Species

Glycyrrhiza spp., one of the most widely used herbal medicine for centuries in the world, contain a large number of bioactive such as triterpene saponins and flavonoids which are the main constituents and show broad biological activity. The present study aimed to evaluate the phytochemical profile of extracts from different parts (roots, stems and leaves) of all wild Glycyrrhiza spp. grown in Turkey and to reveal that other parts besides the roots are a rich source of bioactive compounds with potential use in the pharmaceutical and food industries. For this purpose, extracted bioactive compounds from different parts of five Glycyrrhiza spp. collected in different provinces of Turkey were determined and compared. The microwave-assisted extraction method, which is mentioned as a green technique and requires low solvent and extraction time, was applied. Determination of bioactives was performed using liquid chromatography- electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS). Among the collected Glycyrrhiza spp.; in leaf parts, the highest glycyrrhizin (GL) (2.05±0.07 mg g-1) and glycyrrhetinic acid (GA) (0.107±0.005 mg g-1) contents were found in Glycyrrhiza flavescens ssp. flavescens; the highest carbenoxolone (CBX) (0.133±0.006 mg g-1) and liquiritin (LQ) (1.644±0.014mg g-1) contents were in Glycyrrhiza glabra grown in Polatlı. In stem parts, the highest GL (2.735±0.04 mg g-1), CBX (0.069±0.004 mg g-1) and LQ (0.602±0.010 mg g-1) contents were determined in G. glabra plant growing in Ankara. In root parts, the highest GL (14.68±0.09 mg g-1) and LQ (9.735±0.046 mg g-1) contents were detected in G. glabra plant growing in Gaziantep while the highest GA (0.136±0.005 mg g-1) and CBX (0.188±0.067 mg g-1) contents in Glycyrrhiza flavescens ssp. antalyensis. Thus, it was determined which location in Turkey and which parts of Glycyrrhiza spp. that grow wild in Turkey can be used as a priority for the food and pharmaceutical industry with this study.

Analysis of Complete Chloroplast Genome: Structure, Phylogenetic Relationships of Galega orientalis and Evolutionary Inference of Galegeae.

Galega orientalis, a leguminous herb in the Fabaceae family, is an ecologically and economically important species widely cultivated for its strong stress resistance and high protein content. However, genomic information of Galega orientalis has not been reported, which limiting its evolutionary analysis. The small genome size makes chloroplast relatively easy to obtain genomic sequence for phylogenetic studies and molecular marker development. Here, the chloroplast genome of Galega orientalis was sequenced and annotated. The results showed that the chloroplast genome of G. orientalis is 125,280 bp in length with GC content of 34.11%. A total of 107 genes were identified, including 74 protein-coding genes, 29 tRNAs and four rRNAs. One inverted repeat (IR) region was lost in the chloroplast genome of G. orientalis. In addition, five genes (rpl22, ycf2, rps16, trnE-UUC and pbf1) were lost compared with the chloroplast genome of its related species G. officinalis. A total of 84 long repeats and 68 simple sequence repeats were detected, which could be used as potential markers in the genetic studies of G. orientalis and related species. We found that the Ka/Ks values of three genes petL, rpl20, and ycf4 were higher than one in the pairwise comparation of G. officinalis and other three Galegeae species (Calophaca sinica, Caragana jubata, Caragana korshinskii), which indicated those three genes were under positive selection. A comparative genomic analysis of 15 Galegeae species showed that most conserved non-coding sequence regions and two genic regions (ycf1 and clpP) were highly divergent, which could be used as DNA barcodes for rapid and accurate species identification. Phylogenetic trees constructed based on the ycf1 and clpP genes confirmed the evolutionary relationships among Galegeae species. In addition, among the 15 Galegeae species analyzed, Galega orientalis had a unique 30-bp intron in the ycf1 gene and Tibetia liangshanensis lacked two introns in the clpP gene, which is contrary to existing conclusion that only Glycyrrhiza species in the IR lacking clade (IRLC) lack two introns. In conclusion, for the first time, the complete chloroplast genome of G. orientalis was determined and annotated, which could provide insights into the unsolved evolutionary relationships within the genus Galegeae.

THE PROTECTIVE EFFECTS OF GLYCYRRHIZIN ON DOXORUBICIN-INDUCED CARDIOTOXICITY IN RATS

ABSTRACT Objective: Doxorubicin (DOX) is a type of chemotherapy drug frequently used to treat different malignancies. However, one of the most serious adverse effects of DOX usage is the potential of cardiotoxicity. Cardioprotective medications may be used to reduce cardiac damage because of DOX therapy. Glycyrrhizin (GL) is found in high amounts in the roots of the ‘Licorice’ plant from the Glycyrrhiza species. Due to its possible effects on blood pressure (BP) and cardiovascular health, GL has attracted attention concerning the heart. Oxidative stress and inflammatory process have been shown to be responsible for DOX-induced cardiotoxicity (DIC). For this reason, in consequence of its possible pharmacological benefits, such as antiinflammatory and antioxidant GL has been researched in this study. Here in, we aimed to investigate the protective effects of GL on DIC. Material and Methods: In this study, thirty-two male Wistar albino adult male rats were used. Four groups of rats were assigned at randomly: Control, DOX, GL+DOX, and GL groups. DOX was given 20 mg/kg intraperitoneally (i.p.) and 100 mg/kg GL was administered orally (p.o.) once a day for 14 days. Electrocardiography (ECG) and BP records of the rats were obtained. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels in the tissue were measured. Histopathological analyses were performed on the myocardium and descending aorta. Results: In the DOX group, mean and diastolic BP were higher than in the control group (p&lt;0.05). In the GL+DOX group, diastolic BP was lower than in the DOX group (p&lt;0.05). Pathological ECG changes such as ST segment changes and T negativity were observed in DOX-treated groups. MDA, SOD, CAT, and GSH levels studied in heart tissue were similar in all groups (p&gt;0.05). GSH level in descending aorta was significantly lower in the GL+DOX group compared to the other groups (p&lt;0.05). In the DOX group, degenerated cardiomyocyte density, interstitial edema, and severity of congestion-hemorrhage were statistically significantly increased compared to the control group (p&lt;0.05). On the other hand, degenerated cardiomyocyte density was found to be significantly decreased in the GL+DOX group compared to the DOX group (p&lt;0.05). In the DOX group, thinning of elastic lamellae and loss of myofibrils in muscle cells were observed in the descending aorta. Therefore, the histopathological alterations identified in the DOX group exhibited a significant statistical improvement in the GL+DOX group (p&lt;0.05). Conclusion: Based on the study's findings, GL can regulate high blood pressure caused by DOX and also alleviate the toxic effects of DOX on both the myocardium and descending aorta.

Application of Microscopy in the Quality Control of Licorice Roots: Comparative Anatomy of the Roots and Rhizomes of Five Species of Glycyrrhiza.

The raw materials of “licorice root” in the commerce consist of roots and/or rhizomes (stolons) of different species of Glycyrrhiza. Licorice products and raw materials are frequently mislabeled and often have mixed, misidentified, or unidentified species and parts. This paper provides a detailed comparative analysis of the morpho-anatomies of the rhizomes and roots of five species of Glycyrrhiza, namely G. glabra, G. uralensis, G. echinata, G. inflata, and G. lepidota, by bright-field light microscopy and scanning electron microscopy. The studied species showed some similarities in their basic anatomical features due to the fact that they are phylogenetically closely related and belong to the same genus. However, differences in microscopic features such as the thickness of cork and medullary rays, pore frequency, and size of the vessels were observed. The rhizomes can readily be distinguished by the presence of a distinct pith. The roots lack a well-defined pith and instead have primary xylem in the center.

Analysis of the network pharmacology and the structure-activity relationship of glycyrrhizic acid and glycyrrhetinic acid.

Licorice, a herbal product derived from the root of Glycyrrhiza species, has been used as a sweetening agent and traditional herbal medicine for hundreds of years. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Both GL and GA have pharmacological effects against tumors, inflammation, viral infection, liver diseases, neurological diseases, and metabolic diseases. However, they also exhibit differences. KEGG analysis indicated that licorice is involved in neuroactive ligand‒receptor interactions, while 18β-GA is mostly involved in arrhythmogenic right ventricular cardiomyopathy. In this article, we comprehensively review the therapeutic potential of GL and GA by focusing on their pharmacological effects and working mechanisms. We systemically examine the structure-activity relationship of GL, GA and their isomers. Based on the various pharmacological activities of GL, GA and their isomers, we propose further development of structural derivatives of GA after chemical structure modification, with less cytotoxicity but higher targeting specificity. More research is needed on the clinical applications of licorice and its active ingredients.