The progression from hepatitis to liver fibrosis (LF) and ultimately to hepatic carcinoma (HCC) represents the advanced stages of various liver diseases. Currently, no universal treatment effectively addresses all three conditions. The Traditional Chinese Medicine formula Xiao-Chai-Hu decoction (XCHD) has shown promise in treating hepatitis, inhibiting LF, and serving as an adjunct therapy for HCC. This study evaluates the efficacy and optimal treatment durations of XCHD in managing these liver diseases using meta-analysis and machine learning techniques.

Registered in the PROSPERO database (CRD42024534445), this meta-analysis systematically searched seven databases, including 54 studies with a total of 5,710 patients. Statistical analysis was performed using Stata 17.0. Five machine learning models-Random Forest (RF), XGBoost, Lasso, Multilayer Perceptron (MLP), and a stacking model combining these algorithms-were employed to analyze the data and predict the time-effect relationships. The optimal durations of XCHD treatment for the liver disease trilogy were subsequently projected.

XCHD significantly improved the primary outcome indicators for hepatitis, liver fibrosis, and HCC. Additionally, XCHD demonstrated a beneficial effect on liver dysfunction caused by these diseases. Machine learning predicted the optimal treatment durations of XCHD as 12 weeks for hepatitis, 20.31 weeks for liver fibrosis, and 12 weeks for HCC.

XCHD is effective in treating the liver disease trilogy, with optimal treatment durations of 12 weeks for hepatitis and HCC, and 20.31 weeks for liver fibrosis. These findings support the potential of XCHD in developing precise clinical strategies for managing liver diseases. This study innovatively integrates meta-analysis with machine learning to determine the optimal treatment durations, providing a novel approach for evidence-based precision medicine in Traditional Chinese Medicine.

Lower extremity deep vein thrombosis (LEDVT) is a common vascular disease, with its pathogenesis mainly involving inflammatory responses and oxidative stress. Liquiritin (LIQ) is a flavonoid that exhibits pharmacological effects such as anti-inflammatory and antioxidant properties. This study aimed to investigate the role of LIQ in LEDVT and its potential mechanisms.

We established an LEDVT model in mice by ligating the inferior vena cava (IVC) and performed in vitro experiments by stimulating human umbilical vein endothelial cells (HUVECs) with IL-1β (10 ng/mL) to simulate endothelial cell injury.

We found that LIQ significantly reduced the size and weight of thrombi and decreased the concentrations of inflammatory factors TNF-α and IL-6 in the IVC of LEDVT mice. Furthermore, LIQ inhibited the secretion of prothrombotic mediators such as tissue factor (TF) and vascular cell adhesion molecule-1 (VCAM-1). Administration of LIQ resulted in a notable reduction in immune inflammatory cells in the IVC of LEDVT mice. LIQ also demonstrated antioxidant properties, as the treatment of LIQ enhanced SOD activity and restored ROS levels to normal in the IVC. Similarly, LIQ reduced the formation of inflammatory factors and the secretion of prothrombotic mediators by HUVECs while inhibiting oxidative stress in HUVECs. Finally, LIQ effectively suppressed the levels of phosphorylated p65 in both the IVC and HUVECs.

LIQ reduces inflammatory responses and oxidative stress in LEDVT by inhibiting the NF-κB signaling pathway. This finding provides new insights into the prevention and treatment of LEDVT.

The Chinese herbal formula YangxinDingji (YXDJ), derived from the classic ancient formula Zhigancao decoction that originated from Zhang Zhongjing's "shang han lun", is a modern preparation of a classic prescription, and is used for arrhythmia treatment in China. However, its antiarrhythmic mechanisms are not fully elucidated.

This study aimed to investigate the pharmacological and molecular mechanisms of YXDJ.

Antiarrhythmic effects were evaluated in isolated guinea pig hearts subjected to ischemia/reperfusion (I/R) or isoproterenol (ISO) challenge, and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) utilizing a multi-electrode array (MEA). Patch clamp recordings assessed the effects of YXDJ on sodium (INa, INa-L) and L-type calcium (ICa-L) currents, while potassium currents (IKr, IKs) were studied in heterologous cells. Optical mapping observed electrical activities and calcium transients.

YXDJ pretreatment at concentrations of 0.25, 0.5, and 1.0 mg/ml effectively prevented ventricular arrhythmias induced by I/R or ISO challenge, and mitigated electrical stimulation-induced arrhythmias in hiPSC-CMs. YXDJ inhibited INa, INa-L, and ICa-L currents in a concentration-dependent manner without affecting IKr and IKs, inhibited abnormal electrical activities and excitation reentry, decreased action potential duration dispersion and heterogeneity of excitation conduction, and restored intracellular calcium homeostasis.

Our results demonstrate that YXDJ exerts its antiarrhythmic effect through the inhibition of inward depolarizing currents, which prevents alterations in left ventricular repolarization dispersion. This leads to synchronized repolarization and a reduction in excitation reentry. Collectively, these findings suggest that YXDJ is a promising candidate for the treatment of arrhythmias.

Adding plant extracts to diets to enhance sow performance and health is widely regarded as a healthy and sustainable practice. In promoting antibiotic-free farming, plant extracts have emerged as a leading solution for enhancing sow fertility through nutritional strategies. The aim of this study was to investigate the biochemical impacts of supplementation of sows with ALAEm (composed of nine plant extracts) on blood and placental indices of sows in late gestation. The components of ALAEm were determined by UPLC-MS/MS. 196 normal gestation parturient sows were randomly allocated into two groups (n = 98 per group): the control group and the test group fed 20 g/d ALAEm supplementation at 74-114 d of gestation. The study examined the various clinical indexes in the blood, the expression of genes and proteins and metabolomics in the placenta. Dietary ALAEm supplementation improved sow reproductive performance (total number of piglets born alive, number of piglets weaned, wean weight), serum biochemical indices, placental structure and increased gene and protein expression of ZO-1, Claudin-1 and other placental junction-associated factors. ALAEm attenuated placental tissue oxidation, inflammation, and apoptosis, promoted placental growth (EGF and IGF-1) and angiogenesis factors (VEGFA, PIGF and other factors), and increased the nutrient transport in placental (GLUT1 and SNAT2). Dietary ALAEm supplementation decreased the number of metabolites associated with lipid metabolism through alpha-linolenic acid metabolism. Therefore, dietary supplementation of ALAEm in the late gestation may improve fertility by reducing the levels of inflammation, oxidation and apoptosis in placental tissues via the EGFR/VEGFR2-PI3K-AKT1 pathway, promoting placental growth, angiogenesis and nutrient transport, and altering the levels of placental lipid metabolites via α-linolenic acid metabolism.

Cardiovascular disease poses a significant risk to human health and remains the leading cause of illness and death globally, with its incidence continuing to rise. The intricate pathophysiological mechanisms of CVDs include inflammation, oxidative stress, autophagy, and myocardial fibrosis. In light of these underlying mechanisms, traditional Chinese medicine (TCM) and its constituents have demonstrated distinct advantages in managing CVDs. By exerting synergistic effects across multiple components and targets, traditional Chinese medicine can modulate the inflammatory response, mitigate oxidative stress, regulate excessive autophagy, and enhance myocardial fibrosis repair. This article reviews the latest advancements in understanding how TCM compounds regulate signaling pathways involved in the treatment of CVDs.

Huangqin Decoction (HQD), a traditional Chinese medicine prescription, was first recorded in Treatise on Febrile Diseases 2000 years ago. It is widely used in the treatment of ulcerative colitis (UC). The purpose of the study was to investigate and compare the pharmacokinetic behaviors of the main bioactive components of HQD in UC and normal rats. A simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of eight components of HQD in rat plasma. Analytes were separated on a C18 column under gradient elution with a mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Multiple reaction monitoring mode was used to acquire mass transitions. Method validation results showed good specificity and good linearity, with a limit of quantification ranging from 2.5 to 5.0 ng/mL which were sufficient for the pharmacokinetic study. The accuracy and precision were within 12.1% and 11.8%, respectively. Extraction recovery and matrix effect were from 81.8% to 98.8% and 83.6% to 98.4%, respectively. The relative error values of stability under different storage conditions were within 12.8%. The method was successfully applied to study the pharmacokinetics of eight components in UC and normal rat plasma after oral administration of HQD. Pharmacokinetic parameters of analytes were calculated. Results showed that the pharmacokinetic behaviors in UC and normal rats were significantly different, especially time to peak drug concentration (Tmax), peak concentration (Cmax), and area under the curve (AUC). In general, the Cmax of all analytes and AUCs of most analytes in UC rats were markedly lower than in normal rats, which might be related to the pathological state of UC influencing the exposure levels of bioactive components of HQD, and reducing the absorption of them, resulting differences in pharmacokinetic behaviors. This study could provide a reference for the future clinical application of this classical traditional Chinese medicine formula.

Licorice (Glycyrrhiza L.) is a globally popular medicinal and edible plant, with nearly 30 species distributed across all continents. The usable part is primarily the root. To understand the metabolic differences among different Glycyrrhiza species, we selected four species and performed comprehensive analyses of their roots. Metabolomic profiling was conducted using UPLC-MS/MS and GC-MS, while transcriptomic analysis was carried out using RNA-sequencing. A total of 2716 metabolites were identified, including flavonoids (527 types) and terpenoids (251 types), among various other components. Subsequently, network pharmacology was employed to explore the medicinal value and potential pharmacological ingredients of these metabolites. Joint analysis of transcriptomic and metabolomic data revealed significant differences in differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) in pairwise comparisons among the four species. These differences were primarily enriched in the isoflavone pathway. Further investigation into the regulatory mechanisms of isoflavone biosynthesis in different Glycyrrhiza species identified key genes and metabolites involved in isoflavone biosynthesis. Finally, we made reasonable predictions of the potential suitable habitats for the four Glycyrrhiza species, aiming to provide new insights for the development and utilization of licorice resources. The results of this study can serve as a basis for the development and utilization of licorice and for in-depth research on the regulation of isoflavone biosynthesis in licorice.

Tinospora cordifolia has been used for thousands of years to treat various health conditions, including neurodegenerative diseases. The study aimed to elucidate the mechanism of action and protein targets of T. cordifolia in the context of Alzheimer's disease through untargeted metabolomics and network pharmacology. LC-MS/MS analysis resulted in 1186 metabolites, including known bioactive compounds such as liquiritin, Plastoquinone 3, and Shoyuflavone A, to name a few. The network pharmacology analysis highlighted the metabolite-protein interaction with the enrichment of 591 human proteins, including neurotransmitter receptors and other regulatory proteins. Pathway analysis highlighted the enrichment of cAMP, mTOR, MAPK, and PI3K-Akt signaling pathways along with cholinergic, dopaminergic, serotonergic, glutamatergic synapse, and apoptosis. The docking results suggest that T. cordifolia metabolites could interact with key Alzheimer's disease targets BACE1 and MAO-B, suggesting its role in neuroprotection. These findings provide insights into the biochemical pathways underlying T. cordifolia's therapeutic effects and provides a foundation for future exploration of T. cordifolia in the context of translational research.

Ginsenosides are a group of tetracyclic triterpenoids with promising health benefits, consisting of ginseng aglycone attached to various glycans. Pq3-O-UGT2, an important UDP-dependent glycosyltransferase (UGT), catalyzes the production of Ginsenoside Rg3 and Rd by extending the glycan chain of Ginsenoside Rh2 and F2, respectively, with higher selectivity for F2. However, the mechanism underlying its substrate recognition remains unclear. In this study, the crystal structures of Pq3-O-UGT2 in complex with its acceptor substrates are solved. The structures revealed a Nα5-oriented acceptor binding pocket in Pq3-O-UGT2, shaped by the unique conformation of the Nα5-Nα6 linker. Hydrophobic interactions play a pivotal role in the recognition of both Rh2 and F2, while hydrogen bonds specifically aid in F2 recognition due to its additional glucose moiety. The hydrophobic nature of the acceptor binding pocket also enables Pq3-O-UGT2 to recognize flavonoids. Overall, this study provides novel insights into the substrate recognition mechanisms of ginsenoside UGTs, advancing the understanding of their function and specificity.

Two new crystalline compounds, named [LG·H2O] n (1; LG = liquiritigenin) and [LQ·C2H5OH·H2O] n (2; LQ = liquiritin), have been synthesized and structurally characterized by single-crystal and powder X-ray diffraction, thermogravimetric analyses (TGA), nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and infrared spectra (IR). 1 and 2 crystallize in space groups Pna21 and P212121, respectively. In the structure of 1, liquiritigenin and water molecules are connected by hydrogen bonds for the construction of a novel 3,5-connected network topology with a point symbol of (63)(67·83), in which each liquiritigenin and water molecule acts as a 5-connected and 3-connected node, respectively. Both 1 and 2 reduce amyloid-β-induced toxicity in Caenorhabditis elegans (CL4176 strain) by improving the expression level of SOD. Gene expression studies by RT-qPCR indicate upregulation of skn-1 and sod-3 expression while downregulation of daf-16 and hsf-1 expression in C. elegans. Molecular docking studies indicate that LG and LQ combine well with vascular endothelial growth factor A (VEGFA), with free binding energies calculated to be -6.7 and -7.9 kcal·mol-1, respectively. Moreover, the anti-amyloid-β ability of crystalline and amorphous LG or LQ has been studied.

The objective is to develop a natural and stable anti-oxidative stress and anti-ageing ingredient. In this study, we evaluated the changes in white tea leaves fermented with Eurotium cristatum PLT-PE and Saccharomyces boulardii PLT-HZ and their efficacy against skin oxidative stress.

We employed untargeted metabolomics technology to analyse the differential metabolites between tea extract (TE) and fermented tea extract (FTE). In vitro, using H2O2-induced HaCaT cells, we evaluated cell vitality, ROS, and inflammatory factors (TNF-α, IL-1β, and IL-6). Additionally, we verified the effects on the extracellular matrix and nuclear DNA using fibroblasts or reconstructed skin models. We measured skin hydration, elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio in volunteers after using an emulsion containing 3% FTE for 28 and 56 days.

Targeted metabolomics analysis of white tea leaves yielded more than 20 differential metabolites with antioxidant and anti-inflammatory activities, including amino acids, polypeptides, quercetin, and liquiritin post-fermentation. FTE, compared to TE, can significantly reduce reactive oxygen species (ROS) and protect against oxidative stress-induced skin damage in H2O2-induced HaCaT cells. FTE can inhibit H2O2-induced collagen degradation by suppressing the MAPK/c-Jun signalling pathway and can also mitigate the reactive oxygen species damage to nuclear DNA. Clinical studies showed that the volunteers' stratum corneum water content, skin elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio significantly improved from the baseline after 28 and 56 days of FTE use.

This study contributes to the growing body of literature supporting the protective effects against skin oxidative stress and ageing from fermented plant extracts. Moreover, our findings might inspire multidisciplinary efforts to investigate new fermentation techniques that could produce even more potent anti-ageing solutions.

Doxorubicin (DOX) is a chemotherapy drug widely used in clinical settings, acting as a first-line treatment for various malignant tumors. However, its use is greatly limited by the cardiotoxicity it induces, including doxorubicin-induced cardiomyopathy (DIC). The mechanisms behind DIC are not fully understood, but its potential biological mechanisms are thought to include oxidative stress, inflammation, energy metabolism disorders, mitochondrial damage, autophagy, apoptosis, and ferroptosis. Recent studies have shown that cardiac injury induced by DOX is closely related to ferroptosis. Due to their high efficacy, availability, and low side effects, natural medicine treatments hold strong clinical potential. Currently, natural medicines have been shown to mitigate DOX-induced ferroptosis and ease DIC through various functions such as antioxidation, iron ion homeostasis correction, lipid metabolism regulation, and mitochondrial function improvement. Therefore, this review summarizes the mechanisms of ferroptosis in DIC and the regulation by natural plant products, with the expectation of providing a reference for future research and development of inhibitors targeting ferroptosis in DIC. This review explores the mechanisms of ferroptosis in doxorubicin-induced cardiomyopathy (DIC) and summarizes how natural plant products can alleviate DIC by inhibiting ferroptosis through reducing oxidative stress, correcting iron ion homeostasis, regulating lipid metabolism, and improving mitochondrial function.

Fangji Huangqi Decoction (FJHQD), a famous Traditional Chinese Medicine (TCM) formula, has been widely applied in improving renal function. However, the interaction of bioactives from FJHQD with the targets involved in acute renal injury (AKI) has not been elucidated yet.

A network pharmacology-based approach combined with molecular docking and in vitro and in vivo validation was performed to determine the bioactives, key targets, and potential pharmacological mechanism of FJHQD against AKI.

The model of mouse renal ischemic reperfusion was adopted to verify the curative effect of FJHQD against renal injury. FJHQD was analyzed and separated by Ultra-High performance liquid chromatography (UHPLC). Bioactives and potential targets of FJHQD, as well as AKI-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Besides, in vivo and vitro experiments were conducted to verify the findings.

A total of 20 bioactive ingredients of FJHQD (top 10 positive ion and negative ion compounds) and 274 FJHQD-AKI overlaped targets were screened. Bioinformatics analysis revealed that apoptosis mediated by PI3K-AKT signaling pathway might play an important role in FJHQD against AKI. Further experiments showed that FJHQD alleviated I/R-induced renal injury and OGD/R induced TEC apoptosis by activating PI3K-AKT signaling pathway. Moreover, molecular docking suggested (9Z,12Z,14E)-16-Hydroxy-9,12,14-octadecatrienoic acid, 2-Hydroxyacetophenone, Liquiritigenin, (S)-[10]-Gingerol and Isookanin-7-O-glucoside may be potential candidate agents, among which, PIK3CA interacted with Liquiritigenin, (S)-[10]-Gingerol, Isookanin-7-O-glucoside and 2-Hydroxyacetophenone respectively. AKT1 interacted with (9Z,12Z,14E)-16-Hydroxy-9,12,14-octadecatrienoic acid and 2-Hydroxyacetophenone. Cell experiments showed that the most important ingredient of FJHQD, Liquiritigenin, could inhibit the TEC apoptosis and up-regulate PI3K-Akt signaling pathway, which further confirmed the prediction by network pharmacology strategy and molecular docking.

Our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of FJHQD against AKI. It also provided a promising strategy to uncover the scientific basis and therapeutic mechanism of TCM formulae in treating diseases.

Acute lung injury (ALI) is the main cause of death in clinical respiratory virus infection. Liang-Ge-San (LGS), a famous traditional Chinese formula, has been proved to be effective in treating ALI caused by lipopolysaccharide. However, the effects of LGS on ALI induced by viral infections remain uncertain.

To investigate the effect and mechanism of action of LGS on viral infection-induced ALI.

The inhibitory effects of LGS on virus-induced inflammation in vitro were evaluated by qRT-PCR and ELISA. The protein expression of α7nAChR was examined by Western blotting. α7nAChR was inhibited by the transfection of siRNA or methyllycaconitine citrate (MLA, an α7nAChR inhibitor) to investigate the role of α7nAChR in the anti-inflammatory effect of LGS. Adoptive culture and co-culture systems of macrophages RAW264.7 and alveolar epithelial cells MLE-12 were established to mimic their interaction. Western blotting, immunofluorescence, flow cytometry and transmission electron microscopy were used to examine the effects of LGS on mitophagy inhibition. In vivo, ALI mouse models induced by SARS-CoV-2, H1N1 or Poly(I:C) infection were established to explore the therapeutic effect and mechanism of LGS.

LGS reduced the release of IL-6, TNF-α and IL-1β and increased the expression of α7nAChR in virus-infected RAW264.7 cells. The blockage of α7nAChR counteracted the anti-inflammatory effect of LGS. Moreover, LGS significantly inhibited autophagy in MLE-12 cells induced by Poly(I:C) in adoptive culture and co-culture systems of RAW264.7 and MLE-12 cells, which could be attenuated after the inhibition of α7nAChR in RAW264.7 cells by decreasing the secretion of IL-6, TNF-α and IL-1β. Further study showed that LGS suppressed TNF-α-induced mitochondrial damage and mitophagy by inhibiting the generation of ROS in MLE-12 cells. In vivo, LGS significantly prolonged the survival time, alleviated pathological injury and acute inflammation of ALI mice induced by SARS-CoV-2, H1N1 or Poly(I:C) infection which were associated with the inhibition of α7nAChR-mediated mitophagy.

This study first demonstrates that LGS inhibits virus infection-induced inflammation in RAW246.7 cells by increasing the expression of α7nAChR, thereby inhibiting mitophagy induction in MLE-12 cells to alleviate ALI. This work indicates that LGS may serve as a candidate drug for treating ALI/ARDS caused by viral infection.

In traditional Chinese medicine (TCM), Yigong San (YGS) is mainly used to treat dyspepsia caused by deficiency of spleen and stomach qi. Although the chemical composition and bioactivity of YGS has been well studied, the main in vivo compounds and their distribution in tissues still need to be made clearer.

To elucidate the pharmacokinetic profiles and tissue distribution of eight main compounds of YGS in rats, and provide a reference for clinical application and new drug development.

UPLC-Q-Exactive-Orbitrap-MS was used to qualitatively characterize the parent compounds and their metabolites in the plasma of rats after oral administration of YGS. A sensitive, reliable, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method using UPLC-AB Sciex QTRAP 5500 MS was established to quantitatively determine eight main compounds of YGS in rat plasma and tissues, including liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re and Rg1, atractylenolides I and II.

The mean area under the concentration-time curve (AUC) values of ginsenoside Rb1, hesperidin, and liquiritin at low, medium, and high doses were greater than 150 ng h/mL. The elimination half-life (t1/2) values of ginsenoside Rb1, atractylenolides I and II (low and medium doses) were longer than 10 h. Peak time (Tmax) values of all compounds were shorter than 10 h. Except for atractylenolides, the maximum concentration (Cmax) values of the compounds were greater than 10 ng/mL. The eight compounds were detected in the heart, brain, liver, spleen and kidney at 0.25 h after oral administration. Liquiritin and isoliquiritin had higher exposure in the liver and heart. Hesperidin and ginsenosides Rb1, Re, and Rg1 are mainly distributed in the spleen and kidney. Atractylenolides I and II are mainly distributed in spleen, liver and kidney.

All main compounds of YGS, i.e., liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re, and Rg1, and atractylenolides I and II are absorbed into plasma and widely distributed in various tissues. Among them, hesperidin, ginsenoside Rb1, and atractylenolide I are main in vivo compounds. They are mainly distributed in spleen, liver and kidney. The results of this study provide a basis for further in-depth development and application of YGS.

This research was designed to elucidate the anti-inflammatory impacts of liquiritin on lipopolysaccharide (LPS)-activated human corneal epithelial cells (HCECs).

The Cell Counting kit-8 (CCK-8) assay was adopted to assess cell viability. The enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α. Transcriptome analysis was conducted to identify the genes that exhibited differential expression between different treatment. The model group included cells treated with LPS (10 µg/mL), the treatment group comprised cells treated with liquiritin (80 µM) and LPS (10 µg/mL), and the control group consisted of untreated cells. To further validate the expression levels of the selected genes, including CSF2, CXCL1, CXCL2, CXCL8, IL1A, IL1B, IL24, IL6, and LTB, quantitative real-time PCR was performed. The expression of proteins related to the Akt/NF-κB signaling pathway was assessed through western blot analysis. NF-κB nuclear translocation was evaluated through immunofluorescence staining.

The secretion of IL-6, IL-8, and TNF-α in LPS-induced HCECs was significantly downregulated by liquiritin. Based on the transcriptome analysis, the mRNA expression of pro-inflammatory cytokines, namely IL-6, IL-8, IL-1β, IL-24, TNF-α, and IL-1α was overproduced by LPS stimulation, and suppressed after liquiritin treatment. Furthermore, the Western blot results revealed a remarkable reduction in the phosphorylation degrees of NF-κB p65, IκB, and Akt upon treatment with liquiritin. Additionally, immunofluorescence analysis confirmed liquiritin's inhibition of LPS-induced p65 nuclear translocation.

Collectively, these findings imply that liquiritin suppresses the expression of proinflammatory cytokines, and the anti-inflammatory impacts of liquiritin may be caused by its repression of the Akt/NF-κB signaling pathway in LPS-induced HCECs. These data indicate that liquiritin could provide a potential therapeutic application for inflammation-associated corneal diseases.

Liquiritin (LQ), a kind of flavonoid isolated from licorice, was proven to have great potential in treating heart failure. Pharmacokinetic evaluation is important for demonstrating clinical efficacy and mechanisms, and the prototype drug and its metabolite profiling are important for drug discovery and development. However, the metabolism of LQ in acute myocardial infarction (AMI) model rats still needs to be studied in depth. An information-dependent acquisition (IDA)-ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was applied to profile LQ metabolites in AMI model rat plasma. Protein precipitation and extraction were used for sample preparation. Chromatographic separation was achieved using an XSelect BEH C18 column (2.1 × 150 mm, 2.5 μm) using gradient elution method combining 0.1% formic acid and acetonitrile with a flow rate of 0.3 mL/min. Twelve metabolites were identified in IDA mode, sulfation, glucuronidation, methylation, methyl esterification, glutamine conjugation, and valine conjugation, and their composite reactions were presumed as the primary pathways of LQ metabolism. The variation in the peak areas showed that the time to reach the peak drug concentration of LQ and 12 metabolites was within 5 h. In summary, IDA-bridged UHPLC-MS/MS from characteristic fragment ions toward confidence-enhanced identification could effectively screen and profile metabolites.

Glucocorticoids are often used and highly effective anti-inflammatory medications, but prolonged topical application may alter the epidermis' normal structure and function, potentially resulting in a number of adverse effects. Topical glucocorticoid-induced skin inflammation is a dangerous condition that develops after topical glucocorticoid use. The patients become dependent on the medication and, even after the medication is stopped, the dermatitis symptoms recur, severely impairing their quality of life. Thus, the need to aggressively confront Topical glucocorticoid-induced skin inflammation is critical. Prior research has demonstrated that topical administration of licorice's flavonoid component liquiritin stimulates epidermal proliferation, which in turn enhances the creation of collagen and the healing of wounds. Therefore, the purpose of this work was to determine if topical use of liquiritin carbomer gel can treat glucocorticoid-induced changes in mice skin epidermal function, and the mechanisms involved. The findings demonstrated that, in the mice model of topical glucocorticoid-induced skin inflammation, liquiritin carbomer gel aided in the restoration of skin barrier function. These outcomes may have been caused by enhanced expression of the proteins Aquaporin 3, Keratin 10, and Claudin-1, as well as the restoration of epidermal hyaluronan content. In the meantime, liquiritin carbomer gel dramatically decreased the expression of TNF-α, IL-1β, IL-6, IFN-γ, and IgE in mice, according to ELISA tests. Furthermore, topical treatment of liquiritin carbomer gel boosted the expression of superoxide dismutase, catalase, and decreased malondialdehyde expression, potentially counteracting the detrimental effects of glucocorticoids on the epidermis. In summary, these findings imply that topical liquiritin carbomer gel can treat glucocorticoid-induced skin damage through various mechanisms of action.

Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances and develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink and other databases to find the relevant literature in the last two decades. Using "gastric cancer", "stomach cancers", "flavonoid", "bioflavonoid", "2-Phenyl-Chromene" as keywords, were searched, then analyzed and summarized the mechanism of flavonoids in the treatment of GC. It was revealed that the anti-tumor mechanism of flavonoids involves inhibiting tumor growth, proliferation, invasion, and metastasis, as well as inducing cell death through various processes such as apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, combining flavonoids with other chemotherapeutic agents like 5-FU and platinum compounds can potentially reduce chemoresistance. Flavonoids have also demonstrated enhanced biological activity when used in combination with other natural products. Consequently, this review proposes innovative perspectives for the development of flavonoids as new anti-GC agents.

Thromboangiitis obliterans (TAO) is a non-atherosclerotic segmental inflammatory occlusive disease with a high recurrence rate, high disability rate, difficulty to cure, and poor prognosis. It has been clinically proven that Mailuoshutong pill (MLSTP) is an effective traditional Chinese medicine for treating TAO. As MLSTP contains hundreds of chemical components, the quality control of which is a challenge in the development of reliable quality evaluation metrics. This study aimed to evaluate the quality uniformity of MLSTP by establishing a multi-strategy platform. In the present study, the key targets and signaling pathways of MLSTP treating TAO were predicted by network pharmacology. It was further shown by in vivo validation experiments that MLSTP exerted therapeutic effects on TAO by modulating the PI3K-AKT signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway. In addition, UPLC fingerprints of MLSTP were established and screened for potential Q-markers of MLSTP in combination with network pharmacology results. Six components, including chlorogenic acid, liquiritin, paeoniflorin, calycosin-7-glucoside, berberine, and formononetin, were selected as potential quality markers (Q-markers) in MLSTP. Finally, the quantitative analysis of multi-components by single marker (QAMS) method was established to quantitatively analyze the six potential Q-markers, and the results were consistent with those obtained by the external standard method (ESM). Taken together, the multi-strategy platform established in this study would be conducive to the Q-markers screening and quality control of MLSTP, improving the quality standard of MLSTP and providing favorable assurance for the clinical management of TAO.

Psoriasis is a chronic autoimmune inflammatory skin disorder that affects approximately 2-3% of the global population due to significant genetic predisposition. It is characterized by an uncontrolled growth and differentiation of keratinocytes, leading to the formation of scaly erythematous plaques. Psoriasis extends beyond dermatological manifestations to impact joints and nails and is often associated with systemic disorders. Although traditional treatments provide relief, their use is limited by potential side effects and the chronic nature of the disease. This review aims to discuss the therapeutic potential of keratinocyte-targeting natural products in psoriasis and highlight their efficacy and safety in comparison with conventional treatments. This review comprehensively examines psoriasis pathogenesis within keratinocytes and the various related signaling pathways (such as JAK-STAT and NF-κB) and cytokines. It presents molecular targets such as high-mobility group box-1 (HMGB1), dual-specificity phosphatase-1 (DUSP1), and the aryl hydrocarbon receptor (AhR) for treating psoriasis. It evaluates the ability of natural compounds such as luteolin, piperine, and glycyrrhizin to modulate psoriasis-related pathways. Finally, it offers insights into alternative and sustainable treatment options with fewer side effects.

Rheumatoid arthritis is a chronic immunological disease leading to the progressive bone and joint destruction. Angiogenesis, accompanied by synovial hyperplasia and inflammation underlies joint destruction. Delaying or even blocking synovial angiogenesis has emerged as an important target of RA treatment. Natural medicines has a long history of treating RA, and numerous reports have suggested that natural medicines have a strong inhibitory activity on synovial angiogenesis, thereby improving the progression of RA. Natural medicines could regulate the following signaling pathways: HIF/VEGF/ANG, PI3K/Akt pathway, MAPKs pathway, NF-κB pathway, PPARγ pathway, JAK2/STAT3 pathway, etc., thereby inhibiting angiogenesis. Tripterygium wilfordii Hook. f. (TwHF), sinomenine, and total glucoside of Paeonia lactiflora Pall. Are currently the most representative of all natural products worthy of development and utilization. In this paper, the main factors affecting angiogenesis were discussed and different types of natural medicines that inhibit angiogenesis were systematically summarized. Their specific anti-angiogenesis mechanisms are also reviewed which aiming to provide new perspective and options for the management of RA by targeting angiogenesis.

Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).

The main pathological features of osteoarthritis (OA) include the degeneration of articular cartilage and a decrease in matrix synthesis. Chondrocytes, which contribute to matrix synthesis, play a crucial role in the development of OA. Liquiritin, an effective ingredient extracted from Glycyrrhiza uralensis Fisch., has been used for over 1000 years to treat OA. This study aims to investigate the impact of liquiritin on OA and its underlying mechanism.

Gait and hot plate tests assessed mouse behavior, while Micro-CT and ABH/OG staining observed joint morphological changes. The TUNEL kit detected chondrocyte apoptosis. Western blot and immunofluorescence techniques determined the expression levels of cartilage metabolism markers COL2 and MMP13, as well as apoptosis markers caspase3, bcl2, P53, and PUMA. KEGG analysis and molecular docking technology were used to verify the relationship between liquiritin and P53.

Liquiritin alleviated pain sensitivity and improved gait impairment in OA mice. Additionally, we found that liquiritin could increase COL2 levels and decrease MMP13 levels both in vivo and in vitro. Importantly, liquiritin reduced chondrocyte apoptosis induced by OA, through decreased expression of caspase3 expression and increased expression of bcl2 expression. Molecular docking revealed a strong binding affinity between liquiritin and P53. Both in vivo and in vitro studies demonstrated that liquiritin suppressed the expression of P53 and PUMA in cartilage.

This indicated that liquiritin may alleviate OA progression by inhibiting the P53/PUMA signaling pathway, suggesting that liquiritin is a potential strategy for the treatment of OA.

Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb-compound-biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)-saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)-lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)-glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA's downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG's effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.

Phenolic compounds are the main phytochemical constituents of many higher plants. They play an important role in synthesizing metal nanoparticles using green technology due to their ability to reduce metal salts and stabilize them through physical interaction/conjugation to the metal surface. Six pure phenolic compounds were isolated from licorice (Glycyrrhiza glabra) and employed in synthesizing gold nanoparticles (AuNPs). The isolated compounds were identified as liquiritin (1), isoliquiritin (2), neoisoliquiritin (3), isoliquiritin apioside (4), liquiritin apioside (5), and glabridin (6). The synthesized AuNPs were characterized using UV, zeta sizer, HRTEM, and IR and tested for their stability in different biological media. The phenolic isolates and their corresponding synthesized NP conjugates were tested for their potential in vitro cytotoxicity. The anti-inflammatory effects were investigated in both normal and inflammation-induced settings, where inflammatory biomarkers were stimulated using lipopolysaccharides (LPSs) in the RAW 264.7 macrophage cell line. LPS, functioning as a mitogen, promotes cell growth by reducing apoptosis, potentially contributing to observed outcomes. Results indicated that all six pure phenolic isolates inhibited cell proliferation. The AuNP conjugates of all the phenolic isolates, except liquiritin apioside (5), inhibited cell viability. LPS initiates inflammatory markers by binding to cell receptors and setting off a cascade of events leading to inflammation. All the pure phenolic isolates, except isoliquiritin, neoisoliquiritin, and isoliquiritin apioside inhibited the inflammatory activity of RAW cells in vitro.

Psoriasis is a chronic inflammation and relapsing disease that affected approximately 100 million individuals worldwide. In previous clinical study, it was observed that the topical application of Si Cao Formula (SCF) ameliorated psoriasis skin lesions and reduced the recurrence rate of patients over a period of three months. However, the precise mechanism remains unclear.

The objective of this study was to assess the effectiveness and safety of SCF in patients diagnosed with psoriasis and explore the molecular mechanisms that contribute to SCF's therapeutic efficacy in psoriasis treatment.

A randomized, controlled, and pilot clinical study was performed. This study assessed 30 individuals diagnosed with mild to moderate plaque psoriasis. 15 of them underwent local SCF treatment, the others received calcipotriol intervention. The outcome measure focused on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and recurrence rate. In addition, IMQ-induced psoriasis-like mice model were used to assess the impact of SCF on ameliorating epidermal hyperplasia, suppressing angiogenesis, and modulating immune response. Furthermore, we performed bioinformatics analysis on transcriptome data obtained from skin lesions of mice model. This analysis allowed us to identify the targets and signaling pathways associated with the action of SCF. Subsequently, we conducted experimental validation to confirm the core targets.

Our clinical pilot study demonstrated that SCF could ameliorate skin lesions in psoriasis patients with comparable efficacy of calcipotriol in drop of PASI and DLQI scores. SCF exhibited a significantly reduced recurrence rate within 12 weeks (33.3%). Liquid Chromatography Mass Spectrometry (LC-MS) identified 41 active constituents of SCF (26 cations and 15 anions). Animal experiments showed SCF ameliorates the skin lesions of IMQ-induced psoriasis like mice model and suppresses epidermal hyperkeratosis and angiogenesis. There were 845 up-regulated and 764 down-regulated DEGs between IMQ and IMQ + SCF groups. GO analysis revealed that DEGs were linked to keratinization, keratinocyte differentiation, organic acid transport epidermal cell differentiation, and carboxylic acid transport interferon-gamma production. KEGG pathway analysis showed that SCF may play a vital part through IL-17 and JAK/STAT signaling pathway. In addition, SCF could reduce the number of positive cells expressing PCNA, CD31, pSTAT3, CD3, and F4/80 within the epidermis of psoriatic lesions, as well as the expression of Il-17a and Stat3 in IMQ-induced psoriasis mice.

Our research suggests that SCF serves as a reliable and efficient local approach for preventing and treating psoriasis. The discovery of plausible molecular mechanisms and therapeutic targets associated with SCF may support its broad implementation in clinical settings.

Serine proteases are a class of hydrolytic enzymes involved in various physiological functions like digestion, coagulation, fibrinolysis and immunity. The present study evaluates the serine protease inhibitory potential of phytochemicals liquiritin and terpinen-4-ol present in the herb Glycyrrhiza glabra L. using trypsin as the model enzyme. In silico studies showed that both the compounds have a significant binding affinity towards trypsin with a binding energy of -26.66 kcal/mol and -19.79 kcal/mol for liquiritin and terpinen-4-ol, respectively. Their binding affinity was confirmed through in vitro enzyme inhibition assays. The mode of inhibition was found to be uncompetitive. In order to explain the mode of inhibition, docking of the ligands to the enzyme-substrate complex was also done and binding energy was calculated after MD simulation. The energy values showed that the binding affinities of these compounds towards the enzyme substrate complex are more than that towards the enzyme alone. This explains the uncompetitive mode of inhibition.Communicated by Ramaswamy H. Sarma.

Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people's lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of 40 μg/mL and below and cell damage at UVB irradiation doses above 60 mJ/cm2. Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, 2% LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF-α, IL-1β, and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis.

Accumulating evidence has highlighted a strong association between gut microbiota and the occurrence, development, prevention, and treatment of atopic dermatitis (AD). The regulation of gut microbial dysbiosis by oral traditional Chinese medicine (TCM) has garnered significant attention. In the treatment of AD, the TCM formula Qingre-Qushi Recipe (QRQS) has demonstrated clinical efficacy. However, both the therapeutic mechanisms of QRQS and its impact on gut microbiota remain unclear. Thus, our study aimed to assess the efficacy of QRQS and evaluate its influence on the composition and diversity of gut microbiota in AD animal models. First, we investigated the therapeutic effect of QRQS on AD using two animal models: filaggrin-deficient mice (Flaky tail, ft/ft) and MC903-induced AD-like mice. Subsequently, we explored its influence on the composition and diversity of gut microbiota. Our results demonstrated that QRQS treatment ameliorated the symptoms in both ft/ft mice and MC903-induced AD-like mice. It also reduced the levels of serum IgE and pro-inflammatory cytokines, including IL-1β, IL-4, IL-5, IL-9, IL-13, IL-17A, and TNF-α. Furthermore, QRQS remarkably regulated gut microbiota diversity by increasing Lactobacillaceae and decreasing Bacteroidales. The inflammatory factors in peripheral serum of ft/ft mice showed a close correlation with gut microbiota, as determined using the Spearman correlation coefficient. Additionally, PICRUSt analysis revealed an enrichment in ascorbate and aldarate metabolism, fatty acid metabolism and biosynthesis, and propanoate metabolism in the QRQS group compared to the ft/ft group. Finally, we identified liquiritin as the primary active ingredient of QRQS using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Our findings revealed that QRQS improved AD-like symptoms and alleviated skin inflammation in ft/ft and MC903-induced mice. This suggests that modulating the gut microbiota may help elucidate its anti-inflammation activation mechanism, highlighting a new therapeutic strategy that targets the intestinal flora to prevent and treat AD.

Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.

The aim of this study is to use modeling methods to estimate the antiviral activity of natural molecules extracted from Ginkgo biloba for the treatment of variola which is a zoonotic disease posing a growing threat to human survival. The recent spread of variola in nonendemic countries and the possibility of its use as a bioterrorism weapon have made it a global threat once again. Therefore, the search for new antiviral therapies with reduced side effects is necessary.

In this study, we examined the interactions between polyphenolic compounds from Ginkgo biloba, a plant known for its antiviral activity, and two enzymes involved in variola treatment, VarTMPK and HssTMPK, using molecular docking.

The obtained docking scores showed that among the 152 selected polyphenolic compounds; many ligands had high inhibitory potential according to the energy affinity. By considering Lipinski's rules, we found that Liquiritin and Olivil molecules are the best candidates to be developed into drugs that inhibit VarTMPK because of their high obtained scores compared to reference ligands, and zero violations of Lipinski's rules. We also found that ginkgolic acids have good affinities with HssTMPK and acceptable physicochemical properties to be developed into drugs administered orally.

Based on the obtained scores and Lipinski's rules, Liquiritin, Olivil, and ginkgolic acids molecules showed interesting results for both studied enzymes, indicating the existence of promising and moderate activity of these polyphenols for the treatment of variola and for possible multi-targeting. Liquiritin has been shown to exhibit anti-inflammatory effects on various inflammation- related diseases such as skin injury, hepatic inflammatory injury, and rheumatoid arthritis. Olivil has been shown to have antioxidant activity. Olivil derivatives have also been studied for their potential use as anticancer agents. Ginkgolic acids have been shown to have antimicrobial and antifungal properties. However, ginkgolic acids are also known to cause allergic reactions in some people. Therefore, future studies should consider these results and explore the potential of these compounds as antiviral agents. Further experimental studies in-vitro and in-vivo are required to validate and scale up these findings.

Parkinson disease (PD) is characterized by the loss of dopaminergic neurons because of oxidative stress and neuroinflammation. Polyphenols in vegetables, known for their high antioxidant capacity, may prevent the onset, or delay the progression of the disease; among these, flavonoids are the most abundant class of polyphenols in foods. Clinical and cohort studies have evaluated the effect of polyphenol consumption on the risk of developing PD or of attenuating the symptoms after diagnosis; therefore, it is necessary to integrate the scientific evidence into making dietary recommendations. The objective of this study was to perform a systematic review of randomized controlled trials and cohort studies that have investigated the use of polyphenols in PD. The studies were identified through the PubMed, Science Direct, Scielo, and Web of Science databases. A total of 1100 studies were found; these were analyzed and filtered by 2 independent reviewers. After completion, 5 studies were included (3 randomized controlled trials and 2 cohort studies). The consumption of flavonoids, anthocyanins, or 2-5 servings/week of specific foods (apples, red wine, blueberries, and strawberries) reduces the risk of PD and associated mortality. Treatment with licorice, curcumin, or cocoa, which are rich in flavonoids and other polyphenols, improves motor function in PD patients. No statistically significant differences were found in quality of life, disease progression or nonmotor symptoms such as cognitive ability and mood. Although cohort studies suggest a neuroprotective effect, further clinical studies are urgently needed to evaluate the effect of specific flavonoids and other polyphenols in PD.

Transient receptor potential vanilloid 1 (TRPV1) channels are widely distributed in sensory nerve endings, the central nervous system, and other tissues, functioning as ion channel proteins responsive to thermal pain and chemical stimuli. In recent years, the TRPV1 receptor has garnered significant interest as a potential therapeutic approach for various pain-related disorders, particularly TRPV1 antagonists. The present review offers a comprehensive, systematic exploration of both first- and second-generation TRPV1 antagonists in the context of pain management. Antagonists are categorized and explicated according to their structural characteristics. Detailed examination of binding modes, structural features, and pharmacological activities, alongside a critical appraisal of the advantages and limitations inherent to typical compounds within each structural category, are undertaken. Detailed discussions of the binding modes, structural features, pharmacological activities, advantages, and limitations of typical compounds within each structural category offer valuable insights and guidance for the future research and development of safer, more effective, and more targeted TRPV1 antagonists.

Osteoporosis, a prevalent osteolytic condition worldwide, necessitates effective strategies to inhibit excessive bone resorption by curbing osteoclast hyperactivation. Liquiritin (LIQ), an flavanone derivative employed in acute lung injury and rheumatoid arthritis treatment, possesses an unclear role in addressing excessive bone resorption. In this investigation, we found that LIQ demonstrates the ability to inhibit osteoclast formation and the bone-resorbing activity induced by RANKL. At a specific concentration, LIQ significantly attenuated NF-κB-Luc activity induced by RANKL and curtailed NF-κB activation in RANKL-stimulated RAW264.7 cells, resulting in reduced IκB-α breakdown and diminished nuclear NF-κB levels. Furthermore, LIQ markedly inhibited RANKL-induced NFATc1 activation, as evidenced by diminished NFATc1 luciferase activity, reduced NFATc1 mRNA levels, and decreased nuclear NFATc1 protein levels. Subsequent experiments demonstrated that LIQ effectively restrained the RANKL-induced elevation of intracellular calcium as well as reactive oxygen species. Additionally, LIQ exhibited a downregulating effect on the expression of osteoclast-specific genes, which include Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-Fos, and Mmp9. Notably, our findings revealed the potential of LIQ to counteract decreased bone density in mice that underwent ovariectomy. Collectively, the data indicate that LIQ impedes osteoclast formation triggered by RANKL and the subsequent reduction in bone mass by mitigating ROS levels and suppressing the Ca2+/MAPK-NFATc1 signaling pathway, suggesting its promising candidacy as a therapeutic agent for RANKL-mediated osteoporosis.

Background: Xiao-Er-An-Shen decoction (XEASD), a TCM formula composed of sixteen Chinese medicinal herbs, has been used to alleviate tic disorders (TD) in clinical practice for many years. However, the chemical basis underlying the therapeutic effects of XEASD in the treatment of TD remains unknown. Purpose: The present study aimed to determine the major chemical components of XEASD and its prototype compounds and metabolites in mice biological samples. Methods: The chemical constituents in XEASD were identified using ultra-high Performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Following this, XEASD was orally administered to mice, and samples of plasma, urine, feces, bile, and tissue were collected in order to identify effective compounds for the prevention or treatment of TD. Result: Of the total 184 compounds identified to be discriminated in the XEASD, comprising 44 flavonoids, 26 phenylpropanoids, 16 coumarins, 16 triterpenoids, 14 amino acids, 13 organic acids, 13 alkaloids, 13 ketones, 10 cyclic enol ether terpenes, 7 citrullines, 3 steroids, and 5 anthraquinones, and others. Furthermore, we summarized 54 prototype components and 78 metabolic products of XEASD, measured with biological samples, by estimating metabolic principal components, with four prototype compounds detected in plasma, 58 prototypes discriminated in urine, and 40 prototypes identified in feces. These results indicate that the Oroxylin A glucuronide from Citri reticulatae pericarpium (CRP) is a major compound with potential therapeutic effects identified in brain, while operating positive effect in inhibiting oxidative stress in vitro. Conclusion: In summary, our work delineates the chemical basis underlying the complexity of XEASD, providing insights into the therapeutic and metabolic pathways for TD. Various types of chemicals were explored in XEASD, including flavonoids, phenylpropanoids, coumarins, organic acids, triterpenoid saponins, and so on. This study can promote the further pharmacokinetic and pharmacological evaluation of XEASD.