An integrative pharmacology-based study on the efficacy and mechanism of essential oil of Chaihu Guizhi Decoction on influenza A virus induced pneumonia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. AIM OF THE STUDY: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. MATERIALS AND METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 µg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.

Exploring the action mechanism and effective components of Yupingfeng powder on influenza based on computational system pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Yupingfeng powder (YPF) is a classic traditional Chinese medicine prescription with a long history of clinical application. However, there is a consensus on the clinical efficacy of YPF in the prevention and treatment of influenza, the underlying pharmacological mechanisms and functional substances have not been thoroughly investigated. AIM OF THE STUDY: This study aimed to elucidate the functional substances and potential mechanisms of YPF against influenza infections by integrating network analysis, metabolomics, computational system pharmacology, and in vitro experiments. MATERIALS AND METHODS: In this study, the active ingredients, related targets, and potential mechanisms of YPF against influenza were identified through network pharmacology and GEO database mining. Combined with metabolomics to corroborate the results of network pharmacology analysis and construct C-T-P-D-M network. Based on this, the key network motifs (KNM) with significance were predicted by system pharmacology algorithm. Finally, the key components as functional substances in the KNM were validated by the coverage of influenza-causing genes and functional pathways, and in vitro experiments. RESULTS: A total of 238 active components and 158 potential target genes intersecting with influenza infection differential genes were screened from YPF. KEGG enrichment analysis indicated that metabolism participated in YPF-provided prevention and treatment on influenza, and metabolomic results further corroborated the significance of the metabolic pathways intervened by YPF included pyruvate metabolism, Valine, leucine and isoleucine degradation, etc. The KNM prediction strategy was computed to include wogonin and isoimperaporin, a group of 48 potential functional components. This functional component group maintained a high degree of consistency with the corresponding C-T network in terms of the coverage of influenza pathogenic genes, and the coverage of functional pathways. Meanwhile, the in vitro results showed that wogonin and isoimperaporin had significant inhibitory effects on inflammation induced by influenza infection, confirming the reliability and accuracy of the KNM prediction strategy. CONCLUSION: YPF against influenza has multi-target and multi-pathway effects, and the underlying mechanisms may be related to metabolism. The pharmacodynamic effects of core components such as wogonin and isoimperaporin on influenza prevention and treatment were confirmed, which represent promising functional candidates for subsequent influenza prevention and treatment, and provide references for the pharmacological and mechanistic analyses of subsequent formulas.

Traditional uses, botany, phytochemistry, pharmacology and applications of Labisia pumila: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Labisia pumila (Blume) Fern.-Vill, also known as Kacip Fatimah, is a traditional medicinal herb common throughout Southeast Asia. It is primarily used to facilitate childbirth and postpartum recovery in women. Additionally, it can also be used to treat dysentery, rheumatism, gonorrhea, and as an anti-flatulent. AIM OF THIS REVIEW: This article aims to provide a comprehensive review of the traditional uses, botany, cultivation, phytochemistry, pharmacological effects, practical applications, and potential uses of L. pumila (LP). Furthermore, we also explore the safety of this plant and its potential prospects for application. MATERIALS AND METHODS: The keywords "Labisia pumila," "Kacip Fatimah," and "Marantodes pumilum" were used to collect relevant information through electronic searches (including Elsevier, PubMed, Google Scholar, Baidu Scholar, CNKI, ScienceDirect, and Web of Science). RESULTS: This review summarizes 102 chemical components from different parts of the plant, including flavonoids, phenolic acids, saponins, and other chemical components. In addition, we also address the associated cultivation conditions, traditional uses, pharmacological effects and toxicity. A large number of reports indicate that LP has various pharmacological effects such as antioxidant, phytoestrogenic, anti-inflammtory, antimicrobial, anti-osteoporosis and anti-obesity properties. These results provide valuable references for future research on LP. In addition, LP is also a potential medicinal and edible plant, and is currently sold on the market as a dietary supplement. CONCLUSIONS: LP is a renowned traditional ethnic medicine with numerous pharmacological activities attributed to its bioactive components. Therefore, isolation and identification of the chemical components in LP can be a focus of our future research. Current studies have focused only on the effects of LP on estrogen deficiency-related diseases in women and bone diseases. There is no scientific evidence for other traditional uses. Therefore, it is important to further explore its pharmacological activities and fill the research gaps related to other traditional uses. Furthermore, research on its safety should be expanded to prepare clinical applications.

Exploring antithrombotic mechanisms and effective constituents of Lagopsis supina using an integrated strategy based on network pharmacology, molecular docking, metabolomics, and experimental verification in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Thrombosis is a common cause of morbidity and mortality worldwide. Lagopsis supina (Stephan ex Willd.) Ikonn.-Gal. ex Knorring is an ancient Chinese herbal medicine used for treating thrombotic diseases. Nevertheless, the antithrombotic mechanisms and effective constituents of this plant have not been clarified. AIM OF THE STUDY: This work aimed to elucidate the pharmacodynamics and mechanism of L. supina against thrombosis. MATERIALS AND METHODS: Systematic network pharmacology was used to explore candidate effective constituents and hub targets of L. supina against thrombosis. Subsequently, the binding affinities of major constituents with core targets were verified by molecular docking analysis. Afterward, the therapeutic effect and mechanism were evaluated in an arteriovenous bypass thrombosis rat model. In addition, the serum metabolomics analysis was conducted using ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrometry. RESULTS: A total of 124 intersected targets of L. supina against thrombosis were predicted. Among them, 24 hub targets were obtained and their mainly associated with inflammation, angiogenesis, and thrombosis approaches. Furthermore, 9 candidate effective constituents, including (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol, aurantiamide, (22E,24R)-5α,8α-epidioxyergosta-6,9 (11),22-trien-3ß-ol, lagopsinA, lagopsin C, 15-epi-lagopsin C, lagopsin D, 15-epi-lagopsin D, and lagopsin G in L. supina and 6 potential core targets (TLR-4, TNF-α, HIF-1α, VEGF-A, VEGFR-2, and CLEC1B) were acquired. Then, these 9 constituents demonstrated strong binding affinities with the 6 targets, with their lowest binding energies were all less than -5.0 kcal/mol. The antithrombotic effect and potential mechanisms of L. supina were verified, showing a positively associated with the inhibition of inflammation (TNF-α, IL-1ß, IL-6, IL-8, and IL-10) and coagulation cascade (TT, APTT, PT, FIB, AT-III), promotion of angiogenesis (VEGF), suppression of platelet activation (TXB2, 6-keto-PGF1α, and TXB2/6-keto-PGF1α), and prevention of fibrinolysis (t-PA, u-PA, PAI-1, PAI-1/t-PA, PAI-1/u-PA, and PLG). Finally, 14 endogenous differential metabolites from serum samples of rats were intervened by L. supina based on untargeted metabolomics analysis, which were closely related to amino acid metabolism, inflammatory and angiogenic pathways. CONCLUSION: Our integrated strategy based on network pharmacology, molecular docking, metabolomics, and in vivo experiments revealed for the first time that L. supina exerts a significant antithrombotic effect through the inhibition of inflammation and coagulation cascade, promotion of angiogenesis, and suppression of platelet activation. This paper provides novel insight into the potential of L. supina as a candidate agent to treat thrombosis.

Uncovering the pharmacological mechanisms of Patchouli essential oil for treating ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemonis Herba has long been used in traditional Chinese medicine to treat inflammatory disorders. Patchouli essential oil (PEO) is the primary component of Pogostemonis Herba, and it has been suggested to offer curative potential when applied to treat ulcerative colitis (UC). However, the pharmacological mechanisms of PEO for treating UC remain to be clarified. AIM OF THE STUDY: To elucidate the pharmacological mechanisms of PEO for treating UC. METHODS AND RESULTS: In the present study, transcriptomic and network pharmacology approaches were combined to clarify the mechanisms of PEO for treating UC. Our results reveal that rectal PEO administration in UC model mice significantly alleviated symptoms of UC. In addition, PEO effectively suppressed colonic inflammation and oxidative stress. Mechanistically, PEO can ameliorate UC mice by modulating gut microbiota, inhibiting inflammatory targets (OPTC, PTN, IFIT3, EGFR, and TLR4), and inhibiting the PI3K-AKT pathway. Next, the 11 potential bioactive components that play a role in PEO's anti-UC mechanism were identified, and the therapeutic efficacy of the pogostone (a bioactive component) in UC mice was partially validated. CONCLUSION: This study highlights the mechanisms through which PEO can treat UC, providing a rigorous scientific foundation for future efforts to develop and apply PEO for treating UC.

Uncovering the mechanisms of Zhubi decoction against rheumatoid arthritis through an integrated study of network pharmacology, metabolomics, and intestinal flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription "Er-Xian Decoction" documented in the esteemed "Clinical Manual of Chinese Medical Prescription". While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. AIM OF THE STUDY: This study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. MATERIALS AND METHODS: Utilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. RESULTS: ZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1ß and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. CONCLUSION: ZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.

In vivo and in vitro study on the regulatory mechanism of XiaoChaiHu decoction on PANoptosis in sepsis-induced cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: In accordance with the tenets of traditional Chinese medicine, sepsis is categorized into three distinct syndromes: heat syndrome, blood stasis syndrome, and deficiency syndrome. Xiaochaihu decoction (XCHD) has many functions, including the capacity to protect the liver, cholagogue, antipyretic, anti-inflammatory, and anti-pathogenic microorganisms. XCHD exerts the effect of clearing heat and reconciling Shaoyang. The XCHD contains many efficacious active ingredients, yet the mechanism of sepsis-induced cardiomyopathy (SIC) remains elusive. AIM OF THE STUDY: To investigate the molecular mechanisms underlying the protective effects of XCHD against SIC using an integrated approach combining network pharmacology and molecular biology techniques. MATERIALS AND METHODS: Network pharmacology methods identified the active ingredients, target proteins, and pathways affected by XCHD in the context of SIC. We conducted in vivo experiments using mice with lipopolysaccharide-induced SIC, evaluating cardiac function through echocardiography and histology. XCHD-containing serum was analyzed to determine its principal active components using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The effects of XCHD-containing serum on SIC were further tested in vitro in LPS-treated H9c2 cardiac cells. Protein expression levels were quantified via Western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, molecular docking was performed between the active components and ZBP1, a potential target protein. Overexpression of ZBP1 in H9c2 cells allowed for a deeper exploration of its role in modulating SIC-associated gene expression. RESULTS: UPLC-MS/MS identified 31 shared XCHD and XCHD-containing serum components. These included organic acids, terpenoids, and flavonoids, which have been identified as the active components of XCHD. Our findings revealed that XCHD alleviated LPS-induced myocardial injury, improved cardiac function, and preserved cardiomyocyte morphology in mice. In vitro studies, we demonstrated that XCHD-containing serum significantly suppressed the expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in LPS-induced H9c2 cells. Mechanistic investigations showed that XCHD downregulated genes associated with PANoptosis, a novel cell death pathway, suggesting its protective role in sepsis-damaged hearts. Conversely, overexpression of ZBP1 abolished the protective effects of XCHD and amplified PANoptosis-related gene expression. CONCLUSIONS: Our study provides the first evidence supporting the protective effects of XCHD against SIC, both in vitro and in vivo. The underlying mechanism involves the inhibition of ZBP1-initiated PANoptosis, offering new insights into treating SIC using XCHD.

Integration of network pharmacology and experimental verification to reveal the active components and molecular mechanism of modified Danzhi Xiaoyao San in the treatment of depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. AIM OF THE STUDY: To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro. MATERIALS AND METHODS: UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. RESULTS: There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. CONCLUSIONS: These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.

Integration of network pharmacology, UHPLC-Q exactive orbitrap HRMS technique and metabolomics to elucidate the active ingredients and mechanisms of compound danshen pills in treating hypercholesterolemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypercholesterolemia (HLC) was a key risk factor for cardiovascular disease (CVD) characterized by elevated cholesterol levels, particularly LDL. While traditional Chinese medicine preparations Compound Danshen Pills(CDP) has been clinically used for hypercholesterolemia and coronary heart disease, its specific therapeutic effect on HLC remains understudied, necessitating further investigation into its mechanisms. AIM OF THE STUDY: The aim of this study was to explore the potential of CDP in treating HLC and elucidate its underlying mechanisms and active components. MATERIALS AND METHODS: A hypercholesterolemic lipemia rat model induced by a high-fat diet was employed. Network pharmacology combined with UHPLC-Q exactive orbitrap HRMS technique was used to predict the active components, targets and mechanisms of CDP for HLC. Histological analysis and serum biochemical assays were used to assess the therapeutic effect of CDP and its main active ingredient Sa B on hypercholesterolemic lipemia rat model. Immunofluorescence assays and western blotting were used to verify the mechanism of CDP and Sa B in the treatment of HLC. Metabolomics approach was used to demonstrate that CDP and Sa B affected the metabolic profile of HLC. RESULTS: Our findings demonstrated that both CDP and its main active ingredient Sa B significantly ameliorated hypercholesterolemic lipemic lesions, reducing levels of TC, LDL, AST, ALT, and ALP. Histological analysis revealed a decrease in lipid droplet accumulation and collagen fiber deposition in the liver, as well as reduced collagen fiber deposition in the aorta. Network pharmacology predicted potential targets such as PPARα and CYP27A1. Immunofluorescence assays and western blotting confirmed that CDP and Sa B upregulated the expression of Adipor1, PPARα and CYP27A1. Metabolomics analyses further indicated improvements in ABC transporters metabolic pathways, with differential metabolites such as riboflavin, taurine, and choline showed regression in levels after CDP treatment and riboflavin, L-Threonine, Thiamine, L-Leucine, and Adenosine showed improved expression after Sa B treatment. CONCLUSION: CDP and Sa B have been shown to alleviate high-fat diet-induced hypercholesterolemia by activating the PPAR pathway and improving hepatic lipid metabolism. Our study demonstrated, for the first time, the complex mechanism of CDP, Sa B in the treatment of hypercholesterolemia at the protein and metabolic levels and provided a new reference that could elucidate the pharmacological effects of traditional Chinese medicine on hypercholesterolemia from multiple perspectives.

Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism.

Objective: To explore the pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction (HYD) in treating hyperthyroidism via an analysis integrating network pharmacology, molecular docking, and non-targeted serum metabolomics. Methods: Therapeutic targets of hyperthyroidism were searched through multi-array analyses in the Gene Expression Omnibus (GEO) database. Hub genes were subjected to the construction of a protein-protein interaction (PPI) network, and GO and KEGG enrichment analyses. Targets of active pharmaceutical ingredients (APIs) in HYD and those of hyperthyroidism were intersected to yield hub genes, followed by validations via molecular docking and non-targeted serum metabolomics. Results: 112 hub genes were identified by intersecting APIs of HYD and therapeutic targets of hyperthyroidism. Using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) in both negative and positive ion polarity modes, 279 compounds of HYD absorbed in the plasma were fingerprinted. Through summarizing data yielded from network pharmacology and non-targeted serum metabolomics, 214 common targets were identified from compounds of HYD absorbed in the plasma and therapeutic targets of hyperthyroidism, including PTPN11, PIK3CD, EGFR, HRAS, PIK3CA, AKT1, SRC, PIK3CB, and PIK3R1. They were mainly enriched in the biological processes of positive regulation of gene expression, positive regulation of MAPK cascade, signal transduction, protein phosphorylation, negative regulation of apoptotic process, positive regulation of protein kinase B signaling and positive regulation of MAP kinase activity; and molecular functions of identical protein binding, protein serine/threonine/tyrosine kinase activity, protein kinase activity, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding and protein binding. A total of 185 signaling pathways enriched in the 214 common targets were associated with cell proliferation and angiogenesis. Conclusion: HYD exerts a pharmacological effect on hyperthyroidism via inhibiting pathological angiogenesis in the thyroid and rebalancing immunity.

Dauricine: Review of Pharmacological Activity.

Background: Dauricine is an important natural organic compound in Menispermum dauricum, which often has significant biological activity. Purpose: The purpose of this review is to systemically summarize and discuss the pharmacological activity and underlying mechanisms of dauricine in recent years. Methods: Web of Science (121 articles) and PubMed databases (97 articles) were used to search for articles related to "dauricine" published from 2000 to 2024. Meanwhile, we classified the pharmacological activity of dauricine by screening these articles. Results: Emerging evidence suggests that dauricine possesses numerous pharmacological activities, including neuroprotection, anti-cancer, anti-arrhythmia, anti-inflammatory and anti-diabetes. Conclusion: Dauricine has a potential value in the treatment of many diseases. We hope that this review will contribute to therapeutic development and future studies of dauricine.

Network pharmacology and molecular docking approach to elucidate the mechanisms of safflower, phellodendron, scutellaria baicalensis, coptis, and gardenia in hand-foot syndrome.

Background: Safflower, phellodendron, scutellaria baicalensis, coptis, and gardenia (SPSCG) are medicinal plants with a wide range of anti-inflammatory and antioxidant effects. However, the related mechanism of SPSCG against hand-foot syndrome (HFS) has yet to be revealed. Objective: To investigate the mechanisms of SPSCG in the treatment of HFS using the Network Pharmacology. Methods: Active ingredients and targets of SPSCG for HFS were screened by the Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction databases. Potential therapeutic targets were collected from the GeneCards and OMIM databases. Subsequently, protein-protein interactions (PPI), Gene Ontology (GO) annotations, and pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to investigate the potential mechanism of the SPSCG in HFS. Then, molecular docking and molecular dynamics simulations were performed to predict the binding interactions between the active compound and the core target. Finally, vitro experiments were used to verify the repair effect of key ingredients of SPSCG on cell damage caused by 5-Fluorouracil. Results: Quercetin, kaempferol, ß-sitosterol, and stigmasterol were identified as the major active components of SPSCG. GO analysis showed a total of 1,127 biological processes, 42 terms cellular components, and 57 molecular functions. KEGG analysis showed that the MAPK, TNF, and IL-17 signaling pathways were significantly enriched. The PPI analysis discovered that EGFR, CASP3, AKT1, CCND1, and CTNNB1 shared the highest centrality among all target genes. The experimental results confirmed that these SPSCG active ingredients could treat HFS by reducing inflammation reaction and promoting cell damage repair. Conclusion: SPSCG may alleviate HFS by exerting antioxidative effects and suppressing inflammatory responses.

Integrating multiomics and Single-Cell communication analysis to uncover Ankylosing spondylitis mechanisms.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory joint disorder, necessitating early diagnosis and effective treatment. The specific mechanism of action of Cassia twigs in the treatment of AS is not fully understood. METHODS: Blood samples and clinical data from 28,458 individuals (6,101 with AS, 22,357 without AS) were collected. To construct a predictive model, we utilized logistic regressions and machine learning techniques to create a dynamic nomogram. Immune cell infiltration was evaluated using the GSE73754 dataset. Subsequently, we obtained vertebral bone marrow blood from AS patients for 10X single-cell sequencing. We also extracted and purified total RNA from hip joint ligament tissue samples from six AS patients and six non-AS patients. The genes related to the expression of AS and Cassia twigs were analyzed comprehensively, and the specific drug targets were identified by molecular docking. The interactions between immune cells through cell communication analysis were elucidated. RESULTS: We developed a dynamic nomogram incorporating the neutrophil count (NEUT) and other variables. Neutrophil immune responses were confirmed through immune infiltration analysis utilizing GSE73754. We observed the early involvement of neutrophils in the pathology of AS. The CAT-expressing Cassia twigs gene could be used as a drug target for the treatment of AS. Moreover, comprehensive RNA analysis revealed notable CAT expression in neutrophils and various other immune cells. CONCLUSIONS: Neutrophils play dual roles in AS, regulating inflammation and initiating differentiation signals to other cells. The CAT gene, which is expressed in Cassia twigs, has emerged as a potential therapeutic target for AS treatment.

Network pharmacology-based strategy to reveal the mechanism of pinocembrin against ovarian cancer.

Ovarian cancer stands as the foremost cause of mortality among gynaecological diseases globally, characterized by high morbidity and mortality. Pinocembrin, a flavonoid from natural plant sources, exhibits diverse pharmacological properties. Despite its known pharmacological activities, its specific role in ovarian cancer treatment remains scarcely reported, and its precise molecular mechanism remains elusive. This study integrates network pharmacology and molecular docking techniques to explore pinocembrin's potential mechanism in ovarian cancer treatment. The targets of pinocembrin were compiled from the several online databases. Ovarian cancer targets were identified using the GeneCards database, with common target genes determined by data aggregation. Protein-protein interactions were analysed using the STRING platform. Subsequent Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Molecular docking assessed the binding affinity between potential targets and active compounds. Finally, target validity was verified through in vitro experiments. We identified 163 potential pinocembrin targets for ovarian cancer treatment. GO and KEGG analyses revealed pinocembrin's involvement in protein kinase activity, protein phosphorylation, protein kinase complexes and cancer pathways in ovarian cancer treatment. Molecular docking demonstrated strong binding affinity between pinocembrin and most potential target active sites. In vitro experiments suggested pinocembrin's potential to induce apoptosis in ovarian cancer cells through the AKT1-mTOR signalling pathway. This study comprehensively elucidates pinocembrin's potential targets and mechanisms against ovarian cancer, aiming to provide promising candidates for developing novel and effective alternative and/or complementary nutritional supplements for the clinical treatment of ovarian cancer.

Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer.

BACKGROUND: Cancer is one of the most serious threats to human health worldwide. Conventional treatments such as surgery and chemotherapy are associated with some drawbacks. In recent years, traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians, and has become an indispensable part of the comprehensive treatment for gastric cancer. AIM: To investigate the mechanism of Xiaojianzhong decoction (XJZ) in the treatment of gastric cancer (GC) by utilizing network pharmacology and experimental validation, so as to provide a theoretical basis for later experimental research. METHODS: We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics. Subsequently, we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8, apoptosis, cell cycle, and clone formation assays. Additionally, we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins. RESULTS: XJZ mainly regulates IL6, PTGS2, CCL2, MMP9, MMP2, HMOX1, and other target genes and pathways in cancer to treat GC. The inhibition of cell viability, the increase of apoptosis, the blockage of the cell cycle at the G0/G1 phase, and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment. In addition, XJZ induced a decrease in the mRNA expression of IL6, PTGS2, MMP9, MMP2, and CCL2, and an increase in the mRNA expression of HOMX1. XJZ significantly inhibited the expression of IL6, PTGS2, MMP9, MMP2, and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein. CONCLUSION: XJZ exerts therapeutic effects against GC through multiple components, multiple targets, and multiple pathways. Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

Modern technology-based exploration of mechanism of traditional Chinese medicine in prevention and treatment of gastric cancer.

This review comments on the article "To explore the mechanism of Yigong San anti-gastric cancer and immune regulation". We are interested that the article applied network pharmacology and bioinformatics techniques to elucidate the mechanism of action of Yigong Sang, a traditional Chinese medicine (TCM), in the treatment of gastric cancer (GC). The mechanism of action of Yigong Sang in the treatment of GC has not yet been elucidated because it is composed of multiple Chinese medicines with multiple components and multiple targets. The emergence of network pharmacology and bioinformatics analysis helps explain the mechanism of action of TCM in preventing and treating GC, and provides a possibility for TCM to transform from empirical to evidence-based medicine. This is of great significance for the application of TCM in oncology, new drug development, formula optimization, and the improvement of clinical efficacy.

Integrative multi-target analysis of Urtica dioica for gout arthritis treatment: a network pharmacology and clustering approach.

Urtica dioica (stinging nettle) has been traditionally used in Chinese medicine for the treatment of joint pain and rheumatoid arthritis. This study aims to elucidate the active compounds and mechanisms by which it acts against gout arthritis (GA). Gout-related genes were identified from the DisGeNet, GeneCards, and OMIM databases. These genes may play a role in inhibiting corresponding proteins targeted by the active compounds identified from the literature, which have an oral bioavailability of ≥ 30% and a drug-likeness score of ≥ 0.18. A human protein-protein interaction network was constructed, resulting in sixteen clusters containing plant-targeted genes, including ABCG2, SLC22A12, MAP2K7, ADCY10, RELA, and TP53. The key bioactive compounds, apigenin-7-O-glucoside and kaempferol, demonstrated significant binding to SLC22A12 and ABCG2, suggesting their potential to reduce uric acid levels and inflammation. Pathway enrichment analysis further identified key metabolic pathways involved, highlighting a dual mechanism of anti-inflammatory and urate-lowering effects. These findings underscore the potential of U. dioica in targeting multiple pathways involved in GA, combining traditional medicine with modern pharmacology. This integrated approach provides a foundation for future research and the development of multi-target therapeutic strategies for managing gout arthritis. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00254-9.

Integrating network pharmacology and transcriptomics to study the potential mechanism of Jingzhi Niuhuang Jiedu tablet in rats with accumulation of heat in the lungs and stomach.

ETHNOPHARMACOLOGICAL RELEVANCE: Accumulation of heat in the lungs and stomach (AHLS) is an important syndrome within the realm of traditional Chinese medicine (TCM). It is the fundamental reason behind numerous illnesses, including mouth ulcers, dermatological conditions, acne, and pharyngitis. Jingzhi Niuhuang Jiedu tablet (JN) serves as the representative prescription for treatment of AHLS clinically. However, the effective components and mechanism of JN's impact on AHLS remain unexplored. AIM OF THE STUDY: The objective of this research was to analyze the effective components of JN and investigate the therapeutic effect and potential mechanism of JN on AHLS. MATERIALS AND METHODS: The effective compounds of JN extract were analyzed and identified using UHPLC-Q-Exactive/HRMS. Utilizing network pharmacology to investigate JN's multi-target, multi-pathway process in treating AHLS. Subsequently, anti-inflammatory activities of JN extract were evaluated in the RAW264.7 cells stimulated by lipopolysaccharide (LPS). In addition, a rat AHLS model induced by LPS and dried ginger was established. Pathological changes in rat lung and stomach tissues observed by HE staining and Masson's trichrome staining. Additionally, the expression of TNF-α, IL-6, and IL-1ß in bronchoalveolar lavage fluid (BALF) was identified through the ELISA assay. For a deeper understanding of how JN might affect AHLS, transcriptomics was utilized to examine differential genes and their underlying mechanisms. Concurrently, techniques like quantitative polymerase chain reaction (q-PCR), immunofluorescence, and western blotting (WB) were employed to confirm various mRNA and protein expression, including Il17ra, Il17re, IL-17A, IL-1ß, IL-6, PPARγ, PGC1-α and UCP1. RESULTS: We identified 178 potential effective components in the JN extract. Network pharmacology analysis showed that the 144 components in JN act on 200 key targets for the treatment of AHLS by suppressing inflammation, regulating energy metabolism, and gastric function. In addition, JN suppressed the LPS-stimulated generation of NO, TNF-α, IL-1ß, and IL-6 in RAW264.7 cells. And JN treatment effectively alleviated lung and stomach injury and reduced inflammation in rats. Analysis of RNA-seq from lung tissues revealed JN's substantial control over crucial genes in the IL-17 signaling pathway, including Il1b and Il17ra. Likewise, RNA sequencing of stomach tissues revealed that JN markedly decreased crucial genes in the Thermogenesis pathway, including Ppargc1a and Ppara. Additional experimental findings confirmed that treatment with JN significantly reduced the expression levels of mRNA (Il17ra, Il17re, Il1b, Ppargc1a and Ucp1), and the expression levels of protein (IL-17A, IL-1ß, IL-6, PPARγ, PGC1-α and UCP1). CONCLUSION: This study not only analyzes the effective components of JN but also reveals that JN could effectively ameliorate AHLS by inhibiting IL-17 signaling pathway and Thermogenesis pathway, which provides evidence for subsequent clinical studies and drug development.

A network pharmacology approach-based decoding of Resveratrol's anti-fibrotic mechanisms.

BACKGROUND: Inhalation of crystalline silica (CS) frequently leads to chronic lung inflammation and pulmonary fibrosis (PF), a condition with limited effective treatments. Resveratrol (Res) has demonstrated potential in PF treatment; however, its underlying mechanisms remain incompletely elucidated. PURPOSE: This study represents the first comprehensive attempt to uncover the novel mechanisms underlying Res's anti-fibrotic effects against PF through an innovative, integrated approach combining network pharmacology and experimental validation. METHODS: We employed network pharmacology to investigate the holistic pharmacological mechanism of Res, then validated the predicted pharmacological effects using in vivo and in vitro studies. RESULTS: In total, 216 genes were identified to be simultaneously associated with PF and Res. An integrated bioinformatics analysis implicated a crucial role of the autophagy signaling pathway in dominating PF, with AMPK and mTOR showing high docking scores. Animal studies revealed that Res significantly alleviated silica-induced lung damage in silicotic mice, with decreased collagen I (Col-I) levels and reduced expression of vimentin and α-SMA. In-depth investigation demonstrated that Res modulated CS-dysregulated autophagy by targeting the AMPK/mTOR pathway. in vitro, Res treatment significantly reduced lactate dehydrogenase (LDH), TNF-α, and TGF-ß levels and improved cell viability of Raw264.7 cells post-CS exposure. Notably, Res was demonstrated to suppress fibroblast-to-myofibroblast transition via mediating macrophage autophagy through the AMPK/mTOR pathway. CONCLUSION: Res can alleviate CS-induced PF by targeting AMPK in the autophagy signaling pathway, which sheds light on Res' therapeutic potential in treating PF.