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(1) Background: IBD (inflammatory bowel disease) is characterized by chronic intestinal inflammation leading to persistent symptoms and a lack of effective treatments. ZP (Zanthoxyli Pericarpium) has been used in traditional Chinese medicine for its anti-inflammatory and antioxidant properties for the management of intestinal disorders. (2) Methods: This study aimed to investigate the components of ZP, their specific targets, and associated diseases using the TCMSP (Traditional Chinese Medicine Systems Pharmacology) analysis platform, TCMBank database, and ETCM2.0 (Encyclopedia of Traditional Chinese Medicine 2.0) database. Additionally, we explored the protective effects of ZP on the colon and the underlying molecular mechanisms in the treatment of IBD. (3) Results: We identified 59 compounds in ZP that target 38 genes related to IBD, including PTGS2, PPARG, and GPBAR1. In a mice model of DSS (dextran sodium sulfate)-induced colitis, ZP significantly reduced colonic epithelial damage and oxidative stress markers, such as iNOS and nitrotyrosine, demonstrating its antioxidant properties. (4) Conclusions: These findings suggest that ZP has protective effects against DSS-induced colonic damage owing to its anti-inflammatory and antioxidant properties, making it a potential candidate for IBD treatment. However, further research and clinical trials are required to confirm its therapeutic potential and safety in humans. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH) is a predominant metabolic liver disease, typically characterized by hepatic steatosis, oxidative stress, and inflammation. The traditional Chinese medicine Cornus officinalis possesses anti-inflammatory and hepatoprotective pharmacological properties and has shown ameliorative effects on NASH. however, its mechanism of action remains unclear. This study aims to elucidate the mechanisms by which C. officinalis ameliorates NASH. The active components of C. officinalis were analyzed using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the corresponding targets were predicted. Subsequently, the DisGeNET, GeneCards, and GEO databases were employed to identify NASH-related targets. Venn diagrams were used to intersect the C. officinalis targets with the NASH targets. Protein–protein interaction (PPI) networks were constructed using the STRING database, and PPI network analysis was performed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), followed by molecular docking validation. Cornus officinalis was found to contain 20 major active ingredients corresponding to 672 potential targets, 61 of which overlapped with NASH targets. PPI network, GO, and KEGG pathway analyses identified four targets with the highest correlation, and molecular docking results indicated that the active ingredients of C. officinalis exhibited strong binding affinities to NASH targets. The treatment of NASH with C. officinalis is characterized by multiple active ingredients and multiple targets, underscoring the major advantage of traditional Chinese medicine in treating NASH. [ABSTRACT FROM AUTHOR]

Background: Endometritis seriously affects maternal reproductive health and fertility. Natural compounds have the characteristics of high efficiency and low residue in disease treatment. We aimed to discover and reveal the pharmacological effects of naringin, which is widely present in food and plants, on endometritis. Methods: Based on network pharmacology, the potential targets and pathways of naringin's actions on endometritis were predicted. Animal in vivo experiments were conducted to examine the inflammatory response of lipopolysaccharides (LPSs) in uterine tissue and the therapeutic effect of naringin. An in vitro primary bovine endometrial epithelial cell inflammation and drug treatment model was constructed. The production of reactive oxygen species (ROS) was measured using DCFH-DA, and the effect of naringin on LPS-induced endometritis was evaluated using HE staining, real-time quantitative PCR, Western blot, and immunofluorescence staining methods. Results: Naringin alleviated LPS-induced inflammatory injury and oxidative stress in the endometrium of mice and bovine endometrial epithelial cells (bEECs). Furthermore, in vitro studies were carried out to reveal the potential anti- inflammatory mechanisms of naringin based on network pharmacology. We found that naringin significantly inhibited LPS-stimulated endoplasmic reticulum stress (ERS)-related gene and protein expression, thus reducing the unfolded protein response (UPR). Furthermore, treatment of naringin attenuated the autophagic flux induced by ERS. In a further study, we observed that PI3K/AKT pathway inhibitors or ERS inducers partially reverse naringin's inhibition of autophagy and cell apoptosis. Conclusion: It is demonstrated that naringin suppresses autophagy by directly inhibiting the ERS-PI3K/AKT axis and exerting anti-inflammatory and antioxidant effects in endometritis. These findings provide novel insights into the pathogenesis of endometritis, highlighting potential therapeutic targets of traditional herbs and compounds. [ABSTRACT FROM AUTHOR]

Abstract Non-alcoholic steatohepatitis (NASH) is a predominant metabolic liver disease, typically characterized by hepatic steatosis, oxidative stress, and inflammation. The traditional Chinese medicine Cornus officinalis possesses anti-inflammatory and hepatoprotective pharmacological properties and has shown ameliorative effects on NASH. however, its mechanism of action remains unclear. This study aims to elucidate the mechanisms by which C. officinalis ameliorates NASH. The active components of C. officinalis were analyzed using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the corresponding targets were predicted. Subsequently, the DisGeNET, GeneCards, and GEO databases were employed to identify NASH-related targets. Venn diagrams were used to intersect the C. officinalis targets with the NASH targets. Protein–protein interaction (PPI) networks were constructed using the STRING database, and PPI network analysis was performed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), followed by molecular docking validation. Cornus officinalis was found to contain 20 major active ingredients corresponding to 672 potential targets, 61 of which overlapped with NASH targets. PPI network, GO, and KEGG pathway analyses identified four targets with the highest correlation, and molecular docking results indicated that the active ingredients of C. officinalis exhibited strong binding affinities to NASH targets. The treatment of NASH with C. officinalis is characterized by multiple active ingredients and multiple targets, underscoring the major advantage of traditional Chinese medicine in treating NASH.

Abstract The incidence of ulcerative colitis (UC) is on the rise globally. Shen-Zhu-Lian-Bai decoction (SZLBD) can relieve the clinical symptoms of UC. This study aimed to investigate the underlying molecular mechanism of SZLBD in the treatment of UC. The key treatment targets of SZLBD for UC were obtained based on the online database, and combined with the STRING database and Cytoscape 3.7.2 software, PPI network was constructed and visualized. The GEO database was utilized to validate the expression levels of core targets in UC. Metascape database GO functional annotation and KEGG pathway enrichment analysis. Molecular docking technology was used to verify the docking of core compounds with key targets. RT-qPCR and Western Blot were used to detect the expression of key targets in HCoEpiC cells for verification. After screening, 67 targets shared by SZLBD and UC were obtained. It is predicted that IL-6, IL-1B, and AKT1 might be the key targets of SZLBD in the treatment of UC. Quercetin was the main active ingredient. GEO results showed that the expression levels of IL-6, IL-1B and AKT1 were higher in the UC group compared to the control group. GO and KEGG analyses showed that these targets were related to apoptosis and inflammation. The results of molecular docking demonstrated that the AKT1 gene, a key target of quercetin, had the highest affinity of -9.2 kcal/mol. Cell experiments found that quercetin could affect the expression of IL-6, IL-1B, and AKT1. This study preliminarily explored and verified the mechanism of action of SZLBD in the treatment of UC, which provides a theoretical basis for subsequent in vivo mechanism studies.

Abstract Colon cancer (CC) is a prevalent malignant tumor of the gastrointestinal tract and ranks among the leading causes of death in cancer patients worldwide. Cucurbitacin, a group of tetracyclic triterpenoids widely found in Cucurbitaceae plants, exhibits diverse pharmacological activities. However, the pharmacological activity of cucurbitacin C (CuC), a cucurbitacin derivative exclusively present in cucumbers, remains unclear. To investigate CuC's action targets and potential targets for CC, we utilized a database to obtain relevant information. Additionally, we identified differentially expressed genes in CC patients from The Cancer Genome Atlas and discovered 64 crossover targets formed through the intersection of drug‐disease targets. Through the construction of a protein‐protein interaction network, we identified 20 central genes. Enrichment analysis revealed that the cross‐targets were significantly enriched in four signaling pathways, namely, the PI3K‐Akt, Ras, MAPK, and IL‐17 signaling pathways. Correlation and expression analysis of the enriched central genes led to the identification of 7 key targets, among which matrix metalloproteinases (MMP)‐1, MMP‐3, and MMP‐13 demonstrated a significant association with poor prognosis in patients. Furthermore, we validated the network pharmacology results with in vitro and in vivo experiments. CuC can effectively inhibit the proliferation and migration of HCT‐116. CuC also can suppress the colon tumor growth in vivo, while reducing the expression of placental growth factor, MMP‐1, MMP‐3, MMP‐9, and MMP‐13 both in vitro and in vivo, consistent with the predicted results. Together, our results demonstrated that CuC holds promise as a potential agent for CC treatment.

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients for treating AD has attracted much attention. Corydalis rhizome (CR) is a traditional Chinese medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used for treating AD. However, no systematic study has been conducted to explore the anti-AD efficacy of CR, as well as its active compounds and mechanisms of action. Objective: The present study aimed to clarify CR’s active constituents and its pharmacological mechanisms in treating AD. Methods: A D-galactose & scopolamine hydrobromide-induced AD mouse model was used and CR was administered orally. The prototypical alkaloid components were identified in the serum. The core components, key targets, and possible mechanisms of action of these alkaloids were revealed through network pharmacology. Molecular docking of the key target was performed. Finally, the mechanism was validated by lipopolysaccharide (LPS)-induced activation of BV2 microglia. Results: The results showed that CR improved anxiety-like behavior, spatial and non-spatial recognition, and memory capacity in AD mice. It also achieved synergistic AD treatment by modulating neurotransmitter levels, antineuroinflammation, and anti-oxidative stress. The core components that enhance CR’s efficacy in treating AD are protoberberine-type alkaloids. The CR may induce the polarization of LPS-activated BV2 microglia from phenotype M1 to M2. This is partially achieved by modulating the IL-6/JAK2/STAT3 signaling pathway, which could be the mechanism by which CR treats AD through anti-inflammation. Conclusion: The present study provided a theoretical and experimental basis for the clinical application of CR in treating AD. It also provides information that aids the secondary development, and precise clinical use of CR. [ABSTRACT FROM AUTHOR]

The Yiqi Qubai (YQ) formula is a hospital preparation for treating vitiligo in China that has had reliable efficacy for decades. The formula consists of four herbs; however, the extraction process to produce the formula is obsolete and the active ingredients and mechanisms remain unknown. Therefore, in this paper, fingerprints were combined with the chemometrics method to screen high-quality herbs for the preparation of the YQ standard decoction (YQD). Then, the YQD preparation procedure was optimized using response surface methodology. A total of 44 chemical constituents, as well as 36 absorption components (in rat plasma) of YQD, were identified via UPLC-Q-TOF/MS. Based on the ingredients, the quality control system of YQD was optimized by establishing the SPE-UPLC-Q-TOF/MS identification method and the HPLC quantification method. Network pharmacological analysis and molecular docking showed that carasinaurone, calycosin-7-O-β-d-glucoside, methylnissolin-3-O-glucoside, genkwanin, akebia saponin D, formononetin, akebia saponin B, and apigenin may be the key active components for treating vitiligo; the core targets associated with them were AKT1, MAPK1, and mTOR, whereas the related pathways were the PI3K-Akt, MAPK, and FoxO signaling pathways. Cellular assays showed that YQD could promote melanogenesis and tyrosinase activity, as well as the transcription and expression of tyrosinase-associated proteins (i.e., TRP-1) in B16F10 cells. In addition, YQD also increased extracellular tyrosinase activity. Further efficacy validation showed that YQD significantly promotes melanin production in zebrafish. These may be the mechanisms by which YQD improves the symptoms of vitiligo. This is the first systematic study of the YQ formula that has optimized the standard decoction preparation method and investigated the active ingredients, quality control, efficacy, and mechanisms of YQD. The results of this study lay the foundations for the clinical application and further development of the YQ formula. [ABSTRACT FROM AUTHOR]

Abstract Background Rosenroot (Rhodiola rosea) is a traditional Chinese herbal medicine. It has been used to treat patients with coronary artery disease (CAD). Salidroside is the main active constituent of rosenroot. This study was designed to explore the mechanism of salidroside in treating CAD and its role in angiogenesis in CAD systematically. Methods In this study, potential targets related to salidroside and CAD were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and CellMarker enrichment analyses were performed. The binding of salidroside to angiogenesis-related targets was assessed by PyMOL and Ligplot. Furthermore, the effects of salidroside on collateral circulation were evaluated by correlation analysis of these angiogenesis-related targets with the coronary flow index (CFI), and the influence of salidroside on human umbilical vein endothelial cell (HUVEC) proliferation and migration was assessed. Results Eighty-three targets intersected between targets of salidroside and CAD. GO and KEGG analyses indicated that salidroside mainly treated CAD through angiogenesis and anti-inflammatory action. There were 12 angiogenesis-related targets of salidroside in coronary heart disease, among which FGF1 (r = 0.237, P = 2.597E-3), KDR (r = 0.172, P = 3.007E-2) and HIF1A (r = -0.211, P = 7.437E-3) were correlated with the coronary flow index (CFI), and salidroside docked well with them. Finally, cell experiments confirmed that salidroside promoted the proliferation and migration of HUVECs. Conclusions This study revealed the potential molecular mechanism of salidroside on angiogenesis in CAD and provided new ideas for the clinical application of salidroside in the treatment of CAD.

Background: Rosenroot (Rhodiola rosea) is a traditional Chinese herbal medicine. It has been used to treat patients with coronary artery disease (CAD). Salidroside is the main active constituent of rosenroot. This study was designed to explore the mechanism of salidroside in treating CAD and its role in angiogenesis in CAD systematically. Methods: In this study, potential targets related to salidroside and CAD were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and CellMarker enrichment analyses were performed. The binding of salidroside to angiogenesis-related targets was assessed by PyMOL and Ligplot. Furthermore, the effects of salidroside on collateral circulation were evaluated by correlation analysis of these angiogenesis-related targets with the coronary flow index (CFI), and the influence of salidroside on human umbilical vein endothelial cell (HUVEC) proliferation and migration was assessed. Results: Eighty-three targets intersected between targets of salidroside and CAD. GO and KEGG analyses indicated that salidroside mainly treated CAD through angiogenesis and anti-inflammatory action. There were 12 angiogenesis-related targets of salidroside in coronary heart disease, among which FGF1 (r = 0.237, P = 2.597E-3), KDR (r = 0.172, P = 3.007E-2) and HIF1A (r = -0.211, P = 7.437E-3) were correlated with the coronary flow index (CFI), and salidroside docked well with them. Finally, cell experiments confirmed that salidroside promoted the proliferation and migration of HUVECs. Conclusions: This study revealed the potential molecular mechanism of salidroside on angiogenesis in CAD and provided new ideas for the clinical application of salidroside in the treatment of CAD. [ABSTRACT FROM AUTHOR]

Rhododendron simsii Planch, a folk medicine recorded in the ‘Dictionary of Chinese Materia Medica’, has been used by many ethnic regions of China to treat various inflammatory and immune-related diseases such as skin disorders and rheumatoid arthritis. However, its protective effect against autoimmune hepatitis and the underlying mechanisms remain unclear. The present study aimed to aimed to investigate the protective effects on autoimmune hepatitis through an integrated approach established by combining chemical composition identification, network pharmacology and in vivo experimental validation. Animal experiments showed that R. simsii Planch extract ameliorated ConA-induced liver injury, as evidenced by a reduction in ALT and AST levels and varying degrees of improvement in liver histopathology, with the R-EE (R. simsii Planch EtOAc extract) treated group showing the most obvious therapeutic effect. Then, chemical investigations into R-EE yielded 15 flavonoid and phenolic acid derivatives namely quercetin 3-O-α-L-rhamnoside (1), tamarixetin 3-rhamnoside (2), isoquercitrin (3), hyperoside (4), myricetin-3-O-α-L-rhamnopyranoside (5), afzelin (6), quercetin-3-O-α-L-arabinofuranoside (7), quercetin-3-O-α-D-arabinopyranoside (8), (+)-catechin (9), kaempferol (10), dihydromyricetin (11), quercetin (12), vanillic acid (13), gallic acid (14) and farrerol (15). Further network pharmacological analysis indicated that the potential mechanism against ConA-induced liver injury is probably related to the regulation of the NF-κB signaling pathway. Experiments confirmed that R-EE could reduce liver damage and downregulate CD4+ and inflammatory cytokine levels and the expressions of NLPR3, COX-2 and p-IκBα, and exhibited considerable hepatoprotective effects in ConA-induced AIH mice, which may be related to its flavonoids, and the underlying mechanism may involve the regulation of the NF-κB signaling pathway. The present results indicated that R. simsii Planch extract has more therapeutic potential in the treatment of autoimmune hepatitis, and provide the experimental basis for traditional application of R simsii Planch in the treatment of inflammatory diseases, and is a potential treatment agent for AIH that deserves further study.

The Yiqi Qubai (YQ) formula is a hospital preparation for treating vitiligo in China that has had reliable efficacy for decades. The formula consists of four herbs; however, the extraction process to produce the formula is obsolete and the active ingredients and mechanisms remain unknown. Therefore, in this paper, fingerprints were combined with the chemometrics method to screen high-quality herbs for the preparation of the YQ standard decoction (YQD). Then, the YQD preparation procedure was optimized using response surface methodology. A total of 44 chemical constituents, as well as 36 absorption components (in rat plasma) of YQD, were identified via UPLC-Q-TOF/MS. Based on the ingredients, the quality control system of YQD was optimized by establishing the SPE-UPLC-Q-TOF/MS identification method and the HPLC quantification method. Network pharmacological analysis and molecular docking showed that carasinaurone, calycosin-7-O-β-d-glucoside, methylnissolin-3-O-glucoside, genkwanin, akebia saponin D, formononetin, akebia saponin B, and apigenin may be the key active components for treating vitiligo; the core targets associated with them were AKT1, MAPK1, and mTOR, whereas the related pathways were the PI3K-Akt, MAPK, and FoxO signaling pathways. Cellular assays showed that YQD could promote melanogenesis and tyrosinase activity, as well as the transcription and expression of tyrosinase-associated proteins (i.e., TRP-1) in B16F10 cells. In addition, YQD also increased extracellular tyrosinase activity. Further efficacy validation showed that YQD significantly promotes melanin production in zebrafish. These may be the mechanisms by which YQD improves the symptoms of vitiligo. This is the first systematic study of the YQ formula that has optimized the standard decoction preparation method and investigated the active ingredients, quality control, efficacy, and mechanisms of YQD. The results of this study lay the foundations for the clinical application and further development of the YQ formula.

[Display omitted] • Twenty-one undescribed diterpenoids were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. • Compounds 3 , 5 , 6 , and 7 exhibited significant activity against several human cancer cell lines. • Compound 3 showed antitumor activities both in vivo and in vitro. Four new diterpenoid tropolones, salvirrddones A – D (1–4), and four new icetexanes, salvirrddices A – D (9–12), along with thirteen new 11,12-seco-norabietane diterpenoids, salvirrddnor A – M (14–24 , 31 , 32) and sixteen known compounds (5–8 , 13, 25–30 , 33–37), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Their structures were elucidated by comprehensive spectroscopic analyses, quantum chemical calculations, and X-ray crystallography. Structurally, compounds 1–8 represent a class of rare natural products featuring a unique cyclohepta-2,4,6-trienone moiety with diterpenoid skeletons. Bioassays showed that only diterpenoid tropolones 3 , 5 , 6 , and 7 exhibited significant activity against several human cancer cell lines with IC 50 values ranging from 3.01 to 11.63 μM. Additionally, 3 was shown to inhibit Hep3B cell proliferation, block the G0/G1 phase of the cell cycle, induce mitochondrial dysfunction and oxidative stress, promote apoptosis, as well as inhibit migration and invasion in vitro. Meanwhile, 3 demonstrated anti-proliferative, pro-apoptotic, and migration-inhibitory effects in the Hep3B xenograft zebrafish model in vivo. Network pharmacological analysis and molecular docking results suggested that 3 may treat hepatocellular carcinoma (HCC) through the PI3K-Akt signaling pathway, as well as by binding PARP1 and CDK2 targets. Overall, the present results extremely expand the repertoire of diterpenoids from natural products and may provide a novel chemical scaffold for the discovery of new antitumor drugs. [ABSTRACT FROM AUTHOR]

The Chinese traditional medicine KangXianYiAi formula (KXYA) is used to treat hepatic disease in the clinic. Here we aim to confirm the therapeutic effects and explore the pharmacological mechanisms of KXYA on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We first collected and analyzed clinical data of 40 chronic hepatitis B (CHB) patients with precancerous liver lesions under KXYA treatment. Then, the cell viability, migration, cell cycle, and apoptosis of HepAD38 cells with KXYA treatment were examined. Next, we performed network pharmacological analysis based on database mining to obtain the key target pathways and genes of KXYA treatment on HBV-related HCC. We finally analyzed the expression of the key genes between normal and HBV-related HCC tissues in databases and measured the mRNA expression of the key genes in HepAD38 cells after KXYA treatment. The KXYA treatment could reduce the liver nodule size of CHB patients, suppress the proliferation and migration capabilities, and promote apoptosis of HepAD38 cells. The key pathways of KXYA on HBVrelated HCC were Cancer, Hepatitis B, Viral carcinogenesis, Focal adhesion, and PI3K-Akt signaling, and KXYA treatment could regulate the expression of the key genes including HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1. The KXYA exhibited a curative effect via inhibiting proliferation, migration, and promoting apoptosis of HBV-related HCC and the pharmacological mechanism was related to the regulation of the expression of HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1. [ABSTRACT FROM AUTHOR]

Fourteen benzofuran compounds were identified in the fruits of Psoralea corylifolia L., with four previously undescribed compounds (4, 9-11) being discovered. Their chemical structures were definitively determined through comprehensive spectral data analysis. The compounds were investigated for their antioxidant, anti-tumor, and anti-inflammatory properties, revealing that benzofuran compounds exhibit significant anti-inflammatory effects. Compound 2 demonstrated the most potent anti-inflammatory effect, surpassing that of the positive control drug. The potential anti-inflammatory mechanism of 2 was extensively explored through network pharmacology research. Subsequent validation of the selected targets via Western blot analysis confirmed that 2 exerts its anti-inflammatory effects by activating the TLR4/NF-κB pathway. These findings offer a novel perspective on the development of benzofuran glycoside compounds and Psoralea fructus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To explore the effective components of Guishao Yigong decoction (GYD) in the treatment of colorectal cancer and reveal its potential mechanism of action., Methods: Through network pharmacology, the main target and signaling pathway of GYD therapy for colorectal cancer (CRC) were found. Subsequently, the effect of GYD was verified by in vitro cell viability measurements, colony formation, and scratch healing tests. The effects of GYD on metabolic pathways in vivo were found through plasma metabolomics. Finally, flow cytometry and qPCR experiments were used to verify the cycle-blocking effect of GYD on CRC cells., Key Findings: Based on the network pharmacological analysis and molecular docking technology, it was found that GYD could restrain the growth of CRC cells by affecting lipid metabolic pathways and mitogen-activated protein kinase (MAPK) signaling pathways. A series of cell experiments showed that GYD could inhibit the proliferation, migration and clonogenic ability of CRC cells. Furthermore, the plasma metabolomics results showed that GYD could affect the production of unsaturated fatty acids in mice. Flow cytometry and qPCR experiments further proved that GYD blocked the CRC cells in the G1 phase and modulated the expression of cell cycle-related targets, such as AKT, TP53, CDKN1A, and CDK2., Conclusions: All the results indicated that GYD could regulate the related metabolism of unsaturated fatty acids. Thus, the cell cycle was blocked and the expressions of the key proteins such as AKT and TP53 were regulated, which achieved the purpose of intervention in colorectal cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract Background Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism. Methods Network pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation. Results The results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin–eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma. Conclusion By combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.

Fritillaria cirrhosa D. Don (FCD) is a traditional Chinese medicine used to treat respiratory disorders, known for its effects in clearing heat, moistening the lungs, resolving phlegm, and relieving cough. Additionally, the total alkaloids extracted from FCD can alleviate asthma symptoms and reduce airway inflammation. However, no studies have investigated the effects of total alkaloids on lung macrophages. This study explored whether the total alkaloids of FCD (TAs-FCD) reduce M2 macrophage polarization and, consequently, attenuate airway remodeling in asthmatic mice. This study further elucidated its mechanism of action in treating allergic asthma. The extracted TAs-FCD was analyzed for its composition using UPLC-Q-TOF/MS. Network pharmacology was employed to identify the active ingredients and potential mechanisms of TAs-FCD in the treatment of allergic asthma. A mouse model of ovalbumin-induced allergic asthma was established, adopted, and validated through in vivo experiments. Hematoxylin-eosin staining (H&E), immunohistochemistry (IHC), immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time fluorescence quantitative polymerase chain reaction (q-PCR) were used to investigate the role of TAs-FCD in inhibiting M2 macrophage polarization in the context of allergic asthma. A total of 66 active ingredients were screened from 116 compounds using SWISSADME. The targets of these 66 compounds were predicted by SwissTargetPrediction, resulting in 808 unique drug targets after excluding duplicates. Additionally, 1756 targets related to allergic asthma were identified from the DisGeNET, Genecard, and OMIM databases. This led to 267 cross-targets between the active ingredient targets and allergic asthma targets, including interleukin (IL)-1β, tumor necrosis factor (TNF), and STAT3. Animal experiments demonstrated that TAs-FCD improved histopathological injury in mouse lungs, reduced peri-airway collagen fiber accumulation, airway mucus secretion, and airway smooth muscle proliferation. TAs-FCD also lowered IL-1β, TNF-α and IL-4 levels in lung tissues and alleviated airway inflammation. Furthermore, TAs-FCD significantly reduced levels of Arg1 and CD206, which are closely associated with M2 macrophages, and downregulated the expression of p-STAT3 and p-JAK2. TAs-FCD may inhibit M2 macrophage polarization by regulating the JAK2/STAT3 pathway, thereby alleviating airway remodeling and inflammation in allergic asthmatic mice. [Display omitted] • TAs-FCD attenuates OVA-induced allergic asthma in mice. • TAs-FCD reduces M2 macrophages to alleviate airway remodeling in asthmatic mice. • The JAK2/STAT3 pathway is an important pathway for asthma relief by TAs-FCD. [ABSTRACT FROM AUTHOR]

• Compound Shouwu Jiangzhi Granule (CSJG) attenuated NAFLD in both patients and mice. • CSJG moderately regulated FFAs synthesis predicted by network pharmacology. • CSJG significantly regulated TAGs synthesis so as to lower the level of TAGs in the liver. Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with few therapeutic options currently available. Traditional Chinese medicine has been used for thousands of years and exhibited remarkable advantages against such complicated disease for its "multi-component, multi-target and multi-pathway" characteristics. Compound Shouwu Jiangzhi Granule (CSJG) is a clinical empirical prescription for the treatment of NAFLD, but its pharmacological mechanism remains unknown. The clinical efficacy of CSJG was retrospectively analyzed in NAFLD patients by comparing blood biomarkers levels and liver MR images before and after CSJG treatment. Then, high-fat/high-fructose (HFHF) diet-induced NAFLD mice were used to further confirm CSJG's effect against hepatic lipid accumulation through hepatic lipid determination and histopathological staining of liver samples. Next, the ingredients of CSJG were determined, and network pharmacology analysis was performed to predict potential targets of CSJG, followed by quantitative PCR (qPCR) and western blotting for verification. Then, lipidomics study was carried out to further explore the anti-NAFLD mechanism of CSJG from the perspective of triacylglyceride (TAG) synthesis but not free fatty acid (FFA) synthesis. The enzymes involved in this process were assayed by qPCR and western blotting. The potential interactions between the key enzymes of TAG synthesis and the active ingredients of CSJG were analyzed by molecular docking. CSJG attenuated blood lipid levels and hepatic fat accumulation in both NAFLD patients and mice. Although network pharmacology analysis revealed the FFA synthesis pathway, CSJG only slightly affected it. Through lipidomics analysis, GSJG was found to significantly block the synthesis of diglycerides (DAGs) and TAGs in the liver, with decreased DGAT2 and increased PLD1 protein expression, which diverted DAGs from the synthesis of TAGs to the production of PEs, PCs and PAs and thus lowed TAGs level. Molecular docking suggested that rhein, luteolin and liquiritigenin from CSJG might be involved in this regulation. Clinical and experimental evidence demonstrated that CSJG is a promising agent for the treatment of NAFLD. CSJG regulated TAGs synthesis to alleviate hepatic lipid accumulation. Rhein, luteolin and liquiritigenin from CSJG might play a role in it. [Display omitted] [ABSTRACT FROM AUTHOR]

The adverse effects of Fructus Psoraleae (FP), especially liver injury, have attracted wide attention in recent years. To establish a system to explore potential hepatotoxic targets and the chief culprit of liver injury based on clinical experience, network pharmacological method, molecular docking, and in vitro and in vivo experiments. Clinical applications and adverse reactions to FP were obtained from public literatures. Components absorbed in the blood were selected as candidates to search for potential active targets (PATs) of FP. Subsequently, potential pharmacological core targets (PPCTs) were screened through the "drug targets-disease targets" network. Non-drug active targets (NPATs) were obtained by subtracting the PPCTs from the PATs. The potential hepatotoxic targets (PHTs) of FP were the intersection targets obtained from Venn analysis using NPATs, hepatotoxic targets, and adverse drug reaction (ADR) targets provided by the databases. Then, potential hepatotoxic components and targets were obtained using the "NPATS-component" network relationship. Molecular docking and in vitro and in vivo hepatotoxicity experiments were performed to verify the targets and related components. Overall, 234 NPATs were acquired from our analysis, and 6 targets were identified as PHTs. Results from molecular docking and in vitro and in vivo experiments showed that angelicin is the leading cause of liver injury in FP, and VKORC1 plays an important role. The results indicate that six targets, especially VKORC1 , are associated with the PHTs of FP, and angelicin is the leading culprit involved in FP liver injury via inhibition of VKORC1. [Display omitted] • The occurrence of hepatic toxicity and the screening methods of toxic targets of FP are closely related to the practical clinical application. • A robust screening system was established to explore the hepatotoxic targets of FP. • Angelicin participates in Fructus Psoraleae (FP) liver injury by inhibiting VKORC1. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a malignant cancer and lacks ideal drugs. Aged citrus peel (Chenpi, CP) is an easily available traditional Chinese medicine (TCM) with potential anticancer effects. Network pharmacology were used to investigate the potential mechanisms of CP in OSCC. Tangeretin was the most crucial active ingredient in CP, as shown by the establishment of the component-target-disease network (C-T-D). Protein-protein interaction (PPI) analysis and survival analysis showed that PIK3R1, ESR1, and CDK1 are core genes. Pathway enrichment analysis showed that PI3K-AKT is the top essential pathways. Molecular docking was used to predict the binding of targets and compounds. In vitro experiments showed that tangeretin inhibits cell proliferation, blocks the cell cycle in S phase, induces apoptosis, regulates core gene expression in SCC25 cells, and has lower toxicity to HOK cells. In conclusion, our study lays the foundation for the use of CP in the treatment of OSCC.

Background: Endometritis seriously affects maternal reproductive health and fertility. Natural compounds have the characteristics of high efficiency and low residue in disease treatment. We aimed to discover and reveal the pharmacological effects of naringin, which is widely present in food and plants, on endometritis. Methods: Based on network pharmacology, the potential targets and pathways of naringin's actions on endometritis were predicted. Animal in vivo experiments were conducted to examine the inflammatory response of lipopolysaccharides (LPSs) in uterine tissue and the therapeutic effect of naringin. An in vitro primary bovine endometrial epithelial cell inflammation and drug treatment model was constructed. The production of reactive oxygen species (ROS) was measured using DCFH-DA, and the effect of naringin on LPS-induced endometritis was evaluated using HE staining, real-time quantitative PCR, Western blot, and immunofluorescence staining methods. Results: Naringin alleviated LPS-induced inflammatory injury and oxidative stress in the endometrium of mice and bovine endometrial epithelial cells (bEECs). Furthermore, in vitro studies were carried out to reveal the potential anti-inflammatory mechanisms of naringin based on network pharmacology. We found that naringin significantly inhibited LPS-stimulated endoplasmic reticulum stress (ERS)-related gene and protein expression, thus reducing the unfolded protein response (UPR). Furthermore, treatment of naringin attenuated the autophagic flux induced by ERS. In a further study, we observed that PI3K/AKT pathway inhibitors or ERS inducers partially reverse naringin's inhibition of autophagy and cell apoptosis. Conclusion: It is demonstrated that naringin suppresses autophagy by directly inhibiting the ERS-PI3K/AKT axis and exerting anti-inflammatory and antioxidant effects in endometritis. These findings provide novel insights into the pathogenesis of endometritis, highlighting potential therapeutic targets of traditional herbs and compounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Peng, Hu, Wang, Fan and Zhang.)

Background: Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism. Methods: Network pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation. Results: The results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin–eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma. Conclusion: By combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis. [ABSTRACT FROM AUTHOR]

Background: A traditional Chinese medicine formula, Youdujing (YDJ) ointment, is widely used for treatment of human papilloma virus-related diseases, such as cervical cancer. However, the underlying mechanisms by which active compounds of YDJ alleviates cervical cancer are still unclear. Methods: We applied a comprehensive network pharmacology approach to explore the key mechanisms of YDJ by integrating potential target identification, network analysis, and enrichment analysis into classical molecular docking procedures. First, we used network and enrichment analyses to identify potential therapeutic targets. Second, we performed molecular docking to investigate the potential active compounds of YDJ. Finally, we carried out a network-based analysis to unravel potentially effective drug combinations. Results: Network analysis yielded four potential therapeutic targets: ESR1, NFKB1, TNF, and AKT1. Molecular docking highlighted that these proteins may interact with four potential active compounds of YDJ: E4, Y2, Y20, and Y21. Finally, we found that Y2 or Y21 can act alone or together with E4 to trigger apoptotic cascades via the mitochondrial apoptotic pathway and estrogen receptors. Conclusion: Our study not only explained why YDJ is effective for cervical cancer treatment, but also lays a strong foundation for future clinical studies based on this traditional medicine. [ABSTRACT FROM AUTHOR]

Dalbergia benthamii is a traditional Chinese medicine commonly used by Zhuang People in Guangxi, which was reported to possess a variety of biological activities. But their chemical constituents, anti-inflammatory activities and their possible pharmacological mechanism of D. benthamii were unclear yet. The acute inflammation of different doses of dhanol P.xlracls of D. benthamii was obsP.rvP.d by Llw mousP. xylP.nP. inducP.d P.ar P.dP.ma and carragP.P.nan inducP.d paw P.dP.ma modds. Tlwn, Llw dwmical consliluP.nls analysis of LhP. P.xlracls WP.ff'. ddP.rniirwd by liquid chromatography-mass spP.clromdry (LC-MS) and pyrolysis gas chmmalography-mass spP.clromdry (PY-CC/MS). ThP.ir mP.chanism of anliinflammalory aclivily was analyzP.d by ndwork pharmacology al LhP. samP. Linw. Tlw results Wf'.l'f'. as follows: ( 1) Compared wilh LhP. modd gmup, high dosP. gmup ( 8 g · kg·' ) of dhanol P.xlracls of D. benthamii could significantly inhibit LhP. xylP.nf'. inducP.d mousP. P.ar P.dP.ma, ca rragP.P.nan irnlucP.d hind paw P.dP.ma, with inhibition raLP. ovP.r 50%. ( 2) TlwrP. WP.ff'. sixly com1M1umls idP.nLifiP.d from Llw P.xlracls, including somP. repnrfrd a nli-inflammalory aclivP. consliluP.nls, such as isofla vonP. mullP.in, formonondin, s anguinP., pi(lf'.rinP., bda-silosLP.ml, de. ( 3) ThP. ndwork pharmacological analysis wP.re shown Lhat thP. a nti-inflammatory P.ffocLs of D. benthamii mighL bP. rdatP.d Lo poLP.nlial Largds of P 1K3CA, EC.fl{, MAPK, SHC, STAT3, CYP19Al, 1L2 and MAOA, de., which wP.re mainly involving signaling pathways of cC.MP-l'KC., cAMl', Focal adhP.sion and Hapl. ThP. rP.sulLs will provi(fo an impor'lanl rP.forencP. for LhP. furthP.r dP.vdopmP.nl and uLilizalion of LhP. planls of D. benthamii. [ABSTRACT FROM AUTHOR]

IntroductionThe overproduction of cytokines and chemokines caused by excessive and uncontrolled inflammation contributes to the development of COVID-19. Astragaloside IV is considered as an anti-inflammatory and antioxidant agent. This study aimed at undertaking a network pharmacology approach and bioinformatics analysis to uncover the pharmacological mechanisms of Astragaloside IV on COVID-19.MethodsPotential targets of Astragaloside IV were screened from public databases. Differentially expressed genes (DEGs) in SARS-CoV-2 were screened using bioinformatics analysis on the Gene Expression Omnibus (GEO) datasets GSE147507. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. The overlapping genes, GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs were confirmed, and the location of overlapping targets in the key pathways was queried using KEGG Mapper.ResultsA total of 425 potential targets of Astragaloside IV were screened. Besides, a total of 546 DEGs were identified between SARS-CoV-2 infected samples and control samples, including 380 up-regulated and 166 down-regulated genes. There was a significant overlap in GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs. The shared genes included MMP13, NLRP3, TRIM21, GBP1, ADORA2A, PTAFR, TNF, MLNR, IL1B, NFKBIA, ADRB2, and IL6.ConclusionsThis study is the first to propose Astragaloside IV as a new drug candidate for alleviating hyper-inflammation in COVID-19 patients. Besides, the key targets and pathways may reveal the main pharmacological mechanism of Astragaloside IV in the treatment of COVID-19.

Introduction: The overproduction of cytokines and chemokines caused by excessive and uncontrolled inflammation contributes to the development of COVID-19. Astragaloside IV is considered as an anti-inflammatory and antioxidant agent. This study aimed at undertaking a network pharmacology approach and bioinformatics analysis to uncover the pharmacological mechanisms of Astragaloside IV on COVID-19. Methods: Potential targets of Astragaloside IV were screened from public databases. Differentially expressed genes (DEGs) in SARS-CoV-2 were screened using bioinformatics analysis on the Gene Expression Omnibus (GEO) datasets GSE147507. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. The overlapping genes, GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs were confirmed, and the location of overlapping targets in the key pathways was queried using KEGG Mapper. Results: A total of 425 potential targets of Astragaloside IV were screened. Besides, a total of 546 DEGs were identified between SARS-CoV-2 infected samples and control samples, including 380 up-regulated and 166 down-regulated genes. There was a significant overlap in GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs. The shared genes included MMP13, NLRP3, TRIM21, GBP1, ADORA2A, PTAFR, TNF, MLNR, IL1B, NFKBIA, ADRB2, and IL6. Conclusions: This study is the first to propose Astragaloside IV as a new drug candidate for alleviating hyper-inflammation in COVID-19 patients. Besides, the key targets and pathways may reveal the main pharmacological mechanism of Astragaloside IV in the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients for treating AD has attracted much attention. Corydalis rhizome (CR) is a traditional Chinese medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used for treating AD. However, no systematic study has been conducted to explore the anti-AD efficacy of CR, as well as its active compounds and mechanisms of action., Objective: The present study aimed to clarify CR's active constituents and its pharmacological mechanisms in treating AD., Methods: A D-galactose & scopolamine hydrobromide-induced AD mouse model was used and CR was administered orally. The prototypical alkaloid components were identified in the serum. The core components, key targets, and possible mechanisms of action of these alkaloids were revealed through network pharmacology. Molecular docking of the key target was performed. Finally, the mechanism was validated by lipopolysaccharide (LPS)-induced activation of BV2 microglia., Results: The results showed that CR improved anxiety-like behavior, spatial and non-spatial recognition, and memory capacity in AD mice. It also achieved synergistic AD treatment by modulating neurotransmitter levels, anti-neuroinflammation, and anti-oxidative stress. The core components that enhance CR's efficacy in treating AD are protoberberine-type alkaloids. The CR may induce the polarization of LPS-activated BV2 microglia from phenotype M1 to M2. This is partially achieved by modulating the IL-6/JAK2/STAT3 signaling pathway, which could be the mechanism by which CR treats AD through anti-inflammation., Conclusion: The present study provided a theoretical and experimental basis for the clinical application of CR in treating AD. It also provides information that aids the secondary development, and precise clinical use of CR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lyu, Wang, Guo, Wang, Lu, Hao, Jiang, Fan, Li and Shi.)

[Display omitted] Rhododendron simsii Planch, a folk medicine recorded in the 'Dictionary of Chinese Materia Medica', has been used by many ethnic regions of China to treat various inflammatory and immune-related diseases such as skin disorders and rheumatoid arthritis. However, its protective effect against autoimmune hepatitis and the underlying mechanisms remain unclear. The present study aimed to aimed to investigate the protective effects on autoimmune hepatitis through an integrated approach established by combining chemical composition identification, network pharmacology and in vivo experimental validation. Animal experiments showed that R. simsii Planch extract ameliorated ConA-induced liver injury, as evidenced by a reduction in ALT and AST levels and varying degrees of improvement in liver histopathology, with the R - EE (R. simsii Planch EtOAc extract) treated group showing the most obvious therapeutic effect. Then, chemical investigations into R-EE yielded 15 flavonoid and phenolic acid derivatives namely quercetin 3-O- α -L-rhamnoside (1), tamarixetin 3-rhamnoside (2), isoquercitrin (3), hyperoside (4), myricetin-3-O- α -L-rhamnopyranoside (5), afzelin (6), quercetin-3-O- α -L-arabinofuranoside (7), quercetin-3-O- α -D-arabinopyranoside (8), (+)-catechin (9), kaempferol (10), dihydromyricetin (11), quercetin (12), vanillic acid (13), gallic acid (14) and farrerol (15). Further network pharmacological analysis indicated that the potential mechanism against ConA-induced liver injury is probably related to the regulation of the NF-κB signaling pathway. Experiments confirmed that R- EE could reduce liver damage and downregulate CD4+ and inflammatory cytokine levels and the expressions of NLPR3, COX-2 and p-IκBα, and exhibited considerable hepatoprotective effects in ConA-induced AIH mice, which may be related to its flavonoids, and the underlying mechanism may involve the regulation of the NF-κB signaling pathway. The present results indicated that R. simsii Planch extract has more therapeutic potential in the treatment of autoimmune hepatitis, and provide the experimental basis for traditional application of R simsii Planch in the treatment of inflammatory diseases, and is a potential treatment agent for AIH that deserves further study. [ABSTRACT FROM AUTHOR]

Si-Wei-Qiang-Wei Powder (SWQ) is a formulated traditional Tibetan medicine preparation that has been used clinically to treat liver and gallbladder diseases for centuries. Previous work has confirmed its clinical effectiveness, however, the specific mechanism of SWQ is still unknown. Aim of the study : This study aims to explore the anti-inflammatory effect of SWQ on cholecystitis and its possible mechanism. The main chemical components of SWQ were analyzed by HPLC. The network pharmacology database was used to screen and construct the network of the main components and molecular targets of SWQ, and to predict the molecular pathways of its core targets. Cholecystitis guinea pig model and LPS stimulated cultured human gallbladder epithelial cells (HGBEC) were used, as in vivo and in vitro methods respectively, to study the anti-cholecystitis activity of SWQ. Specifically, gallbladder wall thickness, hematoxylin-eosin (H&E) staining, and liver function indexes were used to evaluate the anti-inflammatory activities of SWQ in cholecystitis; qRT-PCR and ELISA were used to detect the changes of the production of inflammatory cytokines; Western blot analysis was used to analyze the effects of SWQ on phosphorylation of P38, ERK1/2, JNK and AKT. SWQ decreased the indexes of ALT, AST, TBA, CHOL, DBIL in serum and TBIL, TC and Ca2+ in bile, and alleviated the wall thickness of gallbladder and hepatobiliary fibrosis in LCA-induced guinea pigs. In addition, SWQ attenuated the expression and production of TNF-α, IL-6, IL-1β, COX-2 both in liver and gallbladder. Moreover, SWQ reversed the up-regulation of p-P38, p-ERK1/2, and p-JNK in animals with cholecystitis and LPS-induced HGBEC. Furthermore, mechanistic studies indicated that SWQ inhibited the activation of ERK1/2, thereby decreasing the expression of TNF-α, IL-6, IL-1β and phosphorylation P38 and JNK. In summary, our research showed that SWQ relieves gallbladder inflammation by inhibiting the MAPK pathway. [Display omitted] • The drug components, theapeutic targets or signaling pathways of SWQ were clarified. • SWQ inhibits cholecystitis via reversing the histological and biochemical changes. • SWQ plays anti-inflammation by reducing the production of IL-1β, IL-6 and TNF-α. • SWQ plays its anti-inflammatory effects by regulating MAPKs signaling pathway. [ABSTRACT FROM AUTHOR]

The Chinese traditional medicine KangXianYiAi formula (KXYA) is used to treat hepatic disease in the clinic. Here we aim to confirm the therapeutic effects and explore the pharmacological mechanisms of KXYA on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We first collected and analyzed clinical data of 40 chronic hepatitis B (CHB) patients with precancerous liver lesions under KXYA treatment. Then, the cell viability, migration, cell cycle, and apoptosis of HepAD38 cells with KXYA treatment were examined. Next, we performed network pharmacological analysis based on database mining to obtain the key target pathways and genes of KXYA treatment on HBV-related HCC. We finally analyzed the expression of the key genes between normal and HBV-related HCC tissues in databases and measured the mRNA expression of the key genes in HepAD38 cells after KXYA treatment. The KXYA treatment could reduce the liver nodule size of CHB patients, suppress the proliferation and migration capabilities, and promote apoptosis of HepAD38 cells. The key pathways of KXYA on HBV-related HCC were Cancer, Hepatitis B, Viral carcinogenesis, Focal adhesion, and PI3K-Akt signaling, and KXYA treatment could regulate the expression of the key genes including HNF4A, MAPK8, NR3C1, PTEN, EGFR , and HDAC1 . The KXYA exhibited a curative effect via inhibiting proliferation, migration, and promoting apoptosis of HBV-related HCC and the pharmacological mechanism was related to the regulation of the expression of HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1 ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, Chen, Li, Li, Yang, Jin, Liang, Zhang, Zhou, Zhang, Chen, Du, Zao and Ye.)

[Display omitted] • Network pharmacology, molecular docking and in vitro experiments were used to study the role of Chenpi in OSCC. • The key component of Chenpi in OSCC is tangeretin, and the key targets are PIK3R1, ESR1, CDK1. • Molecular docking proved that there is a binding force between the components in the Chenpi and key targets. • Cell experiments demonstrated that tangeretin inhibits OSCC cell growth and regulates the mRNA expression of key targets. Oral squamous cell carcinoma (OSCC) is a malignant cancer and lacks ideal drugs. Aged citrus peel (Chenpi, CP) is an easily available traditional Chinese medicine (TCM) with potential anticancer effects. Network pharmacology were used to investigate the potential mechanisms of CP in OSCC. Tangeretin was the most crucial active ingredient in CP, as shown by the establishment of the component-target-disease network (C-T-D). Protein-protein interaction (PPI) analysis and survival analysis showed that PIK3R1, ESR1, and CDK1 are core genes. Pathway enrichment analysis showed that PI3K-AKT is the top essential pathways. Molecular docking was used to predict the binding of targets and compounds. In vitro experiments showed that tangeretin inhibits cell proliferation, blocks the cell cycle in S phase, induces apoptosis, regulates core gene expression in SCC25 cells, and has lower toxicity to HOK cells. In conclusion, our study lays the foundation for the use of CP in the treatment of OSCC. [ABSTRACT FROM AUTHOR]