Study on the active components and mechanism of Atractylodis Macrocephalae Rhizoma for invigorating the spleen and tonifying qi based on spectrum-effect relationship and network pharmacology.

Spleen deficiency can lead to various abnormal physiological functions of the spleen. Atractylodis Macrocephalae Rhizoma (AMR) is a traditional Chinese medicine used to invigorate the spleen and tonify qi. The study aimed to identify the primary active components influencing the efficacy of AMR in strengthening the spleen and replenishing qi through spectrum-effect relationship and chemometrics. Network pharmacology was used to investigate the mechanism by which AMR strengthens the spleen and replenishes qi, with molecular docking utilized for validation purposes. The findings indicated that bran-fried AMR exhibited superior efficacy, with atractylenolides and atractylone identified as the primary active constituents. Atractylenolide II emerged as the most influential component impacting the effectiveness of AMR, while the key target was androgen receptor. Furthermore, crucial pathways implicated included the mitogen-activated protein cascade (MAPK) cascade, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, and RNA polymerase II sequence-specific DNA-binding transcription factor binding. In summary, our study has identified the primary active components associated with the efficacy of AMR and has provided an initial exploration of its mechanism of action. This offers a theoretical foundation for future investigations into the material basis and molecular mechanisms underlying the pharmacodynamics of AMR.

Xanthoceras sorbifolium leaves alleviate hyperuricemic nephropathy by inhibiting the PI3K/AKT signaling pathway to regulate uric acid transport.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Xanthoceras sorbifolium Bunge was first documented as "Wen Guan Hua" in the "Jiu Huang Ben Cao" in 1406 A.D. According to the "National Compilation of Chinese Herbal Medicine," X. sorbifolium leaves are sweet and flat in nature and can dispel wind and dampness, suggesting that their extract can be used to treat rheumatoid arthritis. X. sorbifolium Bunge has also been used to treat arteriosclerosis, hyperlipidemia, hypertension, chronic hepatitis, and rheumatism, complications associated with hyperuricemic nephropathy (HN), a condition characterized by kidney damage resulting from high levels of uric acid (UA) in the blood. AIM OF THE STUDY: The purpose of this study was to investigate the effects and underlying mechanisms of a 70% ethanol extract from X. sorbifolium leaves (EX) in alleviating HN. MATERIALS AND METHODS: A mouse model of hyperuricemia was established to initially evaluate the hypouricemic effects and determine the effective dose of EX. Phytochemical analyses were conducted using ultra high-performance liquid chromatography and liquid chromatography-mass spectroscopy. The potential key pathways of EX in the alleviation of HN were inferred using network pharmacology and bioinformatics. An HN rat model was then established, and experiments including biomarker detection, western blotting, reverse transcription quantitative polymerase chain reaction, immunohistochemical and Masson's trichrome staining, and transmission electron microscopy were conducted to evaluate the effect of EX on UA transporter expression in vitro. RESULTS: Network pharmacology and bioinformatics analyses revealed that the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was the key pathway for the alleviation of HN progression by EX. EX treatment reduced serum biomarkers in HN rats, downregulated the expression of p-PI3K, p-AKT, glucose transporter 9 (GLUT9), urate transporter 1 (URAT1), Collagen I, matrix metalloproteinase (MMP)-2, and MMP-9, and upregulated the expression of ATP binding cassette subfamily G member 2 (ABCG2) to improve renal interstitial fibrosis in HN rats. A high content of both quercitrin and cynaroside were identified in EX; their administration inhibited the increased expression of GLUT9 and URAT1 in damaged HK-2 cells. CONCLUSION: Our study provides evidence that EX alleviates HN. The potential mechanism underlying this effect may be the regulation of UA transporters, such as GLUT9 and URAT1, by limiting the activation of the PI3K/AKT signaling pathway to improve renal injury.

[Research progress on Rhododendron molle in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.

Essential Oils and Antagonistic Microorganisms as Eco-Friendly Alternatives for Coffee Leaf Rust Control.

Coffee leaf rust (CLR) is caused by the biotrophic fungus Hemileia vastatrix Berk. & Br., a disease of economic importance, reducing coffee yield up to 60%. Currently, CLR epidemics have negatively impacted food security. Therefore, the objective of the present research study is to show a current framework of this disease and its effects on diverse areas, as well as the biological systems used for its control, mode of action, and effectiveness. The use of essential plant oils and antagonistic microorganisms to H. vastatrix are highlighted. Terpenes, terpenoids, and aromatic compounds are the main constituents of these oils, which alter the cell wall and membrane composition and modify the basic cell functions. Beneficial microorganisms inhibit urediniospore germination and reduce disease incidence and severity. The antagonistic microorganisms and essential oils of some aromatic plants have great potential in agriculture. These biological systems may have more than one mechanism of action, which reduces the possibility of the emergence of resistant strains of H. vastatrix.

The roles of natural triterpenoid saponins against Alzheimer's disease.

The aging of the world population and increasing stress levels in life are the major cause of the increased incidence of neurological disorders. Alzheimer's disease (AD) creates a huge burden on the lives and health of individuals and has become a big concern for society. Triterpenoid saponins (TS), representative natural product components, have a wide range of pharmacological bioactivities such as anti-inflammation, antioxidation, antiapoptosis, hormone-like, and gut microbiota regulation. Notably, some natural TS exhibited promising neuroprotective activity that can intervene in AD progress, especially in the early stage. Recently, studies have indicated that TS play a pronounced positive role in the prevention and treatment of AD. This review discusses the recent research on the neuroprotection of TS and proceeds to detail the action mechanisms of TS against AD, hoping to provide a reference for drug development for anti-AD.

The Perspective of Psychological Action Mechanism of Mindfulness Meditation: Mindfulness Meditation Blurs the Transparent Boundary Between the Unconscious and the Conscious Mind.

Based on the author's clinical experience, the aim of this paper is to conceptually analyse the theory of psychological functioning and action mechanisms in the way mindfulness meditation works. Meditation is a method of revealing unconsciousness. It works in a similar way to the inhibitory and excitatory mechanisms of neurones. Block pathogenic thoughts and emotions that reach the unconscious to the conscious mind. The long-term implementation of mediation may be more effective than the short-term and interrupted implementation.

Integration of Network Pharmacology and Molecular Docking to Analyse the Mechanism of Action of Oregano Essential Oil in the Treatment of Bovine Mastitis.

The active components, potential targets, and mechanisms of action of oregano essential oil in the treatment of bovine mastitis disease were investigated using network pharmacology and molecular docking approaches. The TCMSP and literature databases were examined for the main compounds in oregano essential oil. Afterward, the physical, chemical, and bioavailability characteristics of the components were evaluated. The PubChem, BATMAN, PharmMapper, and Uniprot databases were utilized to predict the target genes of the major components of oregano essential oil. Via the databases of DrugBank, OMIM, GeneCards, TTD, and DisGenet, the disease targets of bovine mastitis were discovered. We analyzed common targets and built protein-protein interaction (PPI) networks using the STRING database. Key genes were analyzed, obtained, and compound-target-pathway-disease visualization networks were created using Cytoscape. For the GO function and KEGG pathway enrichment analysis, the DAVID database was utilized. Molecular docking via Autodock Tools was utilized to evaluate the reliability of the interactions between oregano essential oil and hub targets. Thymol, carvacrol, and p-cymene are the three major components found in oregano essential oil. The potential targets (TNF, TLR4, ALB, IL-1ß, TLR2, IL-6, IFNG, and MyD88) were screened according to the visual network. The enrichment analysis suggested that the major signaling pathways in network pharmacology may include PI3K-Akt, MAPK, IL-17, and NF-κ B. Molecular docking analysis shows that thymol had good docking activity with TNF, IL-6, and MyD88, carvacrol had good docking activity with TNF, and p-cymene had good docking activity with ALB. This study clarified the mechanism of action of oregano essential oil in the treatment of bovine mastitis, thus providing data supporting the potential for the use of oregano essential oil in the development of new therapeutics for bovine mastitis.

Study on the action mechanism of Buyang Huanwu Decoction against ischemic stroke based on S1P/S1PR1/PI3K/Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke is a common and frequent clinical disease. Recent studies have demonstrated that sphingolipid plays an important role in the pathological process of ischemic stroke. PI3K-Akt is a classic protective signaling pathway of cerebral ischemic injury. After acting on the S1P receptor, S1P can activate the downstream PI3K/Akt signaling pathway and play an anti-cerebral ischemia role. Buyang Huanwu Decoction (BHD) is a traditional Chinese medicine formula used to treat ischemic stroke. However, the mechanisms of BHD on ischemic stroke remain unclear based on S1P/S1PR1/PI3K/Akt signaling pathway. AIM OF THE STUDY: The present study is intended to investigate the action mechanism of BHD on ischemic stroke based on the S1P/S1PR1/PI3K/Akt signaling pathway from multiple perspectives. MATERIALS AND METHODS: The BHD lyophilized product was prepared by vacuum freeze-drying method, of which the chemical composition was determined by UPLC-Q-TOF/MS. The mouse permanent middle cerebral artery occlusion (pMCAO) model was established by the suture-occluded method. Male KM mice were randomly divided into seven groups: sham group, model group, FTY720 (positive control) group, BHD group, BHD + W146 (selective S1PR1 inhibitor) group, SEW2871 (selective S1PR1 agonist) group, and Calycosin group. Each group was administered continuously for 14 days and evaluated with modified neurological severity score (mNSS) and cerebral infarct volume on the 1st, 4th, 7th, and 14th days. The SphK1, SphK2, S1PR1, PI3K, Akt, and p-Akt protein in the prefrontal lobe, hippocampus, and striatum was quantified by Western blot and immunohistochemical (IHC) experiment respectively. The qRT-PCR method was employed to evaluate SphK1, SphK2, and S1PR1 mRNA expression in the above tissue. RESULTS: BHD and Calycosin both effectively improved mNSS scores with smaller infarct volumes. The SphK1 level in the prefrontal lobe, hippocampus, and striatum of mice in the BHD group was significantly lower, and SphK2, PI3K, and p-Akt in the hippocampus and striatum were significantly higher than those in the model group. BHD significantly decreased SphK1 mRNA expression in the prefrontal lobe, hippocampus, and striatum, and significantly up-regulated SphK2 mRNA and S1PR1 mRNA expression. Additionally, SphK1 protein expression levels of the prefrontal lobe, hippocampus, and striatum in the BHD group was significantly lower than model group, and SphK2, S1PR1, PI3K, Akt, and p-Akt protein expressions levels were increased obviously. Furthermore, SEW2871 can increase S1PR1 and Akt expression, and up-regulate SphK2 and S1PR1 mRNA expression. The effect of BHD on the expression of S1P/S1PR1/PI3K/Akt signaling pathway-related proteins and mRNA were weakened by BHD + W146. CONCLUSION: BHD and Calycosin significantly improved the symptoms of neurological deficits in pMCAO mice, reduced the cerebral infarction volume, up-regulated SphK2 and S1PR1 mRNA levels, enhanced SphK2, S1PR1, PI3K, Akt, p-Akt protein expression of the prefrontal lobe, hippocampus and striatum, and down-regulated SphK1 mRNA and protein expression, which may be helpful to clarify the mechanism of BHD through S1P/S1PR1/PI3K/Akt signaling pathway to protect against cerebral ischemic injury.

Synthesis and biological activities of novel chalcone derivatives containing pyrazole oxime ethers.

A series of novel chalcone derivatives containing pyrazole oxime ethers were designed and synthesized. The structures of all the target compounds were determined by NMR and HRMS. The structure of H5 was further confirmed via single-crystal X-ray diffraction analysis. The results of biological activity test showed that some of the target compounds exhibited significant antiviral and antibacterial activities. The test results of EC50 value against tobacco mosaic virus showed that H9 had the best curative and protective effect, and the EC50 value of curative activity of H9 was 166.9 µg/mL, which was superior to ningnanmycin (NNM) 280.4 µg/mL, the EC50 value of protective activity of H9 was 126.5 µg/mL, which was superior to ningnanmycin 227.7 µg/mL. Microscale thermophoresis (MST) experiments demonstrated that H9 (Kd = 0.0096 ± 0.0045 µmol/L) exhibited a strong binding ability with tobacco mosaic virus capsid protein (TMV-CP), which was far superior to ningnanmycin (Kd = 1.2987 ± 0.4577 µmol/L). In addition, molecular docking results showed that the affinity of H9 to TMV protein was significantly higher than ningnanmycin. The results of against bacterial activity showed that H17 has a good inhibiting effect against Xanthomonas oryzae pv. oryzae (Xoo), the EC50 value of H17 was 33.0 µg/mL, which was superior to the commercial drugs thiodiazole copper (68.1 µg/mL) and bismerthiazol (81.6 µg/mL), and the antibacterial activity of H17 was verified by scanning electron microscopy (SEM).

Observation and Analysis of Clinical Efficacy of Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy on Patients with Postherpetic Neuralgia.

OBJECTIVE: To explore the clinical efficacy of Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy on patients with postherpetic neuralgia (PHN) and its action mechanism. METHODS: 36 patients are randomly divided into Lotus Acupuncture Cupping Stasis Therapy group, pure cupping group and gabapentin group, with a total of five observation points for the first, fifth, tenth, fifteenth, and twentieth sessions of therapy (one session every three days). At each observation point, the venous blood of the patients is taken, and the contents of and changes in WNT3a, Frizzled8, ß-catenin, IL-18, TNF-α, NR2B, NK-1 and SP are tested by ELISA, RT-PCR and WesternBlot, respectively. The VAS scores and safety of the patients in the three groups are compared. RESULTS: With increased time spent in therapy, the VAS scores of patients in each group decreased gradually and there was a significant reduction in pain in patients in the Lotus Acupuncture Cupping Stasis Therapy group compared to the gabapentin and pure cupping groups (P<0.05). The levels of IL-18, TNF-α, NK-1, SP, WNT3a, Frizzled 8 and ß-catenin in the serum of all patients experienced a constant decline over time (P<0.05); the levels of the aforesaid factors in the serum of patients in the Lotus Acupuncture Cupping Stasis Therapy group dropped remarkably after the tenth session of therapy compared to those in gabapentin and pure cupping groups (P<0.05). CONCLUSIONS: Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy can significantly reduce the pain of PHN patients, with a good therapeutic effect, and it is worthy of clinical use.

Clinical application and mechanism research progress of Wuling Powder in the treatment of brain edema / 国际中医中药杂志

Brain edema belongs to the category of "stroke" and "true headache", while Traditional Chinese Medicine mostly understands its core disease mechanisms from the perspectives of stasis, deficiency, and heat, and mostly treats the disease by using warming yang to induce diuresis and eliminating stasis to remove water. Wuling Powder has been lauded as the "first party to typhoid and relieving diuresis", which is used to cure clearing damp and promoting diuresis and warming yang and transforming qi, and has been clinically used in the treatment of brain edema caused by various causes such as head trauma, intracerebral hemorrhage, cerebral infarction, and intracranial space occupying, all with remarkable efficacy. Wuling Powder improves cellular energy supply, scavenges excess oxygen radicals and calcium ions in brain tissue, and reduces the damage to brain tissue caused by vascular inflammatory factors and regulates aquaporins and vascular endothelial growth factor, thereby achieving therapeutic effects.

[Combination characteristics of frankincense and myrrh and progress and prospect of their combination efficacy and mechanism].

Herbal pair is formed based on the experience summary of doctors' deep understanding and perception of the medicinal nature in long-term clinical practice. It gradually becomes the exquisite structural unit for preparing traditional Chinese medicine(TCM) prescriptions, and often plays a core bridge role in the prescription combination. Frankincense and myrrh are raw resin materials of incense abroad, which are subsequently included as Chinese medicinal herbs and endowed with rich medicinal connotation. With the functions of relaxing Zang-fu organs, activating blood and relieving pain, they have definite clinical efficacy. From the perspective of herbal description and clinical application, this study systematically analyzed the combination of frankincense and myrrh as well as their combination proportion, efficacy characterization, diseases and syndromes, effective components and action mechanism. On this basis, the focus of in-depth research of frankincense-myrrh and the application prospects were proposed, in order to further reveal the potential meditation law of this herbal pair, thus contributing to clinical practice and drug innovation of traditional Chinese medicine, and providing reference for understanding of TCM medicinal nature and research of herbal pairs.

[Review of classical prescriptions in treatment of ulcerative colitis].

Ulcerative colitis(UC) is a continuous inflammatory bowel disease with the main clinical manifestations of abdominal pain, diarrhea, and mucous bloody stools, mainly attacking the colorectal mucosa and submucosa. It is characterized by high recurrence rate, difficult cure, and clustering and regional occurrence. Chinese medicinal prescriptions for the treatment of UC have good therapeutic effect, multi-target regulation, slight toxicity, and no obvious side effects. In particular, the classical prescriptions highlight the characteristics and advantages of traditional Chinese medicine theory and have attracted much attention in recent years. To enable researchers to timely and comprehensively understand the classical prescriptions in the treatment of UC, we reviewed the studies about the pharmacodynamic material basis, quality control, action mechanism, and clinical application of relevant classical prescriptions. We first introduced the latest research progress in the active components such as alkaloids, polysaccharides, saponins, and flavonoids in relevant classical prescriptions. Then, we reviewed the latest research achievements on the quality control of classical prescriptions for the treatment of UC by gas chromatography, liquid chromatography, mass spectrometry, liquid chromatography-mass spectrometry and the like. Further, we summarized the research advances in the mechanisms of relevant prescriptions in the treatment of UC based on network pharmacology, molecular docking, integrated pharmacology platform, and animal experiments. Finally, we generalized the clinical application of the classical prescriptions for clearing heat and removing dampness, mildly regulating cold and heat, soothing liver and regulating spleen, strengthening spleen and invigorating Qi, and tonifying spleen and stomach. By systematic summary of the research progress in relevant classical prescriptions, we hope to promote the application and development of such prescriptions in UC treatment.

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups.

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, ß-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".

Influence and Action Mechanisms of Governmental Relations Embeddedness for Fostering Green Production Demonstration Household: Evidence from Shaanxi, Sichuan, and Anhui Province, China.

As an innovative tactic, the core aspects of green products should be comprehensively demonstrated and firmly promoted to enhance their adoption. For doing so, continuous governmental support and interventions through distinct sets of networking and relationships could be crucial for synthesizing and diffusing the extent of green production demonstration households. Interestingly, the structural relationship between these two has not yet been evaluated comprehensively by the existing literature. Therefore, the study empirically analyzes the impact and mechanism of government relationships embedded in fostering green production demonstration households. The study compiles the empirical data from 963 farmers which were collected from the major tea-producing areas of Shaanxi, Sichuan, and Anhui provinces, China. In order to craft the findings, first we constructed the ordered Probit for benchmark regression analysis. Meanwhile, the Ordinary Standard Error Ordered Probit model, Ordered Logit model, and multivariate linear model were constructed for the robustness test. Third, the Extended Ordered Probit model and Bootstrap mediation effect model were used to test the path diagram. Finally, robustness testing and endogeneity processing test were used to explore the reliability of the findings. The results showed that: (i) Government relationship embedding has a positive effect on fostering green production demonstration households. In particular, factors such as relationships with general government staff, professional and technical personnel, and village cadre are most significant. (ii) Seemingly, the heterogeneity analysis shows that the farmers with large operating scales and low family economic status have a relatively stronger impact. (iii) Further mechanism research results show that government relations are embedded through government identification (policy identification, government trust), improving farmers' behavioral ability (production knowledge reserve, self-efficacy), and strengthening farmers' perceived value of green production (self-interest perception, altruistic values). Therefore, the government should strengthen the interactive mechanism embedded with farm households and extend support for green production demonstration zones. The farmers' information-sharing facilities and platforms should be modernized and highlighted according to the local conditions and long-term targeted strategies.

Integrated plasma pharmacochemistry and network pharmacology to explore the mechanism of Gerberae Piloselloidis Herba in treatment of allergic asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Gerberae Piloselloidis Herba (GPH), a commonly used traditional medicine in China, is derived from Gerbera piloselloides (Linn.) Cass. It is featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial, anti-tumor, uterine analgesia, and immunity-enhancing. With a long history of medication in ethnic minority areas in China, it is often used as an effective treatment for cough and sore throat as well as allergic asthma. Although our previous investigation also has discovered GPH performed effective treatment on allergic asthma, its underlying mechanism remains unclear. AIM OF THE STUDY: This research aims to reveal the pharmacological mechanism of GPH in the treatment for allergic asthma through combination of plasma pharmacology and network pharmacology. MATERIALS AND METHODS: Firstly, the components of GPH in blood samples were identified using UHPLC- Q-Orbitrap HRMS. An interaction network of "compound-target-disease" was constructed based on the compounds confirmed in blood and on their corresponding targets of allergic asthma acquired from disease gene databases, predicting the possible biological targets and potential signal pathways of GPH with the network pharmacology analysis. Then, a molecular docking between the blood ingredients and the core targets was carried out using the Autodock Vina software. Subsequently, after establishing a mouse model with allergic asthma induced by ovalbumin (OVA), the effect of GPH on allergic asthma was evaluated by analyzing a series of indicators including behavior, lung pathological changes, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF). Finally, the key pathway and targets predicted by network pharmacology and molecular docking were further verified using Western blot analysis. RESULTS: Eleven chemical constituents (such as arbutin, neochlorogenic acid, chlorogenic acid, etc.) were identified through the analysis of plasma samples, on which basis a total of 142 genes intersecting GPH and allergic asthma were collected by network pharmacology. After performing enrichment analysis of these genes in gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG), it was found that arbutin-related targets mainly focused on phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signal pathway, while luteolin and marmesin -related targets tended to locate at Interleukin-17 (IL-17) signal pathway. Meanwhile, the findings of molecular docking suggested that such components as arbutin, luteolin and marmesin entering into blood had good binding with the core targets related to PI3K/Akt and IL-17 pathways. In addition, GPH improved the OVA-induced asthma symptoms, the alveolar septa thickening and the infiltration of inflammatory cell around bronchi and bronchioles as well as reduced the levels of IgE, IL-8 and TNF-α in serum or BALF. Furthermore, GPH could inhibit the phosphorylation level of Akt and the expression of PI3K, an efficacy supported by the findings by way of Western blot which suggests that GPH in the treatment of allergic asthma was linked to PI3K/Akt signal pathway. CONCLUSION: In this study, a comprehensive strategy to combine the UPLC-Q-Orbitrap HRMS with network pharmacology was employed to clarify the mechanism of GPH against allergic asthma, a finding where GPH may inhibit PI3K/Akt signal pathway to protect mice from OVA-induced allergic asthma. This study provides a deeper understanding of the pharmacological mechanism of GPH in treatment of asthma, offering a scientific reference for further research and clinical application of GPH in terms of allergic asthma.

In Vitro Analysis of Extracts of Plant Used in Mexican Traditional Medicine, Which Are Useful to Combat Clostridioides difficile Infection.

Recently, a worrying acceleration of the emergence of antibiotic-resistant bacteria has been reported. The increase in antibiotic-associated diseases, such as Clostridioides difficile infection (CDI), has promoted research on new treatments that could be more effective and less aggressive for CDI patients. This study evaluates eight plants with antimicrobial activity commonly used in Mexican traditional medicine to evaluate their potential against C. difficile. We provide essential information about these plants' activities and action mechanisms against C. difficile and their effect on different bacterial infection activities: motility, adherence, sporulation, and germination. The selected plants are rosemary, estafiate, rue, epazote, mint, toloache, ajenjo, and thyme. We used clinical isolates to test their activity against strains responsible for current outbreaks to provide more information about the clinical impact of these extracts. We found that thyme, ajenjo, and mint were the most effective against the isolates. We identified that the extracts affected protein synthesis. In addition, the extracts affect the strains' motility, and some, such as thyme extract, affect adherence, whereas rue extract affects sporulation. These results led to the identification of new compounds beneficial to CDI treatment.

[Mechanism of Liangfu Pills in treatment of functional dyspepsia: based on network pharmacology and experimental verification].

This study aims to explore the potential mechanism of Liangfu Pills in the treatment of functional dyspepsia(FD) based on network pharmacology and molecular docking, and verify the mechanism by animal experiment. The active components of Liangfu Pills were screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of Liangfu Pills were predicted by SwissTargetPrediction. The targets of FD were retrieved from GeneCards. On this basis, the common targets of the disease and the pills were yielded and the protein interaction was retrieved based on STRING. The core targets were screened out, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis with DAVID. Finally, molecular docking was carried out with the help of AutoDock Tools to predict the binding degree between the effective components of Liangfu Pills and core targets. A total of 19 active components of Liangfu Pills and 591 FD-related targets were screened out by network pharmacology, of which 253 were common targets of the disease and the prescription. Liangfu Pills was mainly involved in the biological processes of response to drug, negative regulation of transcription, positive regulation of apoptotic process, and cell surface receptor signaling pathway, and the KEGG pathways of hypoxia-inducible factor-1(HIF-1) signaling pathway, serotonergic synapse, tumor necrosis factor(TNF) signaling pathway, cyclic adenosine monophosphate(cAMP) signaling pathway, calcium signal pathway, and inflammatory mediator regulation of transient receptor potential(TRP) channels. The results of molecular docking showed that the key active components of Liangfu Pills had certain binding activity to the targets mitogen-activated protein kinase 1(MAPK1), protein kinase B(AKT1), transient receptor potential cation channel subfamily V member 1(TRPV1), 5-hydroxytryptamine receptor 1 A(HTR1 A), and 5-hydroxytryptamine receptor 2 A(HTR2 A). FD was induced in rats, and then Liangfu Pills was given to FD rats for 7 days. The results showed that Liangfu Pills could significantly relieve the symptoms of FD rats, significantly increase the expression of 5-hydroxytryptamine(5-HT), and down-regulate the expression of TRPV1. Through network pharmacology, molecular docking, and experimental verification, this study proved that Liangfu Pills improved FD through multiple components and multiple targets. The result lays a basis for further research on the mechanism and clinical application of Liangfu Pills in the treatment of FD.

[Prediction of material basis and mechanism of Curcumae Rhizoma in treatment of coronary heart disease].

Coronary heart disease(CHD) is a common cardiovascular disease in clinical practice. Curcumae Rhizoma(CR), an important herbal medicine for breaking blood stasis and resolving mass, is often used for the treatment of CHD caused by blood stasis syndrome. However, the anti-CHD components, targets, and mechanism are still unclear. Therefore, in this study, the chemical components of CR were separated and identified by ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS). Based on the identified components, network pharmacology analysis, including target prediction and functional enrichment, was applied to screen out the main active components against CHD, and the potential mechanism was discussed. Finally, molecular docking was performed to verify the binding between the active components and the targets. The results showed that among the 52 chemical components identified in CR, 28 were related to CHD, involving 75 core targets. The core components included(4S)-4-hydroxy-gweicurculactone, curcumadione, and curcumenone, and the core targets included phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha(PIK3 CA), mitogen-activated protein kinase 1(MAPK1), and mitogen-activated protein kinase 3(MAPK3). In summary, through the active components, such as(4S)-4-hydroxy-gweicurculactone, curcumadione, and curcumenone, CR regulates the nerve repair, vasoconstriction, lipid metabolism, and inflammatory response, thereby exerts therapeutic effect on CHD.

[Exploration on mechanism of Polygalae Radix and Acori Tatarinowii Rhizoma in treating Alzheimer's disease based on network pharmacology and experimental verification].

This study aimed to explore the action targets and mechanisms of Polygala tenuifolia and Acorus tatarinowii in treating Alzheimer's disease(AD) based on network pharmacology, molecular docking, and animal tests. The AD-related targets were collec-ted from GeneCard and the main active ingredients and targets of P. tenuifolia and A. tatarinowii from the TCMSP. Cytoscape was applied to construct the "Chinese herb-active ingredient-target-disease" network, followed by the construction of protein-protein interaction(PPI) network using STRING. GO biological function and KEGG pathway enrichment analysis was performed by DAVID and Metascape. The main active components of P. tenuifolia and A. tatarinowii and their potential core targets were docking using AutoDock Vina. The effects of P. tenuifolia and A. tatarinowii on the cognitive function were verified in mice with scopolamine(SCOP)-induced cognitive impairment. A total of seven active ingredients including kaempferol, onjixanthone Ⅰ, and marmesin and 56 potential targets of P. tenuifolia and A. tatarinowii were screened out, with the core targets covering AKT1, PTGS2, TNF, and NF-κB inflammation pathway mainly involved. The results of molecular docking also showed that the main active components of P. tenuifolia and A. tatarinowii stably bond to the core targets predicted by network pharmacology. The new object recognition experiment suggested that P. tenuifolia and A. tatarinowii improved the learning and memory abilities of mice after SCOP induction. As revealed by pathological section observation and relevant kit assay, P. tenuifolia and A. tatarinowii reduced the damage of central cholinergic neurons and enhanced the antioxidant ability of SCOP-induced mice. Western blot confirmed that P. tenuifolia and A. tatarinowii down-regulated the protein expression levels of TLR4, NF-κB, and related inflammatory factors(TNF-α, IL-1ß, and IL-6). All these have suggested that P. tenuifolia and A. tatarinowii inhibits AD via multiple components, multiple targets, and multiple pathways, which has provided an experimental basis for the clinical application of P. tenuifolia and A. tatarinowii for the treatment of AD.