The mechanism of L-perilla alcohol(L-POH) in intervening hypoxic pulmonary hypertension(HPAH) was discussed based on network pharmacology, and experimental verification. The active components and potential targets of the volatile oil of Rhodiola tangutica(VORA) in the intervention of HPAH were screened by network pharmacology. The biological process of Gene Ontology(GO) and the signaling pathway enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) were analyzed for the core targets, and a "component-common target-disease" network was constructed. Four active components were screened from VORA: L-POH, linalool, geraniol, and(-)-myrtenol. The core targets for treating HPAH were HSP90AA1, AKT1, ESR1, PIK3CA, EP300, EGFR, and JAK2. GO enrichment analysis mainly involved biological processes such as reaction to hypoxia, heme binding, and steroid binding. KEGG enrichment analysis mainly involved hypoxia-inducing factor 1(HIF-1) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and Janus kinase/activator of signal transduction and transcription(JAK/STAT) signaling pathway. The vasodilation effects of the four active components were screened by perfusion experiment of extracorporeal vascular rings, and the mechanism of the main active component L-POH was studied by channel blockers. The inhibitory effects of the four active components on the proliferation of pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia were screened by cell proliferation experiment, and the mechanism of the main active component L-POH was studied by flow cytometry, cell cycle experiment, and Western blot. The results showed that L-POH could directly act on vascular smooth muscle to relax pulmonary arterioles, induce ATP-sensitive potassium channels to open, and inhibit extracellular Ca~(2+) influx through voltage-gated calcium channels to relax blood vessels. In addition, L-POH could inhibit the abnormal proliferation of PASMCs induced by hypoxia and promote its apoptosis, and its mechanism may be related to the increase in Bax protein expression and the decrease in p-JAK2, p-STAT3, Bcl-2, and cyclinA2 protein expression. In summary, L-POH can interfere with HPAH by relaxing pulmonary arterioles and inhibiting the proliferation of smooth muscle cells.
Network Pharmacology ; Animals ; Hypertension, Pulmonary/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Hypoxia/metabolism* ; Rhodiola/chemistry* ; Signal Transduction/drug effects* ; Humans ; Monoterpenes/chemistry* ; Male ; Cell Proliferation/drug effects* ; Rats, Sprague-Dawley

Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

Abelmoschi Corolla, the dried corolla of Abelmoschus manihot, has anti-inflammatory, antioxidant, and anti-fibrosis activities. Its chemical constituents mainly include flavonoids, organic acids, steroids, and polysaccharides. This study reviewed the research progress in the chemical constituents and pharmacological activities of Abelmoschi Corolla in recent 20 years. According to the concept of quality marker(Q-marker), the Q-markers of Abelmoschi Corolla were predicted from plant phylogeny, chemical constituent specificity, traditional efficacy, chemical constituent measurability, and absorbed constituents. The primary Q-markers for Abelmoschi Corolla were anticipated to include quercetin-3'-O-β-D-glucopyranoside, gossypetin-8-O-β-D-glucuronide, isoquercetin, myricetin,quercetin, and hyperoside, with the aim of providing reference data for improving the quality evaluation system of Abelmoschi Corolla.
Abelmoschus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Flowers/chemistry* ; Humans ; Animals ; Quality Control ; Flavonoids/chemistry*

Rubi Fructus has a long history of medicinal and edible use in China. It contains chemical components such as terpenes, flavonoids, phenolic acids, fatty acids, and alkaloids, and possesses various pharmacological activities, including antioxidant, anti-inflammatory, hypoglycemic, anti-tumor, anti-osteoporosis, and liver-protective effects. Rubi Fructus is widely applied in medical, health, and food fields. The quality of Rubi Fructus can directly affect the safety and effectiveness of clinical medication. Therefore, this article reviews the research progress on the chemical constituents and pharmacological effects of Rubi Fructus. Based on the concept of traditional Chinese medicine(TCM) quality markers(Q-markers), the article explores the screening and determination of Q-markers for Rubi Fructus from various aspects, including plant kinship, traditional efficacy, medicinal properties, measurability of chemical composition, different processing methods, producing areas, harvesting periods, and planting conditions. The components ellagic acid, kaempferol, quercetin, kaempferol-3-O-rutinoside, rutin, astragalin, tiliroside, and hyperoside are preliminarily proposed as Q-markers for Rubi Fructus, providing a reference for the quality control of Rubi Fructus.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Rubus/chemistry* ; Fruit/chemistry* ; Quality Control ; Animals

Anemarrhenae Rhizoma is bitter, sweet, and cold in nature, and has the effects of clearing heat, dispelling fire, nourishing Yin, and moisturizing dryness. It is associated with the lung, stomach, and kidney meridians, and is mainly distributed in the northwestern and northern regions of China. Modern research has shown that Anemarrhenae Rhizoma contains various chemical active constituents, including steroidal saponins, flavonoids, polysaccharides, lignans, volatile oils, and alkaloids. These constituents exhibit pharmacological effects such as anti-tumor, hypoglycemic, anti-inflammatory, and neuroprotective activities. However, there have been few comprehensive summaries of Anemarrhenae Rhizoma in recent years, which has limited its in-depth research and development. The complexity of traditional Chinese medicine constituents, along with their quality and efficacy, is easily influenced by processing, preparation, and the growing environment and resource distribution. This paper summarizes the resources, chemical constituents, and pharmacological effects of Anemarrhenae Rhizoma, and predicts its quality markers(Q-markers) from several aspects, including the specificity of chemical composition, properties related to preparation and active ingredients, measurability of chemical components, compounding environment, construction of the ″active ingredient-target″ network pathway, and differences in active ingredient content from different origins and parts. These predicted Q-markers may provide a basis for improving the quality evaluation system of Anemarrhenae Rhizoma.
Anemarrhena/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Rhizome/chemistry* ; Humans ; Animals ; Quality Control

Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Quality Control ; Humans ; Animals

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

In this study, potential quality markers(Q-markers) of Schisandrae Chinensis Fructus for treating bronchial asthma were predicted based on analytic hierarchy process(AHP), entropy weight method(EWM), fingerprint, and network pharmacology. AHPEWM was employed to quantitatively identify the Q-markers of Schisandrae Chinensis Fructus. AHP was used to weight the primary indicators(effectiveness, measurability, and specificity), while EWM was employed to analyze the secondary indicators of each primer indicator. Further, through fingerprint combined with network pharmacology, a ″component-target-pathway″ network was constructed to screen the components of Schisandrae Chinensis Fructus for treating bronchial asthma. It was finally determined that schisandrol A,schisandrin A, and schisandrin B were potential Q-markers of Schisandrae Chinensis Fructus in the treatment of bronchial asthma. This study is the first to comprehensively use AHP-EWM, fingerprint, and network pharmacology to screen the key Q-markers of Schisandrae Chinensis Fructus in the treatment of bronchial asthma. This study provides a scientific basis for improving the quality standard of Schisandrae Chinensis Fructus and lays a foundation for studying its material basis in treating bronchial asthma.
Schisandra/chemistry* ; Asthma/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Humans ; Entropy ; Lignans/analysis* ; Fruit/chemistry* ; Quality Control ; Cyclooctanes ; Polycyclic Compounds/analysis*

This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*