Capsules ; Drugs, Chinese Herbal ; pharmacology ; Humans

The quality markers(Q-markers) of Shujin Huoxue Capsules were comprehensively discriminated based on the five principles of transfer and traceability, specificity, compatibility, effectiveness and measurability. The compounds that could be transferred from the original medicinal materials to the preparation were selected with the principle of transfer and traceability. The specific components in the prescription were screened by reviewing literature with the principle of specificity. According to the principle of compatibility, the attributes of compounds were evaluated by the sovereign, minister, assistant and guide combination rules of the original medicinal materials in the prescription. According to the principle of measurability, the measurable components were summarized by reference to the pharmacopoeia and literature combined with the content. The mechanism of Shujin Huoxue Capsules in the treatment of osteoporosis was studied through network pharmacology based on the principle of effectiveness, which was the evaluation index of effectiveness. The chemical components screened out above were regarded as candidate Q-markers, and the cobweb model was plotted to obtain the comprehensive score of Q-markers. Hydroxysafflor yellow A, trachelosid, eleutheroside B, α-cyperone, protocatechuic acid, protocatechualdehyde and 4-methoxy salicylaldehyde were discriminated as the Q-markers of Shujin Huoxue Capsules based on the five principles combined with cobweb model.
Biomarkers ; Capsules ; Drugs, Chinese Herbal/pharmacology*

Qijiao Shengbai Capsules(QJ) can invigorate Qi and replenish the blood, which is commonly used clinically for adjuvant treatment of cancer and leukopenia due to chemoradiotherapy. However, the pharmacological mechanism of QJ is still unclear. This work aims to combine the high-performance liquid chromatography(HPLC) fingerprints and network pharmacology to clarify the effective components and mechanism of QJ. The HPLC fingerprints of 20 batches of QJ were established. The similarity evaluation among 20 batches of QJ was performed by using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012), resulting in a similarity greater than 0.97. Eleven common peaks were identified by reference standard, including ferulic acid, calycosin 7-O-glucoside, ononin, calycosin, epimedin A, epimedin B, epimedin C, icariin, formononetin, baohuoside I, and Z-ligustilide. The "component-target-pathway" network was constructed by network pharmacy, and 10 key components in QJ were identified, such as ferulic acid, calycosin 7-O-glucoside, ononin, and calycosin. The components were involved in the phosphoinositide 3 kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and other signaling pathways by regulating potential targets, including EGFR, RAF1, PIK3R1, and RELA, to auxiliarily treat tumors, cancers, and leukopenia. The molecular docking conducted on the AutoDock Vina platform confirmed the high binding activity of 10 key effective components with core targets, with the binding energy less than-5 kcal·mol~(-1). In this study, the effective components and mechanism of QJ have been preliminary revealed based on HPLC fingerprint and network pharmacology, which provided a basis for quality control of QJ and a refe-rence for further study on its mechanism.
Network Pharmacology ; Capsules ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Drugs, Chinese Herbal/pharmacology*

The antipyretic effects of Qingkailing soft capsules and hard capsules were compared based on metabonomics technology,so as to provide basis for clinical rational use and quality control evaluation of its preparations. By using ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry( UPLC-LTQ/Orbitrap),and multivariate tatistical methods such as principal component analysis( PCA),partial least squares-discriminate analysis( PLS-DA) and orthogonal signal correction partial least square discriminant analysis( OPLS-DA),the changes of plasma endogenous metabolites in rat fever model induced by dry yeast were studied,so as to look for biomarkers related to fever. Based on these results,the antipyretic effects of two types of Qingkailing preparations were compared. The results indicated that metabolic profiles of the experimental groups could be distinguished distinctly,and 8 endogenous metabolites showed differences as compared with the normal control group( P<0. 05),including nicotinic acid,choline,hippuric acid,phosphocholine,Lyso PC( 14 ∶ 0),Lyso PC [16 ∶ 1( 9 Z) ],Lyso PC( 18 ∶ 0) and Lyso PC [20 ∶ 3( 5 Z,8 Z,11 Z) ]. They could be regarded as biomarkers related to fever. Qingkailing soft capsule and hard capsule had different effects on the regulation of plasma metabolites in yeast-induced fever model rats. Qingkailing soft capsule had different degrees of callbacks on eight biomarkers,including significant callbacks on nicotinic acid( P<0. 05),hippuric acid( P< 0. 01),phosphocholine( P< 0. 05),and Lyso PC [20 ∶3( 5 Z,8 Z,11 Z) ]( P<0. 05),while hard capsule only had significant callbacks on nicotinic acid( P<0. 05),hippuric acid( P<0. 01),and phosphocholine( P< 0. 05),with no callbacks on choline,Lyso PC( 14 ∶ 0),Lyso PC [16 ∶ 1( 9 Z) ],Lyso PC( 18 ∶0),and Lyso PC [20 ∶3( 5 Z,8 Z,11 Z) ]. This indicated that Qingkailing soft capsule had better callback effect than hard capsule. In this study,Qingkailing soft capsules and hard capsules were used to intervene the changes of related biomarkers in yeast-induced fever rat models,and then the antipyretic effect and mechanism between these two kinds of capsules were compared. The two dosage forms played an antipyretic role mainly by regulating lipid metabolism and controlling inflammation. The callback effect of soft capsule on the potential biomarkers of lysophosphatidylcholine was significantly higher than that of hard capsule. The differences in antipyretic effect of Qingkailing soft capsule and hard capsule were expounded from the point of metabonomics,providing experimental data and theoretical basis for the selection of clinical dosage forms.
Animals ; Antipyretics/pharmacology* ; Biomarkers/blood* ; Capsules ; Drugs, Chinese Herbal/pharmacology* ; Metabolomics ; Rats

OBJECTIVETo study mechanismt of Fufang Haishe capsule for dementia by observing the effect of it on PC-12 cell apoptosis, which was induced by beta-amyloid protein (Abl-42).

METHODNerve growth factor (NGF) was used to cultivate the PC-12 cells. Fufang Haishe capsule at different concentrations was added into the culture medium so as to identify the nontoxic concentrations with MTT. To analyze the PC-12 cell apoptosis respectively by MTT assay, Flow cytometry (FCM technique) with different concentrations of Fufang Haishe capsule (0.01, 0.1, 1, 5 mg x mL(-1)), adding Ab or not Western blot was used to detect apoptosis which was measured on the implementation of caspase-9 and caspase-3 activity.

RESULTFufang Haishe capsule could significantly inhibit the apoptosis of PC-12 cells induced by Abeta with increased colorimetric MTT asay ( compare among the control group and concentration 0, 0.01, 0.1, 1 and 5 mg x mL(-1) group, which is the same below: 1.75 +/- 0.12, 0.73 +/- 0.35, 0.79 +/- 0.11, 0.83 +/- 0.07, 1.31 +/- 0.07, 1.80 +/- 0.38, P < 0.01) and the decreased apoptosis rate of the cells which was analysed by flow cytometry (1.93 +/- 0.41)%, (46.17 +/- 4.08)%, (35.35 +/- 4.63)%, (28.62 +/- 3.81)%, (15.13 +/- 3.15)%, (7.84 +/- 1.76)%, P < 0.01. In addition, Fufang Haishe capsule inhibited the activity of caspase-9 and caspase-3 of PC-12 cells which was induced by Abeta.

CONCLUSIONFufang Haishe capsule significantly inhibite apoptosis of PC-12 cells induced by Abeta. The mechanism might be that Fufang Haishe capsule decrease the activity of the apoptosis implementing protein,caspase-9 and caspase-3.

Animals ; Apoptosis ; drug effects ; Capsules ; Caspases ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; PC12 Cells ; Rats

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term "gastric ulcer". The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.
Animal Experimentation ; Animals ; Capsules ; Gastric Mucosa/metabolism* ; Humans ; Network Pharmacology ; Rats ; Stomach Ulcer/genetics*

This study analyzed the quality markers(Q-markers) of Yuquan Capsules(YQC) based on serum pharmacochemistry of Chinese medicine and detected the components and metabolites of YQC absorbed into the blood by UPLC-Q-TOF-MS and UNIFI systems. As a result, 32 components of YQC were detected, including 17 prototype components and 15 metabolized components. Among them, 12 prototype components(ginsenoside Rh_2, genistein, formononetin, puerarin, daidzein, schizandrin A, schizandrin B, schizandrin C, schizandrol A, schizandrol B, gomisin D, and ononin) and 12 metabolized components(ginsenoside Rg_1, ginsenoside Rg_2, ginsenoside Rg_3, ginsenoside Ro, 3'-methoxypuerarin, daidzin, astragaloside Ⅱ, astragaloside Ⅳ, glycyrrhizic acid, liquiritigenin, isoliquiritin, and verbascoside) showed inhibitory effects and pharmacological activities against diabetes, and these 24 blood-entering components against diabetes were identified as Q-markers of YQC.
Capsules ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacology* ; Ginsenosides/analysis* ; Medicine, Chinese Traditional ; Serum/chemistry*

Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) is traditional Chinese medicine that has been used to treat diarrhea caused by acute enteritis (AE) and bacillary dysentery in Xinjiang (China) for many years. However, the potential therapeutic mechanism of MMRAC for AE and its regulatory mechanism on host metabolism is unclear. This study used fecal metabolomics profiling with GC/MS and 16S rRNA gene sequencing analysis to explore the potential regulatory mechanisms of MMRAC on a dextran sulfate sodium salt (DSS)-induced mouse model of AE. Fecal metabolomics-based analyses were performed to detect the differentially expressed metabolites and metabolic pathways. The 16S rRNA gene sequencing analysis was used to assess the altered gut microbes at the genus level and for functional prediction. Moreover, Pearson correlation analysis was used to integrate differentially expressed metabolites and altered bacterial genera. The results revealed that six intestinal bacteria and seven metabolites mediated metabolic disorders (i.e., metabolism of amino acid, carbohydrate, cofactors and vitamins, and lipid) in AE mice. Besides, ten altered microbes mediated the differential expression of eight metabolites and regulated these metabolisms after MMRAC administration. Overall, these findings demonstrate that AE is associated with metabolic disorders and microbial dysbiosis. Further, we present that MMRAC exerts protective effects against AE by improving host metabolism through the intestinal flora.
Animals ; Antidiarrheals/pharmacology* ; Capsules ; Enteritis/genetics* ; Feces/microbiology* ; Genes, rRNA ; Metabolomics ; Mice ; RNA, Ribosomal, 16S/genetics*

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with Fe^III/tannic acid coordination network to obtain spheroid@[Fe^III-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.
Anti-Bacterial Agents/pharmacology* ; Capsules/pharmacology* ; Cell Differentiation ; Cell Encapsulation ; Cells, Cultured ; Ferric Compounds/pharmacology* ; Osteogenesis/physiology* ; Periodontal Ligament ; Polyphenols/pharmacology* ; Stem Cells ; Tannins/pharmacology*

OBJECTIVEOur study aims to evaluate the antiviral effects of Ouyi antipyretic detoxicate soft capsule against influenza A virus H1N1 in vivo, so as to find an effective Chinese medicinal formulae for the treatment of the virus infection, which may lay a theoretical foundation for clinic treatment of patient infected with Influenza A Virus H1N1.

METHODWith the observation of cytopathic effect (CPE) that induced by virus ,we investigated viral inhibition rate by MTT colorimetric assay and valued antiviral activity of drugs by therapeutic index (TI) . Meanwhile, Oseltamivir phosphate capsule (Tamiflu) was used as positive control , we carried out experiments through the three ways of preventive effect, direct inactivation and propagation inhibition.

RESULTOuyi antipyretic detoxicate soft capsule could effectively inhibit cytopathic effect (CPE) that induced by Influenza A Virus H1N1. The preventive effect, direct inactivation , and inhibition of endogenous multiplication of Ouyi antipyretic detoxicate soft capsule and Tamiflu against influenza A virus H1N1 were observed. And three types of action therapeutic index (TI) from Ouyi antipyretic detoxicate soft capsule were (15.5 +/- 0.71), (0.55 +/- 0.071), (6.4 +/- 1.27) severally, comparing Tamiflu with (0.4 +/- 0.14), (1.88 +/- 0.29), (4.6 +/- 0.15), respectively.

CONCLUSIONOuyi antipyretic detoxicate soft capsule showed more remarkable preventive effect than Tamiflu in vitro (P<0.01). The possible mechanism of the antiviral activity observed in our study might be the protection of the MDCK cells from viral infection by inhibiting the viral absorption. We need a further study to certify three effects in vivo.

Animals ; Antipyretics ; pharmacology ; Antiviral Agents ; pharmacology ; Capsules ; Cell Line ; Dogs ; Influenza A Virus, H1N1 Subtype ; drug effects ; Inhibitory Concentration 50