Zhongguo Zhongyao Zazhi最新文献

Based on the experimental autoimmune prostatitis(EAP) rat model, this study investigated the effects and mechanisms of Jingangteng Capsules(JGTCs) in ameliorating chronic nonbacterial prostatitis(CNP) to lay a foundation for the development of improved new drugs with expanded indications for JGTCs. Hematoxylin-eosin(HE) staining was used to observe pathological changes in the prostate tissue of rats. A microscope was used to measure the number of white blood cells and the density of lecithin bodies in prostate tissue homogenates. Biochemical analysis was employed to detect the levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in serum. Enzyme-linked immunosorbent assay(ELISA) was used to measure the level of inflammatory factors in serum. The 16S rDNA sequencing was applied to explore the effect of JGTCs on the changes in intestinal microbiota. Non-targeted metabolomics was used to predict the mechanism of JGTCs in ameliorating CNP. Western blot(WB) was utilized to validate the effects of JGTCs on the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate receptor 1(S1P1)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) pathway. The results show that JGTCs can ameliorate pathological injury of the prostate, enhance the density of lecithin bodies, reduce the number of white blood cells, decrease the levels of pro-inflammatory factors in serum, including tumor necrosis factor alpha(TNF-α), inducible nitric oxide synthase(iNOS), interleukin(IL)-1β, IL-6, IL-8, and IL-2, and increase the level of anti-inflammatory factor IL-10. JGTCs can modulate the structure of intestinal microbiota, increase the relative abundance of Lactobacillus and Bifidobacterium animalis, and decrease the relative abundance of unclassified＿f＿Prevotellaceae and Veillonella. JGTCs can alter the content of 10 metabolites, including sphingosine and retinoyl β-glucuronide and be involved in five metabolic pathways such as sphingolipid metabolism and retinol metabolism. The WB experiment reveals that JGTCs can inhibit the expressions of SPHK1 and S1P1 and the phosphorylation of PI3K and Akt. The results indicate that JGTCs can significantly alleviate inflammatory injury in the prostate tissue of EAP rats. Its mechanism may involve regulating intestinal microbiota dysbiosis and metabolic disorders and inhibiting the activation of the SPHK1/S1P1/PI3K/Akt signaling pathway.

This study reformulated antiviral granules into orally disintegrating granules to achieve instant dissolution and water-free administration and improve compliance and convenience of drug administration for patients. The type of hydrophilic excipients, the ratio of drug-to-excipient, and the grinding time were optimized by a vibration mill to prepare orally disintegrating powder. With the powder used as the raw material, the heating temperature and time were investigated to obtain the optimal granulation process. The differences before and after the preparation of orally disintegrating powder and granules were evaluated by a laser particle size analyzer, an X-ray diffractometer, a scanning electron microscope, and a multiple light scattering analyzer. The results showed that the orally disintegrating powder obtained by grinding the extract powder and xylitol at a ratio of 1∶1 for 3 min had the best instant solubility and taste. The optimal molding rate, instant solubility, and taste of the orally disintegrating granules were obtained by heating the orally disintegrating powder at 90 ℃ for 10 min. Compared with those of the extract powder, the particle size d_(0.9) of the orally disintegrating powder decreased from 846.29 to 44.57 μm; the specific surface area increased from 0.27 to 0.50 m~2·g~(-1), and the total adsorption volume increased from 0.001 5 to 0.002 6 cm~3·g~(-1). The multiple light scattering analysis showed that the orally disintegrating powder could be better dispersed in water. The X-ray diffraction experiment indicated that the crystal structure of xylitol did not change significantly before and after the preparation of orally disintegrating powder and the hot melt bonding process. Scanning electron microscopy showed that the spherical structure of the extract powder was broken into larger irregular fragments, and smaller xylitol particles were adsorbed and wrapped on the surface of the extract powder. After hot melt bonding, the surface or edges of xylitol were melted, and the surrounding extract powder was bonded together, thereby achieving bonding granulation. The orally disintegrating granules catered to the properties of granules, and the taste score and in vitro and in vivo instant solubility were better. In summary, by proposing a new molding process based on instant formulation and hot melt bonding granulation technology and preparing orally disintegrating antiviral granules, the study improves the convenience and compliance of drug administration for patients and provides a useful exploration of the innovation and improvement of traditional Chinese medicine forms.

This study systematically revealed the inflammatory mechanism of action of the Qibai Pingfei Capsules in intervening in phlegm-stasis obstructing lung syndrome in chronic obstructive pulmonary disease(COPD) based on network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation. Core components such as kaempferol and inosine, as well as key targets such as hypoxia-inducible factor-1α(HIF-1α) and prostaglandin-endoperoxide synthase 2(PTGS2)/cyclooxygenase-2(COX-2), were identified via network pharmacology, and a multidimensional interaction network was constructed. Enrichment analysis suggested that these core targets may exert regulatory effects by modulating biological processes such as hypoxic stress response, inflammatory mediator release, and angiogenesis, with potential mechanisms related to the regulation of inflammation-related signaling pathways. Molecular dynamics simulations confirmed that the key components stably bound to targets such as HIF-1α, COX-2, and tumor necrosis factor-α(TNF-α). A rat model of COPD with phlegm-stasis obstructing lung syndrome was established using a composite stimulation method(hypoxia + swimming + cigarette smoke). The results demonstrated that Qibai Pingfei Capsules could significantly improve lung function, as evidenced by increased lung function parameters(FVC, FEV_(0.3), FEV_(0.3)/FVC), and reduced inflammatory cell infiltration in lung tissue. Pathological damage to bronchi and alveolar structures in the Qibai Pingfei Capsules group was significantly alleviated, characterized by reduced airway remodeling and thinning of alveolar septa. Qibai Pingfei Capsules inhibited the expression of HIF-1α and COX-2 proteins(P<0.01) and significantly downregulated the level of the pro-inflammatory factor TNF-α. Co-immunoprecipitation confirmed the interaction between HIF-1α and COX-2 proteins in rat lung tissue. In-depth analysis revealed that the therapeutic mechanism of Qibai Pingfei Capsules may involve targeting and regulating the HIF-1α/COX-2 signaling pathway to intervene in the hypoxic stress response, thereby modulating TNF-α-mediated inflammatory cascades. This mechanism effectively modulated hypoxic stress and the inflammatory microenvironment, promoted lung tissue repair, and significantly reduced pulmonary inflammation levels in the rat model of COPD with phlegm-stasis obstructing the lung syndrome.

Escherichia coli Nissle 1917(EcN), a non-pathogenic probiotic strain isolated from the human gut, exhibits intrinsic intestinal colonization, tumor-targeting capability, and proven biosafety, which make it an ideal live delivery system. This study engineered EcN to achieve dual functionality in intestinal colonization and controlled release of active compounds. Starting with wild-type EcN, this study used lycopene biosynthesis as a proof-of-concept. First, lycopene biosynthetic genes under arabinose-inducible promoters were integrated into the EcN genome via CRISPR/Cas9, which generated the base strain EcN-C1. Subsequent overexpression of rate-limiting genes in the endogenous methylerythritol phosphate(MEP) pathway: including isopentenyl diphosphate isomerase(idi), 1-deoxy-D-xylulose-5-phosphate synthase(dxs), and farnesyl diphosphate synthase(ispA): enhanced lycopene production by 4.28-fold. Further integration of a heterologous mevalonate(MVA) pathway augmented precursor supply, resulting in a further 2.58-fold increase in yield, elevating titer to(15.24±0.87)mg·L~(-1)(11.04-fold over initial strain). Dose-and time-dependent arabinose induction enabled precise control of lycopene release across engineered strains: EcN-C1 to EcN-C4 exhibited titers spanning 0.02-1.38, 0.22-2.81, 0.67-5.90, and 1.24-15.24 mg·L~(-1), respectively. This system achieved an 800-fold dynamic range(0.02-15.24 mg·L~(-1)), demonstrating fine-tuned control over compound delivery. This work lays an important foundation for the development of novel delivery systems based on probiotics for active compound release.

This study aims to explore the effects and mechanism of Jintiange Capsules-containing serum(JTG-CS) on fibroblast-like synoviocytes(FLS) in human rheumatoid arthritis. The blank serum from SD rats and low, medium, and high-dose JTG-CS samples were prepared. Ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) was employed to determine the amino acid composition and content in the blank serum and JTG-CS. Tumor necrosis factor-α(TNF-α) was used to stimulate FLS for the modeling of inflammation. The proliferation of FLS was determined by the CCK-8 assay. The migration and invasion of FLS were examined by wound healing and Transwell assays. The protein expression of FLS was analyzed by Western blot. JTG-CS significantly inhibited the proliferation, migration, wound healing, and invasion of FLS stimulated by TNF-α, down-regulated the expression of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase(MMP)2, and MMP3, lowered the levels of TNF-α, interleukin(IL)-6, and IL-1β, and inhibited the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor(NF)-κB, and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathways. The treatment with the PI3K agonist reversed the inhibitory effects of JTG-CS on inflammatory cytokines and invasion of FLS stimulated by TNF-α. Compared with the blank serum, JTG-CS showed increased content of 46 amino acids and decreased content of 20 amino acids. JTG-CS inhibited the proliferation, migration, invasion, and inflammation of FLS stimulated by TNF-α by inhibiting the activation of the PI3K/Akt pathway.

To investigate the protective effect and mechanism of Qingdu Wenxin Formula(QD-WXF) against doxorubicin-induced cardiotoxicity(DIC), as well as the regulatory effect of QD-WXF on the cyclic guanosine monophosphate-adenosine monophosphate synthetase(cGAS)/stimulator of interferon genes(STING)/nuclear factor(NF)-κB signaling pathway. C57BL/6J mice were randomized into control, model, pravastatin(40 mg·kg~(-1)), and low-(1.3 g·kg~(-1)), medium-(2.6 g·kg~(-1)), and high-dose(5.2 g·kg~(-1)) QD-WXF groups. The mouse model of DIC was established through tail vein injection of doxorubicin, followed by four weeks of gavage. The cardiac function was evaluated by echocardiography, lactate dehydrogenase(LDH) assay, and troponin Ⅰ(TNⅠ) assay. Myocardial histopathology was assessed via hematoxylin-eosin and Masson's trichrome staining. RT-qPCR was conducted to measure the mRNA levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, and IL-1β in the cardiac tissue. Network pharmacology and molecular docking were employed to predict key pathways associated with QD-WXF and DIC, while Western blot to assess the protein level of STING. The mice with STING knockout(STING~(KO)) were prepared to validate the expression changes of proteins involved in the STING pathway and inflammation. The results of the animal experiment showed the low, medium and high doses of QD-WXF increased the ejection fraction(EF) and fractional shortening(FS) to different extents, reduced the myocardial injury markers LDH and TNⅠ, down-regulated the mRNA levels of IL-6, IL-1β, and TNF-α in the cardiac tissue, significantly reduced the inflammatory cells, recovered the regular arrangement of myocardial cells, and decreased the area of perivascular fibrosis. The high-dose group of QD-WXF had the best effect. According to the prediction results of network pharmacology and molecular docking, the key pathway between QD-WXF and DIC was the STING pathway. In addition, QD-WXF up-regulated the level of phosphorylated STING(p-STING)/STING. In the STING~(KO) mouse experiment, the results of cardiac function evaluation and inflammatory index detection of the wild type(WT) group were consistent with those of C57BL/6J mice. QD-WXF downregulated the protein levels of phosphorylated TANK-binding kinase 1(p-TBK1), phosphorylated interferon regulatory factor 3(p-IRF3), and phosphorylated nuclear factor κB(p-NF-κB). In the experiment with STING~(KO), there was no significant difference between the QD-WXF group and the model group, while significant differences existed between the WT model group and the STING~(KO) model group. The above results indicate that QD-WXF can effectively alleviate doxorubicin-induced cardiotoxicity by inhibiting the inflammation via the cGAS/STING/NF-κB pathway.

This study aims to explore the mechanism of Anshen Dingxin Granules in improving isoproterenol(ISO)-induced ventricular premature beats(VPB) in rats. Sixty rats were randomly divided into six groups: a control group, a model group, a low-dose Anshen Dingxin Granules group, a middle-dose Anshen Dingxin Granules group, a high-dose Anshen Dingxin Granules group, and a propranolol group. The control and model groups were given physiological saline. Two hours after gavage, ISO was injected to induce VPB in all groups except the control group. The injection continued for 7 days. Afterward, the VPB occurrence in each group was monitored by electrocardiogram. Histopathological changes in myocardial tissues were observed by HE and Masson staining. Ultrastructural changes in myocardial tissues were examined by transmission electron microscopy(TEM). The serum superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) levels were measured using biochemical methods. The hypoxia-inducible factor-1α(HIF-1α) protein expression in myocardial tissues was analyzed by immunohistochemistry. The HIF-1α, nuclear factor E2-related factor 2(Nrf2), heme oxygenase 1(HO-1), and glutathione peroxidase 4(GPX4) protein expressions in myocardial tissues were detected by Western blot. The Nrf2, HO-1, and GPX4 mRNA expressions in myocardial tissues were measured by PCR. The results show that, compared with the control group, the model group exhibits frequent VPBs and significantly increased arrhythmia scores(P<0.01), significantly increased heart weight index(HWI)(P<0.01), significant pathological damage in myocardial tissues, elevated levels of the oxidative stress marker MDA(P<0.01), and decreased SOD and GSH levels(P<0.01), increased HIF-1α protein expression(P<0.01), decreased Nrf2, HO-1, and GPX4 protein expressions(P<0.01), as well as decreased Nrf2, HO-1, and GPX4 mRNA expressions(P<0.01). Compared with the model group, the propranolol group and the high-dose Anshen Dingxin Granules group exhibit delayed onset and reduced frequency of VPBs(P<0.01). Besides, in the two groups of the above comparison, a significant decrease occurs as follows: arrhythmia scores(P<0.05), HWI(P<0.05 or P<0.01), myocardial tissue pathological damage, oxidative stress indicator MDA level(P<0.05 or P<0.01), HIF-1α protein expression(P<0.01) while significant increase is found in the items below: SOD and GSH levels(P<0.01), Nrf2, HO-1, and GPX4 protein expressions(P<0.05 or P<0.01), Nrf2, HO-1, and GPX4 mRNA expressions(P<0.05 or P<0.01). In conclusion, Anshen Dingxin Granules can improve ISO-induced VPB in rats. This effect may stem from HIF-1 signaling pathway regulation, which inhibits oxidative stress and in turn reduces myocardial cell damage.