Zhongguo Zhongyao Zazhi最新文献

Epilepsy is a clinical syndrome caused by abnormal synchronous discharges of neurons in the brain resulting from multiple etiological factors. Its pathogenesis is complex, and the number of patients is increasing year by year. Existing antiepileptic drugs have problems of drug resistance and various adverse reactions, making it difficult to completely and effectively control the persistent or recurrent seizures of epilepsy. This has become an important issue urgently needing resolution in the field of epilepsy treatment. α-Asarone is an active component of the volatile oil of Acori Tatarinowii Rhizoma. Studies have shown that α-asarone exerts therapeutic effects against epilepsy through multiple mechanisms, including anti-apoptosis, anti-inflammation, antioxidation, regulation of neurotransmitter balance, modulation of ion channels, and protection of the blood-brain barrier. The synergistic effect among these mechanisms reflects the unique advantages of α-asarone in multi-level, multi-target, and comprehensive treatment. Therefore, this article reviews the relevant pharmacological mechanisms of α-asarone in epilepsy treatment and the synergistic effects among these mechanisms by searching relevant literature in China and abroad, aiming to provide a theoretical basis for the basic research and clinical application of α-asarone.

Chronic atrophic gastritis(CAG) represents a critical precancerous stage in gastric carcinogenesis, and its pathogenesis involves circadian rhythm disruption, chronic inflammation, and lipid metabolism reprogramming. Employing an integrative Chinese-western medical approach, this study systematically elucidated the molecular mechanisms whereby the core circadian clock gene BMAL1 promotes "inflammation to cancer" transformation through modulating the HIF-1α-FABP axis, driving lipid metabolism reprogramming, exacerbating oxidative stress, and disrupting immune homeostasis. The study revealed that compound traditional Chinese medicine(TCM) formulas(including Huangqi Jianzhong Tang, Xianglian Huazhuo Fang, and Lizhong Tang) intervened in the BMAL1-mediated "circadian-metabolic-immune" network, significantly ameliorated pathological damage to the gastric mucosa, suppressed inflammatory responses, alleviated lipid metabolism disorder, and reversed the "inflammation to cancer" transformation through multi-target effects. The TCM concept of "Taiyin disease resolution period"(21:00-03:00) gave insights into the link between spleen and stomach functions and circadian rhythms, with its therapeutic time window exhibiting remarkable synchronization with BMAL1 expression rhythms. Clinical studies further demonstrated that chronotherapy strategies based on chronopharmacological principles can significantly enhance the therapeutic efficacy of TCM. Based on these findings, the theory of "Taiyin disease resolution period" provides guidance for chronotherapeutic intervention in CAG management. Through innovative integration of modern chronobiology and traditional temporal medicine principles, the study illuminates the central role of the circadian clock gene in the CAG "inflammation to cancer" transformation and emphasizes the potential of the circadian clock and chronotherapy in reversing the "inflammation to cancer" transformation, offering both mechanistic insights and clinically actionable strategies for CAG treatment via chronobiology.

This study aims to investigate the chemical constituents of Syringa pinnatifolia. The lignan subfraction I_3 was isolated and purified by the ODS column chromatography and semi-preparative HPLC and structurally elucidated by ~1H-NMR, ~(13)C-NMR, 2D NMR, MS, and ECD data analysis. The protective effect was evaluated based on the model of oxygen-glucose deprivation(OGD)-induced injury in HL-1 cardiomyocytes. Two lignans were isolated and identified as(-)-alashinol A(1) and alashinol A(2), of which 1 was a new lignan and exhibited a significant protective effect against the OGD-induced injury in HL-1 cardiomyocytes. A new lignan with cardioprotective activity in vitro was described in the stem of S. pinnatifolia, which provided a reference for clarifying the pharmacological substances of this herbal medicine.

Premature ovarian failure(POF) has been a global public health concern with a rising incidence, severely affecting women's reproductive health and quality of life. This study aims to investigate the mechanisms by which Bushen Culuan Decoction(BCD) ameliorates ovarian mitochondrial dysfunction to improve POF. Fifty female BALB/c mice were randomly divided into control group, model group, positive drug group, low-, and high-dose BCD group. POF mouse model was established by subcutaneous injection of D-gal. Body weight and gonadal indices were observed, and changes in the estrous cycle were monitored. The level of FSH, E_2, and LH in serum was measured using ELISA. Ovarian tissue morphology and follicle counts were assessed via HE staining. In vitro model of human ovarian granulosa cells(KGN) injury was established to quantify mitochondrial number and ROS level. Protein expression of SIRT1 and PGC-1α was analyzed using Western blot. The results showed that compared with control group, model group reduced body weight gain, disordered estrous cycles, decreased ovarian and uterine indices, elevated serum FSH and LH levels, reduced E_2 level, decreased number of follicles at all developmental stages, and increased number of atretic follicles. Compared with model group, BCD group increased in ovarian and uterine indices, decreased in serum FSH and LH levels, increased in E_2 level, and decreased number of atretic follicles in mice. In vitro, BCD increased mitochondrial number, reduced ROS production, and upregulated SIRT1 and PGC-1α expressions in KGN. In conclusion, BCD improves the estrous cycle, increases ovarian and uterine indices, lowers serum FSH and LH levels, elevates E_2 level, reduces the number of atretic follicles, and protects ovarian function in POF mice. These effects may be associated with activation of the SIRT1 signaling pathway, thereby improving mitochondrial function and reducing oxidative stress in KGN.

This study aims to elucidate the mechanism by which Xuebijing Injection ameliorates acute lung injury(ALI) through promoting efferocytosis and suppressing inflammatory responses based on proteomics and experimental validation. Forty male Sprague Dawley(SD) rats were randomly divided into a normal control group and a model group. An ALI rat model was established by intraperitoneal injection of lipopolysaccharide(LPS). Successfully modeled rats were then randomized into three groups: a model control group, an Xuebijing Injection(8 mL·kg~(-1)) group, and a dexamethasone(5 mg·kg~(-1)) group, with 10 rats in each group. Intraperitoneal injection was administered for three days. Lung edema was evaluated by the wet/dry weight(W/D) ratio of lung tissue. Inflammatory infiltration and injury in lung tissue were assessed by hematoxylin-eosin(HE) staining, and the level of inflammatory cytokines, including interleukin(IL)-17, IL-18, and IL-4, as well as the anti-inflammatory molecule transforming growth factor-β1(TGF-β1) in serum was measured by enzyme-linked immunosorbent assay(ELISA). Differentially expressed genes(DEGs) in lung tissue among the normal control group, the model control group, and the Xuebijing Injection group were analyzed by proteomic sequencing, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were utilized for pathway enrichment analysis. Apoptotic cells were quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) assay, and the expression of efferocytosis-related key factors in lung tissue including protein S1(ProS1), Mer proto-oncogene tyrosine kinase(MerTK), and Ras-related C3 botulinum toxin substrate 1(Rac1) was evaluated by quantitative polymerase chain reaction(qPCR), Western blot, and immunofluorescence. The results of the W/D ratio of lung tissue and pathological staining showed that lung edema, inflammatory infiltration, and injury in ALI rats were ameliorated after Xuebijing Injection intervention. ELISA demonstrated that Xuebijing Injection significantly increased the TGF-β1 level and decreased the levels of IL-17, IL-18, and IL-4. Proteomics and KEGG analysis revealed that DEGs associated with anti-ALI treatment by Xuebijing Injection were enriched in signaling pathways such as efferocytosis, apoptosis, and inflammatory response. The TUNEL staining results showed that Xuebijing Injection could significantly reduce the apoptosis rate of cells in lung tissue. qPCR, Western blot, and immunofluorescence showed that Xuebijing Injection could promote the expression of key factors ProS1, MerTK, and Rac1 involved in efferocytosis. Xuebijing Injection significantly alleviates inflammatory infiltration and injury in the lung tissue of ALI rats by enhancing efferocytosis in alveolar macrophages and promoting apoptotic cell clearance to suppress inflammation.

Polygonatum, Chinese medicinal and edible plants, are renowned for various health benefits including replenishing Qi, nourishing Yin, moistening the lungs, invigorating the spleen, and benefiting the kidneys. MADS-box genes are widely present in plants and play roles as transcription factors in multiple growth and developmental processes. In this study, 74 MADS-box genes in Polygonatum cyrtonema were identified via bioinformatics methods. These genes were classified into 14 subfamilies, with members of the same subfamily clustering together on the phylogenetic tree and sharing conserved motifs and domains. They were unevenly distributed across 11 chromosomes. Additionally, in a naturally sterile P. cyrtonema mutant(QyS1), cytological observations revealed that the floral organs were homologously transformed into structures resembling filaments or perianths, leading to sterility. Correspondingly, transcriptome analysis identified that the expression levels of three AGAMOUS homologous genes, PcMADS46, PcMADS56, and PcMADS68, were significantly downregulated in the floral buds of QyS1 compared with those of the wild type, possibly leading to the sterility of QyS1. Through weighted co-expression network analysis, a regulatory model for the abnormal development of QyS1 floral organs was further proposed. That is, the expression levels of C-class genes in sterile lines decreased, leading to downregulation of downstream epigenetic inhibitory factors, upregulation of auxin signaling pathways and transporter genes, resulting in homologous transformation and infertility of stamen and carpel organs. This study identified and analyzed the MADS-box gene family and the sterility phenomenon in P. cyrtonema, providing theoretical insights and practical guidance for the germplasm resource conservation and breeding of P. cyrtonema.

Based on proteomic approaches, this study investigated the anti-breast cancer targets and mechanisms of ergosterol peroxide. The MTT assay was used to evaluate the effect of ergosterol peroxide on the viability of MCF-7 breast cancer cells. Flow cytometry was employed to assess the effects of ergosterol peroxide on apoptosis, mitochondrial membrane potential, reactive oxygen species(ROS), and cell cycle progression in MCF-7 cells. Tandem mass spectrometry-based proteomic analysis was used to determine the subcellular localization and differentially expressed proteins(DEPs) in MCF-7 cells following ergosterol peroxide treatment. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed using the EggNOG and KAAS databases. A protein-protein interaction(PPI) network was constructed via the STRING database. Western blot was conducted to detect the expression levels of relevant proteins. Molecular docking was used to verify the binding affinity of ergosterol peroxide to core target proteins. MTT assay results showed that ergosterol peroxide significantly inhibited MCF-7 cell viability in a time-and concentration-dependent manner. Flow cytometry analysis revealed that treatment with 10, 20, 40 μmol·L~(-1) ergosterol peroxide for 48 hours significantly increased the total apoptosis rate of MCF-7 cells, markedly increased mitochondrial membrane potential, significantly elevated ROS levels, and caused cell cycle arrest at the G_0/G_1 phase. Proteomic analysis identified a total of 385 DEPs between the ergosterol peroxide-treated and control groups, including 64 upregulated and 321 downregulated proteins. Bioinformatics pathway enrichment analysis indicated significant enrichment of the transforming growth factor-β(TGF-β), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), and tumor protein p53(p53) signaling pathways among the DEPs, suggesting that ergosterol peroxide may mediate cell cycle arrest and proliferation inhibition through multiple pathways. Western blot results demonstrated increased expression levels of phosphorylated(p)-p53, cytochrome C(CytC), B-cell lymphoma2(Bcl-2)-associated X protein(Bax), and cleaved cysteine-aspartic protease-7(cleaved caspase-7), and decreased expression levels of TGF-β, p-Smad2, p-Smad3, p-PI3K, p-Akt, Bcl-2, cyclin D1(CCND1), and cyclin-dependent kinase 4(CDK4) in MCF-7 cells after ergosterol peroxide treatment. These findings indicate that ergosterol peroxide may inhibit the proliferation and induce apoptosis of MCF-7 breast cancer cells by regulating the TGF-β, PI3K/Akt, and p53 signaling pathways.

The present work aims to study the mechanism by which Xianglian Pills(XLP) treat ulcerative colitis(UC) combined with depression. The mouse model of UC combined with depression was induced by dextran sulfate sodium(DSS) in combination with chronic unpredictable mild stress(CUMS). Fifty male C57BL/6 mice were randomized into control, model, XLP(2.7, 5.4 mg·g~(-1)), and 5-aminosalicylic acid+fluoxetine groups. The disease activity index(DAI) and colon length were monitored and pathologic examination was conducted to assess UC conditions in mice. The sucrose preference test, tail suspension test, and forced swimming test were performed to assess depressive-like behavior in mice. Microglia activation status was determined by immunofluorescence detection of ionized calcium-binding adaptor molecule 1(Iba-1). The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6, and IL-23 in the cerebral cortical area and the colon tissue were determined by ELISA. The transcript levels of IL-6 and IL-23α were measured by RT-qPCR. The levels of lysine demethylase 5B(KDM5B) and trimethylation of histone H3 lysine 4(H3K4me3) were determined by Western blot. Chromatin immunoprecipitation was adopted to examine the binding of KDM5B to the promoters of IL-6 and IL-23α. The results showed that XLP treatment reduced DAI and protected the colonic tissue structure. XLP increased the sucrose preference rate and decreased the immobilization time and the number of Iba-1-positive cells, compared with the model group. Furthermore, XLP lowered the levels of TNF-α, IL-1β, IL-6, and IL-23, down-regulated the transcript levels of IL-6 and IL-23α and the protein level of H3K4me3 while up-regulating the protein level of KDM5B in the cerebral cortical area and the colon tissue, and increased the binding of KDM5B to the IL-6 and IL-23α promoters. XLP may affect H3K4me3 demethylation through KDM5B to reduce the production of inflammatory factors and alleviate the inflammatory response, thus ameliorating UC combined with depression.

This study aims to explore the synergistic effect of triptolide(TP) combined with methotrexate(MTX) on lipopolysaccharide(LPS)-induced RAW264.7 macrophages and its potential mechanism based on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway, in order to infer the therapeutic effect of the combination of the two drugs on rheumatoid arthritis. RAW264.7 cells were cultured in vitro, and cell counting kit-8(CCK-8) assay was used to detect cell survival rates under the intervention of different concentrations of drugs and STING activator 5,6-dimethylxanthenone-4-acetic acid(DMXAA) and to evaluate the synergistic effect of the combination of TP and MTX by the combination index(CI). RAW264.7 cells were divided into a control group(normal cells), a model group(1 μg·mL~(-1) LPS), a TP group(0.025 μmol·L~(-1)), a MTX group(0.1 μmol·L~(-1)), combination groups(TP+MTX), and an activator group(TP+MTX+DMXAA). Cell migration and invasion abilities were detected by cell scratch and Transwell invasion assays. Levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in cell supernatants were determined by enzyme-linked immunosorbent assay(ELISA). cGAS and STING protein expression levels were analyzed in cells by Western blot. The results showed that the expression levels of IL-6, TNF-α, cGAS, and STING increased, and the cell migration and invasion abilities were enhanced in the model group compared with the control group. CCK-8 results showed that TP and MTX had a certain inhibitory effect on the proliferation of RAW264.7 cells, and there was a trend of concentration-and time-dependence. The six combination groups had a synergistic inhibitory effect on the proliferation of RAW264.7 cells(CI<1). The results of cell scratch and Transwell invasion assays showed that the migration and invasion of cells were decreased in each drug-treated group compared with the model group, and the decrease was more obvious in the combination groups(P<0.05). The results of ELISA and Western blot showed that the expression of IL-6, TNF-α, cGAS, and STING was down-regulated in the cells of each drug-treated group compared with the model group, and the effect of the combination groups was more favorable(P<0.05). In addition, the STING activator DMXAA attenuated the inhibitory effect of TP combined with MTX on LPS-induced RAW264.7 cell viability and inflammatory response(P<0.05). In conclusion, TP combined with MTX synergistically inhibited LPS-induced proliferation of RAW264.7 cells, and its mechanism of action may be related to the down-regulation of the cGAS-STING pathway and the influence on macrophage migration and invasion, which provides further evidence for the treatment of rheumatoid arthritis with TP combined with MTX.