Zhongguo Zhongyao Zazhi最新文献

Depression is a common mental disorder in clinical practice, and its clinical manifestations can be classified under the category of ″Yubing″ in traditional Chinese medicine(TCM). According to TCM theory, the onset of depression is closely related to emotional imbalance, disharmony of Qi and blood, and dysfunction of internal organs. Among them, deficiency of kidney Yang syndrome is one of the important syndromes of depression. Modern research shows that the pathogenesis of depression is complex, involving hypothalamic-pituitary-adrenal(HPA) axis dysfunction, neuroinflammation, oxidative stress, and other mechanisms. Epimedii Folium is a classic TCM for tonifying Yang, first recorded in the Shennong's Classic Materia Medica. It has the functions of tonifying kidney Yang and dispelling rheumatism. Its bioactive components are complex, mainly including flavonoids, polysaccharides, and alkaloids, which exert pharmacological effects such as neuroprotection, anti-inflammation, antioxidation, anti-tumor, and anti-osteoporosis activities. In recent years, an increasing number of studies have focused on the pharmacological effects and molecular mechanisms of Epimedii Folium in the treatment of depression. Studies have shown that Epimedii Folium can exert antidepressant effects by regulating the levels of neurotransmitters and the function of the HPA axis, reducing inflammatory responses, and alleviating oxidative stress. In addition, Epimedii Folium can promote the expression of neurotrophic factors and improve synaptic plasticity of hippocampal neurons, thereby achieving antidepressant efficacy. Based on existing research, this article systematically summarized the chemical components of Epimedii Folium and reviewed the mechanism underlying its antidepressant effects, as well as those of its compound preparations, particularly in relation to HPA axis regulation and anti-inflammatory responses. These findings provide a more solid scientific basis for studying the pathogenesis of depression from multiple perspectives, improving the prevention and treatment of depression, and developing new drugs.

This study investigates the molecular targets of Shenyan Fangshuai Liquid(SYFSL) in the treatment of diabetic kidney disease(DKD) based on renal tissue transcriptomics. A DKD model was established in C57BL/6J mice by high-fat diet combined with streptozotocin induction. Mice were divided into six groups: normal group, model group, low-, medium-, and high-dose SYFSL groups, and dapagliflozin group, with 12 mice in each group. The low-,medium-, and high-dose SYFSL groups received oral gavage of the herbal suspension at corresponding doses. The dapagliflozin group received dapagliflozin suspension by gavage. The normal and model groups received an equal volume of physiological saline by gavage for 12 consecutive weeks. After treatment, blood glucose, kidney function indicators, and urine albumin-to-creatinine ratio(UACR) were measured. Kidney tissue pathological changes were observed, and RNA-Seq sequencing was used to analyze the renal transcriptome and identify differentially expressed genes(DEGs), followed by Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses. Additionally, weighted gene co-expression network analysis(WGCNA) was performed to identify module genes, and the intersection of DEGs and module genes was used to determine hub genes. Hub gene expression was validated by RT-qPCR and further confirmed with the NephroSeq database. Single-cell sequencing data were analyzed to explore hub gene expression in different cell types, and a hub gene-miRNA regulatory network was constructed. SYFSL significantly reduced blood glucose, kidney index, serum creatinine, blood urea nitrogen, and UACR in DKD mice, and improved kidney pathological damage. Transcriptome sequencing identified 1 284 DEGs, among which 95 genes were related to SYFSL intervention in DKD. Six hub genes(S100A6, EPHA2, TNC, SPON1, CLDN4, and TACSTD2) were identified. These genes were mainly enriched in biological processes such as extracellular matrix, basement membrane, and epithelial formation, as well as signaling pathways including extracellular matrix-receptor interaction, and showed correlations with kidney function and UACR. The expression patterns of hub genes in the NephroSeq database were consistent with sequencing results. Single-cell sequencing analysis revealed specific expression patterns of these hub genes in different cell types, and the constructed gene-miRNA network revealed complex interactions among them. This study, based on transcriptomic technology, demonstrates that SYFSL exerts therapeutic effects on DKD by regulating the expression of S100A6, EPHA2, TNC, SPON1, CLDN4, and TACSTD2 and their related signaling pathways, providing a scientific basis for its clinical use in DKD treatment.

Phlorizin has antioxidant and anti-aging pharmacological activities, which render it a highly promising candidate for applications in functional foods and the pharmaceutical industry. However, the incomplete elucidation of phlorizin biosynthesis in plants has constrained its large-scale production and application. Lithocarpus litseifolius, which contains a notably higher level of phlorizin than most plant species, serves as an ideal model for identifying key enzymes involved in phlorizin biosynthesis. The genes MdDBR, MdCHS, and MdMYB10 from Malus domestica Borkh. and LlP2'GT from L. litseifolius were introduced exogenously, and the successful production of phlorizin was detected using the Agrobacterium-mediated transient expression system in Nicotiana benthamiana L. as a platform. Further investigation revealed that the transcription factor AtMYB12 from Arabidopsis thaliana significantly enhanced the yield of phlorizin, outperforming MdMYB10 from M. domestica. Furthermore, substituting M. domestica-derived MdCHS with L. litseifolius-derived chalcone synthase LlCHS1 further increased phlorizin accumulation. Subsequently, a double bond reductase gene LlDBR4 was cloned from L. litseifolius, which promoted efficient phlorizin synthesis in N. benthamiana. Co-expression of LlDBR4 with AtMYB12, LlCHS1, and LlP2'GT achieved a phlorizin yield of 2 407.57 μg·g~(-1), setting the current highest record for heterologous production in N. benthamiana. This research used Agrobacterium-mediated transient expression system in N. benthamiana as a platform. By introducing the highly efficient AtMYB12 transcription factor and exploring the double bond reductase gene from L. litseifolius, a plant production platform for phlorizin was successfully constructed, providing critical theoretical and technical frameworks for the efficient heterologous production of phloridzin in plant chassis. These findings hold significant implications for advancing phlorizin industrialization.

This study aims to evaluate the potential of Sini Power combined with Linggui Zhugan Decoction(SLD) in alleviating non-alcoholic fatty liver disease(NAFLD) and explore its mechanisms. A NAFLD model was constructed via high-fat diet(HFD) feeding for male Sprague-Dawley rats, followed by oral gavage administration of SLD for two weeks. Comprehensive evaluations included serum biochemical analysis, enzyme-linked immunosorbent assay(ELISA), and hepatic histopathological examination. Transcriptomics and metabolomics were employed to analyze the potential mechanisms, with the protein expression validated by Western blot(WB) technique. Animal experiments showed that SLD exerted hepatoprotective effects by improving liver function, inhibiting inflammatory response, and reducing hepatic cell injury. Metabolomics analysis identified 28 differential metabolites, involving metabolic pathways such as vitamin B6, thiamine, nicotinic acid/nicotinamide, and aldonic acid metabolism. The transcriptomics study indicated that SLD significantly regulated the expression of 189 genes, involving biological processes such as fatty acid biosynthesis, butanoic acid metabolism, caffeine metabolism, and eukaryotic ribosome biogenesis. Additionally, SLD regulated key signaling pathways including peroxisome proliferator-activated receptor(PPAR), tumor protein P53(P53), and Hippo. Further studies revealed that SLD activated the PPAR signaling pathway by upregulating key targets such as peroxisome proliferator-activated receptor δ(PPARδ) and fatty acid desaturase 2(FADS2) and downregulating Acyl-CoA synthetase long chain family member 3(ACSL3) and 3-hydroxy-3-methylglutaryl-CoA synthase 1(HMGCS1), which promoted fatty acid β-oxidation, inhibited fatty acid synthesis, improved hepatic lipid metabolism, and ultimately exerted the effects of protecting liver function and alleviating liver injury.

This study aims to investigate the effect of Bufei Decoction on the immune response and apoptosis of Th17 cells in chronic obstructive pulmonary disease(COPD) mice characterized by emphysema. Fifty C57BL/6 mice were randomly divided into a blank group, a model group, a Bufei Decoction group, an interleukin-17A(IL-17A) group, and a methylprednisolone group. A COPD mouse model characterized by emphysema was constructed by smoking and intraperitoneal injection of elastase and intervened by Bufei Decoction and IL-17A monoclonal antibody. An animal lung function analyzer was used to detect mouse lung function. Hematoxylin and eosin(HE) staining was utilized to observe pathological changes. Western blot was employed to detect the expression of B-cell lymphoma/leukemia-2 protein(Bcl-2), Bcl-2-associated X protein(Bax), cysteine aspartic acid protease-3(caspase-3), and cleaved cysteine aspartic acid protease-3(cleaved caspase-3) in lung tissue, and enzyme-linked immunosorbent assay(ELISA) was used to measure the content of matrix metalloproteinase 12(MMP12) and IL-17A and the expression of inflammatory factors interleukin-6(IL-6) and interleukin-8(IL-8) in bronchoalveolar lavage fluid. Flow cytometry was used to detect the apoptosis rate and T lymphocytes CD4~+ and CD8~+. The results showed that compared with that in the blank group, HE staining of lung tissue in the model group was consistent with the pathological changes of COPD. The ratio of the maximum expiratory volume 0.2 seconds after expiration to the forced expiratory volume(FEV0.2/FVC), the average flow rate of expiratory volume accounting for 25% to 75% of lung capacity(MMEF), and peak expiratory flow(PEF) in lung function testing were significantly reduced, and the content of MMP12, IL-17A, IL-6, IL-8, and CD8~+ was significantly increased. The apoptosis rate of lung tissue cells and the expression of pro-apoptotic proteins Bax and cleaved caspase-3 were significantly increased, and the expression of anti-apoptotic protein Bcl-2 was significantly reduced. Compared with the model group, the Bufei Decoction group showed a significant decrease in the expression of MMP12, IL-17A, Bax, and cleaved caspase-3, a significant reduction in the content of CD8~+ and the apoptosis rate, and a significant increase in the expression of anti-apoptotic protein Bcl-2. Bufei Decoction may regulate the immune and inflammatory responses mediated by MMP12 and IL-17A and reduce the apoptosis of lung tissue cells to alleviate COPD characterized by emphysema.

This study aims to investigate the anti-gastric cancer effects and mechanisms of Actinidia eriantha polysaccharides(AEPS) through the regulation of energy metabolism. In the animal experiment, 615 mice were used to establish a subcutaneous gastric cancer xenograft model, and the modeled mice were allocated into a model group and low-(50 mg·kg~(-1)·d~(-1)) and high-dose(100 mg·kg~(-1)·d~(-1)) AEPS groups. AEPS was administered via intraperitoneal injection for 14 days, and the tumor volume was measured via a caliper. Targeted energy metabolomics analysis was conducted on the tumor tissue. In the cell experiment, human gastric cancer HGC-27 cells were allocated into a control group and low-, medium-, and high-dose AEPS-containing serum groups. The CCK-8, wound healing, and Transwell assays were employed to assess the cell viability, migration, and invasion, respectively. The adenosine triphosphate(ATP) content, reactive oxygen species(ROS) level, activities of pyruvate dehydrogenase(PDH) and alpha-ketoglutarate dehydrogenase(α-KGDH), and nicotinamide adenine dinucleotide(NADH) level were measured via corresponding kits. The protein level of hypoxia-inducible factor-1alpha(HIF-1α) was determined by Western blot. The results showed that compared with that in the model group, the tumor volume in the AEPS high-dose group was significantly reduced. Metabolomics analysis revealed significant differences in 17 metabolites between the AEPS and model groups. KEGG pathway enrichment indicated involvement of the tricarboxylic acid(TCA) cycle, arginine metabolism, and glucose metabolism. Notably, key TCA intermediates including citrate, isocitrate, malate, and α-ketoglutarate presented reduced levels in the AEPS group compared with the model group. The cell experiment showed that compared with the control group, AEPS-containing serum treatment reduced gastric cancer cell viability, especially in the medium-and high-dose groups(P<0.05, P<0.01), and inhibited cell migration and invasion(P<0.05, P<0.01, P<0.001). The AEPS-containing serum treatment decreased the ATP content, ROS levels, PDH and α-KGDH activities, and NADH levels, particularly in the high-dose group(P<0.01). The protein level of HIF-1α was upregulated in the high-dose AEPS group(P<0.05). These results indicate that AEPS inhibits the TCA cycle by downregulating the expression of PDH, α-KGDH, and NADH and reducing the levels of citrate, isocitrate, malate, and α-ketoglutarate, thereby disrupting energy metabolism reprogramming, lowering ATP and ROS production, and ultimately suppressing the viability, invasion, and migration of gastric cancer cells. The underlying molecular mechanism may be associated with regulation of HIF-1α expression.

Based on network pharmacology, molecular docking, and in vivo zebrafish experiments, this study investigated the effects of Ginseng Radix-Rhei Radix et Rhizoma(RS-DH) on angiogenesis in ischemic stroke(IS) and its potential mechanisms. First, network pharmacology was used to analyze the active components of RS-DH and IS-associated targets and signaling pathways. Molecular docking was then employed to screen key targets. The chemical composition of RS-DH was identified using UHPLC-Q-Orbitrap HRMS. Zebrafish model of thrombosis and vessel injuries was established. The effects of different concentrations of RS-DH on blood flow and vessel injury repair in zebrafish were observed. Real-time quantitative PCR(RT-qPCR) was used to detect the changes in the expression of angiogenesis-related pathways and genes. Kits were used to measure the levels of reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), and superoxide dismutase(SOD) in zebrafish. Network pharmacology identified 37 active components of RS-DH and 461 potential targets, with 53 overlapping targets between the drug and disease. Molecular docking showed that the main components of RS-DH exhibited strong binding affinity to the JAK2/STAT3 pathway and angiogenesis-related targets. A total of 153 compounds were preliminarily identified from RS-DH using UHPLC-Q-Orbitrap HRMS. In vivo experiments showed that low-, medium-, and high-doses of RS-DH significantly inhibited thrombosis formation and repaired vessel injuries in zebrafish, with the medium dose showing the optimal effect. RT-qPCR indicated that RS-DH significantly upregulated mRNA expression levels of JAK2, STAT3, VEGF, HIF-1α, and Ang-1. Meanwhile, ROS and MDA activity levels in zebrafish were significantly reduced, while GSH and SOD activity levels were significantly increased. RS-DH can promote angiogenesis through multiple components, targets, and pathways. The mechanism of action may involve the reduction of oxidative stress via the JAK2/STAT3 pathway and the upregulation of angiogenesis-related factors such as VEGF, HIF-1α, and Ang-1.

This study explored the rationality of incorporating ammonium glycyrrhizinate in Yanlishuang Oral Dripping Pills from the perspectives of pharmacodynamics and pharmacokinetics. An acute pharyngitis rat model was established using 10% ammonia solution. From the pharmacodynamic perspective, the rationality of ammonium glycyrrhizinate in the formulation was evaluated by detecting routine blood indices, serum levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and pathological changes of pharyngeal tissue. A two-preparation, two-period, self-crossover design was adopted to conduct a bioequivalence study between Yanlishuang Oral Dripping Pills(R) and a preparation without ammonium glycyrrhizinate(T). Rabbits were divided into two groups, namely the T/R group and the R/T group. Gas chromatography-tandem mass spectrometry(GC-MS/MS) was used to investigate the pharmacokinetic characteristics of menthol, borneol, and camphor, thereby exploring the rationality of ammonium glycyrrhizinate in the formulation from the pharmacokinetic perspective. Pharmacodynamic results showed that both Yanlishuang Oral Dripping Pills and ammonium glycyrrhizinate alone reduced serum IL-6 and TNF-α levels, decreased white blood cell counts in rats with pharyngitis, and improved pathological injury of pharyngeal tissue. However, when ammonium glycyrrhizinate was absent, the therapeutic effect of Yanlishuang Oral Dripping Pills on acute pharyngitis was weakened, indicating that ammonium glycyrrhizinate enhances the anti-inflammatory effect and plays a synergistic role in the formulation. Pharmacokinetic results showed that, compared with the ammonium glycyrrhizinate-deficient preparation, Yanlishuang Oral Dripping Pills accelerated the absorption of menthol, borneol, and camphor and increased their systemic exposure, suggesting that ammonium glycyrrhizinate promotes the absorption of other components and increases their exposure in vivo. This reveals, from the pharmacokinetic perspective, the reason why ammonium glycyrrhizinate enhances the efficacy of Yanlishuang Oral Dripping Pills and further supports the rationality of its formulation. In conclusion, ammonium glycyrrhizinate significantly enhances the anti-inflammatory effect of Yanlishuang Oral Dripping Pills, promotes the absorption of active components, and increases bioavailability. The rationality of its formulation was explored through pharmacodynamic and pharmacokinetic experiments, providing a theoretical basis for the further development and clinical application of Yanlishuang Oral Dripping Pills.

Anoectochilus roxburghii is a precious Chinese herbal medicine, in which flavonoids are the primary active components. Phytohormones play key roles in regulating flavonoid biosynthesis. However, the regulatory mechanisms of endogenous hormones on flavonoid synthesis in A. roxburghii remain unclear. In this study, integrated metabolomic and transcriptomic analyses were conducted to systematically investigate the distribution differences of endogenous phytohormones and flavonoid metabolites in the roots, stems, and leaves of A. roxburghii, as well as their regulatory networks. Metabolomic analysis identified a total of 17 endogenous hormones and 49 flavonoid metabolites. Among them, salicylic acid(SA), zeatin(ZT), and gibberellin A7(GA7), together with 21 flavonoids such as naringenin 7-O-glucoside and peonidin 3-O-glucoside, were enriched in the roots; melatonin(MT) and S-adenosyl-L-methionine, along with eight flavonoids including 3'-O-methylluteolin, showed the highest abundance in the stems; gibberellin A24(GA24) and L-phenylalanine, together with 20 flavonoids such as kaempferol and quercetin, were enriched in the leaves. Transcriptomic analysis revealed 382 genes related to flavonoid biosynthesis, encoding 23 metabolic enzymes in total. Correlation analysis indicated that hormones such as SA, ZT, and GA7 were significantly positively correlated with the expression of key enzyme genes, including chalcone synthase(CHS), flavonoid 3',5'-hydroxylase(CYP75A), and flavonol synthase(FLS). Furthermore, transcription factors from the MYB, bHLH, and WRKY families(such as GL3, MYB12, and WRKY41) were predicted to participate in regulating the flavonoid biosynthetic pathway through hormone-responsive elements. This study preliminarily constructed an endogenous hormone-transcription factor-metabolic enzyme gene regulatory network, providing a theoretical basis for elucidating the organ-specific accumulation of flavonoids in A. roxburghii and its regulation by exogenous hormones.