Zhuyeqing liquor (ZYQL) is a traditional Chinese herbal health liquor produced by macerating medicinal herbs in a base liquor. This study aimed to systematically characterize its potential bioactive components using UPLC-Q-TOF-MS and quantify 24 major components via UPLC-QqQ-MS. ZYQL and its herbal extract concentrate (ZYQ HEC) were profiled using UPLC-Q-TOF-MS with UNIFI-assisted processing, annotating compounds through accurate-mass and database matching, and verifying them against reference standards. Subsequently, a validated multiple-reaction monitoring method on UPLC-QqQ-MS was established for targeted quantification. A total of 82 constituents were identified (including 32 flavonoids, 11 carotenoids, 11 terpenoids, 8 iridoids, 7 phenolic acids, 6 phthalides, and 7 others), with 24 confirmed by standards. The quantitative method demonstrated excellent linearity (r >= 0.994) alongside acceptable precision, stability, and recovery. Hesperidin, genipin 1-gentiobioside, and crocin were present at relatively high levels, and active components were significantly more concentrated in ZYQ HEC than in the finished liquor. Ultimately, this integrated screening and targeted quantification workflow provides a sensitive, accurate, and reproducible approach, serving as a robust basis for advancing ZYQL quality control and process optimization.

Background Blood stasis constitution ointment (BSCO) is based on the classic formulas Xuefu Zhuyu and Buyang Huanwu decoctions described in Yilin Gaicuo by Wang Qingren of the Qing Dynasty. These formulas have been used to effectively treat blood stasis, which is identified as a pathological factor of lung cancer in traditional Chinese medicine theory. Aim of the study : To analyze the chemical components of BSCO, predict target pathways, and evaluate its effects on lung cancer through in vivo and in vitro experiments. Methods Ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was used to identify components of BSCO, and network pharmacology was used to predict their targets and signaling pathways associated with lung cancer. A Lewis lung cancer model was established in mice to evaluate the effects of BSCO by observing tissue morphology, whole animal imaging, and determination of serum biochemical indicators. The effects of BSCO on Lewis cancer cells in vitro were assessed using a CCK-8 cell proliferation assay. Results Twenty major chemical components of BSCO were identified, with 341 potential targets identified by network pharmacology. BSCO effectively inhibited tumor growth in the Lewis lung cancer mouse model and normalized serum markers of cancer to varying degrees. The IC50 of BSCO on Lewis cell proliferation was 173 mg/mL. Low- and high-dose BSCO-containing drug serum inhibited proliferation of Lewis cells after 24 and 48 h incubation. Conclusion The results suggest that BSCO may exert anticancer effects through targets including GAPDH, AKT1, TP53, TNF, IL6, and the PI3K-Akt signaling pathway, providing a reference for its clinical application in the prevention and treatment of lung cancer.

Insomnia is a prevalent sleep disorder and it affects brain development, with pediatric populations being particularly vulnerable. Cinnabar, a mineral drug composed of HgS, has demonstrated efficacy in alleviating insomnia through suppressing the overactivity of glutamate receptors (NMDA/AMPA), etc. However, oral administration of cinnabar poses risks, including binding with hemoglobin and accumulation in tissues and organs, resulting in neurotoxicity. To overcome these limitations, we developed a novel transdermal and intestinal targeting programmed nanoplatform for cinnabar delivery (TAT/CSK-cinnabar vesicle, TCCV), of which, cinnabar was encapsulated within a lipid vesicle, which was then co-engineered with cell-penetrating peptide TAT and the intestinal-targeting CSK ligand. Accordingly, TCCV showed exceptional sequential penetration through the stratum corneum (SC) and intestinal barriers, and also actively targeted intestinal goblet cells with a 15-fold increase in efficiency compared to non-engineered vesicles. Furthermore, TCCV forms a reservoir releasing cinnabar at the intestinal site with controlled manner, significantly reducing fluctuations in cinnabar concentration in blood and organs, thereby reducing toxicity. In current anti-insomnia studies, TCCV exhibited predominantly enhanced therapeutic efficiency compared to the oral control group, with drug efficiency increased by 1.5 to 2.5-fold. With the analysis of RNA sequencing and 16S rRNA, the regulation of the serotonin (5-HT) production in gut microbes and activating the Htr1d-cAMP pathway of cerebral cortex through the ''brain-gut axis'' by TCCV is identified as the novel mechanism for the insomnia mitigation effect of cinnabar. This study offers a novel non-invasive transdermal and targeted nanoplatform that significantly improves the efficacy and biosafety of cinnabar delivery and highlights a new gut-brain axis-mediated mechanism in insomnia mitigation.

Aim of the Study:To analyze the chemical components of BSCO, evaluate its effects on lung cancer through vivo and vitro experiments, reveal its underlying mechanism in a rat model of LC. Methods:Ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was used to identify components of BSCO. A Lewis lung cancer model was established in mice to evaluate the effects of BSCO by observing tissue morphology, whole animal imaging, and determination of serum biochemical indicators. The effects of BSCO on Lewis cancer cells in vitro were assessed using a CCK-8 cell proliferation assay. Network pharmacology and transcriptomics analysis was used to predict their targets and signaling pathways associated with lung cancer. The mRNA expressions of target genes were measured by RT-qPCR. Results:Twenty major chemical components of BSCO were identified. BSCO effectively inhibited tumor growth in the Lewis lung cancer mouse model and normalized serum markers of cancer to varying degrees. The IC50 of BSCO on Lewis cell proliferation was 173 mg/mL. Low- and high-dose BSCO-containing drug serum inhibited proliferation of Lewis cells after 24 and 48 h incubation. Integrated network pharmacology and transcriptomic analyses suggest that BSCO may exert anti-tumor effects through the PI3K-Akt signaling pathway, with TP53, IL6, CDKN1A, and KIT identified as potential key targets within this pathway. The reliability of the transcriptomic results was confirmed by verifying some lung cancer-related genes through RT-qPCR. BSCO was evaluated against model control and cyclophosphamide. A key follow-up step will be to perform protein-level validation, which confirms the observed transcriptomic signals. Conclusion:BSCO significantly inhibited lung cancer growth in vitro and in vivo. Network pharmacology and transcriptomics suggested that its anti-cancer effects might involve the PI3K-Akt signaling pathway, TP53, IL6, CDKN1A, and KIT may be its key targets.

Background: Psoriasis is a chronic inflammatory skin disorder for which topical medications are the preferred treatment option. However, current therapies are limited by adverse reactions, drug resistance, and economic burdens. Dictamni Cortex (DC; the root bark of Dictamnus dasycarpus Turcz.) has a long history in the treatment of psoriasis, with its transdermal bioactive constituents serving as the pharmacodynamic foundation for topical anti-psoriatic therapy. Methods: Building on the separation of DC’s chemical constituents, this study integrated ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and network pharmacology, along with activity verification, to investigate the anti-psoriatic active components among the transdermal constituents of DC. Results: Forty-one chemical constituents were characterized in DC, including 26 transdermally permeable compounds, predominantly alkaloids and limonoids. Network pharmacological analysis revealed core targets, including MMP9 and TLR4, as well as multiple pathways related to inflammatory and immune responses. Molecular docking studies identified dictamnine, jangomolide, rutaevin, and other key transdermal constituents that exhibited high binding affinity to core targets. In vitro validation showed that these compounds significantly suppressed cellular proliferation (p < 0.05) and downregulated Ki67 mRNA expression (p < 0.05) in the psoriasis-like HaCaT cell model. Concurrently, they significantly reduced secretion of key pro-inflammatory cytokines, including IL-17A, IL-22, IL-1β, IL-6, and IL-8 (p < 0.05). Comprehensive comparative analyses confirmed that dictamnine exhibited ideal anti-psoriatic efficacy. Conclusions: These results provide a pharmacological substance basis for the development of external preparations of DC for treating psoriasis and provide novel research concepts for investigating the pharmacodynamic material basis of Traditional Chinese Medicine topical drugs.

ObjectiveThe study aims to investigate the protective effect of Mingjing granule (MG) in a fibrovascular membrane rat model of neovascular age-related macular degeneration (nAMD) and explore the underlying mechanism.MethodsThe nAMD fibrovascular membrane model was established by two-stage laser photocoagulation. BN rats were randomly divided into four groups: the model group was gavaged with distilled water, the anti-VEGF group was given an intravitreous injection of ranibizumab, the MG + anti-VEGF group was gavaged with MG combined with an intravitreous injection of ranibizumab, and the normal group not modeled only fed conventionally. Lesions were evaluated by color fundus photograph, optical coherence tomography, fundus fluorescein angiography, and retinal pigment epithelial–choroid–sclera flat mount. The changes in the retinal structure were observed by histopathology. The expression of inflammatory cell markers F4/80, Iba-1, and glial fibrillary acidic protein (GFAP); the fibrosis-related factors collagen-1, fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor-beta (TGF-β); and the complement system-related factors C3a and C3aR in the retina were detected by immunofluorescence or qRT-PCR.ResultsThe current study revealed that MG + anti-VEGF administration more significantly reduced the thickness of fibrovascular lesions, suppressed vascular leakage (exudation area and mean density value), inhibited the area of fibrovascular lesions, and restrained the formation of the fibrovascular membrane than the anti-VEGF agent alone in the two-stage laser-induced rat model. The fluorescence intensities of F4/80, Iba-1, collagen-1, fibronectin, TGF-β, and C3aR showed more significant inhibition in MG + anti-VEGF-treated rats than the anti-VEGF agent alone. The mRNA expression levels of F4/80, Iba-1, GFAP, collagen-1, fibronectin, α-SMA, TGF-β, and C3a showed lower levels in rats treated with MG + anti-VEGF than the anti-VEGF agent alone.ConclusionCombining MG with anti-VEGF treatment inhibits the growth of the fibrovascular membrane more effectively than using anti-VEGF treatment alone. The mechanism underlying this effect may involve limiting inflammatory cell aggregation, controlling complement system activation, and decreasing the expression of the fibrotic protein.

Background and Objective:Peptic ulcer is a high incidence gastrointestinal disease in China. Berberine (BBR) is a natural product isolated from the Chinese herb Coptis chinensis Franch that has protective effects in digestive diseases. We aimed to evaluate the ability of BBR to attenuate acute gastric ulcer induced by one-time administration of ethanol in the rat.Methods:Tissue pathological morphology, macroscopic score, ulcer healing rate, and serum levels of the inflammatory cytokines nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), and anti-inflammatory interleukin-10 (IL-10) were used to determine the efficacy of BBR and evaluated to identify the optimal dosage. Subsequently, transcriptome and metabolome sequencing were conducted in Control, Model, and optimal dosage groups to explore the pathogenesis of the disease and the mechanism of action of the drug. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), as well as those of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined by enzyme-linked immunosorbent assay to verify the results of transcriptomics and metabolomics analyses.Results:BBR significantly improved the pathological morphology of gastric ulcers, increased the macroscopic score and healing rate, decreased serum levels of NO, IL-6, and PGE2, and increased serum levels of IL-10, thus effectively alleviating gastric ulcer severity. Transcriptome results showed that the therapeutic effect of BBR was mainly mediated by the arachidonic acid metabolism pathway at the gene level, which is closely associated with inflammation and increased levels of reactive oxygen species (ROS). The differentially accumulated metabolite prostaglandin E1, which is a negative regulator of ROS, was significantly up-regulated after BBR administration. The validation results indicated that BBR pretreatment increased SOD and GSH-Px enzyme activities, while reducing levels of the oxidative products MDA and MPO.Conclusion:This study demonstrated that BBR exerts a protective effect on acute gastric ulcer by promoting tricarboxylic acid cycle-mediated arachidonic acid metabolism.

Ulcerative colitis (UC), characterized by disrupted intestinal barrier integrity and chronic inflammation, was modeled in mice via dextran sulfate sodium (DSS) induction. This study explored the therapeutic potential of berberine-evodiamine (BBR-EVO), bioactive components of the traditional Chinese medicine Yulian decoction, in DSS colitis. BBR-EVO intervention ameliorated weight loss, diarrhea, colonic shortening, and histopathological damage in colitic mice. The substance increased antioxidant activity while reducing high levels of pro-inflammatory cytokines in the colon, including as TNF-α, IL-1β, and IL-6. BBR-EVO inhibited the DSS-induced decrease in the tight junction proteins ZO-1 and occludin, according to immunohistochemistry. 16S rRNA sequencing demonstrated BBR-EVO partially attenuated DSS-elicited intestinal dysbiosis, reducing opportunistic pathogens and restoring diminished beneficial taxa. Critically, BBR-EVO alleviated secondary hepatic injury in colitic mice, mitigating immune cell infiltration, oxidative stress, cytokine production, and ultrastructural damage, likely by beneficially modulating gut-liver crosstalk. This study reveals BBR-EVO, derived from a traditional Chinese medicine, confers multi-target protective effects in experimental colitis and associated hepatic pathology, warranting further evaluation as a potential therapy for inflammatory bowel diseases like UC. The mechanisms may involve simultaneous augmentation of intestinal barrier integrity, inhibition of inflammation, microbiota regulation, and gut-liver axis optimization.

采用超高效液相色谱-四极杆飞行时间串联质谱(UPLC-Q-TOF/MS)法对甘舒诺丹胶囊的化学成分进行快速鉴定.根据质谱数据结合自建数据库,利用相对分子质量、碎片离子信息以及裂解规律等方式鉴定甘舒诺丹胶囊中的化学成分,应用UNIFI 2.0软件的二元比较功能实现了各化合物的归属.从甘舒诺丹胶囊中鉴定出76种化学成分,包括21种醌类成分,18种黄酮类成分,11种有机酸类成分,7种萜类成分,3种香豆素类成分,1种木脂素类成分,15种其它成分,全面反映了甘舒诺丹胶囊中具有药理活性的化学物质和各个药材的特征性成分,为中药复方胶囊化学成分的快速鉴定、药效物质基础的发现以及临床的合理应用提供了数据参考.

Objective:To study the improvement effect of Zhibao Sanbian Pill on adenine-induced kidney yang deficiency in rat model.Methods:A total of 98 SD rats were selected.Two hours after the last administration,the body weight of rats in each group was measured,and the testis coefficient,epididymis coefficient and seminal vesicle coefficient were also detected.The number,mor-phology and motility of spermatozoa were observed by microscope.Serum levels of estradiol(E2),testosterone(T),follicle-stimula-ting hormone(FSH),luteinizing hormone(LH),dopamine(DA),5-hydroxytrypsin(5-HT)and norepinephrine(NE)were deter-mined by enzyme-linked immunosorbent assay(ELIS A).Hematoxylin and eosin(HE)staining was used to observe the pathological changes of kidney,testis and epididymis.Masson staining was used to detect renal fibrosis.Results:Compared with the normal group,the Zhibao Sanbian groups had alleviated kidney yang deficiency,increased body weight,testis coefficient,epididymis coeffi-cient and seminal vesicle coefficient,increased number of spermatozoa with low malformation,and enhanced motility.Additionally,the pathological changes of kidney,testis,epididymis and other reproductive organs as well as renal fibrosis were reduced.The pre-scription also lowered the contents of E2,FSH,LH,DA,NE and 5-HT,while increased T.Conclusion:Zhibao Sanbian Pill can im-prove the adenine-induced kidney yang deficiency in rat model based on the regulation of the hypothalamic-pituitary-gonadal(HPG)axis,showing a good effect of tonifying kidney to strengthen yang.

Objective:To study the hypoglycemic effect of Quercus mongolica leaves total flavonoids on alloxan-induced hyperglycemia mice; To discuss its underlying mechanism and pharmacodynamic material basis.Methods:The healthy ICR mice were divided into control group and diabetic mice group according to random number table method. The diabetic mouse model was established by intravenously injected with streptozotocin solution (45 mg/kg) via the tail vein. The model diabetic mice were divided into model group, positive drug group (150 mg/kg metformin hydrochloride), total flavonoids low (100 mg/kg), medium (200 mg/kg) and high (400 mg/kg) dose groups, and monomer flavonoids low (25 mg/kg), medium (50 mg/kg) and high (100 mg/kg) dose groups. Each group of mice received 0.2 ml/10 g body weight for gavage, once a day for 14 consecutive days. The control and model group were given an equal volume of physiological saline. On the 7th and 14th day of administration, the body weight, fasting blood glucose, area under the curve (AUC) of blood glucose, serum insulin and insulin receptor beta concentrations, and insulin sensitivity index were measured. The main chemical components of total flavonoids from Quercus mongolica leaves were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology.Results:Compared with the model group, after 14 days of administration, the total flavonoids of Quercus mongolica leaves at different doses and quercetin-3-O-β-D-glucopyranoside and astragalin at different doses all significantly reduced blood glucose levels ( P<0.01 or P<0.05), decreased AUC ( P<0.01 or P<0.05), and increased insulin sensitivity index ( P<0.01 or P<0.05). The 12 flavone glycosides and aglycone components were identified by UPLC-MS/MS. Conclusions:Flavonoids are speculated to be the material basis for the hypoglycemic effect of Quercus mongolica leaves. Among them, total flavonoids of Quercus mongolica leaves and monomeric flavonoids such as quercetin 3-O-β-D-glucopyranoside and astragalin have certain hypoglycemic activity, which can lower blood glucose levels by improving insulin resistance.

ObjectiveTo study the anti-fatigue effect and mechanism of Zhibao Sanbian Pills（ZB） on mice by observing its effect on Nrf2/HO-1 signaling pathway.MethodsThe ICR mice were randomly divided into four groups,including the control group,ZB low-dose(0.958 g·kg -1 )group,ZB medium-dose(4.79 g·kg -1 )group and ZB high-dose(9.58 g · kg -1 ) group, 25 mice in each group, then they were intragastrically administered for35 days, and the body mass were recorded. Weight-bearing swimming test was used to evaluate the antifatigue effect of ZB. Colorimetry was used to detect urea nitrogen（UN）and lactic acid（LA）level in the serum of each group, as well as the content of liver glycogen（LG） in liver tissue. The protein expressions of nuclear factor erythroid 2-related factor 2（Nrf2）, sequestosome 1（P62/SQSTM1）, heme oxygenase-1（HO-1）and quinone oxidoreductase 1（NQO-1） in liver tissue were detected by Western Blot.ResultsCompared with the control group,each dose group of ZB can prolong the exhaustive swimming time of mice in different degree,increase the content of LG in liver tissue, and decrease the content of serum UN. ZB high-dose group(9.58 g · kg -1 ) had significant statistical difference（P＜0.05）. ZB can reduce lactic acid accumulation, but there is no statistical difference（P＞0.05）. In addition,the protein expression levels of Nrf2,P62,HO-1 and NQO-1 in liver tissue were increased in all ZB administration groups（P＜0.05,P＜0.01）.ConclusionZB plays an obvious anti-fatigue role by regulating Nrf2/HO-1 signaling pathway to improve antioxidant capacity of the body.

目的:研究参蓝口服液对大鼠血栓形成及高脂饮食引起的小鼠高血脂的影响.方法:将Wistar大鼠随机分为空白对照组、阳性对照组及参蓝口服液高、低剂量组;空白对照组用去离子水灌胃,以临床使用剂量的阿司匹林灌胃作为阳性对照,参蓝口服液高、低剂量连续灌胃22天,观察每组大鼠实验性血栓形成情况及其对凝血功能的影响.用高脂饲料喂养的方法造成高脂血症小鼠模型,随机分为正常对照组、空白对照组、阿托伐他汀钙组及参蓝口服液高、低剂量组连续给药6周,观察参蓝口服液对模型小鼠血脂的影响.本实验中,参蓝口服液高低剂量分别为临床使用剂量的6倍和2倍.结果:抗血栓实验中,参蓝口服液高低剂量组、阳性对照组大鼠血管最大堵塞率和刺激后平均堵塞率与模型对照组相比显著降低(P<0.05或P<0.01),最大聚集率较模型对照组显著降低(P<0.05或P<0.01),同时并不影响正常的凝血功能.在治疗高脂血症实验中,检查了小鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)等高脂血症的重要检测指标,发现参蓝口服液高低剂量组小鼠TG从给药后第2周开始出现降低趋势;第4周开始,参蓝口服液高剂量组TG与模型组相比显著降低(P<0.05);给药6周后,参蓝口服液高低剂量组和阳性药物一样,显著降低了(P<0.05或P<0.01,与模型组相比)血清中TG水平.结论:参蓝口服液不但能够抑制实验性大鼠血栓形成,还可降低大鼠血脂中TG水平;同时具有良好的抗血栓和降血脂作用.

IntroductionGanshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown.MethodsA mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology.ResultsGanshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan.ConclusionGanshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.

IntroductionXuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism.MethodsThe hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology.ResultsThe current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP’s effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment.ConclusionIn summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease.

目的:考察红花口服液(HOL)缓解神经病理性疼痛(NP)的药效作用特点并探究其分子作用机制.方法:基于脊神经结扎(SNL)大鼠模型,将健康雄性SD大鼠随机分为假手术组,模型组,HOL低、中、高剂量组(0.5、1.0、2.0 mL·kg-1·d-1)及阳性药普瑞巴林组(25mg·kg-1·d-1),每组6只.在脊神经结扎手术恢复3d后,连续灌胃给药14d并采集样本.期间检测各组大鼠的机械痛阈值和冷痛阈值,考察HOL的镇痛作用特点.将假手术组、模型组、HOL高剂量组的海马组织样本进行转录组测序,获取不同组别之间的差异表达基因,并进行通路富集分析,进而,选择与NP密切相关的靶标进行验证,进一步通过分子对接寻找HOL关键活性成分与靶标分子的具体结合位点.此外,检测血清中肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)的表达水平,评价HOL对NP大鼠的影响.结果:与假手术组比较,模型组大鼠的机械痛阈值及冷痛阈值均明显降低(P＜0.05).与模型组比较,HOL组可有效升高其机械痛阈值及冷痛阈值(P＜0.05);转录组分析发现,模型组与假手术组比较共有376个差异表达基因,其中上调基因124个、下调基因252个,模型组与HOL组比较共有194个差异表达基因,其中上调基因33个、下调基因161个.其中,类胰岛素一号生长因子(IGF1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-14(MMP-14)、酪氨酸激酶受体2(ERBB2)和整合素A5(ITGA5)与NP密切相关.实时荧光定量聚合酶链式反应(Real-time PCR)结果显示,与假手术组比较,模型组大鼠海马中上述各分子的mRNA表达量均显著升高(P＜0.01).与模型组比较,HOL组可有效降低其mRNA表达量(P＜0.01).分子对接结果显示,红花主要活性成分羟基红花黄色素A、山奈酚和槲皮素与上述靶标分子IGF1、MMP-2、MMP-14、ERBB2、ITGA5的氨基酸残基形成稳定的氢键作用力.酶联免疫吸附测定法(ELISA)检测结果显示,与假手术组比较,模型组大鼠血清中TNF-α/IL-10表达失衡(P＜0.01),与模型组比较,HOL组可显著减少促炎细胞因子TNF-α的含量(P＜0.01),增加抗炎细胞因子IL-10的含量(P＜0.05).结论:HOL对SNL大鼠具有镇痛作用,其机制与抑制神经炎症密切相关.

Objective:This study aims to investigate the effects of Zhibao Sanbian Pills on learning and memory ability and explore its mechanism.Methods:Cognitive decline and memory impairment in mice was induced by scopolamine. Morris water maze test, platform jumping test and dark avoidance test were used to evaluate the learning and memory ability of mice. TCMSP, TCMID database and literature search were used to search the chemical components of Zhibao Sanbian Pills. The potential active components were screened through ADMETlab 2.0. The targets were predicted by Swiss Target Prediction. GO function and KEGG pathway enrichment analysis were conducted through the Metascape database, and a PPI network was constructed for MCODE module analysis.Results:Compared with the model group, the latency of water maze test in the high-dose group of Zhibao Sanbian Pills was shortened ( P<0.05), and the time of platform quadrant and the number of crossing increased ( P<0.05). 863 active components and 401 potential targets of Zhibao Sanbian Pills were collected. The enrichment analysis of MCODE, GO and KEGG pathways found that the action pathways of Zhibao Sanbian Pills to improve cognitive impairment involve neuroactive ligand receptor pathway, calcium signal pathway, Rap1 signal pathway, PI3K-Akt signal pathway, MAPK signal transduction pathway, 5-hydroxytryptamine receptor pathway, etc. Conclusion:Zhibao Sanbian Pills have the potential to improve the learning and memory ability of mice, which may be realized through MAPK signaling pathway and other neural related signaling pathways.

Tripterygium glycosides tablet (TGT), the classical commercial drug of Tripterygium wilfordii Hook. F. has been effectively used in the treatment of rheumatoid arthritis, nephrotic syndrome, leprosy, Behcet's syndrome, leprosy reaction and autoimmune hepatitis. However, due to its narrow and limited treatment window, TGT-induced organ toxicity (among which liver injury accounts for about 40% of clinical reports) has gained increasing attention. The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing (scRNA-seq) technology. The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Using the mouse model, we identified 15 specific subtypes of cells in the liver tissue, including endothelial cells, hepatocytes, cholangiocytes, and hepatic stellate cells. Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations; led to marked inflammatory response, apoptosis and fatty acid metabolism dysfunction in hepatocytes; activated hepatic stellate cells; brought about the activation, inflammation, and phagocytosis of liver capsular macrophages cells; resulted in immune dysfunction of liver lymphocytes; disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways. Thus, these findings elaborate the mechanism underlying TGT-induced acute liver injury, provide new insights into the safe and rational applications in the clinic, and complement the identification of new biomarkers and therapeutic targets for liver protection.

目的 分析张家口市第一医院口服中成药使用情况,为临床合理用药提供参考.方法 从HIS中调取2019—2021年医院口服中成药的使用数据,采用Excel统计用药品种、用量、销售金额、计算其年增长率、用药频度(DDDs)和日均费用(DDC).结果 2019—2021年,中成药处方量逐年增加,年增长率在10％左右;以不同类别口服中成药销售金额排序,祛瘀剂、扶正剂、清热剂、祛湿剂连续3年排在前4位;以DDDs排序,复方丹参滴丸、脑心通胶囊和银杏叶滴丸连续3年排序在前3位;以DDC排序,安宫牛黄丸连续3年排在首位.结论 医院口服中成药使用基本合理,但部分品种DDC较高,患者经济负担较大,须进一步加强管理.

The lipopolysaccharide(LPS)-indused RAW264.7 cells inflammation model was used as a carrier to investigated the effects of the preparation quality markers of Yulian Tang with anti-inflammatory activity in vitro. RAW264.7 cells were treated with LPS(50 ng·mL~(-1)) or/and different concentrations(low dose 0.1 μmol·L~(-1); medium dose 1 μmol·L~(-1); high dose 10 μmol·L~(-1)) of 18 chemical components in Yulian Tang for 24 h. Then the activity of RAW264.7 cell was detected using Cell Counting Kit-8(CCK-8) and the concentrations of inflammatory factors TNF-α and IL-6 in the supernatant of RAW264.7 cell were detected by ELISA assay. As the concentrations of chemical components in Yulian Tang increased, berberine, coptisine, magnoflorine, epiberberine, columbamine and costunolide had stronger inhibitory effects on TNF-α, whereas limonin, dehydroevodiamine, chlorogenic acid, neochlorogenic acid, groenlandicine, evodiamine, rutaecarpine and phellodendrine showed weakened inhibitory effects on TNF-α. The concentrations of palmatine, jatrorrhizine, dehydrocostus lactone and cryptochlorogenic acid had no significant effect on their inhibitory effect on TNF-α. Furthermore, dehydrorutaecarpine, chlorogenic acid, neochlorogenic acid, evodiamine, rutaecarpine, costunolide, phellodendrine and cryptochlorogenic acid showed stronger inhibitory effect on IL-6 as their concentrations increased; berberine, coptisine, magnoflorine, epiberberine, limonin, columbamine, groenlandicine and dehydrocostus lactone had no changes in their inhibitory effects on IL-6 as the concentrations increased. Palmatine and jatrorrhizine had the best inhibitory effect on IL-6. Combining the previous analysis of qualitative and quantitative preparation quality markers of Yulian Tang with the above result of dose-response relationship, we finally identified 15 preparation quality markers of Yulian Tang with anti-inflammatory activity, namely berberine, coptisine, palmatine, magnoflorine, epiberberine, limonin, columbamine, jatrorrhizine, neochlorogenic acid, chlorogenic acid, groenlandicine, evodiamine, rutaecarpine, dehydrocostus lactone and costunolide. In conclusion, our study provides a quick strategy for screening the qualitative preparation quality markers of Yulian Tang with anti-inflammatory activity. Moreover, it also provides an explicit route for the determination of preparation quality markers of Yulian Tang with other activities.