1.Exploring the mechanism of Licorice in the treatment of liver injury induced by Semen Strychni based on network pharmacology,molecu-lar docking and animal experiments
Xiaoyan FU ; Zihan GONG ; Guangmiao GAO ; Biqian YANG ; Yi DENG ; Liping WANG ; Xiujuan YANG ; Zhijun YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1326-1341
AIM:To investigate the potential mechanism of licorice on liver injury induced by Se-men Strychni based on network pharmacology,mo-lecular docking combined with animal experiments,providing an effective strategy for prevention and treatment of liver injury induced by Semen Strych-ni.METHODS:Firstly,the active ingredients of Se-men Strychni and licorice were obtained through the ETCM,TCMSP database and analysis platform,CTD database and literature supplementation.Then,the potential toxic ingredients of Semen Strychni were further screened based on the Swis-sADME platform,and the targets corresponding to the active ingredients were predicted through the SwissTargetPrediction platform.By using the Gene-Cards and OMIM databases to collect DILI-related targets,the potential targets for licorice to alleviate liver injury caused by Semen Strychni were ob-tained.By constructing the active ingredient-target network,the core ingredients of licorice in alleviat-ing liver injury caused by Semen Strychni were screened.The key targets obtained were used to construct and analyze the protein-protein interac-tion networks(PPI)through the STRING database and Cytoscape 3.9.0 software.The potential targets were subjected to GO and KEGG pathway enrich-ment analysis with the aid of the DAVID database,and constructed a network of active ingredient-tar-get-pathway.Molecular docking study was ap-proved for the core targets and the active ingredi-ents by using Schrodinger 2023-1 software,and the visualization operation was conducted through Py-mol.Finally,the regulatory effect of licorice on the key pathway of liver injury caused by Semen Strych-ni was validated by establishing a rat model of liver injury induced by Semen Strychni.RESULTS:After screening,6 potential toxic components of Semen Strychni and 104 corresponding targets,89 active components of licorice and 347 corresponding tar-gets,and 3 200 DILI targets were obtained.A total of 23 intersection targets were obtained through Venn analysis.By constructing the active ingredi-ent-target network,it was found that the main core ingredients were 7-methoxy-2-methyl isofla-vone,medicarpin,shinpterocarpin,quercetin,for-mononetin and isoliquiritigenin.The PPI network indicated that the core targets were protein kinase B1(AKT1),epidermal growth factor receptor(EG-FR),human epidermal growth factor receptor 2(ERBB2),glycogen synthase kinase 3 beta(GSK3B),kinase insert domain receptor(KDR)and Janus ki-nase 2(JAK2).A total of 39 relevant pathways were enriched in KEGG(P<0.01),among which the phos-phatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)(PI3K-AKT)signaling pathway,which has been confirmed and ranks first in enrichment,and was closely related to liver injury.Molecular docking re-sults showed that the core components have good binding ability with the core targets.In vivo animal experiments demonstrated that,compared to the model group,licorice significantly reduced the liver index(P<0.01),serum levels of alkaline phospha-tase(ALP),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),indirect bilirubin(IBIL),and total bilirubin(TBIL)in rats with liver in-jury,while increasing total protein(TP)levels(P<0.05 or P<0.01).Additionally,licorice alleviated con-gestion in the central veins and hepatic sinusoids,improved the alignment of hepatocytes,and re-duced inflammatory cell infiltration.Furthermore,licorice significantly decreased the levels of malo-ndialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the liver tissue of injured rats,while elevating the levels of superoxide dismutase(SOD)and glutathi-one peroxidase(GSH-Px)(P<0.01).It also markedly downregulated the phosphorylation levels of PI3K and AKT(P<0.01).CONCLUSION:Licorice has multi-component and multi-target properties in the treat-ment of liver injury induced by Semen Strychni,which may play a hepatoprotective role by inhibit-ing the activation of PI3K-AKT signaling pathway.
2.Mechanism study on the improvement of lung injury in mice with in-fluenza A virus pneumonia by Shufeng Jiedu capsules based on regu-lating intestinal microflora
Yikun WU ; Hongmin GUO ; Yan LI ; Weige MU ; Shuyun HUANG ; Jiuling ZHU ; Zhu YANG ; Shuzhi ZHONG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1351-1360
AIM:To study the improvement effect and possible mechanism of Shufeng Jiedu capsules(SFJDC)on viral pneumonia.METHODS:Forty-eight BALB/c mice were used to establish a viral pneumo-nia model by intranasal administration of influenza A virus H1N1.They were randomly divided into 4 groups,with twelve mice in each group.Except for the Model group,the treatment group was given oseltamivir(OSTW),low and high dose groups of Shufeng Jiedu capsules(SFJDC-L,SFJD-H)by gavage,take another 12 mice as the normal group,continu-ously administered for 7 days.The physical signs of each group of mice were observed during the ad-ministration process,and the daily body weight change rate and disease activity index was calculat-ed;After administration,lung,intestinal tissue,and intestinal contents were taken,and the pathological changes in mouse lung tissue were detected using hematoxylin eosin(HE)staining method,Alisin blue staining was used to detect goblet cells in the intes-tinal wall;RT-qPCR method for detecting viral load influenza(infA)and the expression of tumor necro-sis factor-a(TNF-α)and interleukin-6(IL-6)mRNA in mouse lung tissue;Detection of mouse gut mi-crobiota using 16S rRNA high-throughput sequenc-ing;ELISA method for detecting lipopolysaccharide(LPS),TNF-α and IL-6 level in mouse serum;The ex-pression of cyclic GMP AMP synthase(cGAS),inter-feron gene stimulating protein(STING),phospho-STING(p-STING),nuclear factor-κB(NF-κB)phos-pho-nuclear factor-κB(p-NF-κB)in lung tissue and ZO-1,Occludin in small small intestine was detected by Western Blotting.RESULTS:Compared with the model group,the lung index and viral load of mice in the Shufeng Jiedu capsules group were signifi-cantly reduced(P<0.01);significant reduction in lung tissue inflammation accompanied by TNF-α;The expression level of IL-6 mRNA decreased(P<0.01);The abundance of Firmicutes and Lachnospi-raceae in the intestine significantly increased(P<0.01),while the abundance of Bacteroidetes and Bacteroidaceae communities significantly de-creased(P<0.05 or 0.01);The number of goblet cells in the small intestine epithelium significantly increased(P<0.01);the levels of serum LPS and TNF-α,IL-6 were significantly reduced(P<0.01);The protein expression level of cGAS,p-STING,p-NF-κB significantly decreased in lung tissue(P<0.05 or 0.01),ZO-1,Occludin significantly decreased in small intestine(P<0.05).CONCLUSION:Shufeng Jie-du capsules reduces the inflammatory response of mice lung tissue,and its mechanism may be relat-ed to its regulation of intestinal flora,protection of intestinal mucosal barrier,and reduction the activa-tion of cGAS/STING/NF-κB signaling pathway ac-tived by LPS leakaging from the intestine.
3.Research progress on the effect and mechanism of natural products of traditional Chinese medicine in preventing vascular restenosis
Jiawei LUO ; Tianwang CHEN ; Xinyu WANG ; Juan LIU ; Bo HUANG ; Lisheng LI ; Shangfu XU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1408-1416
Percutaneous coronary intervention(PCI)has been widely applied in the clinical treat-ment of coronary atherosclerotic heart disease and achieved good therapeutic effects.However,vascu-lar restenosis caused by postoperative vascular re-modeling still needs attention,which seriously af-fects the long-term efficacy of PCI.The prevention of vascular restenosis is of great significance for cardiovascular diseases.Traditional Chinese medi-cine natural products,with their characteristics of multiple targets,low toxicity and high safety,have attracted increasing attention in recent years.More and more studies have found that traditional Chi-nese medicine natural products have the effect of preventing and treating vascular restenosis and can effectively control its occurrence and development.This article reviews the effects and mechanisms of flavonoids,alkaloids,terpenoids and glycosides,polysaccharides and polyphenols and other tradi-tional Chinese medicine natural products in pre-venting vascular restenosis,and analyzes and sum-marizes the differences in the effects and mecha-nisms of various natural products,providing new ideas for the development of safe and effective drugs to prevent vascular restenosis.
4.Research progress of hydromorphone in postoperative analgesia for obstetrics and gynecology
Xuedong JIN ; Xin CAO ; Tang GUO ; Dikun CHEN ; Yan WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1305-1311
Hydromorphone,a semi-synthetic morphine derivative,offers strong analgesia with fewer side effects than traditional opioids.It has been widely used in multimodal analgesia proto-cols in obstetrics and gynecology.This paper re-views the current applications and research prog-ress of hydromorphone in postoperative pain man-agement for gynecological patients,assessing its ef-ficacy and safety to provide evidence for clinical practice.
5.Effects of esketamine-mediated opioid-free anesthesia on postopera-tive gastrointestinal function in patients undergoing laparoscopic rad-ical resection of distal gastric cancer
Yidong XU ; Siqi YANG ; Tao WANG ; Liuyan WU ; Ting PAN ; Sen WANG ; Zhenhui ZHOU ; Shasha YOU ; Xingzi CHEN ; Saifu WANG ; Linjun WANG ; Cunming LIU ; Chun YANG ; Di WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1297-1304
AIM:To investigate the impact of es-ketamine-mediated opioid-free anesthesia(OFA)on postoperative gastrointestinal function in patients undergoing laparoscopic distal gastrectomy for gas-tric cancer.METHODS:A total of 150 pa-tients,scheduled for elective laparoscopic distal gas-trectomy for gastric cancer and meeting the inclu-sion and exclusion criteria,were randomly assigned to either the OFA group or the opioid-based anes-thesia(OBA)group using a random number ta-ble,with 75 patients in each group.The OFA group was administered an anesthesia regimen pri-marily consisting of esketamine,while the OBA group received conventional opioid anesthesia,pri-marily consisting of sufentanil and remifentanil.The primary outcome measure was postoperative flatus time,defined as the interval from the end of sur-gery to the first passage of gas.RESULTS:The OFA group exhibited a shorter postoperative flatus time compared to the OBA group(P<0.01).Intraopera-tive blood loss and norepinephrine consumption were significantly less in the OFA group compared to the OBA group(P<0.05);the postoperative HADS-D score was better in the OFA group than in the OBA group,and both the OFA and OBA groups showed significantly lower postoperative HADS-A and HADS-D scores compared to their preoperative levels(P<0.05);the incidence rate of abdominal distension was significantly lower in the OFA group compared to the OBA group(P<0.05).CONCLUSION:The use of esketamine-mediated opioid-free anesthesia can expedite gastrointestinal function recovery,reduce hospital stay duration,and decrease postoperative adverse reactions in patients undergoing laparo-scopic distal gastrectomy for gastric cancer.
6.Effect of Angong Niuhuang pill combined with conventional treat-ment on neurological function recovery in patients with phlegm-heat internal closed cerebral hemorrhage:A randomized controlled trial based on the AMPK-PGC1α-NRF2 pathway
Yuxing WU ; Yi LI ; Xiaoqing YUE ; Chenlu ZHANG ; Yanping ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1391-1399
AIM:To examine the impact of An-gong Niuhuang pill in conjunction with convention-al therapy on the recovery of neurological function in patients with cerebral hemorrhage(ICH)charac-terized by phlegm-heat internal obstruction,and to evaluate its efficacy in enhancing neurological func-tion,promoting brain tissue repair,and mitigating oxidative stress.Additionally,this study aims to elu-cidate the potential mechanisms underlying these effects through the AMPK-PGC1α-Nrf2 pathway.METHODS:A total of 130 patients with ICH charac-terized by phlegm-heat internal closure were re-cruited and randomly allocated into a control group(receiving conventional treatment)and a study group(receiving Angong Niuhuang pill in combination with conventional treatment)using the random number table method,with 65 cases in each group.Post-treatment assessments included the National Institutes of Health Stroke Scale(NI-HSS)score,Glasgow Coma Scale(GCS)score,modi-fied Rankin scale(mRS)score,as well as tissue lev-els of AMP-activated protein kinase(AMPK),peroxi-some proliferator-activated receptor gamma coacti-vator-1α(PGC1α),and nuclear factor erythroid 2-related factor 2(NRF2).Additionally,serum levels of superoxide dismutase(SOD),malondialdehyde(MDA),reactive oxygen species(ROS),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),inter-leukin-6(IL-6),glutathione peroxidase 4(GPX4),ac-yl-coenzyme A synthetase long-chain family mem-ber 4(ACSL4),iron ions,tumor volume,brain ede-ma volume,and the incidence of adverse reactions were evaluated.RESULTS:Each group comprised 65 cases.Post-treatment,the NIHSS score(9.97±1.22)and mRS score(2.29±0.33)in the Research Group were significantly lower than those in the Control Group(11.17±1.52 and 2.64±0.45,respec-tively),with p-values less than 0.05.Additionally,the GCS score for the Research Group(14.57±1.19)was notably higher compared to the control group(13.18±1.05)(P<0.05).After treatment,the expres-sions of AMPK[(3.34±0.81)ng/mL],PGC1α[(2.30±0.67)ng/mL]and NRF2[(3.72±0.85)ng/mL]in the tissues of the group were higher than those of the control group[(2.63±0.65)ng/mL,(1.83±0.70)ng/mL,(2.91±0.96)ng/mL](P<0.05).After treatment,the levels of serum SOD[(98.76±6.67)U/mL]and IL-10[(40.37±5.61)pg/mL]in the research group were higher than those in the Control group group[(89.65±6.89)U/mL,(35.69±4.65)pg/mL](P<0.05);the serum levels of MDA[(3.36±0.62)nmol/mL],ROS[(126.35±23.74)U/mL],TNF-α[(17.22±2.07)pg/mL]and IL-6[(33.37±3.76)pg/mL]in the group were lower than those in the control group group[(3.76±0.83)nmol/mL,(159.85±26.67)nmol/mL,(19.15±2.34)nmol/mL,(41.26±4.91)nmol/mL](P<0.05).After treatment,the serum GPX4 level in the Research Group[(9.87±1.25)ng/mL]was higher than that in the control group[(8.16±1.12)ng/mL](P<0.05).The serum levels of ACSL4[(8.74±1.45)ng/mL]and iron ion[(27.44±3.35)μmol/L]in the study group were lower than those in the control group(10.12±2.11)ng/mL,(30.46±3.17)μmol/L](P<0.05).After treatment,the hematoma volume[(6.46±1.13)mL]and brain edema volume[(11.47±1.76)mL]in the research group were bet-ter than those in the Control group[(8.71±1.02)mL,(3.41±2.04)mL](P<0.05).CONCLUSION:The combination of Angong Niuhuang pill with conven-tional treatment demonstrates significant efficacy in improving neurological function,promoting brain tissue repair,and alleviating oxidative stress,thereby exhibiting high application value in clinical practice.
7.PCSK9 through non-lipid pathways in the pathogenesis of atheroscle-rosis:a review of progress in research
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1400-1407
Proprotein convertase subtilisin/KEXIN type 9(PCSK9)is the ninth member of the pro pro-tein convertase family and released into the blood-stream.It reduces the availability of low-density li-poprotein receptors and leads to the accumulation of low-density lipoprotein cholesterol in plasma,thereby promoting the development of atheroscle-rotic plaques and thrombotic events.In addition to its classical pathway,recent studies have demon-strated multiple non-classical pathways by which PCSK9 influences the development of atherosclero-sis-related diseases,including participation in in-flammatory responses,regulation of autophagy and cell apoptosis,promotion of platelet activation and thrombus formation,etc.This article provides an overview of the latest progress in the molecular mechanism by which PCSK9 affects atherosclerotic diseases through non-lipid-dependent pathways.
8.Research progress of lemborexant in the treatment of insomnia disor-der
Lijia GUO ; Zixuan DONG ; Huizhen WU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1429-1435
Lemborexant is a new drug for the treatment of insomnia.It is a dual orexin receptor antagonist that competitively binds to two orexin receptors,OX1R and OX2R,inhibits orexin neuro-transmission,and regulates the sleep-wake rhythm.This article comprehensively reviews the discovery of the drug target,basic information,clin-ical studies,safety assessment,and limitation anal-ysis of lemborexant,aiming to provide a compre-hensive understanding of the current research sta-tus and achievements of this drug in clinical prac-tice.
9.A clinical study on the preventive and therapeutic effects of oxycodo-ne administered at different timings on rebound pain following the wearing off of intercostal nerve block in thoracic surgery
Luxiang JIANG ; Jianyou ZHANG ; Zhuan ZHANG ; Miao GUO ; Suhong TANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1312-1318
AIM:To evaluate the effect of intrave-nous oxycodone administration at different timing on rebound pain following the resolution of inter-costal nerve blockade after thoracoscopic surgery.METHODS:A total of 114 patients undergoing elec-tive thoracoscopic surgery under general anesthe-sia between January and July 2024 were selected.The patients were aged 18 to 64 years,regardless of gender,with a BMI of 18 to 30 kg/m2,and classi-fied as ASA Ⅰ-Ⅱ.The patients were randomly divided into three groups using a random number table:control group(Group C),oxycodone administration at the end of surgery group(Group Q1),and oxyco-done administration 6 hours postoperatively group(Group Q2),with 38 patients in each group.Group C received a normal saline injection at the end of surgery,Group Q1 received an intravenous injec-tion of oxycodone 0.04 mg/kg at the end of sur-gery,and Group Q2 received an intravenous injec-tion of oxycodone 0.04 mg/kg at 6 hours postoper-atively.Patients in the three groups were treated with a postoperative intravenous self-control anal-gesic pump(PCIA).The occurrence of rebound pain was recorded,the time of the first analgesic pump press,the number of presses,the dosage of sufent-anil,and the need for rescue analgesia were also recorded.Numerical Rating Scale(NRS)scores at rest and during movement were recorded at 6,8,12,24,48 and 72 hours postoperatively.The Pitts-burgh Sleep Quality Index(PSQI)was used to as-sess the sleep quality of patients the night before surgery and for two nights postoperatively.Adverse reactions such as respiratory depression,postoper-ative nausea and vomiting(PONV),and pruritus were recorded.RESULTS:Compared with group C and Q1,the incidence of rebound pain,postopera-tive sufentanil consumption,effective compression frequency of PCIA from 0-24 hours after surgery,and the rate of rescue analgesia were lower in Groups Q2(P<0.05);Compared to Group C,the NRS scores at rest and during movement at 8,12,and 24 hours postoperatively were significantly lower in Groups Q1 and Q2(P<0.05).However,compared to Group Q1,Group Q2 exhibited lower NRS scores at rest and during movement at 8,12,and 24 hours postoperatively(P<0.05).On the first postoperative night,the PSQI scores of patients in Group Q2 were significantly better than those in Groups C and Q1(P<0.05).There was no statistical-ly significant difference in the incidence of PONV among the three groups(P>0.05).No respiratory depression,drowsiness,or pruritus were observed postoperatively in any of the groups.CONCLUSION:Intravenous injection of 0.04 mg/kg oxycodone 6 hours after surgery can reduce the occurrence of rebound pain after intercostal nerve block resolu-tion in thoracoscopic surgery and improves pa-tients' sleep quality.
10.Advances in the pharmacological mechanisms of monomers from Chinese medicine that target pathways involved in Alzheimer's dis-ease
Chengtian CHANG ; Zhihua LIU ; Shuaifang CHENG ; Xueke WANG ; Qianqian ZHAO ; Lit-ing GAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1417-1428
Alzheimer's disease(AD)is a preva-lent neurodegenerative disorder,characterized by the accumulation of beta-amyloid plaques,the phosphorylation of Tau proteins,and neuronal loss.As the global population ages,the incidence of AD is rising,and there is currently no effective cure.Herbal monomers have garnered interest due to their multifaceted pharmacological effects and low toxicity.This paper aims to provide a comprehen-sive overview of the mechanisms of Nrf2,NF-κB,PI3K/Akt,MAPK and other signalling pathways in the pathogenesis of AD.It also explores the modu-lation of these pathways by various TCM mono-mers,such as leptomeningine and tanshinone ⅡA,and details the research progress to date.For in-stance,Leptosine has been shown to activate Nrf2,thereby reducing oxidative stress,while Tanshinone ⅡA has been observed to inhibit the NF-κB path-way,leading to a reduction in inflammation.Not-withstanding the encouraging indications for the treatment of AD with TCM monomers,there are several challenges that must be addressed.Firstly,the precise mechanism of action remains to be ful-ly elucidated.Secondly,there are significant chal-lenges related to pharmacokinetics and bioavailabil-ity.Thirdly,the sample size of clinical studies is lim-ited and of variable quality.Fourthly,the quality control process is complex.Finally,interactions with other drugs must be taken into account.

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