Latest Issue
      Vol. 30 ， Issue 8 ， 2024

        Original Article

      • HE Qiu,LIN Fu-xin,SU Jin-ye,ZHUO Ling-yun,ZHU Qing,SUN Xiao-chuan,JIANG Rong-cai,YAO Zhi-gang,WANG Lei,DANG Yan-wei,LIU De-zhong,LIU Yang,FANG Wen-hua,WANG Fang-yu,LIN Yuan-xiang,WANG An-xin,WANG Deng-liang,KANG De-zhi
        Vol. 30, Issue 8, Pages: 675-683(2024) DOI: 10.1007/s11655-024-3902-6
        Abstract：Objective:To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients.Methods:This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18–80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH).Results:A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P < 0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P > 0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P < 0.05).Conclusions:The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981)  
        Keywords：post-craniotomy hematoma;Naoxueshu Oral Liquid;hematoma absorption;randomized controlled trial;Chinese medicine   
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        Published：2024-07-22
      • CAO Wei,WANG Lu,HOU Ting-hui,SHI Yun-zhou,ZHENG Qian-hua,ZHENG Hui,ZOU Zi-hao,QIN Di,YANG Qian,CHEN Si-jue,WANG Hai-yan,XIAO Xian-jun,LI Ying
        Vol. 30, Issue 8, Pages: 684-691(2024) DOI: 10.1007/s11655-023-3615-2
        Abstract：Objective:To explore the demographic and disease-related factors associated with acupuncture response in patients with chronic tension-type headache (CTTH).Methods:Using data from the randomized clinical trial (218 cases) consisting of 4 weeks of baseline assessment, 8 weeks of treatment, and 24 weeks of follow-up, participants were regrouped into responders (at least a 50% reduction in monthly headache days at week 16 compared with baseline) and non-responders. Twenty-three demographic and disease-related factors associated with acupuncture response in 183 participants were analyzed by multivariable logistic regression.Results:One hundred and nineteen (65.0%) participants were classified as responders. Four factors were significantly independently associated with acupuncture response, including treatment assignment, headache intensity at baseline, and 2 domains [general health (GH) and social functioning (SF)] from the 36-Item Short Form Health Survey quality of life questionnaire. Treatment assignment was associated with non-response: participants receiving true acupuncture were 3-time more likely to achieve a CTTH response than those receiving superficial acupuncture [odds ratio (OR) 0.322, 95% confidence interval (CI) 0.162 to 0.625, P=0.001]. Compared with patients with mild-intensity headache, patients with moderate-intensity headache were twice as likely to respond to acupuncture (OR 2.001, 95% CI 1.020 to 4.011, P=0.046). The likelihood of non-response increased by 4.5% with each unit increase in the GH grade (OR 0.955, 95% CI 0.917 to 0.993, P=0.024) while decreased by 3.8% with each unit increase in the SF grade (OR 1.038, 95% CI 1.009 to 1.069, P=0.011).Conclusions:Greater headache intensity, lower GH score, and higher SF score were associated with better acupuncture responses in CTTH patients. These 3 factors require independent validation as predictors of acupuncture effectiveness in CTTH.  
        Keywords：acupuncture;chronic tension-type headache;logistic regression;quality of life;Chinese medicine   
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        Published：2024-07-22
      • LU Chao,GAO Zi-wei,XING Shan,WANG Hui-hui,HUANG Yun-ke,ZHOU Hang,WU Lei
        Vol. 30, Issue 8, Pages: 692-700(2024) DOI: 10.1007/s11655-024-3906-2
        Abstract：Objective:To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San (CSS) in female mice.Methods:Liquid chromatography mass spectrometry (LC-MS)/MS was used to determine the content of main components in CSS to determine its stability. Female C57BL/6J mice were randomly divided into 4 groups, including control (saline), vehicle (saline), CSS (4 g/kg) and ketamine (30 mg/kg) groups. Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress (CMS) model, then received a single administration of drugs. Two hours later, the behavioral tests were performed, including open field test, tail suspension test (TST), forced swimming test (FST), novelty suppression feeding test (NSF), and sucrose preference test (SPT). Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor (NMDA) subtypes [N-methyl-D-aspartate receptor 1 (NR1), NR2A, NR2B], synaptic proteins [synapsin1 and post synaptic density protein 95 (PSD95)], and brain-derived neurotrophic factor (BDNF). Moreover, the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors, NMDA.Results:Compared with the vehicle group, a single administration of CSS (4 g/kg) reversed all behavioral defects in TST, FST, SPT and NSF caused by CMS (P< 0.05 or P < 0.01). CSS also significantly decreased the expressions of NMDA subtypes (NR1, NR2A, NR2B) at 2 h in hippocampus of mice (all P< 0.01). In addition, similar to ketamine, CSS increased levels of synaptic proteins and BDNF (P < 0.05 or P< 0.01). Furthermore, the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus (all P < 0.01).Conclusion:Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.  
        Keywords：Chaihu Shugan San;female;rapid antidepressant potential;N-methyl-D-aspartate receptor;synaptic protein;optogenetic;Chinese medicine   
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        Published：2024-07-22
      • GAO Chen-yan,QIN Gao-feng,ZHENG Ming-cui,TIAN Mei-jing,HE Yan-nan,WANG Peng-wen
        Vol. 30, Issue 8, Pages: 701-712(2024) DOI: 10.1007/s11655-023-3606-3
        Abstract：Objective:To identify whether Banxia Xiexin Decoction (BXD) alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice.Methods:Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table (n=15 per group), including a model group (MG), a liraglutide group (LG) and a BXD group (BG). Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group (CG). Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg•d) for 3 months, while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection (25 nmol/kg) for 3 months. Firstly, liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD. Then, the cognitive deficits, Aβ pathological change and synaptic plasticity markers, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), were measured in APP/PS1 mice. Brain glucose uptake was detected by micro-positron emission tomography. Intestinal microbial constituents were detected by 16S rRNA sequencing. The levels of intestinal glucagon-like peptide 1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R), as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β (PI3K/Akt/GSK3β) insulin signaling pathway were determined by immunohistochemical (IHC) staining and Western blot analysis, respectively.Results:BXD ameliorated cognitive deficits and Aβ pathological features (P < 0.01). The expressions of SYP and PSD95 in the BG were higher than those in the MG (P < 0.01). Brain glucose uptake in the BG was higher than that in the MG (P < 0.01). The intestinal microbial composition in the BG was partially reversed. The levels of intestinal GLP-1 in the BG were higher than those in the MG (P < 0.01). Compared with the MG, the expression levels of hippocampal GLP-1R, Akt, PI3K and p-PI3K in the BG were significantly increased (P < 0.01), while the levels of GSK3β were reduced (P < 0.01).Conclusion:BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R, enhancing PI3K/Akt/GSK3β insulin signaling pathway, and improving brain glucose metabolism.  
        Keywords：Banxia Xiexin Decoction;Alzheimer's disease;intestinal microbiota;glucagon-like peptide 1;cerebral insulin resistance;phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β;Chinese medicine   
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        Published：2024-07-22
      • LI Zhong-hao,PU Xiao-qi,LI Sha-sha,DONG Xiao-ke,ZHANG Guo-qiang,WANG Yu,LIU Jin-min
        Vol. 30, Issue 8, Pages: 713-720(2024) DOI: 10.1007/s11655-024-3910-6
        Abstract：Objective:To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation.Methods:The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2, 3, 5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions.Results:We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P < 0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P < 0.05). In addition, 41 chemical compounds in TRQ could bind to APJ.Conclusions:The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.  
        Keywords：Tanreqing Injection;Chinese medicine;ischemic stroke;middle cerebral artery occlusion;quantitative estimate of drug-likeness   
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        Published：2024-07-22
      • WANG Bi-yan,BU Hong-shi,XIA Li-bo,JIANG Xiang-yu,TONG Yan-qing
        Vol. 30, Issue 8, Pages: 721-728(2024) DOI: 10.1007/s11655-024-3904-4
        Abstract：Objective:To investigate the effect of low concentration of Wenyang Tonglin Decoction (WTD) on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism.Methods:Escherichia coli CP9 (R45) and Staphylococcus aureus RN450RF were cultured in medium containing WTD, and their minimum inhibitory concentration (MIC) values were obtained. Using promoter fusion technology, E. coli CP9 (R45) containing a promoter fusion was obtained. β-Galactosidase activity of TrfAp and TrbBp was tested, and the mRNA expression of regulatory factors (TrbA, KorA, and KorB) was detected by real-time fluorescent quantitative polymerase chain reaction.Results:The MIC of E. coli CP9 (R45) was 400 g/L and that of S. aureus RN450RF was 200 g/L. When the drug concentration in the culture medium was 200 g/L, the highest number of conjugants was (3.47±0.20)×107 CFU/mL. At 90 h of conjugation, the maximum number of conjugants was (1.15±0.06)×108 CFU/mL. When the initial bacterial concentration was 108 CFU/mL, the maximum number of conjugants was (3.47±0.20)×107 CFU/mL. When the drug concentration was 200 g/L, the β-galactosidase activity of TrfAp and TrbBp significantly increased; the relative quantification of TrbA, KorA and KorB were significantly inhibited.Conclusion:Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors.  
        Keywords：urinary tract infection;Chinese medicine;drug-resistant plasmid;heterozygous strains;conjugation;transfer   
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        Published：2024-07-22

        Acupuncture Research

      • WANG Yuan,ZHENG A-ni,YANG Huan,WANG Qiang,DAI Biao,WANG Jia-ju,WAN Yi-tong,LIU Zhi-bin,LIU Si-yang
        Vol. 30, Issue 8, Pages: 729-741(2024) DOI: 10.1007/s11655-023-3614-3
        Abstract：Objective:To investigate the effects and mechanisms of olfactory three-needle (OTN) electroacupuncture (EA) stimulation of the olfactory system on cognitive dysfunction, synaptic plasticity, and the gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice.Methods:Thirty-six SAMP8 mice were randomly divided into the SAMP8 (P8), SAMP8+OTN (P8-OT), and SAMP8+nerve transection+OTN (P8-N-OT) groups according to a random number table (n=12 per group), and 12 accelerated senescence-resistant (SAMR1) mice were used as the control (R1) group. EA was performed at the Yintang (GV 29) and bilateral Yingxiang (LI 20) acupoints of SAMP8 mice for 4 weeks. The Morris water maze test, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, Nissl staining, Golgi staining, Western blot, and 16S rRNA sequencing were performed, respectively.Results:Compared with the P8 group, OTN improved the cognitive behavior of SAMP8 mice, inhibited neuronal apoptosis, increased neuronal activity, and attenuated hippocampal synaptic dysfunction (P < 0.05 or P < 0.01). Moreover, the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1 (NMDAR1), NMDAR2B, synaptophysin (SYN), and postsynaptic density protein-95 (PSD95) in hippocampus were increased by OTN treatment (P < 0.05 or P < 0.01). Furthermore, OTN greatly enhanced the brain-derived neurotrophic factor (BDNF)/cAMP-response element binding (CREB) signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling compared with the P8 group (P < 0.05 or P < 0.01). However, the neuroprotective effect of OTN was attenuated by olfactory nerve truncation. Compared with the P8 group, OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice, while specifically increased the genera Oscillospira and Sutterella(P < 0.05). Interestingly, the P8-N-OT group showed an abnormal fecal microbiota with higher microbial α-diversity, Firmicutes/Bacteroidetes ratio and pathogenic bacteria (P < 0.05 or P < 0.01).Conclusions:OTN improved cognitive deficits and hippocampal synaptic plasticity by stimulating the olfactory nerve and activating the BDNF/CREB and PI3K/AKT/mTOR signaling pathways. Although the gut microbiota was not the main therapeutic target of OTN for Alzheimer's disease, the olfactory nerve was essential to maintain the homeostasis of gut microbiota.  
        Keywords：Alzheimer's disease;olfactory three-needle;electroacupuncture;olfactory nerve;synaptic plasticity;gut microbiota;Chinese medicine   
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        Published：2024-07-22

        Review

      • ZHANG Wu-jing,GUO Ze-xuan,WANG Yi-di,FANG Shao-yi,WAN Chun-miao,YU Xiao-long,GUO Xiao-fang,CHEN Yue-yue,ZHOU Xuan,HUANG Jun-qing,LI Xiao-juan,CHEN Jia-xu,FAN Li-li
        Vol. 30, Issue 8, Pages: 747-758(2024) DOI: 10.1007/s11655-024-3908-0
        Abstract：The hippocampus is one of the most commonly studied brain regions in the context of depression. The volume of the hippocampus is significantly reduced in patients with depression, which severely disrupts hippocampal neuroplasticity. However, antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet. Chinese medicine (CM) can slow the progression of depression, potentially by modulating hippocampal neuroplasticity. Xiaoyaosan (XYS) is a CM formula that has been clinically used for the treatment of depression. It is known to protect Gan (Liver) and Pi (Spleen) function, and may exert its antidepressant effects by regulating hippocampal neuroplasticity. In this review, we have summarized the association between depression and aberrant hippocampal neuroplasticity. Furthermore, we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression. The results of this review can aid future research on XYS for the treatment of depression.  
        Keywords：depression;hippocampal neuroplasticity;Xiaoyaosan;Chinese medicine   
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        Published：2024-07-22

        Herbal and Botanical Review

      • WU Yong-rong,XIONG Wei,DONG Ying-jing,CHEN Xin,ZHONG Yuan-yuan,HE Xin-ling,WANG Yu-jia,LIN Qun-fang,TIAN Xue-fei,ZHOU Qing
        Vol. 30, Issue 8, Pages: 759-767(2024) DOI: 10.1007/s11655-024-4105-x
        Abstract：The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.  
        Keywords：frankincense;species;chemical constituents;anticancer therapy;Chinese medicine   
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        Published：2024-07-22
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