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Table of Content

    03 March 2024, Volume 33 Issue 2
    Review
    Advancements in anti-tuberculosis drug potentiators: targeting mechanisms of tuberculosis resistance
    Jianhui Yang, Xiao Wang, Jinbo Zhang, Yishuang Liu
    2024, 33(2):  89-97.  DOI: 10.5246/jcps.2024.02.008
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    Tuberculosis (TB) constitutes a formidable global health challenge, exacerbated by the rise of multidrug-resistant TB (MDR-TB) strains. The effectiveness of anti-TB drugs has been hindered by this emergence of resistance. To address this, the development of synergistic compounds, informed by drug resistance mechanisms, holds promise for mitigating resistance emergence and shortening treatment durations. This review focuses on the amalgamation of anti-TB drugs with potentiators targeting the cell wall, efflux pump, and β-lactamase. Our aim is to offer insights that guide the future development of novel potentiators with enhanced efficacy and reduced toxicity.

    Original articles
    HH-A, a honokiol derivative, alleviates hypoxic brain injury in the animal ischemic model by interacting with hemoglobin
    Yuying Zhang, Pingping Zhang, Hanxin Ding, Xin Zhang, Ye Liu
    2024, 33(2):  98-109.  DOI: 10.5246/jcps.2024.02.009
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    Exposure to hypoxic conditions can result in significant brain damage, such as that experienced during an ischemic stroke. Thus, finding ways to mitigate ischemia/hypoxia-induced brain tissue damage is a critical issue that needs addressing. HH-A, a derivative of honokiol, has demonstrated potent pharmacological activities and medicinal properties in treating brain ischemia/reperfusion injury. However, its effect on anti-hypoxic responses during stroke remains largely unexplored. In the present study, we subjected male Sprague-Dawley rats to 24 h of hypoxia (oxygen content at 11%) or to 7 d of permanent middle cerebral artery occlusion. We discovered that both 1 mg/kg (i.v.) and 40 mg/kg (i.g.) of HH-A elevated arterial oxygen saturation after 24 h of hypoxia and significantly reduced the infarct volume after 7 d of ischemia. Furthermore, fluorescence staining with hypoxyprobe-1 indicated that HH-A significantly mitigated the severity of hypoxia in brain tissue. Hematoxylin and eosin staining, along with neuronal nuclei immunofluorescent staining, further revealed that HH-A curbed the death of brain cells. To identify potential protein partners of HH-A, we used a molecular fishing approach based on surface plasmon resonance technology. A high binding affinity was detected between HH-A and the hemoglobin subunit beta, with an estimated binding free energy of –8.7 kcal/mol. These findings suggested that HH-A was capable of enhancing hypoxia tolerance and alleviating brain injury caused by ischemia.

    Exploring dosage patterns of Chinese herbal medicine for recurrent headaches: A data mining analysis
    Xiao Zhang, Chunxing Wu, Bolong Wang
    2024, 33(2):  110-122.  DOI: 10.5246/jcps.2024.02.010
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    This study was carried out based on data mining methods aimed at exploring the medication patterns of Chinese medicine in the treatment of recurrent headaches, thereby providing valuable references for the clinical treatment of this condition. Initially, relevant databases and classical traditional Chinese medicine (TCM) books containing prescriptions for treating recurrent headaches were gathered. Subsequently, various techniques, such as frequency analysis, association rule analysis, cluster analysis, and decision tree analysis, were employed to investigate the prescription patterns of Chinese medicine for recurrent headaches. Following the screening process, a total of 174 prescriptions were obtained, encompassing 227 Chinese medicinal ingredients that were utilized cumulatively 1622 times. The findings indicated that Chinese medicine commonly employed in treating recurrent headaches predominantly fell under the categories of dispersing wind, promoting blood circulation and removing blood stasis, and tonifying deficiency. These medicines often possessed warm and pungent flavors and had an affinity for the liver meridian or spleen meridian. Key Chinese medicine identified included Chuanxiong rhizoma, Angelicae dahuricae radix, Asariradix et rhizoma, Saposhnikoviae radix, and Glycyrrhizae radix et rhizoma. Furthermore, through association rule analysis, a total of 92 combinations of Chinese medicine were identified. Cluster analysis yielded six distinct clusters of prescriptions for treating recurrent headaches. Simultaneously, decision tree analysis demonstrated that Angelicae dahuricae radix emerged as the most influential drug, with the CHAID algorithm exhibiting the highest accuracy rate. This study successfully employed data mining techniques to identify the core Chinese medicine used in treating recurrent headaches. It unveiled potential prescription patterns within these prescriptions and clarified the medication strategies for managing this condition. Consequently, these findings provided valuable insights for clinical diagnosis and treatment of recurrent headaches.

    Hugan Buzure granule ameliorates immune liver injury through the EGFR/Ras/PI3K/AKT signaling pathway: A network pharmacology study and experimental validation
    Zhengru Han, Wanci Song, Yang Luo, Min Xiao, Mengheng Wang, Wuyinxiao Zheng, Hanxiong Dan, Qiang Yin, Hailong Yin, Pengtao You
    2024, 33(2):  123-141.  DOI: 10.5246/jcps.2024.02.011
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    Hugan Buzure granule (HBG) is a traditional prescription in Uygur medicine that is known for its hepatoprotective properties. In a previous study, the authors have investigated the mechanism through which HBG protects against immune liver injury (ILI) by regulating immune balance and inhibiting apoptosis mediated by the IRF1/JNK signaling pathway. However, not all mechanisms are thoroughly explored. To address this issue, the present study further investigated the mechanism by which HBG reduced concanavalin A (ConA)-induced ILI in mice using network pharmacology and in vivo experiments. Initially, the livers of the mice were examined through pathological sections, which prompted further screening. The TCMSP, PharmMapper, and GeneCards databases were employed to identify the active compounds and key targets of HBG in the treatment of ILI. Subsequently, the key targets and related signaling pathways were screened using network pharmacology and molecular docking. The efficacy and mechanism of HBG against ILI were explored in a ConA-induced mouse model. Key proteins were analyzed, and their expression levels were detected using Western blotting analysis. The network pharmacology analysis revealed 16 compounds and 53 targets associated with HBG. The component-target-pathway (C-T-P) network and molecular docking indicated that EGFR, HRAS, AKT1, and PIK3R1 were the key targets of HBG in the context of ILI. TUNEL staining results demonstrated that HBG significantly reduced apoptosis in mice with ILI. Moreover, HBG markedly upregulated the expression of p-EGFR, Ras, p-AKT, p-PI3K, p-BAD, and Bcl-2, while down-regulating the levels of Bax, cleaved-caspase 9, and cleaved-caspase 3 proteins, as compared to the ConA group. These findings suggested that HBG alleviated ILI by inhibiting apoptosis through the EGFR/Ras/PI3K/AKT signaling pathway.

    Mechanism of Citri Reticulatae Pericarpium in treating Alzheimer’s disease based on network pharmacology and molecular docking
    Yunli Chen, Renliang Yan, Lisha Li, Yamin Zhang, Xiaomei Xu, Xuehua Lu, Rongqing Xu, Wenjin Lin
    2024, 33(2):  142-155.  DOI: 10.5246/jcps.2024.02.012
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    The objective of this study was to elucidate the mechanism by which Citri Reticulatae Pericarpium (CRP) treated Alzheimer’s disease (AD) using network pharmacology and molecular docking. Initially, a screening process identified 98 target compounds and 628 related component targets within CRP. Additionally, 2483 AD targets were retrieved from disease databases. Subsequently, an overlapping targets map was constructed, integrating CRP and AD targets, followed by the creation of a protein-protein interaction network map to identify 66 targets closely associated with the treatment of AD using CRP. These targets were identified through topological attribute analysis. To gain further insights, GO function and KEGG pathway enrichment analyses were conducted on the 66 identified targets. The results revealed enrichment in various biological pathways, including the relaxin signaling pathway, calcium signaling pathway, HIF-1 signaling pathway, and IL-17 signaling pathway. Finally, molecular docking verification was performed on the targets and active components of CRP. Active components, such as flavanone, tangeretin, flavonol, carvacrol, and perillaldehyde, were found to form hydrogen bonds with targets, with binding energies below 0 kg/mol. This study utilized network pharmacology and molecular docking methods to systematically elucidate the mechanism by which CRP treats AD. The findings provided a theoretical foundation for future research and clinical investigations.

    Integrated serum pharmacochemistry and network pharmacology analyses reveal the bioactive metabolites and potential functional mechanism of Piper longum L. in the treatment of gastric ulcer in rats
    Hong Zhang, Shasha Zhang, Huanyun Wang, Yue Liang, Shikui Wu, Lijun Sun, Huimin Xia, Yunxia Bai, Huiwen Zhang
    2024, 33(2):  156-168.  DOI: 10.5246/jcps.2024.02.013
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    The fruit of Piper longum L. (PL) is widely utilized in China for medicinal and dietary purposes, and it is also used in Ayurvedic medicine in India to treat gastric disorders and other ailments. In the present study, a strategy combining serum pharmacochemistry with network pharmacology was proposed to screen the bioactive metabolites derived from PL and explore their potential functional mechanisms. The strategy primarily involved investigating the anti-gastric ulcer activities, network pharmacology analysis, and metabolite identification. The results demonstrated the efficacy of PL in protecting against ethanol-induced gastric ulcers. Through network pharmacology approaches, potential drug-disease common targets were identified. GO enrichment analysis predicted that PL might influence multiple biological processes, such as lipid metabolism and inflammatory response. KEGG enrichment analysis suggested the involvement of the TNF and AGE-RAGE signaling pathways. Molecular docking further indicated that the synergistic effect of sesamin, piperine, and other ingredients could be the main contributors to PL’s anti-inflammatory and antibacterial activities. Additionally, the serum pharmacochemistry of PL was established, enabling the screening of absorbed components and metabolites for their anti-gastric ulcer activity. A total of 23 prototypes and 17 metabolites were found to significantly contribute to the anti-gastric ulcer activity, suggesting that these bioactive compounds could serve as potential active components of PL. Overall, this investigation provided an experimental foundation to support the clinical application of PL in gastric ulcer therapy.

    A network pharmacology for exploring the pharmacological mechanism of the herbal formula Xiaoyao pills on insomnia
    Dan Wang
    2024, 33(2):  169-177.  DOI: 10.5246/jcps.2024.02.014
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    The study aimed to investigate the potential mechanism of the Xiaoyao pills (XYP) for treating insomnia using network pharmacology. The researchers employed several analytical methods and databases to predict and screen the active components and targets of XYP, as well as potential targets related to insomnia. Comparative analysis was then conducted to identify overlapping genes between the active component targets and insomnia-related targets. The researchers constructed networks of the active component-target and target pathways using Cytoscape software and the STRING database. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID database. The findings revealed 161 active components present in XYP and identified 76 potential targets associated with these active components. Furthermore, 36 overlapping genes were identified as both active component targets and targets related to insomnia treatment. The network pharmacology analysis highlighted the potential significance of radix bupleuri, Chinese angelica, and liquorice in the treatment of insomnia. The proposed mechanism of XYP in treating insomnia involved 10 core targets: TNF, IL1B, CASP3, TP53, HSP90AA1, PPARG, SLC6A4, ESR1, GSK3B, and AChE. The treatment of insomnia using XYP was found to primarily affect seven enriched GO terms and six related pathways. Notably, XYP targeted TNF, IL1B, CASP3, TP53, HSP90AA1, PPARG, SLC6A4, ESR1, GSK3B, and AChE, while participating in pathways such as neuroactive ligand-receptor interaction, pathways in cancer, and calcium signaling pathway. These findings provided valuable insights into the potential molecular targets and pathways through which XYP might exert its therapeutic effects in treating insomnia.

    News
    The research group of Prof. Wanliang Lu has made progress in the research of genetically engineered PD1 protein preparations in cancer immunotherap
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center
    2024, 33(2):  178-179. 
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    The research group of Prof. Wanliang Lu has made progress in the research of genetically engineered PD1 protein preparations in cancer immunotherap.
    The research group of Prof. Tao Liu has made important progress in the field of tracking endogenous proteins
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center
    2024, 33(2):  180-183. 
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    The research group of Prof. Tao Liu has made important progress in the field of tracking endogenous proteins.
    Dr. Xiaoru Huang and Dr. Xuening Liu reviewed the role and mechanism of bile acids and their receptors in coronavirus disease 2019
    Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center
    2024, 33(2):  184-186. 
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    Dr. Xiaoru Huang and Dr. Xuening Liu reviewed the role and mechanism of bile acids and their receptors in coronavirus disease 2019.
    The research group of Prof. Yanxing Jia has made new progress in the field of total synthesis of natural products
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center
    2024, 33(2):  187-188. 
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    The research group of Prof. Yanxing Jia has made new progress in the field of total synthesis of natural products.