Table of Content

30 September 2023, Volume 32 Issue 9

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Original articles

Exploring the mechanism of Buxue Yimu Pills on postpartum abdominal pain through network pharmacology and experimental validation

Mengyao Wu, Lu Liu, Peng Zhang, Lele Zhang, Yun Gong, Xiuwei Yang

2023, 32(9):  691-703.  DOI: 10.5246/jcps.2023.09.057

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To investigate the molecular mechanisms of Buxue Yimu Pills (BYP) on postpartum abdominal pain (PAP) through network pharmacology and experimental validation, we filtered the main active components of BYP using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP), Symptom Mapping (SymMap), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, and Pharmacopoeia of the People’s Republic of China (ChP). The targets related to PAP were obtained from Genecards, and an intersection of genes was discovered. Subsequently, protein-protein interaction (PPI) networks were constructed using Cytoscape 3.9.0 and the String database. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to analyze the intersection of targets using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8. We constructed a compound-target (C-T) network based on the above analysis. Animal experiments were performed to verify the core targets, and immunohistochemistry was used to detect protein expression in incomplete abortion rats. Network pharmacology analysis suggested that 40 potentially active ingredients in BYP might affect 40 potential disease-related targets, such as ESR1, PGR, and MMP2, and regulate pathways, such as the HIF-1 signaling pathway, TNF signaling pathway, and Estrogen signaling pathway. According to immunohistochemistry, the protein expression levels of ERα, PR, and MMP2 in the model rats were significantly increased (P < 0.01). After administration of BYP, the expression level of PR was increased (P < 0.01), and the expression levels of ERα and MMP2 were decreased significantly (P < 0.05 or P < 0.01). BYP could treat PAP through a multi-component, multi-target, and multi-pathway approach, regulating estrogen and progesterone receptors and improving collagen metabolism, thereby promoting postpartum uterine recovery.



Investigating the mechanism of action of Gui Zhi Fu Ling Wan in the treatment of endometriosis based on network pharmacology and molecular docking

Ping Shang, Lin Liu, Yi Fang

2023, 32(9):  704-719.  DOI: 10.5246/jcps.2023.09.058

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Endometriosis (EMT) is a prevalent gynecological disorder that significantly impacts the physical and mental well-being of patients. Gui Zhi Fu Ling Wan (GZFLW), a Chinese herbal compound, has shown the potential to alleviate the symptoms of EMT. However, the molecular mechanism of action of GZFLW remains unclear. This study aimed to determine the possible molecular mechanism of GZFLW for treating EMT using network pharmacology and molecular docking techniques. Initially, the TCMSP platform was used to screen the active ingredients of GZFLW, while GeneCards, OMIM, PharmGkb, Disgenet, Drugbank, and TTD databases were employed to identify the relevant target genes of EMT. The data were analyzed using R language, Cytoscapes, and STRING, and the traditional Chinese medicine (TCM) regulatory network and protein-protein interaction (PPI) network maps were constructed by screening the TCM target genes and the disease-related genes. The GO and KEGG enrichment analyses were performed using the R language. Finally, molecular docking was performed between the protein receptors of the core genes and the corresponding small-molecule ligands. After de-duplication, a total of 49 ingredients and 189 predicted targets of GZFLW, along with 1115 EMT targets, were screened. Eighty potential genes were identified by comparing the common targets of GZFLW and EMT. The PPI network of the intersecting genes of GZFLW and the disease included 1218 edges and 80 nodes, and the core genes were AKT1, TP53, TNF, and IL6. The molecular docking results showed that the core genes of GZFLW exhibited good binding affinity to the ingredients.



Therapeutic efficacy evaluation and mechanism of action based on meta-analysis and network pharmacology of Li Chong Decoction (Bolus) for cancer treatment

Gedi Zhang, Gengxin Liu, Ziyou Yan

2023, 32(9):  720-735.  DOI: 10.5246/jcps.2023.09.059

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Li Chong Decoction (Bolus) is a traditional Chinese medicine (TCM) prescription with notable antitumor efficacy. This study focused on evaluating the therapeutic efficacy and mechanism of action of Li Chong Decoction (Bolus) for cancer treatment, using meta-analysis and network pharmacology. Firstly, we adopted an evidence-based medicine research method to collect as many clinical research reports as possible on the treatment of tumors with Li Chong Decoction (Bolus). We then conducted a meta-analysis to confirm the efficacy and safety of Li Chong Decoction (Bolus) in treating tumors. Lastly, we used the network pharmacology method to predict the intervention mechanism of Li Chong Decoction (Bolus) in treating tumors. The meta-analysis showed that the total effective rate and safety of Li Chong Decoction (Bolus) were significantly higher than those of the control group (P < 0.01). From network pharmacology, we identified 111 compounds in Li Chong Decoction (Bolus) and 339 targets shared between Li Chong Decoction (Bolus) and cancer. The significant protein targets of Li Chong Decoction (Bolus) for cancer intervention were AKT1, TP53, TNF, IL6, JUN, VEGFA, MYC, ESR1, EGFR, and CASP3. GO analysis was performed, in which the entries with the highest number of enriched genes were protein binding, cytosol, and nucleus, with 291, 179, and 166 genes distributed, respectively. For KEGG analysis, 1894 channels were enriched, with pathways related to cancer among the top 20, such as pathways in cancer, prostate cancer, endocrine resistance, proteoglycans in cancer, EGFR tyrosine kinase inhibitor resistance, bladder cancer, pancreatic cancer, IL-17 signaling pathway, C-type lectin receptor signaling pathway, and hepatocellular carcinoma. Molecular docking results showed that quercetin, luteolin, and kaempferol could dock well with AKT1, TNF, VEGFA, and EGFR, and luteolin-AKT1 and quercetin-AKT1 had the best binding degree. Li Chong Decoction (Bolus) maintained its efficacy and safety in cancer treatment. The effective TCM components of Li Chong Decoction (Bolus) might inhibit cancer by targeting multiple biological processes of hub genes mentioned above. Currently, research on the treatment of non-gynecological cancers with Li Chong Decoction (Bolus) mainly focuses on hepatocellular carcinoma.



Efficacy of eltrombopag on refractory primary immune thrombocytopenia and its effect on cellular immune function

Hanchun Yang, Fei Cheng, Juanjuan Huang

2023, 32(9):  736-743.  DOI: 10.5246/jcps.2023.09.060

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To investigate the clinical effects of eltrombopag in treating refractory primary immune thrombocytopenia (ITP) and its impact on cellular immune function, we selected 132 patients with refractory ITP admitted to our hospital between January 2019 and October 2022. They were divided into three groups: the combined treatment group (44 cases), the single treatment group (44 cases), and the complete control group (44 cases). The combined treatment group received etrapopa combined with vindesine, the single treatment group received eltrombopag, and the complete control group only received lifestyle intervention. The treatment course was 12 weeks. We compared the clinical efficacy and adverse reactions of the three groups and collected peripheral blood samples before and after treatment to detect changes in platelet count (PLT), bleeding time (BT), T lymphocyte subsets (CD₄⁺, CD₈⁺), B lymphocyte subsets (CD₁₉⁺, CD₂₀⁺), Th1 cytokines (IFN-γ, IL-2), and Th2 cytokines (IL-5, IL-4). After treatment, the complete response rate in the single treatment group was significantly higher than that in the complete control group, and the complete response rate in the combined treatment group was significantly higher than that in the single treatment group (both P < 0.05). The total effective rate in the combined treatment group was also higher than that in the single treatment group (P < 0.05). Compared with the complete control group, the PLT and BT values in the single treatment group were significantly improved after treatment (P < 0.05), and the combined treatment group had significantly improved PLT and BT values compared to the single treatment group (P < 0.05). The CD₄⁺/CD₈⁺ and CD₁₉⁺/CD₂₀⁺ values in the single treatment group were significantly improved after treatment compared with the complete control group (P < 0.05), and the combined treatment group showed significantly improved CD₄⁺/CD₈⁺ and CD₁₉⁺/CD₂₀⁺ values compared to the single treatment group (P < 0.05). Serum IFN-γ and IL-2 levels in the single and combined treatment groups were significantly lower than those in the complete control group after 12 weeks of treatment, while the levels of serum IL-5 and IL-4 were significantly higher (P < 0.05). The combined treatment group had significantly higher serum IL-5 and IL-4 levels than the single treatment group after 12 weeks of treatment (P < 0.05). The incidence of adverse reactions among the three groups was not significantly different (P > 0.05). In conclusion, for patients with refractory primary ITP, combined therapy of eltrombopag and immunosuppressants is safe and effective, improving cellular immune function.



Drug administration and clinical pharmacy column

Health status of middle-aged and elderly cancer survivors in China

Haoxin Du, Qi Bao, Huangqianyu Li, Yichen Zhang, Haishaerjiang Wushouer, Luwen Shi, Xiaodong Guan

2023, 32(9):  744-754.  DOI: 10.5246/jcps.2023.09.061

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There is a growing population of cancer survivors, and their health poses a significant challenge for the Chinese healthcare system. However, research related to this topic remains limited. In the present study, we presented an overview of the health status of middle-aged and elderly cancer survivors in China and investigated the association between cancer history and health status. To conduct our research, we utilized data from the China Health and Retirement Longitudinal Study (CHARLS), where we identified cancer survivors and individuals without a history of cancer. We evaluated the self-reported health, depression levels, and activities of daily living of both groups using survey data collected in 2018. We performed intergroup analysis using chi-squared tests and logistic regression. The analysis included 447 cancer survivors and 19 051 respondents without a history of cancer. In comparison to those without cancer history, cancer survivors exhibited higher rates of poor health (90.2% vs. 76.6%, P < 0.001), depression (43.6% vs. 34.3%, P < 0.001), and inadequate daily activities (46.5% vs. 29.1%, P < 0.001). After adjusting for respondents’ demographic characteristics, disease status, and health behaviors, we found that a history of cancer was significantly associated with worse self-reported health (OR 1.62; 95% CI, 1.38–1.96, P < 0.001), a higher risk of depression (OR 1.21; 95% CI, 1.10–1.34, P < 0.001), and insufficient activities of daily living (OR 1.43; 95% CI, 1.29–1.58, P < 0.001). Our findings indicated that cancer survivors aged over 45 in China experience poorer physical and psychological conditions, underscoring the need for considerate support and care.



Investigation and research on medication risk of Shijiazhuang urban residents based on KAP Theory

Kexin Wang, Shengnan Tian, Jia Wang, Jin Jin, Tingting Wang, Licang Zhang, Huanlong Liu

2023, 32(9):  755-763.  DOI: 10.5246/jcps.2023.09.062

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In the present study, we aimed to evaluate the medication knowledge, attitude, and practices (KAP) of urban residents in Shijiazhuang, while also analyzing potential risks and influencing factors in the medication process. An online questionnaire was used to investigate the current medication situation among Shijiazhuang residents. Statistical analyses, such as one-way ANOVA, Student’s t-test, logistic regression, and Spearman correlation, were employed. The results showed that the average scores of resident’ knowledge, attitudes, and practices were (110.4 ± 18.3) points, (39.0 ± 12.2) points, and (91.3 ± 11.5) points, respectively. Logistic regression analysis indicated that age, education, and occupation were the main factors affecting medication knowledge; education and occupation were the primary factors affecting medication attitude; and medication practices were mainly influenced by gender and age. The study found that as age increased, the level of medication knowledge and practices among residents also improved, with those aged 36–65 showing higher knowledge. Male residents exhibited lower knowledge, attitude, and practices of medication than their female counterparts. Non-medical and health industries, as well as low education levels, were important factors for the lack of medication knowledge and poor attitude among residents. The correlation coefficient between medication knowledge and practices was 0.331 (P < 0.01). In conclusion, the KAP of safe medication among residents in Shijiazhuang was generally moderate. Medication education should target special groups, such as those with low education levels, non-medical and health practitioners, males, and specific age groups, to promote safe and rational medication. This study provides a reference for public education on safe medication practices.



Study on quality control of Xiaozhong Ointment NO. 1 based on the relationship between quality fractions of main components in monarch and minister drugs and the clinical efficacy

Shi Jin, Chengyin Li, Xinyue Jing, Yunru Peng, Shaohua Dong, Wanjin Sun

2023, 32(9):  764-771.  DOI: 10.5246/jcps.2023.09.063

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In the present study, we aimed to determine the mass fractions of caudatin in cynanchum auriculatum, a component of monarch drug, and ferulic acid in ferulae resina, a component of minister drug, in Xiaozhong Ointment NO.1 using high-performance liquid chromatography (HPLC). The relationship between the mass fractions and clinical efficacy, which was expressed by the degree of pain relief, was explored in several batches of samples to establish the quality control ranges of active ingredients. A Waters X-Bridge column (250 mm × 4.6 mm, 5 μm) was used for separation at 30 °C. The optimized mobile phase consisted of acetonitrile and a 0.1% phosphoric acid water solution and was delivered by gradient elution at a flow rate of 1.0 mL/min. The PDA detector was set at 210 nm, and the injection volume was 10 μL. The intensity of pain was indicated using the Numeric Rating Scale (NRS) method. The percentage of pain relief was calculated using the formula (A – B)/A × 100%, where A and B are the pre- and post-medication scores, respectively. The pain relief degrees were categorized into 0–4 degrees. After the methodology study, the mass fractions of caudatin and ferulic acid were obtained from 10 batches of samples, and the percentage reductions in NRS were recorded in the patients using these samples. The results showed that the two groups with lower mass fractions also achieved lower percentage decreases in NRS than the other groups. An additional five batches of samples were tested, and the mass fractions were greater than the averages minus the standard deviation of the previous 10 batches. Therefore, the proposed quality control ranges were that the mass fractions of caudatin and ferulic acid should not be less than 0.4087 and 0.8511 mg/g, respectively. This accurate, sensitive, convenient, and reproducible HPLC method and the research on the consistent correlation between mass fraction and clinical efficacy laid a foundation for better quality control and further mechanism study of this preparation.



News

The research team of Prof. Yiguang Wang developed a new strategy for specifically regulating the lysosomal function of tumor-associated macrophages for cancer immunotherapy

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center

2023, 32(9):  772-772. 

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The research team of Prof. Yiguang Wang developed a new strategy for specifically regulating the lysosomal function of tumor-associated macrophages for cancer immunotherapy.