Journal of Chinese Pharmaceutical Sciences

Advancements in sequential and combination treatments for osteoporosis

Jia Zheng, Ying Fu

2024, 33(7): 587-596. DOI: 10.5246/jcps.2024.07.043

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Osteoporosis, a prevalent systemic degenerative disease, poses significant challenges to China’s national health, particularly due to complications such as fractures. Therapeutic interventions for osteoporosis primarily involve bone resorption inhibitors (antiresorptive) and bone formation promoters (anabolic). Numerous studies underscore the importance of sequential and combination treatments using diverse drug types. Such approaches have shown considerable efficacy in increasing bone mineral density, reducing fracture risk, and preventing the progression of osteoporosis. This article aimed to consolidate various sequential treatment schemes, offering valuable insights for clinicians in their practice.

Failure mode and effect analysis of the risk management of non-integral-dosage drug dispensing in PIVAS

Kuikui Geng, Juan He, Sheng Rong, Zhaohu Jia, Xiangxiang Zhang, Tianlu Shi

2024, 33(7): 597-608. DOI: 10.5246/jcps.2024.07.044

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To mitigate risks associated with the prescription examination, marking, dispensing, checking, and review of non-integral-dosage drugs in Pharmacy Intravenous Admixture Service (PIVAS), we formed a project team. Employing the failure mode and effect analysis (FMEA) management method, we identified potential risks in four critical steps of the non-integral-dosage drug dispensing process within PIVAS drug management: prescription verification, mixed allocation, and verification. For each step, we assigned scores for severity, incidence, and detectability, subsequently calculating the Risk Priority Number (RPN) to prioritize identified risks. Targeted measures for improvement were developed for steps with the highest RPN values. A total of 31 risk factors were documented in the management of non-integral-dosage drugs, with the dispensing process being particularly vulnerable. Specific measures were devised for eight high RPN risks. Following a 3-month optimization and improvement period, RPN values and incidences of internal differences were significantly reduced. The implemented measures demonstrated effective risk control. Notably, we established a comprehensive conversion system for partial-dose drug dispensing, directly translating into a volume of suction fluid for dispensing personnel based on doctor orders. This eliminated the need for manual secondary calculations, thereby standardizing and automating the dispensing of non-integral-dosage drugs in PIVAS. Simultaneously, our project team conducted a dissolution test on 23 types of drugs with non-integral dosage, revealing that the solvent volume increased for 11 types after dissolution. The dosage conversion for partial dosage was recalibrated based on the volume of the final solution to ensure dosage accuracy. Through the application of failure mode and effect analysis, we systematically managed the risks associated with non-integral-dosage drugs in PIVAS. This approach addressed safety concerns in the dispensing process, reduced errors, and ensured the safe and precise administration of medication to patients.

Effect of Huanglian Jiedu Decoction on cardiac endoplasmic reticulum stress in spontaneously hypertensive rats

Xiaoming Zhang, Shihui Zhu, Yiwen Gao, Jianxiang Li, Nan Zhang, Guihua Yue

2024, 33(7): 609-619. DOI: 10.5246/jcps.2024.07.045

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Huanglian Jiedu Decoction (HLJDD) is a quintessential prescription renowned for its heat-clearing and detoxifying properties. It is primarily prescribed to counteract the syndrome characterized by the excessive heat of the Sanjiao fire. Notably, the hyperactivity of liver fire is frequently linked with hypertension, where wind fire and wind toxicity emerge as pivotal pathogenic factors. This study aimed to investigate the impact of HLJDD on the endoplasmic reticulum in spontaneously hypertensive rats (SHR), further delving into the interplay between endoplasmic reticulum stress (ERS) and myocardial remodeling and damage. Fifty SHR rats were stratified randomly into five cohorts: model, low-dose HLJDD, medium-dose HLJDD, high-dose HLJDD, and captopril groups. For comparison, a set of Wistar-Kyoto (WKY ) rats served as the baseline control group, with each group comprising 10 rats. While the model and control groups received equivalent volumes of normal saline via gavage, the other groups were administered the respective drug dosages through the same route daily for a span of 6 weeks. Upon the experiment’s conclusion, metrics such as the heart mass index (HWI) and left ventricular mass index (LVWI) were assessed. Cardiac tissue anomalies were identified using H&E staining, while ERS-related protein and mRNA expression levels were ascertained via Western blotting analysis and qPCR. Moreover, TUNEL staining was employed to detect cardiomyocyte apoptosis. The findings indicated that increasing HLJDD concentrations corresponded with escalated HWI and LVWI in rat hearts (P < 0.05). There was a marked enhancement in myocardial structural integrity, accompanied by a notable reduction in collagen fibers. The mRNA and protein expressions of myocardial inositol-dependent enzyme 1α (IRE1α), X-box binding protein 1 (XBP1), glycoregulatory protein 78 (GRP78), and CCAAT enhancer binding protein homologous protein (CHOP) in the medium and high-dose groups saw significant declines (P < 0.05). These effects mirrored those observed in the captopril group. The study underscored HLJDD’s efficacy in mitigating myocardial tissue damage in SHR. This therapeutic effect was potentially attributed to the downregulation of IRE1α, XBP1, GRP78, and CHOP, curbing excessive ERS, diminishing cardiomyocyte apoptosis, and thereby conferring cardioprotection.

Exploring the mechanism of Astragalus and Salvia miltiorrhiza in the treatment of chronic glomerulonephritis: A network pharmacology approach

Nianjing Qi, Mingxun Yang, Shan Mao

2024, 33(7): 620-630. DOI: 10.5246/jcps.2024.07.046

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To elucidate the mechanism underlying the therapeutic impact of Astragalus-Danshen in chronic glomerulonephritis (CGN), a comprehensive exploration was conducted utilizing network pharmacology. The TCMSP database was employed to aggregate the chemical constituents and targets associated with Astragalus and Danshen. Simultaneously, disease targets specific to CGN were sourced from the Genecards database. The convergence of these datasets yielded a set of intersection genes, representing potential targets for CGN treatment through Astragalus-Danshen formulations. Subsequently, protein interaction networks and "chemical composition-target" networks were meticulously constructed. Core targets were subjected to GO and KEGG enrichment analyses. The investigation revealed a total of 240 targets corresponding to 20 and 65 chemical components of Astragalus and Danshen, respectively. From this pool, 86 potential targets associated with CGN treatment were discerned, ultimately identifying 29 core targets. Noteworthy among these were TNF, JUN, TP53, IL1B, RELA, MMP9, CASP3, IL10, MAPK14, MYC, and TGFB1. KEGG enrichment analysis illuminated pathways pertinent to CGN, encompassing the IL-17 signaling pathway, TNF signaling pathway, and the AGE-RAGE signaling pathway in diabetic complications. In summary, Astragalus-Danshen exhibited a potential anti-inflammatory and renoprotective effect on CGN, particularly through modulating the IL-17 signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway in diabetic complications, involving key regulators such as TNF, JUN, TP53, IL1B, MAPK14, and others.

A network pharmacological study to investigate the combination of LHQW-XYS in the treatment of COVID-19 olfactory impairment-associated

Xiaoyu Wei, Luhang Yu, Mengru Li, Qiang Xu

2024, 33(7): 631-646. DOI: 10.5246/jcps.2024.07.047

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To explore the target of action of LHQW-XYS on the main components of COVID-19 olfactory impairment by using network pharmacological methods and try to reveal its mechanism of action in the treatment related to COVID-19 induced olfactory impairment, we used the TCMSP platform to obtain potential active ingredients through oral utilization and drug-like properties screening; the Swiss TargetPrediction platform to predict the targets of the active ingredients and construct a drug-ingredient-target network, and then obtained the gene targets of COVID-19 olfactory injury through GeneCards, OMIM, and TTD platforms to intersect the drug targets and disease genes to obtain common targets. The drug targets and disease genes were intersected to obtain common targets. STRING and Cytoscape 3.8.2 software were used to construct the target-disease gene PPI network, screen the key targets and core gene clusters, and analyze the key targets by GO and KEGG enrichment analyses with the help of the Metascape platform, and then map the screened core active ingredients and their targets into the pathway to construct the core active ingredients-targets-pathway network. The core active ingredient-target-pathway network was constructed, and finally, molecular docking was carried out. The results showed that there were 4669 potential targets, 5609 disease targets, and 17 drug-disease cross-targets for the active ingredients of LHQW-XYS. The GO and KEGG enrichment analyses indicated that the mechanism of LHQW-XYS in the treatment of olfactory impairment in COVID-19 may be due to the regulation of related signaling pathways, such as Serotonergic synapse and Regulation of lipolysis in adipocytes. Molecular docking showed that six active components (quercetin, luteolin, kaempferol, 7-methoxy-2-methylisoflavone, wogonin, medicarpin) and two key genes (PTGS2, PPARG) had good binding properties. In the end, we conclude that LHQW-XYS may act on Serotonergic synapse and Regulation of lipolysis in adipocyte pathways to achieve anti-COVID-19 olfactory impairment-associated effects.

Optimizing medication strategies for liver cancer: unraveling the mechanisms of key drug combinations in the comprehensive guide to effective tumor prescriptions

Xiao Zhang, Ye Zhong, Yongsheng Hu, Bolong Wang

2024, 33(7): 647-658. DOI: 10.5246/jcps.2024.07.048

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This study delved into the formulaic patterns of liver cancer treatment outlined in "The Complete Book of Good Tumor Prescriptions" and explored the action mechanisms of core traditional Chinese medicine (TCM) combinations. Initially, liver cancer treatment formulas were extracted from the aforementioned book, and Excel 2017 was employed for calculating the frequency, properties, and meridians associated with the TCMs. IBM SPSS Modeler 18.0 was utilized for the analysis of TCM association rules, and Cytoscape 3.7.2 was employed for the visualization of these rules. Subsequently, network pharmacology was utilized to analyze the action mechanisms of core TCM combinations, leveraging TCMSP, TCMID, Genecards, DAVID, and other databases. The results revealed the inclusion of 131 prescriptions encompassing 303 TCMs. The core TCMs predominantly comprised those invigorating blood circulation and removing blood stasis, clearing heat, and tonifying deficiencies. The flavor of the TCMs was chiefly bitter or pungent, with a prevailing cold property entering the liver and spleen meridians. Association analysis indicated that the support of Angelicae sinensis radix-Trionycis carapax was the highest. Network pharmacology predictions indicated that Angelicae sinensis radix-Trionycis carapax possessed 20 target genes associated with anti-liver cancer properties, including IL-6, MAPK3, and SRC. Gene survival analysis demonstrated high expression of MAPK3 and SRC in liver cancer patients, correlating with a poor prognosis. KEGG analysis identified major anti-liver cancer pathways for Angelicae sinensis radix-Trionycis carapax, encompassing the cancer pathway, TNF signaling pathway, and prolactin signaling pathway. In summary, this study elucidated that TCMs for liver cancer treatment primarily consisted of invigorating blood circulation and removing blood stasis, antipyretic, and tonifying medicines. The core TCM pair, Angelicae sinensis radix-Trionycis carapax, appeared pivotal in this context. The underlying mechanism might involve the modulation of key genes, such as MAPK3 and SRC, and the regulation of pathways, including the cancer pathway, TNF signaling pathway, and prolactin signaling pathway.

Flavonoid from the twigs and leaves of Erythrina variegata

Yongchun Gao, Xi Yang, Liqin Wang

2024, 33(7): 659-665. DOI: 10.5246/jcps.2024.07.049

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In the present study, 17 flavonoids, including 9 prenylated isoflavones, 4 isoflavones, 3 flavanones and 1 flavone, were isolated from the twigs and leaves of Erythrina variegata. By NMR spectroscopic means and comparision with the data in the leteratures, their structures were elucidated to be euchrenone b₁₀(1), senegalensin (2), erythrinin C (3), scandenone (4), osajin (5), alpinum isoflavone (6), isoerysenegalensein E (7), erysenegalensein E (8), diprenylgenistein (9), abyssinone V (10), abyssinone V 4′-methyl ether (11), 4′,7-dihydroxyflavanone (12), 3′,5,7-trihydroxy-4′-methoxyisoflavone (13), 2′,4′,5,7-tetrahydroxyisoflavone (14), genistein (15), daidzein (16), and apigenin (17). Except for compounds 1, 4–7, and 9–10, other compounds were isolated from E. variegata for the first time.

The research group of Prof. Suwei Dong has made progress in the study of chemical glycoprotein synthesis

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

2024, 33(7): 666-666.

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