Journal of Chinese Pharmaceutical Sciences

Effect of Nrf2 on the testicular microenvironment and its research progress in male diseases

Hui Wu, Gang Ning, Bonan Li, Xing Zhou

2023, 32(7): 513-526. DOI: 10.5246/jcps.2023.07.043

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Oxidative stress (OS) is an imbalanced state between the production of reactive oxygen species (ROS) and antioxidation, and plays a crucial role in the development and progression of various diseases. Nrf2, a major regulator of ROS production and restoration of redox balance, exerts significant regulatory effects on the body and cells. For example, by regulating the testis microenvironment, Nrf2 can improve oxidative damage to Leydig, Sertoli, and spermatogenic cells, thus affecting testosterone synthesis and protecting male reproductive health. Moreover, Nrf2 is crucial in regulating late-onset hypogonadism in males and male infertility. Nrf2 is also involved in the pathogenesis of many other male diseases, such as benign prostatic hyperplasia, prostate cancer, prostatitis, erectile dysfunction, and varicocele. Therefore, Nrf2 could be a promising target for treating and preventing male diseases, and it holds great potential in clinical practice.

Study on the mechanism of Danggui Buxue decoction in the treatment of diabetic retinopathy based on network pharmacology and experiment

Dongyan Wu, Xiaodan Wang, Jinmiao Chai, Qinqing Li, Yue Li, Mei Bi, Wanwei Gui, Huimin Cao

2023, 32(7): 527-538. DOI: 10.5246/jcps.2023.07.044

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In the present study, we investigated the mechanism of action of Danggui Buxue decoction (DBD) in diabetic retinopathy (DR) using network pharmacology and molecular docking combined with experimental validation. GeneCards and DisGeNET were used to collect DR targets. The intersection of the two targets was obtained using Venny 2.1. Cytoscape was used to construct "disease-drug-component-target" and protein-protein interaction (PPI) networks. DAVID database was used to enrich key targets with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). AutoDockVina was used to perform molecular docking of primary active ingredients with key targets. Molecular docking validation was performed with key targets by AutoDockVina. Finally, the network pharmacological results were validated by animal experiments. A total of 84 common targets of DBD and DR were collected, 220 entries were revealed by GO analysis, and 113 signaling pathways were obtained by KEGG enrichment analysis. Molecular docking results showed that the key targets had suitable docking activities with quercetin, dousterol and other active ingredients. Animal experiments showed that DBD could improve retinal tissue morphology, lower blood glucose, increase insulin secretion, reduce VEGF and TNF-α protein expression levels and increase PI3K and Akt1 expression levels in the retinal tissues of DR rats (P < 0.05, P < 0.01). The treatment of DR by DBD had the characteristics of multiple active ingredients, multiple targets and multiple pathways, which could exert therapeutic effects on DR by regulating the core targets of TNF-α, VEGFA, PI3K, and AKT and affecting the signaling pathways of PI3K/AKT and TNF.

α-Boswellic acid ameliorates acute kidney injury by inhibiting the TLR4-mediated inflammatory pathway

Fan Wang, Ruili Li, Wenjun Wang, Xiaoyan Zhou, Meiyou Liu, Jinyi Zhao, Aidong Wen, Jingwen Wang, Yanyan Jia

2023, 32(7): 539-550. DOI: 10.5246/jcps.2023.07.045

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α-Boswellic acid (α-BA) is a bioactive compound derived from the resin of the African myrrh tree, which has been shown to have therapeutic potential for a range of inflammatory disorders. In the present study, we aimed to evaluate the effects of α-BA on improving ischemia-reperfusion injury (IRI)-induced acute kidney injury (AKI), both in vivo and in vitro. In this experiment, rats that underwent right nephrectomy and left kidney IRI were administered with α-BA 30 min before IRI. The rats’ renal function was evaluated, and their kidney tissues were subjected to histopathological analysis and TUNEL staining. For in vitro evaluation, the proximal renal tubular cells (HK-2) were subjected to oxygen-glucose deprivation (OGD). Cell viability, immunofluorescence staining, and Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB expressions were investigated. After treatment with α-BA, the levels of serum creatinine and blood urea nitrogen were significantly reduced in the rats subjected to IRI, and apoptosis was alleviated, along with improvements in renal morphological changes. Moreover, the treatment of HK-2 cells with α-BA effectively reduced the expression of NF-κB p65. Collectively, the results suggested that α-BA improved IRI-induced AKI in part by promoting the survival of renal tubular cells through the TLR4-mediated inflammatory pathway, thereby improving renal function.

Vortex-assisted switchable solvent liquid-phase microextraction for preconcentration of cinnamic acid derivatives in traditional Chinese medicine

Bo Fan, Xiao Yang, Shuang Hu

2023, 32(7): 551-559. DOI: 10.5246/jcps.2023.07.046

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In the present study, we developed a vortex-assisted switchable solvent liquid-phase microextraction (VA-SSLPME) approach to extract four cinnamic acid derivatives in traditional Chinese medicinal samples prior to HPLC analysis. During the extraction process, hypotoxic hexanoic acid was used as a switchable polarity extraction solvent. First, hydrophobic hexanoic acid was converted into a hydrophilic form by the addition of sodium carbonate. Then, sulfuric acid was added to lower the pH value of the mixture, which induced the retransition of hexanoate ion into hexanoic acid, generating carbon dioxide (CO₂) bubbles in situ. The formation of CO₂ bubbles further facilitated the rise of hexanoic acid and expedited the separation of the organic phase from the aqueous phase. Herein, the critical parameters that affect the enrichment factor were optimized, including the type and amount of extractant, the volume of sodium carbonate solution, ionic strength, mineral acid type, and extraction time. Under the optimized conditions, enrichment factors of target analytes were 7–57 with satisfactory accuracies and precision. The limits of detection and quantitation were 2.0–7.0 and 5.0–15 ng/mL, respectively. In the present work, we successfully applied the proposed method for the simultaneous extraction, enrichment, and determination of four cinnamic acid derivatives in traditional Chinese medicinal samples.

Simultaneous quantification of 37 constituents in Duliang Pill by UPLC-MS/MS: Application to the pharmacokinetic studies in rat plasma

Yanfang Yang, Wei Wei, Lei Zhang, Wei Xu, Xiuwei Yang

2023, 32(7): 560-573. DOI: 10.5246/jcps.2023.07.047

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Duliang Pill (DLP), consisting of Baizhi and Chuanxiong, is the classical formula of traditional Chinese medicine. In order to investigate the substance basis of DLP, we developed a highly sensitive and reliable UPLC-MS/MS method capable of simultaneously detecting 37 constituents from both Baizhi and Chuanxiong. To achieve chromatographic separation, we utilized a Diamonsil C₁₈ column along with a mobile phase consisting of acetonitrile and 0.05% formic acid in water. MS analysis was conducted in the multiple reaction monitoring mode, utilizing electrospray ionization in either the positive or negative mode, depending on the compound being analyzed. The method was validated for specificity, linearity, sensitivity, precision, accuracy, recovery, matrix effect, and stability, and found to be satisfactory. The validated method was then applied to a pharmacokinetic study in rat plasma following oral administration of DLP extract. Our findings revealed that all compounds were rapidly absorbed from the gastrointestinal tract into the plasma, with most being eliminated completely within 24 h. Notably, coumarins derived from Baizhi exhibited superior oral absorption effects compared to ligustilides from Chuanxiong. Furthermore, we observed that the elimination of coumarins from Baizhi within DLP was slower compared to their elimination in single Baizhi. These results provided valuable insights for the overall study of active substances within the DLP formula and further research into the interaction mechanisms of Baizhi-Chuanxiong compatibility.

Evaluation of the stability of droplets in emulsion using multisample analytical centrifugation

Chunyan Xie, Feng Yue, Haoquan Yu, Canzhong Huang, Shaoqun Zeng

2023, 32(7): 574-586. DOI: 10.5246/jcps.2023.07.048

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In the present study, we aimed to evaluate the stability of droplets in the emulsion during storage and distinguish the stability of different prescriptions. The multisample analytical centrifugation-LUMisizer was applied to evaluate the impact of freeze-thaw cycles on droplets, combined with droplet size parameters, zeta potential, and observation by cryo-transmission electronic microscopy. After freeze-thaw cycles, the droplets showed significant changes in characters, globule size distribution, and light transmission. After freeze-thaw cycles, the droplets were demulsified (oil droplets and creaming were observed). Formulations with different contents of propofol (10:1 and 20:1, m/v) showed significant differences in the behavior of the droplets. Droplets by accelerated destruction could be distinguished by LUMisizer, which could quickly identify the stability and effectively supplement the traditional methods, offering better quality control of droplets in the emulsion.

Combination of pembrolizumab and chemotherapy as first-line treatment in advanced triple-negative breast cancer: a cost-effectiveness analysis

Wentao Zhu, Wanglong Hong, Miaomiao Zheng, Guoqiang Ma, Aizong Shen

2023, 32(7): 587-597. DOI: 10.5246/jcps.2023.07.049

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The purpose of this study was to assess the cost-effectiveness of using pembrolizumab plus chemotherapy for advanced triple-negative breast cancer (TNBC) in the context of China’s healthcare system. To achieve this, we developed a Markov model with three health states, a time horizon of 10 years, and a cycle length of 21 days. Additionally, we conducted one-way sensitivity analyses and probabilistic sensitivity analyses to test the model’s stability. Scenario analyses were also performed to explore the cost-effectiveness of pembrolizumab plus chemotherapy based on the Patient Assistance Program (PAP). The base-case analysis demonstrated that pembrolizumab plus chemotherapy provided an additional 0.67 QALYs, with an incremental cost of \$ 77 096.78, resulting in an ICER of \$ 115 896.30/QALY. One-way sensitivity analyses revealed that pembrolizumab cost had the greatest impact on the results. In probabilistic sensitivity analyses, pembrolizumab plus chemotherapy was found to be cost-effective in 0% of cases at willingness-to-pay thresholds of \$ 33 782.23/QALY. Considering China’s healthcare system, pembrolizumab plus chemotherapy as first-line treatment for advanced TNBC was unlikely to be cost-effective when compared to placebo plus chemotherapy. Even if pembrolizumab was to be included in the PAP, it would still not be considered cost-effective, although the ICER would be much closer to three times China’s GDP per capita (\$ 33 782.23/QALY).

The team of Prof. Zhenjun Yang have made continuous progress in the delivery of antisense nucleic acid structural modifications in vivo and the treatment of liver cancer

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

2023, 32(7): 598-599.

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