Journal of Chinese Pharmaceutical Sciences

Possible mechanism of benvitimod in atopic dermatitis and psoriasis

Jin Hu, Jiajun Xue, Juan Shen

2022, 31(12): 901-911. DOI: 10.5246/jcps.2022.12.076

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Atopic dermatitis (AD) and psoriasis are common chronic and relapsing inflammatory skin diseases mainly mediated by T cells. Type 2 and 17 inflammations are essential in the pathogenesis of AD and psoriasis, respectively. Clinical evidence suggests that benvitimod, a natural metabolite produced by bacterial symbionts, plays a therapeutic role in the development and progression of both AD and psoriasis. Mechanistically, the two most potent interactions with benvitimod are observed in the aryl hydrocarbon receptor (AhR) and nuclear factor-erythroid 2-related factor-2 (Nrf2) pathways. However, it remains largely unknown how is the local interplay among benvitimod, AhR, and Nrf2, and how the epithelial microenvironment contributes to the complex inflammatory context that results in the treatment of AD and psoriasis. In the present study, the modulatory effects of benvitimod on treating AD and psoriasis.

Integrating bioinformatics to identify and analyze feature genes of acute myocardial infarction and potential Chinese medicine prediction

Kunpeng Yao, Daoping Zhang, Qili Liu, Huzhi Cai, Qingyang Chen, Xinyu Chen

2022, 31(12): 912-927. DOI: 10.5246/jcps.2022.12.077

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In the present study, the Gene Expression Omnibus (GEO) dataset combined with machine learning was used to study differential genes in acute myocardial infarction (AMI) and to predict potential components and herbal medicines with regulatory effects. The human genome datasets of AMI (GSE66360 and GSE61145) were downloaded from the GEO database, and GSE66360 was used as the test set. After correction by normalization Between Arrays package of R, the limma package was used to obtain differentially expressed genes (DEGs). Then, we carried out Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analysis of DEGs. The feature genes were screened by SVM and random forest tree method, and the obtained feature genes were verified by the GSE61145 dataset. The components of traditional Chinese medicine (TCM) corresponding to AMI feature genes were found by the CTD database, and the corresponding TCM components were mapped by the Coremine database. According to the Dictionary of Traditional Chinese Medicine, Chinese Materia Medica, and Chinese Pharmacopoeia, the frequency, the four qi, five flavors, and meridian tropism of the obtained TCM were summarized. Through the analysis of the GSE66360 dataset, 317 DEGs were obtained, of which 306 were up-regulated, and 11 were down-regulated. GO and KEGG enrichment analyses showed that the DEGs of AMI were mainly involved in neutrophil-mediated inflammation and immune response, abnormal lipid metabolism, lipid, and atherosclerosis-related pathways. DO enrichment analysis showed that the DEGs were closely related to atherosclerotic cardiovascular diseases and lung diseases. Six feature genes were obtained by SVM and random forest tree method, including ZFP36, GADD45A, PELI1, METRNL, MMP9, and CXCL16. Moreover, we found that the treatment of AMI Chinese medicine to sweet, bitter, and warm mostly attributed to the spleen, stomach, and liver. Besides, the components corresponding to the feature genes regulating AMI (ZFP36, GADD45A, PELI1, METRNL, MMP9, CXCL16) mainly included benzo(a)pyrene, tetrachlorodibenzodioxin, acetaminophen, and so on, and the corresponding TCMs included Camellia sinensis, Curcumaaromatica Salisb, Panax ginseng, and so on. In addition, a sweet taste, bitter taste, warm taste, and channel entry mainly belonged to the spleen, stomach, and liver meridians.

Icaritin enhances sorafenib-induced apoptosis through a mitochondria-dependent pathway

Axi Shi, Tiantian Shen, Wenbin Xia, Lili Xi, Lijun Wang, Yuhui Wei

2022, 31(12): 928-937. DOI: 10.5246/jcps.2022.12.078

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Sorafenib remains the standard systemic treatment for advanced human hepatocellular carcinoma (HCC). However, the low response rate, high recurrence, and high progression limit the therapeutic efficacy. Therefore, a combination therapy strategy was advanced to strengthen the antitumor effects of sorafenib. In the present study, we aimed to evaluate whether icaritin could enhance the inhibitory effects of sorafenib on HCC cells and clarify the underlying mechanism. The cell viability was evaluated via MTT assay, and the synergistic inhibitory effects of sorafenib and icaritin were verified by calculating the combination index (CI). Their combined effects on cell proliferation or apoptosis were investigated using colony formation assay and flow cytometry. Mitochondrial membrane potential (MMP) was detected by flow cytometric assay. The protein expressions associated with the apoptotic pathway were determined by Western blotting analysis. The data demonstrated that sorafenib and icaritin exerted synergistic inhibitory effects on cell viability (CI < 1). Icaritin enhanced the inhibitory effect of sorafenib on colony formation and sorafenib-induced apoptosis of HCC cells. We discovered a reduced level of antiapoptotic Bcl-2 and an elevated level of proapoptotic protein Bax when the cells were exposed to the combination. The effect of cleaved and activated PARP was also enhanced. Cleaved caspase-9 and cleaved caspase-3 were increased markedly in the combination group. Furthermore, the combination of icaritin and sorafenib significantly increased the loss of MMP compared with the single treatment group and induced the release of cytochrome c from the mitochondria to the cytosol. These findings indicated that icaritin could enhance sorafenib-induced cytotoxicity and trigger sorafenib-induced apoptosis through a mitochondria-dependent pathway.

Continuous-flow, one-pot synthesis of asymmetrical aromatic ureas from acids and amines via curtius rearrangement

Meng Tong, Wei Zhan, Chengcheng Niu, Zemei Ge, Runtao Li, Xin Wang

2022, 31(12): 938-945. DOI: 10.5246/jcps.2022.12.079

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In the present study, we described a continuous-flow, one-pot synthesis of asymmetrical ureas using nucleophilic addition reaction of amines to isocyanates derived from acids’ Curtius rearrangement. The advantages of this method included broad substrate scope, high yields, rapid reaction, simplicity, extraordinary safety, and easy scale-up.

The synthesis and antibacterial activity evaluation of oxazolidinone-deferasirox conjugates

Xintong Zhao, Yuhua Hu, Tong Qin, Tianlei Li, Wenxuan Zhang, Song Wu

2022, 31(12): 946-952. DOI: 10.5246/jcps.2022.12.080

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We reported herein the synthesis and antibacterial activity evaluation of two oxazolidinone-deferasirox conjugates with different linkers that were designed based on the "Trojan horse" strategy. The conjugates could combine with Fe³⁺ ions as the deferasirox. However, both conjugates were inactive against tested bacteria, including S. aureus, E. coli, A. baumannii, and P. aeruginosa. The results suggested that the synthesized iron chelator deferasirox was not suitable as a siderophore of the bacteria to transport the antibiotic, or the coupling linker of the synthesized conjugates could not be hydrolyzed to release the oxazolidinone in the cytoplasm. Therefore, the design and synthesis of oxazolidinone-deferasirox conjugates need further exploration.

Analysis of influencing factors and preventive strategies for severe infusion reactions induced by mannatide

Zhipeng Wang, Hualian Zha, Bingqin Wen, Jianen Zhu, Li Wei, Pengjiu Yu

2022, 31(12): 953-958. DOI: 10.5246/jcps.2022.12.081

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In recent years, the number of intravenous infusion reactions has been increasing with the wide application of mannatide in clinical practice. In the present study, 38 cases of mannatide-induced infusion reactions reported in a single medical center from 2017 to 2021 were retrospectively analyzed. Moreover, independent high-risk factors for severe infusion reactions were assessed by the Chi-square test. The results showed that infusion reactions caused by mannatide mainly occurred in patients over 50 years old (71.05%) and primarily occurred within 10 min of drug administration (86.84%), and patients with underlying diseases or drug allergies suffered from severe infusion reactions caused by mannatide. Therefore, the patients with advanced age, previous history of drug allergy, basic medical history, and the first use of this drug, especially within 10 min after administration, should be highly vigilant and closely monitored.

In 2022 the research group of Prof. Qiang Zhang/Prof. Bing He/Prof. Wenbing Dai/Prof. Xueqing Wang have made a series of advances in the field of nanodelivery

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

2022, 31(12): 959-962.

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In 2022 the research group of Prof. Qiang Zhang/Prof. Bing He/Prof. Wenbing Dai/Prof. Xueqing Wang have made a series of advances in the field of nanodelivery.