Journal of Chinese Pharmaceutical Sciences

Matrine, oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities

Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan

2022, 31(5): 321-333. DOI: 10.5246/jcps.2022.05.028

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In the present review, we updated current information on the chemistry, contents, and anticancer properties of matrine (MT), oxymatrine (OMT), and compound Kushen injection (CKI). The anticancer properties were focused on lung, breast, and liver cancer cells because they are most susceptible. Sources of information were from Google, Google Scholar, PubMed, PubMed Central, Science Direct, PubChem, J-Stage, Directory of Open Access Journals (DOAJ), and China National Knowledge Infrastructure (CNKI). Reference was also made on botanical websites, such as Flora of China and World Flora Online. MT and OMT are dominant quinolizidine alkaloids from the roots of Sophora flavescens (Kushen) of the family Fabaceae. Against lung, breast, and liver cancer cells, MT and OMT inhibit cell proliferation; induce cell cycle arrest, apoptosis, and autophagy; restrict angiogenesis; and inhibit cell metastasis, invasion, and migration. The processes involve various molecular targets and signaling pathways. CKI is a traditional Chinese medicine (TCM) composed of root extracts of S. flavescens and Smilax glabra (Baituling) of the family Smilacaceae. With MT and OMT as major components, CKI has been approved for the treatment of cancer in China more than 20 years ago. In recent years, systematic reviews and meta-analysis have been undertaken to evaluate the anticancer effects of CKI. When CKI is used alone and in combination with chemotherapy of western medicine, there is much to be learned concerning their interactions besides their individual and integrated efficacy. Some perspectives of MT, OMT, and CKI are discussed, and their suggestions for future research are provided.

Progression of anti-mycoplasma drug therapy in children with refractory mycoplasma pneumonia

Haiyan Wu, Xiang Zhang, Shanshan Ding, Guohua Zhang, Linlin Tang, Lin Tang

2022, 31(5): 334-342. DOI: 10.5246/jcps.2022.05.029

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The incidence of refractory mycoplasma pneumoniae pneumonia (RMPP) in children is increasing year by year, and the disease is progressing rapidly. It is accompanied by serious complications and legacy effects, seriously affecting the quality of life of children. The selection, dosage, and course of anti-MP drugs in children with RMPP have brought a lot of troubles to pediatric hospitals. In the present study, the characteristics, usage and dosage, drug resistance mechanism, and treatment progress of anti-MP drugs for the treatment of RMPP in children were reviewed. Collectively, our findings provided ideas for the treatment of children with RMPP using anti-MP drugs.

Network pharmacological analysis of Xiao-Xu-Ming decoction against ischemic stroke and verification of its mechanism of anti-inflammation and neurovascular protection in vivo

Yinglin Yang, Shanshan Zhang, Man Liu, Dongni Liu, Yuehua Wang, Guanhua Du

2022, 31(5): 343-359. DOI: 10.5246/jcps.2022.05.030

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Stroke is a major cause of severe disability and death. Xiao-Xu-Ming decoction (XXMD) is an effective prescription for stroke and its sequelae, while its effective ingredients and mechanism are still unclear. In the present study, we aimed to explore the effective ingredients and mechanism of XXMD in treating cerebral ischemia using network pharmacology. The main chemical components and targets of 12 herbs of?XXMD were obtained by the TCMSP database and analysis platform database. The active components in XXMD were screened according to oral utilization and drug-like properties. Then, the cerebral ischemia targets were obtained through GeneCards, OMIM, TTD, Diligent and Drugbank databases. We analyzed the pathophysiological processes and pathways involved in the treatment of cerebral ischemia with XXMD by using the Metascape data analysis platform. Results showed that β-sitosterol, kaempferol, quercetin, stigmasterol, wogonin, and catechins might be the potential core active ingredients of XXMD in the treatment of cerebral ischemia. The therapeutic effect of XXMD on stroke was mainly exerted through regulating neuroinflammatory response and neurovascular protection. Furthermore, the anti-neuroinflammation and neurovascular protection of XXMD were further confirmed using?cerebral ischemia rats. Collectively, our findings revealed that the mechanism of XXMD on the treatment of cerebral ischemia was related to anti-neuroinflammation and neurovascular protection.

Fluvastatin protects against puromycin aminonucleoside-induced podocyte injury by inhibiting TRPC6

Hui Gao, Yunjing Zhang, Jing Lin, Xifeng Sun

2022, 31(5): 360-368. DOI: 10.5246/jcps.2022.05.031

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In the present study, we aimed to investigate the effect of puromycin aminonucleoside (PAN) on the expression and distribution of transient receptor potential canonical 6 (TRPC6) of murine podocytes and further study the protective mechanism of fluvastatin on podocyte injury by TRPC6 in vitro. Podocytes were treated by PAN at different doses and at different time points. The expressions of TRPC6 at mRNA and protein levels were assessed. An immunofluorescent assay was used to observe the distribution of TRPC6. Cultured podocytes were then divided into four groups. The expressions of TRPC6 at mRNA and protein levels were measured. The intracellular calcium concentration of podocytes was measured with a laser-scanning confocal microscope. The paracellular permeability to BSA was evaluated using Millicell-PCF Inserts. The expressions of TRPC6 at mRNA and protein levels were increased in a dose and time-dependent manner after exposure to PAN. Immunofluorescence showed that the expression intensity of TRPC6 was significantly increased, and the distribution of TRPC6 was changed after PAN was applied to podocytes. With fluvastatin intervention, PAN-induced up-regulation of TRPC6 was significantly reversed. The ratio of the peak value of intracellular calcium to the basic calcium value in the PAN group was significantly higher after TRPC6 was activated by OAG, while it is obviously reversed under the action of fluvastatin. The podocyte permeability was significantly increased after 48 h of PAN treatment, while the above situation was effectively improved after fluvastatin intervention. The changes of distribution and expression of TRPC6 were related to podocyte injury induced by PAN. Fluvastatin could exert its protective effects on podocytes by down-regulating TRPC6.

Analysis of alternation with ibuprofen and acetaminophen in outpatient and emergency departments of a children’s hospital

Yingyan Yan, Peizhi Mao, Yi Chen, Longhui Shen

2022, 31(5): 369-373. DOI: 10.5246/jcps.2022.05.032

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In the present study, we retrospectively analyzed 105 382 prescriptions of antipyretic drugs for children (0–14 years of age) in the outpatient and emergency departments of Ningbo Women and Children’s Hospital from January to December 2019. Ibuprofen and acetaminophen are relatively safe and the most commonly used drugs in daily life. Due to different dosage forms, there are acetaminophen suspension drops, acetaminophen oral solution, ibuprofen suspension, and ibuprofen suppositories for children. Through investigation, we found that the age of antipyretic drugs used by children in our hospital ranged from 3 months to 14 years old, which could be divided into two groups: single drug use and alternating use of ibuprofen and acetaminophen, with an alternating use rate of 3.19%. There were differences between the two groups in terms of age, gender, the proportion of emergency departments use, and the amount of single prescription (P < 0.05). The age of the alternating use group was younger, and the male proportion, the proportion of emergency departments use, single prescription amount of the alternating use group were higher. In the alternating use group, ibuprofen and acetaminophen of different dosage forms were used alternatively. After pair comparison analysis, they only had an age difference (P < 0.008), which was in line with the principle that different dosage forms are suitable for different ages. The method of alternation with ibuprofen and acetaminophen is mainly used in the emergency departments and children of younger age because most of the children have a refractory fever, which is complicated and changes relatively fast. There was no record of adverse reactions about alternation of ibuprofen and acetaminophen in the software system of adverse reactions. However, this study was a retrospective analysis, and there were risks of missing records. Therefore, alternating use of ibuprofen and acetaminophen still couldn’t ignore the risk of adverse reactions.

Sonogashira coupling reaction in the synthesis of novel positive allosteric modulators of α7 nicotinic acetylcholine receptors

Wenjun Xie, Haoran Xiao, Xintong Wang, Zongze Huang, Xiling Bian, Kewei Wang, Qi Sun

2022, 31(5): 374-381. DOI: 10.5246/jcps.2022.05.033

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A series of 2-arylamino-1,3,5-triazine derivatives (4a–4g), which were designed and synthesized via Sonogashira coupling reaction, were evaluated using two-electrode voltage clamp (TEVC) recordings of human α7 nAChR expressed in Xenopus ooctyes. Compound 4g as a positive allosteric modulator (PAM) showed better efficacy than lead compound 3 (HZZ-A-11) with an EC₅₀ value of 1.23 ± 0.41 μM. Further pharmacological evaluation of compound 4g might lead to the developmental potential for therapy of cognitive deficits commonly shared by neuropsychiatric disorders, such as schizophrenia and Alzheimer’s disease.

Evaluation of ceftriaxone dosing regimens based on PK/PD models and Monte Carlo simulations

Ye Yuan, Yanan Li, Qing Zhao, Bo Yu, Xiuling Yang

2022, 31(5): 382-388. DOI: 10.5246/jcps.2022.05.034

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In the present study, we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic (PK/PD) principles using Monte Carlo simulation (MCS). Based on PK/PD theory, MCS was performed using Crystal Ball software combining PK and PD parameters with 10 000 simulation runs to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) for the seven clinically common dosing regimens of ceftriaxone (1 g qd, 1.5 g qd, 1 g bid, 2 g qd, 1 g tid, 1.5 g bid, and 2 g bid). A %fT ≥ 50 as the target value expected to achieve satisfactory clinical efficacy and a dosing regimen with an obtained CFR ≥ 90% or the ability to achieve the highest PTA was used as a reasonable choice for empirical antimicrobial therapy, i.e. the clinically optimal regimen. All eight pathogenic bacteria had a CFR > 90% when the dosing regimen was 2 g bid and 1 g tid, seven pathogenic bacteria had a CFR > 90% when the dosing regimen was 1 g bid and 1.5 g bid, except for Pseudomonas aeruginosa, and all pathogenic bacteria had a CFR< 90% when the dosing regimen was 1 g qd and 1.5 g qd. The dosing regimens of 2 g bid and 1 g tid were effective against all eight pathogenic bacteria infections, and 1 g bid and 1.5 g bid dosing regimens were effective against the other seven pathogenic bacteria except for Pseudomonas aeruginosa.