Genus Ilex L.: Phytochemistry, Ethnopharmacology, and Pharmacology

The genus Ilex L. has been used as remedies in traditional Chinese medicine in Aquifoliaceae and beverages for thousands of years due to abundant pharmaceutical bioactivities. There are 600 species in genus Ilex L. containing various compounds such as terpenoids, saponins, glycosides, etc. Three species, I. cornuta, I. chinensis, and I. rotunda have been admitted in Chinese Pharmacopoeia 2015 to treat dyspepsia, stomatitis, and hyperactivity cough and protect the liver and kidney. Recent studies showed that several species have been daily drunk to promote human health and prevent cardiovascular diseases in the folk. Here we reviewed the genus Ilex L. in phytochemistry, ethnopharmacology, and pharmacology.     

Chemistry and pharmacology of the Citrus bioflavonoid hesperidin.

Hesperidin, a bioflavonoid, is an abundant and inexpensive by-product of Citrus cultivation. A deficiency of this substance in the diet has been linked with abnormal capillary leakiness as well as pain in the extremities causing aches, weakness and night leg cramps. No signs of toxicity have been observed with the normal intake of hesperidin or related compounds. Both hesperidin and its aglycone hesperetin have been reported to possess a wide range of pharmacological properties. This paper reviews various aspects of hesperidin and its related compounds, including their occurrence, physical and chemical properties, analysis, pharmacokinetics, safety and toxicity and the marketed products available. A special emphasis has been laid on the pharmacological properties and medicinal uses of these compounds.     

低剂量纳洛酮对芬太尼镇痛效应的影响

目的 观察低剂量纳洛酮(naloxone)对芬太尼(fentanvyl)镇痛效应的影响.方法 将试验小鼠80只随机分为两组,分别采用扭体法(40只,雌雄各半)和热板法(40只,均为雌性)观察纳洛酮对芬太尼镇痛小鼠热板法痛阈(HPPT)和扭体次数的影响.各组按分层随机设计分为Fs组(芬太尼与生理盐水合用)及FNl、FN2和FN3组(芬太尼分别与纳洛酮100、10、10ng,1n/kg合用组)四组.结果 与Fs组相比,FN2组HPPT在第5 min增大(P＜0.05);扭体次数FN1和FN2组均显著减少(P＜0.05).结论 纳洛酮在一定剂量范围内能够增强芬太尼的镇痛效应.     

非核苷类逆转录酶抑制剂奈韦拉平

艾滋病是严重威胁人类健康的传染性疾病，它是由HIV引发，特别是HIV-1。奈韦拉平是一种新型的非核苷类逆转录酶抑制剂，该药与核苷类逆转录酶抑制剂或蛋白酶抑制剂合用可用于治疗艾滋病，单独用药可用于预防HIV感染和母婴传播。     

The changing epidemiology of opioid overdose in Baltimore,Maryland, 2012–2017: insights from emergency medical services

IntroductionAn estimated 100,306 people died from an overdose from May 2020 to April 2021. Emergency Medical Services (EMS) are often the first responder to opioid overdose, and EMS encounter records can provide granular epidemiologic data on opioid overdose. This study describes the demographic, temporal, and geographic epidemiology of suspected opioid overdose in Baltimore City using data from Baltimore City Fire Department EMS encounters with the administration of the opioid antagonist naloxone.MethodThe present analyses used patient encounter data from 2012 to 2017 from the Baltimore City Fire Department, the city’s primary provider of EMS services. The analytic sample included patient encounters within the city that involved naloxone administration to patients 15 years of age or older (n = 20,592). Negative binomial regression was used to calculate the incidence rates based on demographic characteristics, year, and census tract. Choropleth maps were used to show the geographic distribution of overdose incidence across census tracts in 2013, 2015, and 2017.ResultsFrom 2012 to 2017, the annual number of EMS encounters with naloxone administrations approximately doubled every 2 years, and the temporal pattern of naloxone administration was similar to the pattern of fatal opioid-related overdoses. For most census tracts, incidence rates significantly increased over time. Population-based incidence of naloxone administration varied significantly by socio-demographic characteristics. Males, non-whites, and those 25–69 years of age had the highest incidence rates.ConclusionThe incidence of naloxone administration increased dramatically over the study period. Despite significant cross-sectional variation in incidence across demographically and geographically defined groups, there were significant proportional increases in incidence rates, consistent with fatal overdose rates over the period. This study demonstrated the value of EMS data for understanding the local epidemiology of opioid-related overdose.

Key Messages

• Patterns of EMS encounters with naloxone administration appear to be an excellent proxy for patterns of opioid-related overdoses based on the consistency of fatal overdose rates over time.
• EMS plays a central role in preventing fatal opioid-related overdoses through the administration of naloxone, provision of other emergency services, and transportation to medical facilities.
• EMS encounters with naloxone administration could also be used to evaluate the impact of overdose prevention interventions and public health services.

     

Anti-tumor pharmacology of natural products targeting mitosis

Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation of cancer cells is one of cancer’s main characteristics, which is closely associated with abnormal mitosis. Targeting mitosis is an effective method for cancer treatment. This review summarizes several natural products with anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, the main disadvantages of several typical compounds, including drug resistance, toxicity to non-tumor tissues, and poor aqueous solubility and pharmacokinetic properties, are also discussed, together with strategies to address them. Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.     

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.     

Network pharmacology-based pharmacological mechanism prediction on Eucommia ulmoides against rheumatoid arthritis

Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Eucommia ulmoides (EU) is a kidney-tonifying Chinese medicine that has been applied to treat RA for decides. The present study aims to explore pharmacological mechanisms of EU against RA using network pharmacology approach. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of EU, and their relative targets were fished from UniProt database. RA-related targets were screened from GeneCards database and DisGeNET database. The overlapping genes between EU and RA were identified by Venn diagram, and further analyzed for protein-protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). Fifty active ingredients were identified in EU, and corresponded to 207 targets. Meanwhile, 499 targets were closely associated with RA development. A total of 50 overlapping genes between EU and RA were identified, which were regarded as therapeutically relevant. GO enrichment analysis indicated that EU exerted antiRA effects depending on regulating multiple biological processes including inflammatory response, oxidative stress, cell apoptosis and matrix catabolism. Several key pathways such as TNF pathway, IL-17 pathway, T cell receptor pathway, NOD-like receptor pathway and Toll-like receptor pathway, were involved in the above biological processes. Network pharmacology revealed that EU exerts therapeutic effects on RA through multi-ingredients, multi-targets and multi-pathways, which provides basis for its clinical application and promising directions for subsequent research.     

肠易激综合征的药物治疗

肠易激综合征(IBS)是常见功能性肠病，其药物治疗效果未尽人意，控制症状是治疗的目标。对腹痛症状，解痛药有一定疗效，三环类抗抑郁药对症状顽固者有帮助，但需注意副作用，选择性5-羟色胺重摄取抑制剂(SSRI)副反应少，但作用未完全确定。对腹泻症状，阿片类似药洛哌丁胺有效，胆盐结合剂可对某些病例奏效，5羟色胺3(5-HT3)拮抗剂阿洛斯琼疗效好，但担心副作用，应限用于严重病例。对便秘症状，膳食纤维和膨胀剂可能有效，泻药在治疗中的地位未确定，但患者常服用。5-HT4部分类似剂替加色罗是有效和安全的新药。益生菌和抗生素作用未确定，可对某些病例有效。研制中的新药包括降低内脏感知性止痛药和多种激素的类似剂和拮抗剂，为提高疗效提供了新的希望。     

Functional antagonism by calcium of an intrinsic opioid mechanism in the guinea-pig isolated ileum

In the guinea-pig isolated ileum, elevation of the extracellular concentration of calcium attenuated the excitatory influence of the opiate antagonist, naloxone, upon peristalsis. Application of 4-aminopyridine, which enhances calcium influx into cells, had a still more pronounced effect. Further, 4-aminopyridine impaired the inhibitory action of both morphine and the presynaptic α-adrenergic agonist, clonidine, upon peristalsis.The present data are consistent with the view that the intestinal mechanism subjected to naloxone blockade may function similarly to that proposed to explain the action of narcotics or of presynaptic α-adrenergic agonists upon other preparations. This mode of action may involve a reduction in the quantity of intracellular free ionized calcium available to the stimulus-release-coupling mechanism.