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Journal of Pharmacy and Pharmacology
Pharmaceutical Society of Great Britain
Journal of Pharmacy and Pharmacology

Pharmaceutical Society of Great Britain

0022-3573

Journal of Pharmacy and Pharmacology/Journal Journal of Pharmacy and PharmacologySCIICCCRAHCI
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    Curcumae Radix: a review of its botany, traditional uses, phytochemistry, pharmacology and toxicology

    Ao, MingyueLi, XingLiao, YujiaoZhang, Chunling...
    14页
    查看更多>>摘要：Objectives Curcumae Radix, the medicinal part is radix, commonly called as Yujin (Chinese:郁(sic)), is a widely used traditional Chinese medicine for its high medicinal value and health benefits. Curcumae Radix has been used to treat conditions such as syndrome of heat disease and unconsciousness, epilepsy and internal stagnation of phlegm, qi stagnation and blood stasis, dysmenorrhoea, jaundice, cholelithiasis caused by dampness heat of liver and gallbladder. This review aims to summarize the botany, traditional usages, processing, phytochemistry, quality control, pharmacology and toxicology of Curcumae Radix to better understand its therapeutic potential. Key findings So far, a variety of chemical constituents have been isolated and identified from Curcumae Radix, mainly including volatile oil and diphenylheptanes. Modern research shows that the extracts and compounds from Curcumae Radix possess wide-ranging pharmacological effects, including anti-tumour, hepatoprotective, anti-inflammatory and analgesic, anti-thrombosis, as well as effects on the nervous system and others. Curcumae Radix holds an important position in traditional system of medicine. It is cost-effective and an important plant with curative application in contemporary medicine. However, further in-depth studies are also needed to determine the medical uses of this plant and its chemical constituents, pharmacological activity, quality control and toxicology.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Rhamnetin: a review of its pharmacology and toxicity

    Medeiros, Debora LimaLima, Edson Thiago GomesSilva, Jefferson CamposMedeiros, Monica Alves...
    7页
    查看更多>>摘要：Objectives Numerous natural products, including rhamnetin, have been studied in recent years owing to the need for new herbal remedies to treat different illnesses. This study aimed to review the salient properties of rhamnetin and its pharmacological potential and possible toxicological effects. Key findings A search carried out in the ScienceDirect database using the term 'rhamnetin' yielded 573 articles published between 1977 and 2021. However, only those studies that mentioned pharmacological activity of rhamnetin were included in this study. As a result of this selection process, this study included reports that describe rhamnetin as a secondary metabolite with several pharmacological properties. Rhamnetin (2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxychromen-4-one) is a secondary metabolite, belonging to the flavonoid class, present in various plants and fruits; it has different pharmacological properties, including antioxidant, anticancer, anti-inflammatory, antiviral and antibacterial activity. However, conclusive results on the toxicology of rhamnetin have not been reported yet. Therefore, further research is needed to gather detailed information about the effects of rhamnetin.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Emerging avenues for the management of cerebral malaria

    Das, NiveditaPrabhu, Priyanka
    12页
    查看更多>>摘要：Objectives Cerebral malaria (CM) is a lethal complication of Plasmodium falciparum infection. The multifactorial pathogenesis of the disease involving parasitic invasion of erythrocytes and sequestration of infected erythrocytes within the cerebral blood vessels leading to neuroinflammation and blood-brain barrier (BBB) disruption demands a multi-pronged treatment strategy. This article gives a brief overview of the pathogenesis of CM, challenges associated with its treatment and potential strategies to combat the same. Key findings There are several roadblocks in the successful treatment of CM. Resistance to artemisinin-based therapies has been reported in malaria-endemic regions. The paucity of targeted delivery to the brain necessitates the administration of antimalarials such as quinine in large doses causing toxic effects. There is a need for compounds to prevent oxidative stress, neuroinflammation and BBB disruption to decrease the menace of neurological sequelae associated with CM. Extensive research endeavours are now oriented towards investigating compounds that can act against neuroinflammation; developing brain-targeted nanocarriers to selectively deliver therapeutics against CM; and repurposing existing drugs and a combination of antimalarial and anti-inflammatory or immunomodulatory molecules for the treatment of CM. Protocols for evaluating novel proposed therapies against CM should be revisited to integrate monitoring of neurological parameters in parallel with the estimation of parasite load and survival.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Genus Barleria L. (Acanthaceae): a review of its taxonomy, cytogenetics, phytochemistry and pharmacological potential

    Lekhak, Manoj M.Patil, Suraj S.Deshmukh, Pradip, VLekhak, Utkarsha M....
    31页
    查看更多>>摘要：Objectives Barleria, a large genus of the Acanthaceae family, comprises more than 300 species with diverse taxonomy, cytogenetics, phytochemistry and pharmacological potential. Therefore, the aim of this review is to critically assess the research on Barleria and provide guidance for future investigations. Methods The data were obtained from different sources, such as books, theses, journals and some of the websites and internet-based searches, published from 1901 to 2020. Data obtained from PubMed, Google Scholar, ScienceDirect, online electronic journals, SpringerLink, Wiley, etc. have also been used. Key findings The species of this genus exhibit considerable medicinal properties. Cytogenetical data are scantily available with chromosome counts available for only 24 species. The most common chromosome number is 2n = 2x = 40. So far, 187 compounds are reported from Barleria species. The active principles, their uses, toxicity and pharmacological effects are discussed. Essential oils, flavones, flavonoids, glycosides, terpenes and terpenoids form the major compounds. It is highly recommended that the pharmacological and economic potential of Barleria species should be exploited and more detailed studies and attention be geared towards its utilization and conservation. In addition, to ensure maximum pharmacological benefits and sustainable use, it is necessary to have empirical information explaining its ethnobotanical values as well as commercial potential.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Research progress on the pharmacy of tetramethylpyrazine and its pharmacological activity in cardiovascular and cerebrovascular diseases

    Zhang, YafangHe, LinfengMa, ChengWang, Cheng...
    18页
    查看更多>>摘要：Objectives The role and mechanism of tetramethylpyrazine (TMP) in cardio-cerebrovascular diseases (CCVDs), as well as the research of its new formulations are reviewed, which provides a new strategy for the clinical application of TMP. Methods We searched the databases including PubMed, Web of Science, Google Scholar and CNKI for relevant literature from 1991 to 2021 by searching for the keywords "TMP", "ligustrazine", "cardiovascular disease" and "nanoformulation". The inclusion criteria are as follows: (1) the literature is an experimental article, (2) the article studies cardiovascular and cerebrovascular-related diseases and (3) the article also includes the pharmacy research of TMP. A total of 160 articles were screened. Key findings TMP has various pharmacological effects in the treatment of many CCVDs, such as atherosclerosis, myocardium, cerebral ischemia, reperfusion injury and hypertension. Its protective effects are mainly related to its anti-platelet activity, protection of endothelial cells, and anti-inflammation, anti-oxidant and anti-apoptotic effects. In addition to pharmacological activity studies, the information of the new formulations is also significant for the further development and utilization of TMP. Conclusions Above all, TMP can protect cardio-cerebro vessels, and preparing new formulations can improve its bioavailability, indicating that TMP has broad prospects in the treatment of CCVDs.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Circ_UTRN ameliorates caerulein-induced acute pancreatitis in vitro via reducing inflammation and promoting apoptosis through miR-320-3p/PTK2 axis

    Sun, QiangLiang, RanLi, MingdongZhou, Hua...
    8页
    查看更多>>摘要：Objectives Circular RNAs (circRNAs) have been demonstrated to play important roles in acute pancreatitis (AP). Herein, this study aimed to investigate the role and mechanism of circRNAs utrophin (circ_UTRN) in AP. Methods In vitro cultured rat pancreatic acinar cell line AR42J was exposed to caerulein (10 nmol/L) to mimic an AP cell model. The levels of circ_UTRN and microRNA (miR)-320-3p and protein tyrosine kinase 2 (PTK2) were examined using quantitative real-time polymerase chain reaction and Western blot assays. Cell apoptosis was analysed by flow cytometry and Western blot assays. ELISA was employed to detect the levels of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6. The binding interaction between miR-320-3p and circ_UTRN or PTK2 was verified using dual-luciferase reporter assay. Key findings The expression of circ_UTRN was decreased by caerulein in pancreatic acinar cells, ectopic overexpression of circ_UTRN reduced inflammation and promoted apoptosis in caerulein-mediated pancreatic acinar cells. In a mechanical study, circ_UTRN served as a sponge of miR-320-3p, and miR-320-3p directly targeted PTK2. Rescue assay suggested that the promotion of apoptosis and inhibition of inflammation induced by circ_UTRN re-expression in caerulein-mediated pancreatic acinar cells were partially abolished by miR-320-3p overexpression or PTK2 knockdown. Besides that, miR-320-3p inhibition impaired caerulein-induced cell apoptosis arrest and inflammation via targeting PTK2. Conclusions Up-regulation of circ_UTRN in pancreatic acinar cells attenuates caerulein-evoked cell apoptosis arrest and inflammation enhancement via miR-320-3p/PTK2, suggesting that circ_UTRN/miR-320-3p/PTK2 axis might be engaged in caerulein-induced AP.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Prediction of the potential mechanism of compound gingerol against liver cancer based on network pharmacology and experimental verification

    Su, MinWang, XueqinCao, GangSun, Li...
    18页
    查看更多>>摘要：Objectives To explore gingerol's potential mechanism for treating liver cancer using network pharmacology and molecular docking technology and to conduct in-vitro experiments of human liver cancer cell HepG2 to verify important signalling pathways. Methods We obtained potential targets of gingerol derivatives (6-gingerol, 8-gingerol and 10-gingerol) from PubChem and SwissTargetPrediction websites and collected related targets for liver cancer with the help of GeneCards. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on key targets using the DAVID data platform and combined with Cytoscape 3.7.1 software to construct a component-target-signal pathway interaction map to study its mechanism of action. Subsequently, the components and key proteins were molecularly docked through Autodock Vina software. Finally, the important signal pathways were verified by HepG2 cell in-vitro experiments. Key findings A total of 318 drug targets were screened for gingerol derivatives, and 2509 gene targets related to liver cancer were collected. The Venn diagram showed that there were 104 intersection targets between gingerol derivatives and liver cancer. Module analysis results show that these intersection targets can be divided into 5 modules and 49 nodes. Bioinformatics analysis found that GO obtained 20 important functional items including cancer cell proliferation, protein kinase activity, phosphotransferase activity and kinase activity; KEGG enrichment analysis yielded a total of 20 key signal pathways including the PI3K-Akt signalling pathway. The results of molecular docking show that the binding energy of gingerol derivatives has good binding activity with PI3K and Akt. In-vitro experimental results show that gingerol derivatives and compound gingerol (compound gingerol is composed of 6-gingerol, 8-gingerol and 10-gingerol in a ratio of 7:1.5:1.5) can produce HepG2 cell proliferation inhibition, and each administration group can significantly increase the apoptosis rate of HepG2 cells and the fluorescence intensity of the nucleus and block the cell cycle in the S phase; the results of Western Blot and real-time quantitative PCR show that gingerol derivatives and compound gingerol can down-regulate the expression of Akt and p-Akt and up-regulate the expression of Bax/Bcl-2. And the effect of compound gingerol is more obvious than that of gingerol derivatives. Conclusions The results of network pharmacology and experimental validation suggest that gingerol derivatives and compound gingerol can act against liver cancer by acting on the PI3K-Akt signalling pathway.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Synthesis of 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines and their antiplatelet and vasodilatory activity

    Sirakanyan, Samvel N.Hrubsa, MarcelSpinelli, DomenicoDias, Patricia...
    9页
    查看更多>>摘要：Objectives Both pyridine and pyrano derivatives have been previously shown to possess biologically relevant activity. In this study, we report the incorporation of these two scaffolds into one molecule. Methods The designed 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines were synthesized by the acylation of enamine under Stork conditions followed by condensation of formed beta-diketones with 2-cyanoacetamide. The structures of these compounds were confirmed by using a wide spectrum of physico-chemical methods. Their antiplatelet, anticoagulant and vasodilatory activity together with toxicity were evaluated. Key findings A series of 6-oxopyrano[3,4-c]pyridines 3a-j was obtained. Four of these compounds were reported for the first time. None of the tested compounds demonstrated anticoagulant effect but 8-methyl derivative (3a) was a potent antiplatelet compound with IC50 numerically twice as low as the clinically used acetylsalicylic acid. A series of further mechanistic tests showed that 3a interferes with calcium signaling. The compound is also not toxic and in addition possesses vasodilatory activity as well. Conclusions Compound 3a is a promising inhibitor of platelet aggregation, whose mechanism of action should be studied in detail.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Improved efficacy of meglumine antimoniate incorporated in anionic liposomes against Leishmania infantum infecting canine macrophages

    Ortega, VanessaRadaic, Allande Jesus, Marcelo Bispode Paula, Eneida...
    9页
    查看更多>>摘要：Objectives Leishmaniasis is a zoonotic disease and several drugs have been used in the treatment, including meglumine antimoniate (AME). The chemotherapy reaches clinical cure but does not eliminate parasites, contributing to drug resistance. To improve AME efficacy we incorporated it in anionic liposomes. The antiparasitic activity and intracellular localization were investigated in canine macrophages infected with Leishmania infantum. Methods Liposomes (L-AME) is composed of egg phosphatidylcholine, cholesterol, palmitoyl oleoyl phosphatidyl serine and alpha-tocopherol (4 : 3 : 0.4 : 0.07 mol%) plus AME. L-AME size, polydispersity, zeta potential and morphology were analysed as well as antileishmanial activity and intracellular localization in DH82 macrophages. Key findings Liposomes (360 nm) zeta potential range from -40 to -65 mV, had 23% encapsulation efficiency and were stable for 180 days at 4 degrees C. Free AME was cytotoxic towards L. infantum infected macrophages (ID50 = 0.012 M) while L-AME did not reduce cell viability. L-AME colocalized with parasites inside macrophages in a time-dependent manner, and reduced the percentage of infected cells and the number of intracellular parasites, decreasing the infection index (75-80%) twice as compared with AME treatment. Conclusions Liposomal AME is a promising delivery system for treating visceral leishmaniasis, improving meglumine efficacy against L. infantum and minimizing its cytotoxicity towards canine macrophages
      原文链接:
    • NSTL
    • Oxford Univ Press

    Efficacy and safety of daily treatments for drug-susceptible pulmonary tuberculosis: a systematic review and network meta-analysis

    Imazu, PriscilaSantos, Josiane M.Beraldi-Magalhaes, FranciscoFernandez-Llimos, Fernando...
    13页
    查看更多>>摘要：Objectives To evaluate and update the evidence on the comparative efficacy and safety of antimicrobial drugs regimens for treating pulmonary drug-susceptible tuberculosis (DS-TB). Methods A systematic review was performed with searches in PubMed and Scopus (PROSPERO-CRD42019141463). We included randomised controlled trials comparing the effect of any antimicrobial regimen lasting at least 2 weeks. The outcomes of interest were culture conversion and incidence of adverse events. Bayesian network meta-analyses and surface under the cumulative ranking curve (SUCRA) analyses were performed. Results were reported as odds ratio with 95% credibility intervals. Key findings Fifteen studies were included the meta-analysis (n = 7560 patients). No regimen was statistically more effective than the WHO standard approach (rifampicin, isoniazid, ethambutol, and pyrazinamide). The use of rifapentine 450 mg instead of rifampicin in the standard regimen demonstrated to be statistically safer than all other options for serious adverse events (e.g. hepatotoxicity, arthralgia) (OR ranging from 0.0 [Crl 0.00-0.04] to 0.0 [0.00-0.97]; SUCRA probabilities of 10%). Therapies containing rifapentine (Rp1500HEZ, Rp900HEZ) and moxifloxacin (RMEZ, RHMZ) are effective regarding culture conversion, but statistical uncertainty on their safety profile exists. Conclusion The WHO standard regimen remains an overall effective and safe alternative for DS-TB. For intensive phase treatments, drugs combinations with rifapentine and moxifloxacin seem to reduce treatment duration while maintaining efficacy.
      原文链接:
    • NSTL
    • Oxford Univ Press