Drug Target Insights

Background: Edible fruits and resins provide various benefits to mankind including potential medicinal applications. This study aimed to determine the cytotoxicity, selectivity, and clonogenicity of fruits and exudates of certain Saudi medicinal plants (Anethum graveolens (BEP-09), Opuntia ficus-indica (L.) Miller (BEP-10), Boswellia serrata Roxb. ex Colebr. (BEP-11), and Commiphora myrrha (BEP-12)) against human liver adenocarcinoma (HepG2). Methods: Initial cytotoxicity and cell line selectivity against different cell lines were screened using MTT assay. The most promising extract was subjected to gas chromatography-mass spectrometry (GC-MS) analysis to determine the main phytoconstituents. Clonogenicity was checked for the most active extract. Results: The selected plants’ fruits and resins possess a significant cytotoxic activity estimated as IC50. The fruit of BEP-10 was found to be the most active extract against liver cancer cells (IC50 = 2.82) comparable to both doxorubicin (IC50 = 1.40) and camptothecin (IC50 = 1.11). It showed a selectivity index of 4.47 compared to the normal human foetal lung fibroblast (MRC5) cells. BEP-10 showed a dose-dependent clonogenic effect against HepG2 cells comparable to the effect of doxorubicin. The GC-MS chromatogram of BEP-10 extract revealed the presence of eight small polar molecules, representing 73% of the total identified compounds and the rest three molecules (27%) were non-polar constituents. The furan derivatives represent the chief components in BEP-10 (16.3%), while the aldehyde 5-(hydroxymethyl)-2-furancarboxaldehyde was found to be the main molecule (13.2%). Conclusion: The fruits of BEP-10 have a potential cytotoxic effect particularly against HepG2. The identified phytoconstituents in the tested plant extract might contribute to the investigated cytotoxic activity.

Ali Hendi Alghamdi

Aimun A E Ahmed

Mahadi Bashir

Haidar Abdalgadir

Asaad Khalid

Mohamed E Abdallah

Riyad Almaimani

Bassem Refaat

Ashraf N Abdalla

Cytotoxic activity, selectivity, and clonogenicity of fruits and resins of Saudi medicinal plants against human liver adenocarcinoma

沙特药用植物果实和树脂对人肝腺癌的细胞毒性活性、选择性和克隆形成能力

Multidrug-resistant (MDR) extended-spectrum beta-lactamase (ESBL)-producing bacterial isolates have emerged as a global threat to human health. Little is known about the overall prevalence of multidrug resistance profile and ESBL-producing gram-negative bacilli (GNB) in Ethiopia. Therefore, this meta-analysis was performed to produce proportional estimates of multidrug resistance and ESBL-producing GNB in Ethiopia.&#x0D; A web-based search was conducted in PubMed, Google Scholar, Research Gate, Scopus and other databases. Articles published till 2019 on the prevalence and antimicrobial resistance profiles of ESBL-producing GNB in Ethiopia were included in the study. Relevant data were extracted and statistical analysis was performed using comprehensive meta-analysis version 3.3.0 software. Publication bias was analyzed and presented with funnel plots.&#x0D; In this meta-analysis, the overall proportional estimate of ESBL-producing GNB was 48.9% (95% confidence interval [CI]: 0.402, 0.577). The pooled proportional estimates of ESBL-producing Klebsiella pneumoniae, Escherichia coli and other GNB were 61.8%, 41.2% and 42.9%, respectively. Regarding antimicrobial resistance profiles against selected drugs, the pooled proportional estimates of resistance against amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, cefotaxime, ceftazidime, tetracycline, gentamicin and ciprofloxacin was 79.0%, 78.4%, 78.0%, 72.4%, 72.7%, 58.9% and 43.8%, respectively. The pooled proportional estimates of MDR isolates were found to be 82.7% (95% CI: 0.726, 0.896), which are relatively high as compared to other countries. This highlights a need for active surveillance systems which can help understand the actual epidemiology of ESBL, aid in formulating national guidelines for proper screening of ESBL and support developing standardized approaches for managing patients colonized with ESBL

Mengistu Abayneh

Teshale Worku

Prevalence of multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli: A meta-analysis report in Ethiopia

埃塞俄比亚多重耐药和产超广谱β-内酰胺酶（ESBL）革兰氏阴性杆菌的流行情况：一项Meta分析报告

Salbutamol and terbutaline are short-acting β2 adrenergic agonists that produce bronchial smooth muscle relaxation and are widely used in obstructive pulmonary diseases. Nevertheless, their use has been the cause of a paradoxical bronchoconstriction, which is a rare and potentially serious adverse reaction. The aim of this study is to report a case of paradoxical bronchoconstriction caused by β2 adrenergic agonists.This case is about a 50-year-old asthmatic patient who describes a history of repeated acute asthma attacks after salbutamol inhalation or terbutaline nebulization. A double-blind crossover study was performed over 3 days, in order to compare the effects of each bronchodilator. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal expiratory flow 25-75 (MEF25-75) were measured.On the first day, a bronchoconstriction caused by deep and repeated inhalations was eliminated. On the second day, an airway obstruction was confirmed by a decrease in FEV1 at 40% from baseline values after nebulization of a standard dose of terbutaline. On the third day, a spirometry was performed before and after nebulization of a standard dose of ipratropium bromide, and there were no significant changes in the spirometric parameters. Finally the patient was discharged with a written warning mentioning the danger of salbutamol and terbutaline use.Salbutamol and terbutaline are generally well-tolerated β2 adrenergic agonists. Nevertheless, in rare cases, these substances can cause a paradoxical bronchoconstriction. Doctors must therefore remain vigilant about its side effect and possibly investigate each case.

Khadija Ayed

Islam Latifa Hadi Khalifa

Salma Mokaddem

Saloua Ben Khamsa Jameleddine

Paradoxical bronchoconstriction caused by β2-adrenoceptor agonists

β2-肾上腺素受体激动剂引起的矛盾性支气管收缩

Genome plasticity of Streptococcus pneumoniae is responsible for the reduced efficacy of various antibiotics and capsular polysaccharide-based vaccines. Therefore, targets independent of capsular types are sought to control the pneumococcal pathogenicity. UDP-glucose pyrophosphorylase (UGPase) is one such desired candidate being responsible for the synthesis of UDP-glucose, a sugar precursor in capsular biosynthesis and metabolic Leloir pathway. Being crucial to pneumococcal pathobiology, the effect of UGPase inhibition on virulence was evaluated in vitro.A putative inhibitor, uridine diphosphate (UDP), was evaluated for effective inhibitory concentration in S. pneumoniae and A549 cells, its efficacy and toxicity. The effect of UDP on adherence and phagocytosis was measured in human respiratory epithelial (A549 and HEp-2) and macrophage (THP1 and J774.A.1) cell lines respectively.A differential effective inhibitory concentration of UDP for UGPase inhibition was observed in S. pneumoniae and A549 cells, that is, 5 and 100 µM respectively. UDP treatments lowered percent cytotoxicity in pneumococcal-infected monolayers and didn't exert adverse effects on viabilities. S. pneumoniae adherence to host cells decreased significantly with UDP treatments. UDP induced the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-8 and increased pneumococcal phagocytosis.Our study shows UDP-mediated decrease in the virulence of S. pneumoniae and demonstrates UDP as an effective inhibitor of pneumococcal UGPase.

Monica Sharma

Swati Sharma

Pallab Ray

Anuradha Chakraborti

Targeting Streptococcus pneumoniae UDP-glucose pyrophosphorylase (UGPase): in vitro validation of a putative inhibitor

靶向肺炎链球菌尿苷二磷酸葡萄糖焦磷酸化酶（UGPase）：潜在抑制剂的体外验证

Introduction: Plasma membranes are not the homogeneous bilayers of uniformly distributed lipids but the lipid complex with laterally separated lipid raft membrane domains, which provide receptor, ion channel and enzyme proteins with a platform. The aim of this article is to review the mechanistic interaction of drugs with membrane lipid rafts and address the question whether drugs induce physicochemical changes in raft-constituting and raft-surrounding membranes.&#x0D; Methods: Literature searches of PubMed/MEDLINE and Google Scholar databases from 2000 to 2020 were conducted to include articles published in English in internationally recognized journals. Collected articles were independently reviewed by title, abstract and text for relevance.&#x0D; Results: The literature search indicated that pharmacologically diverse drugs interact with raft model membranes and cellular membrane lipid rafts. They could physicochemically modify functional protein-localizing membrane lipid rafts and the membranes surrounding such domains, affecting the raft organizational integrity with the resultant exhibition of pharmacological activity. Raft-acting drugs were characterized as ones to decrease membrane fluidity, induce liquid-ordered phase or order plasma membranes, leading to lipid raft formation; and ones to increase membrane fluidity, induce liquid-disordered phase or reduce phase transition temperature, leading to lipid raft disruption.&#x0D; Conclusion: Targeting lipid raft membrane domains would open a new way for drug design and development. Since angiotensin-converting enzyme 2 receptors which are a cell-specific target of and responsible for the cellular entry of novel coronavirus are localized in lipid rafts, agents that specifically disrupt the relevant rafts may be a drug against coronavirus disease 2019.

Hironori Tsuchiya

Maki Mizogami

Interaction of drugs with lipid raft membrane domains as a possible target

药物与脂筏膜域相互作用作为可能靶点的研究

Levofloxacin, a fluoroquinolone, is an extensively used antibiotic effective against both positively and negatively staining bacteria. It works by inhibiting bacterial topoisomerase type II and topoisomerase type IV, resulting in impaired DNA synthesis and bacterial cell death. Eryptosis is another term for apoptotic cell death of erythrocyte marked by cell shrinkage, phosphatidylserine (PS) flipping, and membrane blebbing.

Hafiz Muhammad Aslam

Azka Sohail

Ammara Shahid

Maham Abdul Bari Khan

None Muhammad Umar Sharif

Razia Kausar

Samia Nawab

Waqas Farooq

Dr. Kashif Jilani

Majeeda Rasheed

Levofloxacin induces erythrocyte contraction leading to red cell death

左氧氟沙星诱导红细胞收缩导致红细胞死亡

Objective: Cancer or neoplasm is a cosmopolitan catastrophe that results in more than 20 million new cases and 10 million deaths every year. Some factors lead to carcinogenesis like infectious diseases. Parasites like Toxoplasma gondii, by its components, could modulate the cancer system by inducing apoptosis. The objective of this investigation is to assess the potential of peptides derived from T. gondii in combating cancer by examining their effects on Caco-2, Hep-G2, and HT29 cell lines. Materials and methods: Candidate peptide by its similarity to anticancer compounds was predicted through the computer-based analysis/platform. The impact of the peptide on cell viability, cell proliferation, and gene expression was evaluated through the utilization of MTT assay, flow cytometry, and real-time polymerase chain reaction (PCR) methodologies. Results: The cell viability rate exhibited a significant decrease (p &lt; 0.001) across all cell lines when exposed to a concentration of ≤160 μg. Within the 48-hour timeframe, the half maximal inhibitory concentration (IC50) for HT29 and Hep-G2 cell lines was determined to be 107.2 and 140.6 μg/mL, respectively. Notably, a marked decrease in the expression levels of Bcl2 and APAF1 genes was observed in both the Hep-G2 and HT29 cell lines. Conclusion: These findings indicate that the T. gondii peptide affected cancer cell mortality and led to changes in the expression of genes associated with apoptosis.

Firooz Shahrivar

Javid Sadraei

Majid Pirestani

Ehsan Ahmadpour

Enhancement of apoptosis in Caco-2, Hep-G2, and HT29 cancer cell lines following exposure to Toxoplasma gondii peptides

弓形虫肽暴露后Caco-2、Hep-G2和HT29癌细胞系凋亡增强

Anti-pathogenic potential of a polyherbal formulation Enteropan® was investigated against a multidrug-resistant strain of the bacterium

Sweety Parmar

Gemini Gajera

Nidhi Thakkar

Hanmanthrao S. Palep

Vijay Kothari

Deciphering the molecular mechanisms underlying anti-pathogenic potential of a polyherbal formulation Enteropan® against multidrug-resistant Pseudomonas aeruginosa

解析多药耐药铜绿假单胞菌抗性多草药配方Enteropan®的分子机制

Background: Pistacia chinensis is extensively employed in traditional medicine. This study aimed to isolate and evaluate the therapeutic effects of 3’4’78-tetrahydroxy-3-methoxyflavone from P. chinensis crude extract. Materials and Methods: The study utilized column chromatography for isolation. The plant extract and its isolated compound were assessed for in vivo analgesic (hot plate model), anti-inflammatory (carrageenan-induced paw edema), sedative (open field model), and muscle relaxing properties (inclined plane and traction test). Results: In the thermal-induced analgesic model, a significant analgesic effect was observed for the extract (25, 50, and 100 mg/kg) and the isolated compound (2.5, 5, 10, and 15 mg/kg) at higher doses. The extract (100 mg/kg) significantly prolonged latency time (21.98 seconds) after 120 minutes of administration. The isolated compound elevated the latency time (20.03 seconds) after 30 minutes, remaining significant up to 120 minutes with a latency time of 24.11 seconds. The anti-inflammatory effect showed a reduction in inflammatory reactions by 50.23% (extract) and 67.09% (compound) after the fifth hour of treatment. Both samples demonstrated significant sedative effects, with the extract hindering movement by 54.11 lines crossed compared to the negative control (180.99 lines). The isolated compound reduced the number of lines crossed to 15.23±SEM compared to the negative control. Both samples were also significant muscle relaxants. Docking studies indicated that the compound’s therapeutic effect is due to inhibiting COX and nociceptive pathways. Conclusion: The isolated compound from Pistacia chinensis exhibits significant analgesic, anti-inflammatory, sedative, and muscle relaxing properties, with potential therapeutic applications by inhibiting COX and nociceptive pathways.

Abdur Rauf

Umer Rashid

Zuneera Akram

Anees Saeed

Naveed Muhammad

Najla Al Masoud

Taghrid S. Alomar

Saima Naz

Marcello Iriti

In vivo analgesic, anti-inflammatory, sedative, muscle relaxant activities, and docking studies of 3’,4’,7,8-tetrahydroxy-3-methoxyflavone isolated from Pistacia chinensis

体内镇痛、抗炎、镇静、肌肉松弛活性及对接研究：从黄连木中分离得到的3’,4’,7,8-四羟基-3-甲氧基黄酮

Abbreviation	Drug Target Insights
Journal Impact	2.16
Quartiles(Global)	PHARMACOLOGY & PHARMACY(Q3)

ISSN	1177-3928
h-index	16

Publication Information	Publisher: AboutScience Srl，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2011，Proportion of original research papers: 81.82%，Self Citation Rate:5.00%， Gold OA Rate: 93.10%
Journal Fees	$Details
Average review cycle	8 weeks

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Cytotoxic activity, selectivity, and clonogenicity of fruits and resins of Saudi medicinal plants against human liver adenocarcinoma

Prevalence of multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli: A meta-analysis report in Ethiopia

Paradoxical bronchoconstriction caused by β2-adrenoceptor agonists

Targeting Streptococcus pneumoniae UDP-glucose pyrophosphorylase (UGPase): in vitro validation of a putative inhibitor

Interaction of drugs with lipid raft membrane domains as a possible target

Cytotoxic activity, selectivity, and clonogenicity of fruits and resins of Saudi medicinal plants against human liver adenocarcinoma

Levofloxacin induces erythrocyte contraction leading to red cell death

Enhancement of apoptosis in Caco-2, Hep-G2, and HT29 cancer cell lines following exposure to Toxoplasma gondii peptides

Deciphering the molecular mechanisms underlying anti-pathogenic potential of a polyherbal formulation Enteropan® against multidrug-resistant Pseudomonas aeruginosa

In vivo analgesic, anti-inflammatory, sedative, muscle relaxant activities, and docking studies of 3’,4’,7,8-tetrahydroxy-3-methoxyflavone isolated from Pistacia chinensis