Current Drug Research Reviews最新文献

Neurodegeneration is an elucidating feature of many neuronal disorders including Alz- heimer's, disease, Parkinson's disease, and cerebral ischemia. These neurodegenerative disorders are a major public health concern with high mortality and morbidity rates around the world. Pres- ently, researchers have concentrated their efforts on determining the neuroprotective activity of natural products for the management of neurological manifestation associated with neurodegener- ation or aging. Silibinin, an active component of the plant Silybum marianum (family: Asteraceae) was used for the treatment of liver diseases from ancient times. Recently several preclinical stud- ies provide supportive evidence for the neuroprotective activity of silibinin in experimental ani- mals. Besides its antioxidant effect, silibinin exhibits neuroprotective activities by altering several cellular and molecular signaling pathways like BDNF, ER/PI3/Akt, NfκB, JNK, IR & IGF-IR, mTOR, and many more against brain-related neurotoxicity. This review provided a comprehen- sive summary of the chemistry, pharmacokinetics, side effects, and pharmacological effects of silibinin against various neurodegenerative disorders with a prominent cellular and molecular mechanism. The literature reviews and preclinical studies demonstrated that silibinin could be an alternate candidate for the management of neurodegenerative disorders. Thus, there is a scope for further preclinical and clinical research to introduce this phytoconstituent as a therapeutic alterna- tive candidate.

Odevixibat is synthesized through chemical modification of Benzothiazepine's structure. It is a tiny chemical that inhibits the ileal bile acid transporter and is used to treat a variety of cholestatic illnesses, including progressive familial intrahepatic cholestasis (PFIC). For cholestatic pruritus and liver disease development, bile acid transporter inhibition is a unique treatment strategy. Odevixibat reduces enteric bile acid reuptake. Oral odevixibat was also studied in children with cholestatic liver disease. Odevixibat received its first approval in the European Union (EU) in July 2021 for the treatment of PFIC in patients aged 6 months, followed by approval in the USA in August 2021 for the treatment of pruritus in PFIC patients aged 3 months. Bile acids in the distal ileum can be reabsorbed by the ileal sodium/bile acid cotransporter, a transport glycoprotein. Odevixibat is a sodium/bile acid co-transporter reversible inhibitor. An average 3 mg once-daily dose of odevixibat for a week resulted in a 56% reduction in the area under the curve of bile acid. A daily dose of 1.5 mg resulted in a 43% decrease in the area under the curve for bile acid. Odevixibat is also being evaluated in many countries for the treatment of other cholestatic illnesses, including Alagille syndrome and biliary atresia. This article reviews the updated information on odevixibat with respect to its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism, drug-drug interactions, pre-clinical studies, and clinical trials.

Background: Plant antiviral peptides (AVP) are macromolecules that can inhibit the pathogenesis of viruses by affecting their pathogenic mechanism, but most of these peptides can bind to cell membranes, inhibit viral receptors, and prevent viruses. Recently, due to the coronavirus pandemic, the availability of appropriate drugs with low side effects is needed. In this article, the importance of plant peptides in viral inhibition, especially viral inhibition of the coronavirus family, will be discussed.

Methods: By searching the databases of PubMed, Scopus, Web of Science, the latest articles on plant peptides effective on the COVID-19 virus were collected and reviewed.

Results: Some proteins can act against the COVID-19 virus by blocking sensitive receptors in COVID-19, such as angiotensin-converting enzyme 2 (ACE2). The 23bp sequence of the ACE2 alpha receptor chain can be considered as a target for therapeutic peptides. Protease and RNAP inhibitors and other important receptors that are active against COVID-19 should also be considered.

Conclusion: Herbal medicines with AVP, especially those with a long history of antiviral effects, might be a good choice in complement therapy against the COVID-19 virus.

Engulfing almost 537 million people, the most commonly occurring metabolic disorder, diabetes mellitus, is emerging as an epidemic worldwide. Diabetes mellitus is identified as a heterogeneous pathological condition that is marked by extreme hyperglycemic (glucose) levels caused by reduced insulin sensitivity. Synthetic antidiabetic medications are widely commercialized but have slowly expressed several inevitable side effects and limitations in treated diabetic subjects. Researchers have been exploring herbal medicine due to its esteemed therapeutic effects. WHO have enlisted almost 21,000 herbal components that have established therapeutic benefit. Several herbs, most of them widely available, have been studied to extract their active phytoconstituents that have effective diabetes management potential with the least risk factor for side effects and acute toxicity. Though acceptable standardization, awareness, and clinical trials are yet to be established before mainstreaming herbal formulation, preclinical studies have confirmed the higher safety and efficacy of several extracted phytoconstituents and formulation in comparative analysis with synthetic products. The authors have also discussed their opinions with regard to the vast usability of herbal components along with the multi-target functionality of several phytoconstituents, as well as the challenges faced for standardizing, formulating, and marketing herbal medicines. Other than this, several cases of clinical trials showing effectivity of herbal antidiabetic aid are mentioned. In this review, an attempt has been made to summarize the potential antidiabetic herbs, marketed herbal formulations, and patented formulations that have established therapeutic prospects to downregulate diabetic conditions.

Oral disintegrating tablets (ODT) offer an attractive choice for Gastroesophageal Reflux Disease (GERD) patients suffering from dysphagia. In chronic condition, GERD patient suffers from severe erosive esophagitis. Thus patients feel difficulty and pain during swallowing, which results in patient in-compliance toward medication of tablets or capsules- especially in geriatrics and pediatric patients. These symptoms of GERD patients have attracted the formulation scientists in improving the formulation methodology for such patients. Orally disintegrating tablets could increase the therapeutic impact and drug compliance in these patients. The aim of this compilation is to provide a more convenient way to develop an oral disintegrating drug delivery system of proton pump inhibitors in patients suffering from odynophagia, associated with chronic Gastroesophageal Reflux Disease (GERD). Oral disintegrating tablets (ODT), when placed on the tongue, can quickly disintegrate and release the medicament. It later dissolves or disperses in saliva without any additional water. The saliva containing drug can easily be swallowed and descends into the stomach leading to maximum absorption from the mouth, throat, and upper esophagus. The patient compliance and bio-availability of Oral disintegrating tablets (ODT) are high compared to other conventional tablets.

Personalized medicine (PM) is about developing an individualized approach to each patient's illness. Understanding how a patient's genomic portfolio renders them prone to various diseases may be enhanced by discovering genetic, epigenetic, and medical evidence. Medical therapy that is safe and effective for specific individuals may be predicted using the PM approach, which is a complete expansion of an older methodology (One-Size-Fits-All). Patient's well-being and longevity may improve and costs are reduced if PM is used. Using existing biomarkers and early genome and epigenomic processes to better understand PM may lead to earlier diagnosis of the disease, including carcinogenesis. A key focus of the PM technique is preventative medicine, which emphasizes proactive actions rather than depending only on reactive ones. More intrusive procedures may be avoided or postponed using this technique, resulting in a higher quality of life and lower financial burdens for patients. End-of-life care costs are putting a strain on governmentfunded healthcare systems across the globe, notably in the United States. When used in conjunction with present treatments, PM may help them work better and lessen the disadvantages of just non-PM methods. Using genetic profiling, doctors may choose a drug based on a participant's genetic profile that minimizes unwanted side effects and ensures a better result while also being less costly than a 'trial-and-error' approach to sickness treatment. The less effective non- PM ('trial-and-error') strategy leads to drug toxicity, severe adverse effects, reactive treatment, and misdiagnosis. PM and proactive therapeutic regimens should be used more often to save costs and enhance overall well-being.

Introduction and aim: Esophageal adenocarcinoma (EAC) mortality continues to increase across the world. This meta-analysis was aimed to investigate the relationship between proton pump inhibitors (PPIs) and the risk of EAC.

Methods: This meta-analysis was done as per the PRISMA checklist using relevant keywords. To this end, an extensive search was done on 29/6/2022 in EMBASE, Web of Science (ISI), PubMed, and Scopus. In this study, 95% confidence interval (CI) and standardized mean difference (SMD) were used to estimate the overall effect size. Analysis of the odds ratio (OR) for EAC was done using a random effects model.

Results: A total of 20 studies were included in the review. Compared to the group that received PPIs, the OR of EAC in the recipients of the PPIs group was obtained at 0.67 (95% CI = 0.39-1.29, P = 0.240). The meta-regression, including year, follow-up time, study design, sample size, quality of the study, study period, and geographical location, demonstrated no source of heterogeneity (P > 0.10).

Conclusion: No significant relationship was found between PPIs use and the risk of EAC. Accordingly, PPIs do not have a protective or risk factor effect on EAC.

Background: Breast cancer is the most commonly diagnosed and major cause of cancer-related deaths in women worldwide. Disruption of the normal regulation of cell cycle progression and proliferation are the major events leading to cancer. Human Polo-like Kinase 1 (PLK1) plays an important role in the regulation of cellular division. High PLK1 expression is observed in various types of cancer including breast cancer. 1,3,4-oxadiazoles are the fivemembered heterocycles, that serve as versatile lead molecules for designing novel anticancer agents and they mainly act by inhibiting various enzymes and kinases.

Objective: A novel series of 1,3,4-oxadiazole derivatives (A1-A26) were designed and subjected to an in-silico analysis against PLK1 enzyme (PDB ID:1q4k), targeting breast cancer.

Methods: The chemical structure of each compound (A1-26) was drawn using ChemDraw software. The 3D structure model of protein target (PDB ID:1q4k) was built using the SWISSMODEL server. Molecular docking simulation was performed to determine the designed compound's probable binding mode and affinity towards the protein target (PDB ID:1q4k). The designed compounds were subjected to ADME screening, as well as Prime MM/GBSA simulations using Schrodinger suite 2020-4. Furthermore, the safety profile of compounds was examined through the OSIRIS property explorer program and the results were compared with the standard drugs, 5-fluorouracil and cyclophosphamide.

Results: Based on the binding affinity scores, the compounds were found selective to target protein 1q4k through hydrogen bonding and hydrophobic interactions. The compounds A11, A12, and A13 were found to have higher G scores and binding free energy values. The ADME screening results were also found to be within the acceptable range. Moreover, the in-silico toxicity prediction assessments suggest that all designed compounds have a low risk of toxicity, and have higher efficiency for the target receptor.

Conclusion: The study showed that the substitution of electron-donating groups at the various position of the aromatic ring, which is bonded at the second position of the substituted 1,3,4- oxadiazole nucleus resulted in compounds with good binding energy and G score compared to the standard drugs, and hence, they can be further developed as potent PLK1 enzyme inhibitors.

Introduction: Poly-drug use has increased in recent decades, especially in young drugusing groups. Classic epidemiological indicators of drug use, such as prevalence and incidence of users of specific substances, are not adequate as measures of the possible harms of poly-drug use. We applied poly-drug use indicators, based on substance-specific harm scores reported by van Amsterdam and Nutt in 2015, to data from high school student surveys, showing their usefulness in identifying high-risk drug consumption. Analysing the 'correlation' between high-risk drug use of high school students and school dropout allows the evaluation of adopted prevention policies and may suggest more suitable approaches.

Methods: Each drug user is characterized by two specific scores: overall frequency of use of substances during the period of interest (FUS) and poly-drug use score (PDS). The poly-drug use score is a weighted average of the harm scores of the individual substances used multiplied by their respective frequencies of use. The PDS increases with the frequency of use, with the number of substances used, and with the specific harm scores of each substance. This indicator consists of two components, one representing the health harm score toward self and the other the social harm score toward others.

Results: The indicators have been applied to sample data involving youth population, specifically the ESPAD®Italia survey data on high school students conducted annually in Italy. The trends of poly-drug use at different ages of students, 15-19 years, over time, and gender have been studied. The results have been linked to educational outcomes, early school leaving and social aspects, making it possible to assess present prevention interventions and suggest appropriate planning of future prevention interventions.

Conclusion: Poly-drug use indicators allow a comprehensive quantitative evaluation of the risks of drug use. The analysis of the links between heavy use of drugs, school performance and dropout, and the social variables that influence them, shown in this work, suggests how best to plan secondary or indicated prevention interventions at school. The problem of including "new" NPS in analyses is also briefly discussed.

Diabetes Mellitus (DM) is one of the highest contributors to global mortality, exceeding numbers of even the three major infectious diseases in the world, namely Tuberculosis, HIV AIDS, and Malaria. DM is characterised by increased serum levels of glucose caused by a loss of beta cells of the pancreatic islets, responsible for the secretion of insulin. Upon accumulation of data via a wide array of literature surveys, it has been found that Thioredoxin Interacting Protein (TXNIP) presents itself as a vital factor in controlling the production and loss of beta islet cells. TXNIP inhibits the action of the Thioredoxin (TRX) protein found in the beta cells thereby rendering it ineffective in maintaining the cellular redox balance causing oxidative stress and subsequent consequences ultimately leading to aggravation of the disease. TRX exists in the form of two isoforms - TRX1, which is located in the cytosol and at times translocates to the nucleus, and TRX2, which is located in the nucleus. TRX is responsible for the maintenance of the normal cellular redox balance by reducing the oxidised proteins formed by the Reactive Oxygen Species (ROS) with the help of NADPH dependent TRX Reductase enzyme. This proves to be essential in the pathogenesis of Diabetes Mellitus as the beta cells of the pancreatic islets lack a sufficient amount of antioxidant systems. Thus, inhibition of TXNIP has become essential in the survival of beta cells, not only enhancing insulin secretion and sensitivity but also alleviating the diseases associated with Diabetes. Hence, TXNIP is discovered to be a unique therapeutic target in the management of DM.