Drug ResearchPub Date : 2025-01-01Epub Date: 2024-10-15DOI: 10.1055/a-2423-3533
J S Gayathri, S Swathi Krishna, M P Rakesh
{"title":"Tyrosine Kinase Inhibitor Induced Proteinuria - A Review.","authors":"J S Gayathri, S Swathi Krishna, M P Rakesh","doi":"10.1055/a-2423-3533","DOIUrl":"10.1055/a-2423-3533","url":null,"abstract":"<p><p>Tyrosine Kinase inhibitor (TKI) is a class of drugs that interfere with protein kinases' signal transduction pathways through an array of inhibitory mechanisms. Tyrosine kinases (TK) have an inevitable role in downstream signal transduction and the proliferation of tumour cells. Hence, tyrosine kinase inhibitors (TKIs) are frequently employed as anti-neoplastic agents in the treatment of colon, breast, kidney, and lung cancers. They can be used as single or combination therapy with other targeted therapies. It is understood that TKIs pose a risk of developing proteinuria in some patients as it can primarily result in dysfunction of the split diaphragm, constriction or blockage of capillary lumens mediated by the basement membrane, acute interstitial nephritis, or acute tubular necrosis. This paper reviews the mechanism of action of TKIs, the pathophysiological mechanism of TKI-induced proteinuria, and its management Fig. 1.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"5-11"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In Silico Identification of Promising PDE5 Inhibitors Against Hepatocellular Carcinoma Among Natural Derivatives: A Study Involving Docking and ADMET Analysis.","authors":"Anil Kumar, Dharmendra Rajput, Naveen Gupta, Harpreet Singh, Shivani Chopra, Hitesh Chopra","doi":"10.1055/a-2435-4709","DOIUrl":"10.1055/a-2435-4709","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) represents a significant worldwide health challenge due to its high mortality rate, underscoring the need for advanced therapeutic strategies. This study employs a computer-based method to identify potential phosphodiesterase 5 (PDE5) inhibitors from a library of approved IBS_Scaff 532 natural compounds. PDE5 inhibitors have gained attention for their potential anti-tumor effects. Using molecular docking simulations, the researchers assessed how well these compounds bind to the PDE5 enzyme, which regulates cellular cGMP pathways. Additionally, ADMET profiling predicted the pharmacological and safety properties of candidate inhibitors. Notably, compounds like IBS_NC-0322 and IBS_NC-0320 exhibited favorable ADMET properties and strong binding affinities. These findings suggest their potential as therapeutic agents for treating HCC. While in silico methods serve as valuable screening tools, subsequent experimental validation and clinical trials are essential for confirmation.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"21-33"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-11-01Epub Date: 2024-09-26DOI: 10.1055/a-2413-3740
Babita Shukla, Poonam Kushwaha
{"title":"Exploring the HPLC Profiling and Antioxidant Potency in Methanolic Extracts of Curcuma longa L. Rhizomes.","authors":"Babita Shukla, Poonam Kushwaha","doi":"10.1055/a-2413-3740","DOIUrl":"10.1055/a-2413-3740","url":null,"abstract":"<p><p>In this exploration of <i>Curcuma longa</i> Linn., commonly known as turmeric, renowned for its therapeutic history, our study focuses on the bioactive compound curcumin. We established and validated an HPLC method for precise curcumin quantification, complemented by an examination of total phenolic and flavonoid content, as well as antioxidant capabilities in a methanolic extract from <i>C. longa</i> rhizomes obtained through a methanol-based Soxhlet extraction. The HPLC analysis utilized a C18 column with a mobile phase of 70:30 V/V Acetonitrile (ACN) to Water (with 1% Glacial Acetic Acid) under an isocratic elution at 1 mL/min, detection at 420 nm, and a reference standard. The method exhibited notable accuracy, precision, and reproducibility. Antioxidant potential, assessed through DPPH, nitric oxide, and hydroxyl radical scavenging assays, unveiled significant total phenol and total flavonoid quantities, highlighting <i>C. longa's</i> potent antioxidant capacity. The study demonstrated a correlation between antioxidant activities and phenolic and flavonoid concentrations, reinforcing the robustness of our method. In conclusion, this method offers an effective means of quantifying curcumin within <i>C. longa</i> rhizomes and holds promise as a valuable tool for maintaining quality control in the production of this botanical material.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"475-482"},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-11-01Epub Date: 2024-09-23DOI: 10.1055/a-2401-4700
Meng Zhu, Linghui Tao, Feiye Zhu, Yongsheng Zhang
{"title":"A Comparative Analysis of ADRs under Obeticholic Acid and Ursodeoxycholic Acid in Cholestatic Liver Diseases Using the FAERS Database.","authors":"Meng Zhu, Linghui Tao, Feiye Zhu, Yongsheng Zhang","doi":"10.1055/a-2401-4700","DOIUrl":"10.1055/a-2401-4700","url":null,"abstract":"<p><strong>Background: </strong>The objective of this study was to compare the safety profiles of OCA and UDCA for the treatment of PBC using the FDA Adverse Event Reporting System database.</p><p><strong>Methods: </strong>We extracted reports for OCA from 2016 to 2023 and UDCA from 2004 to 2023. Demographic details, adverse events (AEs), and concomitant medications were analyzed using descriptive statistics and signal detection methods.</p><p><strong>Results: </strong>The most common for OCA were pruritus (1345 cases, ROR 20.96) and fatigue (528 cases, ROR 3.46). UDCA was more frequently associated with hepatocellular carcinoma (22 cases, ROR 16.37) and type I hypersensitivity reactions (11 cases, ROR 12.77). OCA was also linked to a higher frequency of constipation (161 cases, ROR 3.92) and increased blood alkaline phosphatase levels (145 cases, ROR 44.27).</p><p><strong>Conclusion: </strong>This study reveals distinct safety profiles for OCA and UDCA in the treatment of PBC. OCA is associated with a higher frequency of pruritus, fatigue, constipation, and increased blood alkaline phosphatase levels, while UDCA is linked to hepatocellular carcinoma and type I hypersensitivity reactions. These findings support personalized treatment approaches based on individual patient characteristics.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"464-474"},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-11-01Epub Date: 2024-09-19DOI: 10.1055/a-2406-5340
Samane Jahanabadi, Mohammadreza Riahi Madvar
{"title":"Unraveling the Interplay of 5-hydroxytryptamine-3 and N-methyl-d-aspartate Receptors in Seizure Susceptibility.","authors":"Samane Jahanabadi, Mohammadreza Riahi Madvar","doi":"10.1055/a-2406-5340","DOIUrl":"10.1055/a-2406-5340","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, presents significant challenges in treatment and management. This study aimed to evaluate the effect of tropisetron, a selective 5-HT3 receptor antagonist on pentylenetetrazole (PTZ) - induced seizure in mice by exploring the potential role of the NMDA receptor and inflammatory responses.</p><p><strong>Methods: </strong>For this purpose, seizures were induced by intravenous PTZ infusion. Tropisetron at 1-, 2-, 3-, 5-, 10- mg/kg were administered intraperitoneally 30 minutes before PTZ. To evaluate probable role of NMDA signaling, selective NMDAR antagonists, ketamine and MK-801, were injected 15 minutes before tropisetron. Also, TNF-α level of hippocampus were measured following administration of mentioned drugs in mice.</p><p><strong>Results: </strong>Our results demonstrate that tropisetron displayed a dose-dependent impact on seizure threshold, with certain doses (5 and 10 mg/kg) exhibiting anticonvulsant properties. In addition, the noncompetitive NMDAR antagonists, ketamine (1 mg/kg) and MK-801 (0.5 mg/kg), at doses that had no effect on seizure threshold, augmented the anticonvulsant effect of tropisetron (3 mg/kg). Also, tropisetron led to a reduction in hippocampal TNF-α levels, indicating its anti-inflammatory potential independent of 5-HT receptor activity.</p><p><strong>Conclusion: </strong>In conclusion, we demonstrated that the anticonvulsant effect of tropisetron is mediated by the inhibition of NMDA receptors and a decline in hippocampal TNF-α level. These findings highlight a potential connection between 5-HT3 and NMDA receptors in the pharmacological treatment of inflammatory diseases, such as seizure, warranting further investigation into their combined therapeutic effects.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"456-463"},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-11-01Epub Date: 2024-08-02DOI: 10.1055/a-2366-8999
Farazul Hoda, Mohammad Chand Jamali, Mawrah Arshad, Mohammad Anwar Habib, Mohd Akhtar, Abul Kalam Najmi
{"title":"Amputation Risk in Type II Diabetes Mellitus Patients Treated with SGLT-2 Inhibitors: A Systematic Literature Review of Randomized Clinical Trials.","authors":"Farazul Hoda, Mohammad Chand Jamali, Mawrah Arshad, Mohammad Anwar Habib, Mohd Akhtar, Abul Kalam Najmi","doi":"10.1055/a-2366-8999","DOIUrl":"10.1055/a-2366-8999","url":null,"abstract":"<p><strong>Background: </strong>SGLT-2 inhibitors, prescribed for type 2 diabetes, have a heightened risk of amputation. The FDA issued a warning in May 2017, leading to the inclusion of a cautionary label. Vigilance is essential for patients and healthcare providers to promptly identify and address potential limb complications associated with the use of SGLT-2 inhibitors.</p><p><strong>Method: </strong>A comprehensive search of electronic databases was conducted, covering the period from inception to May 2024. This systematic literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Cochrane risk of bias (ROB) tool. Inclusion and exclusion criteria were predefined, and data extraction was performed to summarize the findings.</p><p><strong>Result: </strong>A total of 12 randomized control trial (RCT) studies were included in the present systematic review. 37,657 (54.89%) participants were randomly assigned to receive the different interventions of SGLT-2 inhibitor, whereas 30,959 (45.11%) received a placebo. Overall, 618 events were reported in the treatment group, whereas 396 events were reported in the placebo group.</p><p><strong>Conclusion: </strong>In conclusion, patients treated with SGLT-2 inhibitors did not have any significant difference in amputation occurrences compared to placebo across various studies. However, canagliflozin usage has led to higher amputation events in certain trials.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"425-432"},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-11-01Epub Date: 2024-09-19DOI: 10.1055/a-2379-6849
Sana Ahmad, Farogh Ahsan, Javed Akhtar Ansari, Tarique Mahmood, Shahzadi Bano, Mo Shahanawaz
{"title":"Bioflavonoid Daidzein: Therapeutic Insights, Formulation Advances, and Future Directions.","authors":"Sana Ahmad, Farogh Ahsan, Javed Akhtar Ansari, Tarique Mahmood, Shahzadi Bano, Mo Shahanawaz","doi":"10.1055/a-2379-6849","DOIUrl":"10.1055/a-2379-6849","url":null,"abstract":"<p><p>Bioflavonoids, are a diverse group of phytonutrients that are widely distributed in fruits, vegetables, grains, teas, and certain medicinal herbs. They are characterized by their antioxidant properties and play essential roles in plant biology, such as providing color to fruits and flowers, protecting plants from environmental stresses. Daidzein, a bioflavonoid classified under natural products, is sourced from plants like soybeans and legumes. It exists in forms such as glycosides and aglycones, with equol and trihydroxy isoflavone being key metabolites formed by gut bacteria. Known for its wide-ranging therapeutic potential, daidzein has shown effects on cardiovascular health, cancer, diabetes, skin conditions, osteoporosis, and neurodegenerative disorders. Its mechanisms include interaction with estrogen receptors, antioxidative and anti-inflammatory properties, and modulation of apoptosis and cell cycles. Recent advances in formulation technologies aimed at enhancing daidzein's bioavailability and efficacy are critically evaluated, including nanoparticle-based delivery systems and encapsulation strategies. Researchers have developed advanced formulations like nanoparticles and liposomes to enhance daidzein's solubility, stability, bioavailability, and targeted delivery. Considered a promising nutraceutical, daidzein warrants further exploration into its molecular actions and safety profile to fully realize its clinical potential. This review offers a succinct overview encompassing therapeutic benefits, chemical characteristics, historical uses, toxicology insights, recent advancements in delivery systems, and future directions for daidzein research.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"433-455"},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibacterial Efficacy of Hiora: An Ayurvedic Mouthwash in Children.","authors":"Sonali Saha, Kongkana Kalita, Kavita Dhinsa, Deval Kumar Arora, Brinda Suhas Godhi, Vidya Gowdappa Doddawad","doi":"10.1055/a-2368-4336","DOIUrl":"10.1055/a-2368-4336","url":null,"abstract":"<p><strong>Background: </strong>Mouthwashes, as a form of antimicrobial delivery system, rank among the safest and most effective vehicles, particularly in the case of young children. This is attributed to their ability to distribute therapeutic components across all accessible oral surfaces, including interproximal areas.</p><p><strong>Objective: </strong>To evaluate the antibacterial efficacy of recently introduced Ayurvedic (Hiora) and triclosan-based mouthwashes among children.</p><p><strong>Materials and methods: </strong>A total of 45 healthy children aged 10-15 years were randomly assigned to three groups: Herbal mouthwash (Hiora), triclosan-based mouthwash (Kidodent), and normal saline as the control group. Saliva samples were collected pre-rinse, 2 minutes, 30 minutes, and 60 minutes post-rinsing with the study mouthwashes. These samples were then inoculated onto Petri dishes containing blood agar culture media, followed by incubation under both aerobic and anaerobic conditions at 37°C for 48 hours. The resulting bacterial colonies of <i>Streptococcus spp.</i> and <i>Lactobacillus spp.</i> were counted (CFU/ml x 105). Statistical analysis, including ANOVA, Newman Keul's Post-hoc test, and a two-tailed 't' test, was conducted to determine the significance of the results.</p><p><strong>Results: </strong>The Ayurvedic Hiora mouthwash demonstrated the most substantial reduction in salivary bacterial colony counts of <i>Streptococcus spp</i>. and <i>Lactobacillus spp.</i> with statistically significant results (p<0.01).</p><p><strong>Conclusion: </strong>The Ayurvedic Hiora mouthwash exhibited the highest antibacterial effectiveness, followed by the triclosan-based mouthwash in decreasing order, with saline showing the least efficacy.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"415-420"},"PeriodicalIF":1.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of the Efficacy of Tofacitinib, a JAK Inhibitor, in Alleviating Sepsis-Induced Multiple Organ Dysfunction Syndrome.","authors":"Vaishnavi Singh, Kavita Joshi, Samit Chatterjee, Sameer Qureshi, Snigdha Siddh, Vandana Nunia","doi":"10.1055/a-2372-3446","DOIUrl":"10.1055/a-2372-3446","url":null,"abstract":"<p><p>Sepsis, a life-threatening condition triggered by an uncontrolled response to infection, results in a systemic inflammatory response syndrome (SIRS) and the failure of multiple organs leading to multiple organ dysfunction (MODS). In the present study, we investigated the therapeutic potential of tofacitinib (TOFA), an FDA-approved inhibitor of JAK1 and JAK3 against sepsis, using a mouse model induced by cecal ligation puncture (CLP). Swiss albino mice were employed to replicate the CLP-induced sepsis model and were randomly divided into four groups: control, CLP, 150 mg/kg TOFA, and 300 mg/kg TOFA. Six hours after the last TOFA dose, we collected blood and tissue samples from the liver, lungs, kidneys, and spleen for histological analysis. Blood samples were used to assess granulocyte and lymphocyte percentages. Throughout the experiment, we monitored body weight and short-term survival. Our comparative histological analysis revealed that 150 mg/kg TOFA had a protective effect against multiple organ damage. Conversely, the study highlighted the harmful effects of 300 mg/kg TOFA, primarily due to liver and renal toxicity within this group. In summary, our findings demonstrate that tofacitinib at an optimal dose of 150 mg/kg showed promise as a potential therapeutic intervention for sepsis-induced multiple organ failure. However, caution is warranted when considering higher dosages.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"394-404"},"PeriodicalIF":1.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-10-01DOI: 10.1055/a-2401-4578
Manoj Bisht, Jai Parkash Kadian, Tanuj Hooda, Neelam Jain, Amit Lather, Navidha Aggarwal
{"title":"Explore the Role of the Sphingosine-1-Phosphate Signalling as a Novel Promising Therapeutic Target for the Management of Parkinson's Disease.","authors":"Manoj Bisht, Jai Parkash Kadian, Tanuj Hooda, Neelam Jain, Amit Lather, Navidha Aggarwal","doi":"10.1055/a-2401-4578","DOIUrl":"10.1055/a-2401-4578","url":null,"abstract":"<p><p>Sphingosine-1-phosphate (S1P) is a cellular signalling molecule derived from sphingosine, which is a pro-apoptotic sphingolipid. Sphingolipids control various cellular actions like growth, homeostasis, and stress-related responses. The main sources of S1P in our body are erythrocytes. S1P controls both cellular mediators and other second messengers intracellularly. The S1P receptor also helps in inflammatory and neuroprotective effects (required to manage of Parkinson's). A large number of anti-Parkinson drugs are available, but still, there is a need for more effective and safer drugs. S1P and its receptors could be targeted as novel drugs due to their involvement in neuro-inflammation and Parkinson's. The present review effort to explore the biological role of S1P and related receptors, for their possible involvement in PD; furthermore. Overall, S1P and other related metabolizing enzymes have significant therapeutic opportunities for Parkinson's disease along with other neurological disorders.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"74 8","pages":"365-378"},"PeriodicalIF":1.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}