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.
{"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":"https://doi.org/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":""},"PeriodicalIF":1.7,"publicationDate":"2024-11-12","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}
Pub Date : 2024-11-01Epub Date: 2024-09-26DOI: 10.1055/a-2413-3740
Babita Shukla, Poonam Kushwaha
In this exploration of Curcuma longa 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 C. longa 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 C. longa's 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 C. longa rhizomes and holds promise as a valuable tool for maintaining quality control in the production of this botanical material.
{"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}
Pub Date : 2024-11-01Epub Date: 2024-09-23DOI: 10.1055/a-2401-4700
Meng Zhu, Linghui Tao, Feiye Zhu, Yongsheng Zhang
Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
{"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}
Pub Date : 2024-11-01Epub Date: 2024-09-19DOI: 10.1055/a-2406-5340
Samane Jahanabadi, Mohammadreza Riahi Madvar
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
{"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}
Pub 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
Background: 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.
Method: 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.
Result: 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.
Conclusion: 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.
{"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}
Pub 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
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.
{"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}
Bahareh Farasati Far, Partow Mirzaee Saffari, Razieh Mohammad Jafari, Ramin Goudarzi, Ahmad Reza Dehpour, Alireza Partoazar
Background: Psoriasis is a chronic skin condition that is associated with persistent inflammation and skin lesions. Topical therapy has been a promising approach to the alleviation of psoriasis through the application of anti-inflammatory agents. Phosphatidylserine (PS) administration has shown anti-inflammatory effects in the trials. Consequently, the objective of this study was to evaluate the effects of topical PS on the potential improvement of an imiquimod (IMQ)-induced psoriasis model. Additionally, cyclosporine A was utilized as a comparative anti-psoriatic agent in our study.
Methods: The psoriasis model was established by topically applying IMQ to the dorsal skin of mice once daily for five consecutive days. The efficacy of topical PS was assessed using the Psoriasis Area and Severity Index (PASI) score to evaluate skin lesions. Subsequently, the skin samples were analyzed using Baker's scoring system, Masson's trichrome staining, immunohistochemistry, and real-time PCR analysis.
Results: IMQ-induced plaque-type psoriasis resulted in a significant increase (P<0.05) in dermal thickness, hyperkeratosis, PASI score, and inflammatory cytokines at the lesion site. The topical PS and cyclosporine A significantly (P<0.05) reduced PASI score and dermal thickness, while also alleviating erythema and scaling when compared to untreated mice. Furthermore, biomolecular assessments revealed that PS significantly (P<0.05) inhibited the gene expression of IL-17, IL-23, and TNF-α cytokines in the IMQ-induced lesions.
Conclusion: Topical PS may pointedly alleviate psoriasis through the inhibition of inflammation. The beneficial effects of the PS recommend further investigation in both experimental and clinical studies in the control of skin psoriasis.
背景:银屑病是一种慢性皮肤病,与持续的炎症和皮损有关。通过使用抗炎药物,外用疗法一直是缓解银屑病的有效方法。试验表明,磷脂酰丝氨酸(PS)具有抗炎作用。因此,本研究旨在评估外用 PS 对改善咪喹莫特(IMQ)诱导的银屑病模型的潜在影响。此外,我们还使用环孢素 A 作为抗银屑病的对比药物:牛皮癣模型的建立是通过在小鼠背侧皮肤上局部涂抹 IMQ,每天一次,连续五天。使用银屑病面积和严重程度指数(PASI)来评估外用 PS 的疗效。随后,使用贝克评分系统、马森三色染色法、免疫组化法和实时 PCR 分析法对皮肤样本进行分析:结果:IMQ诱导的斑块型银屑病导致皮损部位的真皮厚度、角化过度、PASI评分和炎症细胞因子显著增加(P)。与未经处理的小鼠相比,外用 PS 和环孢素 A 能显著降低 PASI 评分和真皮厚度,同时还能减轻红斑和鳞屑。此外,生物分子评估显示,PS 能明显抑制 IMQ 诱导的皮损中 IL-17、IL-23 和 TNF-α 细胞因子的基因表达:结论:外用 PS 可通过抑制炎症明显缓解银屑病。结论:外用 PS 可通过抑制炎症显著缓解银屑病,建议在控制皮肤银屑病的实验和临床研究中进一步探讨 PS 的有益作用。
{"title":"Phosphatidylserine Topically Attenuates Imiquimod-induced Psoriasis Through Inflammation Inhibition in Mice.","authors":"Bahareh Farasati Far, Partow Mirzaee Saffari, Razieh Mohammad Jafari, Ramin Goudarzi, Ahmad Reza Dehpour, Alireza Partoazar","doi":"10.1055/a-2419-9616","DOIUrl":"https://doi.org/10.1055/a-2419-9616","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic skin condition that is associated with persistent inflammation and skin lesions. Topical therapy has been a promising approach to the alleviation of psoriasis through the application of anti-inflammatory agents. Phosphatidylserine (PS) administration has shown anti-inflammatory effects in the trials. Consequently, the objective of this study was to evaluate the effects of topical PS on the potential improvement of an imiquimod (IMQ)-induced psoriasis model. Additionally, cyclosporine A was utilized as a comparative anti-psoriatic agent in our study.</p><p><strong>Methods: </strong>The psoriasis model was established by topically applying IMQ to the dorsal skin of mice once daily for five consecutive days. The efficacy of topical PS was assessed using the Psoriasis Area and Severity Index (PASI) score to evaluate skin lesions. Subsequently, the skin samples were analyzed using Baker's scoring system, Masson's trichrome staining, immunohistochemistry, and real-time PCR analysis.</p><p><strong>Results: </strong>IMQ-induced plaque-type psoriasis resulted in a significant increase <i>(P<0.05)</i> in dermal thickness, hyperkeratosis, PASI score, and inflammatory cytokines at the lesion site. The topical PS and cyclosporine A significantly <i>(P<0.05)</i> reduced PASI score and dermal thickness, while also alleviating erythema and scaling when compared to untreated mice. Furthermore, biomolecular assessments revealed that PS significantly <i>(P<0.05)</i> inhibited the gene expression of IL-17, IL-23, and TNF-α cytokines in the IMQ-induced lesions.</p><p><strong>Conclusion: </strong>Topical PS may pointedly alleviate psoriasis through the inhibition of inflammation. The beneficial effects of the PS recommend further investigation in both experimental and clinical studies in the control of skin psoriasis.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460611","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}
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.
{"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":"https://doi.org/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":""},"PeriodicalIF":1.7,"publicationDate":"2024-10-15","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}
The targeted delivery of drugs is vital in breast cancer treatment due to its ability to produce long-lasting therapeutic effects with minimal side effects. This study reports the successful development of doxorubicin hydrochloride (DOX)-loaded colloidal gold nanoparticles stabilized with acacia gum (AG). Optimization studies varied AG concentrations (0.25% to 3% w/v) to determine optimal conditions for nanoparticle synthesis. The resulting acacia stabilized gold nanoparticles (AGNPs) were characterized using various techniques including high-resolution transmission electron microscopy (HR-TEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), and selected area electron diffraction (SAED). In vitro drug release studies demonstrated a higher release rate of DOX in sodium acetate buffer (pH 5.0) compared to phosphate buffer saline (pH 7.4), suggesting an enhanced therapeutic efficacy in acidic tumor environments. Cytotoxicity of DOX-AGNPs and free DOX was assessed in human breast cancer cells (MDA-MB-231). The DOX-AGNPs exhibited significantly greater cytotoxicity, indicating enhanced efficacy in targeting cancer cells. This enhancement suggests that adsorbing DOX on the surface of gold nanoparticles can improve drug delivery and effectiveness, potentially reducing side effects compared to pure DOX and traditional delivery methods. Stability tests conducted over six months at 25±1°C showed significant changes in particle size and PDI, suggesting limited stability under these conditions. Overall, the acacia-stabilized gold nanoparticles synthesized in this study exhibit promising characteristics for drug delivery applications, particularly in cancer therapy, with effective drug loading, controlled release, and favorable physicochemical properties.
{"title":"Synthesis and Characterization of Acacia-Stabilized Doxorubicin-Loaded Gold Nanoparticles for Breast Cancer Therapy.","authors":"Laxmi Devi, Poonam Kushwaha, Tarique Mahmood Ansari, Amit Rao, Ashish Kumar","doi":"10.1055/a-2418-2200","DOIUrl":"https://doi.org/10.1055/a-2418-2200","url":null,"abstract":"<p><p>The targeted delivery of drugs is vital in breast cancer treatment due to its ability to produce long-lasting therapeutic effects with minimal side effects. This study reports the successful development of doxorubicin hydrochloride (DOX)-loaded colloidal gold nanoparticles stabilized with acacia gum (AG). Optimization studies varied AG concentrations (0.25% to 3% w/v) to determine optimal conditions for nanoparticle synthesis. The resulting acacia stabilized gold nanoparticles (AGNPs) were characterized using various techniques including high-resolution transmission electron microscopy (HR-TEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), and selected area electron diffraction (SAED). In vitro drug release studies demonstrated a higher release rate of DOX in sodium acetate buffer (pH 5.0) compared to phosphate buffer saline (pH 7.4), suggesting an enhanced therapeutic efficacy in acidic tumor environments. Cytotoxicity of DOX-AGNPs and free DOX was assessed in human breast cancer cells (MDA-MB-231). The DOX-AGNPs exhibited significantly greater cytotoxicity, indicating enhanced efficacy in targeting cancer cells. This enhancement suggests that adsorbing DOX on the surface of gold nanoparticles can improve drug delivery and effectiveness, potentially reducing side effects compared to pure DOX and traditional delivery methods. Stability tests conducted over six months at 25±1°C showed significant changes in particle size and PDI, suggesting limited stability under these conditions. Overall, the acacia-stabilized gold nanoparticles synthesized in this study exhibit promising characteristics for drug delivery applications, particularly in cancer therapy, with effective drug loading, controlled release, and favorable physicochemical properties.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388877","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}
Background: 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.
Objective: To evaluate the antibacterial efficacy of recently introduced Ayurvedic (Hiora) and triclosan-based mouthwashes among children.
Materials and methods: 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 Streptococcus spp. and Lactobacillus spp. 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.
Results: The Ayurvedic Hiora mouthwash demonstrated the most substantial reduction in salivary bacterial colony counts of Streptococcus spp. and Lactobacillus spp. with statistically significant results (p<0.01).
Conclusion: The Ayurvedic Hiora mouthwash exhibited the highest antibacterial effectiveness, followed by the triclosan-based mouthwash in decreasing order, with saline showing the least efficacy.
{"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}