{"title":"Emerging role of antioxidants in Alzheimer's disease: Insight into physiological, pathological mechanisms and management","authors":"Kamaljeet , Shamsher Singh , G.D. Gupta , Khadga Raj Aran","doi":"10.1016/j.pscia.2023.100021","DOIUrl":"10.1016/j.pscia.2023.100021","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, cognitive decline, impairment in activities of daily living, and loss of independent function. Cognitive decline and brain shrinkage, particularly hippocampal atrophy, are associated with the accumulation of tau proteins. They cause inflammation, amyloid plaque deposition, neuronal loss, temporofrontal cortex atrophy, aberrant protein fragment clusters, and twisted fiber bundles. Given the significant role of oxidative processes in neurodegeneration, it is logical to consider the potential of antioxidants in the treatment of AD. Several antioxidants, including glutathione, astaxanthin, ascorbyl palmitate, catalase, and molecular hydrogen, play important roles in AD. Antioxidants interact with free radicals to neutralize them. Several studies have suggested that oxidative stress or damage is involved in the development of AD via different mechanisms and pathways. Thus, new approaches are needed to reduce the extent of oxidative damage that may be therapeutically effective against AD. Although certain antioxidants have exhibited notable benefits in animal models, their efficacy in human clinical trials has been limited, casting doubt regarding the efficacy of antioxidant treatments for AD. Therefore, a more focused and precise strategy that incorporates antioxidants is essential for slowing or stopping AD progression. The integrated role of antioxidants in reducing inflammation must be considered, because the link between inflammation and AD is undeniable. Therefore, the present study aimed to elucidate the role of antioxidants in AD, with the goal of aiding researchers in developing effective and potentially enhanced antioxidant-based therapeutic strategies.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000193/pdfft?md5=c7c26eaad3d7e2ef2bbe5909ed329030&pid=1-s2.0-S2773216923000193-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136007628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pratik R. Dhake , Smita T. Kumbhar , Vinod L. Gaikwad
{"title":"Biowaiver based on biopharmaceutics classification system: Considerations and requirements","authors":"Pratik R. Dhake , Smita T. Kumbhar , Vinod L. Gaikwad","doi":"10.1016/j.pscia.2023.100020","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100020","url":null,"abstract":"<div><p>Biowaiver allows for the waiver of bioequivalence studies for regulatory approval of certain drug products with saving of time, and money. Before approval of the application for biowaivers, studies based on the Biopharmaceutical Classification System (BCS) are required to satisfy regulators in the US, Europe, and other developing markets. Only pharmaceutical products that meet the regulatory requirements for solubility, diffusion, and permeability will be granted a biowaiver. Due to high solubility and considerable permeability, BCS class I and class III drugs are highly preferred for biowaiver by regulatory agencies. The World Health Organization recently expanded the scope of the biowaiver acceptance by considering all BCS classes. These techniques can cut down on time and money spent on ineffective bioequivalence studies. In the present article, an attempt has been made to cover the prerequisites and guidelines for biowaiver approval of a generic product, a topical system, oral films, and BCS class II and IV drugs.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000181/pdfft?md5=7157f3d3138990657264b234d0fabc3c&pid=1-s2.0-S2773216923000181-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92150350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analysis of the underlying mechanism of Ziziphi Spinosae Semen for treating anxiety disorder in a zebrafish sleep deprivation model","authors":"Jian Zhang , Junli Feng , Chenyu Feng","doi":"10.1016/j.pscia.2023.100019","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100019","url":null,"abstract":"<div><p>Anxiety and depression are the most prevalent psychiatric disorders in the world, and they are highly comorbid with each other. <em>Ziziphi Spinosae Semen</em> (ZSS) is a traditional Chinese herbal medicine widely used in the treatment of insomnia and anxiety in clinical practice. To explore the effects of ZSS in alleviating anxiety in a sleep deprivation (SD) zebrafish model, the locomotor activity performance and anxiety behavior of these experimental fish were evaluated, and the underlying mechanisms of its anti-anxiety effect were examined by analyzing the transcriptomics of brain tissues. Results indicated that ZSS could significantly reduce the freezing duration and alleviate anxiety-like behavior. Moreover, ZSS was effective in promoting melatonin biosynthesis and synaptic transmission, modulating circadian rhythm, and preventing inflammatory response and oxidative stress, as evidenced by the expression alterations of the key anti-oxidation genes (<em>GCLC</em>, <em>GPX1A</em>, <em>GSR</em>, <em>NRF2A</em> and <em>PRDX1</em>) and pro-inflammatory cytokine (<em>IL2RGA</em>, <em>IL6</em> and <em>IL17A/F1</em>). These findings will contribute to the understanding of how ZSS alleviates SD-induced anxiety, and provide a theoretical basis for the clinical application of ZSS.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277321692300017X/pdfft?md5=9f120bcfb614ca105e90736b266f8718&pid=1-s2.0-S277321692300017X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92107640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fanfan Yang , Wang-jing Zhong , Jialin Cao , Junyu Tan , Bohong Li , Lingdi Ma
{"title":"Matrine induces V-ATPase-dependent cytoplasmic vacuolation and inhibits the function of the lysosome in leukemia cells","authors":"Fanfan Yang , Wang-jing Zhong , Jialin Cao , Junyu Tan , Bohong Li , Lingdi Ma","doi":"10.1016/j.pscia.2023.100013","DOIUrl":"10.1016/j.pscia.2023.100013","url":null,"abstract":"<div><p>Matrine is the main component extracted from legumes and has extensive anti-cancer effects; however, its molecular mechanism is unclear. In our study, we found that matrine induced vacuolation in leukemia cells is closely related to cell proliferation inhibition. Vacuolization was reversed after matrine removal. The neutral red staining assay indicated that the matrine-induced vacuoles were acidic, and the vacuoles originated mostly from the lysosome or endosome, as observed by transmission electron microscope (TEM) and fluorescence microscopy localization of LAMP-GFP. Furthermore, single-cell RNA sequencing (RNA-seq) demonstrated that the expression of vacuolation- and lysosomal-related genes were up-regulated after matrine treatment, and western blot (WB) and flow cytometry (FCM) analysis confirmed that matrine inhibits intracellular proteolytic enzyme expression and activity, suggesting that matrine may inhibit lysosomal function. In addition, we identified that matrine significantly up-regulated the expression levels of vacuolar ATPase (V-ATPase) subunits in cells, and the V-ATPase inhibitor effectively reversed the occurrence of cell vacuoles, suggesting that V-ATPase plays an important role in matrine-induced vacuoles. The molecular structure of matrine was further analyzed, and the protonation of matrine in lysosomes to activate V-ATPase may be a direct cause of vacuole formation. Our results revealed a new molecular mechanism by which matrine inhibit leukemia cell proliferation.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100013"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000119/pdfft?md5=61fa6d3ffb404559344c3c79741c4503&pid=1-s2.0-S2773216923000119-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135809726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Flurbiprofen cataplasms: Development and validation of in-vitro dissolution methods and evaluation of multimedia dissolution profiles","authors":"Rathnakar Nathi , Naga Venkata Durga Prasad Ketha , Leela Prasad Kowtarapu , Siva Krishna Muchakayala , Naresh Konduru , Baby Saroja , Arya Lakshmi Marisetti","doi":"10.1016/j.pscia.2023.100018","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100018","url":null,"abstract":"<div><p>The investigation of the systemic release performance of dosage forms using in vitro tools is a crucial objective in the realm of pharmaceutical development. The dissolution methodology is an effective tool for monitoring batch-to-batch variabilities in quality control and gaining insight into the release mechanisms of pharmaceutical drugs. The majority of the dissolution techniques that have been approved are primarily intended for solid oral dosage forms. Nevertheless, these techniques have also been applied to various other dosage forms, including transdermal drug delivery systems. The administration of medication through cataplasm, a transdermal application, poses challenges in understanding the characteristics of drug release. Flurbiprofen is classified as a class II drug according to the Biopharmaceutics Classification System and is commonly administered in the form of a cataplasm for its analgesic properties. A dissolution method was developed to assess the in vitro release profile of the flurbiprofen transdermal delivery system. This method utilized a United States Pharmacopeia dissolution apparatus V, with a disc assembled over the paddle. Additionally, a method for quantification was developed using liquid chromatography. The discriminatory aspect of the developed method has faced criticism due to substantial alterations in excipient composition. Furthermore, we have developed clearly defined multimedia release profiles within the physiological pH range. The validation of the dissolution and chromatography systems was conducted.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000168/pdfft?md5=1770629bbf17febb9b232f33e2aba851&pid=1-s2.0-S2773216923000168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91986956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential therapeutic effect of Salvia coccinea leaf extract in chronic disorders: Myocardial infarction, cataract, and arthritis in rat","authors":"Arun Sundaramoorthy, Narkunaraja Shanmugam","doi":"10.1016/j.pscia.2023.100017","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100017","url":null,"abstract":"<div><p>Aqueous extract from <em>Salvia coccinea</em> leaf (<em>AESL</em>) has been shown its unique anti-oxidant effect via Nuclear factor (NF)-kappa (κ)B pathway in human monocytic THP-1 cells and pharmacological effect on inflammatory diseases like diabetes in rats. Using <em>AESL,</em> which possess antioxidant activity by scavenging radicals and decreasing oxidative stress, would be a promising strategy for the treatment of other inflammatory disorders like myocardial infarction, arthritis, and cataract. This study was designed to evaluate the ameliorating effects of <em>AESL</em> on isoproterenol (Iso)-induced myocardium infarction (MI), selenite-induced cataractogenesis, and complete Freund's adjuvant-induced arthritis in Wistar rats. In this study, <em>AESL</em> ameliorated pathological changes in Iso-induced MI heart muscles and Electro Cardio Gram pattern, 35–80 % protection of the cataractogenesis, and prevented the apoptosis induced by selenite in the rat lens. Both pre and post-treatment of <em>AESL</em> (600 mg/kg, bw) showed no swelling of the joint and, 35 days treatment showed significant prevention against bony destruction as depicted by less narrowing of joint spaces and soft tissue swelling when compared with control rats. Oral administration of <em>AESL</em> inhibited the Iso-induced increase in serum and myocardial lipid peroxidation, aspartate transaminase, alanine transaminase, creatine kinase, troponin-I, and troponin-T, and lactate dehydrogenase of myocardium infarction rats. Significant increases in the activity of superoxide dismutase, catalase, glutathione peroxidase, and a reduced level of glutathione, were observed in <em>AESL</em> treated cataract rat lens. The results demonstrate that <em>AESL</em> is useful in, in addition to diabetes, controlling myocardium infarction, cataracts, and arthritis.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000156/pdfft?md5=8e500d3b1d3b05293dbb64a034e1a5ba&pid=1-s2.0-S2773216923000156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92066987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanoparticle-enhanced mesalazine therapy for inflammatory bowel disease","authors":"Rajvanshi Sutaria, Zi Hong Mok","doi":"10.1016/j.pscia.2023.100014","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100014","url":null,"abstract":"<div><p>Inflammatory bowel disease (IBD) is a chronic inflammatory illness that causes ongoing bodily inflammation in the gastrointestinal tract. Drug-targeted delivery of aminosalicylates such as mesalazine at the inflammation sites, to treat ulcerative colitis (UC) and Crohn's disease (CD) has remained a difficulty. Current mesalazine formulations, including tablets, suppositories, and enemas, are typically associated with adverse systemic effects. The use of nanocarriers however has opened the possibility of improved local targeting and pharmacokinetics of loaded mesalazine, based on the new physicochemical properties of the drug vehicle. The innovative nanoencapsulation of mesalazine has demonstrated success in targeting inflammatory regions and treating mild to moderate IBD. The use of nanocarriers, such as lipid-based, polymeric, and inorganic nanocarriers, has demonstrated improved overall solubility, absorption, and bioavailability of mesalazine while minimising the side effects associated with their absorption. This review aims to offer an insight into what is currently known about IBD, and the nanotechnological approaches for the improvement of mesalazine therapy for IBD.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100014"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000120/pdfft?md5=cce2fa28c0ad0031ff5d2920e9448670&pid=1-s2.0-S2773216923000120-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92066985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Md.Abu Shyeed , Mahci Al Bashera , Ovijit Sarkar Sazal , Md.Moktar Ali , Md Polok Hossain , Henry Sandip Kumar Mondol , Mohammad Ali Chowdhury , Khan Rajib Hossain , Md Tamzid Hossain Molla
{"title":"Investigation of wound healing and anti-inflammatory activity of Senna occidentalis leaf extract, and in silico screening for both activities","authors":"Md.Abu Shyeed , Mahci Al Bashera , Ovijit Sarkar Sazal , Md.Moktar Ali , Md Polok Hossain , Henry Sandip Kumar Mondol , Mohammad Ali Chowdhury , Khan Rajib Hossain , Md Tamzid Hossain Molla","doi":"10.1016/j.pscia.2023.100016","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100016","url":null,"abstract":"<div><p>Senna occidentalis, synonym Cassia occidentalis, is a native American pantropical plant species previously classified under the genus Cassia. This study is for testing and to discover new potent phytochemicals from this plant as wound healing and anti-inflammatory agents. The Excision and Assay of Red Blood Cell (RBC) Membrane Stabilization for Anti-Inflammatory Activity Test Method was used to test how well extracts of <em>S. occidentalis</em> leaves from methanol, n-hexane, chloroform, and absolute alcohol helped wounds heal and stopped inflammation. In silico <strong>is another method</strong> for finding potent phytochemicals for both activities. These leaf extracts effectively <strong>cure wound areas and promote re-epithelialization</strong>. The methanol extract exhibited maximum wound healing (95.04%) and anti-inflammation (62.94%) activity compared to their other extracts, standard, and control groups. In silico <strong>molecular docking of Apigenin</strong>, Aloe-emodin with GSK-3B protein, and 1-Methoxynaphthalene, Quinine with COX-2 protein showed binding affinity in <strong>(kj</strong>J<strong>/mol)</strong> of −8.4, −8.6, and −7.3, −7.7, for wound healing and anti-inflammatory activity, respectively, in their binding sites with stability. They support the <strong>\"Lipinski Rule of Five.\"</strong> This plant leaf extract is recommended as a traditional medicine and an alternative, complementary treatment for its continued contribution to drug discovery and development.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000144/pdfft?md5=d2a6c0e4ef4496fb0dad488e33ce2598&pid=1-s2.0-S2773216923000144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92066690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam A. Al-Shoubki , Mahmoud H. Teaima , Rehab Abdelmonem , Mohamed A. El-Nabarawi , Sammar Fathy Elhabal
{"title":"Potential application of sucrose acetate isobutyrate, and glyceryl monooleate for nanonization and bioavailability enhancement of rivaroxaban tablets","authors":"Adam A. Al-Shoubki , Mahmoud H. Teaima , Rehab Abdelmonem , Mohamed A. El-Nabarawi , Sammar Fathy Elhabal","doi":"10.1016/j.pscia.2023.100015","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100015","url":null,"abstract":"<div><p>This study aimed to investigate the use of Sucrose acetate isobutyrate (SAIB) and Glyceryl monooleate (GMO) as co-formers for creating Cubosomes and SAIB-based nanodispersions of Rivaroxaban (RXB). The process utilized a modified melt dispersion technique with varying polymer: drug ratios (0.5:1, 0.75:1, and 1:1) and a fixed polymer: poloxamer 407 ratio (0.1:1). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE) were measured to determine the optimal formulas. The best-lyophilized formulas were then analyzed using Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), dissolution testing, and Pharmacokinetic (PK) studies. The results revealed significant correlations between polymer concentrations and various variables in cubosomal and SAIB-based nanodispersions. An increase in GMO concentration led to a decrease in PS, PDI, and ZP but an increase in EE and yield. Maintaining optimal GMO concentration is crucial for consistent nanoparticle formulations. In contrast, increasing SAIB concentration led to a decrease in PS and PDI but an increase in EE and yield. The drug release rates of different preparations were measured during the dissolution test. The best-lyophilized cubosome (L4) and the best-lyophilized SAIB-based nanodispersions (L8) showed significantly improved drug release compared to XARELTO®. L4 displayed the best dissolution rate, and L8 also had a reasonable rate. A PK study demonstrated that L4 and L8 had significantly better bioavailability than XARELTO®, possibly due to their improved solubility. This study suggests that SAIB and GMO can significantly enhance the solubility and bioavailability of RXB in nano preparations, leading to more efficient drug delivery. This new approach can also reduce the required dosage for the desired therapeutic effect. However, further research is needed to fully understand these polymers' potential benefits and limitations.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000132/pdfft?md5=8a41cd1940938eea04f0b2f52f4ba13f&pid=1-s2.0-S2773216923000132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92107642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}