Pharmaceutical Science Advances最新文献

{"title":"Intracellularly driven chemical modifications of antimicrobial secondary metabolites: Potent mechanisms of self-resistance","authors":"Xiaohua Li ,&nbsp;Jianhua Ju","doi":"10.1016/j.pscia.2023.100032","DOIUrl":"10.1016/j.pscia.2023.100032","url":null,"abstract":"<div><p>Natural products (NPs), especially antibiotics, exhibit diverse bioactivities and often play critically important roles in dictating and/or driving medical, health, agricultural, animal husbandry, and cosmetic industry initiatives. An important realization in the field of NP applications is that both targeted pathogens and the antibiotic-producing hosts themselves have usually evolved a host of resistance strategies by which to protect themselves. Although the former class of microbes (pathogens) has come to be associated with the global antibiotic resistance crisis, mechanisms by which producing organisms become resistant or tolerant to the ill effects of their bioactive metabolites have begun to attract a great deal of attention. Studies aimed at understanding antibiotic resistance have shown that producer-bourne mechanisms of self-resistance are possible prototypes by which to understand corresponding resistance elements in antibiotic-resistant bacteria. Historically speaking, the most efficient and potent chemistries employed by pathogens to evade harm from antimicrobial NPs have evoked enzymatically-driven transformations. We summarize herein the primary chemical modifications known to impart upon bioactive NP-producing microbes a means of self-defense against their own antimicrobial secondary metabolites; in understanding these chemistries we expect to gain new insights into how antibiotic resistance mechanisms in targeted pathogens might be circumvented or prevented. Such a translation of knowledge has a high likelihood of advancing humanity's ability to counter drug-resistant pathogens.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000302/pdfft?md5=9b7368c90310b0814596be32a9a53382&pid=1-s2.0-S2773216923000302-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139292184","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":"Immune mechanisms and novel therapies for idiopathic pulmonary fibrosis","authors":"Dongyang Gao ,&nbsp;Wenli Gao ,&nbsp;Zhiguang Zhai ,&nbsp;Wenxiang Zhu","doi":"10.1016/j.pscia.2023.100030","DOIUrl":"10.1016/j.pscia.2023.100030","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF), a progressive lung disease characterized by irreversible lung dysfunction caused by fibroblast proliferation and excessive collagen deposition, is the result of persistent chronic inflammation of the lung parenchyma. Although the pathogenesis is not fully understood, the role of immune mechanisms such as innate immune response, adaptive immunity and immune regulation, and cytokines in the pathophysiological mechanism of pulmonary fibrosis have been gradually recognized. There are currently limited drugs available to treat IPF, and long-term use of these drugs may have many adverse effects. With the elucidation of the underlying immunological pathogenesis, the development of more valuable drugs targeting the immune system becomes possible. This review introduces the immunological pathogenesis of pulmonary fibrosis and the emerging drugs targeting the immune system in recent years, aiming to provide insights into the mechanism and treatment direction of pulmonary fibrosis.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000284/pdfft?md5=ede37c38ed8fc0e930b29c60115f85e3&pid=1-s2.0-S2773216923000284-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139296634","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":"Sclareol exerts an anti-inflammatory effect, possibly through COXs inhibition pathway: In vivo and in silico studies","authors":"Abdullah Al Shamsh Prottay ,&nbsp;Mehedi Hasan Bappi ,&nbsp;Md Showkoth Akbor ,&nbsp;Afia Ibnath Asha ,&nbsp;Md Shimul Bhuia ,&nbsp;Aqib Adnan Shafin ,&nbsp;Md Nayem Mia ,&nbsp;Mohammad S. Mubarak ,&nbsp;Micheline de Azevedo Lima ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Muhammad Torequl Islam","doi":"10.1016/j.pscia.2023.100029","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100029","url":null,"abstract":"<div><p>Chronic and severe inflammation results in many diseases and disorders in humans. Currently, available conventional anti-inflammatory drugs have numerous mild-to-severe side effects. Thus, there is a need for safe, effective, affordable, and alternative anti-inflammatory drugs. This study aimed to evaluate the anti-inflammatory effect of sclareol (SCL), a diterpene alcohol that is the principal ingredient in the refined oil of <em>Salvia sclarea</em> (L.), through <em>in vivo</em> and <em>in silico</em> studies. First, we examined the individual and combined effects of SCL (5, 10, and 20 mg/kg) and standard drugs celecoxib (CXB) or ketoprofen (KPN) at 42 mg/kg (p.o.) on the formalin-induced inflammatory <em>Swiss</em> mice. Additionally, an <em>in silico</em> analysis was conducted to evaluate the potential anti-inflammatory mechanism of this study. For this, we examined the potentiality of SCL and standards to interact with cyclooxygenase (COX) -1 and COX-2 receptors. Our findings suggest that SCL exhibits a dose-dependent anti-inflammatory effect in mice. SCL-20 mg/kg significantly reduced the number of paw licks and paw edema diameters. Moreover, SCL-20 combined with CXB-42 and KPN-42 demonstrated better anti-inflammatory effects. In comparison to the standards, SCL revealed a comparable binding interaction with COX-1 and COX-2 receptors in the molecular docking study. Furthermore, SCL displayed remarkable pharmacokinetic characteristics. In conclusion, SCL significantly and dose-dependently reduced the number of paw licks and edema diameters in animals. Thus, SCL may be responsible for producing an anti-inflammatory effect by interacting with COX-1 and COX-2 receptors.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000272/pdfft?md5=c8ae6819910be7c13da5759b87e9ef94&pid=1-s2.0-S2773216923000272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138484084","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":"The effect of particle size on drug bioavailability in various parts of the body","authors":"Zi Hong Mok","doi":"10.1016/j.pscia.2023.100031","DOIUrl":"10.1016/j.pscia.2023.100031","url":null,"abstract":"<div><p>Multiple mechanisms are involved in driving the efficacy of drug delivery. Drug particle size is one of the challenges as particles need to be delivered from the external environment, into the circulation or interstitial fluid and transiting the cell membranes for cellular internalisation. Small particles are presumably easier to be internalised, yet they are not easy to retain as they are subject to fast clearance. Big particles do not cross biological barriers as easily, but their size distribution is easier to be controlled. Because of the various routes of administration, the size range of these particles will also need to be catered for the anatomical, biological, and dynamic barriers involved. This review hopes to provide an insight into the range of particle size that has been engineered for drug delivery via various routes of administration of the body, such as to cross the epithelium of gastrointestinal tract, lungs, skin, blood-brain barrier, kidney and liver, the eye, nose, and ear, the cancer tumour matrix and into the muscles. While successful drug delivery also depends on the material properties of the delivery systems and the bio/nano interface related properties, this review focuses on the importance of particle size for enhancing bioavailability at the various organs of the body.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000296/pdfft?md5=761880ad90cf562b5af20fa305e56c9a&pid=1-s2.0-S2773216923000296-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139296707","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":"Design, synthesis, characterization of ferulic acid and p-coumaric acid amide derivatives as an antibacterial/antioxidant agent","authors":"Chandani G. Halpani,&nbsp;Satyendra Mishra","doi":"10.1016/j.pscia.2023.100023","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100023","url":null,"abstract":"<div><p>Ferulic acid and <em>p</em>-coumaric acid, cinnamic derivatives of phenolic acid, have antibacterial, prooxidant, and antioxidant effects. In this study ferulic acid and <em>p</em>-coumaric acid amide derivatives were investigated for their antibacterial and antioxidant properties are described in this communication. The most effective conjugates against <em>B subtilis</em> were <strong>5b</strong> (IC₅₀: 215 ​± ​1.3 ​μM) and <strong>4d</strong> (IC₅₀: 336 ​± ​2.7 ​μM) and against <em>P. aeruginosa</em> were <strong>4b</strong> (IC₅₀: 365 ​± ​2.8 ​μM) and <strong>5b</strong> (IC₅₀: 341 ​± ​3.6 ​μM), whereas the none of conjugates were more effective against <em>E. coli</em> than reference Kanamycin. Conjugates <strong>5b</strong> was the most effective against <em>B subtilis</em> of all the synthesized conjugates, with IC₅₀ values of (IC₅₀: 215 ​± ​1.3 ​μM). The free radical scavenging capacity of each compound was determined using the DPPH and ABTS assays. Conjugates <strong>4b</strong> (IC₅₀: 53 ​± ​3.6 ​μM)<strong>, 4c</strong> (IC₅₀: 58 ​± ​1.3 ​μM)<strong>, 4d</strong> (IC₅₀: 57 ​± ​2.5 ​μM), <strong>5b</strong> (IC₅₀: 29 ​± ​1.5 ​μM) and <strong>4a</strong> (IC₅₀: 56 ​± ​4.3 ​μM) have greater antioxidant capacity than ferulic acid and ascorbic acid in the DPPH assay. Whereas in the ABTS assay, compounds <strong>4b (</strong>IC₅₀: 7 ​± ​1.8 ​μM), <strong>5b (</strong>IC₅₀: 5 ​± ​0.7 ​μM), <strong>4a (</strong>IC₅₀: 9 ​± ​3.2 ​μM), <strong>4g (</strong>IC₅₀: 7 ​± ​2.3 ​μM), and <strong>5a (</strong>IC₅₀: 8 ​± ​4.3 ​μM) showed more antioxidant activity than ferulic acid, <em>p</em>-coumaric acid and ascorbic acid. Thus, a large library of compounds derived from bile acid can be easily synthesized for extensive structure-activity relationship studies in order to identify the most appropriate antibacterial and antioxidant agents.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100023"},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000211/pdfft?md5=7e8e62c9a09a0b64e96c5bd87a97948f&pid=1-s2.0-S2773216923000211-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92064745","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":"Grafted tamarind kernel polysaccharide based Al3+ cross-linked hydrogel matrices for sustained release of drug in the gastrointestinal milieu","authors":"Arpita Saha ,&nbsp;Kaushik Mukherjee ,&nbsp;Bijaya Ghosh ,&nbsp;Tapan Kumar Giri","doi":"10.1016/j.pscia.2023.100022","DOIUrl":"10.1016/j.pscia.2023.100022","url":null,"abstract":"<div><p>Ionically cross-linked hydrogel serves as an excellent matrix material for the sustained delivery of drugs. Tablets prepared with tamarind kernel polysaccharide (TKP) as the sole matrix material could not provide sustained release of the incorporated drugs. The purpose of the work was to modify TKP and development of ionically cross-linked hydrogel matrix tablets for sustained drug delivery. Grafting of TKP was performed with methacrylic acid (MAA) following the free radical polymerization technique. Hydrogel matrix tablets using Al³⁺ ion cross-linked grafted TKP were prepared by direct compression method. Al³⁺ ions were found to considerably influence the erosion, swelling, and paracetamol release from the matrix tablet. Retardation of the erosion, swelling, and paracetamol release was observed with increasing the concentration of Al³⁺ ions. The hydrogel matrix tablets showed a slow release of drugs in an acidic medium and a relatively faster drug release in an alkaline medium. The optimized formulation having a co-polymer/aluminium hydroxide (Al(OH)₃) ratio of 1:1, exhibited sustained drug release action for more than 10 h with lower swelling and erosion of the gel matrix. We conclude that Al³⁺ ion cross-linked grafted TKP is an excellent matrix material for sustained delivery of drugs in the gastrointestinal milieu.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100022"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277321692300020X/pdfft?md5=158a22a7bf01c086116cfdf429a46e6a&pid=1-s2.0-S277321692300020X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135965854","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":"Emerging role of antioxidants in Alzheimer's disease: Insight into physiological, pathological mechanisms and management","authors":"Kamaljeet ,&nbsp;Shamsher Singh ,&nbsp;G.D. Gupta ,&nbsp;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}

{"title":"Biowaiver based on biopharmaceutics classification system: Considerations and requirements","authors":"Pratik R. Dhake ,&nbsp;Smita T. Kumbhar ,&nbsp;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 ,&nbsp;Junli Feng ,&nbsp;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}

{"title":"Matrine induces V-ATPase-dependent cytoplasmic vacuolation and inhibits the function of the lysosome in leukemia cells","authors":"Fanfan Yang ,&nbsp;Wang-jing Zhong ,&nbsp;Jialin Cao ,&nbsp;Junyu Tan ,&nbsp;Bohong Li ,&nbsp;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}