Pharmaceutical Science Advances最新文献

{"title":"Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice","authors":"Fei Teng,&nbsp;Haina Wang","doi":"10.1016/j.pscia.2025.100063","DOIUrl":"10.1016/j.pscia.2025.100063","url":null,"abstract":"<div><div>Cyclophosphamide (CTX) is a chemotherapeutic agent with cytotoxic and immunosuppressive activity. It is used to treat a wide variety of cancers and autoimmune diseases. However, side effects caused by its toxic metabolites, especially hepatotoxicity, limit its clinical application. The natural dihydroflavonol compound dihydromyricetin (DHM) has anticancer, anti-inflammatory, and antioxidant properties. This study aimed to evaluate the protective effects of DHM against CTX-induced hepatotoxicity in mice. Male ICR mice were pretreated with DHM (100, 200, and 400 ​mg/kg b.w.) orally before intraperitoneal injection with CTX (100 ​mg/kg b.w.) for 7 days. The mice were then sacrificed to analyze biochemical and histological parameters as well as metabolomics profiles. DHM ameliorated CTX-induced elevations in the liver index, alanine aminotransferase, aspartate transaminase, and malondialdehyde levels, and pathological changes and increased levels of glutathione and antioxidant enzymes, such as superoxide dismutase and catalase. Based on a KEGG pathway analysis of altered serum and liver metabolites, OXPHOS may play an important role in the observed protective effects. Further analysis revealed that DHM increased the activity of Na⁺-K⁺-ATPase in mice, which affected CTX-induced mitochondrial energy metabolism. To conclude, DHM protected against CTX-induced hepatotoxicity, possibly through reducing oxidative stress and regulating energy metabolism, providing a potential strategy for treatment and prevention.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437650","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004024","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":"Sample preparation of Hedyotis diffusa Willd. for two-dimensional gas chromatography-time of flight mass spectroscopic analysis enhanced chemical profiling","authors":"Duxin Li ,&nbsp;Xinying Du ,&nbsp;Wanru Bai ,&nbsp;Oliver J. Schmitz","doi":"10.1016/j.pscia.2024.100056","DOIUrl":"10.1016/j.pscia.2024.100056","url":null,"abstract":"<div><div><em>Hedyotis diffusa</em> Willd., a herbal remedy for cancer, has a complex chemical profile that is difficult to analyze in detail. Here, we introduce an optimized sample preparation method coupled with two-dimensional gas chromatography-time-of-flight mass spectrometry (GC ​× ​GC-TOF/MS) to enhance the chemical profiling of <em>H. diffusa</em>. By employing dichloromethane extraction for nonpolar compounds, aqueous extraction, and solid-phase extraction fractionation into moderately polar and polar fractions, we extracted and analyzed a comprehensive range of chemicals from <em>H. diffusa</em>. GC ​× ​GC-TOF/MS analysis revealed a rich chemical landscape, identifying 185, 325, and 483 peaks in the dichloromethane extract, solid-phase extraction elution, and unretained fractions, respectively. Library matching against known compounds confirmed 155, 178, and 184 hits with a similarity of 80% or greater. Notably, this method also involves group-type elution of steroids and anthraquinones, facilitating the identification and screening of similar compounds. This comprehensive approach to herbal chemical analysis offers a high-dimensional perspective and greatly advances our understanding of the chemical constituents of <em>H. diffusa</em>.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702807","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":"Quercetin inhibits malignant progression of high metastatic advanced colon cancer in hypoxia via suppressing ROS and PI3K/AKT pathway","authors":"Pengfei Shang ,&nbsp;Jiawei Yang ,&nbsp;Lijun Shao ,&nbsp;Chao Sun ,&nbsp;Jianbo Ji ,&nbsp;Xiaoyan Wang ,&nbsp;Zongxue Zheng ,&nbsp;Xiuli Guo","doi":"10.1016/j.pscia.2024.100057","DOIUrl":"10.1016/j.pscia.2024.100057","url":null,"abstract":"<div><div>Advanced metastatic colon cancer is difficult to treat with existing chemotherapy medicines, and hypoxic microenvironment is closely related to angiogenesis and distant metastasis of colon cancer. Quercetin, a natural flavonoid, has been shown anti-tumor effects. The aim of this study is to investigate the effect of quercetin alone or combined with 5-FU on the invasion and metastasis of advanced metastatic or primary colorectal cancer in hypoxic environment. The cytotoxicity of quercetin or/and 5-FU on colon cancer cells using CCK8 assay, Hoechst 33342, flow cytometry and AO staining. The effects of quercetin or/and 5-FU on the migration and invasion were determined by transwell, cell scratching method and murine xenograft models. The potential mechanism was explored by Western blot and immunofluorescent assay. The results revealed quercetin effectively inhibited the invasion and migration of high metastatic advanced colon cancer LOVO cells under hypoxia through the inhibition of ROS and the expression of HIF-1α and PI3K/AKT pathway. Combination of quercetin and 5-FU could promote the inhibition of 5-FU on the invasion and migration of LOVO cells. Moreover, quercetin also significantly inhibited the proliferation of either LOVO cells or HT-29 ​cells under hypoxia by inducing apoptosis and autophagy, particularly, showing stronger inhibition on HT-29 ​cells than LOVO cells. In conclusion, quercetin inhibited the invasion and migration of advanced metastatic colon cancer LOVO cells under hypoxia through inhibition of ROS and HIF-1α expression and the downregulation of PI3K/AKT pathway. Moreover, quercetin alone or in combination with 5-FU can effectively inhibit the invasion and migration of high metastatic advanced colon cancer. Quercetin has the potential to be used as an effective anti-colon cancer drug alone or in combination for the clinical treatment of advanced colon cancer.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654966","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":"Corrigendum to “Natural product databases for drug discovery: Features and applications” [Pharmaceut. Sci. Adv. 2 (2024) 100050]","authors":"Tao Zeng,&nbsp;Jiahao Li,&nbsp;Ruibo Wu","doi":"10.1016/j.pscia.2024.100054","DOIUrl":"10.1016/j.pscia.2024.100054","url":null,"abstract":"","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578357","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":"Preparation and characterization of micellar nanoparticles using crude saponins from five Congolese plant species","authors":"Pathy B. Lokole ,&nbsp;Nadège K. Ngombe ,&nbsp;Dave I. Motomba ,&nbsp;Justin B. Safari ,&nbsp;Michel K. Mpuza ,&nbsp;Rui W.M. Krause ,&nbsp;Paulin K. Mutwale ,&nbsp;Christian I. Nkanga","doi":"10.1016/j.pscia.2024.100055","DOIUrl":"10.1016/j.pscia.2024.100055","url":null,"abstract":"<div><div>Nanoparticles (NPs) have significantly advanced medical applications, including drug delivery, immunotherapy, vaccines, and diagnostics. This versatility is partly due to the potential of tailoring NPs from multiple sources. Notably, saponins, amphiphilic plant metabolites, have shown great promise in NP formulation. This study explored the development of micellar NPs using saponin crude fractions (SCFs) extracted from five Congolese plant species: <em>Millettia laurentii, Penthaclethra eetveldeana</em>, <em>Schwenckia americana</em>, <em>Musa paradisiaca,</em> and <em>Musa sapientum</em>. Plant materials were subjected to histological examination through optical microscopy, while phytochemical analyses by thin-layer chromatography confirmed the presence and predominance of saponins in the SCFs. We used a phthalocyanine-isoniazid hybrid (<em>Pc</em>-INH) as a hydrophobic probe to determine the critical micellar concentrations of SCFs and explore the feasibility of developing cost-effective saponin-based micelles (SBMs). Phytochemical screenings indicated saponins in the extracted SCF and other metabolites like flavonoids, phenolic acids, and anthocyanins. Dynamic light scattering and transmission electron microscopy analyses revealed the formation of nano-sized particles, particularly noting SBMs from <em>P. eetveldeana</em> with notable dimensions (157 ​nm, PDI of 0.27, and ZP of −4.01 ​mV) and spherical shape. The micelles from <em>M. laurentii</em> exhibited superior encapsulation efficiency for <em>Pc</em>-INH (55%) compared to control micelles formulated from pure saponin (33%). <em>In vitro</em> tests showed that <em>M. paradisiaca</em> SBMs have the best safety profile for red blood cells, with a 10% hemolysis rate compared to a 150% rate for bulk SCFs. However, there is a significant difference between SCFs and SBMs (<em>p</em> ​&lt; ​0.0001). The release profiles of <em>M. paradisiaca</em> SBMs show a pH-dependent relationship, suggesting potential for stimuli-responsive drug delivery. This work lays the foundation for leveraging plant-derived crude saponins in nanotechnology, emphazising their encapsulation efficiency, controlled release potential, and biocompatibility, paving the way for the cost-effective production of high-value biomedical NPs.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654967","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":"Sos1 deficiency ameliorates oncogenic KRAS-mediated hematopoietic stem cell exhaustion and myeloid progenitor expansion","authors":"Maoshuo Yang ,&nbsp;Lanlan Liu ,&nbsp;Yaqing Miao ,&nbsp;Yongxin Jia ,&nbsp;Sijia Tian ,&nbsp;Limei Wang ,&nbsp;Fabao Liu ,&nbsp;Xiaona You","doi":"10.1016/j.pscia.2024.100053","DOIUrl":"10.1016/j.pscia.2024.100053","url":null,"abstract":"<div><div>Constitutive <em>KRAS</em> activating mutations are prevalent in hematopoietic malignancies. Our previous study showed that the deficiency of <em>Sos1</em> prolongs the survival of <em>Kras</em>^G12D/+ mice. However, whether <em>Sos1</em> deletion ameliorates oncogenic <em>Kras</em>-mediated hematopoietic defects remains unknown. Here, we found that <em>Sos1</em> deletion restored <em>Kras</em>^G12D-mediated hematopoietic stem cell (HSC) and multipotent progenitor (MPP) exhaustion by maintaining quiescent HSC and MPP pools. <em>Sos1</em> knockout attenuates hyperactivation of ERK signaling in <em>Kras</em>^G12D/+ HSCs and MPPs. Additionally, the loss of <em>Sos1</em> reduced the frequency and colony-forming capability of myeloid progenitors in <em>Kras</em>^G12D/+ mice, resulting in a less severe myeloproliferative neoplasm phenotype. Moreover, <em>Sos1</em> knockout prolonged the survival of <em>Kras</em>^G12D/+ mice in a cell-autonomous manner. In general, cells with <em>Sos1</em> deletion remained sensitive to MEK and JAK inhibition, suggesting that combined Sos1 inhibition and other therapies could be a promising strategy for the treatment of oncogenic <em>KRAS</em>-driven leukemia.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323560","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":"Novel targeted therapies in chronic myeloid leukemia","authors":"Muhammad Sameer Ashaq ,&nbsp;Qian Zhou ,&nbsp;Zhuoran Li ,&nbsp;Baobing Zhao","doi":"10.1016/j.pscia.2024.100052","DOIUrl":"10.1016/j.pscia.2024.100052","url":null,"abstract":"<div><div>Chronic myeloid leukemia (CML) is the chronic proliferation of myeloid-lineage cells in hematopoietic stem cells driven by the BCR-ABL1 fusion oncoprotein. The development of tyrosine kinase inhibitors (TKIs) has revolutionized CML treatment; however, resistance and intolerance to these drugs remain key challenges. CML stem cells (CMLSCs) are the root cause of CML relapse and resistance to TKIs. This review discusses novel targeted therapeutic options targeting CMLSCs to address the abovementioned challenges. Numerous novel TKIs, such as flumatinib, vodobatinib, and olverembatinib, have shown remarkable potential against BCR-ABL1, but few, including AT9283, MK0457, and DCC-2036, are still undergoing clinical trials. Targeting CMLSCs is a fundamental therapeutic approach for the treatment of CML progression, relapse, and TKI resistance. In this review, novel agents targeting core signaling pathways and novel molecular targets in CMLSCs are highlighted. Currently, multiple approaches, such as targeting epigenetic modifications or microRNAs and altering metabolism in leukemic cells, have shown desirable effects in treating CML. Immunotherapy, autophagy inhibitors, and protein synthesis inhibitors are novel and effective therapies for the treatment of CML. Although various therapeutic strategies have provided exceptional results in the treatment of CML, the challenges of TKI resistance and CML remission or relapse remain. Therefore, current therapeutic approaches and targeted therapies have practical and clinical implications for achieving desirable outcomes.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000187/pdfft?md5=3000f62f1afd9a230b72a79c8c7aa48b&pid=1-s2.0-S2773216924000187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311478","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":"Chemical composition and neuroprotective activity of hemp seed aqueous extract and their chemotaxonomic significance","authors":"Siqing Bu ,&nbsp;Jianbo Ji ,&nbsp;Mei Yang ,&nbsp;Jieyue Sun ,&nbsp;Jiaozhen Zhang ,&nbsp;Shunmeng Qian ,&nbsp;Hongxiang Lou ,&nbsp;Peihong Fan","doi":"10.1016/j.pscia.2024.100051","DOIUrl":"10.1016/j.pscia.2024.100051","url":null,"abstract":"<div><p>Fructus Cannabis (hemp seed) is important in food and traditional Chinese medicinal applications. Several studies have shown it has antioxidant, antiaging, anti-inflammatory, and neuroprotective properties. Studies have reported its anti-Alzheimer's disease effects. However, its active substances have not been defined, and little is known about the chemical constituents of the aqueous extract. The chemical profile of the aqueous extract of Fructus Cannabis (EFC) was obtained via isolation, structural identification, and qualitative and quantitative analyses. Twenty-seven compounds were identified, including seven nucleosides (<strong>1</strong>–<strong>7</strong>), five phenylpropanamides (<strong>8</strong>–<strong>11</strong>, and <strong>24</strong>), three alkaloids (<strong>15</strong>, <strong>16</strong>, and <strong>26</strong>), two cyclic dipeptides (<strong>17</strong> and <strong>25</strong>), and one pyrimidine (<strong>19</strong>). Compounds <strong>1</strong>, <strong>3</strong>–<strong>7</strong>, <strong>12</strong>, <strong>14</strong>–<strong>19</strong>, and <strong>21</strong>–<strong>27</strong> were not reported previously in the Cannabis genus. Therefore, their chemotaxonomic significance is discussed. Neuroprotective activity screening revealed that EFC and the isolated compounds, particularly <strong>9</strong>, <strong>11</strong>, and 17, showed significant neuroprotective effects in PC12 ​cells (rat pheochromocytoma cells). The novel object recognition experiment and Nissl staining showed that EFC improved cognitive impairment in APP/PS1 mice and that EFC intervention reduced the number of senile plaques. These findings will contribute to the utility of Fructus Cannabis.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000175/pdfft?md5=473f3a295c4cc4dd511a7bb5a3edf272&pid=1-s2.0-S2773216924000175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173750","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":"Natural product databases for drug discovery: Features and applications","authors":"Tao Zeng,&nbsp;Jiahao Li,&nbsp;Ruibo Wu","doi":"10.1016/j.pscia.2024.100050","DOIUrl":"10.1016/j.pscia.2024.100050","url":null,"abstract":"<div><p>Natural products (NPs) exhibit diverse chemical structures and biological activities that make them valuable sources for drug discovery. With advancements in computational technology, computation-enabled natural drug discovery is gaining increasing significance, with NP databases playing a pivotal role. In light of this, we first summarize the key features of NP databases, including structural data, property annotations, biological sources, biosynthetic pathways, and web interfaces. Subsequently, the wide applications of these databases in drug discovery, such as virtual screening, knowledge graph construction, and molecular generation, are reviewed. We further discuss the puzzle of database development, focusing on data quality and updating. Finally, we emphasize the pivotal role of team collaboration and toolkit innovation in harnessing the immense potential of NP-related databases to accelerate bioactivity mining, structure modification, and manufacturing. This review aims to elucidate the key features and applications of NP databases, with the goal of aiding researchers in developing and maintaining high-quality NP databases for drug discovery.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000163/pdfft?md5=d93f2dd8732dd7264d746b01693aaec6&pid=1-s2.0-S2773216924000163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168004","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}