Pharmaceutical Science Advances最新文献

{"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}

{"title":"Delayed treatment with hydro-ethanolic extract of Khaya grandifoliola protects mice from acetaminophen-hepatotoxicity through inhibition of c-Jun N-terminal kinase phosphorylation and mitochondrial dysfunction","authors":"Arnaud Fondjo Kouam ,&nbsp;Ibrahim Njingou ,&nbsp;Nina Jeannette Pekam Magoudjou ,&nbsp;Hamed Bechir Ngoumbe ,&nbsp;Philipe Herman Nfombouot Njitoyap ,&nbsp;Elisabeth Menkem Zeuko'o ,&nbsp;Frédéric Nico Njayou ,&nbsp;Paul Fewou Moundipa","doi":"10.1016/j.pscia.2024.100049","DOIUrl":"10.1016/j.pscia.2024.100049","url":null,"abstract":"<div><p>The use of N-acetylcysteine against acetaminophen(APAP)-induced hepatotoxicity, a leading cause of liver injury, has several drawbacks, including short therapeutic windows. <em>Khaya grandifoliola</em> (Meliaceae) has been traditionally used to manage liver-related diseases, and many reports have confirmed its hepatoprotective properties. However, its therapeutic potential as an antidote against APAP-induced hepatotoxicity has yet to be proven in a clinically relevant model. This study aimed to verify the efficacy of delayed treatment with the hydroethanolic extract of <em>K. grandifoliola</em> (KgE) in suppressing the early injury phase of APAP pathophysiology. KgE was analyzed using HPLC/UV. Acute oral toxicity tests were conducted in mice to determine the therapeutic dose of KgE. Mice were treated with 300 ​mg/kg APAP; 1h and 12h later, they were treated with either predetermined doses of KgE or 20 ​mg/kg c-Jun N-Terminal Kinase (JNK) inhibitor SP600125, which served as a reference antidote. At 6h and 24h after APAP treatment, the parameters of liver damage and mitochondrial dysfunction, phosphorylation of JNK, and mitochondrial translocation were assessed. KgE at a dose of 5000 ​mg/kg was safe for mice. Accordingly, 100, 200, and 400 ​mg/kg were selected as curative treatments. Delayed administration of KgE reversed the histopathological changes in the liver, inhibited serum levels of alanine aminotransferase, reduced the liver content of nitric oxide and malondialdehyde, and restored hepatic glutathione pools and superoxide dismutase and catalase activities in APAP-intoxicated mice. Moreover, KgE prevented APAP-induced JNK phosphorylation and p-JNK mitochondrial translocation and rescued the activities of mitochondrial enzyme complexes II and V. HPLC/UV analysis revealed the presence of gallic acid, Quercetin and Silibinin, with retention times of 3.77, 11.63 and 11.95 ​min as the major active ingredients present in KgE. Our findings demonstrate that post-treatment with KgE protects the mouse liver from APAP-hepatotoxicity through the inhibition of JNK activation and mitochondrial dysfunction<strong>.</strong></p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000151/pdfft?md5=5d0d9d2a2dcad48b981b9abb76c4d105&pid=1-s2.0-S2773216924000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088789","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":"Targeted drug conjugates in cancer therapy: Challenges and opportunities","authors":"Geng Jia,&nbsp;Yuqi Jiang,&nbsp;Xiaoyang Li","doi":"10.1016/j.pscia.2024.100048","DOIUrl":"10.1016/j.pscia.2024.100048","url":null,"abstract":"<div><div>Traditional chemotherapy is often accompanied by off-target toxicity, resulting in adverse side effects and driving the development of targeted therapies. Targeted drug conjugates (TDCs) typically comprise targeting ligands, such as specific antibodies, peptides, or small molecules, attached to a cytotoxic agent via a chemical linker. In this study, we briefly discussed the molecular aspects of the key components of TDCs and the mechanisms by which these key factors exert their activity. Moreover, we reviewed FDA-approved TDCs and promising candidates in clinical trials and discussed current challenges and future directions for TDC development, providing insights for the research and development of novel cancer therapeutics using TDCs. TDCs combine the advantages of highly specific targeting and a potent killing effect, enabling accurate and efficient cancer cell elimination. Food and Drug Administration (FDA)-approved antibody-drug conjugates (ADCs) have shown good efficacy in treating various cancers; however, they still present limitations such as immunogenicity, hematotoxicity, and complex pharmacokinetics. Smaller peptide-drug conjugates (PDCs) and small molecule-drug conjugates (SMDCs) may combine the advantages of ADCs while overcoming some of their limitations, thereby presenting more efficacious and safer alternatives. TDCs enhance the therapeutic effects of cytotoxic agents and reduce their adverse effects. However, tumor heterogeneity, limited transmembrane permeability, and drug resistance pose significant challenges for TDCs, potentially affecting their therapeutic efficacy. Nevertheless, TDCs are a promising therapeutic approach for cancer treatment, achieving precise drug delivery while minimizing toxicity and side effects on normal cells.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277321692400014X/pdfft?md5=846700d9b5859bfcc716e905e2620342&pid=1-s2.0-S277321692400014X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314135","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":"Targeting active RAS with molecular glue","authors":"Wenjing Su ,&nbsp;Xuben Hou","doi":"10.1016/j.pscia.2024.100047","DOIUrl":"10.1016/j.pscia.2024.100047","url":null,"abstract":"<div><p>Activating mutations in RAS genes, notably KRASG12C, are pervasive in numerous cancers, presenting formidable challenges to therapy due to their elusive druggability. The landmark discovery of KRASG12C allosteric inhibitors marked a transformative milestone in cancer treatment, resulting in the approval of sotorasib and adagrasib. However, limitations in the depth and duration of response prompted the quest for alternative strategies. Recently, Holderfield et al., Wasko et al., and Jiang et al. reported on tri-complex inhibitors, namely RMC-7977 and RMC-6236, targeting activated RAS variants, demonstrating promising preclinical efficacy surpassing adagrasib. These advancments signify a paradigm shift in RAS oncology, promising enduring therapeutic benefits and warranting further clinical exploration.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100047"},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000138/pdfft?md5=acdbb72e8561efb2719e3f80e8eeec17&pid=1-s2.0-S2773216924000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622985","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":"Dual-targeting liposomal delivery of sorafenib and docetaxel for enhanced synergistic therapy in advanced hepatocellular carcinoma","authors":"Yawen Yao ,&nbsp;Yue Hu ,&nbsp;Xinwang Meng ,&nbsp;Fenyan Feng ,&nbsp;Feng Xu ,&nbsp;Guangji Wang ,&nbsp;Hua Yu ,&nbsp;Juan Li","doi":"10.1016/j.pscia.2024.100046","DOIUrl":"10.1016/j.pscia.2024.100046","url":null,"abstract":"<div><p>Patients with advanced hepatocellular carcinoma (HCC) are not sensitive to sorafenib (SOR), therefore, combination therapy is required. In this study, an improved thin-film dispersion and post-insertion anchoring technique was utilized to construct a dual-targeted co-delivery SOR and docetaxel (DTX) liposome drug delivery system, folate/chondroitin sulfate with SOR/DTX-modified liposomes (FA/CS@SDLP), to jointly enhance the anti-recurrence and metastasis of HCC. FA/CS@SDLP can establish the gradual release of the two drugs because of successful lysosomal escape in the condensed hyaluronidase environment. The results indicated that modification with folate (FA) and chondroitin sulfate (CS) significantly enhanced the cellular uptake of FA/CS@SDLP and the internalization of SOR/DTX in HepG2 cells through FA and CD44 receptor-mediated endocytosis. Compared to free drugs or the mono-targeted liposomal system (FA@SDLP), FA/CS@SDLP presented higher potency against HepG2 cells regarding pro-apoptosis, anti-proliferation, and anti-metastasis (migration and invasion). Moreover, a more satisfactory antitumor efficacy was observed for FA/CS@SDLP in the pulmonary metastasis of HCC in a mouse model. In summary, dual-targeted co-delivery of liposomes can synergistically treat HCC recurrence and metastasis, providing a new approach for the clinically accurate treatment of HCC.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000126/pdfft?md5=ea9c0c8c42b198b328305e7f15c725ed&pid=1-s2.0-S2773216924000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141697484","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":"Progresses in the study of polysaccharide from medicinal plants of the Asclepiadaceae family","authors":"He Xiao ,&nbsp;Ziqing Zeng ,&nbsp;Wenjie Jiang","doi":"10.1016/j.pscia.2024.100045","DOIUrl":"https://doi.org/10.1016/j.pscia.2024.100045","url":null,"abstract":"<div><p>Medicinal plants from the Asclepiadaceae family, such as Luo Mo (<em>Metaplexis japonica</em> Makino), Xu Changqing (<em>Cynanchum paniculatum</em>), and Bai Wei (<em>Cynanchum atratum</em> Bge.), have long been staples in Traditional Chinese Medicine (TCM) due to their wide range of pharmacological activities (Su et al., 2021) [1]. These beneficial properties are largely attributed to compounds like saponins, alkaloids, and polysaccharides. Polysaccharides, in particular, are vital components in TCM and have garnered increasing attention for their diverse therapeutic effects. Polysaccharides from Asclepiadaceae plants are reported to exhibit a variety of pharmacological activities, including anti-radiation, anti-tumor, anti-fatigue, antioxidant, anti-hyperlipidemic, immune-boosting, and liver-protective effects. These polysaccharides have complex structures made up of different monosaccharides, contributing to their wide range of activities. In this review, we provide a comprehensive summary of the isolation, purification, structural characterization, and pharmacological activities of polysaccharides from medicinal plants in the Asclepiadaceae family. We begin by outlining the methods used for the extraction, isolation, and purification of these polysaccharides. Next, we delve into the pharmacological activities of the isolated polysaccharides. Finally, we discuss the potential clinical applications of these polysaccharides in treating various diseases and highlight areas that require further investigation.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000114/pdfft?md5=d3e3439805917f3195d27ad1e679cd87&pid=1-s2.0-S2773216924000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594753","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":"Fuel-propelled nanomotors for acute kidney injury applications","authors":"Weixin Wang ,&nbsp;Rui Gao ,&nbsp;Lin Zhang ,&nbsp;Zhongchao Wang ,&nbsp;Jiahui Sun ,&nbsp;Lei Luo ,&nbsp;Min Pan ,&nbsp;Miaofang Hong ,&nbsp;Jianming Wu ,&nbsp;Qibing Mei ,&nbsp;Ke Tong ,&nbsp;Yini Wang ,&nbsp;Lingyan Qiao ,&nbsp;Fei Tong","doi":"10.1016/j.pscia.2024.100044","DOIUrl":"https://doi.org/10.1016/j.pscia.2024.100044","url":null,"abstract":"<div><p>Acute kidney injury (AKI) is characterized by a rapid loss of renal metabolic function and a high mortality rate. Although significant progress has been made in developing targeted drugs for AKI treatment, issues such as inadequate antioxidant effects and poor renal enrichment efficiency remain. Nanomotors can enhance drug delivery efficiency in AKI treatments through self-propulsion in the microenvironment or via external stimuli. We reviewed recent progress in the targeted treatment of AKI with nanomotors, focusing on their contribution to targeted drug delivery at different stages and combined treatments. Current limitations and future development directions are also discussed.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000102/pdfft?md5=4504c164042e6d4a1599cfcc3339045c&pid=1-s2.0-S2773216924000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594752","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":"Possible hemoglobin enhancing effect of phytol in methotrexate-induced folate deficient Swiss albino mice: In vivo and in silico studies","authors":"Muhammad Torequl Islam ,&nbsp;Raihan Chowdhury ,&nbsp;Md Sakib Al Hasan ,&nbsp;Salehin Sheikh ,&nbsp;Md Shimul Bhuia ,&nbsp;Sumaya Akter Bithi ,&nbsp;Most Israt Jahan Oni ,&nbsp;Mehedi Hasan Bappi ,&nbsp;Siddique Akber Ansari ,&nbsp;Elaine C.P. Lucetti ,&nbsp;Catarina M. Tahim ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Irfan Aamer Ansari","doi":"10.1016/j.pscia.2024.100043","DOIUrl":"10.1016/j.pscia.2024.100043","url":null,"abstract":"<div><p>The diterpenoid phytol is evidently acting against anemia in experimental animals. However, the molecular mechanisms behind this issue are yet to be discovered. This study aimed to evaluate phytol's effect on methotrexate-induced folate-deficient animals through in vivo and in silico studies. For this, a total of thirty adult male Swiss albino mice were randomly divided into six different groups, namely the normal control (vehicle), the negative control (folate deficiency inducer, methotrexate 3 ​mg/kg), the standard (folic acid 1.5 ​mg/kg), two test groups comprising phytol 25 and 50 ​mg/kg, and a combined group composed of the standard and highest test doses of phytol. Except for the vehicle, all groups were treated with methotrexate for the first 3 days (once/day) to induce folate deficiency. Then followed by the respective treatment once a day for 3 days. Hemoglobin (Hb) level was measured from the peripheral blood (by tail cutting) on days 1st (before treatment), 4th (after methotrexate treatment), and 7th (after treatment). On the other hand, the computational studies were performed by PyMol, PyRex, Discovery Studio, and other complementary tools. Findings suggest that phytol significantly (<em>p</em> ​&lt; ​0.05) augmented Hb levels that are altered by methotrexate-induced reduction of Hb levels in animals dose-dependently. The combination also augmented Hb levels in animals; however, its effect was slightly lower than the individual groups (standard and test). In the in silico study, phytol showed good binding capacity (binding energy: −7.0 ​kcal/mol) with dihydrofolate reductase (DHFR). In conclusion, phytol may act against folate deficiency by altering methotrexate's impacts in animals, possibly through interacting with DHFR. Further validated research is necessary to develop phytol as an anti-anemia drug in the near future.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000096/pdfft?md5=bfaea545e629e34b31944f3178097e2e&pid=1-s2.0-S2773216924000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141407753","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}