Pub Date : 2024-11-19DOI: 10.1016/j.fitote.2024.106307
Li-Fu Liu, Wei Zhao, Patchara Pedpradab, Jun Wu, Li Shen
Ten new limonoids, named xylomolones E-N (1-10), and two new protolimonoids, named xylomolones O (11) and P (12), were isolated from seeds of the Thai mangrove Xylocarpus moluccensis, together with the known compound, hispidone acetonide (13). The structures of these compounds were established by extensive NMR spectroscopic data, single-crystal X-ray diffraction analysis, and comparison of experimental ECD spectra. The absolute configurations of xylomolones E (1) and L (8) were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation. Xylomolones E-L (1-8) are mexicanolide-type limonoids, among which xylomolones J (6) and K (7) contain a C7/C28δ-lactone ring, whereas xylomolones M (9) and N (10) are phragmalin-type limonoids. Xylomolones O (11) and P (12) are two new protolimonoids. In addition, the 1H and 13C NMR spectroscopic data for hispidone acetonide (13) was first assigned completely. In bioassay, xylomolones F (2), M (9), and P (12) exhibited moderate inhibitory activity against the production of NO in LPS-induced RAW 264.7 cells with IC50 values of 31.54 ± 7.27, 62.84 ± 17.62, and 22.7 ± 6.56 μM, respectively.
从泰国红树林 Xylocarpus moluccensis 的种子中分离出了 10 种新的柠檬醛类化合物,分别命名为木犀草酮 E-N (1-10),以及两种新的原木犀草酮类化合物,分别命名为木犀草酮 O (11) 和 P (12),还有已知的化合物--丙酮庚二酮 (13)。这些化合物的结构是通过大量的核磁共振光谱数据、单晶 X 射线衍射分析和实验 ECD 光谱对比确定的。通过使用 Cu Kα 辐射进行单晶 X 射线衍射分析,明确确定了木糖醇酮 E (1) 和 L (8) 的绝对构型。木糖醇内酯 E-L(1-8)属于墨西哥内酯型柠檬酸类化合物,其中木糖醇内酯 J(6)和 K(7)含有一个 C7/C28δ 内酯环,而木糖醇内酯 M(9)和 N(10)属于葭苷型柠檬酸类化合物。木糖醇酮 O (11) 和 P (12) 是两种新的原柠檬酸类化合物。此外,还首次完整地分配了丙酮桧酮(13)的 1H 和 13C NMR 光谱数据。在生物测定中,木犀草酮 F (2)、M (9) 和 P (12) 对 LPS 诱导的 RAW 264.7 细胞产生的 NO 具有中等程度的抑制活性,IC50 值分别为 31.54 ± 7.27、62.84 ± 17.62 和 22.7 ± 6.56 μM。
{"title":"Ten limonoids and three protolimonoids from the Thai mangrove Xylocarpus moluccensis.","authors":"Li-Fu Liu, Wei Zhao, Patchara Pedpradab, Jun Wu, Li Shen","doi":"10.1016/j.fitote.2024.106307","DOIUrl":"https://doi.org/10.1016/j.fitote.2024.106307","url":null,"abstract":"<p><p>Ten new limonoids, named xylomolones E-N (1-10), and two new protolimonoids, named xylomolones O (11) and P (12), were isolated from seeds of the Thai mangrove Xylocarpus moluccensis, together with the known compound, hispidone acetonide (13). The structures of these compounds were established by extensive NMR spectroscopic data, single-crystal X-ray diffraction analysis, and comparison of experimental ECD spectra. The absolute configurations of xylomolones E (1) and L (8) were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation. Xylomolones E-L (1-8) are mexicanolide-type limonoids, among which xylomolones J (6) and K (7) contain a C<sub>7</sub>/C<sub>28</sub>δ-lactone ring, whereas xylomolones M (9) and N (10) are phragmalin-type limonoids. Xylomolones O (11) and P (12) are two new protolimonoids. In addition, the <sup>1</sup>H and <sup>13</sup>C NMR spectroscopic data for hispidone acetonide (13) was first assigned completely. In bioassay, xylomolones F (2), M (9), and P (12) exhibited moderate inhibitory activity against the production of NO in LPS-induced RAW 264.7 cells with IC<sub>50</sub> values of 31.54 ± 7.27, 62.84 ± 17.62, and 22.7 ± 6.56 μM, respectively.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106307"},"PeriodicalIF":2.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.fitote.2024.106304
Zhuoliang Chu, Qingmei Sun, Meiqin Mao, Yutong Wu, Le Yu, Jingyi Xu, Kaohua Liu, Luping Qin, Bo Zhu
Huperzia serrata (HS) has been a staple of traditional Chinese medicine for centuries, revered for its efficacy in treating various ailments such as pain relief, hemostasis, detoxification, dehumidification, and heat clearing. This review offers an in-depth summary of the botany, traditional utilization, pharmacology, pharmacokinetics, phytochemistry, and safety profile of HS and intends to shed light on potential future research directions and applications of this plant. Information on HS was gathered from ScienceDirect, PubMed, Springer, Sci Finder, Baidu Scholar, and Google Scholar. Over 94 compounds have been separated and identified from HS, including alkaloids, terpenoids, volatile oils, flavonoids, and polysaccharides. Both crude extracts and purified compounds from HS have shown promise in treating a spectrum of conditions, including Alzheimer's disease, epilepsy, pain, cancer, and inflammation. These extracts and compounds exhibit diverse pharmacological properties, including neuroprotective, anti-Alzheimer's, anti-epileptic, analgesic, cardioprotective, hepatoprotective, antioxidant, and anticancer activities. Pharmacological investigations support the traditional use of HS and may validate the folk medicinal use of HS to treat many chronic diseases. Current literature suggests that the bioactivity of HS is largely attributed to its alkaloids and polysaccharides. However, further exploration is warranted to comprehensively understand the structure-function relationship of these constituents, molecular mechanisms, and their potential synergistic and antagonistic interactions. Moreover, additional modern pharmacological explorations are necessary to validate the traditional use of HS such as promoting hemostasis, treating tuberculosis, hemorrhoids, and diarrhea. Therefore, there is a pressing need for comprehensive investigations to fully assess HS' medicinal properties and therapeutic potential.
{"title":"Pharmacology, phytochemistry, and traditional uses of Huperzia serrata (Thunb. ex Murray) Trev.","authors":"Zhuoliang Chu, Qingmei Sun, Meiqin Mao, Yutong Wu, Le Yu, Jingyi Xu, Kaohua Liu, Luping Qin, Bo Zhu","doi":"10.1016/j.fitote.2024.106304","DOIUrl":"https://doi.org/10.1016/j.fitote.2024.106304","url":null,"abstract":"<p><p>Huperzia serrata (HS) has been a staple of traditional Chinese medicine for centuries, revered for its efficacy in treating various ailments such as pain relief, hemostasis, detoxification, dehumidification, and heat clearing. This review offers an in-depth summary of the botany, traditional utilization, pharmacology, pharmacokinetics, phytochemistry, and safety profile of HS and intends to shed light on potential future research directions and applications of this plant. Information on HS was gathered from ScienceDirect, PubMed, Springer, Sci Finder, Baidu Scholar, and Google Scholar. Over 94 compounds have been separated and identified from HS, including alkaloids, terpenoids, volatile oils, flavonoids, and polysaccharides. Both crude extracts and purified compounds from HS have shown promise in treating a spectrum of conditions, including Alzheimer's disease, epilepsy, pain, cancer, and inflammation. These extracts and compounds exhibit diverse pharmacological properties, including neuroprotective, anti-Alzheimer's, anti-epileptic, analgesic, cardioprotective, hepatoprotective, antioxidant, and anticancer activities. Pharmacological investigations support the traditional use of HS and may validate the folk medicinal use of HS to treat many chronic diseases. Current literature suggests that the bioactivity of HS is largely attributed to its alkaloids and polysaccharides. However, further exploration is warranted to comprehensively understand the structure-function relationship of these constituents, molecular mechanisms, and their potential synergistic and antagonistic interactions. Moreover, additional modern pharmacological explorations are necessary to validate the traditional use of HS such as promoting hemostasis, treating tuberculosis, hemorrhoids, and diarrhea. Therefore, there is a pressing need for comprehensive investigations to fully assess HS' medicinal properties and therapeutic potential.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106304"},"PeriodicalIF":2.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.fitote.2024.106306
Yulu Tian, Yazi Wei, Haowen Luo, Xinyi Chen, Jie Ma, Yingda Zang, Tiantai Zhang, Dongming Zhang, Chuangjun Li
Two undescribed diterpenoids (1-2) and three lignans (3a/3b, 4a), together with sixteen known compounds (4b, 5-9, 10a/10b-14a/14b) were obtained from the stems of Tripterygium wilfordii (T. wilfordii). The structures of these new compounds were elucidated by detailed spectroscopic analyses, and their absolute configurations were estabished by ECD calculations. Some compounds exhibited moderate inhibitory activities against IL-6 production in LPS-stimulated RAW 264.7 macrophages in vitro. Compound 5 showed significant anti-inflammatory activity in vitro (IC50, 0.77 μM) and inhibited macrophage polarization towards a pro-inflammatory phenotype.
{"title":"Diterpenoids and lignans from the stems of Tripterygium wilfordii and their anti-inflammatory activities.","authors":"Yulu Tian, Yazi Wei, Haowen Luo, Xinyi Chen, Jie Ma, Yingda Zang, Tiantai Zhang, Dongming Zhang, Chuangjun Li","doi":"10.1016/j.fitote.2024.106306","DOIUrl":"https://doi.org/10.1016/j.fitote.2024.106306","url":null,"abstract":"<p><p>Two undescribed diterpenoids (1-2) and three lignans (3a/3b, 4a), together with sixteen known compounds (4b, 5-9, 10a/10b-14a/14b) were obtained from the stems of Tripterygium wilfordii (T. wilfordii). The structures of these new compounds were elucidated by detailed spectroscopic analyses, and their absolute configurations were estabished by ECD calculations. Some compounds exhibited moderate inhibitory activities against IL-6 production in LPS-stimulated RAW 264.7 macrophages in vitro. Compound 5 showed significant anti-inflammatory activity in vitro (IC<sub>50</sub>, 0.77 μM) and inhibited macrophage polarization towards a pro-inflammatory phenotype.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106306"},"PeriodicalIF":2.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sepsis-induced Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) pose life-threatening risks due to an excessive activation of proinflammatory cytokines via the JAK pathway. Currently, no confirmed drug treatment exists for ALI. In this study, we explored JAK1 as a potential therapeutic target to address this issue. This study evaluates lapachol, a bioactive secondary metabolite, for its potential in treating sepsis-induced Acute Lung Injury (ALI). Lapachol was selected based on in-silico analyses such as binding energy, RMSD, RMSF, H-bond graphs, and lig plots supported the hypothesis that Lapachol binds to JAK1 in a manner similar to Tofacitinib JAK1/3 inhibitor (Positive control). Lapachol, derived from the heartwood of Tecomella undulata, was used in this investigation. Swiss albino mice were categorized into control, LPS treated, positive control (Tofacitinib), and experimental groups (Lapachol at 20 and 40 mg/kg doses). Throughout the experiment, mice behaviour was monitored, and euthanasia was performed at 12 and 24-h intervals. Various analyses, including body weight, W/D ratio, lung weight/body weight ratio, flow cytometry of BAL fluid (at 12 and 24 h), histology, myeloperoxidase assays were performed. Results indicated that both Tofacitinib and Lapachol significantly reduced ALI markers, including lung weight/body weight ratio, cell counts, and granulocytes in bronchoalveolar lavage fluid. Moreover, histopathology and MPO analysis suggested that Lapachol, particularly at 40 mg/kg, exhibited anti-inflammatory effects comparable to Tofacitinib. Conclusively, the findings suggest that Lapachol possesses the potential to inhibit JAK1 kinase domains and mitigate ALI associated with sepsis similar to Tofacitinib.
{"title":"Assessment of lapachol's anti-inflammatory effectiveness in mitigating sepsis-induced acute lung injury.","authors":"Kavita Joshi, Vaishnavi Singh, Samit Chatterjee, Poonam Khandelwal, Rashmy Nair, Sameer Qureshi, Snigdha Siddh, Vandana Nunia","doi":"10.1016/j.fitote.2024.106298","DOIUrl":"https://doi.org/10.1016/j.fitote.2024.106298","url":null,"abstract":"<p><p>Sepsis-induced Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) pose life-threatening risks due to an excessive activation of proinflammatory cytokines via the JAK pathway. Currently, no confirmed drug treatment exists for ALI. In this study, we explored JAK1 as a potential therapeutic target to address this issue. This study evaluates lapachol, a bioactive secondary metabolite, for its potential in treating sepsis-induced Acute Lung Injury (ALI). Lapachol was selected based on in-silico analyses such as binding energy, RMSD, RMSF, H-bond graphs, and lig plots supported the hypothesis that Lapachol binds to JAK1 in a manner similar to Tofacitinib JAK1/3 inhibitor (Positive control). Lapachol, derived from the heartwood of Tecomella undulata, was used in this investigation. Swiss albino mice were categorized into control, LPS treated, positive control (Tofacitinib), and experimental groups (Lapachol at 20 and 40 mg/kg doses). Throughout the experiment, mice behaviour was monitored, and euthanasia was performed at 12 and 24-h intervals. Various analyses, including body weight, W/D ratio, lung weight/body weight ratio, flow cytometry of BAL fluid (at 12 and 24 h), histology, myeloperoxidase assays were performed. Results indicated that both Tofacitinib and Lapachol significantly reduced ALI markers, including lung weight/body weight ratio, cell counts, and granulocytes in bronchoalveolar lavage fluid. Moreover, histopathology and MPO analysis suggested that Lapachol, particularly at 40 mg/kg, exhibited anti-inflammatory effects comparable to Tofacitinib. Conclusively, the findings suggest that Lapachol possesses the potential to inhibit JAK1 kinase domains and mitigate ALI associated with sepsis similar to Tofacitinib.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106298"},"PeriodicalIF":2.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.1016/j.fitote.2024.106303
Isaac Moura Araújo, Andressa de Alencar Silva, Luís Pereira-de-Morais, Debora de Menezes Dantas, Maysa de Oliveira Barbosa, Giovana Mendes Lacerda Leite, Carla de Fátima Alves Nonato, José Galberto Martins da Costa, Raimundo Luiz Silva Pereira, Marta Regina Kerntopf Mendonça, Henrique Douglas Melo Coutinho, Gyllyandeson de Araújo Delmondes
Anxiety and depression are mental disorders that have been exponentially increasing over the last decades. Psychopharmacology emerged to try to alleviate the symptoms of these disorders; however, the side effects and the time it takes to achieve the desired effect are factors that decrease the search for and adherence to treatment. To remedy this situation, new compounds capable of improving the performance of these medications and reducing their adverse effects have been sought. The use of medicinal plants has been widely employed for this purpose. Mauritia flexuosa F.L., a palm tree with high incidence in Brazil, has been heavily targeted as all its parts are usable. The objective of this study is to evaluate the effects of fixed oil from the fruit of the buriti palm in models of depression and anxiety. The phytochemical profile of this oil and its toxicity were also investigated. The experiments conducted included the open field, rotarod, forced swim, and elevated plus maze tests. As a result, it was observed that the fixed oil from buriti palm presented 18 compounds, with elaidic acid being the major one, and showed no signs of toxicity. However, it demonstrated a possible stimulating activity in the open field test and had no effect on the motor system in the rotarod test. Furthermore, it exhibited an antidepressant-like effect in the forced swim test but an anxiety-like effect in the elevated plus maze test. Therefore, buriti oil may potentially be used in new formulations to assist in the treatment of anxiety and depression.
{"title":"Phytochemical characterization, toxicity and pharmacological profile of the central effects of the fixed fruit pulp oil of Mauritia flexuosa L.F. (buriti).","authors":"Isaac Moura Araújo, Andressa de Alencar Silva, Luís Pereira-de-Morais, Debora de Menezes Dantas, Maysa de Oliveira Barbosa, Giovana Mendes Lacerda Leite, Carla de Fátima Alves Nonato, José Galberto Martins da Costa, Raimundo Luiz Silva Pereira, Marta Regina Kerntopf Mendonça, Henrique Douglas Melo Coutinho, Gyllyandeson de Araújo Delmondes","doi":"10.1016/j.fitote.2024.106303","DOIUrl":"10.1016/j.fitote.2024.106303","url":null,"abstract":"<p><p>Anxiety and depression are mental disorders that have been exponentially increasing over the last decades. Psychopharmacology emerged to try to alleviate the symptoms of these disorders; however, the side effects and the time it takes to achieve the desired effect are factors that decrease the search for and adherence to treatment. To remedy this situation, new compounds capable of improving the performance of these medications and reducing their adverse effects have been sought. The use of medicinal plants has been widely employed for this purpose. Mauritia flexuosa F.L., a palm tree with high incidence in Brazil, has been heavily targeted as all its parts are usable. The objective of this study is to evaluate the effects of fixed oil from the fruit of the buriti palm in models of depression and anxiety. The phytochemical profile of this oil and its toxicity were also investigated. The experiments conducted included the open field, rotarod, forced swim, and elevated plus maze tests. As a result, it was observed that the fixed oil from buriti palm presented 18 compounds, with elaidic acid being the major one, and showed no signs of toxicity. However, it demonstrated a possible stimulating activity in the open field test and had no effect on the motor system in the rotarod test. Furthermore, it exhibited an antidepressant-like effect in the forced swim test but an anxiety-like effect in the elevated plus maze test. Therefore, buriti oil may potentially be used in new formulations to assist in the treatment of anxiety and depression.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106303"},"PeriodicalIF":2.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.1016/j.fitote.2024.106301
Cláudia Maria da Silva Costa de Oliveira, Milena Costa Bassicheto, Renan Santini Barbosa, Kiandro de Oliveira Gomes Neves, Caroline Dos Santos Monteiro, Miriam Uemi, Renata Castiglioni Pascon, Gilvan Ferreira da Silva, Hector Henrique Ferreira Koolen, Lívia Soman de Medeiros
Cryptococcosis is a fungal infection for which treatment relies on old antifungal agents usually leading to drawbacks such as high toxicity and mainly low efficiency since drug resistance of microorganisms is strongly widespread. The discovery of new antifungal agents is urgent and investigations about underexplored Natural Product (NP) can yield the necessary outcomes to guide the discovery of new prototypes to anti-cryptococcal molecules development. In this scenario, an integrated strategy involving metabolomic data analysis, biological assessement and genome mining of P. setosum CMLD 18, revealed the biosynthesis of bis(methyl-sulfanyl) oxepine-containing diketopiperazine derivative, the bisdethiobis(methylthio)acetylaranotine (1) by the endophyte. The molecule showed a minimum inhibitory concentration (MIC) value of 0.125 mM when tested against C. neoformans. Evidence about the corresponding biosynthetic gene cluster (BGC) responsible for the biosynthesis of (1) in P. setosum were found. Moreover, other putative analogues of (1) were also detected, suggesting this microorganism may represent an important source of likely anti-cryptococcal molecules to be further investigated.
隐球菌病是一种真菌感染,其治疗通常依赖于旧的抗真菌药物,但由于微生物的耐药性非常普遍,因此通常会导致高毒性和低效率等缺点。发现新的抗真菌剂迫在眉睫,而对尚未充分开发的天然产物(NP)的研究可以产生必要的成果,指导发现新的原型,以开发抗隐球菌分子。在这种情况下,一种涉及 P. setosum CMLD 18 的代谢组数据分析、生物评估和基因组挖掘的综合策略揭示了内生菌生物合成含双(甲硫基)氧杂环庚烷的二酮哌嗪衍生物--双硫代双(甲硫基)乙酰aranotine (1)。该分子对新变形杆菌的最低抑制浓度(MIC)值为 0.125 mM。研究还发现了 P. setosum 中负责生物合成(1)的相应生物合成基因簇(BGC)。此外,还检测到了(1)的其他假定类似物,这表明该微生物可能是抗隐球菌分子的重要来源,有待进一步研究。
{"title":"Integrated workflows using metabolomics, genome mining, and biological evaluation reveal oxepine‑sulfur-containing anti-cryptococcal diketopiperazine produced by the endophyte Penicillium setosum.","authors":"Cláudia Maria da Silva Costa de Oliveira, Milena Costa Bassicheto, Renan Santini Barbosa, Kiandro de Oliveira Gomes Neves, Caroline Dos Santos Monteiro, Miriam Uemi, Renata Castiglioni Pascon, Gilvan Ferreira da Silva, Hector Henrique Ferreira Koolen, Lívia Soman de Medeiros","doi":"10.1016/j.fitote.2024.106301","DOIUrl":"10.1016/j.fitote.2024.106301","url":null,"abstract":"<p><p>Cryptococcosis is a fungal infection for which treatment relies on old antifungal agents usually leading to drawbacks such as high toxicity and mainly low efficiency since drug resistance of microorganisms is strongly widespread. The discovery of new antifungal agents is urgent and investigations about underexplored Natural Product (NP) can yield the necessary outcomes to guide the discovery of new prototypes to anti-cryptococcal molecules development. In this scenario, an integrated strategy involving metabolomic data analysis, biological assessement and genome mining of P. setosum CMLD 18, revealed the biosynthesis of bis(methyl-sulfanyl) oxepine-containing diketopiperazine derivative, the bisdethiobis(methylthio)acetylaranotine (1) by the endophyte. The molecule showed a minimum inhibitory concentration (MIC) value of 0.125 mM when tested against C. neoformans. Evidence about the corresponding biosynthetic gene cluster (BGC) responsible for the biosynthesis of (1) in P. setosum were found. Moreover, other putative analogues of (1) were also detected, suggesting this microorganism may represent an important source of likely anti-cryptococcal molecules to be further investigated.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106301"},"PeriodicalIF":2.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.fitote.2024.106297
Ling Jiang, Cai-Bo Tian, Rui-Han Ye, Nian Shi, Xing-Chao He, Yun-Li Zhao, Xiao-Dong Luo
Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro. In addition, HSP90AA1/CDK2/mTOR signaling pathway and five target proteins (CDK2, HSP90AA1, HRAS, MMP1, mTOR) were proposed from network pharmacology and molecular docking prediction, and then the up-regulation of protein expression of CDK2, mTOR and down-regulation of HSP90AA1, HRAS, MMP1 by kakuol and asarinin in western blotting supported their mechanism.
{"title":"Kakuol and asarinin protecting liver injury via HSP90AA1/CDK2/mTOR signaling pathway.","authors":"Ling Jiang, Cai-Bo Tian, Rui-Han Ye, Nian Shi, Xing-Chao He, Yun-Li Zhao, Xiao-Dong Luo","doi":"10.1016/j.fitote.2024.106297","DOIUrl":"https://doi.org/10.1016/j.fitote.2024.106297","url":null,"abstract":"<p><p>Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro. In addition, HSP90AA1/CDK2/mTOR signaling pathway and five target proteins (CDK2, HSP90AA1, HRAS, MMP1, mTOR) were proposed from network pharmacology and molecular docking prediction, and then the up-regulation of protein expression of CDK2, mTOR and down-regulation of HSP90AA1, HRAS, MMP1 by kakuol and asarinin in western blotting supported their mechanism.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106297"},"PeriodicalIF":2.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14DOI: 10.1016/j.fitote.2024.106299
Priscilla O. Aiyedun , Mubo A. Sonibare , Badara Gueye , Dirk C. Albach , Julia Heil , Gertrud E. Morlock
Trifoliate yam (Dioscorea dumetorum) is traditionally used to treat diabetics in Nigeria. However, almost no information is available on its antidiabetic constituents and their natural variance. Hence, the activity of methanolic tuber extracts of 67 trifoliate yam accessions from the largest collection in Africa was proven by four colorimetric antidiabetic and antioxidant in vitro assays, as diabetes is also linked with oxidative stress. For the first time, selected accessions were also analyzed by planar bioactivity profiling. It has a comparatively higher, more differentiated information content, is more sustainable in terms of material consumption, and enables straightforward compound prioritization and characterization. Up to a dozen individual antioxidant zones were revealed as well as one prominent zone inhibiting α-glucosidase and α-amylase. The latter inhibition zone was tentatively assigned to palmitic, linoleic, oleic, linolenic, oxo-nonanoic fatty acids by direct elution to heated electrospray ionization high-resolution mass spectrometry.
{"title":"Antidiabetic and antioxidant profiling of 67 African trifoliate yam accessions by planar on-surface assays versus in vitro assays","authors":"Priscilla O. Aiyedun , Mubo A. Sonibare , Badara Gueye , Dirk C. Albach , Julia Heil , Gertrud E. Morlock","doi":"10.1016/j.fitote.2024.106299","DOIUrl":"10.1016/j.fitote.2024.106299","url":null,"abstract":"<div><div>Trifoliate yam (<em>Dioscorea dumetorum</em>) is traditionally used to treat diabetics in Nigeria. However, almost no information is available on its antidiabetic constituents and their natural variance. Hence, the activity of methanolic tuber extracts of 67 trifoliate yam accessions from the largest collection in Africa was proven by four colorimetric antidiabetic and antioxidant <em>in vitro</em> assays, as diabetes is also linked with oxidative stress. For the first time, selected accessions were also analyzed by planar bioactivity profiling. It has a comparatively higher, more differentiated information content, is more sustainable in terms of material consumption, and enables straightforward compound prioritization and characterization. Up to a dozen individual antioxidant zones were revealed as well as one prominent zone inhibiting α-glucosidase and α-amylase. The latter inhibition zone was tentatively assigned to palmitic, linoleic, oleic, linolenic, oxo-nonanoic fatty acids by direct elution to heated electrospray ionization high-resolution mass spectrometry.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"180 ","pages":"Article 106299"},"PeriodicalIF":2.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.fitote.2024.106296
Mingliang Zhang , Mengrong Niu , Jiangping Fan , Zihan Lu , Zhixiang Zhu , Bowen Gao , She-Po Shi
2-(2-Phenylethyl)chromones (PECs), the pivotal constituents responsible for the distinctive aroma and pharmacological potential of agarwood, are primarily obtained through extraction from natural materials. The restricted availability of agarwood has, however, hindered a comprehensive and systematic evaluation of their biological properties. In this study, we have chemically synthesized a total of 38 PEC derivatives, including 23 new compounds that had not been previously isolated from agarwood. These compounds were then evaluated for their inhibitory effects on nitric oxide release, neutrophil superoxide production, as well as their activities against tyrosinase, acetylcholinesterase, and α-glucosidase. The preliminary screening resulted in the identification of promising leads with potential therapeutic activities, and the structure-activity relationship of the synthesized PECs have also been briefly discussed. The results provide a foundation for the synthesis and pharmacological exploration of PECs, which sheds light on the pharmacological potential of agarwood's secondary metabolites.
{"title":"Synthesis and pharmacological activity evaluation of 2-(2-Phenylethyl)chromone analogues: The principal components in agarwood","authors":"Mingliang Zhang , Mengrong Niu , Jiangping Fan , Zihan Lu , Zhixiang Zhu , Bowen Gao , She-Po Shi","doi":"10.1016/j.fitote.2024.106296","DOIUrl":"10.1016/j.fitote.2024.106296","url":null,"abstract":"<div><div>2-(2-Phenylethyl)chromones (PECs), the pivotal constituents responsible for the distinctive aroma and pharmacological potential of agarwood, are primarily obtained through extraction from natural materials. The restricted availability of agarwood has, however, hindered a comprehensive and systematic evaluation of their biological properties. In this study, we have chemically synthesized a total of 38 PEC derivatives, including 23 new compounds that had not been previously isolated from agarwood. These compounds were then evaluated for their inhibitory effects on nitric oxide release, neutrophil superoxide production, as well as their activities against tyrosinase, acetylcholinesterase, and <em>α</em>-glucosidase. The preliminary screening resulted in the identification of promising leads with potential therapeutic activities, and the structure-activity relationship of the synthesized PECs have also been briefly discussed. The results provide a foundation for the synthesis and pharmacological exploration of PECs, which sheds light on the pharmacological potential of agarwood's secondary metabolites.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"180 ","pages":"Article 106296"},"PeriodicalIF":2.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Foodborne illness caused by pathogens has been a major health problem. Antibacterial resistance renders therapeutic options for treating the condition more limited, hence there is a growing interest in finding novel antibacterial alternatives. Zanthoxylum acanthopodium (Rutaceae) essential oil (ZAEO) has a substantial potential to suppress the growth of bacterial infections. This study was conducted to evaluate antibacterial activity of ZAEO against four species of foodborne pathogens that cause potential infections. The checkerboard assay was used to identify synergistic effect of ZAEO and tetracycline, while bacteriolysis test was applied to evaluate the ability of ZAEO releasing material genetics of bacteria, inhibiting biofilm formation, and suppressing efflux pump. The oils of Z. acanthopodium was evaluated and showed that the highest constituents were limonene and geranyl acetate at 47.13 % and 23.84 %, respectively. These oils have the strongest ability to inhibit Escherichia coli compared to other pathogens with MIC value of 62.5 μg/mL. ZAEO and tetracycline also presented a synergistic effect against E. coli with FICI value of 0.37. Moreover, this combination of ZAEO and antibiotic shown as potential antibacterial agent by several mechanisms such as, decreasing biofilm formation, releasing ions, rupturing membrane cells, and suppressing the efflux pump of E. coli. It can be concluded that ZAEO and tetracycline presented a promising antibacterial activity, which can be explored further to develops antibacterial agents against foodborne pathogens.
{"title":"Chemical profiles and antibacterial actions of Zanthoxylum acanthopodium DC. Essential oil growing in Indonesia","authors":"Abdi Wira Septama , Eldiza Puji Rahmi , Aprilia Nur Tasfiyati , Nur Aini Khairunnisa , Halimah Raina Nasution , Nilesh Nirmal , Sofna Dewita Sari Banjarnahor , Nurhadi , Dadang Priyatmojo","doi":"10.1016/j.fitote.2024.106300","DOIUrl":"10.1016/j.fitote.2024.106300","url":null,"abstract":"<div><div>Foodborne illness caused by pathogens has been a major health problem. Antibacterial resistance renders therapeutic options for treating the condition more limited, hence there is a growing interest in finding novel antibacterial alternatives. <em>Zanthoxylum acanthopodium</em> (Rutaceae) essential oil (ZAEO) has a substantial potential to suppress the growth of bacterial infections. This study was conducted to evaluate antibacterial activity of ZAEO against four species of foodborne pathogens that cause potential infections. The checkerboard assay was used to identify synergistic effect of ZAEO and tetracycline, while bacteriolysis test was applied to evaluate the ability of ZAEO releasing material genetics of bacteria, inhibiting biofilm formation, and suppressing efflux pump. The oils of <em>Z. acanthopodium</em> was evaluated and showed that the highest constituents were limonene and geranyl acetate at 47.13 % and 23.84 %, respectively. These oils have the strongest ability to inhibit <em>Escherichia coli</em> compared to other pathogens with MIC value of 62.5 μg/mL. ZAEO and tetracycline also presented a synergistic effect against <em>E. coli</em> with FICI value of 0.37. Moreover, this combination of ZAEO and antibiotic shown as potential antibacterial agent by several mechanisms such as, decreasing biofilm formation, releasing ions, rupturing membrane cells, and suppressing the efflux pump of <em>E. coli.</em> It can be concluded that ZAEO and tetracycline presented a promising antibacterial activity, which can be explored further to develops antibacterial agents against foodborne pathogens.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"180 ","pages":"Article 106300"},"PeriodicalIF":2.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}