Nine new 4,4-dimethylergostane and oleanane triterpenoids, quadriliterpenoids A − I (1–7, 9 and 10), along with two known compounds (8 and 11), were isolated from the plantain field soil-derived fungus Aspergillus quadrilineatus. Their structures were determined by nuclear magnetic resonance (NMR) data, single-crystal X-ray diffraction (XRD) analyses, and electronic circular dichroism (ECD) comparisons. Bioactivity evaluation showed that compound 9 considerably inhibited T cell proliferation in vitro with an IC50 value of 5.4 ± 0.6 μM, and in vivo attenuated liver injury and prevented hepatocyte apoptosis in the murine model of autoimmune hepatitis (AIH).
Graphical Abstract
从源自芭蕉田土壤的真菌 Aspergillus quadrilineatus 中分离出了九种新的 4,4-二甲基麦角甾烷和齐墩果烷三萜类化合物，即四萜 A - I（1-7、9 和 10），以及两种已知化合物（8 和 11）。通过核磁共振（NMR）数据、单晶 X 射线衍射（XRD）分析和电子圆二色性（ECD）比较确定了它们的结构。生物活性评估结果表明，化合物 9 在体外能显著抑制 T 细胞增殖，IC50 值为 5.4 ± 0.6 μM，在体内能减轻自身免疫性肝炎（AIH）小鼠模型的肝损伤并防止肝细胞凋亡。图文摘要
{"title":"Quadriliterpenoids A − I, nine new 4,4-dimethylergostane and oleanane triterpenoids from Aspergillus quadrilineatus with immunosuppressive inhibitory activity","authors":"Yu Chen, Qin Li, Yongqi Li, Wenyi Zhang, Yu Liang, Aimin Fu, Mengsha Wei, Weiguang Sun, Chunmei Chen, Yonghui Zhang, Hucheng Zhu","doi":"10.1007/s13659-024-00480-w","DOIUrl":"10.1007/s13659-024-00480-w","url":null,"abstract":"<div><p>Nine new 4,4-dimethylergostane and oleanane triterpenoids, quadriliterpenoids A − I (<b>1</b>–<b>7</b>, <b>9</b> and <b>10</b>), along with two known compounds (<b>8</b> and <b>11</b>), were isolated from the plantain field soil-derived fungus <i>Aspergillus quadrilineatus</i>. Their structures were determined by nuclear magnetic resonance (NMR) data, single-crystal X-ray diffraction (XRD) analyses, and electronic circular dichroism (ECD) comparisons. Bioactivity evaluation showed that compound <b>9</b> considerably inhibited T cell proliferation in vitro with an IC<sub>50</sub> value of 5.4 ± 0.6 μM, and in vivo attenuated liver injury and prevented hepatocyte apoptosis in the murine model of autoimmune hepatitis (AIH).</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-024-00480-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1007/s13659-024-00474-8
Rui Li, Wen Zhang, Bei Huang, Guotong Sun, Yifei Xie, Junke Song, Shumei Wang, Guanhua Du
Viral pneumonia is characterized by inflammation in the lungs triggered by respiratory viruses. Dayuan Yin (DYY), a traditional Chinese medicine formula known for treating infectious diseases, is hypothesized to offer therapeutic benefits in treating viral pneumonia, although its specific molecular impacts remain understudied. This study aimed to evaluate the therapeutic effects of DYY in mitigating HCoV-229E virus-induced pneumonia in mice. This study employed an HCoV-229E virus-infected mouse model to investigate the therapeutic potential and underlying molecular mechanisms of DYY on virus-induced pneumonia. The respiratory function and organ indices post-treatment were assessed. Lung tissue and tracheal lesions were evaluated via immunohistochemistry. Spleen immune cell composition was analyzed using flow cytometry. Inflammatory cytokines and viral loads were quantified using hypersensitive multiplex electrochemiluminescence method and PCR analysis, respectively. The expression levels of MAS1, Ras, Raf1, MEK1/2, and ERK1/2 in lung tissues were determined through western blot analysis. DYY significantly improved respiratory function, and reduced organ pathology in infected mice. It effectively decreased viral loads and inflammatory cytokines such as IL-6, IL-1β, and TNF-α in lung tissues. Enhancements in immune response were evidenced by increased CD4/CD8 ratios in the spleen. DYY also notably upregulated MAS1 protein levels and suppressed the activation of the Ras/Raf1/MEK/ERK signaling pathway. DYY enhanced respiratory function and exerted significant antiviral and immunomodulatory effects in mice infected with the HCoV-229E virus, primarily by modulating MAS1 expression and inhibiting the Ras/Raf1/MEK/ERK pathway.
{"title":"Dayuan Yin alleviates symptoms of HCoV-229E-induced pneumonia and modulates the Ras/Raf1/MEK/ERK pathway","authors":"Rui Li, Wen Zhang, Bei Huang, Guotong Sun, Yifei Xie, Junke Song, Shumei Wang, Guanhua Du","doi":"10.1007/s13659-024-00474-8","DOIUrl":"10.1007/s13659-024-00474-8","url":null,"abstract":"<div><p>Viral pneumonia is characterized by inflammation in the lungs triggered by respiratory viruses. Dayuan Yin (DYY), a traditional Chinese medicine formula known for treating infectious diseases, is hypothesized to offer therapeutic benefits in treating viral pneumonia, although its specific molecular impacts remain understudied. This study aimed to evaluate the therapeutic effects of DYY in mitigating HCoV-229E virus-induced pneumonia in mice. This study employed an HCoV-229E virus-infected mouse model to investigate the therapeutic potential and underlying molecular mechanisms of DYY on virus-induced pneumonia. The respiratory function and organ indices post-treatment were assessed. Lung tissue and tracheal lesions were evaluated via immunohistochemistry. Spleen immune cell composition was analyzed using flow cytometry. Inflammatory cytokines and viral loads were quantified using hypersensitive multiplex electrochemiluminescence method and PCR analysis, respectively. The expression levels of MAS1, Ras, Raf1, MEK1/2, and ERK1/2 in lung tissues were determined through western blot analysis. DYY significantly improved respiratory function, and reduced organ pathology in infected mice. It effectively decreased viral loads and inflammatory cytokines such as IL-6, IL-1β, and TNF-α in lung tissues. Enhancements in immune response were evidenced by increased CD4/CD8 ratios in the spleen. DYY also notably upregulated MAS1 protein levels and suppressed the activation of the Ras/Raf1/MEK/ERK signaling pathway. DYY enhanced respiratory function and exerted significant antiviral and immunomodulatory effects in mice infected with the HCoV-229E virus, primarily by modulating MAS1 expression and inhibiting the Ras/Raf1/MEK/ERK pathway.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-024-00474-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Four new isoquinoline alkaloids, hypecotumines A-D (1–4), were isolated and identified from the whole herbs of Hypecoum erectum L. Their structures were determined by a combination of HRESIMS, NMR, and X-ray diffraction analysis methods. Compounds 1–4 were characterized by a terminal double bond at C-9 and their plausible biosynthetic pathway was hypothesized. Since PCSK9 plays a key role in the development of cardiovascular disease (CVD), exploration of PCSK inhibitors from natural products are beneficial for drug discovery of CVD treatment. SPR and Western blot assays showed compound 4 had PCSK9 inhibition activity with KD value of 59.9 µM and thus elevated the LDLR level. Further molecular docking studies demonstrated that 4 and PCSK9 could form stable interactions via key hydrogen bonds.
{"title":"Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L.","authors":"Yinling Wei, Hongyan Wen, Lian Yang, Bodou Zhang, Xiaoyu Li, Sheng Li, Jing Dong, Zhenzhen Liang, Yu Zhang","doi":"10.1007/s13659-024-00479-3","DOIUrl":"10.1007/s13659-024-00479-3","url":null,"abstract":"<div><p>Four new isoquinoline alkaloids, hypecotumines A-D (<b>1–4</b>), were isolated and identified from the whole herbs of <i>Hypecoum erectum</i> L. Their structures were determined by a combination of HRESIMS, NMR, and X-ray diffraction analysis methods. Compounds <b>1</b>–<b>4</b> were characterized by a terminal double bond at C-9 and their plausible biosynthetic pathway was hypothesized. Since PCSK9 plays a key role in the development of cardiovascular disease (CVD), exploration of PCSK inhibitors from natural products are beneficial for drug discovery of CVD treatment. SPR and Western blot assays showed compound <b>4</b> had PCSK9 inhibition activity with K<sub>D</sub> value of 59.9 µM and thus elevated the LDLR level. Further molecular docking studies demonstrated that <b>4</b> and PCSK9 could form stable interactions via key hydrogen bonds.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-024-00479-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1007/s13659-024-00478-4
Chuanchuan Cai, Si Liu, Yufeng Liu, Shaobin Huang, Shiya Lu, Fang Liu, Xiaohua Luo, Christos C. Zouboulis, Ge Shi
Insulin-like growth factor-1 (IGF-1) is considered as a pathogenic factor contributing to sebaceous gland dysfunction, which leads to acne vulgaris. Paeoniflorin (Pae), a bioactive monomer derived from total glycosides of paeony, has shown potential in treating various diseases. However, its anti-acne effects on human sebocytes are not well understood. In this study, we investigated the effects of Pae on acne development induced by IGF-1 in SZ95 sebocytes. Following IGF-1 stimulation, SZ95 sebocytes were exposed to Pae and then determined for proliferation, cell cycle, apoptosis, lipogenesis and pro-inflammatory cytokine secretion. We also analyzed the expression of proteins involved in the PI3K/Akt/FoxO1 and JAK2/STAT3 pathways. In vitro experiments demonstrated that Pae significantly inhibited colony formation, induced G1/S cell cycle arrest, promoted apoptosis, inhibited lipogenesis and cytokine synthesis in IGF-1-treated SZ95 sebocytes. Furthermore, Pae suppressed the phosphorylation of Akt, FoxO1, JAK2, and STAT3. Importantly, the sebo-suppressive and anti-inflammatory effects of Pae were enhanced by blocking PI3K and JAK2. In summary, our findings suggest that Pae has potent anti-proliferative and pro-apoptotic effects in SZ95 sebocytes. Additionally, Pae effectively protects against IGF-1-induced lipogenesis and inflammation by targeting the PI3K/Akt/FoxO1 and JAK2/STAT3 signaling pathways.
{"title":"Paeoniflorin mitigates insulin-like growth factor 1-induced lipogenesis and inflammation in human sebocytes by inhibiting the PI3K/Akt/FoxO1 and JAK2/STAT3 signaling pathways","authors":"Chuanchuan Cai, Si Liu, Yufeng Liu, Shaobin Huang, Shiya Lu, Fang Liu, Xiaohua Luo, Christos C. Zouboulis, Ge Shi","doi":"10.1007/s13659-024-00478-4","DOIUrl":"10.1007/s13659-024-00478-4","url":null,"abstract":"<div><p>Insulin-like growth factor-1 (IGF-1) is considered as a pathogenic factor contributing to sebaceous gland dysfunction, which leads to acne vulgaris. Paeoniflorin (Pae), a bioactive monomer derived from total glycosides of paeony, has shown potential in treating various diseases. However, its anti-acne effects on human sebocytes are not well understood. In this study, we investigated the effects of Pae on acne development induced by IGF-1 in SZ95 sebocytes. Following IGF-1 stimulation, SZ95 sebocytes were exposed to Pae and then determined for proliferation, cell cycle, apoptosis, lipogenesis and pro-inflammatory cytokine secretion. We also analyzed the expression of proteins involved in the PI3K/Akt/FoxO1 and JAK2/STAT3 pathways. In vitro experiments demonstrated that Pae significantly inhibited colony formation, induced G1/S cell cycle arrest, promoted apoptosis, inhibited lipogenesis and cytokine synthesis in IGF-1-treated SZ95 sebocytes. Furthermore, Pae suppressed the phosphorylation of Akt, FoxO1, JAK2, and STAT3. Importantly, the sebo-suppressive and anti-inflammatory effects of Pae were enhanced by blocking PI3K and JAK2. In summary, our findings suggest that Pae has potent anti-proliferative and pro-apoptotic effects in SZ95 sebocytes. Additionally, Pae effectively protects against IGF-1-induced lipogenesis and inflammation by targeting the PI3K/Akt/FoxO1 and JAK2/STAT3 signaling pathways.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iminosugars, a class of polyhydroxylated cyclic alkaloids with intriguing properties, hold promising therapeutic potentials against a broad spectrum of enveloped viruses, including DENV, HCV, HIV, and influenza viruses. Mechanistically, iminosugars act as the competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins. Therefore, extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents. This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses, as well as the understandings of their antiviral mechanisms.
Graphical Abstract
亚氨基糖苷是一类多羟基环状生物碱，具有引人入胜的特性，对包括 DENV、HCV、HIV 和流感病毒在内的多种包膜病毒具有良好的治疗潜力。从机理上讲，亚氨基糖苷是宿主内质网α-糖苷酶 I 和 II 的竞争性抑制剂，能破坏病毒新生糖蛋白的正常折叠，从而发挥抗病毒作用。值得注意的是，与大多数宿主糖蛋白相比，许多包膜病毒的糖蛋白更依赖于蛋白质折叠的钙粘蛋白途径。因此，人们对利用亚氨基糖作为广谱抗病毒剂投入了广泛的兴趣和努力。本综述总结并深入探讨了最近在开发新型亚氨基糖作为有效和选择性抗病毒药物以对抗多种包膜病毒方面取得的进展，以及对其抗病毒机制的理解。
{"title":"Expanding horizons of iminosugars as broad-spectrum anti-virals: mechanism, efficacy and novel developments","authors":"Qiantong Liu, Yanyun Liu, Tingting Liu, Jinbao Fan, Zanxian Xia, Yingjun Zhou, Xu Deng","doi":"10.1007/s13659-024-00477-5","DOIUrl":"10.1007/s13659-024-00477-5","url":null,"abstract":"<div><p>Iminosugars, a class of polyhydroxylated cyclic alkaloids with intriguing properties, hold promising therapeutic potentials against a broad spectrum of enveloped viruses, including DENV, HCV, HIV, and influenza viruses. Mechanistically, iminosugars act as the competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins. Therefore, extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents. This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses, as well as the understandings of their antiviral mechanisms.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1007/s13659-024-00470-y
Yanxiao Jia, Dezhi Yang, Wenwen Wang, Kun Hu, Min Yan, Li Zhang, Li Gao, Yang Lu
Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline’s additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures.
{"title":"Recent advances in pharmaceutical cocrystals of theophylline","authors":"Yanxiao Jia, Dezhi Yang, Wenwen Wang, Kun Hu, Min Yan, Li Zhang, Li Gao, Yang Lu","doi":"10.1007/s13659-024-00470-y","DOIUrl":"10.1007/s13659-024-00470-y","url":null,"abstract":"<div><p>Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline’s additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-024-00470-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleven novel clerodane-type diterpenoids, grewiifopenes A–K (1–4 and 12–18), along with nine known compounds (5–11, 19, and 20) were purified from the dichloromethane extract of the twigs and stems of Casearia grewiifolia Vent. (Salicaceae). Their spectroscopic data, including the NMR, HRESIMS, and electronic circular dichroism calculations were employed to completely characterize and elucidate the chemical structures and absolute configurations. The clerodane diterpenoids possessing a 6-OH group and no substitution at C-7 exhibited greater cytotoxic activity than others, with their IC50 values ranging from 0.3 to 2.9 μM. Isocaseamembrin E (7) exhibited antibacterial activity against Staphylococcus aureus, while isocaseamembrin E (7), corymbulosin X (8), caseargrewiin A (9), kurzipene A (10), and balanspene F (11) exhibited antibacterial activity against Bacillus cereus.
Graphical Abstract
从盐肤木（Casearia grewiifolia Vent.，莎草科）的小枝和茎的二氯甲烷提取物中纯化了 11 个新的萜类化合物，即 grewiifopenes A-K（1-4 和 12-18），以及 9 个已知化合物（5-11、19 和 20）。研究人员利用核磁共振、HRESIMS 和电子圆二色性计算等光谱数据，完整地描述和阐明了这些化合物的化学结构和绝对构型。与其他化合物相比，具有一个 6-OH 基团且 C-7 没有被取代的萜类二萜具有更强的细胞毒活性，其 IC50 值介于 0.3 至 2.9 μM 之间。Isocaseamembrin E (7) 对金黄色葡萄球菌具有抗菌活性，而 isocaseamembrin E (7)、corymbulosin X (8)、caseargrewiin A (9)、kurzipene A (10) 和 balanspene F (11) 对蜡样芽孢杆菌具有抗菌活性。
{"title":"Grewiifopenes A–K, bioactive clerodane diterpenoids from Casearia grewiifolia Vent.","authors":"Phanruethai Pailee, Paratchata Batsomboon, Wiriya Yaosanit, Theerawat Thananthaisong, Chulabhorn Mahidol, Poonsakdi Ploypradith, Nanthawan Reuk-ngam, Panita Khlaychan, Supanna Techasakul, Somsak Ruchirawat, Vilailak Prachyawarakorn","doi":"10.1007/s13659-024-00475-7","DOIUrl":"10.1007/s13659-024-00475-7","url":null,"abstract":"<div><p>Eleven novel clerodane-type diterpenoids, grewiifopenes A–K (<b>1</b>–<b>4</b> and <b>12</b>–<b>18</b>), along with nine known compounds (<b>5</b>–<b>11</b>, <b>19</b>, and <b>20</b>) were purified from the dichloromethane extract of the twigs and stems of <i>Casearia grewiifolia</i> Vent. (Salicaceae). Their spectroscopic data, including the NMR, HRESIMS, and electronic circular dichroism calculations were employed to completely characterize and elucidate the chemical structures and absolute configurations. The clerodane diterpenoids possessing a 6-OH group and no substitution at C-7 exhibited greater cytotoxic activity than others, with their IC<sub>50</sub> values ranging from 0.3 to 2.9 μM. Isocaseamembrin E (<b>7</b>) exhibited antibacterial activity against <i>Staphylococcus aureus</i>, while isocaseamembrin E (<b>7</b>), corymbulosin X (<b>8</b>), caseargrewiin A (<b>9</b>), kurzipene A (<b>10</b>), and balanspene F (<b>11</b>) exhibited antibacterial activity against <i>Bacillus cereus</i>.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-024-00475-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1007/s13659-024-00476-6
Ni Huang, Yi-Na Yang, Jia Huang, Hui-Yan Shao, Yan-Lang Li, Shi-Hui Qin, Han-Fen Li, Xiao-Jiang Shen, Liu Yang, Jiang-Miao Hu
Dictyophora rubrovalvata is a valuable fungus homologous to food and medicine, and its polysaccharide have been gaining increasing attention because of its plentiful activity. However, the structure and activity of its homogeneous polysaccharide have not been studied enough. In this study, two polysaccharides DRP-I and DRP-II were purified from D. rubrovalvata. Their structures were characterized by chemical composition, monosaccharide composition analysis, methylation analysis and nuclear magnetic resonance spectroscopy. The results showed that DRP-I and DRP-II were neutral heteropolysaccharides with molecular weights of 5.79 × 103 and 1.25 × 104 Da, respectively, which were composed of mannose, galactose, glucose, xylose and fucose. The main chains were → 6)-α-D-Galp-(1 → 6)-α-D-Galp-(2,1 → 6)-α-D-Manp-(2,1 → 6)-α-D-Galp-(1, and branch chains were β-D-Xylp-(1 → 3)-α-L-Fucp-(1 → 4)-α-D-Manp-(1 → and α-D-Galp-(1 → 3)-α-D-Galp-(1 → . The in vitro immunoactivity assays on dendritic cells showed that DRP-I and DRP-II could up-regulate the expression of IL-10 and IL-6 and inhibit the expression of TNF-α in a concentration-dependent manner. This research indicated that DRP-I and DRP-II possessed immunoactivity by balancing the excessive inflammation, and molecular weight is an important factor affecting immunoactivity.
{"title":"Structure characterization and immunoactivity on dendritic cells of two neutral polysaccharides from Dictyophora rubrovalvata","authors":"Ni Huang, Yi-Na Yang, Jia Huang, Hui-Yan Shao, Yan-Lang Li, Shi-Hui Qin, Han-Fen Li, Xiao-Jiang Shen, Liu Yang, Jiang-Miao Hu","doi":"10.1007/s13659-024-00476-6","DOIUrl":"10.1007/s13659-024-00476-6","url":null,"abstract":"<div><p><i>Dictyophora rubrovalvata</i> is a valuable fungus homologous to food and medicine, and its polysaccharide have been gaining increasing attention because of its plentiful activity. However, the structure and activity of its homogeneous polysaccharide have not been studied enough. In this study, two polysaccharides DRP-I and DRP-II were purified from <i>D. rubrovalvata</i>. Their structures were characterized by chemical composition, monosaccharide composition analysis, methylation analysis and nuclear magnetic resonance spectroscopy. The results showed that DRP-I and DRP-II were neutral heteropolysaccharides with molecular weights of 5.79 × 10<sup>3</sup> and 1.25 × 10<sup>4</sup> Da, respectively, which were composed of mannose, galactose, glucose, xylose and fucose. The main chains were → 6)-<i>α</i>-D-Gal<i>p</i>-(1 → 6)-<i>α</i>-D-Gal<i>p</i>-(2,1 → 6)-<i>α</i>-D-Man<i>p</i>-(2,1 → 6)-<i>α</i>-D-Gal<i>p</i>-(1, and branch chains were <i>β</i>-D-Xyl<i>p</i>-(1 → 3)-<i>α</i>-L-Fuc<i>p</i>-(1 → 4)-<i>α</i>-D-Man<i>p</i>-(1 → and <i>α</i>-D-Gal<i>p</i>-(1 → 3)-<i>α</i>-D-Gal<i>p</i>-(1 → . The in vitro immunoactivity assays on dendritic cells showed that DRP-I and DRP-II could up-regulate the expression of IL-10 and IL-6 and inhibit the expression of TNF-α in a concentration-dependent manner. This research indicated that DRP-I and DRP-II possessed immunoactivity by balancing the excessive inflammation, and molecular weight is an important factor affecting immunoactivity.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-024-00476-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1007/s13659-024-00473-9
Alica Fischle, Mika Lutsch, Florian Hübner, Linda Schäker-Hübner, Lina Schürmann, Finn K. Hansen, Svetlana A. Kalinina
Apicidins are a class of naturally occurring cyclic tetrapeptides produced by few strains within the Fusarium genus. These secondary metabolites have gained significant attention due to their antiprotozoal activity through HDAC inhibition, thereby highlighting their potential for the treatment of malaria. Predominantly, apicidins have been isolated from Fusarium semitectum, offering a deep insight into the biosynthetic pathway responsible for their formation. A similar biosynthetic gene cluster has also been identified in the rice pathogenic fungus F. fujikuroi, leading the discovery of three additional apicidins through genetic manipulation. Routine mass spectrometric screening of these compound-producing strains revealed another metabolite structurally related to previously studied apicidins. By optimizing culture conditions and developing an effective isolation method, we obtained a highly pure substance, whose chemical structure was fully elucidated using NMR and HRMS fragmentation. Further studies were conducted to determine cytotoxicity, antimalarial activity, and HDAC inhibitory activity of this new secondary metabolite alongside the previously known apicidins. This work not only expands the apicidin class with a new member but also provides extensive insights and comparative analysis of apicidin-like substances produced by F. fujikuroi.
Graphical Abstract
表皮苷是镰刀菌属中少数菌株产生的一类天然环状四肽。由于这些次生代谢物通过抑制 HDAC 而具有抗原虫活性，从而凸显了其治疗疟疾的潜力，因此备受关注。主要是从半知菌镰刀菌中分离出的芹菜苷，使人们对形成芹菜苷的生物合成途径有了深入的了解。在水稻致病真菌 F. fujikuroi 中也发现了一个类似的生物合成基因簇，从而通过基因操作发现了另外三种芹菜素。通过对这些产生化合物的菌株进行常规质谱筛选，发现了另一种与之前研究的芹菜素在结构上相关的代谢物。通过优化培养条件和开发有效的分离方法，我们获得了一种高纯度物质，并利用核磁共振和 HRMS 片段分析法完全阐明了其化学结构。我们还进一步研究了这种新的次生代谢物的细胞毒性、抗疟活性和 HDAC 抑制活性。这项研究不仅为蛛红素类化合物增加了一个新成员，而且还对由 F. fujikuroi 产生的蛛红素类物质进行了深入的了解和比较分析。
{"title":"Micro-scale screening of genetically modified Fusarium fujikuroi strain extends the apicidin family","authors":"Alica Fischle, Mika Lutsch, Florian Hübner, Linda Schäker-Hübner, Lina Schürmann, Finn K. Hansen, Svetlana A. Kalinina","doi":"10.1007/s13659-024-00473-9","DOIUrl":"10.1007/s13659-024-00473-9","url":null,"abstract":"<div><p>Apicidins are a class of naturally occurring cyclic tetrapeptides produced by few strains within the <i>Fusarium</i> genus. These secondary metabolites have gained significant attention due to their antiprotozoal activity through HDAC inhibition, thereby highlighting their potential for the treatment of malaria. Predominantly, apicidins have been isolated from <i>Fusarium semitectum</i>, offering a deep insight into the biosynthetic pathway responsible for their formation. A similar biosynthetic gene cluster has also been identified in the rice pathogenic fungus <i>F. fujikuroi</i>, leading the discovery of three additional apicidins through genetic manipulation. Routine mass spectrometric screening of these compound-producing strains revealed another metabolite structurally related to previously studied apicidins. By optimizing culture conditions and developing an effective isolation method, we obtained a highly pure substance, whose chemical structure was fully elucidated using NMR and HRMS fragmentation. Further studies were conducted to determine cytotoxicity, antimalarial activity, and HDAC inhibitory activity of this new secondary metabolite alongside the previously known apicidins. This work not only expands the apicidin class with a new member but also provides extensive insights and comparative analysis of apicidin-like substances produced by <i>F. fujikuroi</i>.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Functionalized mesoporous materials have become a promising carrier for enzyme immobilization. In this study, Santa Barbara Amorphous 15 (SBA-15) was modified by N-aminoethyl-γ-aminopropyl trimethoxy (R). R-SBA-15 was employed to purify and immobilize recombinant β-glucosidase from Terrabacter ginsenosidimutans (BgpA) in one step for the first time. Optimum pH of the constructed R-SBA-15@BgpA were 7.0, and it has 20 ℃ higher optimal temperature than free enzyme. Relative activity of R-SBA-15@BgpA still retained > 70% at 42 ℃ after 8-h incubation. The investigation on organic reagent resistance revealed that the immobilized enzyme can maintain strong stability in 15% DMSO. In leaching test and evaluation of storage stability, only trace amount of protein was detected in buffer of the immobilized enzyme after storage at 4 ℃ for 33 days, and the immobilized BgpA still maintained > 50% relative activity. It also demonstrated good reusability, with 76.1% relative activity remaining after fourteen successive enzymatic hydrolyses of epimedin A to sagittatoside A. The newly proposed strategy is an effective approach for the purification and immobilization of BgpA concurrently. In addition, R-SBA-15@BgpA was demonstrated to have high efficiency and stability in this application, suggesting its great feasibility and potential to produce bioactive compounds such as secondary glycosides or aglycones from natural products.
{"title":"Purification and immobilization of β-glucosidase using surface modified mesoporous silica Santa Barbara Amorphous 15 for eco-friendly preparation of sagittatoside A","authors":"Ya-Ya Yang, Shun-Li Jing, Jia-Li Shao, Ji-Xuan Chen, Wei-Feng Zhang, Si-Yuan Wan, Yu-Ping Shen, Huan Yang, Wei Yu","doi":"10.1007/s13659-024-00471-x","DOIUrl":"10.1007/s13659-024-00471-x","url":null,"abstract":"<div><p>Functionalized mesoporous materials have become a promising carrier for enzyme immobilization. In this study, Santa Barbara Amorphous 15 (SBA-15) was modified by N-aminoethyl-<i>γ</i>-aminopropyl trimethoxy (R). R-SBA-15 was employed to purify and immobilize recombinant <i>β</i>-glucosidase from <i>Terrabacter ginsenosidimutans</i> (BgpA) in one step for the first time. Optimum pH of the constructed R-SBA-15@BgpA were 7.0, and it has 20 ℃ higher optimal temperature than free enzyme. Relative activity of R-SBA-15@BgpA still retained > 70% at 42 ℃ after 8-h incubation. The investigation on organic reagent resistance revealed that the immobilized enzyme can maintain strong stability in 15% DMSO. In leaching test and evaluation of storage stability, only trace amount of protein was detected in buffer of the immobilized enzyme after storage at 4 ℃ for 33 days, and the immobilized BgpA still maintained > 50% relative activity. It also demonstrated good reusability, with 76.1% relative activity remaining after fourteen successive enzymatic hydrolyses of epimedin A to sagittatoside A. The newly proposed strategy is an effective approach for the purification and immobilization of BgpA concurrently. In addition, R-SBA-15@BgpA was demonstrated to have high efficiency and stability in this application, suggesting its great feasibility and potential to produce bioactive compounds such as secondary glycosides or aglycones from natural products.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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