Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60555-8
Miao LI , Jiacong XIAO , Baihao CHEN , Zhaofeng PAN , Fanchen WANG , Weijian CHEN , Qi HE , Jianliang LI , Shaocong LI , Ting WANG , Gangyu ZHANG , Haibin WANG , Jianfa CHEN
Loganin (LOG), a bioactive compound derived from Cornus officinalis Siebold & Zucc, has been understudied in the context of osteoarthritis (OA) treatment. In this study, we induced an inflammatory response in chondrocytes using lipopolysaccharide (LPS) and subsequently treated these cells with LOG. We employed fluorescence analysis to quantify reactive oxygen species (ROS) levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2 (NRF2) using real-time quantitative polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence (IF) techniques. Additionally, we developed an OA mouse model by performing medial meniscus destabilization (DMM) surgery and monitored disease progression through micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, safranin O and fast green (S&F) staining, and immunohistochemical (IHC) analysis. Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes, inhibited the activation of the NLRP3 inflammasome, and enhanced NRF2/heme oxygenase 1 (HO-1) signaling. In vivo, LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery, decreased NLRP3 expression, and increased NRF2 expression. These findings suggest that LOG has a protective effect against OA, potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.
Loganin（LOG）是从山茱萸（Cornus officinalis Siebold & Zucc）中提取的一种生物活性化合物，在骨关节炎（OA）治疗方面的研究一直不足。在这项研究中，我们使用脂多糖（LPS）诱导软骨细胞产生炎症反应，然后用 LOG 处理这些细胞。我们采用荧光分析量化活性氧（ROS）水平，并使用实时定量聚合酶链反应（qRT-PCR）、Western 印迹和免疫荧光（IF）技术测量了 NLRP3 和核因子促红细胞生成素-2 相关因子 2（NRF2）的表达。此外，我们还通过内侧半月板失稳（DMM）手术建立了一个 OA 小鼠模型，并通过显微计算机断层扫描（micro-CT）、苏木精和伊红（H&E）染色、黄蓍素 O 和快绿（S&F）染色以及免疫组化（IHC）分析监测疾病进展。我们的研究结果表明，LOG能明显降低LPS诱导的软骨细胞中的ROS水平，抑制NLRP3炎性体的活化，并增强NRF2/血红素加氧酶1（HO-1）信号传导。在体内，LOG治疗减轻了DMM手术引发的软骨退化和骨质增生的形成，降低了NLRP3的表达，增加了NRF2的表达。这些研究结果表明，LOG对OA具有保护作用，可能通过抑制ROS-NLRP3-IL-1β轴和激活NRF2/HO-1通路来延缓疾病进展。
{"title":"Loganin inhibits the ROS-NLRP3-IL-1β axis by activating the NRF2/HO-1 pathway against osteoarthritis","authors":"Miao LI , Jiacong XIAO , Baihao CHEN , Zhaofeng PAN , Fanchen WANG , Weijian CHEN , Qi HE , Jianliang LI , Shaocong LI , Ting WANG , Gangyu ZHANG , Haibin WANG , Jianfa CHEN","doi":"10.1016/S1875-5364(24)60555-8","DOIUrl":"10.1016/S1875-5364(24)60555-8","url":null,"abstract":"<div><div>Loganin (LOG), a bioactive compound derived from <em>Cornus officinalis</em> Siebold & Zucc, has been understudied in the context of osteoarthritis (OA) treatment. In this study, we induced an inflammatory response in chondrocytes using lipopolysaccharide (LPS) and subsequently treated these cells with LOG. We employed fluorescence analysis to quantify reactive oxygen species (ROS) levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2 (NRF2) using real-time quantitative polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence (IF) techniques. Additionally, we developed an OA mouse model by performing medial meniscus destabilization (DMM) surgery and monitored disease progression through micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, safranin O and fast green (S&F) staining, and immunohistochemical (IHC) analysis. Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes, inhibited the activation of the NLRP3 inflammasome, and enhanced NRF2/heme oxygenase 1 (HO-1) signaling. <em>In vivo</em>, LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery, decreased NLRP3 expression, and increased NRF2 expression. These findings suggest that LOG has a protective effect against OA, potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 977-990"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60592-3
Longgao XIAO , Yueqin ZHAO , Xiao DING , Hui LIU , Guangyu ZHU , Yanxi LI , Huan YAN , Xin FANG , Yuhan ZHAO , Haiyang LIU
Three novel sesquiterpenoid heterodimers, designated as auckcostusolides A–C (1–3), were isolated from Aucklandia costus leaves. The structures of compounds 1–3 were elucidated through comprehensive spectroscopic analysis, with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism (ECD) calculations. Notably, compounds 1 and 2, despite sharing identical planar structures derived from two identical sesquiterpenoids, exhibited opposite configurations at C-11 and C-8′. This configurational difference can be attributed to distinct Diels−Alder cycloaddition processes between the sesquiterpenoid monomers. Additionally, the cytotoxic effects of compounds 1–3 were evaluated against colorectal cancer HCT116 cells, fibrosarcoma HT1080 cells, and hepatocellular carcinoma HepG2 cells. Compounds 1–3 induced cell death was characterized by endoplasmic reticulum (ER) swelling and cytoplasmic vacuolization, typical morphological changes associated with paraptosis. Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of reactive oxygen species (ROS), activation of ER stress, and stimulation of the MAPK signaling pathway.
{"title":"Eudesmane-guaiane sesquiterpenoid dimers from Aucklandia costus trigger paraptosis-like cell death via ROS accumulation and MAPK hyperactivation","authors":"Longgao XIAO , Yueqin ZHAO , Xiao DING , Hui LIU , Guangyu ZHU , Yanxi LI , Huan YAN , Xin FANG , Yuhan ZHAO , Haiyang LIU","doi":"10.1016/S1875-5364(24)60592-3","DOIUrl":"10.1016/S1875-5364(24)60592-3","url":null,"abstract":"<div><div>Three novel sesquiterpenoid heterodimers, designated as auckcostusolides A–C (<strong>1</strong>–<strong>3</strong>), were isolated from <em>Aucklandia costus</em> leaves. The structures of compounds <strong>1</strong>–<strong>3</strong> were elucidated through comprehensive spectroscopic analysis, with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism (ECD) calculations. Notably, compounds <strong>1</strong> and <strong>2</strong>, despite sharing identical planar structures derived from two identical sesquiterpenoids, exhibited opposite configurations at C-11 and C-8′. This configurational difference can be attributed to distinct Diels−Alder cycloaddition processes between the sesquiterpenoid monomers. Additionally, the cytotoxic effects of compounds <strong>1</strong>–<strong>3</strong> were evaluated against colorectal cancer HCT116 cells, fibrosarcoma HT1080 cells, and hepatocellular carcinoma HepG2 cells. Compounds <strong>1</strong>–<strong>3</strong> induced cell death was characterized by endoplasmic reticulum (ER) swelling and cytoplasmic vacuolization, typical morphological changes associated with paraptosis. Mechanistic studies revealed that compounds <strong>1</strong> and <strong>3</strong> triggered paraptosis-like cell death through the accumulation of reactive oxygen species (ROS), activation of ER stress, and stimulation of the MAPK signaling pathway.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 1011-1019"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60607-2
An JIN , Fangfang DUAN , Hanli RUAN
A phytochemical investigation of the whole plant of Parasenecio rubescens (S. Moore) Y. L. Chen yielded 14 previously undescribed, highly oxidized bisabolane-type sesquiterpenoids, named pararunines L–Y, along with one known oplopane-type sesquiterpenoid. The structural elucidation of these compounds was accomplished through comprehensive spectroscopic analysis, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) techniques. Motivated by traditional uses and previous studies on this genus, all isolated compounds were subjected to in vitro cytotoxicity assays against four human cancer cell lines (MCF-7, Hela, HCT116, and HT-29). Considering that the reported chemical constituents of numerous other species within this genus primarily consist of eremophilane-type sesquiterpenoids, our findings not only expand the structural diversity of bisabolane-type sesquiterpenoids but also contribute valuable scientific evidence to the chemotaxonomy of this genus.
通过对 Parasenecio rubescens (S. Moore) Y. L. Chen 的全草进行植物化学研究，发现了 14 种以前未曾描述过的、高度氧化的双苯甲酸酯类倍半萜化合物，命名为 Pararunines L-Y，以及一种已知的 oplopane 类倍半萜化合物。通过全面的光谱分析，包括核磁共振（NMR）和高分辨率电喷雾质谱（HR-ESI-MS）技术，对这些化合物的结构进行了阐明。受该属植物的传统用途和先前研究的启发，对所有分离出的化合物进行了体外细胞毒性试验，以检测其对四种人类癌细胞系（MCF-7、Hela、HCT116 和 HT-29）的毒性。考虑到已报道的该属中许多其他物种的化学成分主要由酯类倍半萜类化合物组成，我们的研究结果不仅扩大了双香蒲烷类倍半萜类化合物的结构多样性，还为该属的化学分类学提供了宝贵的科学证据。
{"title":"Highly oxidized sesquiterpenoids from Parasenecio rubescens and assessment of their cytotoxicity","authors":"An JIN , Fangfang DUAN , Hanli RUAN","doi":"10.1016/S1875-5364(24)60607-2","DOIUrl":"10.1016/S1875-5364(24)60607-2","url":null,"abstract":"<div><div>A phytochemical investigation of the whole plant of <em>Parasenecio rubescens</em> (S. Moore) Y. L. Chen yielded 14 previously undescribed, highly oxidized bisabolane-type sesquiterpenoids, named pararunines L–Y, along with one known oplopane-type sesquiterpenoid. The structural elucidation of these compounds was accomplished through comprehensive spectroscopic analysis, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) techniques. Motivated by traditional uses and previous studies on this genus, all isolated compounds were subjected to <em>in vitro</em> cytotoxicity assays against four human cancer cell lines (MCF-7, Hela, HCT116, and HT-29). Considering that the reported chemical constituents of numerous other species within this genus primarily consist of eremophilane-type sesquiterpenoids, our findings not only expand the structural diversity of bisabolane-type sesquiterpenoids but also contribute valuable scientific evidence to the chemotaxonomy of this genus.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 1020-1029"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60632-1
Hongwei CHEN , Meng DING , Jun LIN , Shuo YUAN , Kewu ZENG , Pengfei TU , Yong JIANG
Six novel compounds, comprising three quinolones (1a, 1b, and 2) and three flavanones (3–5), along with seven known analogs (6–13), were isolated from the 95% EtOH extract of the stems and leaves of Glycosmis craibii var. glabra. The structures of the new compounds were elucidated using HR-ESI-MS, UV, and 1D and 2D nuclear magnetic resonance (NMR) data analysis. The absolute configurations were determined through Mosher ester and electronic circular dichroism (ECD) spectral analysis. Compounds 2, 6, 9, and 10 demonstrated inhibition of nitric oxide (NO) production stimulated by lipopolysaccharide in BV-2 microglial cells, with IC50 values ranging from 13.5 to 20.1 μmol·L−1, comparable to the positive control, dexamethasone.
{"title":"NO inhibitory constituents from Glycosmis craibii var. glabra","authors":"Hongwei CHEN , Meng DING , Jun LIN , Shuo YUAN , Kewu ZENG , Pengfei TU , Yong JIANG","doi":"10.1016/S1875-5364(24)60632-1","DOIUrl":"10.1016/S1875-5364(24)60632-1","url":null,"abstract":"<div><div>Six novel compounds, comprising three quinolones (<strong>1a</strong>, <strong>1b</strong>, and <strong>2</strong>) and three flavanones (<strong>3</strong>–<strong>5</strong>), along with seven known analogs (<strong>6</strong>–<strong>13</strong>), were isolated from the 95% EtOH extract of the stems and leaves of <em>Glycosmis craibii</em> var. <em>glabra</em>. The structures of the new compounds were elucidated using HR-ESI-MS, UV, and 1D and 2D nuclear magnetic resonance (NMR) data analysis. The absolute configurations were determined through Mosher ester and electronic circular dichroism (ECD) spectral analysis. Compounds <strong>2, 6, 9</strong>, and <strong>10</strong> demonstrated inhibition of nitric oxide (NO) production stimulated by lipopolysaccharide in BV-2 microglial cells, with IC<sub>50</sub> values ranging from 13.5 to 20.1 μmol·L<sup>−1</sup>, comparable to the positive control, dexamethasone.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 1040-1046"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60575-3
Mengru WANG , Qi WANG , Yanzi MA , Muhammad Aurang ZEB , Xiaoli LI , Feng SHEN , Weilie XIAO
Two new nor-ent-halimane diterpenes and three previously unreported nor-clerodane diterpenes, designated callicaintides A−E (1−5), were isolated from Callicarpa integerrima. Compounds 1 and 2 feature a distinctive 5/6-membered ring system, while compounds 3−5 are characterized by progressively truncated carbon skeletons, containing 18, 17, and 16 carbons, respectively. In addition, four known compounds 6−9 were also identified. Their structures were elucidated using advanced spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared radiation (IR), optical rotatory dispersion (ORD), DP4+ analysis and electronic circular dichroism (ECD), supported by quantum chemical calculations. Compounds 1−9 were evaluated for their anti-MRSA activity. Among them, compound 6 demonstrated significant anti-MRSA activity, with a minimum inhibitory concentration (MIC) of 16 μg·mL−1.
{"title":"New nor-ent-halimane and nor-clerodane diterpenes from Callicarpa integerrima with anti-MRSA activity","authors":"Mengru WANG , Qi WANG , Yanzi MA , Muhammad Aurang ZEB , Xiaoli LI , Feng SHEN , Weilie XIAO","doi":"10.1016/S1875-5364(24)60575-3","DOIUrl":"10.1016/S1875-5364(24)60575-3","url":null,"abstract":"<div><div>Two new <em>nor-ent-halimane</em> diterpenes and three previously unreported <em>nor</em>-clerodane diterpenes, designated callicaintides A−E (<strong>1−5</strong>), were isolated from <em>Callicarpa integerrima</em>. Compounds <strong>1</strong> and <strong>2</strong> feature a distinctive 5/6-membered ring system, while compounds <strong>3−5</strong> are characterized by progressively truncated carbon skeletons, containing 18, 17, and 16 carbons, respectively. In addition, four known compounds <strong>6−9</strong> were also identified. Their structures were elucidated using advanced spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared radiation (IR), optical rotatory dispersion (ORD), DP4<sup>+</sup> analysis and electronic circular dichroism (ECD), supported by quantum chemical calculations. Compounds <strong>1−9</strong> were evaluated for their anti-MRSA activity. Among them, compound <strong>6</strong> demonstrated significant anti-MRSA activity, with a minimum inhibitory concentration (MIC) of 16 μg·mL<sup>−1</sup>.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 1003-1010"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60706-5
Kang WANG , Pengfei ZHANG , Huiyong SUN , Shuang CUI , Lanjia AO , Ming CUI , Xiaowei XU , Lin WANG , Yuanyuan XU , Guangji WANG , Hong WANG , Haiping HAO
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, with only one Food and Drug Administration (FDA)-approved drug for its treatment. Given MASLD’s complex pathophysiology, therapies that simultaneously target multiple pathways are highly desirable. One promising approach is dual-modulation of the farnesoid X receptor (FXR), which regulates lipid and bile acid metabolism. However, FXR agonists alone are insufficient due to their limited anti-inflammatory effects. This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD. Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger (2018) for molecular docking. Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance (SPR) binding assay, reporter gene analysis, and reverse transcription-polymerase chain reaction (RT-PCR). The anti-inflammatory properties of these compounds were evaluated in AML12 cells treated with tumor necrosis factor-alpha (TNF-α). Dual-function compounds with FXR agonism and inflammation inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α. The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid. Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists, with 15 exhibiting a strong affinity for FXR recombinant protein. Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb. Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones. Three compounds (2, 6, and 8) were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors, while one compound (12) acted as an FXR agonist to inhibit inflammation. These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and inflammation. In conclusion, compounds 2, 6, and 8 (genistein, biochanin A, and 7-methoxyisoflavone, respectively) were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation, serving as potential candidates or lead compounds for MASLD therapy.
{"title":"Dual-function natural products: Farnesoid X receptor agonist/inflammation inhibitor for metabolic dysfunction-associated steatotic liver disease therapy","authors":"Kang WANG , Pengfei ZHANG , Huiyong SUN , Shuang CUI , Lanjia AO , Ming CUI , Xiaowei XU , Lin WANG , Yuanyuan XU , Guangji WANG , Hong WANG , Haiping HAO","doi":"10.1016/S1875-5364(24)60706-5","DOIUrl":"10.1016/S1875-5364(24)60706-5","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, with only one Food and Drug Administration (FDA)-approved drug for its treatment. Given MASLD’s complex pathophysiology, therapies that simultaneously target multiple pathways are highly desirable. One promising approach is dual-modulation of the farnesoid X receptor (FXR), which regulates lipid and bile acid metabolism. However, FXR agonists alone are insufficient due to their limited anti-inflammatory effects. This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD. Potential FXR ligands from the Natural Product Library were predicted <em>via</em> virtual screening using the Protein Preparation Wizard module in Schrodinger (2018) for molecular docking. Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance (SPR) binding assay, reporter gene analysis, and reverse transcription-polymerase chain reaction (RT-PCR). The anti-inflammatory properties of these compounds were evaluated in AML12 cells treated with tumor necrosis factor-alpha (TNF-α). Dual-function compounds with FXR agonism and inflammation inhibition were further identified in cells transfected with <em>Fxr</em> siRNA and treated with TNF-α. The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid. Results revealed that 17 natural products were predicted <em>via</em> computational molecular docking as potential FXR agonists, with 15 exhibiting a strong affinity for FXR recombinant protein. Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of <em>Shp</em> and <em>Ostb</em>. Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones. Three compounds (<strong>2</strong>, <strong>6</strong>, and <strong>8</strong>) were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors, while one compound (<strong>12</strong>) acted as an FXR agonist to inhibit inflammation. These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and inflammation. In conclusion, compounds <strong>2</strong>, <strong>6</strong>, and <strong>8</strong> (genistein, biochanin A, and 7-methoxyisoflavone, respectively) were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation, serving as potential candidates or lead compounds for MASLD therapy.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 965-976"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60568-6
Xueqian XIE , Pengcheng LI , Meng ZHAO , Bo XU , Guixing ZHANG , Qing WANG , Chen NI , Xia LUO , Lian ZHOU
The disorder of group 3 innate lymphoid cells (ILC3) subgroup, such as the predominance of NCR-ILC3 but the depletion of NCR+ILC3, is unfavorable to damaged intestinal barrier repair, which leads to the prolongations and obstinacy of ulcerative colitis (UC). Our previous studies had shown that luteolin promoted NCR−ILC3 differentitating into NCR+ILC3 to improving the depletion of NCR+ILC3 in UC mice, while the mechanism is unclear. This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3. UC mice model was established with 2% DSS and Notch signaling was blocked, then luteolin was used to intervene. The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice, including inhibiting the weight loss, reducing the pathological damage of colon mucosa, etc., was diminished with blocking Notch signaling pathway. In addition, luteolin increased the proportion of NCR+ILC3, NCR+MNK3 and IL-22+ILC3, decreased intestinal permeability, promoted mucin secretion, and promoted ZO-1 and Occludin expression, the above effect of luteolin was neutralized by Notch inhibitor LY-411575. Luteolin activated the abnormally blocked Notch signaling pathway in UC mice. And molecular docking predicted the affinity of luteolin for RBPJ to be −7.5 kcal·mol−1 in mouse, respectively; the affinity of luteolin for Notch1 and RBPJ was respectively scored to be −6.4 kcal·mol−1 and −7.7 kcal·mol−1 homo sapiens. These results proved that luteolin is positive for enhancing the proportion of NCR+ILC3 via Notch signaling, and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alleviating ulcerative colitis.
{"title":"Luteolin ameliorates ulcerative colitis in mice via reducing the depletion of NCR+ILC3 through Notch signaling pathway","authors":"Xueqian XIE , Pengcheng LI , Meng ZHAO , Bo XU , Guixing ZHANG , Qing WANG , Chen NI , Xia LUO , Lian ZHOU","doi":"10.1016/S1875-5364(24)60568-6","DOIUrl":"10.1016/S1875-5364(24)60568-6","url":null,"abstract":"<div><div>The disorder of group 3 innate lymphoid cells (ILC3) subgroup, such as the predominance of NCR<sup>-</sup>ILC3 but the depletion of NCR<sup>+</sup>ILC3, is unfavorable to damaged intestinal barrier repair, which leads to the prolongations and obstinacy of ulcerative colitis (UC). Our previous studies had shown that luteolin promoted NCR<sup>−</sup>ILC3 differentitating into NCR<sup>+</sup>ILC3 to improving the depletion of NCR<sup>+</sup>ILC3 in UC mice, while the mechanism is unclear. This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR<sup>+</sup>ILC3. UC mice model was established with 2% DSS and Notch signaling was blocked, then luteolin was used to intervene. The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice, including inhibiting the weight loss, reducing the pathological damage of colon mucosa, <em>etc.</em>, was diminished with blocking Notch signaling pathway. In addition, luteolin increased the proportion of NCR<sup>+</sup>ILC3, NCR<sup>+</sup>MNK3 and IL-22<sup>+</sup>ILC3, decreased intestinal permeability, promoted mucin secretion, and promoted ZO-1 and Occludin expression, the above effect of luteolin was neutralized by Notch inhibitor LY-411575. Luteolin activated the abnormally blocked Notch signaling pathway in UC mice. And molecular docking predicted the affinity of luteolin for RBPJ to be −7.5 kcal·mol<sup>−1</sup> in mouse, respectively; the affinity of luteolin for Notch1 and RBPJ was respectively scored to be −6.4 kcal·mol<sup>−1</sup> and −7.7 kcal·mol<sup>−1</sup> homo sapiens. These results proved that luteolin is positive for enhancing the proportion of NCR<sup>+</sup>ILC3 <em>via</em> Notch signaling, and it provides a basis for targeting NCR<sup>+</sup>ILC3 for restoring intestinal barrier function to alleviating ulcerative colitis.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 991-1002"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60611-4
Xinyuan ZHANG , Mingzhi SU , Mingxin ZHU , Sha CHEN , Zhen GAO , Yuewei GUO , Xuwen LI
A novel amide alkaloid, bursatamide A (1), featuring an unprecedented propyl-hexahydronaphthalene carbon framework, was isolated from the infrequently studied sea hare Bursatella leachi, alongside a new 3-phenoxypropanenitrile alkaloid, bursatellin B (2), and twelve known compounds. The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses, while their relative and absolute configurations (ACs) were established through total synthesis and a series of quantum chemical calculations, including calculated electronic circular dichroism (ECD) spectra, optical rotatory dispersion (ORD) methods, and DP4+ probability analyses. Bursatamide A (1) demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocytogenes and Vibrio cholerae. Erythro-bursatellin B (21), a diastereoisomer of 2, exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28, with an MIC90 value of 0.0472 μg·mL−1.
{"title":"The biologically and ecologically important natural products from the Chinese sea hare Bursatella leachii: structures, stereochemistry and beyond","authors":"Xinyuan ZHANG , Mingzhi SU , Mingxin ZHU , Sha CHEN , Zhen GAO , Yuewei GUO , Xuwen LI","doi":"10.1016/S1875-5364(24)60611-4","DOIUrl":"10.1016/S1875-5364(24)60611-4","url":null,"abstract":"<div><div>A novel amide alkaloid, bursatamide A (<strong>1</strong>), featuring an unprecedented propyl-hexahydronaphthalene carbon framework, was isolated from the infrequently studied sea hare <em>Bursatella leachi</em>, alongside a new 3-phenoxypropanenitrile alkaloid, bursatellin B (<strong>2</strong>), and twelve known compounds. The structures of <strong>1</strong> and <strong>2</strong> were elucidated through comprehensive spectroscopic data analyses, while their relative and absolute configurations (ACs) were established through total synthesis and a series of quantum chemical calculations, including calculated electronic circular dichroism (ECD) spectra, optical rotatory dispersion (ORD) methods, and DP4+ probability analyses. Bursatamide A (<strong>1</strong>) demonstrated inhibitory effects against the human pathogenic bacteria <em>Listeria monocytogenes</em> and <em>Vibrio cholerae. Erythro</em>-bursatellin B (<strong>21</strong>), a diastereoisomer of <strong>2</strong>, exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28, with an MIC<sub>90</sub> value of 0.0472 μg·mL<sup>−1</sup>.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 1030-1039"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60724-7
Hongtao LI , Ruining YANG , Fei XIE , Tianpeng XIE , Linhuan TANG , Hao ZHOU , Zhongtao DING
Three novel, highly oxygenated polyketides, multioketides A−C (1−3), and three previously described multioxidized aromatic polyketides (4−6), were isolated from an endophytic Penicillium sp. YUD17006 associated with Gastrodia elata. Their chemical structures were elucidated using extensive spectroscopic data, electronic circular dichroism calculations, and single X-ray diffraction analysis. All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation. Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core. Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities. Plausible biosynthetic pathways for 1−6 were proposed. Additionally, compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyrosine phosphatase 1B.
从与 Gastrodia elata 相关的内生青霉 YUD17006 中分离出了三种新型高含氧多酮苷，多酮苷 A-C (1-3)，以及之前描述过的三种多氧化芳香族多酮苷 (4-6)。通过大量光谱数据、电子圆二色性计算和单 X 射线衍射分析，阐明了它们的化学结构。所有代谢物都具有典型的 α、β-不饱和酮片段，并表现出高度氧化性。经鉴定，多酮类化合物 A 和 B 是一对具有罕见二氢异苯并呋喃酮核心的表聚物。多酮类化合物 C 具有新颖的 5/6/6/6 杂四环化学结构和不寻常的 1,4-二恶英官能团。提出了 1-6 的合理生物合成途径。此外，化合物 3 对乙酰胆碱酯酶和蛋白酪氨酸磷酸酶 1B 都有微弱的抑制活性。
{"title":"Multioxidized polyketides from an endophytic Penicillium sp. YUD17006 associated with Gastrodia elata","authors":"Hongtao LI , Ruining YANG , Fei XIE , Tianpeng XIE , Linhuan TANG , Hao ZHOU , Zhongtao DING","doi":"10.1016/S1875-5364(24)60724-7","DOIUrl":"10.1016/S1875-5364(24)60724-7","url":null,"abstract":"<div><div>Three novel, highly oxygenated polyketides, multioketides A−C (<strong>1</strong>−<strong>3</strong>), and three previously described multioxidized aromatic polyketides (<strong>4−6</strong>), were isolated from an endophytic <em>Penicillium</em> sp. YUD17006 associated with <em>Gastrodia elata</em>. Their chemical structures were elucidated using extensive spectroscopic data, electronic circular dichroism calculations, and single X-ray diffraction analysis. All metabolites were characterized by a typical <em>α</em>,<em>β</em>-unsaturated ketone fragment and exhibited a high degree of oxidation. Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core. Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities. Plausible biosynthetic pathways for <strong>1−6</strong> were proposed. Additionally, compound <strong>3</strong> demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyrosine phosphatase 1B.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 1057-1064"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S1875-5364(24)60659-X
Chunmei CHEN , Xueni WANG , Wenxuan FANG , Jiaqi LIANG , Jian CAI , Dehua YANG , Xiaowei LUO , Chenghai GAO , Xiangxi YI , Yonghong LIU , Xuefeng ZHOU
Seven novel linear polyketides, talaketides A−G (1−7), were isolated from the rice media cultures of the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027. Among these, talaketides A−E (1−5) represented unprecedented unsaturated linear polyketides with an epoxy ring structure. The structures, including absolute configurations of these compounds, were elucidated through detailed analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HR-MS) data, as well as electronic custom distributors (ECD) calculations. In the cytotoxicity screening against prostate cancer cell lines, talaketide E (5) demonstrated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines, with an IC50 value of 14.44 μmol·L−1 . Moreover, compound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase, ultimately inducing apoptosis. These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treatment for prostate cancer.
{"title":"Talaketides A−G, linear polyketides with prostate cancer cytotoxic activity from the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027","authors":"Chunmei CHEN , Xueni WANG , Wenxuan FANG , Jiaqi LIANG , Jian CAI , Dehua YANG , Xiaowei LUO , Chenghai GAO , Xiangxi YI , Yonghong LIU , Xuefeng ZHOU","doi":"10.1016/S1875-5364(24)60659-X","DOIUrl":"10.1016/S1875-5364(24)60659-X","url":null,"abstract":"<div><div>Seven novel linear polyketides, talaketides A−G (<strong>1</strong>−<strong>7</strong>), were isolated from the rice media cultures of the mangrove sediment-derived fungus <em>Talaromyces</em> sp. SCSIO 41027. Among these, talaketides A−E (<strong>1</strong>−<strong>5</strong>) represented unprecedented unsaturated linear polyketides with an epoxy ring structure. The structures, including absolute configurations of these compounds, were elucidated through detailed analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HR-MS) data, as well as electronic custom distributors (ECD) calculations. In the cytotoxicity screening against prostate cancer cell lines, talaketide E (<strong>5</strong>) demonstrated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines, with an IC<sub>50</sub> value of 14.44 μmol·L<sup>−1</sup> . Moreover, compound <strong>5</strong> significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase, ultimately inducing apoptosis. These findings indicate that compound <strong>5</strong> may serve as a promising lead compound for the development of a potential treatment for prostate cancer.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"22 11","pages":"Pages 1047-1056"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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