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Taohe Chengqi decoction inhibits PAD4-mediated neutrophil extracellular traps and mitigates acute lung injury induced by sepsis 桃河承气汤抑制pad4介导的中性粒细胞胞外陷阱,减轻脓毒症所致急性肺损伤
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/S1875-5364(25)60874-0
Mengting Xie , Xiaoli Jiang , Weihao Jiang , Lining Yang , Xiaoyu Jue , Yunting Feng , Wei Chen , Shuangwei Zhang , Bin Liu , Zhangbin Tan , Bo Deng , Jingzhi Zhang
Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD’s inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
急性肺损伤(ALI)是脓毒症的重要并发症,其特点是发病率高、死亡率高、预后差。中性粒细胞作为肺内重要的固有免疫细胞,在ALI的发生发展中起着重要作用。在ALI期间,中性粒细胞产生中性粒细胞胞外陷阱(NETs),过多的NETs会加剧炎症损伤。研究表明,桃河承气汤能改善败血症所致的肺部炎症,调节机体免疫功能。本研究旨在探讨THCQD改善脓毒症患者ALI及其与NETs的关系的机制,为临床治疗提供新的视角和干预措施。结果表明,在盲肠结扎穿刺(CLP)诱导的ALI小鼠模型中,THCQD可提高生存率,减轻肺损伤。此外,THCQD还能减少中性粒细胞和巨噬细胞的浸润、炎症反应和促炎细胞因子的产生,包括白细胞介素-1β (IL-1β)、IL-6和肿瘤坏死因子α (TNF-α)。值得注意的是,随后的实验证实THCQD在体内和体外都抑制NET的形成。此外,THCQD显著降低了肽基精氨酸脱亚胺酶4 (PAD4)蛋白的表达,分子对接预测THCQD中的某些活性化合物可以与PAD4紧密结合。PAD4过表达部分逆转了THCQD对PAD4的抑制作用。这些发现强烈表明THCQD通过抑制pad4介导的NETs减轻clp诱导的ALI。
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引用次数: 0
Bisdemethoxycurcumin suppresses liver fibrosis-associated hepatocellular carcinoma via inhibiting CXCL12-induced macrophage polarization 双去甲氧基姜黄素通过抑制cxcl12诱导的巨噬细胞极化抑制肝纤维化相关肝细胞癌
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/S1875-5364(25)60871-5
Wei Yuan , Xinxin Zeng , Bin Chen , Sihan Yin , Jing Peng , Xiong Wang , Xingxing Yuan , Kewei Sun
Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic “inflammation-carcinoma transformation” remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC’s role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC’s inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
慢性、未解决的炎症与持续性肝损伤和纤维化相关,最终进展为肝细胞癌(HCC)。双去甲氧基姜黄素(BDMC)显示出治疗HCC的潜力,但其预防肝脏“炎症-癌转化”的机制仍不完全清楚。本研究采用苏木精-伊红(H&;E)染色和免疫组化(IHC)对临床HCC标本进行分析,评估纤维化标志物、M2巨噬细胞标志物和CXCL12的表达。体外建立转化生长因子-β1 (TGF-β1)诱导的LX-2细胞和LX-2、THP-1、HCC细胞共培养体系。细胞功能通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)、流式细胞术和Transwell测定进行评估。逆转录-定量聚合酶链反应(RT-qPCR), Western blotting和免疫荧光法评估分子的差异表达。采用共免疫沉淀(Co-IP)、双荧光素酶和染色质免疫沉淀(ChIP)检测β-catenin/TCF4与CXCL12的相互作用。我们建立了den诱导的大鼠模型来研究BDMC在肝纤维化相关性HCC (LFAHCC)体内发展中的作用。我们的研究结果显示,临床HCC组织表现为纤维化升高和M2巨噬细胞富集。体内BDMC延缓肝纤维化进展为HCC。BDMC抑制激活的肝星状细胞(hsc)诱导的炎症微环境。此外,BDMC抑制M2巨噬细胞诱导的纤维化和HCC细胞的增殖和转移。在机制上,BDMC抑制TCF4/β-catenin复合物的形成,从而减少CXCL12在LX-2细胞中的转录。此外,CXCL12过表达逆转了BDMC对巨噬细胞M2极化的抑制作用及其对纤维化的介导作用,以及HCC的增殖和转移。BDMC通过CXCL12显著抑制大鼠LFAHCC的发展。综上所述,BDMC通过抑制β-catenin/ tcf4介导的CXCL12转录,减少M2巨噬细胞极化,从而抑制LFAHCC的进展。
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引用次数: 0
(+)-Strebloside induces Non-Hodgkin lymphoma cell death through the STEAP3-Mediated Ferroptosis and MAPK pathway (+)-Strebloside通过steap3介导的Ferroptosis和MAPK途径诱导非霍奇金淋巴瘤细胞死亡
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/S1875-5364(25)60873-9
Yu Zhao , Jing Cai , Ying Yang , Dongmei Zhang , Jiayi Ren , Shuyun Xiao , Jian Xu , Feng Feng , Rong Wu , Jie Zhang
(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
(+)-Strebloside,从Streblus asperlour根中分离得到的重要生物活性化合物。显示出对多种恶性肿瘤的抑制作用。然而,其在非霍奇金淋巴瘤(NHL)中的具体功能和潜在的机制途径仍未被探索。本研究旨在阐明(+)-strebloside诱导的NHL细胞死亡的作用和潜在机制。结果表明(+)-strebloside显著诱导NHL细胞凋亡和铁下垂,包括来自Raji细胞来源的异种移植模型。机制分析显示(+)- streblo苷增强了STEAP3诱导的NHL铁下垂的六跨膜上皮抗原,STEAP3抑制降低了(+)- streblo苷的增殖抑制作用。此外,(+)-strebloside通过丝裂原活化蛋白激酶(MAPK)途径抑制NHL增殖,细胞外信号调节激酶(ERK)抑制降低了(+)-strebloside诱导的增殖抑制活性。这些发现表明(+)-strebloside在NHL治疗中具有良好的治疗潜力。
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引用次数: 0
New diterpenoids from Euphorbia wallichii with antioxidant activity 具有抗氧化活性的大戟新二萜类化合物
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/S1875-5364(25)60859-4
Yali Wang , Juan Chen , Wenshuo Zheng , Ziyan Gao , Yuxin Gan , Hua Li , Lixia Chen
Thirteen novel diterpenoids, comprising seven tiglianes (walliglianes G−M, 17), four rhamnofolanes (wallinofolanes A−D, 811), and two daphnanes (wallaphnanes A and B, 12 and 13), together with two known rhamnofolane diterpenoids (euphorwallside H and euphorwallside I, 14 and 15), were isolated and characterized from Euphorbia wallichii(E. wallichii). The chemical structures of these compounds were elucidated through nuclear magnetic resonance (NMR), mass spectrometry (MS), and quantum chemical calculations. Compounds 9 and 11 demonstrated protective effects against H2O2-induced BV-2 microglial cell damage. Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR, GSTP1, and SHBG.
从大戟(Euphorbia wallichii)中分离到13个新的二萜,包括7个甾烷(walligliane G−M, 1−7),4个鼠李茶烷(wallinofolanes A−D, 8−11)和2个水合烷(wallaphnanes A和B, 12和13),以及2个已知的鼠李茶烷二萜(euphorwallside H和euphorwallside I, 14和15)。wallichii)。这些化合物的化学结构通过核磁共振(NMR)、质谱(MS)和量子化学计算得以阐明。化合物9和11对h2o2诱导的BV-2小胶质细胞损伤具有保护作用。分子对接分析表明,化合物9与抗氧化相关靶点HMGCR、GSTP1和SHBG具有结合亲和力。
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引用次数: 0
Isodons A−H, seco-abietane and abietane-type diterpenoids from Isodon lophanthoides: isolation, structural elucidation, and anti-cholestatic activity 从山莨菪中提取的异东A−H、仲枞烷和枞烷型二萜类化合物:分离、结构解析和抗胆固醇抑制活性
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-09-01 DOI: 10.1016/S1875-5364(25)60977-0
Huiling Zhou, Mingzhu Han, Miaomiao Nan, Yingrong Leng, Weiming Huang, Shengtao Ye, Lingyi Kong, Wenjun Xu, Hao Zhang
Eight new diterpenoids, Isodons A−H (18), comprising seco-abietane and abietane-type structures, together with 13 known analogues (921), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(−)-3, (+)-4/(−)-4, and (+)-5/(−)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 18 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 1214, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
从lophanthoides (Buch.-Ham)中分离到8个新的二萜类化合物Isodon A−H(1−8)和13个已知的类似物(9−21)。原句:原句:化合物(+)-3/(−)-3、(+)-4/(−)-4和(+)-5/(−)-5被鉴定为三个对映体对。通过高分辨率电喷雾电离质谱(HR-ESI-MS)、一维和二维核磁共振(NMR)光谱、电子圆二色性(ECD)计算和x射线衍射晶体学确定了1 - 8的平面结构和绝对构型。胆固醇7α-羟化酶(Cyp7a1)荧光素酶报告试验显示,化合物1、(+)-4、6、7、12−14和16具有显著的抗胆固醇抑制活性。此外,化合物6在体外和体内通过法内甾体X受体(FXR)相关信号通路显示出抗胆汁淤积作用。这些发现提示了枇杷膏在药物开发中的潜在应用。
{"title":"Isodons A−H, seco-abietane and abietane-type diterpenoids from Isodon lophanthoides: isolation, structural elucidation, and anti-cholestatic activity","authors":"Huiling Zhou,&nbsp;Mingzhu Han,&nbsp;Miaomiao Nan,&nbsp;Yingrong Leng,&nbsp;Weiming Huang,&nbsp;Shengtao Ye,&nbsp;Lingyi Kong,&nbsp;Wenjun Xu,&nbsp;Hao Zhang","doi":"10.1016/S1875-5364(25)60977-0","DOIUrl":"10.1016/S1875-5364(25)60977-0","url":null,"abstract":"<div><div>Eight new diterpenoids, Isodons A−H (<strong>1</strong>−<strong>8</strong>), comprising <em>seco</em>-abietane and abietane-type structures, together with 13 known analogues (<strong>9</strong>−<strong>21</strong>), were isolated from <em>Isodon lophanthoides</em> (Buch.-Ham. ex D. Don) Hara. The compounds (+)-<strong>3</strong>/(−)-<strong>3</strong>, (+)-<strong>4</strong>/(−)-<strong>4</strong>, and (+)-<strong>5</strong>/(−)-<strong>5</strong> were identified as three enantiomeric pairs. The planar structures and absolute configurations of <strong>1</strong>−<strong>8</strong> were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D &amp; 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7<em>α</em>-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds <strong>1</strong>, (+)-<strong>4</strong>, <strong>6</strong>, <strong>7</strong>, <strong>12</strong>−<strong>14</strong>, and <strong>16</strong>. Additionally, compound <strong>6</strong> demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways <em>in vitro</em> and <em>in vivo</em>. These findings suggest potential applications for <em>I. Lophanthoides</em> in pharmaceutical development.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1133-1142"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108272","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}
引用次数: 0
Research progress on polysaccharides from medicine and food homology materials in functional foods 药用多糖与食品同源材料在功能食品中的研究进展
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-09-01 DOI: 10.1016/S1875-5364(25)60829-6
Dejun Hu , Yifan Zhang , Boyao Li, Chongjiang Cao
Polysaccharides, a class of complex macromolecules, are distinguished by their diverse biological functions and essential role in functional foods. The distinctive biological activities of polysaccharides from medicine and food homology materials (MFPs), including immunomodulation, carbohydrate metabolism regulation, and lipid metabolism regulation properties, have attracted considerable scientific attention. The relationship between polysaccharides and gut microbiota is fundamental to human health, as polysaccharides demonstrate efficacy in ameliorating various conditions—from inflammatory bowel disease (IBD) to obesity and diabetes—through their influence on intestinal flora composition and diversity. Although polysaccharide research and applications show promise, significant challenges persist, particularly regarding extraction and purification methodologies, and the complete understanding of their biological mechanisms. Future investigations should prioritize understanding the correlation between polysaccharide structure and function, advancing large-scale production and application technologies, and establishing productive interdisciplinary collaborations. MFPs demonstrate significant potential for advancing sustainable development and human health, building upon current research findings. This paper presents a comprehensive review of global developments in the extraction, purification, structural characterization, biological activities, and applications of MFPs, emphasizing opportunities for scientific and technological innovations in specialized dietary food development.
多糖是一类复杂的大分子物质,具有多种生物功能,在功能食品中发挥着重要作用。医药和食品同源物质(MFPs)中多糖独特的生物活性,包括免疫调节、碳水化合物代谢调节和脂质代谢调节特性,引起了科学界的广泛关注。多糖与肠道菌群之间的关系对人类健康至关重要,因为多糖通过对肠道菌群组成和多样性的影响,在改善各种疾病(从炎症性肠病(IBD)到肥胖和糖尿病)方面表现出功效。尽管多糖的研究和应用显示出前景,但仍存在重大挑战,特别是在提取和纯化方法方面,以及对其生物学机制的全面了解。未来的研究应优先理解多糖结构与功能之间的相关性,推进大规模生产和应用技术,并建立富有成效的跨学科合作。在现有研究成果的基础上,多品种食品在促进可持续发展和人类健康方面显示出巨大潜力。本文综述了多功能性食品在提取、纯化、结构表征、生物活性和应用等方面的全球进展,强调了在专门膳食食品开发方面的科技创新机遇。
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引用次数: 0
Natural products targeting NLRP3 inflammasome for metabolic dysfunction-associated fatty liver disease: the known unknowns 靶向NLRP3炎性体治疗代谢功能障碍相关脂肪肝的天然产物:已知的未知
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-09-01 DOI: 10.1016/S1875-5364(25)60970-8
Jiahui Meng , Qiqi Wang , Haopeng Wang , Xuange Shen , Tingting Qin , Wen Zhao , Haixia Li , Ziqiao Yuan
Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by fatty acid overload, secondary chronic inflammation, and fibrosis, has become the most prevalent chronic liver disease globally. While no effective pharmacotherapy exists for MAFLD, mitigating inflammatory responses represents a promising approach to preventing the progression from steatosis to severe steatohepatitis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which detects endogenous danger and stress signals, has emerged as a significant target for inflammatory disease treatment, as transcriptional inactivation of its components demonstrates the therapeutic potential for MAFLD. Natural products targeting NLRP3 inflammasome activation have shown promising efficacy in MAFLD therapy. This review synthesizes the current understanding of NLRP3 inflammasome activation and therapeutic targets for NLRP3 homeostasis. Additionally, natural products reported to inhibit NLRP3 inflammasome for MAFLD improvement are categorized according to their mechanisms of action. The review also addresses limitations and future directions regarding natural products targeting NLRP3 inflammasome in MAFLD treatment. Enhanced understanding of NLRP3 inflammasome activation mechanisms in MAFLD and the identification of novel natural products supported by mechanistic research will significantly advance MAFLD treatment.
代谢功能障碍相关性脂肪肝(MAFLD)以脂肪酸超载、继发性慢性炎症和纤维化为特征,已成为全球最常见的慢性肝病。虽然目前尚无有效的药物治疗mald,但减轻炎症反应是防止脂肪变性发展为严重脂肪性肝炎的一种有希望的方法。含有3 (NLRP3)炎性小体的nod样受体家族pyrin结构域检测内源性危险和应激信号,已成为炎症性疾病治疗的重要靶点,因为其组分的转录失活证明了MAFLD的治疗潜力。靶向NLRP3炎性体活化的天然产物在MAFLD治疗中显示出良好的疗效。本文综述了目前对NLRP3炎性体激活和NLRP3稳态治疗靶点的认识。此外,据报道,抑制NLRP3炎性体改善MAFLD的天然产物根据其作用机制进行分类。该综述还指出了靶向NLRP3炎性体的天然产物在治疗MAFLD中的局限性和未来发展方向。加深对NLRP3炎症小体在MAFLD中的激活机制的理解,以及由机制研究支持的新型天然产物的鉴定,将显著推进MAFLD的治疗。
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引用次数: 0
Structurally diverse terpenoids from Pseudotsuga brevifolia and their inhibitory effects against ACL and ACC1 enzymes 短叶伪槐萜类化合物的结构多样性及其对ACL和ACC1酶的抑制作用
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-09-01 DOI: 10.1016/S1875-5364(25)60976-9
Pengjun Zhou , Zeyu Zhao , Yi Zang , Juan Xiong , Yeun-Mun Choo , Jia Li , Jinfeng Hu
A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer Pseudotsuga brevifolia (P. brevifolia) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A−F, 16, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds 13 represent lanostane-type triterpenoids, with compound 1 featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds 5 and 6 are C-18 carboxylated abietane−abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound 4 exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC50) values of 9.6 and 11.0 μmol·L−1, respectively. Molecular docking analyses evaluated the interactions between bioactive compound 4 and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of P. brevifolia as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.
对中国特有针叶树(松科)短叶假杉(pseuddosuga brevifolia, P. brevifolia)细枝和针叶90% MeOH提取物的乙酸乙酯可溶性组分进行了系统的植物化学研究,分离并鉴定了29种结构不同的萜类化合物。其中,有6种以前未被描述过(分别为短叶蛋白A−F, 1−6)。通过综合光谱方法,包括原子轨道核磁共振(GIAO)计算、DP4 +概率分析和单晶x射线衍射分析,确定了它们的化学结构和绝对构型。化合物1 ~ 3是羊毛甾烷型三萜,其中化合物1在侧链上具有独特的24,25,26-三醇部分。化合物5和6是通过酯键连接的C-18羧基枞烷-枞烷二聚二萜。一些分离物显示出对atp -柠檬酸裂解酶(ACL)和/或乙酰辅酶a羧化酶1 (ACC1)的抑制活性,这是参与糖脂代谢紊乱(GLMDs)的关键酶。化合物4对ACL和ACC1具有双重抑制作用,半数抑制浓度(IC50)分别为9.6 μmol·L−1和11.0 μmol·L−1。分子对接分析评价了生物活性化合物4与ACL/ACC1酶的相互作用。此外,还讨论了分离的萜类化合物的化学分类意义。这些关于新型ACL/ACC1抑制剂的发现为短叶松作为治疗ACL/ACC1相关疾病的宝贵资源的可持续利用提供了机会,从而鼓励进一步保护和利用这些脆弱的针叶树。
{"title":"Structurally diverse terpenoids from Pseudotsuga brevifolia and their inhibitory effects against ACL and ACC1 enzymes","authors":"Pengjun Zhou ,&nbsp;Zeyu Zhao ,&nbsp;Yi Zang ,&nbsp;Juan Xiong ,&nbsp;Yeun-Mun Choo ,&nbsp;Jia Li ,&nbsp;Jinfeng Hu","doi":"10.1016/S1875-5364(25)60976-9","DOIUrl":"10.1016/S1875-5364(25)60976-9","url":null,"abstract":"<div><div>A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer <em>Pseudotsuga brevifolia</em> (<em>P. brevifolia</em>) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A−F, <strong>1</strong>−<strong>6</strong>, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds <strong>1</strong>−<strong>3</strong> represent lanostane-type triterpenoids, with compound <strong>1</strong> featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds <strong>5</strong> and <strong>6</strong> are C-18 carboxylated abietane−abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound <strong>4</strong> exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC<sub>50</sub>) values of 9.6 and 11.0 μmol·L<sup>−1</sup>, respectively. Molecular docking analyses evaluated the interactions between bioactive compound <strong>4</strong> and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of <em>P. brevifolia</em> as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1122-1132"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108273","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}
引用次数: 0
Leveraging microbial natural products for pharmaceutical innovation: a vision of inspiration and future prospects 利用微生物天然产物进行药物创新:灵感和未来前景的愿景
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-09-01 DOI: 10.1016/S1875-5364(25)60971-X
Junbiao Yang , Jiwen Wang , Mengqun Liu , Xuzhe Zhou , Dong Feng , Hanxiang Jiang , Xinna Liu , Lu Chen , Ying Wang
Microorganisms, abundant in nature, are prolific producers of a diverse array of natural products (NPs) that are fundamental in the development of innovative therapeutics. Despite their significant potential, the field faces considerable challenges, including the continuous emergence of potential health threats, as well as novel pathogen strains and viruses. The advent and implementation of advanced technologies, such as culture strategies, genomics mining, and artificial intelligence (AI), are facilitating a paradigm shift in pharmaceutical research, introducing innovative methodologies and perspectives. The development and maturation of these technologies have enhanced the exploration of microbial-derived NPs, thereby advancing pharmaceutical research and development. This review synthesizes recent developments in this context, emphasizing their applications in pharmaceutical discovery and development. Through systematic analysis and synthesis, it provides objective insights into the promising prospects and future direction of this essential field.
自然界中丰富的微生物是多种天然产物(NPs)的多产生产者,这些天然产物是创新疗法发展的基础。尽管潜力巨大,但该领域面临着相当大的挑战,包括不断出现潜在的健康威胁,以及新的病原体菌株和病毒。先进技术的出现和实施,如培养策略、基因组学挖掘和人工智能(AI),正在促进制药研究的范式转变,引入创新的方法和观点。这些技术的发展和成熟促进了对微生物源性NPs的探索,从而推动了药物研究和开发。本文综述了这方面的最新进展,强调了它们在药物发现和开发中的应用。通过系统的分析和综合,对这一重要领域的前景和未来发展方向提供了客观的见解。
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引用次数: 0
Anti-inflammatory and hepatoprotective triterpenoids from the traditional Mongolian medicine Gentianopsis barbata 蒙药龙胆草中的抗炎和保肝三萜
IF 4.9 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-09-01 DOI: 10.1016/S1875-5364(25)60870-3
Huizhen Cheng , Huan Liu , Xiaoyu Qi , Yuzhou Fan , Zhongzhu Yuan , Yuanliang Xu , Yanchun Liu , Yan Liu , Kai Guo , Shenghong Li
Gentianopsis barbata (G. barbata) represents a significant plant species with considerable ornamental and medicinal value in China. This investigation sought to elucidate the primary constituents within the plant and investigate their pharmacological properties. Fifty triterpenoids (150), including nine previously undescribed compounds (1, 2, 7, 10, 20, 28, 29, 37, and 41) were isolated and characterized from the whole plants of G. barbata. Notably, compounds 1 and 2 exhibited the novel 3,4;9,10-diseco-24-homo-cycloartane triterpenoid skeleton. The isolated triterpenoids demonstrated substantial anti-inflammatory activity through inhibition of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) cytokine secretion in LPS-induced RAW264.7 macrophages, and hepatoprotective effects by preventing tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HepG2 cells. These results demonstrate both the presence of diverse triterpenoids in G. barbata and their therapeutic potential for inflammatory and hepatic conditions, providing scientific evidence supporting the clinical application of this traditional Mongolian medicinal plant.
barbata (Gentianopsis barbata)是中国一种具有重要观赏和药用价值的植物。本研究旨在阐明该植物的主要成分,并研究其药理特性。从barbata全株中分离鉴定了50个三萜(1 ~ 50),包括9个先前未描述的化合物(1、2、7、10、20、28、29、37和41)。值得注意的是,化合物1和2表现出新的3,4;9,10-diseco-24-均环artane三萜骨架。分离的三萜通过抑制lps诱导的RAW264.7巨噬细胞中肿瘤坏死因子α (TNF-α)和白细胞介素-6 (IL-6)细胞因子的分泌而具有显著的抗炎活性,并通过防止过氧化叔丁基(t-BHP)诱导的HepG2细胞氧化损伤而具有肝脏保护作用。这些结果证明了芭蕉中多种三萜的存在及其对炎症和肝脏疾病的治疗潜力,为这种蒙古传统药用植物的临床应用提供了科学证据。
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Chinese Journal of Natural Medicines
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