Fitoterapia最新文献_第9页

Decoding the mechanistic landscape of harpagoside: From molecular targets to translational pharmacology 解码哈巴戈苷的机制景观：从分子靶点到转化药理学。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-12 DOI: 10.1016/j.fitote.2025.107029

Harpreet Kaur , Dinesh Kumar , Vinod Kumar Gauttam , Ashish Suttee , Romanpreet Kaur , Rajni Tanwar , Suresh Babu Kondaveeti , Neeraj Choudhary

Harpagoside, a pharmacologically active iridoid glycoside from Harpagophytum procumbens (Devil’s Claw), exhibits broad therapeutic properties including anti-inflammatory, antioxidant, analgesic, anticancer, and bone-protective effects. Preclinical studies demonstrate pathway modulation at concentrations of 10–50 μM, targeting NF-κB, AP-1, Nrf2/HO-1, PI3K/Akt, and MAPKs, with in vivo evidence for bone preservation, metabolic regulation, and neuroprotection. Clinical trials using standardized extracts (50–100 mg/day harpagoside or 2.6 g/day powdered root) have reported significant improvements in osteoarthritis and chronic low back pain, with fewer gastrointestinal adverse effects compared to NSAIDs.

Unlike previous reviews, this article emphasizes the multi-pathway and systems pharmacology mechanisms of harpagoside, its prodrug-like behavior through biotransformation into active metabolites, and formulation strategies, such as nanoparticles, phospholipid complexes, and semi-synthetic derivatives, to overcome poor oral bioavailability. Current challenges include variability in phytochemical content, limited pharmacokinetic and safety data, and insufficient GLP-compliant long-term toxicity studies. By integrating molecular targets, preclinical and clinical evidence, and advances in delivery technologies, this review positions harpagoside as a prototype multi-target phytochemical with significant translational promise in inflammatory, metabolic, and degenerative disorders.

Harpagoside是一种具有药理活性的环烯醚萜苷类化合物，来自于Harpagophytum proumbens (Devil's Claw)，具有广泛的治疗特性，包括抗炎、抗氧化、镇痛、抗癌和骨骼保护作用。临床前研究表明，10-50 μM的浓度可调节通路，靶向NF-κB、AP-1、Nrf2/HO-1、PI3K/Akt和MAPKs，在体内具有骨保存、代谢调节和神经保护作用。使用标准化提取物（50- 100mg /天哈巴果苷或2.6 g/天哈巴果苷粉）的临床试验报告了骨关节炎和慢性腰痛的显著改善，与非甾体抗炎药相比，胃肠道不良反应更少。与以往的综述不同，本文强调哈巴苷的多途径和系统药理学机制，其前药样行为通过生物转化为活性代谢物，以及配方策略，如纳米颗粒，磷脂复合物和半合成衍生物，以克服口服生物利用度差。目前的挑战包括植物化学成分的可变性，有限的药代动力学和安全性数据，以及缺乏glp合规的长期毒性研究。通过整合分子靶点、临床前和临床证据以及递送技术的进步，本文将哈巴果苷定位为一种原型多靶点植物化学物质，在炎症、代谢和退行性疾病中具有重要的转化前景。

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引用次数: 0

Comparative chemical profiles of fruiting bodies and mycelia of Cordyceps cicadae and Ophiocordyceps sobolifera, and Immunometabolic modulation by liquid-fermented mycelia 蝉虫草和蛇虫草子实体和菌丝的化学成分比较及液体发酵菌丝对免疫代谢的调节作用。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-12 DOI: 10.1016/j.fitote.2025.107028

Jui-Hsia Hsu , Ying-Yu Chen , Ting-Wei Lin , I-Tsang Chiang , Lynn-Huey Chiang , Chin-Chu Chen

Cordyceps cicadae and Ophiocordyceps sobolifera are entomopathogenic fungi often misidentified due to taxonomic ambiguity, leading to confusion in research and applications. This study compared their metabolite compositions and immunomodulatory activities using molecular identification, chemical profiling, and in vitro assays.

High-performance liquid chromatography and LC–MS/MS revealed distinct signatures: C. cicadae lacked myriocin but accumulated N⁶-(2-hydroxyethyl)adenosine (HEA), while O. sobolifera produced abundant myriocin but no HEA. Beauvericin was enriched in wild C. cicadae, whereas adenosine was consistently present in both species, with higher levels in O. sobolifera. Cordycepin was detected only in artificially cultivated C. cicadae. Functional assays showed that C. cicadae extracts, HEA, and adenosine significantly suppressed C48/80-induced histamine release from mast cells, and ethanol extracts of C. cicadae reduced interleukin-33 (IL-33) activation. In contrast, O. sobolifera water extracts enhanced glucagon-like peptide-1 (GLP-1) secretion, while myriocin, beauvericin, and oosporein were inactive in these pathways.

These findings clarify the compositional and functional divergence between the two fungi. The absence of toxic myriocin in C. cicadae supports its safer use in food and medicinal applications, with HEA emerging as a key bioactive marker. Liquid fermentation further enhances HEA levels while reducing beauvericin, suggesting its suitability for controlled production. Meanwhile, O. sobolifera may be explored for GLP-1–related benefits. Overall, this study provides a molecular and functional basis to differentiate the two species and highlights their distinct potential in health applications.

蝉虫草（Cordyceps cicadae）和蛇虫草（Ophiocordyceps sobolifera）是一种昆虫病原真菌，由于分类上的歧义，经常被误认，导致研究和应用上的混乱。本研究通过分子鉴定、化学分析和体外实验比较了它们的代谢物组成和免疫调节活性。高效液相色谱和LC-MS/MS分析结果表明，蝉蝉缺乏肉豆蔻素，但积累了N6-（2-羟乙基）腺苷（HEA）；Beauvericin在野生蝉蝉中富集，而腺苷在两种蝉蝉中均一致存在，其中o.s obolifera含量较高。虫草素仅在人工栽培的蝉虫中检测到。功能实验表明，蝉提取物、HEA和腺苷可显著抑制c48 /80诱导的肥大细胞组胺释放，蝉乙醇提取物可降低白细胞介素-33 （IL-33）的激活。与此相反，水提取物可增强胰高血糖素样肽-1 （GLP-1）的分泌，而肉豆素、beauvericin和oosporein在这些途径中无活性。这些发现澄清了两种真菌在成分和功能上的差异。蝉蝉中不含有毒的肉豆蔻素，这为其在食品和医药领域的安全应用提供了支持，HEA正成为一种关键的生物活性标志物。液体发酵进一步提高HEA水平，同时减少beauvericin，表明其适合控制生产。与此同时，还可以探索O. sobolifera是否具有glp -1相关的益处。总之，这项研究为区分这两个物种提供了分子和功能基础，并突出了它们在健康应用方面的独特潜力。

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引用次数: 0

Sesquiterpenoids from the fruits of Alpinia oxyphylla and their anti-renal fibrosis activities 杉木果实中的倍半萜类化合物及其抗肾纤维化活性。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-11 DOI: 10.1016/j.fitote.2025.107032

Xiao-Ning Liu , Bo-Tao Lu , Mei Wang , Yue-Tong Zhu , Yong-Xian Cheng , Yan-Zhi Wang

Six new sesquiterpenoids, including two cadinane sesquiterpenoids (1 and 2), four eudesmane sesquiterpenoids (3–6), together with seven known analogues (7–13) and two diphenylheptanes (14 and 15) were isolated from the fruits of Alpinia oxyphylla. The structures of these new compounds were elucidated by analysis of spectroscopic data (NMR) and electronic circular dichroism (ECD) calculations. The cell viability and anti-renal fibrotic activity of compounds 1–6 were analyzed by CCK-8 and Western blot, and compounds 2 and 6 exhibited inhibitory renal fibrosis activity in TGF-β1-induced renal proximal renal tubular cells, and dose-effect relationships were observed in compounds 2 and 6.

从杉木果实中分离到6个新的倍半萜类化合物，包括2个癸烷倍半萜类化合物（1和2），4个癸烷倍半萜类化合物（3-6），以及7个已知的类似物（7-13）和2个二苯基庚烷类化合物（14和15）。这些新化合物的结构通过波谱分析（NMR）和电子圆二色性（ECD）计算得到了证实。通过CCK-8和Western blotting分析化合物1-6的细胞活力和抗肾纤维化活性，化合物2和6对TGF-β1诱导的肾近端肾小管细胞具有抑制肾纤维化活性，并观察化合物2和6的剂量效应关系。

引用次数: 0

Protective effect of Maren-Tiaogan Decoction on high-fat diet-induced MASLD in mice 麻调肝汤对高脂饮食致小鼠MASLD的保护作用。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-10 DOI: 10.1016/j.fitote.2025.107023

Qianru Zhu , Yujie Ren , Xujie Tang , Shu Jia , Jingyi Wu , Xiaomin Yao , Junling Zhu

Background and aim

Recent epidemiological studies have highlighted a significant increase in the global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). This study explores the hepatoprotective mechanisms of Maren-Tiaogan Decoction (MRTGD), a traditional Chinese medicine (TCM) formulation, using a high-fat diet (HFD) murine model of MASLD. The findings may provide a safer and more effective TCM-based therapeutic option for patients with MASLD.

Experimental procedure

A 12-week HFD-induced mouse model of MASLD was established. MRTGD was administered at high, medium and low doses via oral gavage twice daily as the therapeutic intervention. The chemical constituents of MRTGD were identified using UPLC-MS/MS. Hepatic steatosis and changes in adipocyte area were assessed using hematoxylin and eosin (H&E) staining and Oil Red O staining. Biochemical analyses were conducted to measure serum aminotransferase levels, serum lipid profiles, hepatic lipid content and oxidative stress. Furthermore, mRNA expression and protein abundance of critical regulators governing lipid homeostasis and autophagic flux were quantitatively analyzed through real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot.

Results

MRTGD, containing 467 constituents, exhibits significant protective effects against HFD-induced MASLD/MASH by suppressing elevated serum transaminases and hyperlipidemia, reducing hepatic lipid accumulation and steatosis, ameliorating histopathological alterations and adipocyte hypertrophy, while alleviating hepatocyte apoptosis and hepatic oxidative stress. MRTGD not only effectively restores the abnormal up-regulation of lipogenic proteins (such as SREBP-1c and ACC) and the down-regulation of lipid-catabolizing proteins (including PPARα), but also normalizes the expression levels of the PI3K/AKT/mTOR signaling pathway.

Conclusion

The experimental results demonstrate that MRTGD effectively prevents HFD-induced MASLD, partially through modulation of lipid metabolism and autophagy pathways.

背景和目的：最近的流行病学研究强调了代谢功能障碍相关脂肪变性肝病（MASLD）的全球患病率显着增加。本研究采用高脂饮食（HFD）小鼠模型，探讨中药制剂麻仁调肝汤（MRTGD）的保肝机制。研究结果可能为MASLD患者提供一种更安全、更有效的基于tcm的治疗选择。实验方法：建立12周hfd诱导的MASLD小鼠模型。MRTGD分别以高、中、低剂量灌胃治疗，每日2次。采用UPLC-MS/MS对MRTGD的化学成分进行鉴定。采用苏木精和伊红（H&E）染色和油红O染色评估肝脂肪变性和脂肪细胞面积的变化。生化分析测定血清转氨酶水平、血脂、肝脏脂质含量和氧化应激。此外，通过实时逆转录定量聚合酶链反应（RT-qPCR）和Western blot，定量分析了控制脂质稳态和自噬通量的关键调控因子的mRNA表达和蛋白质丰度。结果：MRTGD含有467种成分，通过抑制血清转氨酶升高和高脂血症，减少肝脏脂质积累和脂肪变性，改善组织病理改变和脂肪细胞肥大，同时减轻肝细胞凋亡和肝脏氧化应激，对hfd诱导的MASLD/MASH具有显著的保护作用。MRTGD不仅能有效恢复异常上调的脂肪生成蛋白（如SREBP-1c、ACC）和下调的脂质分解代谢蛋白（包括PPARα），还能使PI3K/AKT/mTOR信号通路的表达水平正常化。结论：实验结果表明，MRTGD可有效预防hfd诱导的MASLD，部分通过调节脂质代谢和自噬途径。

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引用次数: 0

Amide alkaloids from the fruits of Piper longum L. and their bioactivities 胡椒果实中的酰胺类生物碱及其生物活性。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-10 DOI: 10.1016/j.fitote.2025.107024

Guanghui Gou , Wenli Bao , Liu Liu , Nannan Xu , Jun Li

Eight previously undescribed amide alkaloids [1–5], including three pairs of enantiomers [(±)-3, (±)-4, and (±)-5], along with 17 known compounds (6–22), were isolated from the fruits of Piper longum L with chromatographic techniques and chiral separation. The planar structures and relative configurations of these compounds were elucidated using HRESIMS and NMR analyses, while the absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1–22 were assessed for their in vitro NO inhibition, cytotoxic, and anti-diabetic activities. Compounds (+)-5, 7, and 8 showed moderate NO inhibitory activity (10 μM < IC₅₀ < 30 μM). Compounds 1, 9, and 13 exhibited significant cytotoxic effects against HeLa cells, with IC₅₀ values of 9.99 ± 0.62, 6.25 ± 0.32, and 9.61 ± 0.48 μM, respectively. Compounds (+)-4, 7, 8, 9, 11, 12, 13, 15, and 16 showed potent cytotoxicity against HT-29 cells with IC₅₀ values ranging from 2.65 to 7.78 μM. Compounds (+)-4, 6, and 16 exhibited weak cytotoxicity against MCF-7 cells (IC₅₀ > 30 μM). Additionally, compound 6 showed moderate inhibitory activity against α-glucosidase with an IC₅₀ of 112.03 ± 3.69 μM, whereas compound 8 significantly inhibited PTP1B, with an IC₅₀ of 9.06 ± 0.68 μM. These findings offer valuable insights into the potential application of amide alkaloids from P. longum in developing functional foods and pharmaceuticals, highlighting their promise in health promotion.

通过色谱技术和手性分离，从胡椒果实中分离得到8种未被描述的酰胺类生物碱[1-5]，包括3对对映体[（±）-3,（±）-4和（±）-5]，以及17种已知化合物（6-22）。这些化合物的平面结构和相对构型通过HR-ESI-MS和NMR分析得到，绝对构型通过电子圆二色性（ECD）计算得到。对化合物1 ~ 22进行体外NO抑制、细胞毒性和抗糖尿病活性评价。化合物(+)5、7和8显示中度没有抑制活性(10 50μM  50值9.99 ± 0.62,6.25 ± 0.32,和9.61 ±0.48  μM,分别。化合物(+)-4、7、8、9、11、12、13、15和16对HT-29细胞具有较强的细胞毒性，IC50值为2.65 ~ 7.78 μM。化合物(+)- 4,6和16对MCF-7细胞表现出弱的细胞毒性（IC50 > 30 μM）。此外，化合物6对α-葡萄糖苷酶具有中等抑制活性，IC50为112.03 ± 3.69 μM，而化合物8对PTP1B具有显著抑制作用，IC50为9.06 ± 0.68 μM。这些发现为龙葵酰胺类生物碱在功能性食品和药物开发中的潜在应用提供了有价值的见解，突出了其在促进健康方面的前景。

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引用次数: 0

Integrating mouse oral trial, LC-HRMS-based untargeted metabolomics and network pharmacology for screening bioactive components of Astragalus membranaceus curing type-II diabetes mellitus (T2DM) 结合小鼠口服试验、lc - hrms非靶向代谢组学和网络药理学筛选黄芪治疗2型糖尿病的生物活性成分。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-10 DOI: 10.1016/j.fitote.2025.107033

Chao Tang , Shuangnan Xie , Hongtao Jia , Qi Shen , Weizhong He , Bin Li , Shiyi Deng , Jing Tang , Zhi Liu , Cheng Wang

Astragalus membranaceus (AM), a well-known traditional Chinese medicine (TCM), has been found to exhibit significant therapeutic effects on T2DM. The mechanism of AM (root) extract ameliorating diabetes and its medicinal components were deep inverstigated in this work. A mouse oral trial, LC-HRMS-based untargeted metabolomics, quantitative spectrum effect relationship analysis (QSERA), and network pharmacology was integrated for this studying. With the aid of data-mining by AntDAS (Automatic Data Analysis Strategy) platform, 59 bioactive compounds involved in the Leprdb/db mouse model of T2DM therapy were screened from LC-HRMS fingerprints of AM (root) extract even in the presence of heavily interfered background. The key bioactive AM (root) metabolites, astragaloside and l-arabinose, influence T2DM targets including IL2 and HSP90AA1. Molecular docking experiment revealed high-affinity binding between astragaloside and l-arabinose and these core targets. QSERA predicted the specific regulatory effects of bioactive compounds on T2DM in mice. This integrated approach provides a novel strategy for interpreting the pharmacodynamic effects of AM (root) extract in T2DM, which may facilitate the clinical application of traditional Chinese medicine.

黄芪（Astragalus aceus， AM）是一种著名的中药，对2型糖尿病有显著的治疗作用。本文对AM（根）提取物改善糖尿病的机制及其药物成分进行了深入的研究。本研究结合小鼠口服试验、基于lc - hrms的非靶向代谢组学、定量谱效应关系分析（QSERA）和网络药理学。利用AntDAS （Automatic Data Analysis Strategy）平台进行数据挖掘，从AM（根）提取物的LC-HRMS指纹图谱中筛选出59种参与Leprdb/db T2DM小鼠模型治疗的生物活性化合物，即使存在严重干扰的背景。关键的生物活性AM（根）代谢物黄芪甲苷和i-阿拉伯糖影响T2DM靶标包括il - 2和HSP90AA1。分子对接实验显示黄芪甲苷和阿拉伯糖与这些核心靶点具有高亲和力结合。QSERA预测了生物活性化合物对小鼠T2DM的特异性调节作用。这种综合方法为解释AM（根）提取物在T2DM中的药效学作用提供了一种新的策略，可能有助于中药的临床应用。

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引用次数: 0

Dimeric Phthalides from an endophytic fungus Phomopsis sp. of Aconitum carmichaeli 乌头内生真菌Phomopsis sp.的二聚体邻苯二甲酸酯。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-09 DOI: 10.1016/j.fitote.2025.107035

Yuan Gao , Jia-Hui Wang , Ming-Qian Han , Rong Huang , Shao-Hua Wu

Three racemic pairs of new dimeric phthalides, (±)-phomophthalides A-C ((±)-1–3), together with eight known compounds (4–11), were obtained from the culture broth of the endophytic fungus Phomopsis sp. YM 355364 isolated from the medicinal plant Aconitum carmichaeli. The chemical structures of the new compounds were established by extensive NMR spectroscopic and HRESI-MS analysis and DP4+ calculations. The new compounds were tested for their antimicrobial activities by broth microdilution method. Compound 1 showed moderate inhibitory activity toward three pathogenic fungal strains Fusarium solani, Candida albicans, and Botrytis cinerea with MIC values of 16, 32, and 32 μg/mL, respectively. Compound 2 exhibited antifungal activity against B. cinerea and C. albicans with MIC values of 16 and 32 μg/mL, respectively.

从药用植物乌头内生真菌Phomopsis sp. YM 355364的培养液中分离得到3对新的二聚体苯酞（±）-phomophthalides A-C（±）-1-3)和8个已知化合物（4-11）。通过NMR、HRESI-MS分析和DP4+计算确定了新化合物的化学结构。用微量肉汤稀释法测定了新化合物的抑菌活性。化合物1对茄灰镰刀菌、白色念珠菌和灰霉病菌具有中等抑制活性，MIC值分别为16、32和32 μg/mL。化合物2对灰绿芽孢杆菌和白色念珠菌的MIC值分别为16和32 μg/mL。

引用次数: 0

Pharmacological insights on multifaceted therapeutic applications of stilbenoids: A comprehensive updates 二苯乙烯类化合物多方面治疗应用的药理学见解：全面更新。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-09 DOI: 10.1016/j.fitote.2025.107034

Chunhong Liu , Zheng Yan , Xueqiang Chen , Sanchita Mandal , Ushasi Das , Sudarshan Singh , Opeyemi Joshua Olatunji

Stilbenoids are naturally existing phenolic chemicals that have a stilbene backbone structure and are found in a variety of plant species. Plants produce these antimicrobial substances, known as phytoalexins, in reaction to stresses such as disease or ultraviolet light. The structure, variety, isomer form, and biosynthesis of stilbenoids are important characteristics. In addition to their anti-inflammatory and anti-diabetic qualities, they also exhibit antibacterial activity, cardioprotective and neuroprotective benefits, and the ability to prevent and treat cancer. The most researched stilbenoid is resveratrol, although related substances such as piceatannol, gnetol, and pterostilbene also have notable bioactivity. In vitro, in vivo, and a few human clinical investigations have all been done on stilbenoids. Although preclinical models show promising results, further clinical data is required to validate their good benefits in people. To completely grasp their therapeutic potential, more investigation is required. This article explores naturally occurring stilbenoids and their therapeutic properties, including preclinical and clinical research, patents, and emerging research. It highlights their abundance, structural traits, bioavailability, safety, and effectiveness. This article also focus on polymeric carriers, such as nanoparticles, micelles, hydrogels, and dendrimers, improve the stability, bioavailability, and therapeutic efficacy of stilbenoids, polyphenolic compounds with multifaceted therapeutic applicationssuch as antioxidant, anti-inflammatory, anti-aging, cardioprotective, anti-diabetes, neurodegeneration, anti-obesity, anticancer, and antimicrobial properties.

二苯乙烯类化合物是天然存在的具有二苯乙烯骨架结构的酚类化学物质，存在于多种植物中。植物产生这些抗微生物物质，被称为植物抗菌素，是对疾病或紫外线等压力的反应。二苯乙烯类化合物的结构、种类、异构体形式和生物合成是其重要的特征。除了抗炎和抗糖尿病外，它们还具有抗菌活性，心脏保护和神经保护作用，以及预防和治疗癌症的能力。研究最多的二苯乙烯类化合物是白藜芦醇，尽管相关物质如皮杉醇、甘油三酯和紫檀二苯乙烯也具有显著的生物活性。在体外，体内和一些人体临床研究都已完成了二苯乙烯类化合物。尽管临床前模型显示出有希望的结果，但需要进一步的临床数据来验证它们对人体的良好益处。为了完全掌握它们的治疗潜力，还需要更多的研究。本文探讨了天然存在的二苯乙烯类化合物及其治疗特性，包括临床前和临床研究、专利和新兴研究。它突出了它们的丰度、结构特征、生物利用度、安全性和有效性。本文还重点介绍了聚合物载体，如纳米颗粒、胶束、水凝胶和树状大分子，提高了二苯乙烯类化合物的稳定性、生物利用度和治疗效果，多酚类化合物具有多方面的治疗应用，如抗氧化、抗炎、抗衰老、心脏保护、抗糖尿病、神经变性、抗肥胖、抗癌和抗菌特性。

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引用次数: 0

The Tetradium ruticarpum–Zingiber officinale Roscoe herb pair inhibits atherogenic events: A study of the synergistic effects and active ingredient combination of a two-herb formula 姜黄-金银花草本对抑制动脉粥样硬化事件：两种草本配方的协同作用和活性成分组合的研究。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-08 DOI: 10.1016/j.fitote.2025.107030

Chenglin Chi, Xiaoli Yang, Can Li, Zongchao Li, Shufang Yang, Yuan Du, Weizhen Huang, Rongxia Liu

The Tetradium ruticarpum (E)–Zingiber officinale Roscoe (Z) herb pair is a well-known herbal formulation with multiple beneficial cardiovascular pharmacological activities. Therefore, E and Z are potentially natural products for Atherosclerosis (AS). However, it is not clear whether E and Z work synergistically in the treatment of AS and which of their components is responsible. This study was to determine the synergistic effect of E and Z in the treatment of AS, to identify the active ingredient combination (AIC) that exerts the action of the original formula and to determine its molecular mechanism. First, the combined effects of E and Z were assessed in an ApoE^−/− mouse model and then confirmed in vascular smooth muscle cells (VSMCs) by the combination index (CI). In addition, the AIC of E-Z was evaluated by cascade analysis and its efficacy was confirmed in vitro and in vivo. The results showed that both E, Z and E-Z had anti-AS effects in ApoE^−/− mice, with E-Z having the most significant effect. Moreover, the CI method demonstrated that E, Z could synergistically inhibit the proliferation of VSMCs. In addition, the AICs obtained by the cascade analysis strategy effectively inhibited VSMCs proliferation in vitro and significantly reduced the formation of neoplastic endothelium in mice in vivo. This inhibitory effect was associated with the reduction of ROS levels and activation of the Nrf2/HO-1 signaling pathway in VSMCs. This study provides an effective method for characterizing herbal combinations, exploring their active ingredients, and promoting efficacy-based herbal quality control.

紫金四合物（Tetradium ruticarpum， E）-黄姜（zingiber officinale Roscoe， Z）是一种众所周知的具有多种有益心血管药理活性的草药配方。因此，E和Z是动脉粥样硬化（AS）的潜在天然产物。然而，尚不清楚E和Z是否在治疗AS中协同作用，以及它们的哪个成分负责。本研究旨在确定E和Z在治疗AS中的协同作用，确定发挥原方作用的有效成分组合（AIC），并确定其分子机制。首先，在ApoE-/-小鼠模型中评估E和Z的联合作用，然后通过联合指数（CI）在血管平滑肌细胞（VSMCs）中证实。此外，通过级联分析评价了E-Z的AIC，并证实了其体外和体内的有效性。结果表明，E、Z和E-Z对ApoE-/-小鼠均有抗as作用，其中E-Z的作用最为显著。此外，CI法显示E、Z能协同抑制VSMCs的增殖。此外，通过级联分析策略获得的aic在体外有效抑制了VSMCs的增殖，并在体内显著减少了小鼠肿瘤内皮的形成。这种抑制作用与VSMCs中ROS水平的降低和Nrf2/HO-1信号通路的激活有关。本研究为中药复方的表征、有效成分的探索以及基于疗效的中药质量控制提供了一种有效的方法。

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引用次数: 0

Bioprospecting and exploration of the chemical profile of Lasiodiplodia sp. extracts: Evaluation of specialized metabolites by similarity calculations, and dereplication with differential 1H NMR Lasiodiplodia sp.提取物化学谱的生物勘探与探索：利用相似性计算评价特化代谢物，并用差异1HNMR进行重复。

IF 2.6 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia

Pub Date : 2025-12-08 DOI: 10.1016/j.fitote.2025.107031

Lucas Silva Tironi , Johan Mateo Rios Marin , Omar Cabezas Gómez , Antonio Gilberto Ferreira , Jan Schripsema , Jaine Honorata Hortolan Luiz

Endophytic fungi are well known for producing a wide variety of specialized metabolites, often characterized by complex and diverse chemical structures. In this study, the differential ¹H NMR technique was used as an innovative tool for dereplication and for supporting compound identification in complex mixtures, complemented by similarity calculations developed to evaluate the similarity of the chemical profiles of the extracts obtained over consecutive cultivation days of Lasiodiplodia sp. One-dimensional (1D) and two-dimensional (2D) NMR analyses of the POLd-14 extract and MLd-1 to MLd-3 subfractions led to the identification of known compounds: 3-carboxy-2-methylene-4-heptanolide (1) and decumbic acid (2) in POLd-14; indole-3-carboxylic acid (3) in MLd-1 and MLd-3; 4-hydroxybenzoic acid (4) and 4-hydroxymellein (5) in MLd-1; and 4-hydroxyphenylacetamide (6) in MLd-2. Differential ¹H NMR enabled the unequivocal identification of compounds (1) and (2). These results contribute to bioprospecting and to a better understanding of the metabolite diversity of Lasiodiplodia sp. under varying culture conditions, including diferences in carbon and nitrogen sources, cultivation periods, and extraction methods. The study also underscore the potential of Lasiodiplodia sp. endophyte as an alternative source of bioactive metabolites with pharmacological relevance, which can be cultivated under different conditions guiding the production of different specialized metabolites.

内生真菌以产生各种各样的特殊代谢物而闻名，这些代谢物通常具有复杂多样的化学结构。在这项研究中，差异1HNMR技术被用作一种创新的工具，用于反复制和支持复杂混合物中的化合物鉴定。通过相似性计算来评估在连续培养几天内获得的Lasiodiplodia sp.提取物的化学特征的相似性。对POLd-14提取物和MLd-1与MLd-3亚组分进行一维（1D）和二维（2D） NMR分析，鉴定出POLd-14中的已知化合物：3-羧基-2-亚甲基-4-七烷内酯(1)和癸二酸(2)；MLd-1和MLd-3中的吲哚-3-羧酸(3)；MLd-1中的4-羟基苯甲酸(4)和4-羟基mellein (5)；和4-羟基苯乙酰胺(6)。差异1HNMR能够明确地识别化合物(1)和(2)。这些结果有助于更好地了解不同培养条件下Lasiodiplodia sp.代谢物的多样性，包括碳氮源、培养周期和提取方法的差异。该研究还强调了Lasiodiplodia sp.内生菌作为具有药理意义的生物活性代谢物的替代来源的潜力，它可以在不同的条件下培养，指导不同专门代谢物的产生。

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