Journal of Natural Medicines最新文献_第7页

Loganin ameliorates left ventricular fibrosis and dysfunction induced by pressure overload via the Sirt1/AKT/TGF-β1 signaling pathway 罗甘素通过Sirt1/AKT/TGF-β1信号通路改善压力过载诱导的左心室纤维化和功能障碍。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-05-10 DOI: 10.1007/s11418-025-01911-9

Changbin Wang, Xiaoli Jiang, Shuhua Han, Huimei Zang, Xiaoyuan Gao

Loganin (LG), a natural compound derived from Cornus officinalis Sieb. et Zucc., possesses diverse pharmacological properties, such as anti-inflammatory, anti-hypertrophic, and antioxidant effects. However, the role of LG in the pathogenesis of Heart Failure (HF) remains unclear. The current work aimed to explore the underlying mechanism of LG in pressure overload-induced HF, both in vivo and in vitro, using transverse aortic constriction (TAC) surgery or isoproterenol (ISO) administration. Following eight weeks of TAC surgery, histological assessments, including hematoxylin and eosin staining, wheat germ agglutinin staining, TUNEL assay, and Masson’s trichrome staining, were conducted to evaluate the extent of cardiomyocyte remodeling. Additionally, RT-PCR and WB analyses were performed to detect the levels of various targets. Furthermore, H9C2 cardiomyocytes were treated with ISO to induce hypertrophy, and the effects of LG on cell viability, α-smooth muscle actin (α-SMA) expression, and molecular targets were investigated. Our findings revealed that LG treatment at 40 mg/kg/day significantly attenuated cardiac dysfunction, decreased left ventricular collagen deposition in both interstitial and perivascular spaces. Mechanistically, LG mitigated ISO-induced toxicity in H9C2 cardiomyocytes, decreasing cellular hypertrophy and α-SMA expression. Moreover, we observed a downregulation of Sirtuin 1 (Sirt1) at the molecular level, accompanied by reduced phosphorylation of Akt and transforming growth factor-β1 (TGF-β1). Notably, the administration of the Sirt1 inhibitor, EX527, effectively abolished the protective effects of LG. Therefore, the cardio-protective effects of LG were mediated through the activation of the Sirt1/Akt/TGF-β1 signaling pathway, leading to reduced fibrosis and improved cardiac function.

Graphical abstract

山茱萸苷（Loganin， LG）是一种从山茱萸中提取的天然化合物。调查。具有多种药理特性，如抗炎、抗肥厚和抗氧化作用。然而，LG在心力衰竭（HF）发病机制中的作用尚不清楚。目前的研究旨在通过横断主动脉收缩（TAC）手术或异丙肾上腺素（ISO）给药，探讨LG在体内和体外压力过载诱导的HF中的潜在机制。TAC手术8周后，进行组织学评估，包括苏木精和伊红染色、小麦胚芽凝集素染色、TUNEL试验和Masson三色染色，以评估心肌细胞重塑的程度。此外，进行RT-PCR和WB分析以检测各种靶标的水平。采用ISO诱导心肌细胞肥厚，观察LG对H9C2心肌细胞活力、α-平滑肌肌动蛋白（α-SMA）表达及分子靶点的影响。我们的研究结果显示，40 mg/kg/天的LG治疗可显著减轻心功能障碍，减少左心室间质和血管周围间隙的胶原沉积。在机制上，LG减轻了iso诱导的H9C2心肌细胞毒性，减少了细胞肥大和α-SMA的表达。此外，我们在分子水平上观察到Sirt1下调，同时Akt和转化生长因子-β1 （TGF-β1）磷酸化降低。值得注意的是，Sirt1抑制剂EX527有效地消除了LG的保护作用。因此，LG的心脏保护作用是通过激活Sirt1/Akt/TGF-β1信号通路介导的，从而减少纤维化，改善心功能。

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引用次数: 0

Chlorinated illudalane sequiterpenoids from Saxiglossum angustissimum 木参中氯代幻烷类四萜化合物。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-05-09 DOI: 10.1007/s11418-025-01910-w

Yu-ting Chen, Jian-hua Hong, Cai-ying Peng, Jian-qun Liu, Yu-ye Zhu, Ji-cheng Shu

Eight chlorinated illudalane sesquiterpenoids were isolated from the aerial parts of Saxiglossum angustissimum, including a pair of new pterosin enantiomers, (2R)-angupterosin (1) and (2S)-angupterosin (2), as well as a new pteroside, angupteroside (3). The structures of these compounds were determined through comprehensive analysis of HRESI-MS, NMR spectral data, ECD, and comparisons with previously reported literature. Remarkably, these chlorine-containing compounds (1–8) are rare and represent the first discovery of such metabolites within the family Pyrrosioideae. The chlorinated illudalane sesquiterpenoids from S. angustissimum may serve as valuable chemotaxonomic markers for this species. Furthermore, compounds 1–8 demonstrated inhibitory effects on LPS-induced NO release in BV2 cells, highlighting their potential anti-inflammatory properties.

Graphical abstract

从沙石竹（Saxiglossum angustissimum）的气相部位分离得到8个氯代倍半萜类化合物，包括一对新的羽翼皂苷对映体(2R)-angupterosin(1)和(2S)-angupterosin(2)，以及一个新的羽翼皂苷(3)。这些化合物的结构通过HRESI-MS， NMR谱数据，ECD综合分析，并与先前报道的文献进行比较来确定。值得注意的是，这些含氯化合物（1-8）是罕见的，并且是首次在pyrosioideae家族中发现此类代谢物。该植物的氯代异丙二烯倍半萜可作为该物种的化学分类标记物。此外，化合物1-8对lps诱导的BV2细胞NO释放有抑制作用，突出了其潜在的抗炎特性。

引用次数: 0

Amyloid-β aggregation inhibitory activity of triterpene saponins from the cactus Stenocereus gummosus 仙人掌三萜皂苷抑制淀粉样蛋白-β聚集活性的研究。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-05-08 DOI: 10.1007/s11418-025-01905-7

Tatsumi Matsumoto, Koji Fujihara, Tomomi Inayama, Hiroaki Sasaki, Kaoru Kinoshita

Seven new triterpene saponins (1–7) and two known saponins (8, 9) were isolated from MeOH extracts of Stenocereus gummosus (Engelm.) A.C.Gibson & K.E.Horak. The structures of the isolated saponins were elucidated using MS, IR and comprehensive NMR measurements. To develop drugs for treating Alzheimer's disease (AD) based on the amyloid cascade hypothesis, the isolated saponins were evaluated for inhibition of amyloid beta (Aβ) aggregation using the thioflavin-T (Th-T) assay. Among the isolated saponins, weak activity was observed for compounds 1, 2, 8 and 9 (IC₅₀ = 39.0, 36.7, 39.5, and 35.7 µM, respectively). The aglycons of the isolated saponins, gummosogenin and alamosenogenin, also showed inhibitory activity related to Aβ aggregation (IC₅₀ = 14.9 and 15.5 µM, respectively).

Graphical abstract

从胶状小木耳（Stenocereus gummosus, Engelm.）的MeOH提取物中分离到7个新的三萜皂苷（1-7）和2个已知的皂苷（8,9）。a.c.吉布森和K.E.Horak。通过质谱、红外光谱和核磁共振综合测定对分离得到的皂苷进行了结构鉴定。为了根据淀粉样蛋白级联假说开发治疗阿尔茨海默病（AD）的药物，采用硫黄素- t （Th-T）试验评估了分离的皂苷对淀粉样蛋白β (Aβ)聚集的抑制作用。其中化合物1、2、8和9活性较弱（IC50分别为39.0、36.7、39.5和35.7µM）。皂苷苷元gummosogenin和alamosenogenin的IC50分别为14.9µM和15.5µM，具有抑制Aβ聚集的活性。

引用次数: 0

Oleanane-type triterpene saponins promote extracellular vesicle secretion of human adipose-derived mesenchymal stem cells 齐墩烷型三萜皂苷促进人脂肪源性间充质干细胞胞外囊泡分泌。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-05-07 DOI: 10.1007/s11418-025-01908-4

Jianyu Lin, Hongqiang Lin, Kohei Sato, Atsushi Kimishima, Satoru Tamura, Kazuki Ujiie, Chitose Oneyama, Jinping Liu, Masayoshi Arai

The application of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) holds significant promise in anti-aging cosmetics, regenerative medicine, and drug delivery systems. However, their limited production efficiency remains a critical barrier to advancing related therapies and pharmaceutical applications. In this study, a library of triterpene saponins was screened, leading to the re-discovery of an oleanane-type triterpene saponin Lucyoside H (1), along with its structural analogs, Chikusetsusaponins IVa (2), IV (3), and V (4), which were found to increase the production of EV from human adipose-derived mesenchymal stem cells (ADMSCs) at a concentration ranging from 10 to 100 µM. A comparative analysis of the chemical structures and activities of all evaluated compounds, along with oleanolic acid (5), revealed that (i) disubstitution of glycosyl on C-3 and C-28 of oleanane aglycone was crucial to the promoting effect; (ii) 3-O-β-D-glucuronopyranosyl substitution achieved the highest efficiency in the promoting effect and alteration of this group attenuated the activity. These results highlight the potential for developing a natural product-based approach to increase EV production by MSCs.

Graphical abstract

间充质干细胞（MSC）衍生的细胞外囊泡（EVs）在抗衰老化妆品、再生医学和药物输送系统方面的应用具有重要的前景。然而，它们有限的生产效率仍然是推进相关治疗和制药应用的关键障碍。在本研究中，筛选了一个三萜皂苷文库，重新发现了齐烷型三萜皂苷Lucyoside H(1)及其结构类似物Chikusetsusaponins IVa(2)、IV(3)和V(4)，发现它们在10至100µM的浓度范围内可以增加人脂肪源性间充质干细胞（ADMSCs）的EV产量。与齐墩果酸(5)相比，对所有被评价化合物的化学结构和活性分析表明：(1)齐墩果酸苷元C-3和C-28上的糖基二取代对促进作用至关重要；（ii） 3-O-β- d -葡萄糖醛酸吡喃基取代的促进作用最高，该组的改变使活性减弱。这些结果强调了开发一种基于天然产物的方法来增加msc的EV产量的潜力。

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引用次数: 0

Identification of specialized metabolites from Artocarpus lacucha as potent α-glucosidase and acetylcholinesterase inhibitors: enzyme kinetic, in vitro and in silico study 石竹特化代谢物α-葡萄糖苷酶和乙酰胆碱酯酶抑制剂的鉴定：酶动力学、体外和室内研究。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-05-06 DOI: 10.1007/s11418-025-01904-8

Weerasak Songoen, Witthawat Phanchai, Johann Schinnerl, Lothar Brecker, Morakot Thabpho, Sorachat Tharamak, Wanchai Pluempanupat, Siriphan Sukkhaeng, Sasiwimol Chansuthep

Artocarpus species play an important role in the folk medicine of various ethnic groups in Africa, South Asia, and Southeast Asia. In the present study, we investigated the potential of Artocarpus lacucha in the treatment of diabetes mellitus and Alzheimer’s disease. During this work, one previously undescribed compound (1), along with 10 known compounds (2–11), were isolated from the leaves of Artocarpus lacucha. Their molecular structures were established using NMR and HRMS experiments. Among the tested compounds, flavan-benzofuran artocarpinol B, displayed significant α-glucosidase inhibitory activity with an IC₅₀ value of 4.01 ± 0.04 µM (positive control acarbose: 475.14 ± 4.65 µM). The conducted enzyme kinetic study revealed their inhibition mode through competitive type. This is also supported by the molecular docking and dynamics simulations which gave insight into the interactions and stability between α-glucosidase and artocarpinol B in the active site. In addition, 4-geranyl-2′,3,4′,5-tetrahydroxy-trans-stilbene (5) further shows potent acetylcholinesterase inhibition, with IC₅₀ = 8.57 ± 0.39 µM. Compounds 5 and 6 displayed moderate activity against Staphylococcus aureus and Streptococcus agalactiae, with MIC and MBC values ranging from 26.9 to 69.9 μM. This study explored the potential of constituents from A. lacucha as α-glucosidase and acetylcholinesterase inhibitors, which are crucial in the treatment of Diabetes mellitus and Alzheimer’s disease.

Graphical abstract

石竹属植物在非洲、南亚和东南亚各民族的民间医学中发挥着重要作用。在本研究中，我们探讨了陷陷树在治疗糖尿病和阿尔茨海默病中的潜力。在这项工作中，从Artocarpus lacucha的叶子中分离出了一个先前未描述的化合物(1)和10个已知化合物（2-11）。通过NMR和HRMS实验确定了它们的分子结构。其中黄烷-苯并呋喃artocarpinol B抑制α-葡萄糖苷酶的IC50值为4.01±0.04µM（阳性对照阿卡波糖为475.14±4.65µM）。酶动力学研究揭示了它们的抑制模式为竞争型。分子对接和动力学模拟也支持了这一观点，揭示了α-葡萄糖苷酶与artcarpinol B在活性位点的相互作用和稳定性。此外，4 -香叶基-2′，3,4′，5-四羟基-反式二苯乙烯(5)进一步表现出较强的乙酰胆碱酯酶抑制作用，IC50 = 8.57±0.39µM。化合物5和6对金黄色葡萄球菌和无乳链球菌具有中等活性，MIC和MBC值在26.9 ~ 69.9 μM之间。本研究探讨了树莓中α-葡萄糖苷酶和乙酰胆碱酯酶抑制剂的潜力，这些抑制剂在糖尿病和阿尔茨海默病的治疗中至关重要。

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引用次数: 0

Mechanism study of the effects of astragaloside IV and quercetin on idiopathic pulmonary fibrosis 黄芪甲苷、槲皮素治疗特发性肺纤维化的机制研究。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-04-30 DOI: 10.1007/s11418-025-01896-5

Ye Luo, Chang-jun Xu, Xing-hui Ai, Yu-ping Li, Xing Zhu, Chang-fu Yang

This study aimed to investigate the effects of astragaloside IV(AS-IV) and quercetin (QCT) on autophagic activity, pyroptosis, and epithelial-mesenchymal transdifferentiation (EMT) in the context of idiopathic pulmonary fibrosis (IPF), utilizing both in vivo and in vitro models. In the in vivo component of the research, C57BL/6 J mice were subjected to bleomycin (BLM) modeling, followed by AS-IV + QCT intervention at low, medium, and high doses for 14 and 28 days. Pathological changes in lung tissue were assessed through HE and Masson staining. Additionally, the expression levels of autophagy and pyroptosis-related proteins in serum and bronchoalveolar lavage fluid were examined via Western blot analysis. In the in vitro experiment, RAW264.7 macrophage cells were co-cultured with MLE-12 alveolar epithelial cells (3:1 ratio), implementing BLM and NLR family pyrin domain-containing protein (NLRP3) + BLM models to induce IPF. The effects of AS-IV and QCT on these cells were evaluated by electron microscopy to observe structural changes, while Western blot and ELISA were used to measure the expression of autophagy and pyroptosis-related proteins. Results showed that AS-IV and QCT significantly enhanced autophagic activity, evidenced by increased levels of LC3II and beclin-1 and decreased levels of P62. Additionally, both compounds reduced the expression of pyroptosis-related proteins (NLRP3, Caspase-1, IL-1β, and IL-18) and slowed the progression of EMT in alveolar epithelial cells. These findings propose that AS-IV and QCT inhibit the EMT process in IPF by activating autophagic mechanisms while suppressing pyroptosis, thereby underscoring their potential as innovative therapeutic strategies for IPF and highlighting the promising implications of herbal compounds in its prevention and treatment.

Graphical Abstract

本研究旨在研究黄芪甲苷IV（AS-IV）和槲皮素（QCT）对特发性肺纤维化（IPF）背景下自噬活性、焦细胞凋亡和上皮-间质转分化（EMT）的影响，利用体内和体外模型。在体内部分研究中，C57BL/6 J小鼠采用博来霉素（BLM）建模，然后进行低、中、高剂量AS-IV + QCT干预，持续14和28天。通过HE和Masson染色观察肺组织病理变化。Western blot检测大鼠血清和支气管肺泡灌洗液中自噬和热噬相关蛋白的表达水平。在体外实验中，将RAW264.7巨噬细胞与MLE-12肺泡上皮细胞（3:1比例）共培养，实施BLM和NLR家族pyrin domain-containing protein (NLRP3) + BLM模型诱导IPF。电镜观察AS-IV和QCT对这些细胞的影响，观察结构变化，Western blot和ELISA检测自噬和热噬相关蛋白的表达。结果显示，AS-IV和QCT显著增强自噬活性，LC3II和beclin-1水平升高，P62水平降低。此外，这两种化合物都降低了焦热相关蛋白（NLRP3、Caspase-1、IL-1β和IL-18）的表达，减缓了肺泡上皮细胞EMT的进展。这些发现表明，as - iv和QCT通过激活自噬机制来抑制IPF中的EMT过程，同时抑制焦亡，从而强调了它们作为IPF创新治疗策略的潜力，并强调了草药化合物在预防和治疗IPF方面的前景。

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引用次数: 0

Natural products that target p53 for cancer therapy 针对癌症治疗的p53的天然产物。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-04-28 DOI: 10.1007/s11418-025-01906-6

Sachiko Tsukamoto

Wild-type p53 acts as a tumor suppressor, but p53 is frequently mutated and inactivated in tumor cells, promoting cancer progression, invasion, and metastasis. Thus, compounds that reactivate p53 may be leveraged for cancer treatment, and the development of drugs targeting p53 reactivation is actively progressing. Notably, natural products exhibit diverse structures and biological activities and are used as therapeutic agents for various diseases worldwide. This review discusses the natural products that inhibit p53 degradation through p53–Mdm2 interaction, promote p53 reactivation by inducing conformational changes, and exhibit p53-dependent growth inhibition.

Graphical abstract

野生型p53作为肿瘤抑制因子，但p53在肿瘤细胞中经常发生突变和失活，促进肿瘤的进展、侵袭和转移。因此，重新激活p53的化合物可能用于癌症治疗，针对p53再激活的药物的开发正在积极进行。值得注意的是，天然产物具有不同的结构和生物活性，并在世界范围内用作各种疾病的治疗剂。本文综述了通过p53- mdm2相互作用抑制p53降解的天然产物，通过诱导构象变化促进p53再激活，并表现出p53依赖性生长抑制。

引用次数: 0

Exploring anti-hyperglycemic potential of Pseuderanthemum crenulatum: isolation, structural elucidation and α-glucosidase inhibition evaluation 探讨假菊的降糖潜能：分离、结构鉴定及α-葡萄糖苷酶抑制作用评价。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-04-23 DOI: 10.1007/s11418-025-01907-5

Dung V. Ngo, Le-Thu T. Nguyen, Ngoc T. N. Ngo, Lien-Hoa D. Nguyen, Binh T. D. Trinh

Pseuderanthemum crenulatum (Acanthaceae) is a medicinal plant traditionally used to manage diabetes. However, its chemical constituents remain unexplored as no studies have been conducted on this species to date. This study aimed to chemically characterize and evaluate the anti-hyperglycemic activity of compounds isolated from the stems and roots of P. crenulatum. The isolation process involved utilizing column chromatography techniques, while structures were characterized mainly by 1D and 2D NMR experiments. Anti-hyperglycemic activity was evaluated by measuring their inhibitory effects on the α-glucosidase enzyme. Following this, a new abietane-type dinorditerpenoid, namely pseuderanthemone (1), along with ten known compounds (2–11), was isolated from an ethyl acetate extract of the stems and roots of P. crenulatum. The investigation into their anti-hyperglycemic effects revealed that compounds 1–3, and 6–10 showed higher α-glucosidase inhibitory activity than positive control, acarbose. Among them, compound 9 demonstrated the most potent activity, with an IC₅₀ value nearly ten times lower than acarbose. Furthermore, kinetic analysis showed that compound 2 displayed mixed-type inhibition, and compound 3 demonstrated uncompetitive inhibition while the remaining compounds exhibited competitive inhibition.

Graphical Abstract

假菊（棘科）是一种传统上用于治疗糖尿病的药用植物。然而，其化学成分仍未被探索，因为迄今为止还没有对该物种进行过研究。本研究旨在化学表征和评价从crenulatum茎和根中分离的化合物的抗高血糖活性。分离过程涉及柱层析技术，而结构主要通过一维和二维核磁共振实验表征。通过测定其对α-葡萄糖苷酶的抑制作用来评价其抗高血糖活性。在此基础上，从crenulatum茎和根的乙酸乙酯萃取物中分离出一种新的二萜类化合物pseudoeranthemone(1)和10个已知化合物（2-11）。对其抗高血糖作用的研究表明，化合物1 ~ 3和6 ~ 10比阳性对照阿卡波糖具有更高的α-葡萄糖苷酶抑制活性。其中化合物9的活性最强，IC50值比阿卡波糖低近10倍。此外，动力学分析表明，化合物2表现为混合型抑制，化合物3表现为非竞争性抑制，其余化合物表现为竞争性抑制。

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引用次数: 0

Dendrobium huoshanense polysaccharide inhibits NSCLC proliferation and immune evasion via FXR1-IL-35 axis signaling pathway 霍山石斛多糖通过FXR1-IL-35轴信号通路抑制NSCLC增殖和免疫逃避。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-04-21 DOI: 10.1007/s11418-025-01894-7

Xinying Zhu, Guoquan Yin, Jiaqian Xu, Xiaolei Tang, Fangliu Yu

Dendrobium huoshanense has received special attention for its advantages in the treatment of lung cancer, but the underlying molecular mechanisms are not yet well understood. First, we obtained 8 active ingredients and 159 effective action targets of Dendrobium huoshanense using network pharmacology, and searching target interactions through STRING, constructing the PPI network and KEGG, GO and Hallmark enrichment analysis. Then, we combined target’s enrichment analysis and GSEA enrichment analysis of IL-35, indicating the mechanism of cDHPs for non-small cell lung cancer (NSCLC) may be related to tight junction and NSCLC pathway. Further, FXR1 and ACTR3 were identified as core therapeutic targets, and high expression of FXR1 or ACTR3 was significantly associated with poor prognosis of patients. The analysis of single-cell data also indicated that the percentage of CD4-CTLA4-Treg cells may be increased by the expression of IL-35, resulting in a suppressive immune microenvironment. Next, In vivo experiment, we detected iTr35 by flow cytometry, detected IL-35 level by RT-PCR, Western blotting and ELISA, and detected NK cell activity to explore the immunomodulatory effects and anti-tumor mechanism of cDHPs. After cDHPs administration, the conversion of CD4⁺ T cells to iTr35 is inhibited, p35 and EBI3 in both protein and mRNA levels, the levels of IL-35 and IL-4 in serum decreased. The levels of IFN-γ, while the activity of NK cells in mice increased, enhancing the anti-tumor immune effect of the organism. Finally, analysis of sequencing data from the immunotherapy cohort of tumor-bearing mice obtained from the TISMO database shows that the combination of cDHPs and PD-1/PD-L1 antibodies improves effector and thus PD-1/PD-L1 antibody efficacy. These findings suggest that cDHPs inhibit NSCLC proliferation and immune escape via the FXR1-IL-35 axis signaling pathway.

Graphical abstract

霍山石斛因其治疗肺癌的优势而备受关注，但其潜在的分子机制尚不清楚。首先，利用网络药理学方法获得霍山石斛的8种有效成分和159个有效作用靶点，并通过STRING搜索靶点相互作用，构建PPI网络，进行KEGG、GO和Hallmark富集分析。然后，我们结合IL-35的靶标富集分析和GSEA富集分析，提示cDHPs治疗非小细胞肺癌（NSCLC）的机制可能与紧密连接和NSCLC通路有关。此外，FXR1和ACTR3被确定为核心治疗靶点，FXR1或ACTR3的高表达与患者预后不良显著相关。单细胞数据分析也表明，CD4-CTLA4-Treg细胞的百分比可能通过IL-35的表达而增加，从而导致免疫微环境的抑制性。接下来，在体内实验中，我们通过流式细胞术检测iTr35， RT-PCR、Western blotting和ELISA检测IL-35水平，检测NK细胞活性，探讨cDHPs的免疫调节作用和抗肿瘤机制。给药后，CD4+ T细胞向iTr35的转化受到抑制，p35和EBI3蛋白和mRNA水平均下降，血清中IL-35和IL-4水平下降。小鼠体内IFN-γ水平升高，同时NK细胞活性增强，增强机体抗肿瘤免疫作用。最后，对TISMO数据库中荷瘤小鼠免疫治疗队列的测序数据分析表明，cDHPs与PD-1/PD-L1抗体联合使用可提高效应，从而提高PD-1/PD-L1抗体的疗效。这些发现提示cDHPs通过FXR1-IL-35轴信号通路抑制NSCLC增殖和免疫逃逸。

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引用次数: 0

Potential of siphonaxanthin, a green algal carotenoid, to prevent obesity and related diseases 绿藻类胡萝卜素siphonaxanthin具有预防肥胖和相关疾病的潜力。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines

Pub Date : 2025-04-12 DOI: 10.1007/s11418-025-01897-4

Yuki Manabe, Tatsuya Sugawara

The increasing prevalence of obesity and its related diseases, including diabetes mellitus and metabolic dysfunction-associated fatty liver disease, has become a significant social problem. These diseases are believed to be preventable through healthy diet and exercise habits, and the investigation of food ingredients that are useful for prevention of these diseases is actively ongoing. Carotenoids are the major lipophilic pigments responsible for yellow-to-red colors in our diet, and the ingestion of certain carotenoids has been reported to prevent obesity. For example, β-carotene suppresses adipogenic differentiation of mouse preadipocyte line 3T3-L1 through its provitamin A activity. Fucoxanthin, a carotenoid found in brown algae, also has the similar effect via a different mechanism and is used as an active ingredient in foods with functional claims in Japan. In contrast, siphonaxanthin, a carotenoid found in some green algae such as Caulerpa lentillifera (commonly known as sea grape), exhibited stronger biological activities than other carotenoids in cell-based studies; it significantly suppressed adipogenic differentiation of 3T3-L1 cells even at low concentrations where β-carotene and fucoxanthin did not show inhibitory effects. However, its practical applications have not yet been realized. This review summarizes the studies on the anti-obesity effects of carotenoids and discusses the potential of siphonaxanthin as a novel functional food ingredient.

Graphical Abstract

肥胖及其相关疾病（包括糖尿病和代谢功能障碍相关的脂肪肝）的患病率日益增加，已成为一个重大的社会问题。这些疾病被认为是可以通过健康的饮食和运动习惯来预防的，对预防这些疾病有用的食物成分的研究正在积极进行中。类胡萝卜素是主要的亲脂色素，在我们的饮食中造成黄到红的颜色，据报道，摄入某些类胡萝卜素可以预防肥胖。例如，β-胡萝卜素通过其维生素A原活性抑制小鼠前脂肪细胞系3T3-L1的成脂分化。褐藻中发现的一种类胡萝卜素岩藻黄质，通过不同的机制也有类似的效果，在日本被用作功能性食品的活性成分。相比之下，在一些绿藻（如Caulerpa lentillifera（俗称海葡萄））中发现的类胡萝卜素siphonaxanthin在细胞基础研究中表现出比其他类胡萝卜素更强的生物活性；在低浓度β-胡萝卜素和岩藻黄素没有抑制作用的情况下，也能显著抑制3T3-L1细胞的成脂分化。然而，它的实际应用尚未实现。本文综述了类胡萝卜素在抗肥胖方面的研究进展，并对siphonaxanthin作为一种新型功能性食品成分的潜力进行了探讨。

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引用次数: 0