Chinese Journal of Natural Medicines最新文献_第2页

Advances in intelligent mass spectrometry data processing technology for in vivo analysis of natural medicines 用于天然药物体内分析的智能质谱数据处理技术的进展。

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-10-01 DOI: 10.1016/S1875-5364(24)60687-4

Simian CHEN , Binxin DAI , Dandan ZHANG , Yuexin YANG , Hairong ZHANG , Junyu ZHANG , Di LU , Caisheng WU

Natural medicines (NMs) are crucial for treating human diseases. Efficiently characterizing their bioactive components in vivo has been a key focus and challenge in NM research. High-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) systems offer high sensitivity, resolution, and precision for conducting in vivo analysis of NMs. However, due to the complexity of NMs, conventional data acquisition, mining, and processing techniques often fail to meet the practical needs of in vivo NM analysis. Over the past two decades, intelligent spectral data-processing techniques based on various principles and algorithms have been developed and applied for in vivo NM analysis. Consequently, improvements have been achieved in the overall analytical performance by relying on these techniques without the need to change the instrument hardware. These improvements include enhanced instrument analysis sensitivity, expanded compound analysis coverage, intelligent identification, and characterization of nontargeted in vivo compounds, providing powerful technical means for studying the in vivo metabolism of NMs and screening for pharmacologically active components. This review summarizes the research progress on in vivo analysis strategies for NMs using intelligent MS data processing techniques reported over the past two decades. It discusses differences in compound structures, variations among biological samples, and the application of artificial intelligence (AI) neural network algorithms. Additionally, the review offers insights into the potential of in vivo tracking of NMs, including the screening of bioactive components and the identification of pharmacokinetic markers. The aim is to provide a reference for the integration and development of new technologies and strategies for future in vivo analysis of NMs.

天然药物（NMs）对治疗人类疾病至关重要。有效表征其体内生物活性成分一直是天然药物研究的重点和难点。高效液相色谱-高分辨质谱（HPLC-HRMS）系统具有高灵敏度、高分辨率和高精确度，可用于对 NMs 进行体内分析。然而，由于核磁共振的复杂性，传统的数据采集、挖掘和处理技术往往无法满足体内核磁共振分析的实际需要。过去二十年来，基于各种原理和算法的智能光谱数据处理技术已被开发并应用于体内核磁共振分析。因此，在无需改变仪器硬件的情况下，依靠这些技术已经实现了整体分析性能的提升。这些改进包括提高仪器分析灵敏度、扩大化合物分析覆盖范围、智能识别和表征非靶向体内化合物，为研究 NMs 体内代谢和筛选药理活性成分提供了强大的技术手段。本综述总结了过去二十年中报道的利用智能质谱数据处理技术对非线性物质进行体内分析策略的研究进展。综述讨论了化合物结构的差异、生物样本之间的变化以及人工智能（AI）神经网络算法的应用。此外，综述还深入探讨了非转基因药物体内追踪的潜力，包括生物活性成分的筛选和药代动力学标记的鉴定。其目的是为整合和开发新技术和新策略提供参考，以便今后对核磁共振进行体内分析。

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引用次数: 0

Chiral resolution of furofuran lignans and their derivatives from the stems of Dendrobium 'Sonia' 从铁皮石斛'Sonia'茎中提取的呋喃木脂素及其衍生物的手性解析。

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-10-01 DOI: 10.1016/S1875-5364(24)60725-9

Kaimei QIU , Hao QIU , Yanqiao XIE , Siyu ZHANG , Qian ZHANG , Zhengtao WANG , Zhuzhen HAN , Li YANG

Five new furofuran lignans and their derivatives, (−)-glaberide I 4-O-β-D-glucopyranoside (1a), (+)-glaberide I 4-O-β-D-glucopyranoside (1b), (+)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside (2a), (−)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside (2b), and (−)-isoeucommin A (3b), along with fifteen known analogs were isolated from the stems of Dendrobium 'Sonia'. These compounds were classified into ten pairs of enantiomers or diastereoisomers via chiral resolution, and their structures were determined based on extensive spectroscopic data. Their absolute configurations were determined by hydrolysis, comparison of experimental and calculated electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analysis. The isolates were evaluated for their ability to inhibit nitric oxide (NO) production in RAW264.7 cells. Among them, syringaresinol (5) exhibited prominent inhibition activity, with an IC₅₀ value of 28.4 ± 3.0 μmol·L⁻¹, and there was a slight difference between 5a, 5b and the racemic mixture 5.

五种新的呋喃木脂素及其衍生物：(-)-木脂素 I 4-O-β-D-吡喃葡萄糖苷(1a)、(+)-木脂素 I 4-O-β-D-吡喃葡萄糖苷(1b)、(+)-木脂素 I 7'-乙氧基-4-O-β-D-吡喃葡萄糖苷(2a)、(-)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside (2b)、(-)-isoeucommin A (3b)以及 15 种已知的类似物都是从铁皮石斛'Sonia'的茎中分离出来的。通过手性解析，这些化合物被分为十对对映体或非对映异构体，并根据大量光谱数据确定了它们的结构。通过水解、比较实验和计算的电子圆二色性（ECD）数据以及单晶 X 射线衍射分析，确定了它们的绝对构型。对这些分离物抑制 RAW264.7 细胞产生一氧化氮（NO）的能力进行了评估。其中，丁香树脂醇（5）的抑制活性突出，其 IC50 值为 28.4 ± 3.0 μmol-L-1，且 5a、5b 和外消旋混合物 5 之间存在微小差异。

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引用次数: 0

Highly oxygenated clerodane furanoditerpenoids from the leaves and twigs of Croton yunnanensis 从云南巴豆的叶子和小枝中提取的高含氧挛烷呋喃二萜。

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-10-01 DOI: 10.1016/S1875-5364(24)60722-3

Didi WANG , Fang MEI , Jinchun NIE , Zhenwei LI , Daidi ZHANG , Dean GUO , Wei LI

The phytochemical investigation of the leaves and twigs of Croton yunnanensis resulted in the isolation of eight new clerodane furanoditerpenoids, named croyunfuranoids A−H (1−8), along with three known analogs (9−11). The structures of these compounds were elucidated using spectroscopic analyses, and their absolute configurations were determined through a combination of electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Notably, Croyunfuranoid D (4) is identified as a rare 18,19-dinor-clerodane diterpenoid. Additionally, the structure of a previously reported diterpenoid, crotonyunnan B, was revised. All isolated compounds were evaluated for their inhibitory activities on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages. Among them, compounds 5 and 6 demonstrated significant inhibitory effects, with IC₅₀ values of 20.33 ± 2.31 and 22.80 ± 1.31 μmol·L⁻¹, respectively.

通过对云南巴豆的叶片和小枝进行植物化学研究，分离出了八种新的萜类呋喃二萜化合物，命名为云南巴豆呋喃二萜 A-H（1-8），以及三种已知的类似物（9-11）。通过光谱分析阐明了这些化合物的结构，并结合电子圆二色性（ECD）计算和单晶 X 射线衍射确定了它们的绝对构型。值得注意的是，Croyunfuranoid D (4) 被鉴定为一种罕见的 18,19-二邻氯二萜类化合物。此外，以前报道过的一种二萜类化合物巴豆呋喃烷 B 的结构也得到了修正。对所有分离出的化合物进行了评估，以确定它们对 LPS 诱导的 RAW 264.7 巨噬细胞产生一氧化氮（NO）的抑制活性。其中，化合物 5 和 6 具有显著的抑制作用，IC50 值分别为 20.33 ± 2.31 和 22.80 ± 1.31 μmol-L-1。

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引用次数: 0

New insight into targeting the DNA damage response in the treatment of glioblastoma 针对 DNA 损伤反应治疗胶质母细胞瘤的新见解。

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-10-01 DOI: 10.1016/S1875-5364(24)60694-1

Tengfei ZHEN , Tianyu SUN , Baichen XIONG , Hui LIU , Lei WANG , Yao CHEN , Haopeng SUN

Glioblastoma (GBM) is the most common invasive malignant tumor in human brain tumors, representing the most severe grade of gliomas. Despite existing therapeutic approaches, patient prognosis remains dismal, necessitating the exploration of novel strategies to enhance treatment efficacy and extend survival. Due to the restrictive nature of the blood-brain barrier (BBB), small-molecule inhibitors are prioritized in the treatment of central nervous system tumors. Among these, DNA damage response (DDR) inhibitors have garnered significant attention due to their potent therapeutic potential across various malignancies. This review provides a detailed analysis of DDR pathways as therapeutic targets in GBM, summarizes recent advancements, therapeutic strategies, and ongoing clinical trials, and offers perspectives on future directions in this rapidly evolving field. The goal is to present a comprehensive outlook on the potential of DDR inhibitors in improving GBM management and outcomes.

胶质母细胞瘤（GBM）是人类脑肿瘤中最常见的侵袭性恶性肿瘤，是胶质瘤中最严重的一种。尽管已有治疗方法，但患者的预后仍然不容乐观，因此有必要探索新的策略来提高疗效和延长生存期。由于血脑屏障（BBB）的限制性，小分子抑制剂成为治疗中枢神经系统肿瘤的优先选择。其中，DNA损伤反应（DDR）抑制剂因其在各种恶性肿瘤中的强大治疗潜力而备受关注。本综述详细分析了作为 GBM 治疗靶点的 DDR 通路，总结了最新进展、治疗策略和正在进行的临床试验，并对这一快速发展领域的未来方向进行了展望。其目的是全面展望 DDR 抑制剂在改善 GBM 治疗和预后方面的潜力。

引用次数: 0

Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury 用穿心莲内酯靶向TLR4并调节Keap1/Nrf2通路，以抑制LPS诱导的急性肺损伤中的炎症和铁变态反应。

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-10-01 DOI: 10.1016/S1875-5364(24)60727-2

Yichen LI , Liting HUANG , Jilang LI , Siyuan LI , Jianzhen LV , Guoyue ZHONG , Ming GAO , Shilin YANG , Shan HAN , Wenhui HAO

Acute lung injury (ALI) is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of ALI involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide (AG), a bioactive compound derived from Andrographis, in mitigating Lipopolysaccharide (LPS)-induced inflammation and ferroptosis. Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. In vivo, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced ALI mice. These protective effects are mediated via the modulation of the Toll-like receptor 4 (TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Molecular docking simulations identified the binding sites of AG on the TLR4 protein (Kd value: −33.5 kcal·mol⁻¹), and these interactions were further corroborated by Cellular Thermal Shift Assay (CETSA) and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG’s potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.

急性肺损伤（ALI）是一种严重的炎症，死亡率很高，通常由败血症诱发。急性肺损伤的病理生理学涉及复杂的机制，包括炎症、氧化应激和铁变态反应（一种新的细胞死亡调节形式）。本研究探讨了穿心莲内酯（AG）（一种从穿心莲中提取的生物活性化合物）在减轻脂多糖（LPS）诱导的炎症和铁细胞凋亡方面的治疗潜力。我们的研究采用了 RAW264.7 巨噬细胞体外实验和 LPS 诱导 ALI 的小鼠模型体内研究。结果表明，AG 能明显抑制促炎细胞因子的产生，并能抑制 LPS 刺激的 RAW264.7 细胞中的铁蛋白沉积。在体内，AG 治疗可明显减轻 LPS 诱导的 ALI 小鼠肺组织的肺水肿、减少炎性细胞浸润并减轻铁细胞沉着。这些保护作用是通过调节 Toll 样受体 4 (TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) 信号通路介导的。分子对接模拟确定了 AG 在 TLR4 蛋白上的结合位点（Kd 值：-33.5 kcal-mol-1），细胞热移试验（CETSA）和 SPR 试验进一步证实了这些相互作用。总之，我们的研究结果表明，AG 通过靶向 TLR4 和调节 Keap1/Nrf2 通路，在 LPS 诱导的 ALI 中发挥了强有力的抗炎和抗铁细胞生成作用。这项研究强调了 AG 作为 ALI 治疗药物的潜力，并对其潜在的作用机制提供了新的见解。

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引用次数: 0

Four new diarylheptanoids and two new terpenoids from the fruits of Alpinia oxyphylla and their anti-inflammatory activities 牛膝草果实中的四种新的二芳基庚酸类化合物和两种新的萜类化合物及其抗炎活性。

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-10-01 DOI: 10.1016/S1875-5364(24)60723-5

Jie DONG , Haibo LI , Mi ZHOU , Xinsheng YAO , Jianliang GENG , Yang YU

Four previously unreported diarylheptanoids (1a/1b−2a/2b), one undescribed sesquiterpenoid (8), one new diterpenoid (12), and twelve known analogs were isolated from the fruits of Alpinia oxyphylla. The structural elucidation of these compounds was achieved through a comprehensive analysis of spectroscopic data, single-crystal X-ray diffraction, electronic circular dichroism (ECD), and modified Mosher’s method. Enantiomeric mixtures (1a/1b, 2a/2b, 3a/3b, 4a/4b, and 5a/5b) were separated on a chiral column using acetonitrile-water mixtures as eluents. Among them, compounds 3a/3b and 4a/4b were isolated as optically pure enantiomers in the initial chiral separation. Furthermore, most of the isolates were evaluated for their inhibitory effects against the production of nitric oxide (NO) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Interestingly, 2 and 4 showed significant inhibitory activities against NO production with IC₅₀ values of 33.65 and 9.88 μmol·L⁻¹ (hydrocortisone: IC₅₀ 34.26 μmol·L⁻¹), respectively. Additionally, they also partially reduced the secretion of IL-6.

通过对光谱数据、单晶 X 射线衍射、电子圆二色性（ECD）和改良莫舍尔法的综合分析，从 Alpinia oxyphylla 果实中分离出了四种以前未报道过的二芳基庚烷类化合物（1a/1b-2a/2b）、一种未报道过的倍半萜类化合物（8）、一种新的二萜类化合物（12）和十二种已知的类似物。通过对光谱数据、单晶 X 射线衍射、电子圆二色性（ECD）和改进的莫舍尔法进行综合分析，这些化合物的结构得以阐明。以乙腈-水混合物为洗脱剂，在手性色谱柱上分离了对映体混合物（1a/1b、2a/2b、3a/3b、4a/4b 和 5a/5b）。其中，化合物 3a/3b 和 4a/4b 在初次手性分离中分离出光学纯对映体。此外，还评估了大部分分离物对脂多糖（LPS）诱导的 RAW264.7 巨噬细胞产生一氧化氮（NO）和白细胞介素-6（IL-6）的抑制作用。有趣的是，2 和 4 对一氧化氮的产生具有显著的抑制作用，IC50 值分别为 33.65 和 9.88 μmol-L-1（氢化可的松：IC50 为 34.26 μmol-L-1）。此外，它们还能部分减少 IL-6 的分泌。

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引用次数: 0

Toosendanin: upgrade of an old agent in cancer treatment Toosendanin: 改良治疗癌症的老药。

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-10-01 DOI: 10.1016/S1875-5364(24)60693-X

Shuwei LI , Qingyi XIONG , Yiwen SHEN , Jiayi LIN , Lijun ZHANG , Ye WU , Jinmei JIN , Xin LUAN

Toosendanin (TSN), a tetracyclic triterpenoid derived from Melia toosendan and M. azedarach, demonstrates broad application prospects in cancer treatment. Although previously employed as a pesticide, recent studies have revealed its potential therapeutic value in treating various types of cancer. TSN exerts an anticancer effect via mechanisms including proliferation inhibition, apoptosis induction, migration suppression, and angiogenesis inhibition. However, TSN’s toxicity, particularly its hepatotoxicity, significantly limits its therapeutic application. This review explored the dual nature of TSN, evaluating both its anticancer potential and toxicological risks, emphasizing the importance of balancing these aspects in therapeutic applications. Furthermore, we investigated the incorporation of TSN into novel therapeutic strategies, such as Proteolysis-targeting chimeras (PROTAC) technology and nanotechnology-based drug delivery systems (DDS), which enhance treatment efficacy while mitigating toxicity in normal tissues.

Toosendanin (TSN)是从 Melia toosendan 和 M. azedarach 中提取的一种四环三萜类化合物，在癌症治疗方面具有广阔的应用前景。虽然以前曾被用作杀虫剂，但最近的研究发现了它在治疗各种癌症方面的潜在治疗价值。TSN 通过抑制增殖、诱导凋亡、抑制迁移和抑制血管生成等机制发挥抗癌作用。然而，TSN 的毒性，尤其是肝毒性，极大地限制了其治疗应用。本综述探讨了 TSN 的双重性质，评估了其抗癌潜力和毒性风险，强调了在治疗应用中平衡这些方面的重要性。此外，我们还研究了将 TSN 纳入新型治疗策略的情况，如蛋白质分解靶向嵌合体（PROTAC）技术和基于纳米技术的给药系统（DDS），它们在提高疗效的同时减轻了对正常组织的毒性。

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引用次数: 0

Cyclocarysaponins A–J, dammarane-type triterpenoid glycosides from the leaves of Cyclocarya paliurus Cyclocarya paliurus叶片中的达玛烷型三萜苷--Cyclocarysaponins A-J。

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-10-01 DOI: 10.1016/S1875-5364(24)60646-1

Huiting XI , Mingming YUAN , Jianhua XIE , Yuanxing WANG

Ten previously undescribed dammarane-type triterpenoid glycosides, cyclocarysaponins A–J (1–10), were isolated from the leaves of Cyclocarya paliurus (Batal.) Iljinskaja. The structures of these compounds were characterized through detailed spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The cytotoxic activities of all isolates were assessed against five human cancer cell lines (Bel-7402, Caski, BGC-823, A2780, and HCT-116). Of the tested compounds, compounds 1, 7, and 9 exhibited selective cytotoxicity against one or more human cancer cell lines.

从 Cyclocarya paliurus (Batal.) Iljinskaja 的叶片中分离出了 10 种以前未曾描述过的达玛烷型三萜类苷，即 cyclocarysaponins A-J (1-10)。通过详细的光谱分析，包括一维和二维核磁共振（NMR）以及高分辨率电喷雾离子化质谱（HR-ESI-MS），对这些化合物的结构进行了表征。评估了所有分离物对五种人类癌症细胞系（Bel-7402、Caski、BGC-823、A2780 和 HCT-116）的细胞毒活性。在测试的化合物中，化合物 1、7 和 9 对一种或多种人类癌细胞系具有选择性细胞毒性。

引用次数: 0

Glasesterterpenoids A−C: three sesterterpenoids with 7-cyclohexyldecahydronaphthalene carbon skeleton isolated from the root of Lindera glauca Glasesterterpenoids A-C：从 Lindera glauca 根部分离出的三种具有 7-环己基十氢萘碳骨架的酯类化合物

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-09-01 DOI: 10.1016/S1875-5364(24)60657-6

Shiting HE , Qinghui ZOU , Qi ZHANG , Yingming LUO , Die YAN , Jingxin HE , Yena LIU , Hui CUI

Three novel sesterterpenoids glasesterterpenoids A−C (1−3), featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton, were isolated from the root of Lindera glauca (L. glauca). Their structures were elucidated by quantum chemical calculations and spectroscopic methods. The biogenetic pathway for 1−3 is proposed. In the bioassay, glasesterterpenoid C exhibited DNA topoisomerase 1 (Top1) inhibitory activity compared with the positive control, camptothecin. These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of L. glauca.

从 Lindera glauca（林达草）的根中分离出了三种新的酯类化合物 glasesterterpenoids A-C（1-3），它们具有前所未有的 7-Cyclohexyldecahydronaphthalene 碳骨架。通过量子化学计算和光谱方法阐明了它们的结构。提出了 1-3 的生物发生途径。在生物测定中，与阳性对照喜树碱相比，glasesterpenoid C 具有 DNA 拓扑异构酶 1（Top1）抑制活性。这些发现代表了从鳞茎草根中首次发现具有 7-环己基十氢萘碳骨架的酯类化合物。

引用次数: 0

Rehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring intracellular iron homeostasis 熟地黄水提取物通过恢复细胞内铁稳态改善肝缺血再灌注损伤

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2024-09-01 DOI: 10.1016/S1875-5364(24)60719-3

Yinhao ZHANG , Kexin JIA , Yufei LI , Zhi MA , Guifang FAN , Ranyi LUO , Yajing LI , Yang YANG , Fanghong LI , Runping LIU , Jia LIU , Xiaojiaoyang LI

Hepatic ischemia/reperfusion injury (HIRI) is a common pathophysiological condition occurring during or after liver resection and transplantation, leading to hepatic viability impairment and functional deterioration. Recently, ferroptosis, a newly recognized form of programmed cell death, has been implicated in IRI. Rehmanniae Radix Praeparata (RRP), extensively used in Chinese herbal medicine for its hepatoprotective, anti-inflammatory, and antioxidant properties, presents a potential therapeutic approach. However, the mechanisms by which RRP mitigates HIRI, particularly through the regulation of ferroptosis, remain unclear. In this study, we developed a HIRI mouse model and monocrotaline (MCT)- and erastin-induced in vitro hepatocyte injury models. We conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on HIRI. The RRP aqueous extract was characterized by the presence of acteoside, rehmannioside D, and 5-hydroxymethylfurfural. Our results demonstrate that the RRP aqueous extract ameliorated oxidative stress, reduced intracellular iron accumulation, and attenuated HIRI-induced liver damage. Additionally, RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in vitro. Mechanistically, the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake, promoting hepcidin- and ferroportin-mediated iron efflux, and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 expression. Moreover, siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract’s inhibitory effect on ferroptosis. In conclusion, our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI, highlighting the restoration of iron metabolic balance. These findings position RRP as a promising candidate for clinical intervention in HIRI treatment.

肝脏缺血/再灌注损伤（HIRI）是一种常见的病理生理状况，发生在肝脏切除和移植过程中或之后，会导致肝脏活力受损和功能衰退。最近，一种新认识到的程序性细胞死亡形式--铁蛋白沉积（ferroptosis）被认为与 IRI 有关。地黄（RRP）因其保肝、抗炎和抗氧化特性而被广泛应用于中药中，是一种潜在的治疗方法。然而，RRP 减轻 HIRI 的机制，特别是通过调节铁蛋白沉积的机制，仍不清楚。在本研究中，我们建立了一个 HIRI 小鼠模型以及单克隆（MCT）和厄拉斯汀诱导的体外肝细胞损伤模型。我们进行了全基因组转录组分析，以阐明 RRP 对 HIRI 的保护作用和机制。RRP 水提取物的特征是含有阳起石苷、雷曼牡蛎苷 D 和 5- 羟甲基糠醛。我们的研究结果表明，RRP 水提取物能改善氧化应激，减少细胞内铁积累，减轻 HIRI 引起的肝损伤。此外，通过恢复细胞内铁的体内和体外平衡，RRP 还能显著抑制肝细胞的死亡。从机理上讲，RRP 水提取物通过抑制 ZIP14 介导的铁吸收、促进肝磷脂素和铁蛋白介导的铁外流，以及通过上调 Cisd1 的表达改善线粒体铁聚集，从而减少肝细胞内铁的积累。此外，siRNA 介导的对 hamp 的抑制协同增强了 RRP 水提取物对铁蛋白沉积的抑制作用。总之，我们的研究阐明了 RRP 水提取物缓解 HIRI 的机制，强调了铁代谢平衡的恢复。这些研究结果将 RRP 定位为治疗 HIRI 的临床干预候选药物。

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引用次数: 0