Chinese Journal of Natural Medicines最新文献_第8页

The role of 8-OxoG and its repair systems in liver diseases progression: responsible mechanisms and promising natural products 8-OxoG及其修复系统在肝脏疾病进展中的作用：负责任的机制和有前途的天然产物

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60848-X

Ying Zheng, Junxin Chen, Ze Liu, Kaibo Wang, Hao Zhang

The accumulation of deoxyribonucleic acid (DNA) oxidative damage mediated by reactive oxygen species (ROS) is closely associated with liver diseases. 8-Oxoguanine (8-OxoG), a prevalent DNA oxidation product, plays a significant role in liver disease progression. The base excision repair (BER) pathway, comprising over 30 proteins including 8-OxoG DNA glycosylase1 (OGG1), MutY homolog (MUTYH), and MutT homolog protein 1 (MTH1), is responsible for the clearance and mismatch repair of 8-OxoG. Abnormally high levels of 8-OxoG and dysregulated expression and function of 8-OxoG repair enzymes contribute to the onset and development of liver diseases. Consequently, targeting the 8-OxoG production and repair system with agonists or inhibitors may offer a promising approach to liver disease treatment. This review summarizes the impact of 8-OxoG accumulation and dysregulated repair enzymes on various liver diseases, including viral liver disease, alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), cholestatic liver disease (CLD), liver fibrosis, cirrhosis, and liver cancer. Additionally, we review natural constituents as potential therapeutic agents that regulate 8-OxoG production, repair enzymes, and repair system-related signal pathways in oxidative damage-induced liver diseases.

活性氧（ROS）介导的脱氧核糖核酸（DNA）氧化损伤积累与肝脏疾病密切相关。8-氧鸟嘌呤（8-OxoG）是一种常见的DNA氧化产物，在肝脏疾病的进展中起着重要作用。碱基切除修复（BER）途径由30多种蛋白质组成，包括8-OxoG DNA糖基化酶1 （OGG1）、MutY同源蛋白（MUTYH）和MutT同源蛋白1 (MTH1)，负责8-OxoG的清除和错配修复。异常高水平的8-OxoG和8-OxoG修复酶的表达和功能失调有助于肝脏疾病的发生和发展。因此，用激动剂或抑制剂靶向8-OxoG的产生和修复系统可能为肝脏疾病的治疗提供了一种有希望的方法。本文综述了8-OxoG积累和修复酶失调对各种肝脏疾病的影响，包括病毒性肝病、酒精性肝病（ALD）、代谢功能障碍相关的脂肪变性肝病（MASLD）、胆汁淤积性肝病（CLD）、肝纤维化、肝硬化和肝癌。此外，我们回顾了天然成分作为潜在的治疗药物，在氧化损伤引起的肝脏疾病中调节8-OxoG的产生、修复酶和修复系统相关信号通路。

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引用次数: 0

Identification and biomimetic synthesis of iphionanes and cyperanes from Artemisia hedinii and their anti-hepatic fibrosis activity 青蒿中伊菲酮类和环己烷类的鉴定、仿生合成及其抗肝纤维化活性

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60915-0

Xiaofei Liu , Xing Wang , Chunping Tang , Changqiang Ke , Bintao Hu , Sheng Yao , Yang Ye

Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2−5) and six new cyperane-type sesquiterpenes (7−11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.

从黄花蒿（Artemisia hedinii， A. hedinii）全株中分离到2个新的骨架倍半萜（1和6），4个新的伊菲烷型倍半萜（2−5）和6个新的环己烷型倍半萜（7−11）。这两个新的骨架化合物（1和6）分别是由伊菲酮型和环己烷型倍半萜脱碳而得。通过对高分辨率电喷雾电离质谱（HR-ESI-MS）和核磁共振（NMR）光谱的综合分析，阐明了它们的结构。通过电子圆二色性（ECD）光谱、单晶x射线晶体学分析、时变密度泛函理论（TDDFT） ECD计算、密度泛函理论（DFT）核磁共振计算和仿生学合成确定了绝对构型。这两种新型骨架（1和6）的仿生合成受到潜在生物遗传途径的启发，利用了a . hedinii中占优势的桉烷型倍半萜(a)作为底物。在LX-2细胞中评估所有化合物的抗肝纤维化活性。化合物2、8和10在下调α-平滑肌肌动蛋白（α-SMA）表达方面表现出显著活性，α-SMA是一种参与肝纤维化的蛋白。

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引用次数: 0

Diterpenoids and lignans from fossil Chinese medicinal succinum and their activity against renal fibrosis 中药古琥珀二萜类、木脂素及其抗肾纤维化活性研究

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60916-2

Yefei Chen , Yunfei Wang , Yunyun Liu , Yongming Yan , Yongxian Cheng

Five previously undescribed diterpenoids, named succipenoids D‒H (1‒5), along with four undescribed lignans, named succignans A‒D (6‒9), were isolated from the dichloromethane extract of Chinese medicinal succinum. Compounds 1‒5 were characterized as nor-abietane diterpenoids, while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units. The structures of these novel compounds, including their absolute configurations, were determined through spectroscopic and computational methods. Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis, including α-smooth muscle actin (α-SMA), collagen I, and fibronectin in transforming growth factor-β1 (TGF-β1) induced normal rat kidney proximal tubular epithelial cells (NRK-52e).

从中药琥珀的二氯甲烷提取物中分离得到5个未被描述的二萜类化合物，分别命名为succipenoids D-H（1-5）和4个未被描述的木脂素，分别命名为succipenoids A-D（6-9）。化合物1 ~ 5被鉴定为非枞烷二萜，而化合物6 ~ 9被鉴定为由两个苯基丙烷单元聚合而成的木脂素。这些新化合物的结构，包括它们的绝对构型，通过光谱和计算方法确定。肾纤维化生物学评估表明，化合物6和7可有效降低转化生长因子-β1 （TGF-β1）诱导的正常大鼠肾近端小管上皮细胞（NRK-52e）中α-平滑肌肌动蛋白（α-SMA）、I型胶原和纤维连接蛋白等肾纤维化相关蛋白的表达。

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引用次数: 0

Naturally occurring seco- and nor-polycyclic polyprenylated acylphloroglucinols: distribution, structural diversity, andbiological activity 天然存在的二环和非多环聚戊烯基酰基间苯三酚：分布、结构多样性和生物活性

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60911-3

Yulin Duan , Ying Tang , Changxing Qi , Yonghui Zhang

Polycyclic polyprenylated acylphloroglucinols (PPAPs) represent a distinct subclass of specialized metabolites predominantly found in the plant kingdom, particularly within the Guttiferae (Clusiaceae) family. These compounds exhibit remarkable structural diversity and a wide range of biological activities. Seco- and nor-PPAPs, two unique variants of PPAPs with diverse skeletal structures, have been extensively investigated. As of June 2023, 200 compounds have been isolated from four genera, with Hypericum being the primary source. Notably, 115 of these compounds were identified in the past four years, indicating a significant increase in research activity. Seco- and nor-PPAPs can be categorized into six main subgroups based on the original PPAP scaffolds. Biological studies have revealed their potential in various therapeutic applications, including anti-cancer, anti-inflammatory, hepatoprotective, anti-Alzheimer's disease (anti-AD), multidrug resistance (MDR) reversal, anti-depressant, neuroprotective, and immunosuppressive effects. This review provides a comprehensive overview of the occurrence, structures, and bioactivities of natural seco- and nor-PPAPs, offering valuable insights for the further development of PPAPs.

多环聚戊烯酰化酰基间苯三酚（PPAPs）是一种独特的代谢物亚类，主要存在于植物界，特别是在木耳科（Clusiaceae）家族中。这些化合物具有显著的结构多样性和广泛的生物活性。Seco和non - ppap是ppap的两种独特变体，具有不同的骨骼结构，已被广泛研究。截至2023年6月，已从4个属中分离到200个化合物，其中金丝桃属为主要来源。值得注意的是，其中115种化合物是在过去四年中发现的，这表明研究活动显著增加。基于原始PPAP支架，Seco和non -PPAP可分为六个主要亚组。生物学研究已经揭示了它们在各种治疗应用中的潜力，包括抗癌、抗炎、保护肝脏、抗阿尔茨海默病（抗ad）、逆转多药耐药（MDR）、抗抑郁、神经保护和免疫抑制作用。本文综述了天然二、非PPAPs的发生、结构和生物活性，为PPAPs的进一步开发提供有价值的见解。

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引用次数: 0

First-in-class drug oroxylin A tablets for treating hepatic and gastrointestinal disorders: from preclinical development to clinical research 治疗肝脏和胃肠道疾病的一流药物奥罗霉素A片：从临床前开发到临床研究

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60910-1

Chengju Luo , Xuhong Li , Yuan Gao , Junyi Yang , Weiming Fang , Libin Wei

Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.

Oroxylum indicum （Oroxylum）和黄芩（Scutellaria baicalensis）是一种主要从黄芩中提取的天然黄酮类化合物。目前，OA可通过化学合成获得，并具有多种药理作用，包括抗癌、抗炎、抗微生物和多器官保护作用。目前，OA片剂正在进行治疗肝细胞癌（HCC）的Ib/IIa期临床试验。大量证据表明，OA具有治疗多种肝脏和胃肠道疾病的潜力，包括HCC、肝纤维化、脂肪肝、肝炎、肝损伤、结肠炎和结直肠癌。OA主要通过调节几个关键的信号通路发挥其治疗作用，包括与凋亡、氧化应激、炎症、糖脂代谢和纤维化激活相关的信号通路。口服OA的药代动力学以II期代谢、水解和肠肝循环为特征。这篇综述提供了OA片剂开发的关键阶段的全面概述，从临床前到临床阶段的整体视角展示了这一一流药物的进展。它包括活性药物成分的合成、药代动力学、药理学功效、毒理学、药物传递和临床试验的最新进展。重要的是，本综述探讨了OA可能影响肠-肝轴的潜在机制，假设这些相互作用可能赋予OA相关的健康益处，超越其低生物利用度造成的限制。

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引用次数: 0

Natural diosmin alleviating obesity and nonalcoholic fatty liver disease by regulating the activating the AMP-activated protein kinase (AMPK) pathway 天然薯蓣皂苷通过调节活化amp活化蛋白激酶（AMPK）途径减轻肥胖和非酒精性脂肪肝疾病

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60914-9

Can Liu , Siyu Hao , Mengdi Zhang , Xueyu Wang , Baiwang Chu , Tingjie Wen , Ruoyu Dang , Hua Sun

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.

肥胖和代谢功能障碍相关的脂肪变性肝病（MASLD）与许多慢性疾病有关，包括心血管疾病、动脉粥样硬化、慢性肾脏疾病和II型糖尿病。先前的研究发现，从菊花中提取的天然类黄酮二司米是葡萄糖代谢的调节剂。然而，其对脂质代谢的影响及其潜在机制仍未被探索。amp激活的蛋白激酶（AMPK）途径在葡萄糖和脂质代谢中起关键作用。地奥司明和AMPK通路之间的关系以前没有文献记载。本研究在肝母细胞瘤细胞系G2 （HepG2）和3T3-L1细胞中检测地奥米明通过AMPK通路激活降低脂质含量的能力。该研究表明，地奥司明抑制脂肪生成，表明其作为肥胖小鼠的抗肥胖剂的潜力。此外，地奥米明在体内显示出有效的MASLD缓解。这些发现表明，地奥米可能是治疗肥胖和MASLD的有希望的治疗候选者。

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引用次数: 0

Five new meroterpenoids from Rhododendron anthopogonoides and their anti-inflammatory activity 五种杜鹃花新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 : 2025-07-01 DOI: 10.1016/S1875-5364(25)60850-8

Mengtian Li , Norbu Kelsang , Yongqin Zhao , Wensen Li , Feng Zhou , Pema , Lu Cui , Xianjie Bao , Qian Wang , Xin Feng , Minghua Yang

Five meroterpenoids, rhodonoids K–M (1–2), daurichromene E (3), and grifolins A–B (4–5), together with seven known compounds (6–12), were isolated from Rhododendron anthopogonoides. The chemical structures of these compounds were elucidated through comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) data. Their absolute configurations were determined by comparing experimental electronic circular dichroism (ECD) spectra with computed values. Notably, compounds 1 and 3 demonstrated significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. These compounds markedly suppressed the mRNA expressions of inflammatory factors, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) while also down-regulating the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).

从anthopogonoides中分离得到5个meroterpenoids， rhodonoids K-M (1-2), daurichromene (3), grifolins A-B（4-5）和7个已知化合物（6-12）。通过高分辨率电喷雾电离质谱（HR-ESI-MS）、紫外（UV）、红外光谱（IR）和核磁共振（NMR）数据的综合分析，对这些化合物的化学结构进行了鉴定。通过比较实验电子圆二色性（ECD）光谱与计算值，确定了它们的绝对构型。值得注意的是，化合物1和3对RAW264.7细胞中脂多糖（LPS）诱导的炎症有明显的抑制作用。这些化合物显著抑制炎症因子，包括白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α (TNF-α) mRNA的表达，同时下调诱导型一氧化氮合酶（iNOS）和环氧合酶-2 （COX-2）蛋白的表达。

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引用次数: 0

Host-microbe co-metabolism system as potential targets: the promising way for natural medicine to treat atherosclerosis 宿主-微生物共代谢系统作为潜在靶点：天然药物治疗动脉粥样硬化的有前景的途径

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60909-5

Yun Wang , Ziwei Zhou , Haiping Hao , Lijuan Cao

The host-microbe co-metabolism system, generating diverse exogenous and endogenous bioactive molecules that influence the host's immune and metabolic functions, plays a crucial role in the pathogenesis of atherosclerosis. Recent studies have elucidated the interaction between natural medicines and this co-metabolism system. Upon oral administration, natural medicine ingredients can undergo transformation by gut microbiota, potentially enhancing their bioavailability or anti-atherogenic efficacy. Furthermore, natural medicines can exert anti-atherogenic effects via modulation of endogenous host-microbe co-metabolism. This review presents an updated understanding of the dual association between natural medicines and host-microbe co-metabolites. It explores the critical function of microbial exogenous metabolites derived from natural medicines and uncovers the mechanisms underlying natural medicines’ intervention on key nodes of endogenous host-microbe co-metabolism. These insights may offer new perspectives for cardiovascular disease (CVD) treatment and guide future drug discovery efforts.

宿主-微生物共代谢系统产生多种影响宿主免疫和代谢功能的外源性和内源性生物活性分子，在动脉粥样硬化的发病机制中起着至关重要的作用。最近的研究已经阐明了天然药物与这一共同代谢系统之间的相互作用。口服后，天然药物成分可以通过肠道微生物群进行转化，潜在地提高其生物利用度或抗动脉粥样硬化的功效。此外，天然药物可以通过调节内源性宿主-微生物共代谢发挥抗动脉粥样硬化作用。这篇综述提出了对天然药物和宿主-微生物共同代谢产物之间双重关联的最新理解。探索天然药物衍生的微生物外源性代谢物的关键功能，揭示天然药物干预内源性宿主-微生物共代谢关键节点的机制。这些见解可能为心血管疾病（CVD）的治疗提供新的视角，并指导未来的药物发现工作。

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引用次数: 0

Paclitaxel anti-cancer therapeutics: from discovery to clinical use 紫杉醇抗癌药物：从发现到临床应用

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60833-8

Haizheng Yu , Fen Lan , Yuan Zhuang , Qizhang Li , Lianqing Zhang , Hongchang Tian , Xiao Bu , Ruibing Chen , Yingying Gao , Zhuo Wang , Lei Zhang

Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.

紫杉醇（Paclitaxel， PTX）是一种从红豆杉属植物中提取的有价值的天然产物，具有显著的抗癌作用。它穿透微管壁的纳米孔，与管腔表面的微管蛋白相互作用，破坏微管动力学，从而诱导癌细胞的细胞毒性作用。PTX及其衍生物因其低毒、高效、广谱应用而被批准用于治疗多种疾病。PTX的广泛成功和不断扩大的应用导致了需求的增加，引起了人们对可及性的关注。因此，全球研究人员一直致力于开发替代生产方法，并在PTX递送系统中应用纳米载体来提高生物利用度。本文综述了PTX的来源、生产、理化性质、抗癌机制、临床应用、试验和化学免疫治疗等方面的挑战和进展。旨在为PTX的合理开发和有效利用提供综合参考。

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引用次数: 0

Platycodon grandiflorus polysaccharides combined with hesperidin exerted the synergistic effect of relieving ulcerative colitis in mice by modulating PI3K/AKT and JAK2/STAT3 signaling pathways 桔梗多糖联合橙皮苷通过调节PI3K/AKT和JAK2/STAT3信号通路发挥缓解小鼠溃疡性结肠炎的协同作用

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2025-07-01 DOI: 10.1016/S1875-5364(25)60913-7

Yang Liu , Quanwei Sun , Xuefei Xu , Mengmeng Li , Wenheng Gao , Yunlong Li , Ye Yang , Dengke Yin

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.

溃疡性结肠炎（UC）是一种病因复杂的慢性炎症性疾病，以肠道炎症和屏障功能障碍为特征。桔梗的主要成分桔梗多糖（PGP）和柑桔中的主要活性成分橙皮苷（Hesp）均具有抗炎作用。本研究旨在阐明PGP联合Hesp对UC协同作用的潜在机制，重点研究磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B （AKT）和Janus激酶2 (JAK2)/信号转导和转录激活因子3 （STAT3）信号通路之间的协同相互作用。采用葡聚糖硫酸钠（DSS）诱导小鼠UC模型和脂多糖（LPS）诱导的RAW264.7/IEC6细胞模型，研究PGP联合Hesp对UC的体外和体内抗炎作用及其可能的作用机制。结果表明，与单独用药相比，PGP和Hesp联合用药可显著调节炎症因子水平，抑制氧化应激，调节结肠黏膜免疫，抑制细胞凋亡，恢复肠道屏障功能。进一步的体外研究发现，PGP显著抑制PI3K/AKT信号通路，Hesp显著抑制JAK2/STAT3信号通路。针对这两种信号通路的抑制剂和激活剂的使用验证了PGP联合Hesp对PI3K/AKT和JAK2/STAT3信号通路的协同作用。这些发现表明PGP联合Hesp对dss诱导的结肠炎具有协同作用，可能通过磷酸酶和紧张素同源物(PTEN)/PI3K/AKT和白细胞介素-6 (IL-6)/JAK2/STAT3信号通路介导。

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引用次数: 0