Chinese Journal of Natural Medicines最新文献

Protective role of natural products in pulmonary fibrosis through immuneregulation 天然产物通过免疫调节在肺纤维化中的保护作用

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61074-6

Yijia Su, Xianhua Che, Yonghu Chen, Xilin Wu, Jiamin Wang, Zhe Jiang, Xuezheng Li

Pulmonary fibrosis (PF) is a progressive, fatal fibrotic disease caused by respiratory conditions. The condition can ultimately lead to severe organ failure and mortality, and is associated with multiple risk factors. Growing evidence highlights the immune system’s role in PF, with various immune components participating in inflammatory and fibrotic processes. Different immune cells, including neutrophils, lymphocytes, and macrophages, demonstrate distinct effects on PF progression and development. Furthermore, key immune system cytokines, including the interleukin (IL) family, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, and connective tissue growth factor (CTGF), contribute to PF initiation and progression through independent mechanisms and mutual regulation. Currently, limited effective treatments exist for PF, with several treatments causing severe adverse reactions. Natural products, characterized by multi-target effects, holistic regulation, and low toxicity, have emerged as a research focus. This review compiles the mechanisms, therapeutic potential, and active components of various natural products. These compounds can ameliorate pulmonary inflammation, epithelial-mesenchymal transition, and collagen deposition through diverse immune mechanisms, acting at specific stages or throughout the fibrotic process, thereby supporting PF management. This review examines current scientific understanding of natural products’ immunological effects in PF, which is crucial for developing future anti-PF therapeutics.

肺纤维化（PF）是一种由呼吸系统疾病引起的进行性、致命性纤维化疾病。这种情况最终会导致严重的器官衰竭和死亡，并与多种危险因素有关。越来越多的证据强调免疫系统在PF中的作用，各种免疫成分参与炎症和纤维化过程。不同的免疫细胞，包括中性粒细胞、淋巴细胞和巨噬细胞，在PF的进展和发展中表现出不同的作用。此外，关键的免疫系统细胞因子，包括白细胞介素（IL）家族、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、转化生长因子(TGF)-β和结缔组织生长因子（CTGF），通过独立的机制和相互调节，促进PF的发生和发展。目前，PF的有效治疗方法有限，有几种治疗方法会引起严重的不良反应。天然产物具有多靶点作用、整体调控、低毒性等特点，已成为研究的热点。本文综述了各种天然产物的机制、治疗潜力和有效成分。这些化合物可以通过不同的免疫机制改善肺部炎症、上皮-间质转化和胶原沉积，在特定阶段或整个纤维化过程中起作用，从而支持PF的治疗。本文综述了目前对天然产物在PF中的免疫作用的科学认识，这对开发未来的抗PF治疗方法至关重要。

{"title":"Protective role of natural products in pulmonary fibrosis through immuneregulation","authors":"Yijia Su, Xianhua Che, Yonghu Chen, Xilin Wu, Jiamin Wang, Zhe Jiang, Xuezheng Li","doi":"10.1016/S1875-5364(26)61074-6","DOIUrl":"10.1016/S1875-5364(26)61074-6","url":null,"abstract":"<div><div>Pulmonary fibrosis (PF) is a progressive, fatal fibrotic disease caused by respiratory conditions. The condition can ultimately lead to severe organ failure and mortality, and is associated with multiple risk factors. Growing evidence highlights the immune system’s role in PF, with various immune components participating in inflammatory and fibrotic processes. Different immune cells, including neutrophils, lymphocytes, and macrophages, demonstrate distinct effects on PF progression and development. Furthermore, key immune system cytokines, including the interleukin (IL) family, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, and connective tissue growth factor (CTGF), contribute to PF initiation and progression through independent mechanisms and mutual regulation. Currently, limited effective treatments exist for PF, with several treatments causing severe adverse reactions. Natural products, characterized by multi-target effects, holistic regulation, and low toxicity, have emerged as a research focus. This review compiles the mechanisms, therapeutic potential, and active components of various natural products. These compounds can ameliorate pulmonary inflammation, epithelial-mesenchymal transition, and collagen deposition through diverse immune mechanisms, acting at specific stages or throughout the fibrotic process, thereby supporting PF management. This review examines current scientific understanding of natural products’ immunological effects in PF, which is crucial for developing future anti-PF therapeutics.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 23-32"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001705","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 of 3-n-butylphthalide and its derivatives in combating cerebral ischemia 3-正丁苯酞及其衍生物抗脑缺血的研究进展

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61073-4

Hongwei Zheng , Yangyang Jiang , Kai Wang , Xiao Liu , Zihan Jia , Xing Su , Yanan Zhang , Yihua Zhang , Zhangjian Huang , Yong Ling

Ischemic stroke (IS) presents a major threat to human life and health due to its high disability and mortality rates. 3-n-Butylphthalide (NBP), derived from celery seeds of the Apiaceae family native to the Mediterranean region, was first introduced in China for acute IS treatment in 2004. NBP demonstrates multiple therapeutic actions, including reconstruction of microcirculation in the cerebral ischemia area, inhibition of platelet aggregation, reduction of cerebral infarction volume, maintenance of blood-brain barrier (BBB) integrity, and enhancement of cerebral blood perfusion. However, its overall efficacy remains moderate, limited by poor water solubility and low bioavailability, which constrains its clinical application. To address these limitations, researchers have actively pursued the development of NBP derivatives and analogs, achieving notable progress. These efforts, including substituent introduction, ring opening derivatization, esterification, and atom substitution, have generated diverse NBP derivatives. Several of these derivatives have advanced to clinical studies. Specifically, potassium 2-(1-hydroxypentyl)-benzoate (PHPB), brozopentyl sodium (BZP), and XY-03-EA (ZONK1103) have reached phase II clinical trials, while (S)-2-(1-acetoxypentyl)benzoic acid L-arginine salt (AAPB) has received clinical trial approval for 2024. This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective, aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.

缺血性中风因其高致残率和高死亡率对人类生命和健康构成重大威胁。3-n-丁苯酞（NBP）是一种源自地中海地区的芹菜科植物，于2004年首次引入中国用于急性IS治疗。NBP具有多种治疗作用，包括重建脑缺血区微循环、抑制血小板聚集、减少脑梗死体积、维持血脑屏障（BBB）完整性、增强脑血流灌注。但其整体疗效一般，水溶性差，生物利用度低，限制了其临床应用。为了解决这些限制，研究人员积极追求NBP衍生物和类似物的发展，取得了显著进展。这些努力，包括取代基引入、开环衍生化、酯化和原子取代，产生了多种NBP衍生物。其中一些衍生物已进入临床研究阶段。其中，2-（1-羟基戊基）-苯甲酸钾（PHPB）、溴苯戊基钠（BZP）和XY-03-EA （ZONK1103）已进入II期临床试验，而(S)-2-（1-乙酰氧基）苯甲酸l -精氨酸盐（AAPB）已获得2024年的临床试验批准。本文从药物化学的角度对近二十年来NBP的结构修饰和优化进行了综述，旨在促进NBP衍生物的开发，促进脑缺血治疗。

{"title":"Research progress of 3-n-butylphthalide and its derivatives in combating cerebral ischemia","authors":"Hongwei Zheng , Yangyang Jiang , Kai Wang , Xiao Liu , Zihan Jia , Xing Su , Yanan Zhang , Yihua Zhang , Zhangjian Huang , Yong Ling","doi":"10.1016/S1875-5364(26)61073-4","DOIUrl":"10.1016/S1875-5364(26)61073-4","url":null,"abstract":"<div><div>Ischemic stroke (IS) presents a major threat to human life and health due to its high disability and mortality rates. 3-<em>n</em>-Butylphthalide (NBP), derived from celery seeds of the Apiaceae family native to the Mediterranean region, was first introduced in China for acute IS treatment in 2004. NBP demonstrates multiple therapeutic actions, including reconstruction of microcirculation in the cerebral ischemia area, inhibition of platelet aggregation, reduction of cerebral infarction volume, maintenance of blood-brain barrier (BBB) integrity, and enhancement of cerebral blood perfusion. However, its overall efficacy remains moderate, limited by poor water solubility and low bioavailability, which constrains its clinical application. To address these limitations, researchers have actively pursued the development of NBP derivatives and analogs, achieving notable progress. These efforts, including substituent introduction, ring opening derivatization, esterification, and atom substitution, have generated diverse NBP derivatives. Several of these derivatives have advanced to clinical studies. Specifically, potassium 2-(1-hydroxypentyl)-benzoate (PHPB), brozopentyl sodium (BZP), and XY-03-EA (ZONK1103) have reached phase II clinical trials, while (<em>S</em>)-2-(1-acetoxypentyl)benzoic acid L-arginine salt (AAPB) has received clinical trial approval for 2024. This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective, aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 13-22"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001704","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

Honokiol attenuates diabetes by enriching Akkermansia muciniphila andregulating tryptophan metabolism in mice 在小鼠中，本木酚通过富集嗜粘杆菌和调节色氨酸代谢来减轻糖尿病

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61077-1

Yang Lin , Zhengmeng Jiang , Zhilu Yu , Tianqing Huang , Wanyu Gui , Ziyuan Wang , Fei Li , Pingting Xiao , Changyin Li , Ehu Liu

Diabetes mellitus (DM) is a chronic disease influenced by gut microbiome disturbances. Honokiol (HON), a low oral bioavailability compound from Magnolia officinalis bark, has demonstrated potential as a treatment for DM. This research investigates the effects of HON on gut microbiota and host metabolism to elucidate its mechanism of action in DM. After 8 weeks of intervention through fecal microbiota transplantation (FMT) or antibiotic treatment, HON improved glucose tolerance and lipid metabolism in a gut microbiota-dependent manner. Specifically, HON administration significantly increased Akkermansia muciniphila (AKK) abundance and modulated tryptophan (TRP) metabolism, as evidenced by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and untargeted/targeted metabolomics analysis. Notably, research revealed that AKK metabolized TRP into tryptamine (TA) and other metabolites in vitro. Both AKK and TA activated the aryl hydrocarbon receptor (AHR) pathway, increasing circulating glucagon-like peptide-1 (GLP-1) levels and ameliorating diabetes-related symptoms in DM mice. These findings indicate that HON’s hypoglycemic effect primarily stems from AHR-GLP-1 pathway activation through targeted modulation of AKK and microbial TRP metabolite TA, potentially enhancing HON’s clinical applications.

糖尿病（DM）是一种由肠道微生物群紊乱影响的慢性疾病。厚朴酚（Honokiol， HON）是一种来自厚朴树皮的低口服生物利用度化合物，已被证明具有治疗糖尿病的潜力。本研究调查了Honokiol对肠道微生物群和宿主代谢的影响，以阐明其在糖尿病中的作用机制。通过粪便微生物群移植（FMT）或抗生素治疗8周后，Honokiol以肠道微生物群依赖的方式改善了糖耐量和脂质代谢。具体而言，通过16S核糖体核糖核酸（rRNA）基因测序和非靶向/靶向代谢组学分析可以证明，HON给药显著增加了嗜muciniphila （Akkermansia muciniphila， AKK）的丰度，并调节了色氨酸（TRP）代谢。值得注意的是，研究表明AKK在体外将TRP代谢为色胺（TA）和其他代谢物。AKK和TA均激活芳烃受体（AHR）通路，增加循环胰高血糖素样肽-1 （GLP-1）水平，改善糖尿病小鼠的糖尿病相关症状。这些发现表明，HON的降糖作用主要源于AHR-GLP-1通路的激活，通过靶向调节AKK和微生物TRP代谢物TA，潜在地增强了HON的临床应用。

{"title":"Honokiol attenuates diabetes by enriching Akkermansia muciniphila andregulating tryptophan metabolism in mice","authors":"Yang Lin , Zhengmeng Jiang , Zhilu Yu , Tianqing Huang , Wanyu Gui , Ziyuan Wang , Fei Li , Pingting Xiao , Changyin Li , Ehu Liu","doi":"10.1016/S1875-5364(26)61077-1","DOIUrl":"10.1016/S1875-5364(26)61077-1","url":null,"abstract":"<div><div>Diabetes mellitus (DM) is a chronic disease influenced by gut microbiome disturbances. Honokiol (HON), a low oral bioavailability compound from <em>Magnolia officinalis</em> bark, has demonstrated potential as a treatment for DM. This research investigates the effects of HON on gut microbiota and host metabolism to elucidate its mechanism of action in DM. After 8 weeks of intervention through fecal microbiota transplantation (FMT) or antibiotic treatment, HON improved glucose tolerance and lipid metabolism in a gut microbiota-dependent manner. Specifically, HON administration significantly increased <em>Akkermansia muciniphila</em> (AKK) abundance and modulated tryptophan (TRP) metabolism, as evidenced by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and untargeted/targeted metabolomics analysis. Notably, research revealed that AKK metabolized TRP into tryptamine (TA) and other metabolites <em>in vitro</em>. Both AKK and TA activated the aryl hydrocarbon receptor (AHR) pathway, increasing circulating glucagon-like peptide-1 (GLP-1) levels and ameliorating diabetes-related symptoms in DM mice. These findings indicate that HON’s hypoglycemic effect primarily stems from AHR-GLP-1 pathway activation through targeted modulation of AKK and microbial TRP metabolite TA, potentially enhancing HON’s clinical applications.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 59-72"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001712","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

Gambogic acid suppresses pancreatic fibrosis via inhibiting YAP1-mediated activation of pancreatic stellate cells 藤黄酸通过抑制yap1介导的胰腺星状细胞活化来抑制胰腺纤维化

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61079-5

Wei Li , Guangming Li , Yi Wang , Yuxin Zhou

The activation of pancreatic stellate cells (PSCs) and the secretion of inflammatory factors play critical roles in the development of pancreatic fibrosis. While gambogic acid (GA), a flavonoid with anti-tumor properties, has been studied, its role in this process remains unclear. This study demonstrated that GA promoted YAP1 degradation and reduced its nuclear localization, thereby inhibiting PSC activation and the progression of pancreatic fibrosis. GA inhibited PSC proliferation, decreased α-smooth muscle actin (α-SMA) expression, and reduced lipid droplets in LTC14 and primary mouse PSCs (mPSCs). Additionally, GA suppressed the expression of inflammatory factors [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), nuclear factor erythroid 2-related factor 2 (NRF2), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and nuclear factor κB (NF-κB)] in PSCs and counteracted the transforming growth factor (TGF)-β-induced increase in these proteins. GA also reduced collagen Ι and tissue inhibitor of metalloproteinase-1 (TΙMP1) expression, thereby attenuating fibrosis. Mechanistically, GA decreased YAP1 expression and nuclear translocation and reversed TGF-β-induced YAP1 upregulation. YAP1 overexpression abrogated GA’s inhibitory effects on PSC activation and inflammation. Furthermore, GA activated the Hippo pathway, increased phosphorylated (p)-LATS1 and p-YAP levels, and promoted ubiquitin-mediated YAP1 degradation. In vivo studies confirmed that GA inhibited dibutyltin dichloride (DBTC)-induced pancreatic fibrosis via suppressing YAP1 and NF-κB in BALB/c mice. In conclusion, GA activates the Hippo pathway and promotes YAP1 translocation to the cytoplasm, leading to its degradation and subsequent inhibition of PSC activation and fibrosis. These findings highlight the critical role of ubiquitin-mediated YAP1 degradation in regulating PSC activity and offer novel insights into the therapeutic potential of GA for treating pancreatic fibrosis.

胰腺星状细胞（PSCs）的激活和炎症因子的分泌在胰腺纤维化的发生发展中起着关键作用。虽然已经研究了具有抗肿瘤特性的黄酮类化合物藤黄酸（GA），但其在这一过程中的作用尚不清楚。本研究表明，GA促进YAP1降解，降低其核定位，从而抑制PSC的激活和胰腺纤维化的进展。GA抑制PSC增殖，降低α-平滑肌肌动蛋白（α-SMA）表达，减少LTC14和原代小鼠pssc （mPSCs）的脂滴。此外，GA抑制炎症因子[核苷酸结合寡聚结构域样受体蛋白3 （NLRP3）、核因子红系2相关因子2 （NRF2）、白细胞介素-6 （IL-6）、肿瘤坏死因子α (TNF-α)、核因子κB (NF-κB)]在PSCs中的表达，并抵消转化生长因子(TGF)-β-诱导的这些蛋白的增加。GA还能降低胶原Ι和金属蛋白酶-1组织抑制剂TΙMP1的表达，从而减轻纤维化。在机制上，GA降低了YAP1的表达和核易位，逆转了TGF-β诱导的YAP1上调。YAP1过表达消除了GA对PSC激活和炎症的抑制作用。此外，GA激活Hippo通路，增加磷酸化(p)-LATS1和p- yap水平，促进泛素介导的YAP1降解。体内研究证实，GA通过抑制BALB/c小鼠的YAP1和NF-κB来抑制二氯化二丁基锡（DBTC）诱导的胰腺纤维化。综上所述，GA激活Hippo通路，促进YAP1易位至细胞质，导致其降解，进而抑制PSC活化和纤维化。这些发现强调了泛素介导的YAP1降解在调节PSC活性中的关键作用，并为GA治疗胰腺纤维化的治疗潜力提供了新的见解。

{"title":"Gambogic acid suppresses pancreatic fibrosis via inhibiting YAP1-mediated activation of pancreatic stellate cells","authors":"Wei Li , Guangming Li , Yi Wang , Yuxin Zhou","doi":"10.1016/S1875-5364(26)61079-5","DOIUrl":"10.1016/S1875-5364(26)61079-5","url":null,"abstract":"<div><div>The activation of pancreatic stellate cells (PSCs) and the secretion of inflammatory factors play critical roles in the development of pancreatic fibrosis. While gambogic acid (GA), a flavonoid with anti-tumor properties, has been studied, its role in this process remains unclear. This study demonstrated that GA promoted YAP1 degradation and reduced its nuclear localization, thereby inhibiting PSC activation and the progression of pancreatic fibrosis. GA inhibited PSC proliferation, decreased <em>α</em>-smooth muscle actin (<em>α</em>-SMA) expression, and reduced lipid droplets in LTC14 and primary mouse PSCs (mPSCs). Additionally, GA suppressed the expression of inflammatory factors [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), nuclear factor erythroid 2-related factor 2 (NRF2), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and nuclear factor <em>κ</em>B (NF-<em>κ</em>B)] in PSCs and counteracted the transforming growth factor (TGF)-β-induced increase in these proteins. GA also reduced collagen Ι and tissue inhibitor of metalloproteinase-1 (TΙMP1) expression, thereby attenuating fibrosis. Mechanistically, GA decreased YAP1 expression and nuclear translocation and reversed TGF-β-induced YAP1 upregulation. YAP1 overexpression abrogated GA’s inhibitory effects on PSC activation and inflammation. Furthermore, GA activated the Hippo pathway, increased phosphorylated (p)-LATS1 and p-YAP levels, and promoted ubiquitin-mediated YAP1 degradation. <em>In vivo</em> studies confirmed that GA inhibited dibutyltin dichloride (DBTC)-induced pancreatic fibrosis <em>via</em> suppressing YAP1 and NF-<em>κ</em>B in BALB/c mice. In conclusion, GA activates the Hippo pathway and promotes YAP1 translocation to the cytoplasm, leading to its degradation and subsequent inhibition of PSC activation and fibrosis. These findings highlight the critical role of ubiquitin-mediated YAP1 degradation in regulating PSC activity and offer novel insights into the therapeutic potential of GA for treating pancreatic fibrosis.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 89-99"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001736","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

Xijiaqi Formula attenuates cognitive dysfunction by inhibiting neuroinflammation and promoting neuroplasticity in rats with chronic heart failure 西甲气方通过抑制神经炎症、促进神经可塑性减轻慢性心力衰竭大鼠认知功能障碍

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61078-3

Jie Chen , Xuefen Wu , Qian Zhang , Hongcai Shang, Wanting Li, Linnan Zhou, Xinyu Chu, Guiyang Xia, Huan Xia, Xiaohong Wei, Sheng Lin

Chronic heart failure (CHF) impairs cognitive function. Xijiaqi Formula (XJQ), a traditional Chinese medicine (TCM) used clinically to treat CHF, demonstrates potential for improving cognition in CHF patients. However, its precise mechanism in treating post-CHF cognitive dysfunction remains unclear. This study systematically investigates XJQ’s effects on post-CHF cognitive dysfunction and the underlying mechanisms. The components of XJQ were identified through liquid chromatography-mass spectrometry. CHF was induced in rats via ligation of the left anterior descending coronary artery, followed by six weeks of XJQ treatment. Cardiac function was evaluated through echocardiography and hemodynamic parameters, while cognitive function was assessed using Morris water maze (MWM) and open field tests (OFT). XJQ treatment enhanced both cardiac and cognitive functions in CHF rats. Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses, inflammation, and phosphodiesterase 4 (PDE4)-dependent cyclic adenosine monophosphate (cAMP) signaling. XJQ inhibited microglial and astrocyte activation, decreased proinflammatory cytokines, and mitigated neuronal damage. Notably, XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP, protein kinase A (PKA), cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), PSD95, and synapsin I levels. Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin, kaempferol, isorhamnetin, and darutoside to PDE4. In conclusion, XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway. These findings provide valuable insight into the heart-brain axis.

慢性心力衰竭（CHF）损害认知功能。临床治疗慢性心力衰竭（CHF）的中药西甲气方（XJQ）显示出改善CHF患者认知能力的潜力。然而，其治疗心力衰竭后认知功能障碍的确切机制尚不清楚。本研究系统探讨XJQ对心力衰竭后认知功能障碍的影响及其机制。采用液相色谱-质谱联用技术对XJQ的成分进行了鉴定。通过结扎左冠状动脉前降支诱导大鼠慢性心力衰竭，随后给予XJQ治疗6周。通过超声心动图和血流动力学参数评估心功能，采用Morris水迷宫（MWM）和开阔场试验（OFT）评估认知功能。XJQ治疗可提高CHF大鼠的心脏功能和认知功能。网络药理学鉴定出XJQ的12个核心活性成分，并表明其对认知功能障碍的作用涉及调节突触、炎症和磷酸二酯酶4 （PDE4）依赖性环腺苷单磷酸（cAMP）信号传导。XJQ抑制小胶质细胞和星形胶质细胞的激活，降低促炎细胞因子，减轻神经元损伤。值得注意的是，XJQ通过下调PDE4和上调cAMP、蛋白激酶A （PKA）、cAMP反应元件结合蛋白（CREB）、脑源性神经营养因子（BDNF）、PSD95和突触素I水平，促进突触修复和树突生长。分子对接和生物层干涉测定证实槲皮素、山奈酚、异鼠李素和达鲁多苷与PDE4直接结合。综上所述，XJQ通过PDE4/cAMP/PKA/CREB信号通路，减轻神经炎症，增强突触可塑性，改善CHF大鼠认知功能障碍。这些发现为了解心脑轴提供了有价值的见解。

{"title":"Xijiaqi Formula attenuates cognitive dysfunction by inhibiting neuroinflammation and promoting neuroplasticity in rats with chronic heart failure","authors":"Jie Chen , Xuefen Wu , Qian Zhang , Hongcai Shang, Wanting Li, Linnan Zhou, Xinyu Chu, Guiyang Xia, Huan Xia, Xiaohong Wei, Sheng Lin","doi":"10.1016/S1875-5364(26)61078-3","DOIUrl":"10.1016/S1875-5364(26)61078-3","url":null,"abstract":"<div><div>Chronic heart failure (CHF) impairs cognitive function. Xijiaqi Formula (XJQ), a traditional Chinese medicine (TCM) used clinically to treat CHF, demonstrates potential for improving cognition in CHF patients. However, its precise mechanism in treating post-CHF cognitive dysfunction remains unclear. This study systematically investigates XJQ’s effects on post-CHF cognitive dysfunction and the underlying mechanisms. The components of XJQ were identified through liquid chromatography-mass spectrometry. CHF was induced in rats <em>via</em> ligation of the left anterior descending coronary artery, followed by six weeks of XJQ treatment. Cardiac function was evaluated through echocardiography and hemodynamic parameters, while cognitive function was assessed using Morris water maze (MWM) and open field tests (OFT). XJQ treatment enhanced both cardiac and cognitive functions in CHF rats. Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses, inflammation, and phosphodiesterase 4 (PDE4)-dependent cyclic adenosine monophosphate (cAMP) signaling. XJQ inhibited microglial and astrocyte activation, decreased proinflammatory cytokines, and mitigated neuronal damage. Notably, XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP, protein kinase A (PKA), cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), PSD95, and synapsin I levels. Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin, kaempferol, isorhamnetin, and darutoside to PDE4. In conclusion, XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats <em>via</em> the PDE4/cAMP/PKA/CREB signaling pathway. These findings provide valuable insight into the heart-brain axis.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 73-88"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001732","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

Atramacronins A−P, eudesmane-type sesquiterpenoid dimers from Atractylodes macrocephala with anti-hepatocellular carcinoma activities 白术中具有抗肝癌活性的苍术素A−P、丹参素型倍半萜类二聚体

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61082-5

Ganggang Zhou , Xinru Li , Jiajia Liu , Jiqiong Wang , Zhaoyue Dong , Ammara Khalid , Yinda Qiu , Zhihua Liao , Guowei Wang , Hui Liu , Qingwen Zhang , Min Chen , Fancheng Meng

Atractylodes macrocephala Koidz. (A. macrocephala) is a medicinal and edible plant species belonging to the Compositae family. Its rhizome serves both therapeutic and nutritional purposes in China. This investigation led to the isolation of thirteen novel rearranged 9(8→7)-abeo-eudesmane-type sesquiterpenoid dimers (SDs), atramacronins A−M (1−13), three eudesmane-type SDs, atramacronins N−P (14−16), and two previously identified meroterpenoids, atrachinenin G (17) and atrachinenin Ι (18), from Atractylodes macrocephala. Structure elucidation was accomplished through comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Compounds 1, 4−7, 9, and 10 exhibited notable cytotoxicity against Hep3B, HepG2, and Huh7 cell lines, with half maximal inhibitory concentration (IC₅₀) values ranging from 3.71 to 13.99 μmol·L⁻¹.

苍术。大头草是菊科的一种药用和食用植物。它的根茎在中国有治疗和营养的双重用途。本研究从苍术中分离到13个新的重排9(8→7)- abo - eudesane型倍半萜类二聚体（SDs）， atramacronins A−M(1−13)，3个eudesane型SDs， atramacronins N−P(14−16)，以及2个先前鉴定的meroterpenids， atrachinenin G（17）和atrachinenin Ι（18）。通过综合光谱分析和单晶x射线衍射完成了结构解析。化合物1、4 ~ 7、9和10对Hep3B、HepG2和Huh7细胞系表现出明显的细胞毒性，半数最大抑制浓度（IC50）为3.71 ~ 13.99 μmol·L−1。

{"title":"Atramacronins A−P, eudesmane-type sesquiterpenoid dimers from Atractylodes macrocephala with anti-hepatocellular carcinoma activities","authors":"Ganggang Zhou , Xinru Li , Jiajia Liu , Jiqiong Wang , Zhaoyue Dong , Ammara Khalid , Yinda Qiu , Zhihua Liao , Guowei Wang , Hui Liu , Qingwen Zhang , Min Chen , Fancheng Meng","doi":"10.1016/S1875-5364(26)61082-5","DOIUrl":"10.1016/S1875-5364(26)61082-5","url":null,"abstract":"<div><div><em>Atractylodes macrocephala</em> Koidz. (<em>A. macrocephala</em>) is a medicinal and edible plant species belonging to the Compositae family. Its rhizome serves both therapeutic and nutritional purposes in China. This investigation led to the isolation of thirteen novel rearranged 9(8→7)-<em>abeo</em>-eudesmane-type sesquiterpenoid dimers (SDs), atramacronins A−M (<strong>1</strong>−<strong>13</strong>), three eudesmane-type SDs, atramacronins N−P (<strong>14</strong>−<strong>16</strong>), and two previously identified meroterpenoids, atrachinenin G (<strong>17</strong>) and atrachinenin Ι (<strong>18</strong>), from <em>Atractylodes macrocephala</em>. Structure elucidation was accomplished through comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Compounds <strong>1</strong>, <strong>4</strong>−<strong>7</strong>, <strong>9</strong>, and <strong>10</strong> exhibited notable cytotoxicity against Hep3B, HepG2, and Huh7 cell lines, with half maximal inhibitory concentration (IC<sub>50</sub>) values ranging from 3.71 to 13.99 μmol·L<sup>−1</sup>.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 119-128"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001734","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

Therapeutic potential of Ziziphora clinopodioides in cardiovascular diseases: a review 紫茎草在心血管疾病中的治疗潜力综述

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61075-8

Xingjie Zhuo , Shuxian Ding , Jinhua Li , Shengli Quan , Yuanxiao Yang , Weijun Yang , Qin Li

Cardiovascular diseases (CVDs) are driven by intricate and multifactorial pathophysiological mechanisms, presenting substantial challenges for the development of effective therapeutic strategies. Recent studies have highlighted the therapeutic potential of various traditional Chinese medicines (TCMs), which exert vasodilatory, anti-inflammatory, and antioxidant effects that may alleviate clinical symptoms and slow CVD progression. Ziziphora clinopodioides, a traditional herbal medicine, contains primarily flavonoids, phenolic acids, and essential oils. These compounds contribute to its pharmacological activities, including inhibition of apoptosis inhibition, inflammation reduction, oxidative stress mitigation, mitochondrial function improvement, and vasodilation promotion, all of which are relevant to CVD treatment. This review comprehensively examines the pathophysiological basis of CVDs, elucidates the molecular mechanisms and signaling pathways involved in the cardioprotective actions of Ziziphora clinopodioides, and summarizes its emerging clinical applications in cardiovascular therapy. The findings aim to inform future research and promote the rational development of this medicinal plant as a complementary or adjunctive treatment for CVDs.

心血管疾病（cvd）是由复杂的多因素病理生理机制驱动的，为开发有效的治疗策略提出了重大挑战。最近的研究强调了各种中药（tcm）的治疗潜力，它们具有血管扩张，抗炎和抗氧化作用，可以缓解临床症状并减缓心血管疾病的进展。紫竹是一种传统的草药，主要含有类黄酮、酚酸和精油。这些化合物有助于其药理活性，包括抑制细胞凋亡，减少炎症，减轻氧化应激，改善线粒体功能和促进血管舒张，所有这些都与CVD治疗有关。本文综述了cvd的病理生理基础，阐述了紫皮草保护心脏的分子机制和信号通路，并对其在心血管治疗中的临床应用进行了综述。这些发现旨在为今后的研究提供信息，并促进该药用植物作为心血管疾病的补充或辅助治疗的合理开发。

{"title":"Therapeutic potential of Ziziphora clinopodioides in cardiovascular diseases: a review","authors":"Xingjie Zhuo , Shuxian Ding , Jinhua Li , Shengli Quan , Yuanxiao Yang , Weijun Yang , Qin Li","doi":"10.1016/S1875-5364(26)61075-8","DOIUrl":"10.1016/S1875-5364(26)61075-8","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) are driven by intricate and multifactorial pathophysiological mechanisms, presenting substantial challenges for the development of effective therapeutic strategies. Recent studies have highlighted the therapeutic potential of various traditional Chinese medicines (TCMs), which exert vasodilatory, anti-inflammatory, and antioxidant effects that may alleviate clinical symptoms and slow CVD progression. <em>Ziziphora clinopodioides</em>, a traditional herbal medicine, contains primarily flavonoids, phenolic acids, and essential oils. These compounds contribute to its pharmacological activities, including inhibition of apoptosis inhibition, inflammation reduction, oxidative stress mitigation, mitochondrial function improvement, and vasodilation promotion, all of which are relevant to CVD treatment. This review comprehensively examines the pathophysiological basis of CVDs, elucidates the molecular mechanisms and signaling pathways involved in the cardioprotective actions of <em>Ziziphora clinopodioides</em>, and summarizes its emerging clinical applications in cardiovascular therapy. The findings aim to inform future research and promote the rational development of this medicinal plant as a complementary or adjunctive treatment for CVDs.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 33-44"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001710","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

New meroterpenoids featuring a rare 3/5/6/6/11/6/6 fused-ring skeleton from Penicillium brefeldianum SMU03 and their antifibrotic activities brefeldium SMU03中含有罕见的3/5/6/6/11/6/6融合环骨架的新型甲萜类化合物及其抗纤维化活性

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61081-3

Xia Cheng , Lei Di , Luying Wu , Qi Luo

Penicine A (1), a meroterpenoid featuring a novel 3/5/6/6/11/6/6 polycyclic backbone, together with two new metabolites, penicines B (2) and C (4), and six known compounds, were isolated from the mangrove rhizosphere soil-derived fungus Penicillium brefeldianum SMU03. The structures of these metabolites were elucidated through extensive spectroscopic analysis combined with quantum chemical calculations. Notably, 1 exhibits a highly unusual molecular architecture, incorporating a dioxaspiro[4.5]decane motif and a rare bridgehead double bond (anti-Bredt system). A plausible biosynthetic pathway, involving sequential intermolecular [4 + 2] cycloaddition reactions, is proposed. Additionally, meroterpenoids 1 and 3 demonstrate significant antifibrotic activity in transforming growth factor β1 (TGF-β1)-induced human renal proximal tubular epithelial cells.

从红树根际土壤来源真菌青霉菌（Penicillium brefeldianum SMU03）中分离到一种新型的3/5/6/6/11/6/6多环骨架的萜类化合物Penicine A(1)、2个新的代谢物Penicine B(2)和C(4)以及6个已知化合物。这些代谢物的结构通过广泛的光谱分析结合量子化学计算得到了阐明。值得注意的是，1展示了一个非常不寻常的分子结构，包含一个二恶斯匹罗[4.5]癸烷基序和一个罕见的桥头堡双键（反bredt系统）。提出了一种可行的生物合成途径，涉及顺序的分子间[4 + 2]环加成反应。此外，巯基萜类化合物1和3在转化生长因子β1 （TGF-β1）诱导的人肾近端小管上皮细胞中显示出显著的抗纤维化活性。

引用次数: 0

An overview of the advantageous effects and underlying mechanisms of natural polysaccharides in inflammatory bowel disease 天然多糖在炎症性肠病中的有利作用及其潜在机制综述

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61076-X

Yating Shao , Bo Li , Yongfang Wang , Chuanjie Zhou , Yunlong Qiao , Xinglishang He , Shengqiang Tong , Guiyuan Lv , Suhong Chen

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition affecting the gastrointestinal tract. The global incidence and prevalence of IBD continue to increase. While multiple clinical treatments exist, conventional therapies frequently present limitations and adverse effects. Natural polysaccharides (PSs) have emerged as a significant focus of research interest due to their therapeutic potential and applications in functional foods and health products. This review synthesizes current understanding of IBD pathophysiology and the mechanisms by which natural PSs counter IBD, including their capacity to restore immune homeostasis and intestinal barrier function, modulate gut microbiota and metabolites, reduce oxidative stress, and address irregularities in autophagy and endoplasmic reticulum stress (ERS). The review examines the structure-activity relationships of PSs demonstrating anti-IBD effects and identifies promising therapeutic products. The discussion encompasses pharmacokinetics, safety evaluations, and clinical applications of these compounds. This comprehensive review establishes a theoretical foundation for developing natural PS-based therapeutic approaches for IBD management.

炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），是一种影响胃肠道的慢性炎症性疾病。IBD的全球发病率和流行率持续上升。虽然存在多种临床治疗方法，但传统治疗方法往往存在局限性和不良反应。天然多糖由于其在功能性食品和保健品中的应用和治疗潜力，已成为研究的重要焦点。本文综述了目前对IBD病理生理和天然PSs对抗IBD的机制的理解，包括它们恢复免疫稳态和肠道屏障功能的能力，调节肠道微生物群和代谢物，减少氧化应激，以及解决自噬和内质网应激（ERS）的异常。本文综述了具有抗ibd作用的PSs的结构-活性关系，并确定了有前景的治疗产品。讨论内容包括这些化合物的药代动力学、安全性评价和临床应用。这一综合综述为开发基于天然ps的IBD治疗方法奠定了理论基础。

{"title":"An overview of the advantageous effects and underlying mechanisms of natural polysaccharides in inflammatory bowel disease","authors":"Yating Shao , Bo Li , Yongfang Wang , Chuanjie Zhou , Yunlong Qiao , Xinglishang He , Shengqiang Tong , Guiyuan Lv , Suhong Chen","doi":"10.1016/S1875-5364(26)61076-X","DOIUrl":"10.1016/S1875-5364(26)61076-X","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition affecting the gastrointestinal tract. The global incidence and prevalence of IBD continue to increase. While multiple clinical treatments exist, conventional therapies frequently present limitations and adverse effects. Natural polysaccharides (PSs) have emerged as a significant focus of research interest due to their therapeutic potential and applications in functional foods and health products. This review synthesizes current understanding of IBD pathophysiology and the mechanisms by which natural PSs counter IBD, including their capacity to restore immune homeostasis and intestinal barrier function, modulate gut microbiota and metabolites, reduce oxidative stress, and address irregularities in autophagy and endoplasmic reticulum stress (ERS). The review examines the structure-activity relationships of PSs demonstrating anti-IBD effects and identifies promising therapeutic products. The discussion encompasses pharmacokinetics, safety evaluations, and clinical applications of these compounds. This comprehensive review establishes a theoretical foundation for developing natural PS-based therapeutic approaches for IBD management.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 45-58"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001711","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

Identification and screening of bioactive peptides against nephropathy derived from Mantidis Oötheca based on complement C3 inhibition 基于补体C3抑制的螳螂Oötheca抗肾病生物活性肽的鉴定和筛选

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines

Pub Date : 2026-01-01 DOI: 10.1016/S1875-5364(26)61080-1

Shanshan Li , Peiling Liu , Tiantian Zhang , Shujun Jiang , Faren Xie , Yanliang Zhang

Insects represent emerging sources of bioactive peptides and functional materials. Mantidis Oötheca (Sang-Piao-Xiao in Chinese, SPX) serves as an insect-derived medicine for treating kidney disease. This study demonstrated that supernatant (SPX) improved kidney function in adriamycin (ADR)-induced nephropathy mice model. Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor (C3aR) pathway. Peptidomic analysis identified 304 peptides from SPX, with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3. Three peptides (PMGFPFDR, FNDPK, AAQFFNR) exhibiting docking scores below −8.0 were synthesized to verify complement inhibition and anti-fibrotic activities. The synthetic peptide AAQFFNR demonstrated complement inhibitory activity, with an inhibitory complement hemolytic 50% (ICH₅₀) value of 24.54 μmol·L⁻¹, and exhibited superior protective effects in ADR-induced HK-2 cells. Surface plasmon resonance (SPR) assay revealed direct interaction between AAQFFNR and complement C3 with K_d value of 16.8 μmol·L⁻¹. The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice. This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.

昆虫是生物活性肽和功能材料的新兴来源。螳螂Oötheca （sangopao - xiao in Chinese， SPX）是一种昆虫衍生的药物，用于治疗肾脏疾病。本研究表明，上清（SPX）可改善阿霉素（ADR）肾病小鼠模型的肾功能。转录组学分析显示，SPX通过靶向MASP1-C3/C3a受体（C3aR）途径抑制补体激活。肽组学分析从SPX中鉴定出304条多肽，其中49条多肽通过预测工具和与补体核心蛋白C3的分子对接进行评估。我们合成了对接评分低于−8.0的三种多肽（PMGFPFDR、FNDPK、AAQFFNR）来验证补体抑制和抗纤维化活性。合成的肽AAQFFNR具有补体抑制活性，其抑制补体溶血50% （ICH50）值为24.54 μmol·L−1，对adr诱导的HK-2细胞具有良好的保护作用。表面等离子体共振（SPR）实验显示AAQFFNR与补体C3直接相互作用，Kd值为16.8 μmol·L−1。随后在adr诱导小鼠中验证了AAQFFNR的肾保护作用。本研究通过计算机和体内验证方法提供了初步证据，证明来自昆虫的补体c3抑制肽具有预防肾病的潜力。

{"title":"Identification and screening of bioactive peptides against nephropathy derived from Mantidis Oötheca based on complement C3 inhibition","authors":"Shanshan Li , Peiling Liu , Tiantian Zhang , Shujun Jiang , Faren Xie , Yanliang Zhang","doi":"10.1016/S1875-5364(26)61080-1","DOIUrl":"10.1016/S1875-5364(26)61080-1","url":null,"abstract":"<div><div>Insects represent emerging sources of bioactive peptides and functional materials. Mantidis Oötheca (Sang-Piao-Xiao in Chinese, SPX) serves as an insect-derived medicine for treating kidney disease. This study demonstrated that supernatant (SPX) improved kidney function in adriamycin (ADR)-induced nephropathy mice model. Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor (C3aR) pathway. Peptidomic analysis identified 304 peptides from SPX, with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3. Three peptides (PMGFPFDR, FNDPK, AAQFFNR) exhibiting docking scores below −8.0 were synthesized to verify complement inhibition and anti-fibrotic activities. The synthetic peptide AAQFFNR demonstrated complement inhibitory activity, with an inhibitory complement hemolytic 50% (ICH<sub>50</sub>) value of 24.54 μmol·L<sup>−1</sup>, and exhibited superior protective effects in ADR-induced HK-2 cells. Surface plasmon resonance (SPR) assay revealed direct interaction between AAQFFNR and complement C3 with <em>K</em><sub>d</sub> value of 16.8 μmol·L<sup>−1</sup>. The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice. This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through <em>in silico</em> and <em>in vivo</em> validation approaches.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"24 1","pages":"Pages 100-111"},"PeriodicalIF":4.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001735","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