Cells
·
2022
·Vol. 11
·期 18
·2927
·
IF 7.666
Dewei He,Yanting Liu,Jie Li,Hefei Wang,Bojian Ye,Yuan He,Zhe Li,Xiyu Gao,Shoupeng Fu,Dianfeng Liu
Parkinson’s disease (PD) is a neurodegenerative disease in which neuronal apoptosis and associated inflammation are involved in its pathogenesis. However, there is still no specific treatment that can stop PD progression. Isoalantolactone (IAL) plays a role in many inflammation-related diseases. However, its effect and mechanism in PD remain unclear. In this study, results showed that IAL administration ameliorated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD-related pathological impairment and decreased motor activity in mice. Results from in vitro mechanistic studies showed that IAL regulated apoptosis-related proteins by activating the AKT/Nrf2 pathway, thereby suppressing the apoptosis of SN4741 cells induced by N-methyl-4-phenylpyridinium Iodide (MPP+). On the other hand, IAL inhibited LPS-induced release of pro-inflammatory mediators in BV2 cells by activating the AKT/Nrf2/HO-1 pathway and inhibiting the NF-κB pathway. In addition, IAL protected SN4741 from microglial activation-mediated neurotoxicity. Taken together, these results highlight the beneficial role of IAL as a novel therapy and potential PD drug due to its pharmacological profile.Keywords:isoalantolactone;PD;neuro-protection;neuro-inflammation;apoptosis
研究领域:
神经科学
·
药理学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
·
2018
·Vol. 44
·期 2
·295-303
·
IF 1.362
Xu Renjie,Peng Ying,Wang Mengyue,Li Xiaobo
Background Isoalantolactone and alantolactone are the main sesquiterpene lactones in Radix Inulae (dried root of Inula helenium L. or I. racemosa Hook. F.), which is a frequently utilized herbal medicine. They also occur in several plants and have various pharmacologic effects. However, they have been found to have poor oral bioavailability in rats. Objectives To understand the intestinal absorptive characteristics of isoalantolactone and alantolactone as well specific influx and efflux transporters in their absorption. Methods Bidirectional permeabilities of isoalantolactone and alantolactone were investigated across Caco-2 cell monolayers. Transport assays were performed using different concentrations of two lactones and specific inhibitors of ATP-binding cassette transporters and influx transporters. Results The absorption permeability of isoalantolactone and alantolactone was high at the tested concentrations (5, 20 and 80 μmol/l), and the major permeation mechanism of both lactones was found to be passive diffusion with active efflux mediated by multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). Conclusion Our results demonstrated that the absorption permeability of isoalantolactone and alantolactone was good in the Caco-2 cell model. The isoalantolactone and alantolactone absorption elucidated in this study provides useful information for further pharmacokinetics studies. Since low intestinal absorption can now be ruled out as a cause, further studies are needed to explain the low oral bioavailability of the two sesquiterpene lactones.
研究领域:
药理学
·
中药学
·
生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 5.4
Ying Zhang,Changquan Liu,Shengjiang Liu,Yanchun Peng,Jigang Pan,Yingnan Song,Hongjin Chen
Background Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common malignancy globally, with tumor uncontrolled angiogenesis being major causes of therapeutic failure and patient death. Isoalantolactone (IATL), a natural compound, exhibits antioxidant, anti-inflammatory, anti-proliferative, and anti-tumor properties. However, its role in inhibiting tumor angiogenesis in pancreatic cancer and the underlying mechanisms remain unclear. This study aims to investigate the anti-angiogenic effects of IATL in PDAC and elucidate the associated molecular pathways. Methods In vitro experiments were performed using PDAC cell lines (Panc02, PANC-1, and SW 1990) and HUVECs. In vivo studies were conducted using an orthotopic pancreatic cancer model in C57BL/6 mice. Cell viability, wound-healing, tube formation, in vivo imaging system analysis, laser speckle contrast imaging, immunohistochemistry, immunofluorescence, RT-qPCR, ELISA, and Western blot assays were used to evaluate the effects of IATL on tumor growth, angiogenesis, and inflammatory responses. Molecular docking and cellular thermal shift assay were performed to assess the interaction between IATL and NLRP3. Results IATL significantly inhibited the proliferation and migration of Panc02, PANC-1, and SW1990 cells. In the orthotopic pancreatic cancer model, IATL dose-dependently suppressed tumor growth, as evidenced by reduced IVIS fluorescence signals and tumor volume. IATL also markedly inhibited angiogenesis, as shown by reduced HUVECs migration and tube formation, decreased tumor blood perfusion detected by laser speckle imaging, and downregulated CD34 and VEGFA expression both in vivo and in vitro . Network pharmacology, molecular docking, and cellular thermal shift assay identified NLRP3 as a direct target of IATL. Mechanistically, IATL suppressed NLRP3 inflammasome activation, reduced ASC speck formation, inhibited the NLRP3/IL-1β signaling axis, and decreased the expression of inflammatory cytokines, including IL-6, TNF-α, IL-1β, and IL-18. NLRP3 knockdown mimicked the effects of IATL, whereas NLRP3 overexpression partially reversed its anti-tumor, anti-angiogenic, and anti-inflammatory effects, further supporting the target specificity of IATL. Conclusion IATL functions as a novel NLRP3 pathway inhibitor, suppressing angiogenesis through anti-inflammatory mechanisms, thereby effectively inhibiting PDAC progression. These findings suggest that IATL holds potential as a therapeutic agent for pancreatic cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2022
·
IF 5.738
Wu Fengjiao,Shao Rongrong,Zheng Peisen,Zhang Tingting,Qiu Chenyu,Sui Hehuan,Li Shaotang,Jin Libo,Pan Huanle,Jin Xiance,Zou Peng,Cui Ri,Xie Congying
Colon cancer is one of the most common cancer in the world. Doxorubicin (DOX) is a classical anti-tumor drug which widely used in treatment of cancers, however, high toxicity limited its further clinical application. Thus, it is urgent to find new drugs with low toxicity and high efficiency to treat colon cancer. Isoalantolactone (IATL), an isomeric sesquiterpene lactone isolated from the plant of inula helenium, has been reported to have anti-cancer activity against a variety of cancer cells. However, the function of IATL in colon cancer remains unclear. Here, we demonstrated that IATL inhibited colon cancer cell growth by increasing cellular reactive oxygen species (ROS) production. Further study showed that ROS accumulation contributed to DNA damage and JNK signaling pathway activation. In addition, we found that IATL markedly enhanced DOX-induced cell cytotoxicity in colon cancer cells. IATL in combination with DOX significantly increased the ROS production, induced DNA damage and activated JNK signaling pathway. Taken together, our data suggested that combined treatment with IATL and DOX may serve as a potential therapeutics for colon cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Fei Lin,Dehong Zhang,Saisai Liu,Bo Wu,Jinyu Wang,Tingxu Yan,Ying Jia
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation, epithelial barrier dysfunction, and gut microbiota imbalance. This study examined the therapeutic potential of isoalantolactone (IAL), a bioactive sesquiterpene lactone naturally occurring in Inula helenium L., using a dextran sulfate sodium–induced murine colitis model. Treatment with IAL significantly mitigated weight loss, improved the disease activity index, preserved colon length, and alleviated goblet cell depletion. Mechanistically, IAL enhanced intestinal barrier integrity by upregulating tight-junction proteins zonula occludens-1, occludin, and mucin 2 and suppressing proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α, and IL-1β. Moreover, IAL rebalanced CD4 + /CD8 + T cell ratios in the colon, mesenteric lymph nodes, and spleen. Gut microbiota analysis revealed increased diversity, enrichment of beneficial taxa ( Muribaculaceae , Prevotellaceae_UCG-001 ), and a reduced Firmicutes -to- Bacteroidetes ratio. Metabolomic profiling identified 130 differentially abundant metabolites, including increased levels of anti-inflammatory compounds (e.g., hydroferulic acid) and decreased levels of proinflammatory lipids (e.g., linoleoylcarnitine). Correlation analysis demonstrated an association between gut microbiota and faecal metabolites. In addition, faecal microbiota transplantation confirmed that IAL-modulated microbiota ameliorated colitis, with pseudo-germ-free recipients exhibiting improved barrier function and immune homeostasis. These findings highlight the importance of IAL as a novel therapeutic candidate for UC by modulating host–microbiota interactions; however, clinical validation is warranted.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）