IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2022
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IF 3.712
Haihua Zhang,Wuying Lang,Sufen Li,Chao Xu,Xiumin Wang,Yunyu Li,Zhiqiang Zhang,Tonglei Wu,Minshan Feng
Objective Corynoline is an active substance extracted from Corydalis bungeana Turcz and exerts a therapeutic effect in multiple diseases by alleviating inflammatory response. The present study sought to elucidate the role of corynoline in ulcerative colitis (UC).Methods The experimental colitis models were induced in BALB/c mice via receiving a drinking water supplemented with 3.5% (I) dextran sulfate sodium (DSS) ad libitum for 7 days.Results Corynoline administration inhibited body weight loss, colon shortening, disease activity index and colonic pathomorphological changes in DSS-treated mice. Besides, corynoline down-regulated the levels of pro-inflammatory interleukin (IL)-1β, IL-6 and tumor necrosis factor Alpha (TNF-α), as well as decreased myeloperoxidase (MPO) activity in the colon of DSS-treated mice. In addition, severe oxidative stress in the colonic tissues of DSS-treated was mitigated by corynoline treatment. However, these beneficial effects were reversed by a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 intervention. Further evidence confirmed that corynoline promoted Nrf2 nuclear migration and heme oxygenase-1 gene expression in the colonic tissues of UC mice. Besides, corynoline treatment restrained colonic nuclear factor-kappa B (NF-κB) activation as proved by the decrease in phosphorylation and nuclear translocation of NF-κB.Conclusions Corynoline ameliorates DSS-induced mouse colitis, which may provide a promising therapeutic strategy for UC treatment.
研究领域:
药理学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2026
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IF 6
Rou Li,Chaochen Wang,Yong Xie,Weitong Gao,Yanning Guo,Yingjie Yu,Sai Luo,Ye Li,Xinyao Chen,Cong Cao,Wei Ji,Chunyu Li,Baohua Xu,Qing Cai,Jing Li
Bone defect repair remains a major clinical challenge, and effective alternatives to autologous bone grafting are urgently needed due to limitations such as donor site scarcity, immune complications, and high long-term resorption rates. In this study, we developed a near-infrared (NIR)-responsive composite scaffold for the controlled and sustained delivery of corynoline (Cor) and extracellular vesicles (EVs) to enhance bone regeneration. The scaffold was constructed from β-tricalcium phosphate (β-TCP) and coated with bioinspired polydopamine (PDA), which enabled efficient immobilization of Cor and EVs via surface adsorption. The PDA layer endowed the scaffold with photothermal properties, allowing NIR irradiation to trigger and accelerate the release of bioactive factors in a sustained manner for at least 14 days. Cor promoted macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype, thereby reducing excessive reactive oxygen species, while EVs derived from osteogenically induced umbilical cord mesenchymal stem cells enhanced angiogenesis and osteogenesis. The photothermal effect of PDA further synergized with these biofactors to modulate the local microenvironment. Under NIR stimulation, the composite scaffold effectively regulated the immune microenvironment and promoted vascularized bone regeneration. In vivo results demonstrated significantly enhanced new bone formation, accompanied by reduced inflammation, increased endogenous cell recruitment, and accelerated vascularization. Overall, this multifunctional, NIR-responsive scaffold provides a promising strategy for efficient and controlled bone defect repair.
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Ziqi Yan,Qiong Shi,Xumei Liu,Jinhua Li,Vidhula Ahire,Shenqiu Zhang,Jing Zhang,Dun Yang,Thaddeus D. Allen
Plants are a rich source for bioactive compounds. However, plant extracts can harbor a mixture of bioactive molecules that promote divergent phenotypes and potentially have confounding effects in bioassays. Even with further purification and identification, target deconvolution can be challenging. Corynoline and acetylcorynoline, are phytochemicals that were previously isolated through a screen for compounds able to induce mitotic arrest and polyploidy in oncogene expressing retinal pigment epithelial (RPE) cells. Here, we shed light on the mechanism by which these phytochemicals can attack human cancer cells. Mitotic arrest was coincident to the induction of centrosome amplification and declustering, causing multi-polar spindle formation. Corynoline was demonstrated to have true centrosome declustering activity in a model where A549 cells were chemically induced to have more than a regular complement of centrosomes. Corynoline could inhibit the centrosome clustering required for pseudo-bipolar spindle formation in these cells. The activity of AURKB, but not AURKA or polo-like kinase 4, was diminished by corynoline. It only partially inhibited AURKB, so it may be a partial antagonist or corynoline may work upstream on an unknown regulator of AURKB activity or localization. Nonetheless, corynoline and acetylcorynoline inhibited the viability of a variety of human cancer derived cell lines. These phytochemicals could serve as prototypes for a next-generation analog with improved potency, selectivity or in vivo bioavailability. Such an analog could be useful as a non-toxic component of combination therapies where inhibiting the chromosomal passenger protein complex is desired.
研究领域:
药理学
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癌症生物学
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细胞生物学
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植物科学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Mengyang Wang,Wu Luo,Tianxiang Yu,Shiqi Liang,Jinfeng Sun,Yi Zhang,Xue Han,Xiaohong Long,Guang Liang,Gao Li
Heart failure is a fairly common outcome of hypertension. Recent studies have highlighted the key role of the non-hemodynamic activity of angiotensin II (Ang II) in hypertensive heart failure via inducing cardiac inflammation. Drugs that disrupt Ang II-induced cardiac inflammation may have clinical utility in the treatment of hypertensive heart failure. A naturally occurring compound, corynoline, exhibit anti-inflammatory activities in other systems. C57BL/6 mice were injected with Ang II via a micro-osmotic pump for four weeks to develop hypertensive heart failure. The mice were treated with corynoline by gavage for two weeks. RNA-sequencing analysis was performed to explore the potential mechanism of corynoline. We found that corynoline could inhibit inflammation, myocardial fibrosis, and hypertrophy to prevent heart dysfunction, without the alteration of blood pressure. RNA-sequencing analysis indicates that the PPARα pathway is involved Ang II-induced cardiac fibrosis and cardiac remodeling. Corynoline reversed Ang II-induced PPARα inhibition both in vitro and in vivo. We further found that corynoline increases the interaction between PPARα and P65 to inhibit the NF-κB pro-inflammatory pathway in H9c2 cells. Our studies show that corynoline relieves Ang II-induced hypertensive heart failure by increasing the interaction between PPARα and P65 to inhibit the NF-κB pathway.
研究领域:
心脏病学
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药理学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）