Frontiers in Cardiovascular Medicine
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2024
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IF 2.8
Wang Aiping,Ning Jie,Zhao Lu,Xu Renjie
Introduction: The incidence of metabolic disorders during pregnancy is increasing year by year, with diseases including hypertension and hyperlipidemia. Statins are the primary drugs for treating hyperlipidemia or atherosclerosis, yet some patients remain unresponsive to them, and pregnant women are prohibited from taking statins. Curculigoside is the major biologically active natural product present in Curculigo orchioides.Methods: In this study, A high-fat mice model was developed to study the lipid-lowering effect of curculigoside. Using intestinal Caco-2 cell monolayer, the curculigoside transport properties at two temperatures and possible transporters were systemically studied.Results: Curculigoside at concentrations used during the experiments have no toxic effect to Caco-2 cells. The curculigoside transfer from the apical to the basolateral side was strongly influenced by temperature. P-glycoprotein, breast cancer resistance protein, and efflux transporters are crucial components of the human intestinal cell line Caco-2. The curculigoside can significantly affect the contents of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in mice.Discussion: The transport properties and potential mechanism of curculigoside offer valuable insights for the design of development of hypolipidemic drugs like anti-atherosclerotic drugs and also be helpful to the further study of the pharmacological activity of curculigoside.
研究领域:
药理学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
LIFE SCIENCES
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2020
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IF 3.647
Shujun Wang,Wei Liu,Jin Wang,Xia Bai
Curculigoside (CUR) is natural ingredient from Curculigo orchioides Gaertn with multiple biological activities. However, whether CUR protects from ulcerative colitis (UC) and underlying mechanisms are unclear. Herein, mice challenged with dextran sulfate sodium (DSS) were established and administrated with CUR for 7 days. Then histological pathologies and ferroptosis regulators were determined in vivo . The ferroptotic IEC-6 cells were prepared to investigate the underlying mechanism of CUR. Results showed that CUR inhibited the disease activity index, histological damage and cell death in mice with colitis. We also found that ferroptosis was induced in mice with colitis, as evidenced by iron overload, GSH depletion, ROS and MDA production, accompanied by decreased expression of SOD and GPX4. CUR treatment significantly reversed these alterations of ferroptotic features in DSS-induced mice. Furthermore, similar effects of CUR on ferroptosis were observed in IEC-6 cells under the combined treatment of H 2 O 2 and iron chloride hexahydrate. Interestingly, we found that CUR could increase the selenium sensitivity and promote GPX4 transcription level in IEC-6 cells. Knockdown of GPX4 significantly blocked the protective effects of CUR on cell death, GSH and MDA contents as well as LDH activity in ferroptotic IEC-6 cells. Taken together, these findings suggest that CUR protects against ferroptosis in UC by the induction of GPX4, which presents a potential agent for UC treatment.
研究领域:
药理学
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胃肠病学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
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2026
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IF 3.5
Mengying Fan,Yangyang Chen,Pingping Yin,Peng Li
ObjectiveCerebral ischemia-reperfusion injury (CIRI) remains a major challenge in clinical practice, without effective and targeted approaches to address it. Curculigoside has been reported to exert beneficial effects in CIRI, yet the underlying novel mechanisms remain unclear. In this work, we aimed to explore whether Curculigoside exerted its protective role by regulating transient receptor potential melastatin 2 (TRPM2)-mediated microglial polarization.MethodsA well-established middle cerebral artery occlusion (MCAO) model was constructed in Sprague-Dawley rats, with Curculigoside administrated via the caudal vein. In vitro, LPS/IFN-γ-stimulated BV2 microglial cells were used to investigate the effects of Curculigoside on polarization and neuroinflammation. High-throughput mRNA sequencing was used to predict key targets of Curculigoside. TRPM2 overexpression and autophagy inhibition assays were conducted to verify the underlying mechanism.ResultsCurculigoside treatment significantly alleviated neurological deficits, reduced cerebral infarction volume, and decreased brain edema, accompanied by inhibited M1 polarization of microglia and mitigated inflammatory injury during CIRI. Curculigoside reduced pro-inflammatory M1 polarization in LPS/IFN-γ–stimulated BV2 microglia, thereby reducing neuronal apoptosis. RNA-seq functional enrichment analysis identified TRPM2 as a key target, and Curculigoside was found to downregulate TRPM2 expression and regulate the mTOR-mediated autophagy pathway. Notably, the protective effects of Curculigoside on microglial polarization were reversed by TRPM2 overexpression or autophagy inhibition.ConclusionCurculigoside mitigates CIRI by promoting beneficial microglial polarization through the TRPM2/mTOR-autophagy axis, supporting its potential as a therapeutic agent for CIRI.
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DOI
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
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2016
·Vol. 15
·期 10
·2165-2172
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IF 0.543
Jing Wang,Xiao-Li Zhao,Lan Gao
Purpose: To investigate the anti-depressant-like activity of curculigoside from Curculigo orchioides Gaertn and its underlying mechanism(s).Methods: Antidepressant-like activity was determined in mice through forced swimming test (FST), tail suspending test (TST), and open field test (OFT). Mechanism of action was investigated by measuring levels of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) in chronic mild stress (CMS) rats using high-performance liquid chromatography-electron capture detector (HPLC-ECD). Western blotting was used to investigate the effect of curculigoside on the expression of brain-derived neurotrophic factor (BDNF) protein in rats.Results: In FST and TST, treatment of mice with curculigoside (10, 20, 40 mg/kg, p.o.) significantly reduced immobility time, which was, however, unaffected by locomotor activity when assessed in the OFT. The treatment led to significant increases in DA, NE and 5-HT, and up-regulation of BDNF protein expression in the hippocampus of the CMS rats.Conclusion: These results demonstrate that curculigoside exerts significant anti-depressant-like activity on mice, the mechanism of which involves increase in the levels of DA, NE, 5-HT, and up-regulation of BDNF expression. Thus, curculigoside can be considered a potential drug candidate for the treatment of depressive disorders.Keywords: Curculigo orchioides Gaertn, Curculigoside, Antidepressant-like activity, Behavioral studies
研究领域:
药理学
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神经科学
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行为科学
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DOI
高影响因子
ACS Omega
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2024
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IF 3.7
Yiping Weng,Xiuchen Yuan,Shijie Fan,Weihao Duan,Yadong Tan,Ruikai Zhou,Jingbin Wu,Yifei Shen,Zhonghua Zhang,Hua Xu
The treatment of various large bone defects has remained a challenge for orthopedic surgeons for a long time. Recent research indicates that curculigoside (CUR) extracted from the curculigo plant exerts a positive influence on bone formation, contributing to fracture healing. In this study, we employed emulsification/solvent evaporation techniques to successfully fabricate poly(ε-caprolactone) nanoparticles loaded with curculigoside (CUR@PM). Subsequently, using three-dimensional (3D) printing technology, we successfully developed a bioinspired composite scaffold named HA/GEL/SA/CUR@PM (HGSC), chemically cross-linked with calcium chloride, to ensure scaffold stability. Further characterization of the scaffold’s physical and chemical properties revealed uniform pore size, good hydrophilicity, and appropriate mechanical properties while achieving sustained drug release for up to 12 days. In vitro experiments demonstrated the nontoxicity, good biocompatibility, and cell proliferative properties of HGSC. Through alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, cell migration assays, tube formation assays, and detection of angiogenic and osteogenic gene proteins, we confirmed the HGSC composite scaffold’s significant angiogenic and osteoinductive capabilities. Eight weeks postimplantation in rat cranial defects, Micro-computed tomography (CT) and histological observations revealed pronounced angiogenesis and new bone growth in areas treated with the HGSC composite scaffold. These findings underscore the scaffold’s exceptional angiogenic and osteogenic properties, providing a solid theoretical basis for clinical bone repair and demonstrating its potential in promoting vascularization and bone regeneration.
研究领域:
生物医学工程
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组织工程
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骨科
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药学
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材料科学
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DOI
PubMed
高影响因子
MOLECULES
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2012
·Vol. 17
·期 9
·10108-10118
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IF 2.386
Bao-Yuan Hou
This study was designed to evaluate the ameliorating effects of curculigoside fromCurculigo orchioidesGaertn on learning and memory in aged rats. In the present study, the ameliorating effects of curculigoside were determined through animal behaviour studies (including step-down test and Y-maze test), and the possible mechanisms were explored by evaluation of the activity of acetylcholinesterase (AchE) and determination of the expression of BACE1. Oral adminstration of the curculigoside (20, 40 mg/kg/day) for 14 days can significantly improve the latency and number of errors in aged rats based on the behaviour study results. In addition, the activity of AchE can be decreased by treatment of the curculigoside (10, 20, 40 mg/kg/day). Moreover, the expression of BACE1 can be down-regulated in the hippocampus of aged rats treated with curculigoside. The results of our present work have indicated that curculigoside can improve cognitive function in aged animals, possibly by decreasing the activity of AchE in the cerebra and inhibiting the expression of BACE1 in the hippocampus. In conclusion, our results suggested that curculigoside can be possible developed as a new drug for the treatment of Alzheimer’s disease in the future.Keywords:curculigoside;Curculigo orchioides;Alzheimer’s disease;behaviour study;ameliorative effects on learning and memory
研究领域:
药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
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