Biomedical Reports
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2025
·Vol. 22
·期 4
·1-9
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IF 1.9
Juan Lang,Zhongkui Xiong
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Currently, no radical treatment is available for this disease. Harpagoside is a proposed neuroprotective iridoid active ingredient that can be derived from Scrophulariae buergeriana, Scrophularia striata and Harpagophytum procumbens. The present study aimed to investigate the effects of harpagoside on mitochondrial functions in rotenone‑induced cell models of Parkinson's disease (PD). Neuro‑2A (N2A) cells were treated with rotenone to establish in vitro cell models of PD. Cell viability and survival were measured using a Cell Counting Kit‑8 assay. Biochemical assays with spectrophotometry were used to measure complex I activity, mitochondrial swelling and caspase 3 activity. The cell survival rate was first found to be significantly decreased by rotenone (20 nmol/l) treatment. However, intervention with harpagoside (10 µmol/l) was found to increase the cell survival rate of rotenone‑induced N2A cell models differentiated with 1 mmol/l of dibutyryl‑cAMP. At ≥0.1 µmol/l concentration, harpagoside significantly alleviated rotenone‑induced mitochondrial swelling, whereas at 1 µmol/l it significantly counteracted the inhibitory effects of rotenone on complex I activity. At 10 µmol/l harpagoside significantly inhibited rotenone‑induced caspase 3 activation. These results suggest that harpagoside has the potential to protect mitochondrial functions against rotenone‑induced injury in N2A cell models of PD.
研究领域:
神经科学
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药理学
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细胞生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Dongchen Xu,Chenyu ShenTu,Chuhong Zong,Weiliang Fu,Jiawei Ling,Ping Shao,Xuesong Liu,Yong Chen,Tengfei Xu
Ethnopharmacological relevance Salvia miltiorrhiza Bunge, a traditional Chinese medicine, has been utilized in the treatment of Parkinson's disease (PD) for thousands of years, as evidenced by its inclusion in ancient formulas such as YangXue XingNao Tang and XingGan ZhenFeng Tang . However, the underlying mechanisms of its therapeutic effects on PD remain unclear. Aim of the study This study aims to evaluate the therapeutic effects of Salvia miltiorrhiza Bunge on a rotenone-induced PD rat model and elucidate its mechanism of action. Methods To explore the efficacy of Salvia miltiorrhiza Bunge extract (SME) in PD, we employed both in vitro and in vivo models using rotenone-induced PC12 cells and rats. Therapeutic effects were assessed through cell viability assays, behavioral tests, and immunohistochemistry. Proteomic analysis and molecular docking experiments were conducted to identify the pathways involved in SME's effects. Immunofluorescence and Western blotting were used to validate the role of mitophagy, while transmission electron microscopy (TEM) provided direct evidence of mitophagy induction by SME. Results Salvia miltiorrhiza Bunge significantly improved motor dysfunction and mitigated dopaminergic neuron degeneration in the substantia nigra of rotenone-exposed rats. Proteomic analysis revealed significant activation of the PINK1/Parkin pathway following SME treatment. Furthermore, molecular experiments confirmed that SME induces mitophagy, which protects PC12 cells from rotenone-induced damage. Conclusion This study demonstrates the therapeutic efficacy of Salvia miltiorrhiza Bunge in mitigating PD-related pathologies. Through proteomic and molecular analyses, we identified SME's ability to activate the PINK1/Parkin pathway and promote mitophagy, offering new insights into its mechanism of action in PD.
研究领域:
药理学
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神经科学
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蛋白质组学
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PubMed
高影响因子
CONNECTIVE TISSUE RESEARCH
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2026
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IF 1.9
Chongjie Zhu,Chi Zhang,Mingjuan Li,Feng Li,Liu Liu,Chenxinzi Lin,Zubing Li,Zhi Li,Qilong Wan
Purpose The migration and fusion of osteoclast precursors (OCPs) are critical steps in osteoclastogenesis and require substantial energy. Although oxidative phosphorylation (OXPHOS) is generally considered the major pathway supplying energy for these processes, it remains unclear how inhibiting OXPHOS affects the migration of OCPs.Materials and Methods To investigate the metabolic regulation of osteoclast migration, we used a recognized OXPHOS inhibitor rotenone to suppress the key energy-producing pathway in OCPs. We combined this intervention with bioinformatics approaches and machine learning algorithms to screen and identify genes associated with osteoclast dysfunction in patients with osteoporosis. The migratory capacity of OCPs was precisely quantified using optical tweezers.Results We found that rotenone inhibited osteoclastogenesis and markedly impaired the migratory capacity of OCPs. Although the level of OXPHOS in OCPs decreased, intracellular ATP content paradoxically increased, suggesting that the impairment of migratory capacity is unlikely to be driven by an overall energy shortage. Through machine learning algorithms, we identified genes associated with abnormal osteoclast function in patients with osteoporosis and discovered their critical regulatory roles in processes such as cell migration, adhesion, and OXPHOS. Rotenone significantly suppressed the expression of these genes in OCPs, suggesting a direct mechanism for the impaired migration.Conclusions In summary, our study reveals a novel mechanism for rotenone-induced inhibition of osteoclastogenesis, which is achieved by impairing the migration of OCPs in a manner uncoupled from overall energy status.
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高影响因子
Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology
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2018
·Vol. 301
·期 6
·1115-1125
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IF 1.373
Hui Wang,Xiaoguang Dong,Zengxun Liu,Shaowei Zhu,Haili Liu,Wenchuang Fan,Yanlai Hu,Tao Hu,Yonghui Yu,Yizhao Li,Tianwei Liu,Chengjia Xie,Qing Gao,Guibao Li,Jing Zhang,Zhaoxi Ding,Jinhao Sun
Rotenone is a common pesticide and has been reported as one of the risk factors for Parkinson disease. Rotenone can cause neuronal death or apoptosis through inducing oxidative injury and inhibiting mitochondrial function. As a natural polyphenolic compound, resveratrol possesses the antioxidant capacity and neuroprotective effect. However, the mechanism underlying the neuroprotective effect of resveratrol against rotenone-induced neurotoxicity remains elusive. Here, we treated PC12 cells with rotenone to induce neurotoxicity, and the neurotoxic cells were subjected to resveratrol treatment. The CCK8 and LDH activity assays demonstrated that resveratrol could suppress neurotoxicity induced by rotenone ( P < 0.01). The DCFH-DA assay indicated that resveratrol reduced the production of reactive oxygen species (ROS). JC-1 and Hoechst 33342/PI staining revealed that resveratrol attenuated mitochondrial dysfunction and cell apoptosis. Moreover, resveratrol reversed rotenone-induced decrease in SIRT1 expression and Akt1 phosphorylation ( P < 0.05). Furthermore, when the SIRT1 and Akt1 activity was inhibited by niacinamide and LY294002, respectively, the neuroprotective effect of resveratrol was remarkably attenuated, which implied that SIRT1 and Akt1 could mediate this process and may be potential molecular targets for intervening rotenone-induced neurotoxicity. In summary, our study demonstrated that resveratrol reduced rotenone-induced oxidative damage, which was partly mediated through activation of the SIRT1/Akt1 signaling pathway. Our study launched a promising avenue for the potential application of resveratrol as a neuroprotective therapeutic agent in Parkinson disease. Anat Rec, 301:1115–1125, 2018. © 2018 Wiley Periodicals, Inc.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
Nanomaterials
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2025
·Vol. 15
·期 14
·1056
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IF 4.3
Yunfei Zhang,Xuesheng Lin,Yunlong Qian,Mingda Qin,Shujing Zhang,Lanying Wang,Yanping Luo
Self-emulsifying solid nanodispersion technology is emerging as an attractive strategy to prepare new eco-friendly and efficient nano-formulations due to its simple, energy efficient and easy scale-up process. However, it is still unknown whether this technology can be employed to cope with the drawbacks of botanical insecticides including poor water solubility, rapid photodegradation and limited targeting efficiency. In this study, rotenone (Rot) was selected as a model of botanical insecticides, and its solid nanodispersion (Rot–SND) was prepared by a self-emulsifying method combined with parameter optimization. Our target nano-formulation, consisting of 5% Rot, 20% surfactant complexes of 8% Ethylan 992 and 12% EL–80, and 75% lactose, exhibited excellent storage stability and significantly improved the pseudo-solubility of Rot by at least 250 times. The average particle size and polydispersity index (PDI) of Rot–SND were determined to be 101.19 nm and 0.21, respectively. Rot–SND displayed smaller contact angles and greater retention on both cucumber and cabbage leaves than those of a commercial emulsifiable concentrates (ECs). Rot–SND was also more resistant to photodegradation, with a degradation rate reduced by 27.01% as compared with the ECs. In addition, the toxicity of Rot–SND towardsAphis gossypiiwas 3.01 times that of the ECs, with a median lethal concentration (LC50) of 1.45 µg a.i./mL. Under the field conditions, Rot–SND showed a prolonged duration forA. gossypiicontrol, with a significantly higher control efficacy (88.10%) on the 10th day than that of the ECs (77.02%). Moreover, a 2.34-fold decline in the toxicity towards nontarget mosquito larvae was observed for Rot–SND as compared with the EC. Overall, for the first time, our results indicate the role of Rot–SND as an eco-friendly and efficient way to improve the solubility, foliar affinity, photostability, bioactivity and eco-safety of Rot. This research also provided a feasible strategy to prepare more eco-friendly botanical pesticide formulations of high efficiency.
研究领域:
植物农药
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纳米制剂
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农业化学
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环境安全
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PubMed
高影响因子
Experimental and Therapeutic Medicine
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2014
·Vol. 9
·期 2
·553-558
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IF 0.941
Zhong‑Kui Xiong,Juan Lang,Gang Xu,Hai‑Yu Li,Yun Zhang,Lei Wang,Yao Su,Ai‑Jing Sun
Systemic rotenone models of Parkinson's disease (PD) are highly reproducible and may provide evidence on the pathogenesis of PD. In the present study, male Sprague‑Dawley rats (1‑year‑old) were subcutaneously administered with rotenone (1.5 mg/kg/day) for six days and observed for the following three weeks. Compared with the control rats, a significant decrease was observed in the body weight and a marked increase was observed in the areas under the behavioral scoring curves in the rotenone‑treated rats. Immunohistochemical staining revealed that the abundance of nigral tyrosine hydroxylase (TH)‑positive neurons was markedly reduced following rotenone treatment. ELISA and neurochemical assays demonstrated a significant increase in the levels of nitric oxide (NO) and NO synthase, whereas a marked decrease was observed in the thiol levels in the brains of the rotenone‑treated rats. Thus, subacute rotenone treatment was found to induce behavioral deficits and the loss of nigral TH‑positive neurons which may be associated with the excessive levels of NO in the rat brains.
研究领域:
神经科学
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药理学
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病理学
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PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2023
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IF 7.4
Peng-Zhou Hang,Feng-Qin Ge,Man-Ru Zhang,Qi-Hang Li,Hua-Qing Yu,Yu-Chen Song,Dan-Dan Guo,Jing Zhao,Hua Zhu
The relationship between mitochondrial dysfunction and cardiovascular disease pathogenesis is well recognized. 7,8-Dihydroxyflavone (7,8-DHF), a mimetic of brain-derived neurotrophic factor, inhibits mitochondrial impairments and improves cardiac function. However, the regulatory role of 7,8-DHF in the mitochondrial function of cardiomyocytes is not fully understood. To investigate the potential mito-protective effects of 7,8-DHF in cardiomyocytes, we treated H9c2 or HL-1 cells with the mitochondrial respiratory complex I inhibitor rotenone (Rot) as an in vitro model of mitochondrial dysfunction. We found that 7,8-DHF effectively eliminated various concentrations of Rot-induced cell death and reduced lactate dehydrogenase release. 7,8-DHF significantly improved mitochondrial membrane potential and inhibited mitochondrial reactive oxygen species . Moreover, 7,8-DHF decreased routine and leak respiration, restored protein levels of mitochondrial complex I-IV, and increased ATP production in Rot-treated H9c2 cells. The protective role of 7,8-DHF in Rot-induced damage was validated in HL-1 cells. Nuclear phosphorylation protein expression of signal transducer and activator of transcription 3 (STAT3) was significantly increased by 7,8-DHF. The present study suggests that 7,8-DHF rescues Rot-induced cytotoxicity by inhibiting mitochondrial dysfunction and promoting nuclear translocation of p-STAT3 in cardiomyocytes, thus nominating 7,8-DHF as a new pharmacological candidate agent against mitochondrial dysfunction in cardiac diseases.
研究领域:
心血管疾病
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分子生物学
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细胞生物学
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药理学
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PubMed
高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-11
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IF 3.8
Xu Li,Wu Zhenghua,Li Jingkun,Xu Yihao,Zhou Feng,Zhang Fulong,Li Dongzhi,Zhou Lin,Liu Runqiang
As an important pest on winter wheat, Rhopalosiphum padi (L.) causes damage to the wheat yield by sucking plant nutrients, transmitting plant viruses and producing mildew. R. padi has been reported to develop resistance to pyrethroids and neonicotinoids. To explore potential alternative approaches for R. padi control, the activity of 10 botanical insecticides was evaluated. Results suggested that the toxicity of rotenone and pyrethrins to R. padi were the highest and near to the commonly used chemical insecticides. When exposed to the low-lethal concentrations (LC 10 , LC 30 ) of rotenone or pyrethrins for 24 h, the lifespan and fecundity of adults in F0 generation decreased significantly compared to control. The negative effect could also be observed in the F1 generation, including the decreased average offspring, longevity of adult, and prolonged nymph period. The population parameters in F1 generation of R. padi were also inhibited by exposing to the low-lethal concentrations of rotenone or pyrethrins, including the decreased net reproductive rate, intrinsic rate of natural increase, finite rate of population increase, and gross reproduction rate. Co-toxocity factor results showed that mixtures of rotenone and thiamethoxam, pyrethrins and thiamethoxam showed synergistic effect. Our work suggested that rotenone and pyrethrins showed negative effect on the population growth under low-lethal concentrations. They are suitable for R. padi control as foliar spraying without causing population resurgence.
研究领域:
植物保护
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昆虫学
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PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2025
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IF 4.3
Li Xinying,Li Weiran,Xie Xinying,Fang Ting,Yang Jingwen,Shen Yue,Wang Yicheng,Wang Hongyan,Tao Liqing,Zhang Heng
Rotenone, a plant-derived natural insecticide, is widely used to induce Parkinson’s disease (PD) models. However, the mechanisms of rotenone-induced cell death remain unclear. Here, we found that rotenone (0.01, 0.1, or 1 μmol/L) suppressed SH-SY5Y dopamine neuron viability and led to PD-like pathological changes, such as reduced tyrosine hydroxylase (TH) but increased α-synuclein. Rotenone increased the levels of intracellular reactive oxygen species (ROS) and mitochondrial ROS, as well as the levels of the antioxidants nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), ultimately resulting in oxidative stress. Moreover, rotenone significantly downregulated the expression of GPX4 and xCT but upregulated the expression of COX2 and NCOA4, which are markers of ferroptosis. Furthermore, rotenone decreased phosphorylated mTOR level but increased Beclin-1, ATG5, LC3 and p62 expression, suggesting that rotenone enhances autophagy and reduces autophagy flux. Additionally, rotenone reduced Bcl-2 levels and the mitochondrial membrane potential (MMP) while promoting BAX and Caspase-3 expression, thus initiating cell apoptosis. N-acetylcysteine (NAC), a ROS scavenger, and ferrostatin-1 (Fer-1) and deferoxamine (DFO), two ferroptosis inhibitors, significantly eliminated rotenone-induced autophagy and apoptosis. Moreover, ML385, a specific inhibitor of Nrf2, suppressed rotenone-induced ferroptosis. Our results demonstrated that ROS might mediate rotenone-induced PD-like pathological changes by regulating iron death, autophagy, and apoptosis. Inhibiting ferroptosis blocked the rotenone-induced increase in autophagy and apoptosis. Thus, the ability of ROS to regulate rotenone-induced death through autophagy and apoptosis is dependent on ferroptosis. The findings require validation in multiple neuronal cell lines and in vivo.
研究领域:
神经科学
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药理学
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细胞生物学
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帕金森病研究
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PubMed
高影响因子
Frontiers in Neuroscience
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2026
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IF 4
Liping Sun,Juan Lang,Zhongkui Xiong
IntroductionParkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is one of the leading causes of neurological disability. Although there are currently no cures or treatments for this disease, many patients with PD may therapeutically benefit from preventing or mitigating mitochondrial dysfunction. This study aimed to investigate the protective effects of paederoside against rotenone-induced neuronal damage in Neuro-2A (N2A) cell models of PD.MethodsFirst, the cytotoxic effects of rotenone on N2A cells were assessed using the cell counting kit-8 assay to establish a cell model of PD. Second, the effects of paederoside on mitochondrial complex I activity, mitochondrial swelling, and caspase-3 activity in the rotenone-induced cellular model were investigated. Finally, the impact of paederoside on tyrosine hydroxylase-positive cells in a rotenone-induced co-culture of N2A cells and BV-2 cells (N2A/BV-2) was studied.ResultsN2A cells were significantly damaged by rotenone in a time- and concentration-dependent manner; a 48 h rotenone treatment at 20 nM was used to create a cell model of PD. Pretreatment with 1 μM paederoside notably increased mitochondrial complex I activity in N2A cells with rotenone-induced impairment, leading to 42.85% increase. Additionally, pretreatment with 0.1, 1, and 10 μM paederoside considerably alleviated rotenone-induced mitochondrial swelling as indicated by the optical density (OD) (10 min)/OD(0 min) ratio, which increased by 1.21-, 1.33-, and 1.37-fold, respectively. Notably, pretreatment with 10 μM paederoside significantly inhibited caspase-3 activation triggered by rotenone in this cellular setting, resulting in a 39.93% decrease in enzyme activity. Moreover, pretreatment with 10 μM of paederoside markedly enhanced the number of TH-positive cells in a co-culture system consisting of N2A/BV-2 cells induced by rotenone, with increases of 82.79%.ConclusionPretreatment with paederoside may protect against mitochondrial dysfunction in cell models of PD induced by rotenone.
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高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Buyong Wang,Rongrong Wen,Xuenan Mao,Jie Chen,Xin Hao
Bursaphelenchus xylophilus is a pathogenic nematode responsible for pine wilt disease, which can cause the demise of pine trees and discoloration of trunks. As rotenone is an important botanical pesticide, its impact on B. xylophilus was investigated through RNA-seq to understand the response mechanism of nematode. The bioassay results yielded the 12-h LC 30 (1.35 mg L −1 ) and LC 50 (2.60 mg L −1 ) values for rotenone. Differential gene expression analysis identified 172 and 614 differentially expressed genes (DEGs) in B. xylophilus exposed to two different concentrations of rotenone (1.35 and 2.60 mg L −1 ). To validate these findings, the expression patterns of 10 DEGs were confirmed through RT-qPCR. Additionally, all DEGs were categorized into eight gene expression profiles using STEM. Notably, the gene ontology (GO) processes of "single-organism process," "metabolic process," and "catalytic activity" were prominently enriched in rotenone-treated samples, suggesting a role for metabolic and catalytic pathways in the nematode's response to rotenone stress. KEGG pathways related to "carbon metabolism," "drug metabolism-cytochrome P450," and "metabolism of xenobiotics by cytochrome P450" were similarly enriched, indicating potential mechanisms for detoxification resistance and oxidative stress resistance. The analysis pointed to the pivotal roles of detoxification- and oxidoreduction-related genes, as well as signal transduction-related genes, in enabling B. xylophilus to adapt to rotenone exposure. These insights could markedly enhance our understanding of nematode resistance mechanisms and potentially inform the development of more effective rotenone-based strategies for controlling B. xylophilus .
研究领域:
植物保护
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分子生物学
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农药科学
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PubMed
高影响因子
Heliyon
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2023
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IF 4
Lanxin Li,Yang Zhang,Zhengqian Chen,Ruyong Yao,Zhongqiu Xu,Can Xu,Fujie He,Haitao Pei,Cui Hao
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, which is distinguished by the loss of dopaminergic (DA) neurons in the substantia nigra and the formation of intraneuronal. Numerous studies showed that the damage and dysfunction of mitochondria may play key roles in DA neuronal loss. Thus, it is necessary to seek therapeutic measures for PD targeting mitochondrial function and biogenesis. In this study, through screening the purchased compound library, we found that marine derived vidarabine had significant neuroprotective effects against rotenone (ROT) induced SH-SY5Y cell injury. Further studies indicated that vidarabine pretreatment significantly protected ROT-treated SH-SY5Y cells from toxicity by preserving mitochondrial morphology, improving mitochondrial function, and reducing cell apoptosis. Vidarabine also reduced the oxidative stress and increased the expression levels of PGC-1α, NRF1, and TFAM proteins, which was accompanied by the increased mitochondrial biogenesis. However, the neuroprotective effects of vidarabine were counteracted in the presence of SIRT1-specific inhibitor Ex-527. Besides, vidarabine treatment attenuated the weight loss, alleviated the motor deficits and inhibited the neuronal injury in the MPTP induced mouse model. Thus, vidarabine may exert neuroprotective effects via a mechanism involving specific connections between the SIRT1-dependent mitochondrial biogenesis and its antioxidant capacity, suggesting that vidarabine has potential to be developed into a novel therapeutic agent for PD.
研究领域:
神经科学
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药理学
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细胞生物学
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神经退行性疾病
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DOI
PubMed
高影响因子
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