Review
Pharmacology & Pharmacy
Yumin Wang, Luyan Gao, Jichao Chen, Qiang Li, Liang Huo, Yanchao Wang, Hongquan Wang, Jichen Du
Summary: Parkinson's disease is a complex neurodegenerative disorder characterized by the loss of dopaminergic neurons in the brain. Oxidative stress has been implicated in its pathogenesis, with the transcription factor Nrf2 playing a key role in activating protective genes against oxidative stress. Recent studies have shown that bioactive compounds can activate Nrf2 and ameliorate neurotoxins associated with PD, suggesting a potential therapeutic target for the treatment of the disease.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Min Liu, Hao Li, Lixia Zhang, Zhipeng Xu, Yuxiang Song, Xiaoyan Wang, Ruitong Chu, Yunming Xiao, Miao Sun, Yulong Ma, Weidong Mi
Summary: The study demonstrated that cottonseed oil has a positive effect on oxidative stress injury induced by ischemic stroke. Treatment with CSO significantly improved neurological deficit, reduced infarction volume, increased antioxidant activity, and activated the Nrf2 signaling pathway in male rats. Additionally, in neuronal cells, CSO treatment increased cell viability, decreased cell apoptosis, and induced Nrf2 nuclear translocation after oxygen and glucose deprivation injury.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Pelin Telkoparan-Akillilar, Emiliano Panieri, Dilek Cevik, Sibel Suzen, Luciano Saso
Summary: Cancer is a fatal disease with increasing mortality worldwide, and dysregulation of the NRF2/KEAP1 signaling pathway promotes tumor cell survival and metastasis in various cancers.
Review
Biochemistry & Molecular Biology
Ignacio Moratilla-Rivera, Marta Sanchez, Jose Antonio Valdes-Gonzalez, Maria Pilar Gomez-Serranillos
Summary: Neurodegenerative diseases (NDs) are common diseases affecting the West due to increased life expectancy. Cells accumulate oxidative damage, triggering neurodegeneration. The transcription factor Nrf2 regulates endogenous antioxidant systems and induces the transcription of genes containing ARE in response to prooxidant conditions. Natural products such as quercetin, curcumin, and terpenoids can positively modulate Nrf2, reducing oxidative damage to the nervous system. This review aims to update knowledge on the potential treatments for NDs by activating the Nrf2 pathway with secondary metabolites of health interest.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hua-Wen Meng, Zhen-Bao Shen, Xian-She Meng, Ze-Qun Yin, Xue-Rui Wang, Ting-Feng Zou, Zhi-Gang Liu, Shuang Zhang, Yuan -Li Chen, Xiao-Xiao Yang, Qing-Shan Li, Ya-Jun Duan
Summary: In this study, a series of novel oxadiazole derivatives were designed and synthesized, among which compound F12 showed the best pharmacological activity. Compound F12 improved the dysfunction in a mouse model of Parkinson's disease by reducing oxidative stress and inflammatory response, and could be a potential treatment for Parkinson's disease.
BIOORGANIC CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Hongri Wang, Xuzheng Chen, Xueqin Miao, Kunbin Lu, Mengjuan He, Xiaomei Wu
Summary: Dendrobium mixture (DMix) improved gestational diabetes mellitus (GDM) by inhibiting oxidative condition, inflammation factors, hyperglycemia, and hyperlipidemia. This research provides a new approach for the prevention and treatment of GDM.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Gaozan Tong, Yiming Chen, Xixi Chen, Junfu Fan, Kunxuan Zhu, ZiJing Hu, Santie Li, Junjie Zhu, Jianjun Feng, Zhaohang Wu, Zhenyu Hu, Bin Zhou, Litai Jin, Hui Chen, Jingling Shen, Weitao Cong, XiaoKun Li
Summary: This study finds that FGF18 can alleviate hepatic IRI through the USP16/KEAP1/Nrf2 signaling pathway, suggesting its potential therapeutic value for hepatic IRI.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Qing Miao, Ruihai Wang, Xiaoxin Sun, Song Du, Limei Liu
Summary: The combination of Puerarin and Tanshinone IIA can alleviate ischemic brain injury by activating the Nrf2/ARE signaling pathway, providing a basis for clinical applications.
PHARMACEUTICAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
ManLi Yuan, Bei Zhao, Huaping Jia, Can Zhang, Xiaowen Zuo
Summary: Sinomenine has been demonstrated to alleviate cardiac hypertrophy by activating the Nrf2/ARE signaling pathway, which leads to reduced cell area, decreased apoptosis rate, and regulation of gene and protein expression levels associated with cardiac hypertrophy. Further research is needed to confirm these findings in human subjects.
Review
Biochemistry & Molecular Biology
Mohammad Yasin Zamanian, Rosario Mireya Romero Parra, Afsaneh Soltani, Malgorzata Kujawska, Yasser Fakri Mustafa, Ghaidaa Raheem, Lateef Al-Awsi, Holya A. Lafta, Niloofar Taheri, Mahsa Heidari, Maryam Golmohammadi, Gholamreza Bazmandegan
Summary: Parkinson's disease (PD) is a prevalent neurodegenerative condition characterized by impaired motor function due to the progressive deterioration of nigrostriatal dopaminergic neurons. Current therapy solutions for PD are ineffective and may have adverse effects. Natural polyphenols, particularly resveratrol (RES), have been found to offer neuroprotection against PD by reducing oxidative stress and upregulating Nrf2. This review examines the molecular mechanisms underlying RES activity and its effects in both in vitro and in vivo PD models, providing scientific evidence for its neuroprotective properties.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Plant Sciences
Qianqian Jiang, Xu Chen, Xue Tian, Jingmei Zhang, Siming Xue, Yanyan Jiang, Tiantian Liu, Xiaoping Wang, Qianbin Sun, Yiqin Hong, Chun Li, Dongqing Guo, Yong Wang, Qiyan Wang
Summary: This study demonstrated that Tanshinone I (Tan I) can protect against Doxorubicin-induced cardiotoxicity (DIC) by reducing oxidative stress and maintaining mitochondrial function. This protective effect is mediated by the activation of the nuclear erythroid factor 2-related factor 2 (Nrf2) pathway.
Review
Pharmacology & Pharmacy
Sepideh Mirzaei, Aliasghar Tabatabaei Mohammadi, Mohammad Hossein Gholami, Farid Hashemi, Ali Zarrabi, Amirhossein Zabolian, Kiavash Hushmandi, Pooyan Makvandi, Marek Samec, Alena Liskova, Peter Kubatka, Noushin Nabavi, Amir Reza Aref, Milad Ashrafizadeh, Haroon Khan, Masoud Najafi
Summary: Nrf2 signaling plays a crucial role in protecting against oxidative damage, but its activation in cancer cells can lead to chemoresistance. Modulating Nrf2 signaling during cisplatin treatment can suppress the development of chemoresistance and alleviate drug toxicity. Activating Nrf2 signaling can help prevent the side effects of cisplatin.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Tsendsuren Tungalag, Kye Won Park, Dong Kwon Yang
Summary: Oxidative stress plays a significant role in the pathogenesis of heart diseases, and butein exhibits potential antioxidant effects in cardiomyocytes, providing protection against oxidative damage and suggesting its therapeutic potential for cardiac diseases.
Review
Biochemistry & Molecular Biology
Manuj Ahuja, Navneet Ammal Kaidery, Debashis Dutta, Otis C. Attucks, Eliot H. Kazakov, Irina Gazaryan, Mitsuyo Matsumoto, Kazuhiko Igarashi, Sudarshana M. Sharma, Bobby Thomas
Summary: Parkinson's disease is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons. Although the exact cause is unclear, oxidative stress, mitochondrial dysfunction, neuroinflammation, and disruption of calcium homeostasis have been proposed as contributing factors. While drugs targeting these pathways have shown promise in preclinical models, a more effective therapeutic approach involving the activation of the Nrf2/Bach1 signaling pathway is being explored. This review discusses the potential benefits of simultaneously inhibiting Bach1 and stabilizing Nrf2 for the treatment of Parkinson's disease.
Article
Plant Sciences
Xiaoju Zhuge, Xiaosheng Jin, Tingting Ji, Rongzhou Li, Liwei Xue, Weilai Yu, Zijiao Quan, Haibin Tong, Fang Xu
Summary: This study aimed to explore the therapeutic effect of geniposide on colitis and uncover the underlying mechanisms of geniposide-mediated antioxidant and anti-inflammatory activities. The study found that geniposide ameliorates colitis by activation of the Nrf2/ARE signaling pathway, preventing colonic redox imbalance and inflammatory damage.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)