Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition

doi:10.1007/s13659-024-00438-y

应用天然产物 ›› 2024, Vol. 14 ›› Issue (2): 5-5.DOI: 10.1007/s13659-024-00438-y

Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition

Jie Cao¹, Lanqin Li², Runge Zhang², Zhou Shu¹, Yaxin Zhang², Weiguang Sun², Yonghui Zhang², Zhengxi Hu²

1. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China;
2. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

收稿日期:2023-12-07 出版日期:2024-04-24 发布日期:2024-05-16
通讯作者: Weiguang Sun,E-mail:weiguang_sun@hust.edu.cn；Yonghui Zhang,E-mail:zhangyh@mails.tjmu.edu.cn；Zhengxi Hu,E-mail:huzhengxi@hust.edu.cn
基金资助:
This research was financially supported by the National Program for Support of Top-notch Young Professionals (No. 0106514050), the National Natural Science Foundation of China (Nos. 82173705, 82273811, and U22A20380), the National Key R&D Program of China (No. 2021YFA0910500), the National Natural Science Foundation for Excellent Young Scholars (No. 81922065); the Science and Technology Major Project of Hubei Province (No. 2021ACA012); the Research and Development Program of Hubei Province (No. 2020BCA058).

Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition

Jie Cao¹, Lanqin Li², Runge Zhang², Zhou Shu¹, Yaxin Zhang², Weiguang Sun², Yonghui Zhang², Zhengxi Hu²

1. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China;
2. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

Received:2023-12-07 Online:2024-04-24 Published:2024-05-16
Contact: Weiguang Sun,E-mail:weiguang_sun@hust.edu.cn；Yonghui Zhang,E-mail:zhangyh@mails.tjmu.edu.cn；Zhengxi Hu,E-mail:huzhengxi@hust.edu.cn
Supported by:
This research was financially supported by the National Program for Support of Top-notch Young Professionals (No. 0106514050), the National Natural Science Foundation of China (Nos. 82173705, 82273811, and U22A20380), the National Key R&D Program of China (No. 2021YFA0910500), the National Natural Science Foundation for Excellent Young Scholars (No. 81922065); the Science and Technology Major Project of Hubei Province (No. 2021ACA012); the Research and Development Program of Hubei Province (No. 2020BCA058).

摘要/Abstract

摘要： Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1β production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.

关键词: Neurodegenerative diseases, Narural products, Libertellenone C, NLRP3 inflammasome

Abstract: Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1β production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.

Key words: Neurodegenerative diseases, Narural products, Libertellenone C, NLRP3 inflammasome

Jie Cao, Lanqin Li, Runge Zhang, Zhou Shu, Yaxin Zhang, Weiguang Sun, Yonghui Zhang, Zhengxi Hu. Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition[J]. 应用天然产物, 2024, 14(2): 5-5.

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Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition

Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition

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