2. Academic Validation
  3. Hydroxysafflor yellow a confers neuroprotection against acute traumatic brain injury by modulating neuronal autophagy to inhibit NLRP3 inflammasomes

Hydroxysafflor yellow a confers neuroprotection against acute traumatic brain injury by modulating neuronal autophagy to inhibit NLRP3 inflammasomes

  • J Ethnopharmacol. 2023 Feb 24;116268. doi: 10.1016/j.jep.2023.116268.
Zelin Lai 1,  Cong Li 1,  Huihan Ma 2,  Shiting Hua 1,  Zhizheng Liu 1,  Sixian Huang 1,  Kunlin Liu 1,  Jinghuan Li 1,  Zhiming Feng 1,  Yingqian Cai 1,  Yuxi Zou 1,  Yanping Tang 1,  Xiaodan Jiang 3
Affiliations

Affiliations

  • 1 Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
  • 2 Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
  • 3 Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China. Electronic address: [email protected].
PMID: 36842723 DOI: 10.1016/j.jep.2023.116268
Abstract

Ethnopharmacological relevance: Hydroxysafflor yellow A (HSYA) is the principal bioactive compound isolated from the plant Carthamus tinctorius L. and has been reported to exert neuroprotective effects against various neurological diseases, including traumatic brain injury (TBI). However, the specific molecular and cellular mechanisms underlying HSYA-mediated neuroprotection against TBI are unclear.

Aim of the study: This study explored the effects of HSYA on Autophagy and the NLRP3 inflammasome in mice with TBI and the related mechanisms.

Materials and methods: Mice were subjected to TBI and treated with or without HSYA. Neurological severity scoring, LDH assays and Apoptosis detection were first performed to assess the effects of HSYA in mice with TBI. RNA-seq was then conducted to explore the mechanisms that contributed to HSYA-mediated neuroprotection. ELISA, western blotting, and immunofluorescence were performed to further investigate the mechanisms of neuroinflammation and Autophagy. Moreover, 3-methyladenine (3-MA), an Autophagy Inhibitor, was applied to determine the connection between Autophagy and the NLRP3 inflammasome.

Results: HSYA significantly decreased the neurological severity score, serum LDH levels and Apoptosis in mice with TBI. A total of 921 differentially expressed genes were identified in the cortices of HSYA-treated mice with TBI and were significantly enriched in the inflammatory response and Autophagy. Furthermore, HSYA treatment markedly reduced inflammatory cytokine levels and astrocyte activation. Importantly, HSYA suppressed neuronal NLRP3 inflammasome activation, as indicated by decreased levels of NLRP3, ASC and cleaved Caspase-1 and a reduced NLRP3+ neuron number. It increased Autophagy and ameliorated autophagic flux dysfunction, as evidenced by increased LC3 II/LC3 I levels and decreased P62 levels. The effects of HSYA on the NLRP3 inflammasome were abolished by 3-MA. Mechanistically, HSYA may enhance Autophagy through AMPK/mTOR signalling.

Conclusion: HSYA enhanced neuronal Autophagy by triggering the AMPK/mTOR signalling pathway, leading to inhibition of the NLRP3 inflammasome to improve neurological recovery after TBI.

Keywords

AMPK signalling; Hydroxysafflor yellow A; NLRP3 inflammasome; Neuronal autophagy; Traumatic brain injury.

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