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Abstract: Ethnopharmacological relevance: Carthamus red isolated from safflower (Carthamus tinctorius L., a Chinese traditional medicine) is evaluated for antioxidant and hepatoprotective activity. Materials and methods: Carthamus red was isolated from a Na2CO3 extract of safflower and its analysis was carried out by HPLC/MS. Acute toxicity study was determined and the antioxidant activity was investigated using various established in vitro systems. An in vivo study against CCl4-induced liver injury was also conducted and compared with that of silymarin, a known hepatoprotective drug. Results: Carthamus red did not show any toxicity and mortality up to 2000mg/kg dose, and it showed strong antioxidant ability in vitro. In the in vivo study, carthamus red treatment lowered the serum levels of ALT, AST, ALP and total protein in liver damage rat models. Meanwhile, Nrf2, GSTα and NQO1 expressions were up-regulated at the protein level by carthamus red intervention. Additionally, the activities of antioxidant enzymes and level of GSH were elevated by carthamus red intervention, while the content of TBARS, which is an oxidative stress marker, was lessened. HE stain analysis showed that the condition of liver damage was mitigated. Conclusion: This study demonstrates that carthamus red may serve as a candidate with strong a hepatoprotective effect and antioxidant activity in liver damage. [Copyright &y& Elsevier]

The unfolded protein response (UPR) is a cellular stress response pathway activated when the endoplasmic reticulum, a crucial organelle for protein folding and modification, encounters an accumulation of unfolded or misfolded proteins. The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity, reducing protein biosynthesis, and promoting protein degradation. It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress. Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system. Here, we provide an overview of recent findings that underscore the UPR's involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions, and highlight the critical role of the UPR in brain development, memory storage, retinal cone development, myelination, and maintenance of myelin thickness., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Endoplasmic reticulum-associated degradation (ERAD) is a principal quality-control mechanism responsible for targeting misfolded ER proteins for cytosolic degradation. Evidence suggests that impairment of ERAD contributes to neuron dysfunction and death in neurodegenerative diseases, many of which are characterized by accumulation and aggregation of misfolded proteins. However, the physiological role of ERAD in neurons remains unclear. The Sel1L-Hrd1 complex consisting of the E3 ubiquitin ligase Hrd1 and its adaptor protein Sel1L is the best-characterized ERAD machinery. Herein, we showed that Sel1L deficiency specifically in neurons of adult mice impaired the ERAD activity of the Sel1L-Hrd1 complex and led to disruption of ER homeostasis, ER stress and activation of the unfold protein response (UPR). Adult mice with Sel1L deficiency in neurons exhibited weight loss and severe motor dysfunction, and rapidly succumbed to death. Interestingly, Sel1L deficiency in neurons caused global brain atrophy, particularly cerebellar and hippocampal atrophy, in adult mice. Moreover, we found that cerebellar and hippocampal atrophy in these mice resulted from degeneration of Purkinje neurons and hippocampal neurons, respectively. These findings indicate that ERAD is required for maintaining ER homeostasis and the viability and function of neurons in adults under physiological conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Liu, Cvetanovic and Lin.)