Gardenia jasminoides Extract GJ-4 Alleviates Memory Deficiency of Vascular Dementia in Rats through PERK-Mediated Endoplasmic Reticulum Stress Pathway

• Published in: The American journal of Chinese medicine (1979) Vol. 51; no. 1; p. 53
• Main Authors: Yuan, Fang-Yu, Ju, Cheng, Zang, Cai-Xia, Liu, Hui, Shang, Mei-Yu, Ning, Jing-Wen, Yang, Yang, Ma, Jing-Wei, Li, Gen, Yu, Yang, Yao, Xin-Sheng, Bao, Xiu-Qi, Zhang, Dan
• Format: Journal Article
• Language: English
• Published: Singapore 01-01-2023
• Subjects: Animals; Apoptosis; Dementia, Vascular - drug therapy; Dementia, Vascular - etiology; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2 - pharmacology; Gardenia; Humans; Neuroblastoma; Rats; GJ-4; Vascular Dementia; Endoplasmic Reticulum Stress; Bilateral Common Carotid Arteries Occlusion; Apoptosis
• ISSN: 1793-6853
• DOI: 10.1142/S0192415X23500040

Endoplasmic reticulum stress (ERS) is involved in the pathological process of vascular dementia (VD). GJ-4 is extracted from
J. Ellis and has been reported to have protective roles in ischemia-related brain damage. However, the role of GJ-4 in ERS has not been elucidated. We established a VD rat model through bilateral common carotid arteries occlusion (2-VO). The rats were intragastrically administrated with GJ-4 (10, 25, and 50[Formula: see text]mg/kg) and nimodipine (10[Formula: see text]mg/kg). Data from a Morris water maze test showed that GJ-4 could significantly alleviate learning and memory deficits in VD rats. Nissl and cleaved caspase-3 staining revealed that GJ-4 can inhibit apoptosis and thus exert a protective role in the brain of 2-VO rats. Western blot results suggested that GJ-4 significantly reduced ERS-related protein expression and inhibited apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. For
studies, the oxygen-glucose deprivation (OGD) SH-SY5Y model was employed. Western blot and Hoechst 33342/PI double staining were utilized to explore the effects of crocetin, the main active metabolite of GJ-4. Like GJ-4
, crocetin
also decreased ERS-related protein expression and inhibited the activation of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. Thus, crocetin exerted similar protective roles on OGD challenged SH-SY5Y cells
. In summary, GJ-4 and crocetin reduce the ERS in the brain of VD rats and SY5Y cells subjected to OGD and inhibit neuronal apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP pathway, suggesting that GJ-4 may be useful for the treatment of VD.