Sensitization of GSH synthesis by curcumin curtails acrolein-induced alveolar epithelial apoptosis via Keap1 cysteine conjugation: A randomized controlled trial and experimental animal model of pneumonitis

姜黄素对 GSH 合成的敏化可通过 Keap1 半胱氨酸结合抑制丙烯醛诱导的肺泡上皮细胞凋亡:一项随机对照试验和肺炎实验动物模型

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作者:Eun Hee Jo, Ji Eun Moon, Moon Han Chang, Ye Jin Lim, Jung Hyun Park, Suk Hee Lee, Young Rae Cho, Art E Cho, Seung Pil Pack, Hyeon-Wee Kim, Liana Crowley, Brandy Le, Aykin-Burns Nukhet, Yinfeng Chen, Yihang Zhong, Jiangchao Zhao, Ying Li, Hanvit Cha, Jeong Hoon Pan, Jae Kyeom Kim, Jin Hyup Lee

Conclusions

Our study collectively suggests that curcumin could provide an effective preventive measure against air pollutant-enhanced pneumonitis and thus COPD.

Methods

A total of 40 subjects was recruited from Chengdu, China which is among the top three cities in terms of respiratory mortality related to air pollution. The participants were randomly provided either placebo or curcumin supplements for 2 weeks and blood samples were collected at the baseline and at the end of the intervention to monitor systemic markers. In our follow up mechanistic study, C57BL/6 mice (n = 40) were randomly allocated into 4 groups: Control group (saline + no acrolein), Curcumin only group (curcumin + no acrolein), Acrolein only group (saline + acrolein), and Acrolein + Curcumin group (curcumin + acrolein). Curcumin was orally administered at 100 mg/kg body weight once a day for 10 days, and then the mice were subjected to nasal instillation of acrolein (5 mg/kg body weight). Twelve hours after single acrolein exposure, all mice were euthanized.

Results

Curcumin supplementation, with no noticeable adverse responses, reduced circulating pro-inflammatory cytokines in association with clinical pneumonitis as positive predictive while improving those of anti-inflammatory cytokines. In the pre-clinical study, curcumin reduced pneumonitis manifestations by suppression of intrinsic and extrinsic apoptotic signaling, which is attributed to enhanced redox sensing of Nrf2 and thus sensitized synthesis and restoration of GSH, at least in part, through curcumin-Keap1 conjugation. Conclusions: Our study collectively suggests that curcumin could provide an effective preventive measure against air pollutant-enhanced pneumonitis and thus COPD.

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