College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University, Republic of Korea.
Biomed Pharmacother. 2018 Nov;107:867-877. doi: 10.1016/j.biopha.2018.08.082. Epub 2018 Aug 22.
The root of Platycodon grandiflorus (Jacq.) A. DC. (P. grandiflorus), Platycodonis Radix, has been commonly applied to prevent and treat human diseases including bronchitis, asthma and excessive phlegm. Platycodin D (PD), one of the most important therapeutic components of P. grandiflorus, has been reported to possess protective effect against alcohol and carbon tetrachloride induced hepatotoxicity. In this study, we examined the protective efficacy of PD on acetaminophen (APAP)-induced liver injury and possible underlying mechanisms in C57BL/6J mice. Administration of PD prior to APAP intoxication significantly ameliorated the increase in serum transferases, interleukin 1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), and hepatic malondialdehyde (MDA) and the depletion of glutathione (GSH) in mice. PD pretreatment decreased the expression of heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) in presence of APAP. Moreover, PD treatment noticeably reduced APAP-induced hepatocyte necrosis and apoptosis evidenced by evaluating physiological and histological hepatocyte changes in mice. Finally, PD pretreatment significantly diminished c-Jun NH-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38 phosphorylation induced by APAP. Collectively, PD pretreatment effectively protects hepatocytes against APAP-induced hepatotoxicity in mice through ameliorating oxidative stress, inflammatory response, and hepatocyte apoptosis.
桔梗（Platycodon grandiflorus）（Jacq.）A. DC.（P. grandiflorus）的根，即桔梗，已被广泛用于预防和治疗人类疾病，包括支气管炎、哮喘和痰多。桔梗皂苷 D（PD）是桔梗中最重要的治疗成分之一，已被报道具有对抗酒精和四氯化碳诱导的肝毒性的保护作用。在这项研究中，我们在 C57BL/6J 小鼠中研究了 PD 对乙酰氨基酚（APAP）诱导的肝损伤的保护作用及其可能的机制。在 APAP 中毒前给予 PD 治疗可显著改善血清转氨酶、白细胞介素 1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）和肝丙二醛（MDA）的增加以及谷胱甘肽（GSH）的消耗。PD 预处理可降低 APAP 存在时血红素加氧酶-1（HO-1）、环氧化酶-2（COX-2）和核因子 kappa B（NF-κB）的表达。此外，PD 治疗可明显减少 APAP 诱导的肝坏死和细胞凋亡，通过评估小鼠的生理和组织学肝细胞变化来证明。最后，PD 预处理可显著减少 APAP 诱导的 c-Jun NH-末端激酶（JNK）、细胞外信号调节激酶 1 和 2（ERK1/2）和 p38 磷酸化。总之，PD 预处理可通过改善氧化应激、炎症反应和肝细胞凋亡，有效保护小鼠的肝细胞免受 APAP 诱导的肝毒性。
