[6]-Gingerol Attenuates Autophagy and Increases Activities of Antioxidative Defense Enzymes in Mice with Cerulein-induced Acute Pancreatitis

The current study investigated the effects of [6]-gingerol, a ginger phytochemical, on the expression of autophagy-related genes and the activation of antioxidative enzymes in the pancreas of mice with cerulein-induced acute pancreatitis. The following were studied: pancreatic edema, ${\alpha}$-amylase activity in serum, expression of autophagy genes, activities of antioxidative defense enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the production of lipid peroxidation (LPO). The results revealed that cerulein-induced edema in the pancreas and ${\alpha}$-amylase activity in the cerulein group significantly increased compared with that of the control. However, that of the [6]-gingerol pretreated group was significantly decreased compared with that of the cerulein-alone injected group (positive control). There was no significant difference compared with that of control. The expression of autophagy-related proteins, including Beclin-1 and cleaved microtubule-associated protein 1 light chain 3, were significantly increased in the positive control but significantly decreased in the [6]-gingerol-pretreated group. Furthermore, the activities of SOD and GSH-Px in the positive control were decreased compared with those of the control. However, those of the [6]-gingerol pretreated group were significantly increased compared with those of the cerulein-alone group. The mRNA levels and antioxidant enzyme activities were similar. The production of LPO in the cerulein with and without [6]-gingerol groups was increased by 133.1% and 26.3%, respectively, compared with that of the control, whereas that of the [6]-gingerol-pretreated group was significantly decreased by 48.5% compared with that of the positive control. Therefore, [6]-gingerol may be a strong candidate in reducing autophagy and LPO production and in enhancing antioxidative enzyme activities to help prevent acute and chronic pancreatitis.

Cerulein 유도 급성췌장염 마우스모델에서 자가분해 조절과 항산화 활성에 미치는 [6]-gingerol의 영향

열대아시아 원산의 다년생 초본 생강의 주성분인 [6]-gingerol은 항산화 및 항염증 등의 특성이 잘 알려져 있지만 cerulein 유도 급성췌장염에서의 자가분해 관련 유전자 발현 조절과 항산화 효소 활성에 대한 연구는 거의 없다. 본 연구에서는 cerulein 유도 급성췌장염 동물모델에서 [6]-gingerold의 자가분해 조절과 항산화 작용을 조사하였다. 급성췌장염 유발 전 4일 동안 [6]-gingerol (0.1 mg/20 g mouse/day)을 경구투여 한 후 $50{\mu}g/kg$ cerulein을 복강주사로 급성 췌장염을 유도하였다. 그 결과 혈중 ${\alpha}$-amyase 활성, 자가분해 표적 유전자(Beclin-1 및 cleaved LC3-II)의 발현, 지질과산화는 [6]-gingerol 투여군에서 유의적으로 감소하였으며, 항산화지표 효소인 SOD와 GSH-Px 활성은 [6]-gingerol 투여군에서 유의적으로 증가하였다. 이상의 결과들은 천연식물소재 생강의 유효성분 중 하나인 [6]-gingerol이 cerulein 유도 급성 췌장염에서 자가분해 조절과 감소된 항산화효소 활성을 강화하는 효과를 나타내므로 생강이 급성췌장염의 예방과 치료에 대한 기능성 식품소재로 그 활용이 매우 높을 것으로 사료된다.