[논문]HCl/ethanol로 유발한 급성 위염 마우스에서 PI3K/Akt/NF-κB 신호전달경로를 통한 진피 열수 추출물의 보호 효과

이세희; 신미래; 박해진; 노성수

doi:10.9721/kjfst.2022.54.3.288

HCl/ethanol로 유발한 급성 위염 마우스에서 PI3K/Akt/NF-κB 신호전달경로를 통한 진피 열수 추출물의 보호 효과
The protective effect of Citrus unshiu Peel water extract through PI3K/Akt/NF-κB signaling pathway in mice with HCl/ethanol-induced acute gastritis 원문보기

한국식품과학회지 = Korean journal of food science and technology, v.54 no.3, 2022년, pp.288 - 296

이세희 (대구한의대학교 한의과대학 본초약리학교실) , 신미래 (대구한의대학교 한의과대학 본초약리학교실) , 박해진 (대구한의대학교 DHU 바이오융복합시험센터) , 노성수 (대구한의대학교 한의과대학 본초약리학교실)

초록
AI-Helper

본 연구에서는 우선 진피 열수 추출물의 in vitro 항산화능을 평가하기 위해 total polyphenol, total flavonoid 함량, DPPH 및 ABTS radical 소거능을 분석한 후, 150 mM/60% ethanol로 유발한 급성 위염 동물 실험을 진행하여 급성 위염 완화 효과를 검증하였다. 약물투여군의 혈청 내 ROS와 MPO 수준, 조직 내 MDA 수준의 유의성 있는 감소를 확인하였으며, western blot을 통해 NOX2와 p22^phox를 포함한 산화적 스트레스 관련 단백질을 억제하였고, PI3K/Akt/NF- κB 신호 전달 경로를 통한 염증성 단백질의 현저한 감소를 확인하였다. 따라서 이러한 결과는 진피 열수 추출물이 급성 위염에 대한 완화 효과를 나타냈으며, 위염 및 천연 치료제의 후보 소재로서 가능성이 있다고 판단된다. 또한, 향후 만성 위염, 위암과 같은 위장 질환에 관한 추가 연구에서 진피 열수 추출물의 활용 가능성을 시사한다.

Abstract ▼ AI-Helper

This study aimed to verify the effect of Citrus unshiu peel water extract (CUP) on a mouse model of acute gastritis (AG) induced by HCl/ethanol. Several studies have found that CUP has anti-inflammatory effects. The AG model was induced by oral administration of 150 mM HCl/60% ethanol (550 µL) to all groups except the control group. Also, for drug treatment, sucralfate (10 mg/kg) and CUP (100 or 200 mg/kg) were orally administered for 90 minutes before induction. The effect of CUP treatment was confirmed by gross gastric mucosal damage measurement, and the levels of Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT), and myeloperoxidase were reduced as well as the levels of oxidative stress biomarkers and their related proteins. In addition, the levels of inflammatory proteins, mediators, and cytokines were significantly downregulated byPI3K/Akt signaling. Taken together, these results show that CUP treatment alleviates AG by regulating PI3K/Akt signaling.

주제어

표/그림 (9)

그림 Fig. 1. Analysis of narirutin and hesperidin in the Citrus unshiu Peel water extract. (A) Chemical structure of narirutin (B) Chemical structure of hesperidin (C) The chromatogram of the CUP. CUP, Citrus unshiu Peel water extract.
그림 Fig. 2. Scavenging activity (IC₅₀) of Citrus unshiu Peel water extract on DPPH and ABTS free radical. CUP, Citrus unshiu Peel water extract. All values are expressed as mean±SEM of three replications.
표 Table 1. Total polyphenol and total flavonoid concents of Citrus unshiu Peel water extract
그림 Fig. 3. Effects of CUP on gross gastric mucosal damage. Control, normal mice; Model, HCl/ethanol-induced mice; SC, HCl/ethanol-induced with sucralfate 10 mg/kg body weight mice; CUPL, HCl/ethanol-induced with Citrus unshiu Peel water extract 200 mg/kg body weight mice. CUPH, HCl/ethanol-induced with Citrus unshiu Peel water extract 200 mg/kg body weight mice. All data are expressed as means±SD (n=8 mice). Significance: ^###p<0.001 vs. Control, ***p<0.001 vs. Model.
그림 Fig. 4. Levels of ROS level in serum and MDA level in tissue. (A) Reactive oxygen species (ROS) level in serum (B) malondialdehyde (MDA) level in tissue. Control, normal mice; Model, HCl/ethanol-induced mice; SC, HCl/ethanol-induced with sucralfate 10 mg/kg body weight mice; CUPL, HCl/ethanol-induced with Citrus unshiu Peel water extract 200 mg/kg body weight mice. CUPH, HCl/ethanol-induced with Citrus unshiu Peel water extract 200 mg/kg body weight mice. All data are expressed as means±SD (n=8 mice). Significance: ^###p < 0.001 vs. Control, *p<0.05, **p<0.01, and ***p<0.001 vs. Model.
그림 Fig. 5. Effect of CUP on NADPH-related proteins expression. (A) NADPH oxidase 2 (NOX2) (B) p22^phox. Control, normal mice; Model, HCl/ethanol-induced mice; SC, HCl/ethanol-induced with sucralfate 10 mg/kg body weight mice; CUPL, HCl/ethanol-induced with Citrus unshiu Peel water extract 200 mg/kg body weight mice. CUPH, HCl/ethanol-induced with Citrus unshiu Peel water extract 200 mg/kg body weight mice. All data are expressed as means±SD (n=8 mice). Significance: ^###p<0.001 vs. Control, *p<0.05, **p<0.01, and ***p<0.001 vs. Model.
표 Table 2. Effect of CUP on liver function indicator analysis and inflammatory biomarker analysis
그림 Fig. 6. Effect of CUP on PI3K/Akt/NF-κB proteins expression. (A) p-PI3K (B) p-Akt (C) p-IκBα (D) NF-κBp65. Control, normal mice; Model, HCl/ethanol-induced mice; SC, HCl/ethanol-induced with sucralfate 10 mg/kg body weight mice; CUPL, HCl/ethanol-induced with Citrus unshiu Peel water extract 100 mg/kg body weight mice; CUPH, HCl/ethanol-induced with Citrus unshiu Peel water extract 200 mg/kg body weight mice. All data are expressed as means±SD (n=8 mice). Significance: ^###p<0.001 vs. Control, **p<0.01, and ***p<0.001 vs. Model.
그림 Fig. 7. Effect of CUP on inflammatory mediators and pro-inflammatory cytokines expression. (A) iNOS (B) Cox-2 (C) TNF-α (D) IL-6. Control, normal mice; Model, HCl/ethanol-induced mice; SC, HCl/ethanol-induced with sucralfate 10 mg/kg body weight mice; CUPL, HCl/ ethanol-induced with Citrus unshiu Peel water extract 100 mg/kg body weight mice; CUPH, HCl/ethanol-induced with Citrus unshiu Peel water extract 200 mg/kg body weight mice. All data are expressed as means±SD (n=8 mice). Significance: ^###p<0.001 vs. Control, **p<0.01, and ***p<0.001 vs. Model.

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