[논문]햄프씨드 오일이 고콜레스테롤식이를 급여한 흰쥐의 지질대사에 미치는 영향

이진아; 노성수; 이우락; 신미래

doi:10.4163/jnh.2023.56.4.361

햄프씨드 오일이 고콜레스테롤식이를 급여한 흰쥐의 지질대사에 미치는 영향
Effect of hemp seed oil on lipid metabolism in rats fed a high-cholesterol diet 원문보기

Journal of nutrition and health, v.56 no.4, 2023년, pp.361 - 376

이진아 (대구한의대학교 한의과대학 본초약리학교실) , 노성수 (대구한의대학교 한의과대학 본초약리학교실) , 이우락 (농업회사법인 주식회사 농부플러스) , 신미래 (대구한의대학교 한의과대학 본초약리학교실)

초록
AI-Helper

본 연구에서는 햄프씨드 오일이 고콜레스테롤혈증을 개선시키는 지 확인하기 위하여 Sprague-Dawley rat에 1.25% 콜레스테롤식이를 8주 동안 급여하였으며, 햄프씨드 오일을 두 농도 (저농도, 고농도)로 경구 투여한 후 혈액, 조직 분석을 통하여 지질개선 및 염증 완화 효과를 발휘하는지 분석하였다. 햄프씨드 오일 식이는AMPK/SREBP-2 경로를 경유하여 혈중 콜레스테롤의 합성을 효과적으로 억제하였으며, PI3IK/Akt/NF-κB의 경로를 유의하게 억제하여 항염증 효과를 발휘함을 알 수 있었다. 이러한 신호전달의 경로는 간 조직에서 지질축적의 감소와도 관련이 있는 것으로 보인다. 이상의 결과를 종합해보면 햄프씨드 오일은 고콜레스테롤혈증의 예방 및 치료를 위한 잠재적 후보소재로서 가능성이 있음을 시사한다.

Abstract ▼ AI-Helper

Purpose: This study evaluates the potential protective effects of hemp (Cannabis sativa L.) seed oil supplementation in rats fed a high-cholesterol diet. Methods: Rats were fed a 1.25% cholesterol diet for 8 weeks, followed by oral administration of either of the two doses of hemp seed oil (HO) (0.5 mL/kg (HOL group) or 1 mL/kg (HOH group) body weight/day) or simvastatin at 10 mg/kg body weight/day. Oxidative stress, lipids, liver enzymes, and renal markers were measured in the serum. Western blot analysis was applied for evaluating the expressions of inflammatory makers. Results: Except for HDL-cholesterol, the altered levels of lipoproteins, aminotransferases, urea, and creatine kinases in hypercholesterolemic rats were significantly corrected by HO administration. Especially, compared to the HOH group, HOL treatment further reduced AST, ALT, creatinine, TC, and LDL-cholesterol levels. Moreover, both the atherogenic index and cardiac risk factor (CRF) in the HOL group were more restrained compared to the HOH group. Increased levels of p-AMPK coincided with the inhibition of SREBP-2 activation which subsequently suppressed the expression of HMGCR. Nuclear factor (NF)-κB activation coincided with the PI3K/Akt pathway activation and the increased phosphorylation of p38; these levels were significantly suppressed by HO treatment. In addition, HO treatment markedly reversed the changes in chemokines such as ICAM-1, VCAM-1, and MCP-1. Histological alterations induced by cholesterol overload in cardiac and hepatic tissues were ameliorated by HO supplementation. Conclusion: Taken together, our results indicate a low concentration of HO demonstrates improved dysfunctions caused by a high-cholesterol diet via inhibition of the PI3K/Akt/NF-κB signaling pathway.

주제어

표/그림 (9)

표 Table 1. Composition of the experimental diet used in this study
그림 Fig. 1. Body weight, liver weights, and serum lipids associated with levels in high-cholesterol fed rats. (A) Body weight, (B) liver weight, (C) serum TG level, (D) serum TC level, (E) serum HDL-c level, (F) serum LDL-c level, (G) LDL-c/HDL-c ratio. After a week of acclimatization, rats were fed a 1.25% hyper-cholesterol diet or normal diet for 8 weeks. After 8 weeks of diet, the rats were administrated simvastatin or HO for 8 weeks. There was no significant difference in the initial body weight between the groups. Rats except for the normal rats were fed a 1.25% hyper-cholesterol and orally administered Simvastatin (10 mg/kg body weight/day), HOL (0.5 mL/kg body weight/day), HOH (1 mL/kg body weight/day) for 8 weeks. Bars represent the average ± SEM (n = 7). HOL, HO-low group; HOH, HO-high group; TG, triglyceride; TC, total cholesterol; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; HO, hemp seed oil. ^##p < 0.01; ^###p < 0.001, as compared with the Normal group and *p < 0.05; **p < 0.01; ***p < 0.001 as compared with the Control group.
그림 Fig. 2. Effects of HO supplementation on serum AST and ALT levels in high-cholesterol fed rats. (A) Serum AST level, (B) Serum ALT level. Rats except for the normal rats were fed a 1.25% hyper-cholesterol and orally administered Simvastatin (10 mg/kg body weight/day), HOL (0.5 mL/kg body weight/day), HOH (1 mL/kg body weight/day) for 8 weeks. Bars represent the average ± SEM (n = 7). AST, aspartate aminotransferase; HOL, HO-low group; HOH, HO-high group; ALT, alanine aminotransferase; HO, hemp seed oil. ^#p < 0.05; ^###p < 0.001, as compared with the Normal group and *p < 0.05; **p < 0.01; ***p < 0.001, as compared with the Control group.
그림 Fig. 3. Expression of atherogenic index and cardiac risk factor levels in serum. (A) AI, (B) CRF. Rats except for the normal rats were fed a 1.25% hyper-cholesterol and orally administered Simvastatin (10 mg/kg body weight/day), HOL (0.5 mL/kg body weight/day), HOH (1 mL/kg body weight/day) for 8 weeks. Bars represent the average ± SEM (n = 7). AI, atherogenic index; HOL, HO-low group; HOH, HO-high group; CRF, Cardiac risk factor. ^###p < 0.001, as compared with the Normal group and *p < 0.05; ***p < 0.001, as compared with the Control group.
그림 Fig. 4. Effects of HO supplementation on p-LKB1, p-AMPK, SREBP-2, and HMGCR expressions in high-cholesterol fed rats. (A) Representative images of Western blot analysis, (B) p-LKB1, (C) p-AMPK, (D) SREBP-2, (E) HMGCR. Rats except for the normal rats were fed a 1.25% hyper-cholesterol and orally administered Simvastatin (10 mg/kg body weight/day), HOL (0.5 mL/kg body weight/day), HOH (1 mL/kg body weight/day) for 8 weeks. Bars represent the average ± SEM (n = 7). HOL, HO-low group; HOH, HO-high group; HO, hemp seed oil. ^###p < 0.001, as compared with the Normal group and **p < 0.01; ***p < 0.001, as compared with the Control group.
그림 Fig. 5. Effects of HO supplementation on PI3K/Akt/NF-κB pathway expressions in high-cholesterol fed rats. (A) Representative images of Western blot analysis, (B) p-PI3K, (C) p-Akt, (D) p-NF-κBp65, (E) p-p38, (F) p-IκBα. Rats except for the normal rats were fed a 1.25% hyper-cholesterol and orally administered Simvastatin (10 mg/kg body weight/day), HOL (0.5 mL/kg body weight/day), HOH (1 mL/kg body weight/day) for 8 weeks. Bars represent the average ± SEM (n = 7). NF, nuclear factor; HOL, HO-low group; HOH, HO-high group; HO, hemp seed oil. ^###p < 0.001, as compared with the Normal group and **p < 0.01; ***p < 0.001, as compared with the Control group.
그림 Fig. 6. Effects of HO supplementation on the expressions of inflammatory proteins in high-cholesterol fed rats. (A) Representative images of Western blot analysis, (B) iNOS, (C) COX-2, (D) TNF-α, (E) IL-6, (F) IL-1β. Rats except for the normal rats were fed a 1.25% hyper-cholesterol and orally administered Simvastatin (10 mg/kg body weight/day), HOL (0.5 mL/kg body weight/day), HOH (1 mL/kg body weight/day) for 8 weeks. Bars represent the average ± SEM (n = 7). TNF, tumor necrosis factor; IL, interleukin; HOL, HO-low group; HOH, HO-high group; HO, hemp seed oil. ^###p < 0.001, as compared with the Normal group and **p < 0.01; ***p < 0.001, as compared with the Control group.
그림 Fig. 7. Effects of HO supplementation on the expressions of adhesion factors and chemokine in high-cholesterol fed rats. (A) Representative images of Western blot analysis, (B) VCAM-1, (C) ICAM-1, (D) MCP-1. Rats except for the normal rats were fed a 1.25% hyper-cholesterol and orally administered Simvastatin (10 mg/kg body weight/day), HOL (0.5 mL/kg body weight/day), HOH (1 mL/kg body weight/day) for 8 weeks. Bars represent the average ± SEM (n = 7). HOL, HO-low group; HOH, HO-high group; HO, hemp seed oil. ^###p < 0.001, as compared with the Normal group and **p < 0.01; ***p < 0.001, as compared with the Control group.
그림 Fig. 8. The histopathological changes through H&E stain in liver and heart tissues in high-cholesterol fed rats. (A) Representative images of H&E stain in liver and heart tissues. (B) H&E staining intensity in liver tissue. Rats except for the normal rats were fed a 1.25% hyper-cholesterol and orally administered Simvastatin (10 mg/kg body weight/day), HOL (0.5 mL/kg body weight/day), HOH (1 mL/kg body weight/day) for 8 weeks. HOL, HO-low group; HOH, HO-high group; HO, hemp seed oil; H&E, hematoxylin & eosin.

참고문헌 (35)

Paramita S, Aminyoto M, Ismail S, Arung ET. Anti-hypercholesterolemic effect of Zingiber montanum extract. F1000 Res 2018; 7: 1798.

상세보기
Majewski M, Jurgonski A, Fotschki B, Juskiewicz J. The toxic effects of monosodium glutamate (MSG) - The involvement of nitric oxide, prostanoids and potassium channels in the reactivity of thoracic arteries in MSG-obese rats. Toxicol Appl Pharmacol 2018; 359: 62-69.

상세보기
Gyawali D, Vohra R, Orme-Johnson D, Ramaratnam S, Schneider RH. A systematic review and meta-analysis of ayurvedic herbal preparations for hypercholesterolemia. Medicina (Kaunas) 2021; 57(6): 546.
Nagashree S, Archana KK, Srinivas P, Srinivasan K, Sowbhagya HB. Anti-hypercholesterolemic influence of the spice cardamom (Elettaria cardamomum) in experimental rats. J Sci Food Agric 2017; 97(10): 3204-3210.

상세보기
Arrigoni E, Del Re M, Fidilio L, Fogli S, Danesi R, Di Paolo A. Pharmacogenetic foundations of therapeutic efficacy and adverse events of statins. Int J Mol Sci 2017; 18(1): 104.
Pangestika I, Oksal E, Tengku Muhammad TS, Amir H, Syamsumir DF, Wahid ME, et al. Inhibitory effects of tangeretin and trans-ethyl caffeate on the HMG-CoA reductase activity: Potential agents for reducing cholesterol levels. Saudi J Biol Sci 2020; 27(8): 1947-1960.？
Guijarro C, Cosin-Sales J. LDL cholesterol and atherosclerosis: the evidence. Clin Investig Arterioscler 2021;33 Suppl 1: 25-32.
Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol 2020; 16(9): 809-822.
Najjar RS, Moore CE, Montgomery BD. A defined, plant-based diet utilized in an outpatient cardiovascular clinic effectively treats hypercholesterolemia and hypertension and reduces medications. Clin Cardiol 2018; 41(3): 307-313.

상세보기
Feuerstein JS, Bjerke WS. Powdered red yeast rice and plant stanols and sterols to lower cholesterol. J Diet Suppl 2012; 9(2): 110-115.
Majewski M, Jurgonski A. The effect of hemp (Cannabis sativa L.) seeds and hemp seed oil on vascular dysfunction in obese male zucker rats. Nutrients 2021; 13(8): 2575.

상세보기
Vodolazska D, Lauridsen C. Effects of dietary hemp seed oil to sows on fatty acid profiles, nutritional and immune status of piglets. J Anim Sci Biotechnol 2020; 11(1): 28.

상세보기
Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome. J Nutr 2001; 131(4): 1129-1132.

상세보기
Vitorovic J, Jokovic N, Radulovic N, Mihajilov-Krstev T, Cvetkovic VJ, Jovanovic N, et al. Antioxidant activity of hemp (Cannabis sativa L.) seed oil in drosophila melanogaster larvae under non-stress and H2O2-induced oxidative stress conditions. Antioxidants 2021; 10(6): 830.

상세보기
Fotschki B, Opyd P, Juskiewicz J, Wiczkowski W, Jurgonski A. Comparative effects of dietary hemp and poppy seed oil on lipid metabolism and the antioxidant status in lean and obese Zucker rats. Molecules 2020; 25(12): 2921.

상세보기
Smeriglio A, Galati EM, Monforte MT, Lanuzza F, D'Angelo V, Circosta C. Polyphenolic compounds and antioxidant activity of cold-pressed seed oil from Finola cultivar of Cannabis sativa L. Phytother Res 2016; 30(8): 1298-1307.
Tura M, Ansorena D, Astiasaran I, Mandrioli M, Toschi TG. Evaluation of hemp seed oils stability under accelerated storage test. Antioxidants 2022; 11(3): 490.

상세보기
Occhiuto C, Aliberto G, Ingegneri M, Trombetta D, Circosta C, Smeriglio A. Comparative evaluation of the nutrients, phytochemicals, and antioxidant activity of two hempseed oils and their byproducts after cold pressing. Molecules 2022; 27(11): 3431.

상세보기
Kitts DD, Singh A, Fathordoobady F, Doi B, Pratap Singh A. Plant extracts inhibit the formation of hydroperoxides and help maintain vitamin E levels and omega-3 fatty acids during high temperature processing and storage of hempseed and soybean oils. J Food Sci 2019; 84(11): 3147-3155.

상세보기
Esmaeilzadeh Kenari R, Dehghan B. Optimization of ultrasound-assisted solvent extraction of hemp (Cannabis sativa L.) seed oil using RSM: evaluation of oxidative stability and physicochemical properties of oil. Food Sci Nutr 2020; 8(9): 4976-4986.

상세보기
Kim SJ, Park SH, Sin HS, Jang SH, Lee SW, Kim SY, et al. Hypocholesterolemic effects of probiotic mixture on diet-induced hypercholesterolemic rats. Nutrients 2017; 9(3): 293.

상세보기
Rosenfeld L. Lipoprotein analysis. Early methods in the diagnosis of atherosclerosis. Arch Pathol Lab Med 1989.113(10): 1101-1110.

상세보기
Lee JA, Shin MR, Roh SS, Park HJ. Effects of a mixture of Citri Pericarpium and Scutellariae Radix on acute reflux esophagitis in rats. J Nutr Health 2021; 54(3): 321-333.？
The Korean Society of Lipid and Atherosclerosis. Dyslipidemia fact sheets in Korea 2022 [Internet]. Seoul: The Korean Society of Lipid and Atherosclerosis; 2022 [cited 2023 Jul 27]. Available from: https://www.lipid.or.kr/bbs/index.html?codefact_sheet&category&gubun&page1&number1264&modeview&keyfield&key.？
Rhee EJ. Prevalence and current management of cardiovascular risk factors in Korean adults based on fact sheets. Endocrinol Metab (Seoul) 2020; 35(1): 85-94.
Vinci P, Panizon E, Tosoni LM, Cerrato C, Pellicori F, Mearelli F, et al. Statin-associated myopathy: emphasis on mechanisms and targeted therapy. Int J Mol Sci 2021; 22(21): 11687.
Soares E, Soares AC, Trindade PL, Monteiro EB, Martins FF, Forgie AJ, et al. Jaboticaba (Myrciaria jaboticaba) powder consumption improves the metabolic profile and regulates gut microbiome composition in high-fat diet-fed mice. Biomed Pharmacother 2021; 144: 112314.

상세보기
Feng RB, Fan CL, Liu Q, Liu Z, Zhang W, Li YL, et al. Crude triterpenoid saponins from Ilex latifolia (Da Ye Dong Qing) ameliorate lipid accumulation by inhibiting SREBP expression via activation of AMPK in a non-alcoholic fatty liver disease model. Chin Med 2015; 10: 23.
Yang J, Lee J, Kim Y. Effect of deglycosylated rutin by acid hydrolysis on obesity and hyperlipidemia in high-fat diet-induced obese mice. Nutrients 2020; 12(5): 1539.

상세보기
Chan KC, Wu CH, Huang CN, Lan KP, Chang WC, Wang CJ. Simvastatin inhibits glucose-stimulated vascular smooth muscle cell migration involving increased expression of RhoB and a block of Ras/Akt signal. Cardiovasc Ther 2012; 30(2): 75-84.
Talebi M, Talebi M, Farkhondeh T, Simal-Gandara J, Kopustinskiene DM, Bernatoniene J, et al. Promising protective effects of chrysin in cardiometabolic diseases. Curr Drug Targets 2022; 23(5): 458-470.
Hadi NR, Yousif NG, Abdulzahra MS, Mohammad BI, Al-Amran FG, Majeed ML, et al. Role of NF-κβ and oxidative pathways in atherosclerosis: cross-talk between dyslipidemia and candesartan. Cardiovasc Ther 2013; 31(6): 381-387.
Xia YF, Liu LP, Zhong CP, Geng JG. NF-kappaB activation for constitutive expression of VCAM-1 and ICAM-1 on B lymphocytes and plasma cells. Biochem Biophys Res Commun 2001; 289(4): 851-856.
Wagner W, Roderburg C, Wein F, Diehlmann A, Frankhauser M, Schubert R, et al. Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors. Stem Cells 2007; 25(10): 2638-2647.

상세보기
Rodriguez-Ayala E, Anderstam B, Suliman ME, Seeberger A, Heimburger O, Lindholm B, et al. Enhanced RAGE-mediated NFkappaB stimulation in inflamed hemodialysis patients. Atherosclerosis 2005; 180(2): 333-340.

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