小檗碱磷脂固体分散体改善氧化应激治疗2型糖尿病

童帅, 尹明星, 马永贵, 施春阳, 方建国

中国药学杂志 ›› 2022, Vol. 57 ›› Issue (5) : 363-372.

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中国药学杂志 ›› 2022, Vol. 57 ›› Issue (5) : 363-372. DOI: 10.11669/cpj.2022.05.006
论著

小檗碱磷脂固体分散体改善氧化应激治疗2型糖尿病

  • 童帅1, 尹明星1, 马永贵1*, 施春阳1, 方建国1,2*
作者信息 +

Berberine Loaded Phospholipid Solid Dispersion for the Treatment of Type 2 Diabetes Mellitus by Ameliorating Oxidative Stress

  • TONG Shuai1, YIN Ming-xing1, MA Yong-gui1*, SHI Chun-yang1, FANG Jian-guo1,2*
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文章历史 +

摘要

目的 制备包载小檗碱(BBR)的磷脂固体分散体促进药物吸收,增强降糖、降脂药效,并初步阐明其抗2型糖尿病(T2DM)作用机制。方法 溶剂挥发法制备小檗碱磷脂固体分散体(SD),对其粒径、形貌、体外释放、胃肠道吸收、治疗T2DM药效和作用机制进行了充分研究。结果 SD在水溶液中粒径约为118 nm,形貌为球形;相比于游离BBR,SD表现出更快的体外释放、胃肠道吸收,显著降低T2DM小鼠空腹血糖和血中胰岛素、甘油三酯、总胆固醇、低密度脂蛋白水平,增加肝实质细胞HO-1蛋白表达,提高肝组织超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)等抗氧化物质水平,降低肝组织丙二醛(MDA)水平,改善T2DM小鼠肝脏脂肪肝等并发症,起到组织保护作用。结论 溶剂挥发法制备的小檗碱磷脂固体分散体能够显著增加BBR胃肠道吸收、提高BBR药效,通过改善氧化应激发挥抗T2DM作用。

Abstract

OBJECTIVE To prepare berberine(BBR) loaded phospholipid solid dispersion and realize the enhanced drug absorption and antidiabetic effect.. METHODS Berberine (BBR) loaded phospholipid solid dispersion (SD) was prepared by solvent evaporation method. The particle size, morphology, in vitro release property, gastrointestinal absorption profile, antidiabetic effect and mechanism of SD were fully investigated. RESULTS SD was with a mean hydrodynamic diameter of ≈118 nm and a near spherical shape. SD exhibited faster in vitro BBR release, enhanced in vivo gastrointestinal absorption than free BBR, and thus resulted in significantly decreased fasting blood glucose, insulin, triglycerides, total cholesterol, low density lipoprotein and liver malondialdehyde levels, and significantly increased the liver superoxide dismutase, glutathione levels and expression of HO-1in T2DM mice compared with free BBR, which demonstrated tissue protection of SD. CONCLUSION SD can significantly increase the gastrointestinal absorption and antidiabetic effect of BBR via ameliorating oxidative stress in T2DM mice.

关键词

小檗碱 / 磷脂固体分散体 / 2型糖尿病 / 氧化应激

Key words

berberine / phospholipid solid dispersion / type 2 diabetesmellitus / oxidative stress

引用本文

导出引用
童帅, 尹明星, 马永贵, 施春阳, 方建国. 小檗碱磷脂固体分散体改善氧化应激治疗2型糖尿病[J]. 中国药学杂志, 2022, 57(5): 363-372 https://doi.org/10.11669/cpj.2022.05.006
TONG Shuai, YIN Ming-xing, MA Yong-gui, SHI Chun-yang, FANG Jian-guo. Berberine Loaded Phospholipid Solid Dispersion for the Treatment of Type 2 Diabetes Mellitus by Ameliorating Oxidative Stress[J]. Chinese Pharmaceutical Journal, 2022, 57(5): 363-372 https://doi.org/10.11669/cpj.2022.05.006
中图分类号: R944   

参考文献

[1] International Diabetes Federation: Global diabetes data report 2010-2045[R]. IDF, 2019.
[2] Manuscript A, Metabolism D: NIH Public Access[J]. Eur J Clin Pharmacol, 2010, 87:507-520.
[3] ZHOU J, PAN J, XIANG Z, et al. Xiaokeyinshui extract combination, a berberine-containing agent, exerts anti-diabetic and renal protective effects on rats in multi-target mechanisms[J]. J Ethnopharmacol, 2020, 262(15):113098.
[4] IMENSHAHIDI M, HOSSEEINZADEH H. Berberine and barberry (Berberis vulgaris): A clinical review[J]. Phytother Res, 2019, 33(3):504-523.
[5] ZHANG Y, LI X, ZOU D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine[J]. J. Clin Endocrinol Metab, 2008, 93(7):2559-2565.
[6] IMENSHAHIDI M, HOSSEEINZADEH H. Berberis vulgaris and berberine: An update review[J]. Phytother Res, 2016, 30(11):1745-1764.
[7] XU X, YI H, WU J, et al. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence[J]. Biomed Pharmacother, 2021, 133(4):110984.
[8] TAPEINOS C, BATTAGLINI M, CIOFANI G. Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases[J]. J Controlled Release, 2017, 264:306-332.
[9] LIU C S, ZHENG Y R, ZHANG Y F, et al. Research progress on berberine with a special focus on its oral bioavailability[J]. Fitoterapia, 2016, 109(1):274-282.
[10] LANZA F L, MARATHI U K, ANAND B S, et al. Clinical Trial: comparison of Ibuprofen-PC and ibuprofen on the GI safety and analgesic efficacy in osteoarthritic patients[J]. Aliment Pharmacol Ther, 2008, 28(4):431-442.
[11] HABTEMARIAM S. The quest to enhance the efficacy of berberine for type-2 diabetes and associated diseases: Physicochemical modification approaches[J]. Biomedicines, 2020, 8(4):1-19.
[12] SHI C Y, TONG Q, FANG J G, et al. Preparation, characterization and in vivo studies of amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine[J]. Eur J Pharm Sci, 2015, 74(1):11-17.
[13] MIRHADI E, REZAEE M, MALAEKEH-NIKOUEI B. Nano strategies for berberine delivery, a natural alkaloid of Berberis[J]. Biomed Pharmacother, 2018, 104(1):465-473.
[14] ZHANG Z, CHEN Y, DENG J, et al. Solid dispersion of berberine-phospholipid complex/TPGS 1000/SiO2: preparation, characterization and in vivo studies[J]. Int J Pharm, 2014, 465(1-2):306-316.
[15] LI C, XU S, LIU Z, DING L, et al. Evaluation of a non-aqueous ibuprofen-phospholipid complex formulation in rats[J]. In Vivo, 2016, 30(4):479-483.
[16] WANG L, LI H, WANG S, et al. Enhancing the antitumor activity of berberine hydrochloride by solid lipid nanoparticle encapsulation[J]. AAPS Pharm Sci Tech. 2014,15(4):834-844.
[17] YU F, LI Y, CHEN Q, et al. Monodisperse microparticles loaded with the self-assembled berberine-phospholipid complex-based phytosomes for improving oral bioavailability and enhancing hypoglycemic efficiency[J]. Eur J Pharm Biopharm, 2016, 103(1):136-148.
[18] XUE M, ZHANG L, YANG MX, et al. Berberine-loaded solid lipid nanoparticles are concentrated in the liver and ameliorate hepatosteatosis in db/db mice[J]. Int J Nanomed, 2015, 10(1):5049-5057.
[19] XUE M,YANG M X,ZHANG W, et al. Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles[J]. Int J Nanomed, 2013, 8(1):4677-4687.
[20] MOGHADDAM HK, BALUCHNEJADMOJARAD T, ROGHANI M, et al. Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ-induced diabetic rats[J]. Mol Neurobiol, 2013, 49(2):820-826.
[21] MA X, CHEN Z, WANG L, et al. The pathogenesis of diabetes mellitus by oxidative stress and inflammation: Its inhibition by berberine[J]. Front Pharmacol, 2018, 9(1):782.
[22] LEE D, BAE J, KIM Y K, et al. Inhibitory effects of berberine on lipopolysaccharide-induced inducible nitric oxide synthase and the high-mobility group box 1 release in macrophages[J]. Biochem Biophys Res Commun, 2013, 431(3):506-511.
[23] TANG LQ, WEI W, CHEN LM, et al. Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats[J]. J Ethnopharmacol, 2006, 108(1):109-115.

基金

湖北省自然科学基金面上项目资助(2019CFB744)
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