1-Deoxynojirimycin is an alkaloid compound found in mulberry leaves and other plants. By inhibiting α-glucosidase and modulating various signaling pathways[1-2]. 1-Deoxynojirimycin exhibits anti-diabetic, anti-obesity, and antiviral effects, and is commonly used in research related to diabetes, obesity, and viral infections[3-4].
In vitro, 1-Deoxynojirimycin (30μM) was used to treat mitochondrial hypertrophic cardiomyopathy (HCM) cell models, including cytoplasmic hybrid cells (cybrids) and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). 1-Deoxynojirimycin significantly improved mitochondrial function, enhanced mitochondrial membrane potential and ATP production, restored mitochondrial cristae structure, improved calcium homeostasis and electrophysiological properties, and reduced cellular hypertrophy[5]. 1-Deoxynojirimycin (10μM) was used to treat 3T3-L1 preadipocytes for 10 days, significantly inhibiting the differentiation of cells into white adipocytes, reducing lipid deposition, and down-regulating the mRNA expression levels of fatty acid-binding protein 4 (aP2), peroxisome proliferator-activated receptor γ (PPARγ), and preadipocyte factor-1 (Pref-1). At the same time, 1-Deoxynojirimycin up-regulated the mRNA and protein expression levels of uncoupling protein 1 (UCP1), PR domain-containing protein 16 (PRDM16), and transmembrane protein 26 (TMEM26), promoting the conversion of white preadipocytes into beige adipocytes[6].
In vivo, 1-Deoxynojirimycin (20, 40, and 80mg/kg) was administered via tail vein injection to treat db/db mouse models, with administration once daily for four consecutive weeks. 1-Deoxynojirimycin significantly reduced body weight, blood glucose, and serum insulin levels in db/db mice in a dose-dependent manner, improving glucose tolerance and insulin tolerance. In addition, 1-Deoxynojirimycin significantly increased GLUT4 translocation in skeletal muscle and the phosphorylation levels of Ser473-AKT, p85-PI3K, Tyr1361-IR-β, and Tyr612-IRS1, thereby improving insulin sensitivity by activating the insulin signaling PI3K/AKT pathway[7]. 1-Deoxynojirimycin (20, 40, and 80mg/kg) was administered via tail vein injection to treat db/db mouse models, with administration once daily for four consecutive weeks. 1-Deoxynojirimycin significantly reduced serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and liver TG levels in db/db mice in a dose-dependent manner, while also reducing the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, 1-Deoxynojirimycin significantly alleviated hepatic steatosis and reduced the levels of tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in liver tissue. 1-Deoxynojirimycin also significantly increased hepatic glycogen content, enhanced the activities of hexokinase (HK) and pyruvate kinase (PK) in liver tissue, and reduced the activities of glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK)[8].
References:
[1] Wang H, Shen Y, Zhao L, et al. 1-Deoxynojirimycin and its Derivatives: A Mini Review of the Literature. Curr Med Chem. 2021;28(3):628-643.
[2] Mehmood A, Battino M, Chen X. 1-Deoxynojirimycin: a comprehensive review of sources, biosynthesis pathways, strategies to enhance its production, and anti-diabetic activities. Food Funct. 2025 Jun 16;16(12):4673-4701.
[3] Zhang W, Mu W, Wu H, et al. An overview of the biological production of 1-deoxynojirimycin: current status and future perspective. Appl Microbiol Biotechnol. 2019 Dec;103(23-24):9335-9344.
[4] Fongsodsri K, Thaipitakwong T, Rujimongkon K, et al. Mulberry-Derived 1-Deoxynojirimycin Prevents Type 2 Diabetes Mellitus Progression via Modulation of Retinol-Binding Protein 4 and Haptoglobin. Nutrients. 2022 Oct 28;14(21):4538.
[5] Zhuang Q, Guo F, Fu L, et al. 1-Deoxynojirimycin promotes cardiac function and rescues mitochondrial cristae in mitochondrial hypertrophic cardiomyopathy. J Clin Invest. 2023 Jul 17;133(14):e164660.
[6] Li AN, Chen JJ, Li QQ, et al. Alpha-glucosidase inhibitor 1-Deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK. Biochem Biophys Res Commun. 2019 Feb 19;509(4):1001-1007.
[7] Liu Q, Li X, Li C, et al. 1-Deoxynojirimycin Alleviates Insulin Resistance via Activation of Insulin Signaling PI3K/AKT Pathway in Skeletal Muscle of db/db Mice. Molecules. 2015 Dec 4;20(12):21700-14.
[8] Liu Q, Li X, Li C, et al. 1-Deoxynojirimycin Alleviates Liver Injury and Improves Hepatic Glucose Metabolism in db/db Mice. Molecules. 2016 Feb 27;21(3):279.
1-Deoxynojirimycin是一种存在于桑叶和其他植物中的生物碱化合物，通过抑制α-葡萄糖苷酶和调节多种信号通路[1-2]。1-Deoxynojirimycin具有抗糖尿病、抗肥胖和抗病毒的作用，常被用于糖尿病、肥胖和病毒感染相关的研究[3-4]。
在体外，1-Deoxynojirimycin（30μM）处理线粒体肥厚型心肌病（HCM）细胞模型，包括细胞质杂交细胞（cybrids）和诱导多能干细胞衍生的心肌细胞（iPSC-CMs），1-Deoxynojirimycin显著改善了细胞的线粒体功能，增强了线粒体膜电位和ATP产生，恢复了线粒体嵴结构，改善了钙离子稳态和电生理特性，减轻了细胞肥大[5]。1-Deoxynojirimycin（10μM）处理3T3-L1前脂肪细胞10天，显著抑制了细胞向白色脂肪细胞的分化，减少了脂质沉积，并下调了脂肪酸结合蛋白4（aP2）、过氧化物酶体增殖物激活受体γ（PPARγ）和前脂肪细胞因子-1（Pref-1）的mRNA表达水平。同时，1-Deoxynojirimycin上调了解偶联蛋白1（UCP1）、PR结构域蛋白16（PRDM16）和跨膜蛋白26（TMEM26）的mRNA和蛋白表达水平，促进了白色前脂肪细胞向米色脂肪细胞的转化[6]。
在体内，1-Deoxynojirimycin（20、40和80mg/kg）通过尾静脉注射给药，用于治疗db/db小鼠模型，给药时间为每天一次，连续四周。1-Deoxynojirimycin以剂量依赖性方式显著降低db/db小鼠的体重、血糖和血清胰岛素水平，改善葡萄糖耐受性和胰岛素耐受性。此外，1-Deoxynojirimycin还显著增加了骨骼肌中GLUT4的转位以及Ser473-AKT、p85-PI3K、Tyr1361-IR-β和Tyr612-IRS1的磷酸化水平，从而通过激活胰岛素信号PI3K/AKT通路改善胰岛素敏感性[7]。1-Deoxynojirimycin（20、40和80mg/kg）通过尾静脉注射给药，用于治疗db/db小鼠模型，给药时间为每天一次，连续四周。1-Deoxynojirimycin以剂量依赖性方式显著降低db/db小鼠的血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和肝脏TG水平，同时降低血清丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）的活性。此外，1-Deoxynojirimycin还显著减轻了肝脏的脂肪变性，并降低了肝组织中肿瘤坏死因子α（TNF-α）、白细胞介素-1（IL-1）和白细胞介素-6（IL-6）的水平。1-Deoxynojirimycin还显著增加了肝糖原含量，提高了肝组织中己糖激酶（HK）和丙酮酸激酶（PK）的活性，同时降低了葡萄糖-6-磷酸酶（G6Pase）、糖原磷酸化酶（GP）和磷酸烯醇丙酮酸羧激酶（PEPCK）的活性[8]