Thiamine (hydrochloride) is a water-soluble essential micronutrient[1]. Thiamine readily crosses the blood–brain barrier and is an important tool compound for studying energy metabolism, neuroinflammation, and aging-related metabolic dysfunction[2]. Thiamine (hydrochloride) is converted into its active coenzyme form, thiamine diphosphate (ThDP), by thiamine diphosphokinase in the liver, kidneys, and leukocytes[3]. ThDP acts as a cofactor for several key metabolic enzymes, including pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase, which are involved in regulating glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway, thereby maintaining cellular energy homeostasis. Thiamine deficiency can lead to lactic acidosis, oxidative stress, and neuronal damage[4].
In vitro, treatment of rat embryonic hippocampal neurons with Thiamine (hydrochloride) (30–300μM) for 72 hours significantly increased the survival of hippocampal neurons in high cell density culture (1×10⁵/cm²), with the maximal effect at 100μM[5]. Pre-treatment of C6 glioma cells with Thiamine (hydrochloride) (0.25–4mg/mL) for 1 hour, followed by exposure to glutamate (10mM) for 24 hours, significantly increased cell viability, reduced levels of the oxidative stress marker malondialdehyde (MDA), while increasing levels of superoxide dismutase (SOD) and catalase (CAT), decreased endoplasmic reticulum stress markers, and reduced the number of apoptotic cells[6].
In vivo, a high-dose Thiamine (hydrochloride) diet (8.50mg/100g) was used to treat Slc19a3 knockout (Slc19a3 KO) mice after 2 or 3 days of a thiamine-restricted diet (0.60mg/100g). Thiamine significantly prolonged the survival of the mice and prevented acute neurodegeneration[7]. Thiamine (200mg/kg) was administered via intraperitoneal injection to Balb/c male mice. Chronic administration of Thiamine alone (once daily for 14 days) significantly increased the threshold for pentylenetetrazole-induced seizures[8].
References:
[1] Polegato BF, Pereira AG, Azevedo PS, et al. Role of Thiamin in Health and Disease. Nutr Clin Pract. 2019 Aug;34(4):558-564.
[2] Kerns JC, Gutierrez JL. Thiamin. Adv Nutr. 2017 Mar 15;8(2):395-397.
[3] Chan AHY, Ho TCS, Irfan R, et al. Design of thiamine analogues for inhibition of thiamine diphosphate (ThDP)-dependent enzymes: Systematic investigation through Scaffold-Hopping and C2-Functionalisation. Bioorg Chem. 2023 Sep;138:106602.
[4] Bettendorff L. Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases. Int J Mol Sci. 2023 Jul 10;24(14):11296.
[5] Geng MY, Saito H, Katsuki H. The effects of thiamine and oxythiamine on the survival of cultured brain neurons. Jpn J Pharmacol. 1995 Jul;68(3):349-52.
[6] Ergül M, Taşkıran AŞ. Thiamine Protects Glioblastoma Cells against Glutamate Toxicity by Suppressing Oxidative/Endoplasmic Reticulum Stress. Chem Pharm Bull (Tokyo). 2021;69(9):832-839.
[7] Suzuki K, Yamada K, Fukuhara Y, et al. High-dose thiamine prevents brain lesions and prolongs survival of Slc19a3-deficient mice. PLoS One. 2017 Jun 30;12(6):e0180279.
[8] Mesdaghinia A, Alinejad M, Abed A, et al. Anticonvulsant effects of thiamine on pentylenetetrazole-induced seizure in mice. Nutr Neurosci. 2019 Mar;22(3):165-173.
Thiamine (hydrochloride)是一种水溶性必需微量营养素[1]，Thiamine易透过血脑屏障，是研究能量代谢、神经炎症及衰老相关代谢功能障碍的重要工具化合物[2]。Thiamine经肝脏、肾脏及白细胞中硫胺素二磷酸激酶催化，转化为其活性辅酶形式焦磷酸硫胺素（ThDP）[3]。ThDP作为丙酮酸脱氢酶、α-酮戊二酸脱氢酶及转酮醇酶等多种关键代谢酶的辅酶，参与调控糖酵解、三羧酸循环及磷酸戊糖途径，维持细胞能量稳态。硫胺素缺乏可致乳酸酸中毒、氧化应激及神经细胞损伤[4]。
在体外，Thiamine（30–300μM）处理大鼠胚胎海马神经元72小时，显著促进了高细胞密度培养（1×10⁵/cm²）中海马神经元的存活，100μM时有最加的促进效果[5]。Thiamine（0.25–4mg/mL）预处理C6胶质瘤细胞1小时，随后用谷氨酸（10mM）处理24小时，显著提高细胞存活率，降低氧化应激标志物丙二醛（MDA）水平，同时增加超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平，减少内质网应激标，降低凋亡细胞数量[6]。
在体内，Thiamine（8.50mg/100g）高剂量饮食用于处理SLC19A3基因敲除（Slc19a3 KO）小鼠，在经过2天或3天的限制饮食（0.60mg/100g）后，Thiamine显著延长了小鼠的生存期，并且高剂量Thiamine饮食防止了急性神经退行性病变的发生[7]。Thiamine（200mg/kg）通过腹腔注射给药，用于处理Balb/c雄性小鼠。Thiamine单独慢性给药（每天一次，连续14天）显著提高了戊四氮诱导的惊厥发作的阈值[8]。