Objective: To investigate whether total glycosides from cornus officinalis (TGCO) can improve cognitive dysfunction caused by hypothyroidism via regulating cholinergic anti-inflammatory pathway (CAP). Methods: Sixty adult male SD rats were randomly divided into model group, blank control group, TGCO low-dose group (3 g/kg·d), TGCO medium-dose group (6 g/kg·d), TGCO high-dose group (12 g/kg·d) and positive control group (Euthyrox). The rat model of hypothyroidism was prepared by intragastric administration of 0.1% propylthiouracil solution for 30 days. After successful modeling, the corresponding doses of TGCO were given to each administration group for 21 days. The learning and cognitive function was tested by Morris water maze. The levels of serum thyroid hormones and related neurotransmitters were measured by ELISA. The expression of inflammatory factors, neurotransmitter synthase and related signaling pathway proteins in the brain were detected by Western blot. Results: Compared with the model group, the escape latency of each TGCO dose group was gradually shortened, the target quadrant residence time and the number of crossing the platform were gradually increased, and the effect of the high dose group was the most significant (P＜0.05). Compared with the model group, the levels of triiodothyronine (T3) and tetraiodothyronine (T4) in the serum of rats in the TGCO high-dose group were increased, and the levels of thyroid stimulating hormone (TSH) were decreased (P＜0.05). At the same time, the levels of acetylcholine (Ach) and dopamine (DA) in the serum of rats in the TGCO high-dose group were increased (P＜0.05), and the level of 5-hydroxytryptamine (5-HT) was decreased (P＜0.05). Compared with the model group, the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in each TGCO dose group were decreased gradually (P＜0.05). The expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) were increased gradually in a dose-dependent manner (P＜0.05). Conclusion: TGCO can effectively improve cognitive dysfunction caused by hypothyroidism, and its mechanism may be related to regulating neurotransmitters, inhibiting inflammatory response and regulating related signaling pathways, which provides a new theoretical basis for clinical treatment.
WANG Jing
,
FANG Gang
. Study on the mechanism of total glycosides from cornus officinalis in improving cognitive dysfunction caused by hypothyroidism[J]. Journal of Baotou Medical College, 2025
, 41(10)
: 22
-27
.
DOI: 10.16833/j.cnki.jbmc.2025.10.005
[1] 官衡, 刘昉. 甲状腺功能减退症影响各系统的机制研究进展[J].中国现代医生, 2024, 62(27): 101-104, 118.
[2] 张涛涛, 苏文秀, 李晓涛, 等. 甲状腺功能减退症焦虑和抑郁及认知障碍机制的研究进展[J].中国临床研究, 2023, 36(11): 1722-1725.
[3] 薛丽萍, 章秋. 合并2型糖尿病的甲状腺疾病的管理[J].中国实用内科杂志, 2021, 41(2): 116-119.
[4] Stasiak M, Lewiński A. New aspects in the pathogenesis and management of subacute thyroiditis[J].Rev Endocr Metab Disord, 2021, 22(4): 1027-1039.
[5] 吴春岚, 王长德, 李红. 红景天苷对甲状腺功能减退模型大鼠抗抑郁作用的疗效与机制研究[J].时珍国医国药, 2024, 35(10): 2369-2373.
[6] Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms[J].CNS Neurosci Ther, 2021, 27(1): 36-47.
[7] de Araujo A, de Lartigue G. Non-canonical cholinergic anti-inflammatory pathway in IBD[J].Nat Rev Gastroenterol Hepatol, 2020, 17(11): 651-652.
[8] Borovikova LV, Ivanova S, Zhang M, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin[J].Nature, 2000, 405(6785): 458-462.
[9] Stakenborg N, Gomez-pinilla PJ, Boeckxstaens GE. Postoperative Ileus: pathophysiology,current therapeutic approaches[J].Handb Exp Pharmacol, 2017, 23939-23957.
[10] Murray K, Reardon C. The cholinergic anti-inflammatory pathway revisited[J].Neurogastroenterol Motil, 2018, 30(3): 10.
[11] Levitsky J. Probiotics:application of "healthy" bacteria to liver transplant recipients[J].Hepatology, 2006, 44(2): 507-510.
[12] Sharon G, Sampson TR, Geschwind DH, et al. The central nervous system and the gut microbiome[J].Cell, 2016, 167(4): 915-932.
[13] Ibáez-Sandoval O, Xenias HS, Tepper JM, et al. Dopaminergic and cholinergic modulation of striatal tyrosine hydroxylase interneurons[J].Neuropharmacology, 2015, 95: 468-476.
[14] Richardson JS, Lamprecht F, Kazic T, et al. Reduction in brain tyrosine hydroxylase activity following acetylcholinesterase blockade in rats[J].Can J Physiol Pharmacol, 1976, 54(5): 774-778.
[15] 王芬. 成年期甲状腺功能减退对SD大鼠旷场行为及脑前额叶内乙酰胆碱含量的影响[D].安徽:安徽医科大学, 2013.
[16] 侯祥平, 匡威, 陈克芳, 等. 山茱萸总苷及多糖对心肌梗死大鼠心肌炎症因子IL-6及IL-10的影响[J].中国中医药科技, 2016, 23(5): 548-550.
[17] 孙志明, 门秀丽. 山茱萸总苷的提取工艺及药理研究[J].科技视界, 2015,(1): 368-369.
[18] Gao X, Liu Y, An Z, et al. Active components and pharmacological effects of cornus officinalis: literature review[J].Front Pharmacol, 2021, 12633447.
[19] 侯祥平, 匡威, 陈克芳, 等. 山茱萸总苷及多糖对心肌梗死大鼠心肌炎症因子IL-6及IL-10的影响[J].中国中医药科技, 2016, 23(5): 548-550.
[20] 孙志明, 李小娜, 陈苹苹, 等. 山茱萸总苷分散片的处方工艺研究[J].中国药房, 2011, 22(3): 219-221.
[21] 夏剑, 陈群, 黄伟. 夏枯草水提液对甲状腺功能减退大鼠认知功能及PGC-1α/FNDC5/BDNF通路的影响[J].中国药师, 2021, 24(8): 457-463.
[22] 郝颖琪. 益生菌联合益生元对临床甲减合并小肠细菌过度生长患者的疗效评价[D].河南: 郑州大学, 2023.
[23] 蒋一凡, 张新, 王世蓉. 左甲状腺素对甲状腺功能减退症患者甲状腺相关激素水平及血管内皮功能的影响[J].中国药物经济学, 2022, 17(12): 54-57.
[24] 刘斌, 吴孟海, 张晋霞, 等. 神经节苷脂对人脂肪基质细胞分化为神经细胞的神经递质关键酶TH、CHAT、GAD的影响[J].中国药房, 2007, (19): 1459-1461.
