Effects of sennoside A on atherosclerotic plaque formation and expression of 5-hydroxytryptamine signal moleculars in mice with diabetes mellitus type 2

doi:10.3969/j.issn.1674-8115.2024.08.008

Abstract

Abstract:

Objective ·To investigate the effects of sennoside A (SA) on the formation of atherosclerotic plaque and the expression of 5-hydroxytryptamine (5-HT) and its receptor in mice with diabetes mellitus type 2 (T2DM). Methods ·Twelve mice with knocked-out apolipoprotein E gene were randomly divided into two groups, namely the model group and the model+SA group, with six mice in each group. Six C57BL/6J mice with the same genetic background were used as the control group. The control group was fed with normal diet, and the model group and the model+SA group were given intraperitoneal injection of streptozotocin (30 mg/kg) daily on the basis of high-fat diet to establish a model of T2DM. The model+SA group was given SA daily by gavage for 8 weeks, and the control group and the model group were given equal volume of distillation-distillation H₂O by gavage. The body weight, fasting blood glucose (FBG) and 2-h postprandial blood glucose of mice were compared before and after modeling and treatment. The area of aortic plaque was observed by oil red O staining and hematoxylin-eosin (H-E) staining, and the level of 5-HT in serum and thoracic aorta was measured by ELISA kit. Western blotting was used to detect the expression of 5-hydroxytryptamine receptor 2B (HTR2B) and serotonin transporter (SERT) in thoracic aorta of mice. Results ·Compared with the control group, the body weight, FBG and 2-h postprandial blood glucose in the model group increased, and glucose metabolism was disordered. The expression of HTR2B and SERT protein in thoracic aorta increased, while the concentration of 5-HT in thoracic aorta decreased. The serum 5-HT concentration increased (all P<0.05). After treatment with SA, compared with the model group, the body weight of the model+SA group decreased, and FBG and 2-h postprandial blood glucose were significantly improved. The area of aortic plaque and the expression of HTR2B and SERT protein in thoracic aorta significantly decreased, while the concentration of 5-HT increased. The serum 5-HT concentration decreased (all P<0.05). Conclusion ·SA can reduce atherosclerotic plaque area in T2DM mice, which may be related to lowering blood glucose and inhibiting the expression of 5-HT and its receptor.

Key words: sennoside A (SA), diabetes mellitus type 2 (T2DM), atherosclerosis, 5-hydroxytryptamine (5-HT), 5-hydroxytryptamine receptor 2B (HTR2B)

CLC Number:

R587.1

LIU Meizhi, WANG Ziyang, JIANG Yaning, MI Meng, SUN Yongning. Effects of sennoside A on atherosclerotic plaque formation and expression of 5-hydroxytryptamine signal moleculars in mice with diabetes mellitus type 2[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(8): 991-998.

Figures/Tables 7

TrendMD

References 35

1	Chinese Diabetes Society. 中国2型糖尿病防治指南 (2020年版) (上)[J]. 中国实用内科杂志, 2021, 41(8): 668-695.
	Chinese Diabetes Society. Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition) (Part 1)[J]. Chinese Journal of Practical Internal Medicine, 2021, 41(8): 668-695.
2	MOSENZON O, ALGUWAIHES A, LEON J L A, et al. CAPTURE: a multinational, cross-sectional study of cardiovascular disease prevalence in adults with type 2 diabetes across 13 countries[J]. Cardiovasc Diabetol, 2021, 20(1): 154.
3	WONG N D, SATTAR N. Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention[J]. Nat Rev Cardiol, 2023, 20(10): 685-695.
4	YAO C Y, WANG Z Y, JIANG H Y, et al. Ganoderma lucidum promotes sleep through a gut microbiota-dependent and serotonin-involved pathway in mice[J]. Sci Rep, 2021, 11(1): 13660.
5	YOUNG R L, LUMSDEN A L, MARTIN A M, et al. Augmented capacity for peripheral serotonin release in human obesity[J]. Int J Obes, 2018, 42(11): 1880-1889.
6	IMAMDIN A, VAN DER VORST E P C. Exploring the role of serotonin as an immune modulatory component in cardiovascular diseases[J]. Int J Mol Sci, 2023, 24(2): 1549.
7	金霄, 吴敏. 动脉粥样硬化从“伏毒”论治[J]. 辽宁中医杂志, 2024, 51(6): 39-42.
	JIN X, WU M. Treatment of atherosclerosis from "Fudu"[J]. Liaoning Journal of Traditional Chinese Medicine, 2024, 51(6): 39-42.
8	谭明义, 陈根成, 唐纯志. 大黄胶囊预防脑梗塞并发应激性胃溃疡的实验研究[J]. 广州中医药大学学报, 2001, 18(2): 149-151.
	TAN M Y, CHEN G C, TANG C Z. Preventive effects of Radix et Rhizoma Rhei Granule on the occurrence of complicated stress ulcer of stomach in rats after cerebral infarction[J]. Journal of Guangzhou University of Traditional Chinese Medicine, 2001, 18(2): 149-151.
9	宋少伟, 路瑷雯, 董燕平, 等. 大黄䗪虫丸防治动脉粥样硬化的作用机制及临床研究进展[J]. 现代中西医结合杂志, 2022, 31(24): 3495-3499.
	SONG S W, LU A W, DONG Y P, et al. The mechanism and clinical research progress of Dahuang Zhechong pills in the prevention and treatment of atherosclerosis[J]. Modern Journal of Integrated Traditional Chinese and Western Medicine, 2022, 31(24): 3495-3499.
10	MA L, CAO X Y, YE X T, et al. Sennoside A induces GLP-1 secretion through activation of the ERK1/2 pathway in L-cells[J]. Diabetes Metab Syndr Obes, 2020, 13: 1407-1415.
11	朱红. 番泻苷A通过抑制DNMT1介导的PTEN高甲基化改善四氯化碳诱导的小鼠肝纤维化[D]. 合肥: 安徽医科大学, 2021.
	ZHU H. Protective effects and mechanisms of sennoside A on CCl₄-induced hepatic fibrosis in mice[D]. Hefei: Anhui Medical University, 2021.
12	LE J M, FU Y, HAN Q Q, et al. Transcriptome analysis of the inhibitory effect of sennoside A on the metastasis of hepatocellular carcinoma cells[J]. Front Pharmacol, 2020, 11: 566099.
13	周吉, 王海燕, 王子晨, 等. 基于“脉络学说”和“瘀血理论”探讨糖尿病大血管病变氧化应激机制[J]. 河北中医, 2024, 46(3): 485-488, 492.
	ZHOU J, WANG H Y, WANG Z C, et al. To explore the mechanism of oxidative stress in diabetic macroangiopathy based on "vein theory" and "blood stasis theory"[J]. Hebei Journal of Traditional Chinese Medicine, 2024, 46(3): 485-488, 492.
14	姚建莉, 梁永林, 任梦函, 等. 大黄糖络丸通过调控PI3K-Akt/NF-κB信号通路减轻糖尿病大鼠大血管炎症反应[J]. 中国病理生理杂志, 2024, 40(4): 646-652.
	YAO J L, LIANG Y L, REN M H, et al. Rhubarb sugar pills attenuate inflammatory response in large blood vessels of diabetic rats by regulating PI3K-Akt/NF-κB signaling pathway[J]. Chinese Journal of Pathophysiology, 2024, 40(4): 646-652.
15	HUANG H H, LIAO D, DONG Y, et al. Effect of quercetin supplementation on plasma lipid profiles, blood pressure, and glucose levels: a systematic review and meta-analysis[J]. Nutr Rev, 2020, 78(8): 615-626.
16	刘亚洲, 姜静雨, 拉毛才旦, 等. 大黄的降血脂生物活性成分及作用机制研究进展[J]. 食品安全质量检测学报, 2023, 14(11): 272-282.
	LIU Y Z, JIANG J Y, LAMAO C D, et al. Research progress on the hypolipidemic bioactive components andmechanism of action of Rheum[J]. Journal of Food Safety & Quality, 2023, 14(11): 272-282.
17	王静, 李玉婷, 刘大伟, 等. 大黄蒽醌类主要有效成分抗肾纤维化作用机制的研究进展[J]. 中医研究, 2023, 36(10): 92-96.
	WANG J, LI Y T, LIU D W, et al. Research progress on the anti-renal fibrosis mechanism of the main active components of anthraquinones in Radix et Rhizoma Rhei[J]. Traditional Chinese Medicinal Research, 2023, 36(10): 92-96.
18	WEI Z H, SHEN P L, CHENG P, et al. Gut bacteria selectively altered by sennoside A alleviate type 2 diabetes and obesity traits[J]. Oxid Med Cell Longev, 2020, 2020: 2375676.
19	LE J M, ZHANG X Y, JIA W P, et al. Regulation of microbiota-GLP1 axis by sennoside A in diet-induced obese mice[J]. Acta Pharm Sin B, 2019, 9(4): 758-768.
20	GOJANI E G, WANG B, LI D P, et al. The impact of psilocybin on high glucose/lipid-induced changes in INS-1 cell viability and dedifferentiation[J]. Genes, 2024, 15(2): 183.
21	ASUAJE PFEIFER M, LIEBMANN M, BEUERLE T, et al. Role of serotonin (5-HT) in GDM prediction considering islet and liver interplay in prediabetic mice during gestation[J]. Int J Mol Sci, 2022, 23(12): 6434.
22	GEORGESCU T, LYONS D, HEISLER L K. Role of serotonin in body weight, insulin secretion and glycaemic control[J]. J Neuroendocrinol, 2021, 33(4): e12960.
23	SANTOS A P, COUTO C F, PEREIRA S S, et al. Is serotonin the missing link between COVID-19 course of severity in patients with diabetes and obesity?[J]. Neuroendocrinology, 2022, 112(11): 1039-1045.
24	CHOI W G, CHOI W, OH T J, et al. Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance[J]. J Clin Invest, 2021, 131(23): e145331.
25	WU B Y, YE Y, XIE S S, et al. Megakaryocytes mediate hyperglycemia-induced tumor metastasis[J]. Cancer Res, 2021, 81(21): 5506-5522.
26	LI L, ZHOU J W, WANG S, et al. Critical role of peroxisome proliferator-activated receptor α in promoting platelet hyperreactivity and thrombosis under hyperlipidemia[J]. Haematologica, 2022, 107(6): 1358-1373.
27	朱奕霖, 彭婕, 施小凤. 整合素αⅡbβ3在血小板中作用的研究现状[J]. 国际输血及血液学杂志, 2023, 46(1): 26-33.
	ZHU Y L, PENG J, SHI X F. Research status on role of integrinαⅡbβ3 in platelets[J]. International Journal of Blood Transfusion and Hematology, 2023, 46(1): 26-33.
28	RIEDER M, GAUCHEL N, BODE C, et al. Serotonin: a platelet hormone modulating cardiovascular disease[J]. J Thromb Thrombolysis, 2021, 52(1): 42-47.
29	ZHU J S, YANG L, JIA Y F, et al. Pathogenic mechanisms of pulmonary arterial hypertension: homeostasis imbalance of endothelium-derived relaxing and contracting factors[J]. JACC Asia, 2022, 2(7): 787-802.
30	BUGA A M, CIOBANU O, BĂDESCU G M, et al. Up-regulation of serotonin receptor 2B mRNA and protein in the peri-infarcted area of aged rats and stroke patients[J]. Oncotarget, 2016, 7(14): 17415-17430.
31	WENGLÉN C, DEMIREL I, EREMO A G, et al. Targeting serotonin receptor 2B inhibits TGFβ induced differentiation of human vascular smooth muscle cells[J]. Eur J Pharmacol, 2023, 944: 175570.
32	FONG F, XIAN J, DEMER L L, et al. Serotonin receptor type 2B activation augments TNF-α-induced matrix mineralization in murine valvular interstitial cells[J]. J Cell Biochem, 2021, 122(2): 249-258.
33	闻松, 杨长坤, 江平. 5-羟色胺及其受体拮抗剂在心血管疾病中的研究现状[J]. 河北医科大学学报, 2021, 42(12): 1475-1481.
	WEN S, YANG C K, JIANG P. Research status of serotonin and its receptor antagonists in cardiovascular diseases[J]. Journal of Hebei Medical University, 2021, 42(12): 1475-1481.
34	ZHANG Y, CHEN Y B, CHEN G, et al. Upregulation of miR-361-3p suppresses serotonin-induced proliferation in human pulmonary artery smooth muscle cells by targeting SERT[J]. Cell Mol Biol Lett, 2020, 25: 45.
35	MAULER M, HERR N, SCHOENICHEN C, et al. Platelet serotonin aggravates myocardial ischemia/reperfusion injury via neutrophil degranulation[J]. Circulation, 2019, 139(7): 918-931.

Item	Control group (n=6)	Model group (n=6)	Model+SA group (n=6)
Before treatment
FBG/(mmol·L^-1)	4.85±0.55	16.87±3.89^①	18.95±4.59
PBG/(mmol·L^-1)	6.67±0.77	21.53±2.96^①	21.07±2.67
After treatment
FBG/(mmol·L^-1)	4.88±1.11	21.97±5.33^①	16.12±2.05^②
PBG/(mmol·L^-1)	7.07±0.64	25.03±4.29^①	19.60±2.70^③

Item	Control group (n=6)	Model group (n=6)	Model+SA group (n=6)
Before treatment
FBG/(mmol·L^-1)	4.85±0.55	16.87±3.89^①	18.95±4.59
PBG/(mmol·L^-1)	6.67±0.77	21.53±2.96^①	21.07±2.67
After treatment
FBG/(mmol·L^-1)	4.88±1.11	21.97±5.33^①	16.12±2.05^②
PBG/(mmol·L^-1)	7.07±0.64	25.03±4.29^①	19.60±2.70^③

[1]	DU Yage, LU Yanhui, AN Yu, SONG Ying, ZHENG Jie. Research progress in mechanisms of gut microbiota in diabetic cognitive impairment and its targeted intervention [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(4): 494-500.
[2]	SI Chunying, WANG Jianru, LI Xiaohui, WANG Yongxia, GUAN Huaimin. Study on intercellular communication and key genes of smooth muscle cells in human coronary atherosclerosis based on single cell sequencing technology [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(2): 169-182.
[3]	ZHAO Qian, WANG Ying, HAMULATI Xieyire, TUERXUN Gulijiehere, LI Xiaomei, YANG Yining. Correlation analysis between sleep quality and carotid atherosclerosis in low and moderate risk individuals for cardiovascular and cerebrovascular diseases [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(11): 1366-1373.
[4]	DONG Ting, YIN Xiaoqin, LI Yan, LI Pin. Effect of decreased 5⁃hydroxytryptamine synthesis during puberty development on the onset of puberty in female rats [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(3): 307-311.
[5]	Xiaowen ZHANG, Yi WANG, Chan ZHANG, Di ZHANG, Hang YUN, Di HUANG. Effects of Pcsk9 gene interference on high fat-induced nonalcoholic fatty liver disease with atherosclerosis in rats [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2022, 42(2): 150-157.
[6]	CHEN Sheng-nan, SHEN Yan. Effect of asymmetric dimethylarginine on development of atherosclerosis in patients with chronic kidney disease [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2020, 40(8): 1131-1136.
[7]	GE Xiao-qian1, LI Xiao2, ZHAO Hui-lin2, SUN Bei-bei2, XU Jian-rong2, LIU Xiao-sheng2. Predictive value of dynamic contrast-enhanced MRI of original plaque on carotid artery in-stent restenosis [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2020, 40(7): 901-907.
[8]	QIAN Yu-jun1, QIN Chun-xia1, SUN Li-li1, DING Hua-min1, LI Tie-jun1, 2. Screening of the anti-atherogenic drugsusing THP-1-HIF-1α-HER-Luciferase cell model [J]. , 2019, 39(1): 33-.
[9]	GUO Xiao-yu, XUE Yu-chen, HE Bin, XUE Xiao-mei, HONG Ting, YOU Sha-sha. Advances of anti-inflammation therapy targeting ApoB-100 against atherosclerosis [J]. , 2018, 38(9): 1104-.
[10]	GUO Dong-hao, LIU Hui, MIAO Ya, ZHONG Yuan. Relationship between homocysteine in plasma and carotid atherosclerosis in the elderly patients [J]. , 2018, 38(11): 1318-.
[11]	XUE Yu-chen, YOU Sha-sha, CAO Hui-min, HE Bin. Vaccine strategies in prevention and treatment of atherosclerosis#br# [J]. , 2018, 38(1): 108-.
[12]	HUA Xiao-han, LIU Ying-feng, ZENG Hui, ZHAO Jun-gong, ZHAO Jun, LIU Fang, JIA Wei-ping . Indicating value of lower extremity atherosclerotic disease ultrasound screening for cardiovascular diseases in type 2 diabetes patients#br# [J]. , 2017, 37(9): 1220-.
[13]	WANG Jian-ru, LIU Ping . Advances in differences between ApoE ^-/- and LDLR^-/- atherosclerotic model mice#br# [J]. , 2017, 37(7): 1033-.
[14]	YOU Sha-sha, CAO Hui-min, XUE Xiao-mei, HE Bin. Clinical research progress in immunotherapy against atherosclerosis [J]. , 2017, 37(6): 836-.
[15]	ZHA Qing, CAO Li-juan*，WANG Yan-ping, YANG Ke, LIU Yan . Molecular mechanism of oxLDL inducing lipid accumulation and inflammation in macrophages to promot atherosclerosis via TLR4 signaling pathway [J]. , 2017, 37(5): 611-.