Effect of Jaceosidin on inflammatory response in gestational diabetes mellitus rats by regulating SDF-1α/CXCR4 signaling pathway

doi:10.11958/20231228

Abstract

Abstract:

Objective To investigate the effect of Jaceosidin on inflammatory response in gestational diabetes mellitus (GDM) rats and its mechanism. Methods The GDM rat model was established by intraperitoneal injection of streptozotocin into pregnant rats. The successfully established rats were separated into the GDM group, the Jaceosidin L, M, H groups and the Jaceosidin+CTCE-0214 [stromal cell-derived factor-1α (SDF-1α)/C-X-C chemokine receptor 4 (CXCR4) activator] group, with 10 rats in each group. Meantime, 10 healthy pregnant rats were taken as the control group. The Jaceosidin L, M and H groups were gavaged with 2, 3 and 4 mg/kg Jaceosidin, respectively. The Jaceosidin+CTCE-0214 group was intraperitoneally injected with 10 mg/kg CTCE-0214 and gavaged with 4 mg/kg Jaceosidin. The control group and the GDM group were given equal amounts of physiological saline. The fasting blood glucose, fasting insulin and insulin resistance index were compared between each group of rats. Enzyme-linked immunosorbent assay was applied to detect levels of IL-1β and TNF-α in placental tissue. HE staining was applied to observe pathological changes of placental tissue. Apoptosis of placental tissue was detected by TUNEL. Western blot assay was applied to detect levels of SDF-1α/CXCR4 pathway related proteins in placental tissue. Results The intervention of different doses of Jaceosidin in GDM rats reduced levels of fasting blood glucose, fasting insulin, insulin resistance index and proinflammatory cytokines, improved the placental injury and apoptosis of GDM rats, and inhibited the activation of SDF-1α/CXCR4 signaling pathway in a dose-dependent manner (P<0.05). SDF-1α/CXCR4 activator combined Jaceosidin could inhibit the above effects of Jaceosidin. Conclusion Jaceosidin can reduce inflammation and insulin resistance in GDM rats by suppressing the activation of SDF-1 α/CXCR4 signaling pathway.

Key words: diabetes, gestational, disease models, animal, chemokine CXCL12, inflammation, Jaceosidin, chemokine ligand 4

CLC Number:

R587.1，R714.256

Figures/Tables 6

References 22

[1]	SWEETING A, WONG J, MURPHY H R, et al. A clinical update on gestational diabetes mellitus[J]. Endocr Rev, 2022, 43(5):763-793. doi:10.1210/endrev/bnac003.
[2]	ZHANG J, CHI H, XIAO H, et al. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) single nucleotide polymorphisms (SNPs),inflammation and metabolism in gestational diabetes mellitus in inner mongolia[J]. Med Sci Monit, 2017, 23(1):4149-4157. doi:10.12659/msm.903565.
[3]	CHEN X, WU J, FU X, et al. Fructus mori polysaccharide alleviates diabetic symptoms by regulating intestinal microbiota and intestinal barrier against TLR4/NF-κB pathway[J]. Int J Biol Macromol, 2023, 2023(1):126038-126049. doi:10.1016/j.ijbiomac.2023.126038.
[4]	QIAO L, WATTEZ J S, LEE S, et al. Adiponectin deficiency impairs maternal metabolic adaptation to pregnancy in mice[J]. Diabetes, 2017, 66(5):1126-1135. doi:10.2337/db16-1096.
[5]	黄春荟, 杜世拔, 翟锐锐. 加味四妙丸介导SDF-1/CXCR4信号通路对痛风性关节炎的治疗作用[J]. 中国老年学杂志, 2023, 43(7):1707-1710.
	HUANG C H, DU S B, ZHAI R R. Therapeutic effect of modified Simiao Pill mediated SDF-1/CXCR4 signaling pathway on gouty arthritis[J]. Chinese Journal of Gerontology, 2019, 43(7):1707-1710. doi:10.3969/j.issn.1005-9202.2023.07.045.
[6]	GLAWE J D, MIJALIS E M, DAVIS W C, et al. SDF-1-CXCR4 differentially regulates autoimmune diabetogenic T cell adhesion through ROBO1-SLIT2 interactions in mice[J]. Diabetologia, 2013, 56(10):2222-2230. doi:10.1007/s00125-013-2978-x.
[7]	王海艳, 秦海霞, 李淑娟. 棕矢车菊素诱导人宫颈癌Hela细胞G₂/M期停滞的机制研究[J]. 现代肿瘤医学, 2022, 30(18):3264-3269.
	WANG H Y, QIN H X, LI S J. Study on mechanism of G_2/M phase stagnation induced by cyanidin in human Cervical cancer Hela cells[J]. Modern Oncology Medicine, 2022, 30(18):3264-3269. doi:10.3969/j.issn.1672-4992.2022.18.002.
[8]	PARK E, HONG K, KWON B M, et al. Jaceosidin ameliorates insulin resistance and kidney dysfunction by enhancing insulin receptor signaling and the antioxidant defense system in type 2 diabetic mice[J]. J Med Food, 2020, 23(10):1083-1092. doi:10.1089/jmf.2020.4739.
[9]	曹小蝶, 马冲, 陈立. 棕矢车菊素的药理作用及其作用机制的研究进展[J]. 现代药物与临床, 2022, 37(11):2653-2658.
	CAO X D, MA C, CHEN L. Research progress on the pharmacological action and mechanism of cyanidin[J]. Modern Medicine and Clinic, 2022, 37(11):2653-2658.
[10]	陈蓓, 连李斌. 丹皮酚抑制Notch1/Jagged1信号通路对妊娠糖尿病大鼠糖代谢紊乱的改善作用[J]. 河北医药, 2023, 45(11):1632-1636.
	CHEN B, LIAN L B. Effects of paeonol inhibition of Notch1/Jagged1 signaling pathway on glucose metabolism disorder in gestational diabetes mellitus rats[J]. Journal of Hebei Medicine, 2023, 45(11):1632-1636. doi:10.3969/j.issn.1002-7386.2023.11.006.
[11]	OUYANG Z, LI W, MENG Q, et al. A natural compound jaceosidin ameliorates endoplasmic reticulum stress and insulin resistance via upregulation of SERCA2b[J]. Biomed Pharmacother, 2017, 89(1):1286-1296. doi:10.1016/j.biopha.2017.03.023.
[12]	潘芸, 杨阳, 刘甜, 等. 大黄素调节SDF-1α/CXCR4轴抑制模型大鼠增生性瘢痕的作用[J]. 中国皮肤性病学杂志, 2023, 37(11):1237-1245.
	PAN Y, YANG Y, LIU T, et al. Emodin modulates SDF-1α/CXCR4 axis to inhibit hypertrophic scar in model rats[J]. Chinese Journal of Dermatology and Venereology, 2023, 37(11):1237-1245. doi:10.13735/j.cjdv.1001-7089.202303148.
[13]	CHOUDHURY A A, DEVI RAJESWARI V. Gestational diabetes mellitus - A metabolic and reproductive disorder[J]. Biomed Pharmacother, 2021, 143(1):112183-112196. doi:10.1016/j.biopha.2021.112183.
[14]	VISIEDO F, VÁZQUEZ-FONSECA L, ÁBALOS-MARTÍNEZ J, et al. Maternal elevated inflammation impairs placental fatty acids β- oxidation in women with gestational diabetes mellitus[J]. Front Endocrinol(Lausanne), 2023, 14(1):1146574-1146585. doi:10.3389/fendo.2023.1146574.
[15]	LIZÁRRAGA D, GARCÍA-GASCA A. The placenta as a target of epigenetic alterations in women with gestational diabetes mellitus and potential implications for the offspring[J]. Epigenomes, 2021, 5(2):13-22. doi:10.3390/epigenomes5020013.
[16]	田亚静, 杨雪, 汪静, 等. 芒柄花素对妊娠期糖尿病大鼠氧化应激损伤的影响[J]. 天津医药, 2023, 51(7):734-738.
	TIAN Y J, YANG X, WANG J, et al. Influence of formononetin on oxidative stress injury in gestational diabetes mellitus rats[J]. Tianjin Med J, 2023, 51(7):734-738. doi: 10.11958/20221450.
[17]	NAGEEN B, RASUL A, HUSSAIN G, et al. Jaceosidin:a natural flavone with versatile pharmacological and biological activities[J]. Curr Pharm Des, 2021, 27(4):456-466. doi:10.2174/1381612826666200429095101.
[18]	CHEN J, CHEN N, ZHANG T, et al. Rongjin Niantong Fang ameliorates cartilage degeneration by regulating the SDF-1/CXCR4-p38MAPK signalling pathway[J]. Pharm Biol, 2022, 60(1):2253-2265. doi:10.1080/13880209.2022.2143533.
[19]	CHATTERJEE T, LEWIS T L, ARORA I, et al. Sex-based disparities in leukocyte migration and activation in response to inhalation lung injury:Role of SDF-1/CXCR4 signaling[J]. Cells, 2023, 12(13):1719-1730. doi:10.3390/cells12131719.
[20]	王雷, 余德涛, 邢祯全. 依托考昔抑制SDF-1/CXCR4信号通路影响骨关节炎软骨细胞增殖、凋亡及炎性因子表达[J]. 现代免疫学, 2021, 41(6):468-472.
	WANG L, YU D T, XING Z Q. Etocoxib inhibits SDF-1/CXCR4 signaling pathway and Influences proliferation,apoptosis and expression of inflammatory factors of chondrocytes in osteoarthritis[J]. Modern Immunology, 2021, 41(6):468-472.
[21]	DARAKHSHAN S, FATEHI A, HASSANSHAHI G, et al. Serum concentration of angiogenic(CXCL1,CXCL12) and angiostasis (CXCL9,CXCL10) CXC chemokines are differentially altered in normal and gestational diabetes mellitus associated pregnancies[J]. J Diabetes Metab Disord, 2019, 18(2):371-378. doi:10.1007/s40200-019-00421-2.
[22]	LIU H, LIU A, KAMINGA A C, et al. Chemokines in gestational diabetes mellitus[J]. Front Immunol, 2022, 13:705852. doi:10.3389/fimmu.2022.705852.

组别	空腹血糖/ （mmol/L）	空腹胰岛素/ （mIU/L）	胰岛素抵抗指数
对照组	7.41±0.89	4.14±0.53	1.36±0.15
GDM组	16.45±1.02^a	13.56±1.54^a	9.91±1.02^a
棕矢车菊素-L组	14.33±1.55^b	10.85±1.11^b	6.91±0.74^b
棕矢车菊素-M组	11.18±1.29^bc	8.65±0.94^bc	4.29±0.45^bc
棕矢车菊素-H组	9.16±0.94^bcd	6.34±0.66^bcd	2.58±0.28^bcd
棕矢车菊素+ CTCE-0214组	15.11±1.66^e	11.32±1.26^e	7.12±0.81^e
F	80.846^＊＊	106.534^＊＊	240.593^＊＊

组别	空腹血糖/ （mmol/L）	空腹胰岛素/ （mIU/L）	胰岛素抵抗指数
对照组	7.41±0.89	4.14±0.53	1.36±0.15
GDM组	16.45±1.02^a	13.56±1.54^a	9.91±1.02^a
棕矢车菊素-L组	14.33±1.55^b	10.85±1.11^b	6.91±0.74^b
棕矢车菊素-M组	11.18±1.29^bc	8.65±0.94^bc	4.29±0.45^bc
棕矢车菊素-H组	9.16±0.94^bcd	6.34±0.66^bcd	2.58±0.28^bcd
棕矢车菊素+ CTCE-0214组	15.11±1.66^e	11.32±1.26^e	7.12±0.81^e
F	80.846^＊＊	106.534^＊＊	240.593^＊＊

组别	IL-1β/（ng/L）	TNF-α/（ng/L）	凋亡率/%
对照组	23.41±2.53	34.15±3.26	1.26±0.13
GDM组	66.45±6.94^a	96.55±10.14^a	13.52±1.42^a
棕矢车菊素-L组	54.33±5.61^b	80.84±8.69^b	10.62±1.10^b
棕矢车菊素-M组	42.18±4.28^bc	65.61±6.28^bc	7.61±0.85^bc
棕矢车菊素-H组	34.12±3.18^bcd	46.34±4.58^bcd	4.62±0.62^bcd
棕矢车菊素+ CTCE-0214组	56.41±5.76^e	84.25±8.64^e	11.32±1.26^e
F	102.559^＊＊	106.091^＊＊	212.626^＊＊

组别	IL-1β/（ng/L）	TNF-α/（ng/L）	凋亡率/%
对照组	23.41±2.53	34.15±3.26	1.26±0.13
GDM组	66.45±6.94^a	96.55±10.14^a	13.52±1.42^a
棕矢车菊素-L组	54.33±5.61^b	80.84±8.69^b	10.62±1.10^b
棕矢车菊素-M组	42.18±4.28^bc	65.61±6.28^bc	7.61±0.85^bc
棕矢车菊素-H组	34.12±3.18^bcd	46.34±4.58^bcd	4.62±0.62^bcd
棕矢车菊素+ CTCE-0214组	56.41±5.76^e	84.25±8.64^e	11.32±1.26^e
F	102.559^＊＊	106.091^＊＊	212.626^＊＊

组别	SDF-1α	CXCR4
对照组	0.34±0.04	0.50±0.05
GDM组	1.48±0.15^a	1.65±0.18^a
棕矢车菊素-L组	1.12±0.13^b	1.26±0.13^b
棕矢车菊素-M组	0.73±0.09^bc	0.99±0.09^bc
棕矢车菊素-H组	0.47±0.06^bcd	0.67±0.07^bcd
棕矢车菊素+CTCE-0214组	1.15±0.12^e	1.30±0.14^e
F	173.952^＊＊	130.277^＊＊