Protective mechanism of total flavonoids from Chrysanthemum morifolium in mice with cardiac hypertrophy based on Notch1 signaling pathway

doi:10.3877/cma.j.issn.1674-6880.2019.05.002

Abstract

Abstract:

Objective

To investigate the protective effect of total flavonoids from Chrysanthemum morifolium in mice with isoprenaline (ISO)-induced cardiac hypertrophy and its mechanism.

Methods

Forty male mice were randomly divided into the control group, total flavonoids group, model group and treatment group, 10 mice in each group. Mice in the total flavonoids group and treatment group were given total flavonoids (100 mg/kg) by gavage for 14 days, and those in the control group and model group were given isotonic NaCl solution by gavage. Mice in the model group and treatment group were subcutaneously injected with ISO (5 mg/kg, 0.5 mL) for 7 consecutive days to establish a mouse model of cardiac hypertrophy on 8 d, and those in the control group and total flavonoids group received the same volume of isotonic NaCl solution by subcutaneous injection. The levels of left ventricular ejection fraction (LVEF), left ventricular short axis fractional shortening (LVFS), left ventricular mass index (LVMI), heart mass index (HMI), and heart weight/tibia length (HW/TL) were calculated. The contents of superoxide dismutase (SOD), malondialdehyde and reactive oxygen species were compared. The mRNA expressions of Collagen-1, Notch1, Hes1, β-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), Nox4 and Nrf2 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results

The levels of LVEF, LVFS, LVMI, HMI, HW/TL, SOD, malondialdehyde and reactive oxygen species among the four groups were significantly different (F = 62.114, 18.814, 59.824, 66.375, 48.362, 59.677, 46.195, 48.257; all P < 0.001). Compared with the control group, the levels of LVEF, LVFS and SOD decreased, and the levels of LVMI, HMI, HW/TL, malondialdehyde and reactive oxygen species increased remarkably in the model group (all P < 0.05). The levels of LVEF [(56 ± 6)% vs. (38 ± 5)%], LVFS [(32 ± 5)% vs. (22 ± 4)%] and SOD were higher, and the levels of LVMI [(4.1 ± 0.4) mg/g vs. (5.8 ± 0.5) mg/g], HMI [(5.3 ± 1.1) mg/g vs. (6.5 ± 0.6) mg/g], HW/TL [(9.8 ± 1.2) mg/mm vs. (12.4 ± 1.3) mg/mm], malondialdehyde and reactive oxygen species were lower in the treatment group than in the model group (all P < 0.05). The mRNA expressions of Collagen-1, Notch1, Hes1, β-MHC, ANP, Nox4 and Nrf2 among the four groups were significantly different (F = 85.372, 43.865, 69.841, 36.358, 23.964, 48.354, 57.781; all P < 0.001). The mRNA expressions of Collagen-1, Notch1, Hes1, β-MHC, ANP and Nox4 obviously up-regulated, and the Nrf2 mRNA expression observably down-regulated in the model group as compared with the control group (all P < 0.05). The mRNA expressions of Collagen-1, Notch1, Hes1, β-MHC, ANP and Nox4 were lower, and the Nrf2 mRNA expression was higher in the treatment group than in the model group (all P < 0.05).

Conclusion

Total flavonoids in Chrysanthemum morifolium can significantly alleviate ISO-induced cardiac hypertrophy, which may be related to the blockade of Notch signaling pathway, reduction of myocardial oxidative stress injury and inhibition of myocardial fibrosis.

Key words: Cardiomyopathy, hypertrophic, Chrysanthemum morifolium, Total flavonoids, Notch1 signaling pathway, Mice

Ke Zhang, Zhiqiang Wu, Wenwei Cai, Shibing Wang. Protective mechanism of total flavonoids from Chrysanthemum morifolium in mice with cardiac hypertrophy based on Notch1 signaling pathway[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2019, 12(05): 295-300.

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Figures/Tables 5

References 20

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组别	例数	LVEF	LVFS
对照组	10	68 ± 4	36 ± 5
总黄酮组	10	66 ± 3	36 ± 6
模型组	10	38 ± 5^a	22 ± 4^a
干预组	10	56 ± 6^b	32 ± 5^b
F值	?	62.114	18.814
P值	?	< 0.001	< 0.001

组别	例数	LVEF	LVFS
对照组	10	68 ± 4	36 ± 5
总黄酮组	10	66 ± 3	36 ± 6
模型组	10	38 ± 5^a	22 ± 4^a
干预组	10	56 ± 6^b	32 ± 5^b
F值	?	62.114	18.814
P值	?	< 0.001	< 0.001

组别	例数	LVMI（mg/g）	HMI（mg/g）	HW/TL（mg/mm）
对照组	10	2.4 ± 0.3	4.1 ± 0.3	5.1 ± 1.2
总黄酮组	10	2.6 ± 1.2	4.0 ± 0.3	5.2 ± 1.1
模型组	10	5.8 ± 0.5^a	6.5 ± 0.6^a	12.4 ± 1.3^a
干预组	10	4.1 ± 0.4^b	5.3 ± 1.1^b	9.8 ± 1.2^b
F值	?	59.824	66.375	48.362
P值	?	< 0.001	< 0.001	< 0.001

组别	例数	LVMI（mg/g）	HMI（mg/g）	HW/TL（mg/mm）
对照组	10	2.4 ± 0.3	4.1 ± 0.3	5.1 ± 1.2
总黄酮组	10	2.6 ± 1.2	4.0 ± 0.3	5.2 ± 1.1
模型组	10	5.8 ± 0.5^a	6.5 ± 0.6^a	12.4 ± 1.3^a
干预组	10	4.1 ± 0.4^b	5.3 ± 1.1^b	9.8 ± 1.2^b
F值	?	59.824	66.375	48.362
P值	?	< 0.001	< 0.001	< 0.001

组别	例数	Collagen-1 mRNA	Notch1 mRNA	Hes1 mRNA	β-MHC mRNA	ANP mRNA
对照组	10	1.00 ± 0.04	1.00 ± 0.03	1.00 ± 0.03	1.00 ± 0.03	1.00 ± 0.03
总黄酮组	10	1.10 ± 0.23	1.05 ± 0.21	0.95 ± 0.14	1.10 ± 0.14	1.30 ± 0.13
模型组	10	9.90 ± 0.45^a	11.20 ± 0.56^a	8.80 ± 0.69^a	7.30 ± 0.67^a	6.40 ± 0.46^a
干预组	10	4.30 ± 0.66^b	5.60 ± 0.48^b	4.50 ± 0.47^b	2.60 ± 0.41^b	2.30 ± 0.34^b
F值	?	85.372	43.865	69.841	36.358	23.964
P值	?	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

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