Qingda granules attenuate hypertensive cardiac remodeling and inflammation in spontaneously hypertensive rats

Wu, Xiangyan; Shen, Aling; Bao, Liya; Lin, Xiaoying; Huai, Wang; Chen, Youqin; Cai, Qingsheng; Lin, Shan; Zhou, Xueling; Lu, Yan; Peng, Meizhong; Chen, Daxin; Chu, Jianfeng; Peng, Jun

doi:10.1016/j.biopha.2020.110367

Cited by 17 publications

(14 citation statements)

References 32 publications

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“…QDG has been proven to lower blood pressure and restore the cardiac function of hypertensive rats ( Wu et al, 2020 ). In this study, using the AngII-induced mice model, we found that various concentrations of QDG treatment lowered the blood pressure, including SBP, DBP, and MAP of hypertensive mice, which provided novel evidence for the anti-hypertensive effect of QDG.…”

Section: Discussionmentioning

confidence: 99%

“…We also have shown that QDG attenuated elevated hypertension and inhibited the proliferation of vascular smooth muscle cells (VSMCs) by suppressing MAPK signaling pathway in AngII-treated mice (Yu et al, 2020). In addition, QDG alleviated the hypertensive cardiac inflammatory infiltrates and cardiac hypertrophy and remodeling in hypertensive rats or mice model (Wu et al, 2020;Yu et al, 2020). However, the effect and precise mechanism of QDG on hypertensive vascular dysfunction remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Qingda Granule Attenuates Angiotensin II-Induced Blood Pressure and Inhibits Ca2+/ERK Signaling Pathway

Cheng

Shen

et al. 2021

Front. Pharmacol.

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Objective: As a well-known traditional Chinese medicine formula prescribed by academician Ke-ji Chen, Qingda granule (QDG) lowered the blood pressure of spontaneously hypertensive rats and attenuated hypertensive cardiac remodeling and inflammation. However, its functional role and underlying mechanisms on hypertensive vascular function remain largely unclear. This study aims to assess the effects of QDG treatment on Angiotensin II- (AngII-) induced hypertension and vascular function and explore its underlying mechanisms both in vitro and in vivo.Methods: In an in vivo study, 25 male C57BL/6 mice were randomly divided into five groups, including Control, AngII, AngII + QDG-L, AngII + QDG-M, and AngII + QDG-H groups (n = 5 for each group). Mice in AngII and AngII + QDG-L/-M/-H groups were infused with AngII (500 ng/kg/min), while in the Control group, they were infused with saline. Mice in AngII + QDG were intragastrically given different concentrations of QDG (0.5725, 1.145, or 2.29 g/kg/day), while in Control and AngII groups, they were intragastrically given equal volumes of double distilled water for 2 weeks. Blood pressure was determined at 0, 1, and 2 weeks of treatment. Ultrasound was used to detect the pulse wave velocity (PWV) and HE staining to detect the pathological change of the abdominal aorta. RNA sequencing (RNA-seq) was performed to identify the differentially expressed transcripts (DETs) and related signaling pathways. IHC was used to detect the expression of p-ERK in the abdominal aorta. Primary isolated rat vascular smooth muscle cells (VSMCs) were used to assess the cellular Ca2+ release and activation of the ERK pathway by confocal microscope and western blotting analysis, respectively.Results: QDG treatment significantly alleviated the elevated blood pressure, the PWV, and the thickness of the abdominal aorta in AngII-induced hypertensive mice. RNA-seq and KEGG analyses identified 1,505 DETs and multiple enriched pathways (including vascular contraction and calcium signaling pathway) after QDG treatment. Furthermore, confocal microscope showed that QDG treatment partially attenuated the increase of Ca2+ release with the stimulation of AngII in cultured VSMCs. In addition, IHC and western blotting indicated that QDG treatment also partially alleviated the increase of phospho-ERK levels in abdominal aorta tissues of mice and cultured VSMCs after the infusion or stimulation of AngII.Conclusion: QDG treatment attenuated the elevation of blood pressure, abdominal aorta dysfunction, pathological changes, Ca2+ release, and activation of the ERK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Qingda Granule Attenuates Angiotensin II-Induced Blood Pressure and Inhibits Ca2+/ERK Signaling Pathway

Cheng

Shen

et al. 2021

Front. Pharmacol.

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“…Long-term hypertension leads to multiple target organ damage, including renal damage. Our previous studies demonstrated that QDG exhibits antihypertension and multiple-target-organ protection ( Huang et al, 2019 ; Wu et al, 2020 ; Yu et al, 2020 ; Zhang et al, 2020 ; Chen et al, 2021 ; Cheng et al, 2021 ; Wu et al, 2021 ). However, the therapeutic effects of QDG on hypertensive renal injury remained to be further explored.…”

Section: Discussionmentioning

confidence: 99%

“…( Huang et al, 2019 ; Yu et al, 2020 ; Wu et al, 2021 ). Moreover, QDG treatment significantly alleviated cardiac inflammation, hypertrophy, apoptosis, and fibrosis and suppressed the activation of NF-κB, ROS/PI3K/AKT, and TGF-β1/Smad2/3 pathways ( Cheng et al, 2021 ; Wu et al, 2020 ; Chen et al, 2021 ). In addition, QDG treatment also exhibited neuroprotective effects in both ischemic stroke mice and Ang II-infused mice with brain nerve injury ( Zhang et al, 2020 ; Zhang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Qingda Granule Attenuates Angiotensin II-Induced Renal Apoptosis and Activation of the p53 Pathway

Long¹,

Zhang²,

Wen³

et al. 2022

Front. Pharmacol.

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Background: Qingda granules (QDG) exhibit antihypertension and multiple-target-organ protection. However, the therapeutic potential of QDG on hypertensive renal injury remains unknown. Therefore, the main objective of the current study is to explore the effects and underlying mechanisms of QDG treatment on renal injury in angiotensin (Ang) II-infused mice.Methods and results: Mice were infused with Ang II (500 ng/kg/min) or saline for 4 weeks with subcutaneously implanted osmotic pumps. After infusion, mice in the Ang II + QDG group were intragastrically administrated with QDG daily (1.145 g/kg/day), whereas the control group and Ang II group were intragastrically administrated with the same amount of double-distilled water. Blood pressure of the mice monitored using the CODA™ noninvasive blood pressure system revealed that QDG treatment significantly attenuated elevated blood pressure. Moreover, hematoxylin–eosin staining indicated that QDG treatment ameliorated Ang II-induced renal morphological changes, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilatation. RNA-sequencing (RNA-seq) identified 662 differentially expressed transcripts (DETs) in renal tissues of Ang II-infused mice, which were reversed after QDG treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis based on DETs in both comparisons of Ang II vs. Control and Ang II + QDG vs. Ang II identified multiple enriched pathways, including apoptosis and p53 pathways. Consistently, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and Annexin V staining revealed that QDG treatment significantly attenuated Ang II-induced cell apoptosis in renal tissues and cultured renal tubular epithelial cell lines (NRK-52E). Furthermore, western blot analysis indicated that Ang II infusion significantly upregulated the protein expression of p53, BCL2-associated X (BAX), cle-caspase-9, and cle-caspase-3, while downregulating the protein expression of BCL-2 in renal tissues, which were attenuated after QDG treatment.Conclusion: Collectively, QDG treatment significantly attenuated hypertensive renal injury, partially by attenuating renal apoptosis and suppressing p53 pathways, which might be the underlying mechanisms.

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“…(Gouteng), and Nelumro nucifera Gaertn . (Lianzixin), can reduce the infiltration of macrophages and the activation of proinflammatory cytokines (TNF-α, IL-6) by inhibiting the NF-κB pathway in spontaneously hypertensive rats ( 38 ).…”

Section: Molecular Pathways Involved In Cardiac Remodelingmentioning

confidence: 99%

Cellular and Molecular Mechanism of Traditional Chinese Medicine on Ventricular Remodeling

Zhu

Liang

2021

Front. Cardiovasc. Med.

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Ventricular remodeling is related to the renin-angiotensin-aldosterone system, immune system, and various cytokines involved in inflammation, apoptosis, and cell signal regulation. Accumulated studies have shown that traditional Chinese medicine can significantly inhibit the process of ventricular remodeling, which may be related to the mechanism mentioned above. Here, we conducted a system overview to critically review the cellular and molecular mechanism of traditional Chinese medicine on ventricular remodeling. We mainly searched PubMed for basic research about the anti-ventricular remodeling of traditional Chinese medicine in 5 recent years, and then objectively summarized these researches. We included more than 25 kinds of Chinese herbal medicines including Qi-Li-Qian-Xin, Qi-Shen-Yi-Qi Pill, Xin-Ji-Er-Kang Formula, and Yi-Qi-Wen-Yang Decoction, and found that they can inhibit ventricular remodeling effectively through multi-components and multi-action targets, which are promoting the clinical application of traditional Chinese medicine.

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Qingda granules attenuate hypertensive cardiac remodeling and inflammation in spontaneously hypertensive rats

Cited by 17 publications

References 32 publications

Qingda Granule Attenuates Angiotensin II-Induced Blood Pressure and Inhibits Ca2+/ERK Signaling Pathway

Qingda Granule Attenuates Angiotensin II-Induced Blood Pressure and Inhibits Ca2+/ERK Signaling Pathway

Qingda Granule Attenuates Angiotensin II-Induced Renal Apoptosis and Activation of the p53 Pathway

Cellular and Molecular Mechanism of Traditional Chinese Medicine on Ventricular Remodeling

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