Abstract |
Hypertension is a major risk factor for the development of cardiovascular diseases. This study aimed to elucidate whether the natural product mixture No-ap (NA) containing Pine densiflora, Annona muricate, and Monordica charantia, or its single components have inhibitory effects on hypertension-related molecules in Angiotensin II (Ang II)-stimulated H9C2 cells. Individual functional components were isolated and purified from NA using various columns and solvents, and then their structures were analyzed using ESI⁻MS, ¹H-NMR, and 13H-NMR spectra. H9C2 cells were stimulated with 300 nM Ang II for 7 h. NA, telmisartan, ginsenoside, roseoside (Roseo), icariside E4 (IE4), or a combination of two components (Roseo and IE4) were administered to the cells 1 h before Ang II stimulation. The expression and activity of hypertension-related molecules or oxidative molecules were determined using RT-PCR, western blot, and ELISA. Ang II stimulation increased the expression of Ang II receptor 1 (AT1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), tumor growth factor-β (TGF-β) mRNA, and nicotinamide adenine dinucleotide phosphate ( NADPH) oxidase activity and the levels of hydrogen peroxide (H₂O₂) and superoxide anion (•O₂-) and reduced anti-oxidant enzyme activity. NA significantly improved the expression or activities of all hypertension-related molecules altered in Ang II-stimulated cells. Roseo or IE4 pretreatment either decreased or increased the expression or activities of all hypertension-related molecules similar to NA, but to a lesser extent. The pretreatment with a combination of Roseo and IE4 (1:1) either decreased or increased the expression of all hypertension-related molecules, compared to each single component, revealing a synergistic action of the two compounds. Thus, the combination of single components could exert promising anti-hypertensive effects similar to NA, which should be examined in future animal and clinical studies.
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Authors | Eun Young Hong, Tae Yang Kim, Gwan Ui Hong, Hanna Kang, Jung-Yun Lee, Jae Yeo Park, Se-Chan Kim, Young Ho Kim, Myung-Hee Chung, Young-In Kwon, Jai Youl Ro |
Journal | Molecules (Basel, Switzerland)
(Molecules)
Vol. 24
Issue 3
(Jan 23 2019)
ISSN: 1420-3049 [Electronic] Switzerland |
PMID | 30678135
(Publication Type: Journal Article)
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Chemical References |
- Agtr1a protein, rat
- Biological Products
- Ccl2 protein, rat
- Chemokine CCL2
- Glucosides
- Glycosides
- Lignans
- Norisoprenoids
- RNA, Messenger
- Receptor, Angiotensin, Type 1
- Transforming Growth Factor beta1
- Tumor Necrosis Factor-alpha
- icariside E4
- roseoside
- Angiotensin II
- Hydrogen Peroxide
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Topics |
- Angiotensin II
(metabolism, pharmacology)
- Animals
- Biological Products
(chemistry, pharmacology)
- Chemokine CCL2
(genetics)
- Gene Expression Regulation
(drug effects)
- Glucosides
(chemistry, pharmacology)
- Glycosides
(chemistry, pharmacology)
- Humans
- Hydrogen Peroxide
(chemistry)
- Lignans
(chemistry, pharmacology)
- Norisoprenoids
(chemistry, pharmacology)
- Oxidation-Reduction
(drug effects)
- Oxidative Stress
(drug effects)
- RNA, Messenger
- Rats
- Receptor, Angiotensin, Type 1
(genetics)
- Transforming Growth Factor beta1
(genetics)
- Tumor Necrosis Factor-alpha
(genetics)
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