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The Therapeutic Approach of Natural Products in Risk Factors of Cardiovascular Disease

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (24 April 2021) | Viewed by 15508

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Dr. Sunoh Kim

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Guest Editor

Central R&D Center, B&Tech Co., Ltd., Gwangju, Republic of Korea
Interests: electroneurophysiology; neuroreceptors; voltage-dependent calcium channels; neurological diseases; cardiovascular disease; neuropharmacology; molecular biology; natural product; Alzheimer’s disease; obesity; hypertension
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Dear Colleagues,

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and there is global concern regarding the alarmingly increasing trend of cardiovascular risk factors. The majority of CVD is caused by metabolic/physiological risk factors that can be controlled, treated or modified, such as hypertension, dyslipidemia, overweight, obesity, and diabetes. Particularly important risk factors contributing to the development of CVD include hypertension and obesity.

Many clinical trials on antihypertensive drugs have confirmed the usefulness of these drugs in regulating blood pressure effectively. Various drugs, such as diuretics, α-blockers, β-blockers, Ca²⁺ channel blockers, ACE inhibitors, angiotensin Ⅱ receptor antagonists, and vasodilators, are used to treat hypertension. However, these drugs are effective but also cause side effects such as dry cough, hyponatremia, impotence, and diabetes.

Studies on the prevention of hypertension have shown that nutritional intervention may reduce the necessary doses and adverse effects of drugs when used in combination with current pharmacological treatments. Approximately 80% of the world’s population uses various herbal medicines because of their low toxicity and better acceptance by the human body. Therefore, natural-product-based approaches are recommended as first-line treatments for the prevention of hypertension in individuals with high–normal blood pressure and as add-on treatments to be used in combination with antihypertensive drugs in patients with hypertension at any stage. Additionally, obesity is a global health problem, with well-documented epidemiological links with the prevalence of CVD. However, the causal links between obesity and CVD are not clear, as clinical studies imply that in advanced disease states, obesity may actually be protective. Therefore, understanding the mechanisms by which adipose tissue affects the cardiovascular system is crucial.

The effects of most natural products on CVD are multiple and complex. Thus, the aim of this Special Issue of IJMS is to focus on research on natural products and CVD risk factors and discuss the state-of-the-art in understanding the link between CVD risk factors such as hypertension and obesity and CVD. In addition, several other morbidities, including novel risk factors of CVD, associated with CVD and submissions dealing with these diseases are welcome.

Topics include but are not limited to the following:

Clinical or preclinical studies investigating natural products in the treatment of CVD;
The role of natural products in the treatment of hypertension;
The use of natural products as lead compounds in drug discovery for the treatment of CVD;
Hypertension control and CVD;
Novel risk factors of CVD;
The relationship between hypertension with other risk factors for CVD;
Obesity and microvascular remodeling;
Obesity and cardiac metabolic dysfunction.

Dr. Sunoh Kim
Guest Editor

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Keywords

Natural products
Phytochemicals
Cardiovascular disease (CVD)
Risk factors of CVD
Hypertension
Obesity
Clinical or preclinical studies

Published Papers (5 papers)

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Research

17 pages, 4623 KiB

Open AccessArticle

Anti-Inflammatory Effect of Allicin Associated with Fibrosis in Pulmonary Arterial Hypertension

by José L. Sánchez-Gloria, Constanza Estefanía Martínez-Olivares, Pedro Rojas-Morales, Rogelio Hernández-Pando, Roxana Carbó, Ivan Rubio-Gayosso, Abraham S. Arellano-Buendía, Karla M. Rada, Fausto Sánchez-Muñoz and Horacio Osorio-Alonso

Int. J. Mol. Sci. 2021, 22(16), 8600; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168600 - 10 Aug 2021

Cited by 16 | Viewed by 3499

Abstract

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling. Recent evidence supports that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Recent studies have shown that garlic extract has protective effects in PAH, but the precise role of allicin, a compound derived from garlic, is unknown. Thus, we used allicin to evaluate its effects on inflammation and fibrosis in PAH. Male Wistar rats were divided into three groups: control (CON), monocrotaline (60 mg/kg) (MCT), and MCT plus allicin (16 mg/kg/oral gavage) (MCT + A). Right ventricle (RV) hypertrophy and pulmonary arterial medial wall thickness were determined. IL-1β, IL-6, TNF-α, NFκB p65, Iκβ, TGF-β, and α-SMA were determined by Western blot analysis. In addition, TNF-α and TGF-β were determined by immunohistochemistry, and miR-21-5p and mRNA expressions of Cd68, Bmpr2, and Smad5 were determined by RT-qPCR. Results: Allicin prevented increases in vessel wall thickness due to TNF-α, IL-6, IL-1β, and Cd68 in the lung. In addition, TGF-β, α-SMA, and fibrosis were lower in the MCT + A group compared with the MCT group. In the RV, allicin prevented increases in TNF-α, IL-6, and TGF-β. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH. Full article

(This article belongs to the Special Issue The Therapeutic Approach of Natural Products in Risk Factors of Cardiovascular Disease)

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13 pages, 2190 KiB

Open AccessArticle

Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

by Ji Hye Yang, Sae Kwang Ku, IL Je Cho, Je Hyeon Lee, Chang-Su Na and Sung Hwan Ki

Int. J. Mol. Sci. 2021, 22(4), 2041; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042041 - 18 Feb 2021

Cited by 9 | Viewed by 2960

Abstract

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway. Full article

(This article belongs to the Special Issue The Therapeutic Approach of Natural Products in Risk Factors of Cardiovascular Disease)

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14 pages, 2332 KiB

Open AccessArticle

Diphlorethohydroxycarmalol Isolated from Ishige okamurae Exerts Vasodilatory Effects via Calcium Signaling and PI3K/Akt/eNOS Pathway

by Yu An Lu, Yunfei Jiang, Hye-Won Yang, Jin Hwang, You-Jin Jeon and Bomi Ryu

Int. J. Mol. Sci. 2021, 22(4), 1610; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041610 - 05 Feb 2021

Cited by 11 | Viewed by 2208

Abstract

Nitric oxide (NO) is released by endothelial cells in the blood vessel wall to enhance vasodilation. Marine polyphenols are known to have protective effects against vascular dysfunction and hypertension. The present study is the first to investigate how diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae affects calcium levels, resulting in enhanced vasodilation. We examined calcium modulation with the well-known receptors, acetylcholine receptor (AchR) and vascular endothelial growth factor 2 (VEGFR2), which are related to NO formation, and further confirmed the vasodilatory effect of DPHC. We confirmed that DPHC stimulated NO production by increasing calcium levels and endothelial nitric oxide synthase (eNOS) expression. DPHC affected AchR and VEGFR2 expression, thereby influencing transient calcium intake. Specific antagonists, atropine and SU5416, were used to verify our findings. Furthermore, based on the results of in vivo experiments, we treated Tg(flk:EGFP) transgenic zebrafish with DPHC to confirm its vasodilatory effect. In conclusion, the present study showed that DPHC modulated calcium transit through AchR and VEGFR2, increasing endothelial-dependent NO production. Thus, DPHC, a natural marine component, can efficiently ameliorate cardiovascular diseases by improving vascular function. Full article

(This article belongs to the Special Issue The Therapeutic Approach of Natural Products in Risk Factors of Cardiovascular Disease)

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13 pages, 1963 KiB

Open AccessArticle

Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice

by Masateru Kondo, Yuki Izawa-Ishizawa, Mitsuhiro Goda, Mayuko Hosooka, Yuu Kagimoto, Naoko Saito, Rie Matsuoka, Yoshito Zamami, Masayuki Chuma, Kenta Yagi, Kenshi Takechi, Koichi Tsuneyama and Keisuke Ishizawa

Int. J. Mol. Sci. 2020, 21(19), 7226; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197226 - 30 Sep 2020

Cited by 13 | Viewed by 3664

Abstract

Atherosclerosis-related acute aortic syndromes, such as aortic aneurysms or aortic dissection are life-threatening diseases. Since they develop suddenly and progress rapidly, the establishment of preventive strategies is urgently needed. Quercetin, a flavonoid abundant in various vegetables and fruits, is suggested to reduce the risk of cardiovascular disease. Therefore, in this study, the preventive effect of quercetin was evaluated using a mouse model of aortic aneurysm and dissection. The model was established by administering angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, to mice to induce hypertension and degeneration of the elastic lamina, which would eventually result in the onset of an aortic aneurysm. Ang II, BAPN, and a nitric oxide synthase inhibitor was administered to induce aortic dissection via endothelial dysfunction. Quercetin (60 mg/kg/day) was administered 2 weeks before inducing aortic diseases by the end of the experiments (8 weeks in the aneurysm model, 6 weeks in the dissection model). It was found to reduce the incidence of aneurysm (from 72 to 45%), dissection (from 17 to 10%), and rupture (from 33 to 15%) in mice. Elastin degradation was ameliorated in the quercetin-treated mice compared to that in the mice without quercetin treatment (degradation score 2.9 ± 0.3 vs 2.2 ± 0.2). Furthermore, quercetin suppressed the expression of vascular cell adhesion molecule-1, macrophage infiltration, and pro-matrix metalloproteinase-9 activity. Our results suggest that quercetin might prevent the onset of atherosclerosis-related acute aortic syndromes through its anti-inflammatory and endothelial cell-protective effects. Full article

(This article belongs to the Special Issue The Therapeutic Approach of Natural Products in Risk Factors of Cardiovascular Disease)

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10 pages, 2417 KiB

Open AccessArticle

Molecular Regulation of α3β4 Nicotinic Acetylcholine Receptors by Lupeol in Cardiovascular System

by Sanung Eom, Chaelin Kim, Hye Duck Yeom, Jaeeun Lee, Shinhui Lee, Yeong-Bin Baek, Jinseong Na, Sang-Ik Park, Gye-Yeop Kim, Chang-Min Lee and Jun-Ho Lee

Int. J. Mol. Sci. 2020, 21(12), 4329; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124329 - 18 Jun 2020

Cited by 6 | Viewed by 2395

Abstract

Cardiovascular disease (CVD) occurs globally and has a high mortality rate. The highest risk factor for developing CVD is high blood pressure. Currently, natural products are emerging for the treatment of hypertension to avoid the side effects of drugs. Among existing natural products, lupeol is known to be effective against hypertension in animal experiments. However, there exists no study regarding the molecular physiological evidence against the effects of lupeol. Consequently, we investigated the interaction of lupeol with α3β4 nicotinic acetylcholine receptors (nAChRs). In this study, we performed a two-electrode voltage-clamp technique to investigate the effect of lupeol on the α3β4 nicotine acetylcholine receptor using the oocytes of Xenopus laevis. Coapplication of acetylcholine and lupeol inhibited the activity of α3β4 nAChRs in a concentration-dependent, voltage-independent, and reversible manner. We also conducted a mutational experiment to investigate the influence of residues of the α3 and β4 subunits on lupeol binding with nAChRs. Double mutants of α3β4 (I37A/N132A), nAChRs significantly attenuated the inhibitory effects of lupeol compared to wild-type α3β4 nAChRs. A characteristic of α3β4 nAChRs is their effect on transmission in the cardiac sympathetic ganglion. Overall, it is hypothesized that lupeol lowers hypertension by mediating its effects on α3β4 nAChRs. The interaction between lupeol and α3β4 nAChRs provides evidence against its effect on hypertension at the molecular-cell level. In conclusion, the inhibitory effect of lupeol is proposed as a novel therapeutic approach involving the antihypertensive targeting of α3β4 nAChRs. Furthermore, it is proposed that the molecular basis of the interaction between lupeol and α3β4 nAChRs would be helpful in cardiac-pharmacology research and therapeutics. Full article

(This article belongs to the Special Issue The Therapeutic Approach of Natural Products in Risk Factors of Cardiovascular Disease)

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