A variety of natural products can protect the cardiovascular system
As the global population ages, chronic age-related diseases such as diabetes, high blood pressure and obesity are on the rise, and these metabolic diseases place a heavy burden on older people and increase the risk of cardiovascular disease. The heart also changes adversely with age, ultimately leading to a range of age-related cardiovascular diseases.
Cardiovascular disease (CVD) is a serious threat to human life and health of common diseases, more common in people over 50 years old, with high incidence, high disability rate and high mortality characteristics. CVD is associated with myocardial fibrosis, decreased autophagy, increased mitochondrial oxidative stress and metabolic imbalance. Therefore, the treatment of the early cause of CVD is still an urgent problem in modern science and medical care.
In recent decades, many studies have highlighted the use of natural products for the prevention and treatment of CVD. Natural products are a large class of chemical entities with a wide range of biological activities, obtained primarily from edible and medicinal plants. Studies have shown that the mechanisms of action of natural product therapy in CVD include: stimulating autophagy, delaying ventricular remodeling, reducing oxidative stress and inflammatory response, inhibiting apoptosis, and protecting the heart muscle against ischemia or ischemia/reperfusion (I/R) injury.
Natural products and their mechanisms of action
Enhanced autophagy
Aging cardiomyocytes rely on autophagy, a lysosomal mediated degradation pathway, to remove potentially toxic protein aggregates and damaged organelles. Loss of autophagy can lead to decreased heart function. Mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, is an important regulator of nutritional homeostasis in mammals. Activation of mTOR inhibits autophagy, while AMP-activated protein kinase (AMPK) acts as a positive regulator of autophagy, primarily by inhibiting the mTOR complex.
Resveratrol is a natural polyphenol found in many plant foods, such as peanuts, cranberries, blueberries, and grapes. It has a variety of potential health benefits, including anti-inflammatory, antioxidant, anti-aging and cardio-protective effects such as enhanced autophagy. Studies have shown that resveratrol can promote autophagy by activating AMPK through a variety of pathways. In addition, resveratrol can induce cell survival by activating the mTOR complex 2(mTORC2) survival pathway.
Berberine is extracted from the roots, rhizome and bark of many medicinal plants and has a variety of pharmacological effects, including anti-inflammatory, antioxidant and autophagy regulation. As an AMPK activator, berberine can induce autophagy by activating AMPK and can also enhance autophagy by inhibiting mTOR.
Curcumin is a spice derived from the ginger family and is often used in curries. Curcumin can induce autophagy by inhibiting PI3K-AKT-mTOR signaling pathway, down-regulating the phosphorylation levels of AKT and mTOR, up-regulating LC3-II, enhancing the expression of BECN1, decreasing the interaction between BECN1 and BCL-2, and enhancing the acetylation of FoxO1.
Inhibits oxidative stress and chronic inflammation
Oxidative stress and chronic inflammation are the main molecular changes occurring in the pathophysiology of CVD. Inflammation is consistently active in the elderly and is a risk factor for CVD. Early regulation of inflammation can prevent or delay the occurrence and progression of CVD.
Sesamin is the most abundant oil-soluble lignin in sesame seeds and oils and has a variety of pharmacological functions, including antioxidant and anti-inflammatory activities. Sesamine can up-regulate the expression of PPARγ, LXRα and ABCG1, stimulate cholesterol outflow in macrophages, and effectively inhibit cholesterol accumulation induced by oxidized LDL, thereby preventing the formation of foam cells in macrophages.
Lycopene is a naturally occurring acyclic carotenoid found in the chloroplasts and chromosomes of plants, as well as in the cytoplasm of certain eukaryotes such as eubacteria and algae. Epidemiological evidence suggests that serum lycopene concentration is inversely associated with CVD risk. Lycopene neutralizes reactive oxygen species (ROS), reduces macrophage secretion of pro-inflammatory cytokines and metalloproteinases, inhibits smooth muscle cell proliferation, and reduces monocytes. Lycopene can inhibit inflammatory responses by inhibiting NF-κB activation, and it can also affect heterobiotic metabolism by activating the Nrf2/ARE transcriptional pathway.
Ginger is a monocotyledonous plant belonging to the genus Zingiberaceae. Ginger has special properties that clear ROS, including peroxides. All the active ingredients in ginger, such as curcumin, gingerol, and gingerone, have shown antioxidant activity. [6]- Gingerol may increase superoxide dismutase (SOD) activity by activating the PI3K/AKT signaling pathway and reduce ROS production and malondialdehyde formation in neonatal rat cardiomyocytes. In addition, ginger extracts rich in 6-curcumin May exert antioxidant effects by inducing Nrf2. Notably, the vascular protective effects of ginger are mediated through a variety of mechanisms, including reducing oxidative stress and inflammation, increasing nitric oxide (NO) synthesis, inhibiting vascular smooth muscle cell proliferation, and promoting autophagy.
Inhibition of myocardial remodeling
Structural changes that occur during cardiac aging, including progressive pathological myocardial remodeling, are known predictors of CVD. The myocardial remodeling process is characterized by physiological and molecular changes that lead to cardiomyocyte hypertrophy, fibrosis, and myocardium inflammation, ultimately leading to increased ventricular stiffness, impaired heart function, and ultimately heart failure. Angiotensin II promotes cardiomyocyte hypertrophy and stimulates fibroblast proliferation and extracellular matrix protein expression. AMPK plays a key role in the development of CVD, and AMPK deficiency exacerbates heart hypertrophy and makes the heart more susceptible to heart failure.
Cytokine transforming growth factor β1(TGF-β1) plays a crucial role in inducing cardiac fibroblasts to differentiate into cardiac fibroblasts. FoxO1 is a transcription factor involved in apoptosis, oxidative stress and cell differentiation. TGF-β1 stimulates FoxO1 expression, and in cardiac fibroblasts,TGF-β1 reduces FoxO1 phosphorylation, increases FoxO1 nuclear localization, increases FoxO1 protein levels, and promotes differentiation of cardiac fibroblasts into cardiac fibroblasts.
Baicalin is a natural compound extracted from the dried roots of scutellaria baicalensis. Baicalin inhibits pressure overload-induced cardiac fibrosis by modulating AMPK/TGF-β/Smads signaling pathways. The positive effects of baicalin include the regulation of cardiac fibrosis in vivo and in vitro by activating the AMPK/TGF-β/Smads signaling pathway. Baicalin also inhibits Smad3 and nuclear translocation of Smad3 with transcription co-activator p300, thereby preventing the development of angiotensin II-mediated cardiac fibrosis.
Epicatechin is the main bioactive polyphenol in green tea and is a powerful antioxidant. Epicatechin reduces angiotensin II and stress overload-mediated cardiac hypertrophy. Epicatechin inhibits the expression of angiotensin II-induced c-Fos and c-Jun proteins, thereby inhibiting AP-1 activity. In addition, epicatechin can inhibit NF-κB activity by blocking ROS-dependent p38 and JNK signaling pathways, and the inhibition of AP-1 activation is a result of epicatechin inhibiting the progression of cardiac hypertrophy by blocking EGFR transactivation and its downstream events ERK/PI3K/AKT/mTOR/p70, ultimately leading to inhibition of atrial natriuretic peptide and B-type sodium Reactivation of urinary peptides and inhibition of cardiac hypertrophy progression. Epicatechin also inhibits angiotensin II-induced ROS production and NADPH oxidase expression, thereby inhibiting cardiac hypertrophy and cardiac remodeling.
This review details the potential of natural products for the prevention and treatment of cardiovascular disease. As the global population ages, aging-related cardiovascular diseases are becoming a serious public health problem. Natural products are widely used in the prevention and treatment of various diseases due to their significant efficacy and high safety.
Studies have shown that a variety of natural products such as resveratrol, berberine, curcumin, lycopene, ginger, baicalein, epicatechin, ellagic acid, honokiol, poria, tanshinone IIA and marigonin E have multiple mechanisms of action in enhancing autophagy, inhibiting oxidative stress and chronic inflammation, inhibiting myocardial remodeling, inhibiting apoptosis, and inhibiting ischemia/reperfusion injury . These natural products play a cardiovascular protective role by regulating a variety of signaling pathways, such as mTOR, AMPK, NF-κB, Nrf2, etc.
In addition, reasonable dietary habits, such as increasing the intake of fruits and vegetables, moderate consumption of green tea, etc., may help reduce the risk of cardiovascular disease. Multiple epidemiological studies and clinical trials support this view. In particular, natural compounds such as catechins in green tea, lycopene in tomatoes, and gingerol in ginger have shown significant cardiovascular protective effects.
However, although natural products hold great promise in the field of cardiovascular disease prevention and control, there are still some challenges and limitations. For example, the bioavailability of some natural products is low, the mechanism of action is not fully understood, and the clinical efficacy needs to be further verified. In addition, there may be interactions between different natural products, and the optimization of dosage and duration of treatment also requires more research.