Results: This article Thermogenic fat burner reviews the cardiovascular effects of four potent caediovascular botanicals viz. Cardiovasc Drugs Ther. Silagy CNeil A Garlic as a lipid lowering agent: a meta-analysis. Get it as soon as Tuesday, Feb

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How Herbal Medicine Can Help With Cardiac Problems And 6 Herbal Remedies

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The extract also reduces the levels of the inflammatory cytokines IL-1β, IL-6, MCP1 and TNFα and downregulated the local activity of the rennin-angiotensin-aldosterone system in the aortic tissue.

et al. These data indicate that fistular onion stalk extract may be useful for the attenuation of atherosclerosis, and the mechanism includes the regulation of the local inflammatory responses.

In addition to the anti-hypertensive effect, there is also wide spread belief among general public that Allium sativum L garlic has beneficial effects on dyslipidemia in patients. Seventy type 2 diabetes patients with newly diagnosed dyslipidemia were divided into two groups and were given tablet garlic mg containing 1.

In a double-blind, crossover study of moderately hypercholesterolemic men, treatment with 7. These effects were Although one recent meta-analysis concluded that garlic decreases TC to a modest extent, an effect driven mostly by the modest decreases in TG, with no appreciable effect on LDL or HDL cholesterol Reinhart et al.

Since some meta-analysis has been based on trials with inadequate study designs, methodological deficiencies, the effect of garlic on atherosclerosis and dyslipidemia awaits further investigation.

The dried root of Astragalus propinquus , Radix Astragali, is also known as Huangqi. Polysaccharides, flavonoids, and sponins are the main active components of membranous milkvetch root. Studies have shown that Huangqi extract significantly decreased the area of atherosclerosis plaques Effects of its extract and components on lipid profile are also summarized in a review, in which the serum of TG, TC, and LDL-C levels were reduced by both Astragalus mongholicus extracts treatment at 0.

Accordingly, the HDL-C levels were increased by these treatments Guo et al. Rhizoma Coptidis, also known as Huanglian, is derived from the dried root and rhizome of Coptis chinensis Franch. Cheng et Hsiao, and Coptis teeta Wall. Its main components include lignans and alkaloid, in which berberine is the active component for lipid lowering.

Studies have shown that berberine administration significantly decreased the serum TG, TC, LDL-C, when taken orally or injected intraperitoneally Zhou et al.

In addition, Caucasian obese human subjects were orally given mg berberine, three times a day for 12 weeks. The blood lipid was significantly reduced and TG, TC were decreased by 23 and In a meta-analysis, berberine induced a significant reduction in these biomarkers in participants in11 randomized controlled trials Ma et al.

Known as hawthorn, its hypolipidemia effect has been investigated widely in animal studies. Then, the specific effects of aqueous and ethanol extracts of hawthorn on lipid profiles were compared. In a high-fat emulsion fed mice, both ethanol and aqueous extracts possessed hypolipidemia activities and the ethanol extract exhibited more favorable effects than the aqueous extract Shao et al.

This lipid lowering effect of hawthorn mostly contributes to inhibition of the progression of atherosclerosis which was evidenced by the significantly inhibited pathological changes and reduced intima-media thickness in the arteries Zhang et al.

In-depth exploration demonstrated that the lipid-lowering action may be due to the anti-inflammation activities, the upregulation of PPARα to facilitate β-oxidation-related enzymes in liver leading to lipid degradation, enhanced expression of hepatic LDL receptors resulting in a greater influx of plasma cholesterol into the liver, and the suppressed cholesterol biosynthesis and increased degradation of cholesterol to bile acids Niu et al.

The hypolipidemic effects of hawthorn in clinic remain further study. Epimedium brevicornum Maxim, an important traditional CHM, has been used widely for s of years in China, Korea, and Japan.

Icariin, a flavonoid isolated from Epimedium brevicornum Maxim, is considered as the main pharmacological active constituent. In the high cholesterol diet-induced atherosclerosis rats, the levels of blood lipids including TC, TG, LDL-C, and malonaldehyde were significantly increased, while HDL-C and SOD were significantly decreased.

Icariin succeeded in improving these biochemical parameters toward the normal values Hu et al. Its dried root tuber is Radix Polygoni Multiflori, also known as Heshouwu.

Raw and prepared pharmaceutical forms are frequently used. Guo et al. Similarly, these lipid profiles in the hyperlipidemic rats were lowered by the treatment of the ethlacetate extracting fraction and stilbene glycoside from the tube of Radix Polygonum Multiflorum too Guo et al.

Fermentum Rubrum, popularly known asred yeast rice, is the fermented product of Monascus purpureus on rice. It is composed of 13 kinds of natural statins, unsaturated fatty acids, ergosterol, amino acids, flavonoids, alkaloid, trace element, and so forth.

Some clinic studies have demonstrated the lipid lowering effects of the red yeast rice. A twice daily dose of red yeast rice at mg for 8 weeks was found to reduce LDL-C by Similar effects were observed in 72 patients with idiopathic persistent nephritic syndrome with secondary dyslipidemia Gheith et al.

Xuezhikang capsule is the extract of red yeast rice. Scholars in China made a systematic review on the clinical randomized controlled trials for hyperlipidemia treatment with Xuezhikang, which included a total of participants in 22 randomized trials.

It was concluded that Xuezhikang remarkably lowered TC, TG, and LDL-C compared with the inositol nicotinate Fallah Huseini et al. The beneficial effects of Olea europaeal L. According to the European Pharmacopeia, the most abundant substances in standardized dry leaf extracts are oleuropein, hydroxytyrosol, caffeic acid, tyrosol, apigenin, and verbascoside, with oleuropein being the major component of olive leaf extract.

Olive leaf extract treatment reduces the atherosclerostic lesions size and the thickness of intima in atherosclerotic rabbits, accompanied with decreased levels of atherosclerotic markers, including serum TG, TC, LDL, HDL, and malonaldehyde with a parallel downregulation of MCP1, vascular cell adhesion molecule-1, NFkB and TNFα Wang et al.

Consistent with it, another animal study showed that a 1-month intake of hydroxytyrosol by rabbits consuming an atherogenic diet results in a reduced size of atherosclerotic lesions compared to control animals Gonzalez-Santiago et al.

However, the results originating from in vivo models are divergent. The intake of hydroxytyrosol in an in vivo apo-E knockout mice model showed that this compound, when administered for 10 weeks, leads to atherosclerotic lesions associated with the activation of monocytes and modification of the blood lipid profile Acin et al.

These studies indicate that under certain conditions the phenol could be rather harmful than cytoprotective. Ginseng saponin is divided into Rb1, Rb2, RC, Rd, Re, and Rl.

Ginseng radix can be metabolized into compound k in small intestinal. In vitro , the metabolites significantly activate the AMP-activated protein kinase AMPK to affect the lipid metabolism in insulin-resistant HepG2 human hepatoma cells Kim et al. Also known as Kudzu Root, its effects on hyperlipidemia are investigated in a series of studies.

Furthermore, hepatic lipid metabolism was also enhanced in ovariectomized rats by oral administration of Kudzu root Wang et al. Reynoutria japonica Houtt is a synonym of Polygonum cuspidatum siebold and Zucc. Its dried root and rhizome is known as Huzhang in Chinese medicine. Polydatin and resveratrol are the primary active components.

Rheum palmatum Linn. Ex Balf. Radix Et. Rhizoma Rhei, also known as Dahuang or rhubarb, is derived from the root and rhizome of Polygonaceae members. The main active component includes rhein, aloe emodin, emodin, chrysophanol, and physcion.

There is a series of studies exhibited the lipid-lowering effects in animals or patients. Thus the lipid-lowering effect of rhubarb, at least, partially dues to the component rhein. Danthron is another extract of rhubarb. It was observed that danthron dose-dependently promoted the phosphorylation of AMPK and acetyl-CoA carboxylase in both HepG2 and C2C12 cells.

Meanwhile, danthron significantly reduced sterol regulatory element-binding protein 1c synthesis and fatty acid synthase gene expressions, contributing to the inhibitory effect on lipid metabolism Han et al. However, some side-effects, including vomiting, headache, diarrhea and abdominal pain, are reported by some volunteers.

Scutellaria baicalensis , known as Huangqin, is derived from the dried root of Scutellaria baicalensis Georgi. The most effective lipid-lowering component is flavonoid compound. In addition, treatment with flavonoids from the Huangqin leaves increased the activity of lecithin cholesterol acyltransferase in hyperlipidemia rats Regulska-Ilow et al.

The ripe seed of Senna obtusifolia Linn. Fabaceae or Cassia tora Linn. Leguminosae is Semen Cassia, known as Juemingzi. Anthraquinone glycosides are the active component. Similar results were induced by administration with the total anthraquinone from Semen Cassia for 2 months in alcohol treated SD rats Guo et al.

There are many other herbs which show the hypolipidemic effects and widely used in Chinese medicine. These herbs include Rhizoma Chuanxiong , Rhizoma Curcumae Longae Jianghuang , Rhizoma Alismatis Zexie , Semen Plantaginis Cheqianzi , and Folium Nelumbinis Heye.

The oral administration of the extracts or the active components exerts the hypolipidemic effects and improving lipid metabolism Guo et al. In addition, there are some formulae for dyslipidemia which are applied in clinic basing on syndrome differentiation China Association of Chinese Medicine, The formulae are listed in Table 2.

Cardiovascular diseases involving the heart includes angina, myocardial infarction, cardiomyopathy, congenital heart disease, and heart failure, etc.

Some of the diseases interact on each other or on other vascular diseases. For example, coronary artery diseases involve atherosclerosis, which may be caused by hypertension, hyperlipidemia, whereas heart failure can arise as consequence of large myocardial infarctions.

Thus, herbs applied in treatment of hypertension, atherosclerosis and lowering lipid profiles should contribute to attenuating heart diseases too.

Here, we present formulae and the natural plants frequently used in clinic and lab studies in alphabetical order. There are some formulae which are frequently used to treat heart diseases. With 1 H NMR and UHPLC-MS measurement, day application of Sini decoction effectively reversed the urinary metabolic profiles in the myocardial infarction rat model Tan et al.

Another formula consists of Terminalia arjuna, Cactus grandiflorous, Crataegus oxyacantha , and Piper nigrum. Preadministration and postadministration of this herbal mixture restore the levels of biomarker of cardiotoxicity, including cardiac marker enzymes, lipids profile, and antioxidant enzymes Lin et al.

Rhodiola formulation is claimed to relieve the symptoms of ischemic heart disease and improve the electrocardiography in a number of clinical studies Yu et al.

In addition, the ORs of symptomatic and electrocardiography improvement in Rhodiola formulations versus other CHMs, versus routine western medicine, and Rhodiola formulations plus routine western medicine versus routine western medicine were 1.

These findings indicate that the formulations have a positive effect on treating ischemic heart disease alone or in combination with routine western medicine. In addition, there are some formulae for angina pectoris or coronary heart disease or heart failure which are based on syndrome differentiation China Association of Chinese Medicine, and are listed in Tables 3 and 4.

TABLE 3. Formulae for coronary heart disease and angina pectoris based on syndrome differentiation. Injection of Astragalus , also known as Huangqi, is one of the most commonly used Chinese patent medicines for the treatment of chronic heart failure in China as complementary treatment to recommended Western therapies.

Fu et al. Although the available studies are not adequate to draw a conclusion on the efficacy of the Huangqi injection, it is observed to enhance myocardial contractility, improve circulation, and protect myocardial cells with modern pharmacological tools.

For example, in an in vivo rat model of persistent myocardial ischemia produced by occlusion of the left anterior descending coronary artery, pretreatment of Huangqi extract significantly decreased the myocardial infarct size and the serum levels of lactate dehydrogenase, creatine kinase isoform MB, and cardiac troponin.

Cecropia pachystachya , popularly called ambay, is extensively used in herbal medicine of South America. Cecropia pachystachya Mart growing in a temperate region produced a positive inotropic effect on isolated rat hearts independent of beta-adrenergic effect.

In contrast, the inotropic effect was prevented by pretreatment with high potassium media stimulating Na-K-ATP pump , indicating an inhibition of the pump by ambay Consolini et al.

It has been described in previous sections hawthorn. In isolated perfused hearts, extracts of hawthorn have been reported to show cardioprotective effects without affecting coronary blood flow Nasa et al.

Simultaneously, they demonstrated vasodilator actions and positive cardiac inotropic effect Blesken, These results were verified in a multicenter, placebo-controlled, double-blind study, in which WS , the special extract of hawthorn, improved cardiac function determined by heart rate product systolic BP × heart rate in patients with NYHA class II heart failure Weikl et al.

More studies are needed to investigate the mechanisms of hawthorn to attenuate CVDs. It has been described in previous sections and the main extract from the olive leaves is oleuropein. The rabbits were subjected to a 30 min period of regional ischemia of the heart followed by a 3 h reperfusion.

Chronic pretreatment with oleuropein reduced the infarct size compared with the control Andreadou et al. In doxorubicin-induced cardiomyopathy, oleuropein effectively improved the impaired cardiac geometry and function evidenced by transthoracic echocardiography Andreadou et al.

Reflow in ischemic hearts induced oxidized glutathione release and membrane lipid peroxidation, which were prevented by oleuropein. The reported data demonstrated the direct cardioprotective effect of oleuropein in the acute events that follow coronary occlusion, and the nutritional benefit of olive oil in the prevention of coronary heart disease Weikl et al.

The root of Panax notoginseng , known as Sanqi, Sanchi or Tianqi in East Asian countries, has been identified over 80 variants according to different substitute patterns. A myriad of studies demonstrate the protective effect of notoginseng in cardiac injury.

Secondly, it could reduce infarct size and serum level of creatine kinase in rat models of myocardial ischemia Yue et al. Thirdly, it decreased serum levels of lactate dehydrogenase, cardiac troponin I, malondialdehyde and several cytokines, including TNF-a, IL-1β and C-reactive protein Han et al.

These findings suggest considerable therapeutic potentials of notoginseng for myocardial infarction. Interestingly, Notoginseng combined with the powdered extract of Carthamus tinctorius , an anti-thrombus herbal medicine, or with Sals, the active ingredient of C.

tinctorius , showed stronger effects to reduce infarct size than either drug alone Yue et al. Thus, combination medication remedy should be considered for CVDs treatment. In addition to hypertension and hyperlipidemia, the dried root of Salviae miltiorrhizae Danshen is widely used in China for the treatment of angina pectoris and acute ischemic stroke.

It has a range of potentially beneficial effects, including improving microcirculation, causing coronary vasodilatation, suppressing the formation of thromboxane, inhibiting platelet adhesion and aggregation, and protecting against myocardial ischemia.

Danshen is widely used either alone or in combination with other herbal ingredients for patients with coronary artery disease or CVDs. An acute myocardial infarction model was induced and both infarct size and echocardiographic response were evaluated at different time after surgery.

Both Sal and tanshinone two hypdrophilic and lipophilic compounds delayed the development of ischemia by decreasing infarct size and improving systolic function post myocardial infarction Wang et al.

However, a recent review of randomized controlled trials of Danshen in ischemic disease published in mainland China identified trials from to , but concluded that the quality of these trials has not improved significantly over recent years and the overall quality is still poor Yu et al.

Since clinical studies have various methodological problems, further high-quality randomized controlled trials should be performed to assess the efficacy of this herb.

For over years, CVDs have been treated with numerous herbal remedies. However, these herbal remedies have not been well studied using modern cellular and molecular techniques.

Based on the existing investigations into mechanisms of single herbal compounds, a summary of these studies is presented in the following section wherein the compounds are discussed according to their target site of activity.

The blood vessel tonicity is principally controlled by the contraction and relaxation of VSMCs. Herbal medicine that regulates proteins or molecules in this pathway would modulate vascular contraction or relaxation.

Firstly, blocking contractile and structural proteins may be one of the ways which natural plants could facilitate vasodilation and vascular remodeling. It has been shown that Tianma the tuber of an orchid enhances acetylcholine-induced vasorelaxation or phenylephrine-induced contraction in aortic rings Feng et al.

Secondly, phosphorylation of myosin light chain protein is another target for herbs to determine vascular smooth muscle contraction. A10 cells, rat smooth muscle cells, were treated with kinds of herbs and it was observed that four herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Danshen and Gegen, reduced phosphorylation of myosin light chain, suggesting that these most common herbs may be beneficial for smooth muscle cell contractility Lin et al.

Extracellular matrix is another target involved in vascular tone regulation. ECM proteins such as Postn is specifically induced upon tissue injury and could promote cellular adhesion and movement as well as collagen fibrillogenesis.

ECM glycoproteins include Eln, Fbln5 and Prelp, being essential to maintain arterial morphogenesis and vessel elasticity. Tianma could induce up-regulation of ECM glycoproteins and down-regulation of ECM proteins in vascular system, thereby regulating blood vessel tonicity by increasing the arterial elasticity and stabilizing the arterial structure Feng et al.

Calcium levels in VSMCs also contribute to regulating the vascular contraction. Tetramethylpyrazine TMP, also known as Ligustrazine , is a vasoactive component derived from Ligustium Wollichii Franchat.

Using dog mesenteric arterial ring preparations, TMP not only caused a dose-dependent inhibition of vascular contractile responses to KCl and phenylephrine in solution with calcium, but also inhibited the responses to phenylephrine in Ca-free medium containing 50 μM EGTA.

This effect was mimicked by a structurally unrelated lipoxygenase inhibitor, 5,8,eicosatriynoic acid and was restored by addition of 12 S -hydroxyeicosatetraenoic acids Saito et al.

Then, the BK Ca -mediated vascular contraction is further explored. The cAMP and the cGMP pathways are major regulators of smooth muscle contractility. By cyclic nucleotide assays, baicalin enhanced both cAMP and cGMP levels in mesenteric arteries. Baicalin was observed to enhance BK Ca currents in a concentration-dependent manner, which were abolished by combining inhibitors of AC SQ and sGC ODQ , by combining inhibitors of PKA KT and PKG KT , and PKC activator PMA in mesenteric artery smooth muscle cells.

These results indicate that baicalin-induced mesenteric artery relaxations could be due to BK Ca channel activation occurs not only as a result of PKA and PKG, but also as a result of cross-interaction with PKC Lin et al.

The effects of Camellia japonica on VSMCs migration was evaluated with a wound healing assay. Camellia japonica concentration-dependently suppressed platelet-derived growth factor-BB induced VSMCs wound healing for 24 and 48 h after injury, indicating the migration inhibiting effects Park et al.

In addition, baicalein and baicalin induced anti-proliferative and anti-mitogenic effects in VSMCs of rabbit, rat and bovine were well summarized Huang et al. These results provide additional evidence for the beneficial cardiovascular effects of natural products. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata , a herbal medicine widely used as an anti-inflammatory drugs in Asia.

The mechanisms of the inflammatory effects of andrographolide in VSMCs were investigated by exposing VSMCs to a proinflammatory stimulus, TNF-α. Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase NOS , JNK, Akt, and p65 phosphorylation.

Thus, andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade mechanism, which is independent of IκBα degradation Chen et al.

These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases. In addition to cellular powerhouses, mitochondria are known as critical regulators of cell death.

And they are the major cellular source of ROS which causes damage to mitochondrial DNA in human VSMCs in a number of cardiovascular pathologies.

Thus, mitochondrial dysfunction may lead to the impairment of various aspects of tissue functioning. It has been known that cultured rat aortic VSMCs treated with AngII for 24 h exhibited mitochondrial dysfunction, including a decrease in mitochondrial oxygen consumption rates, ATP production and mtDNA levels, as well as the disruption of mitochondrial structural integrity Lu et al.

Together with the mitochondrial morphological changes, these alterations were reversed by Astragaloside IV, the major active ingredient of Astragalus membranaceus Fisch. a traditional CHM. Moreover, treatment with Astragaloside IV also reversed the AngII-induced increase in the production of ROS, the increase in NADPH oxidase and xanthine oxidase activity, as well as the decrease in mitochondrial membrane potential and manganese-SOD activity.

These results indicate that Astragaloside IV exerts beneficial effects on AngII-induced mitochondrial dysfunction in rat VSMCs and that these effects are mediated through the inhibition of ROS overproduction, as well as the promotion of mitochondrial autophagy and mitochondrial biogenesis Lu et al.

Overall, herbal medicines discussed here do appear to show pharmacological effects in vitro and in animal studies, which may influence CVDs. FIGURE 1.

Endothelial cells, which constitute the inner cellular lining of blood vessels, have a key role in regulating vascular homeostasis and function, such as vasorelaxation, vascular integrity, and local inflammation. Endothelium-dependent vasodilation was commonly applied to examine the endothelium function, in which NO is a potent vasodilator and plays an important role in regulating vascular tones.

Some herbal medicine functions by targeting at the NO producing process. In studies at the arterial levels, both Lysimachia clethroides and gypenosides elicit vasorelaxation which was abolished by endothelial NOS eNOS or guanylyl cyclase inhibitors Tanner et al.

Sal B, a hydrophilic caffeic acid derivative of Danshen, exerts an important regulatory function on endothelial tissue of isolated mouse aorta by promoting NO production through the inhibition of arginase activity Joe et al.

Fo Shou San, an ancient herbal decoction Chuanxiong Rhizoma and Angelicae Sinensis Radix Danggui in a ratio of , reversed homocysteine-induced impairment of acetylcholine-evoked endothelium-dependent relaxation in rat aortic rings Bi et al. In studies at the cellular levels, gypenosides induced a concentration-dependent increase in NO production from cultured bovine endothelial cells Tanner et al.

Consistent with it, magnesium tanshinoate B another compound purified from Danshen or Fo Shou San, also stimulated the release of NO and its metabolites from a human endothelial cell line ECV O et al. By exploring the mechanisms by which NO production is induced, it was observed that the cellular NOS activities were significantly enhanced with a concomitant increase in the levels of constitutive NOS protein mass O et al.

Inflammation plays a crucial role in the pathophysiology of CVDs, in which adhesion molecules, pro-inflammatory cytokines and chemokines are involved. The anti-inflammatory effects of Danshen and its active ingredients Sal B, Tanshionone IIA, Protoc et al.

were extensively investigated in traditional Chinese medicine for therapy of CVDs. Incubation with TNFα or ADP is widely used to induce inflammation in vitro.

In TNFα treated HUVECs, although neither Sal B nor Tanshinone IIA inhibit the inflammation Stumpf et al. In ADP-treated human platelets, pre-treatment with both Sal B, Tanshionone IIA and Danshen significantly attenuated platelet P-selectin expression Stumpf et al.

Gypenoside XLIX, a dammarane-type glycoside, is a prominent component of G. Studies demonstrate that Gypenoside XLIX inhibits TNFα-induced VCAM-1 over expression and hyperactivity in human endothelial cells via a PPARα-dependent pathway Huang et al.

These findings provide useful insight into the rational basis of CHM in the treatment of CVDs. There are a myriad of herbs that demonstrate effects of endothelial cell protection by different mechanisms.

For example, Sal B decreases ROS production in the aortic rings. Since ROS easily acts with NO to produce peroxynitrite anions, which is a potent and potentially toxic oxidant that damages various types of biomolecules, it can be deduced that Sal B may exert its protective function by precluding NO consumption through adverse reactions such as peroxynitrite formation and preserving NO bioavailability Joe et al.

EGb Ginkgo biloba extract suppresses oxidative stress in a dose-dependent manner in high glucose-stimulated HUVEC. In addition to inhibition of ROS generation and 8-OHdG content, it attenuated oxidative DNA damage, indicating herbs could exert endothelial protection by alleviating endothelial DNA oxidation He Y.

Echium amoenum extract a major source of anthocyanins demonstrated antioxidant and cytoprotective effect in H 2 O 2 -treated HUVECs.

KRGE reduces the H 2 O 2 -induced cell injury in HUVECs too. The inhibited effect on cell death was blunted by HO-1 inhibitor zinc protoporphyrin. HO-1 is considered to augment the cellular defense against various agents inducing cytotoxic injury.

KRGE was observed to induce up-regulation of HO-1 expression in HUVECs, which was abolished by specific silencing of Nuclear factor-eythroid 2-related factor 2 Nrf2, a important anti-oxidant transcription factor expression Yang et al.

These results suggest that Korean Red Ginseng may exert a vascular protective effect through Nrf2-mediated HO-1 induction in human endothelial cells. Ophiopogonin D is one of the most bioactive components of Radix Ophiopogon japonicas.

Its pretreatment showed a series of antioxidation-related protective effects: 1 reducing H 2 O 2 -induced lipid peroxidation and protein carbonylation, 2 attenuating mitochondrial ROS generation and cell apoptosis, 3 restoring cellular total antiboidative capacity, 4 inhibiting the release of inflammatory cytokines and blocking activation of NFκB and ERK signaling cascades, 5 suppressing the enzymatic activity of catalase, HO-1, and caspases Qian et al.

In general, these findings support the protective role of herbs as an effective antioxidant in endothelial injury. Although endothelial cell dysfunction occurs in many different disease processes, caspase-dependent apoptotic cell death induced by the extrinsic or intrinsic pathways is identified as a common denominator.

Protective effect of KRGE was examined in a serum-deprived apoptosis model, which demonstrated that it could prevent serum deprivation-induced HUVEC apoptosis Kim et al. Cytosolic cytochrome c is known to play a crucial role in the activation of the initiator caspase-9 and the effector caspase KRGE prevented subcellular redistribution of cytochrome c from the mitochondrion into the cytosol, resulting in suppression of the extrinsic pathway of apoptosis activation Kim et al.

The cytoprotective property of KRGE may be valuable for developing new pharmaceutical means that limit endothelial cell death induced during the pathogenesis of vascular diseases.

Angiogenesis, the formation of new blood vessels from preexisting endothelium, is critical to a variety of processes, both physiologically embryonic development and wound healing and pathologically malignancy and chronic inflammation.

It is a complex biologic function comprising several steps, including sequential basement membrane degradation, endothelial cell migration and proliferation, tube formation, inhibition of endothelial proliferation, and the stabilization of new vessels.

Modulation of any of these steps would affect new vessel formation. Scutellarin, a known flavone glycoside, is the primary active component of the traditional CHM Erigeron breviscapus Vant. It has been shown to induce endothelial cell proliferation and migration, promote capillary-like tube formation, and significantly upregulate platelet endothelial cell adhesion molecule-1 Gao Z.

These results suggest that herbal medicine promotes angiogenesis and may form a basis for angiogenic therapy. Endothelial cell hyperpermeability is another factor implicated in CVDs, in which the importance of tyrosine phosphorylaton and kinase activity in oxidant-mediated loss of cell junction structures has been demonstrated.

Extract of salvia miltiorrhiza and its major ingredients, Danshensu and Sal B inhibited TNFα-induced endothelial permeability, evidenced by attenuated junctional protein phosphotyrosine and prevention of beta-catenin disassociation from the cytoskeleton Ding and Yuan, The mechanism of pharmacological action was further explored.

The extract, Danshensu and Sal B also repressed expression of vascular endothelial growth factor and ERK activation in TNFα treated HUVEC cells.

In addition, it was found that the extract attenuated the disorganization of vascular endothelial-cadherin, which is likely due to a reduction of vascular endothelial growth factor protein expression as a result of modulation of the ERK signaling pathway Ding et al. These findings suggest that active herbal ingredients may help to attenuate CVDs by maintaining the integrity of endothelial junction structure.

In general, herbal medicines do show the beneficial effects in endothelial cells. As shown in Figure 1 , these natural plants exert the protective effect by inhibition of inflammation, oxidative stress and apoptosis, activation of eNOS-NO signaling pathway, induction of angiogenesis and suppression of endothelial permeability.

Pathological cardiac hypertrophy induced by increased sympathetic drive can subsequently lead to congestive heart failure, which represents the major cause of morbidity and mortality worldwide. In addition, Astragalus polysaccharide pretreatment not only alleviated the augmentation of intracellular free calcium during cardiac hypertrophy but also upregulated expression of calcineurin, translocation of nuclear factor of activated T cells, cytoplasmic 3 into nucleus and activation of calmodulin kinase II reflected by p-CaMKII Dai et al.

Chlorogenic acid is an important component of CHM, which acts as an antioxidant scavenging free radicals and preventing inflammation. Pre-treatment of chlorogenic acid in the isoprenaline-induced neonatal rat myocytes, decreased the levels of the hypertrophic markers, ANP, B-type natriuretic peptide and β-MHC.

The level of the intracellular ROS was reduced and the nuclear translocation of NF-κB was blocked, whereas NF-κBIA, an inhibitor of NF-κB, was upregulated accordingly. These data reveal that chlorogenic acid may inhibit cardiac hypertrophy by attenuating NF-κB signaling pathway and suppressing ROS production Li et al.

Many data have demonstrated that ROS production by myocardial endothelial mitochondria contributes to heart disease and oxidative stress within ventricular myocytes can also be detrimental to the heart.

In fact, much of the contractile dysfunction and adverse myocardial remodeling, which has been observed in a wide range of cardiomyopathies, involves oxidative stress and eNOS uncoupling leading to a decrease in NO. There are a series of targets at which herbal medicine act to improve myocardial endothelial function by attenuation of oxidative stress.

Thus, free radical scavenging and inhibition of oxidases will exert protective effect in cardiac injury. Baicalein may provide such therapy by deletion of free radicals, reducing hydroxyl radicals generation by suppressing iron-catalyzed Fenton reaction or decreasing ROS production by inhibiting activities of NADH-oxidase and xanthine oxidase Huang et al.

Thus it is easy to understand the oxidized LDLs-induced endothelial dysfunction could be restored by L -arginine and NO. The olive products constitute a rich source of polyphenols such as oleuropein and its derivatives, including hydroxytyrosol, which scavenge free radicals and inhibit the chemical oxidation of LDL.

Studies have shown that treatment with high doses of oleuropein at min 1 of reperfusion significantly reduced levels in plasma NOx in hypercholesterolemic rabbits coupled with reduction of infarct size in this group Andreadou et al. Therefore, plant products may function as a NO donor to inhibit formation of peroxynitrite and NOx.

The decrease in these biomarkers indicates the protective action of oleuropein, baicalein, crocetin, Allium chinense and Astragalus against oxidative stress by scavenging free radicals Nasa et al.

Qian-Kun-Nin, a CHM formulation was observed to significantly decreased cell death and attenuate oxidation of DCFH in cells exposed to the mitochondrial site III inhibitor, antimycin A, consistent with a decrease in oxidative stress Shao et al. These findings indicate herbal medicine may inhibit oxidative stress by improving mitochondrial function.

Thus, keeping the function of antioxidant enzymes standards for another target to inhibit oxidative stress and protect cardiac injury. Herbs such as American ginseng could enhance this antioxidant system in rat cardiac H9C2 cells Li et al. The antioxidant systems include Nrf2 protein expression, Nrf2 nuclear translocation, Nrf2 transcriptional activity, direct Nrf2 binding to its target gene promoters, and expression of a group of anti-oxidative genes.

Thus, herbs may serve as antioxidant enhancer to provide cardioprotection against pathological cardiac injury and remodeling. This may help indentifying novel therapeutic targets in the effect of plant products to protect the heart from injury.

H 2 O 2 treatment induces both oxidative damage and apoptosis, contributing to cardiac injury in cultured rat cardiomyocytes. Cynaroside, a flavonoid compound, has been shown to enhance the endogenous anti-oxidative activity, thereby inhibiting intracellular ROS generation.

It also showed the protective effects against H 2 O 2 -induced apoptosis in H9c2 rat cardiomyoblasts. The mechanism by which cynaroside reduced the apoptotic rate were further explored.

Moreover, cynaroside pretreatment showed an inhibitory effect on the H 2 O 2 -induced increase in JNK and P53 protein expression Sun et al. These findings suggest that flavonoid products prevent cardiomyocytes apoptosis in vitro by reducing the endogenous production of ROS, maintaining mitochondrial function, and modulating the JNK and P53 pathways.

Cardiac myocyte is the cell types in which K ATP channels were originally discovered. It is well established that K ATP channels are present at high density in the sarcolemma of cardiac myocytes where they link membrane excitability with the cellular bioenergetic state.

Pinacidil is a potassium channel opener which mediate preconditioning at the beginning of sustained hypoxia by opening of sarcolemmal K ATP channels Budas et al. Similar to it, Guanxinkang treatment benefit the heart function by increasing mRNA and protein expression of K ATP subunits Kir6.

Keep in line with it, extracts of Astragalus demonstrated its anti-apoptotic effect in H 2 O 2 -injured cardiomyocytes only when the K ATP channels were open, whereas the protective effect was not observed when the channels were inhibited by the K ATP channel blocker 5-HD, glibenclamide Nasa et al.

These findings suggest enhancing the open of K ATP channel is one of the important mechanisms by which herbs protect myocardial cells from ischemic injury. Atrial natriuretic peptide is secreted by the heart atrium cells. ANP binds to a specific set of receptors and acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing cardiac output and systemic BP.

Emodin, an active anthraquinone constituent isolated from the rhubarb, was observed to increase ANP secretion concomitantly with a decrease in atrial pulse pressure and stroke volume in a concentration-dependent manner.

This study provides a rationale for the use of herbal medicine in the treatment of impairment of the regulation of the cardiovascular homeostasis.

In the milieu of cardiovascular risk factors that disturb vascular homeostasis, inflammation represents a key early event in vascular pathology, in which monocytes activation, adhesion to the endothelium and infiltration of macrophages into blood vessels are thought to play important pathogenic roles in atherosclerosis and other inflammatory CVDs.

The transcriptional and translational regulation of iNOS in various cell types can be induced by cytokines, growth factors, and endotoxins. Lipopolysaccharide LPS stimulation has been shown to enhance iNOS expression, NO production, and macrophage arginase activity in RAW In addition, cytoprotective molecule HO-1 expression was upregulated by these Danshen products too Joe et al.

SnPP is well characterized as a potent competitive inhibitor of HO activity. Since the iNOS expression, NO production, and TNFα production, were completely abolished by SnPP, the anti-inflammatory effect of Sal B in macrophages may be related to modulation of HO Hb serves as a CO scavenging compound.

Preincubation of Hb for 30 min reversed the inhibitory effect of Sal B on LPS-induced iNOS expression, NO production and NFκB activation in the RAW Although the mechanism by which HO-1 down-regulates iNOS is incompletely clear, it may involve transcriptional inhibition through CO formation or reduction of heme bioavailability for iNOS synthesis.

Consistent with the effect of Sal B, Tanshinone IIA another major compound extracted from Danshen exerts its anti-inflammatory effects by inhibition of iNOS gene expression and NO production, as well as inhibition of inflammatory cytokine IL-1β, IL-6 and TNFα expression in RAW Since Tan IIA has a similar structure to that of 17β-estradiol, the estrogenic activities was examined in the immune cells.

In fact, the most commonly used alternative herbal medicines for estrogen replacement are soy, black cohosh, dong quai and ginseng. Thus, these herbal medicines may serve as a potential selective estrogen receptor modulator to treat inflammation-associated CVDs without increasing the risk of breast cancer.

Activation of the nuclear receptor, PPARα, has been demonstrated to modulate many aspects of lipoprotein metabolism and inflammation both in vitro as well as in vivo.

The tissue distribution of PPARα is extensive and it may mediate many of anti-inflammatory and anti-atherogenic effects. Gypenoside XLIX, a dammarane-type glycoside, is one of the prominent components in Gynostemma pentaphyllum. It has been identified as a potent PPARα activator in HUVEC study Huang et al.

Tissue factor is involved in many diseases including CVDs and hence may be an attractive target for directed CVDs therapeutics. In human monocytic THP-1 cells transfected with promoter reporter constructs pTF-LUC, Gyp XLIX 0— mM concentration-dependently inhibited LPS-stimulated tissue factor promoter activity, mRNA and protein overexpression.

This effect was similar to those of Wy, a potent synthetic PPARα activator, and completely abolished in the presence of the PPARα selective antagonist MK Huang et al.

These data indicate that Gyp XLIX inhibits LPS-induced tissue factor overexpression and enhancement of its activity in human THP-1 monocytic cells via PPARα-dependent pathways, providing new insights into the mechanism of the Chinese herbal plants in CVDs treatment.

These effects are achieved by inhibition of iNOS-NO signaling pathway, which may be through activation of estrogen receptor and nuclear receptor PPARα-dependent signaling pathways Figure 1. One may predict that herbal remedies will receive even more attention in the coming years.

However, some objective limitations should be considered based on the existing literature. Firstly, the CHM are widely studied in China. Accordingly, many articles published on the Chinese literature which may limit these work to be retrieved and public to the world.

In addition, a location bias cannot be excluded since trials published in local journals are more likely to report significant results than those published in worldwide mainstream medical journals. Poorly designed and reported clinic trails usually exaggerate the treatment effects which will misled decision making in clinic.

Thirdly, compounds contained in one herb, even in an extract of one herb are very complicated. Fourthly, many herbal medicine remedies used today have not undergone careful scientific assessment and there still lack preclinical study on the side effects, toxic effects and major drug-to-drug interactions in record.

Therefore, to develop new agents with effectiveness and safety from traditional Chinese medicine is a promising way for prevention and treatment of patients with CVDs. In addition, international collaboration may be encouraged, promoted and financed from the governments in order to improve the overall research quality.

CL drafted the work; YH revised the manuscript. Both CL and YH contributed substantially to the conception or design of the work, approved the final version to be published, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

This work was supported by National Natural Science Foundation of China , Zhejiang Provincial Natural Science Fund for Distinguished Young Scholars of China LR17H, Hangzhou Science and Technology Plan Project of China B36 and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education of China to CL.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Efficacy and safety of Monascus purpureus Went rice in children and young adults with secondary hyperlipidemia: a preliminary report. Although these plants have been used in the treatment of heart disease for hundreds of years, current research methods show us they can be utilized effectively in the treatment of cardiovascular diseases including ischemic heart disease, congestive heart failure, arrhythmias and hypertension.

Conclusion: Although the mechanisms of action are not very clear, there is enough evidence of their efficacy in various cardiovascular disorders. However, for bringing more objectivity and also to confirm traditional claims, more systematic, well-designed animal and randomized clinical studies with sufficient sample sizes are necessary.

Multidisciplinary research is still required to exploit the vast potential of these plants. Potential synergistic and adverse side effects of herb-drug interactions also need to be studied. These approaches will help in establishing them as remedies for cardiovascular diseases and including them in the mainstream of healthcare system.

Keywords: Allium sativum; Cardiovascular disorders; Commiphora wightii; Crataegus oxyacantha; Medicinal plants; Terminalia arjuna. Abstract Background: Medicinal plants have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency and arrhythmia since centuries.

Mashour NHCarbohydrate metabolism in adipose tissue GI Cardiovasculad, Frishman Cardiovasscular. Herbal cardiovascular support Suport for the Treatment of Cardiovascular Disease Hrrbal Clinical Considerations. Arch Intern Med. Herbs have been used as medical treatments since the beginning of civilization and some derivatives eg, aspirin, reserpine, and digitalis have become mainstays of human pharmacotherapy. For cardiovascular diseases, herbal treatments have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency, and arrhythmia. Over the past few years, Suport amount Herbal cardiovascular support herbal products consumed in the United States has cardiovasculaf substantially. Although a significant number of patients are using herbal remedies, few physicians understand the use and potential adverse effects of these products. The U. Food and Drug Administration does not monitor the safety of herbal remedies. Manufacturers are expected to ensure their safety.