A review on function of the Naoxintong Capsule in anti atherosclerosis and protection of vascular endothelium

Zho Buchng(赵步长), Zho To(赵涛), Song Linlin(宋琳琳)＊, Liu N(刘娜), Wu Di(吴迪), Jing Xioyun(姜晓媛), nd Ci Lingling(蔡玲玲)

A review on function of the Naoxintong Capsule in anti atherosclerosis and protection of vascular endothelium

Zhao Buchang(赵步长)a, Zhao Tao(赵涛)a, Song Linlin(宋琳琳)a＊, Liu Na(刘娜)a, Wu Di(吴迪)b, Jiang Xiaoyuan(姜晓媛)b, and Cai Lingling(蔡玲玲)b

Atherosclerosis (As) is the common pathological basis of cardiovascular and cerebrovascular diseases, it starts with the injury of vascular endothelial. The Naoxintong Capsule, a modern patent traditional Chinese medicine, is composed of Huangqi, Danshen, Quanxie, Shuizhi and other sixteen herbs. It is extensively used to treat coronary heart disease, stroke and other cardiovascular and cerebrovascular diseases, with the activity of anti-coagulation, anti-inflammatory, protecting endothelial cells, anti-atherogenic and plaque stabilization.

The Naoxintong Capsule; Endothelial cells; Atherosclerosis

Atherosclerosis (AS), a chronic multiple endanguim disease, is based on vascular endothelial injury and characterized by chronic inflammation of vascular. AS starts with the injury of vascular endothelial. For the primary lesion site of AS is coronary artery and cerebral artery, it is the common pathological basis of cardiovascular and cerebrovascular diseases. The pathogenesis of AS is related to endothelial cell abnormality, inflammatory reaction induced by inflammation cytokine, and lipid metabolism disorder. Therefore, the key to treat cardiovascular and cerebrovascular diseases is protecting vascular endothelium and antiatherosclerosis.

The Naoxintong Capsule inherits classic famous prescription of Wang Qingren in Qing dynasty “the Buyang Huanwu decoction”with the guidance of “Simultaneous treatment of the brain and the heart” and “Insufficient blood supply is the source of diseases”. Combining with the characteristics of modern constitution and clin-ical characteristic, it adds insect drugs and drugs for promoting blood cir-culation to remove blood stasis. The Naoxintong Capsule has the function to benefit Qi, activate blood circulation, resolve blood-stasis and unblock collater-als. Besides, it can protect vascylar endothelium and improve endothelial and antiatherosclerosis function. It is used in the treatment of cerebral infarction, coronary heart disease and other cardiovascular and cerebrovas-cular diseases.

AS AND VASCULAR ENDOTHELIAL FUNCTION

Vascular endothelial system plays a significant role in maintaining vasc-ular homeostasis and preventing tarombokinesis. Vascular endothelial cell（VEC）is not only the barrier of blood and blood vessels, it also hasendocrine function of secretion and releases biological substances. Besides, VEC participates in repairing of injured vessels, immune response andregulating the body. And it plays an important role in maintaining arterial tension, blood flow regulation. VEC is able to secrete anticoagulan, antipl-atelet substances, which prevents cells in the vascular wall from sticking together and inhibits the activation of platelets and leokocytes1. Damage and dysfunction of endothlial cells is the initial event at the onset of AS. Besides, endothlial cells mediated by NO, prostacyclin, angiotensin, ET could increase permeability of lipid metabolisam and other plasma component. Dama-ge and dysfunction of arterial endothlial cells is the initial factor in the AS2-4. The balance of vasonstrictor and vasodilator produced by endothlial cells is the sign of normal endothelial function. No is compounded by VEC is a kind of biological activity and major vasodilatation factor. It has powerful vasodilation function and inhibits the aggregation and adhesiveness of platelet. ET is a kind of vasonstrictor secreted by VEC, it maintains vascular tension with NO, adjusts endothelial function, and plays a central role in maintaining structure and function of vascular. Once out-of-balance, it is endothelial cell dysfunction. When endothelial cell function is incompetent, vasodilation function declines, blood flow reduces, cell adhesion increases, and cardiac output drops. Damage of endangium lead to impaired endothelial function. The level of ET increases, the level of NO reduces, the imbalance of ET and NOcauses vasomotor dysfunction5,6. Vasomotor dysfunction is related to genesis and development of AS. The damaged endothelial cells can promote the adhesion and aggregation of leuko-cytes, accelerates lipid accumulation and plaque formation and rupture.

THE COMPONENT AND CHARACTERISTIC OF THE NAOXINTONG CAPSULE

The Naoxintong Capsule, a pure Chine se Medicincal Prepration, is composed of Huangqi, Chishao, Danshen, Danggui, Chuanxiong, Taoren, Honghua, Ruxiang, Moyao, Jixueteng, Niuxi, Guizhi, Sangzhi, Dilong, Quanxie,Shuizhi. It has the ability to benefit Qi, activate blood circulation, resolving blood-stasis and unblocking collaterals. And it is used to treat the symptoms of stroke in channels and collaterals, hemiplegia, numbness of the limbs, facial paralysis, stiff tongue and sluggish speech, chest distress, palpitation, short breath, which are caused by qi and blood stasis, venation with blood stasis group.

The Naoxintong Capsule inherits classic famous prescription of Wang Qingren in Qing dynasty with the guidance of “Simultaneous treatment of the brain and the heart” and “Insufficient blood supply is the source of diseases” from professor Zhao Buchang. Combining with more than 30 years clinical experience, characteris-tics of modern constitution and clinical characteristic, it adds insect drugs and drugs for promoting blood circulation to remove blood stasis. Naoxintong can tonify Qi and activate blood as the Buyang Huanwu decoction7.

Huangqi is main herb of prescription

The Naoxintong capsule uses Huangqi as the main herb of prescription, which can reinforce vital energy. Traditional Chinese medicine holds that “Qi is the commander of blood”,“Qi can produce blood and promote blood circulation”. When Qi is sufficient, blood would be sufficient; when Qi is insufficient, blood would be in deficiency, Qi promots blood circulation, Qi stagnation would cause blood stasis. Deficiency of vital energy makes blood running abnormally, and causes blood stasis. To cure Qi deficiency and blood stasis the circulation of Qi must be promoted firstly. Huangqi in this prescription is nice Qitonifying drug. It reinforces Qi with sweet and warm drug, promotes blood circulation to remove blood stasis by reinforcing Qi. Modern pharmacology study shows that Huangqi has cardiac effect. It can increase cardiac contraction amplitude, increase the output, and protect heart. Besides; it has a protective effect of cerebralischemia injury8, enhances and regulates immunity. It can reduce the blood viscosity, expand blood vessel, increase blood flow, improve microcirculation, and prevent thrombosis. Considering the sign of Qi deficiency and blood stasis of patients with cardiovascular and cerebrovascular disease, the Naoxintong Capsule uses Huangqi as the main herb of prescription, supplementing Qi and activating blood circulation as therapeutic principle.9

The combination of insect grugs

The other characteristic of the Naoxintong Capsule is adding Shuizhi, Quanxie, Dilong and other insects in the Buyang Huanwu decoction. Insect drugs have violent effect, it can go up, access channels and collaterals, blood exorcism, open Qi and blood agglutination, increase the function of promoting blood circulation to remove blood stasis, clearing and activating the channels and collaterals.These three drugs are minister drugs of the Naoxintong Capsule.

In the process of AS, vascular endothelial injury and vascular endoth-elial dysfunction can cause platelet activation. Hirudin in Shuizhi can inhibit the platelet activation induces by thrombin, inhibit platelet aggregation, and has antiplatele effect. Hirudin, a kind of thrombin inhibitor, can selectively inhibit thrombin and has strong anticoagulant effect. Shuizhi can not only prevent fibrinogen coagulation, but also can promote the dissolution of fiber, decrease the activity of plasminogen activator inhibitor and increase the activity of plasminogen activator. Shuizhi can inhibit the increaseing of serum Total cholesterol (TC), triglycerides (TG) and have effect of reducing lipid, improving hemodynamic parameter, anti-arteriosclerosis10. Dilong contains lumbrokinase, it can dissolve fibrin, directly inhibits fibrin and clotting enzyme. Accordingly, Dilong also has anticoagulation effect, promote the dissolution of fibre, and play a role in blood viscosity, inhibiting platelet aggregation and thrombosis. Besides, Dilong has function of enhancing immunity, expanding blood vessel, decreasing blood pressure11. Quanxie has a large number of BDF, so it has anticoagulant, antithr-ombotic effect. It can inhibit platelet aggregation, promote the dissolution of fibre and thrombosis, decrease cholesterol, reduce vascular resistance, improve microcirculation, eliminate atherosclerosis plaques, and dissolve intravascular thrombus.

Large proportion of promoting blood circulation to remove blood stasis drugs

The Naoxintong Capsule contains large proportion of promoting blood circulation to remove blood stasis drugs, such as the blood breaking force of peach kernel, safflower, can activate blood circulation and remove blood stasis, improve myocardial ischemia, inhibit platelet aggregation12. Angelica sinensis has effects of activating blood circulation and tonifying the blood,can remove oxygen-free-perssad, activate the SOD, reduce the content of MDA. Salvia miltiorrhiza has effects of activating blood circulation and removing stasis, clearing heat and nourishing blood, can reduce the content of LDL and TG of blood by lowering cholesterol content of aortic wall and showing the function of, anti-platelet aggregation. It could also significantly decrease the content of TXB2 in plasma and the content of TXA2, showing protective effect against ischemia.

The effective components of Salvia miltiorrhiza, such as salvianolic acid and tanshinone, can dilate the blood vessels, reduce the vascular resistance, low the viscosity of blood, remove oxygen-free-perssad, anti-hypoxia, antithrombosis and improve microcirculation13,14. The effect position of Cassia (Rou gui) is into Ying and Blood, connecting the heart and blood vessel, can dilate the blood vessels, regulate the circulation of blood. According to the research15-21, all the promoting blood circulation and removing blood stasis drugs in the Naoxintong Capsule, could regulate blood lipid and atherosclerosis via lowing the content of cholesterol, TG and LDL. It could also inhibit inflammatory responses by inhibiting the inflammatory factor such as NF-kB, reduce the content of CRP, IL-6, mcp-1, TNF,IL-1; raise the content of NO and SOD, low the content of ET, MDA etc., reduce the injury of oxidative stress in the vascular wall in order to protecting endothelium, antioxidation, inhibiting the aggregation of platelet and thrombosis, improvecruor, finally to make efforts in anti atherosclerosis and stabilizing the plaque.

The Naoxintong Capsule is a decently combined prescription, which is scientific in compatibility. The perfect combination of plant medicine and animal medicine, leads to a result of treatment focusing on relieving both the secondary and primary symptoms, and a combination of reinforcement and elimination. A large number of basic researchs show that22,23, the Naoxintong Capsule can raise atherosclerotic content of NO and Prostaglandin PGI2, decreased the content of endothelin ET, serum thromboxane B2 and the expression of LOX-1, LOX-mRNA of aortic, to reduce damage of vascular endothelium. the Naoxintong Capsule can protect the vascular endothelium and improve vascular endothelial function, stabilize the plaque, anti AS and delay the development of AS, improve the rheology index of blood, dilate the blood vessels, reduce the vascular resistance, improve the microcirculation, lower the blood lipid; inhibit the activation of platelet, reduce the adhesion and aggregation of platelet; have the function of anti-inflammat and anti thrombosis; have the protective function on injury of myocardial reperfusion; also have the protective effect on the whole brain. As the ideal Chinese patent drug for treating cardiovascular and cerebrovascular diseases, it is used in clinical treatment of coronary heart disease, stroke and secondary diseases, showning a definite curative curative effect.

MECHANISM STUDY OF THE NAOXINTONG CAPSULE INTERVENING ON VASCULAR ENDOTHELIAL FUNCTION

Chen.b.j24studied the effect of Buchang the Naoxintong Capsule on endothelial function in rabbits with acute myocardial infarction, the result showed that, the Naoxintong Capsule can improve or recover the rabbits’ vascular endothelial function with myocardial infarction, increase the amount of NO, improve the function of blood vessel contraction, reduce the content of ET and von Willebrand factor, improve endothelialdiastolic function, have the effect of Anti thrombosis, improve the prognosis of myocardial infarction; Dong.b25established a rabbit model of AS, to observe theprophylaxis and treatment of Naoxintong on atherosclerosis and its mechanisms, the result showed that, the Naoxintong Capsule can decrease the expression of LOX-1 receptor gene and protein, have the function of protecting vascular endothelium, to control the occurrence and development of AS; Cui.c.c.26studied the protective effect of Naoxintong on vascular endothelial cells. The result indicated that Naoxintong can promote vascular endothelial cell to release NO; Ox-LDL induced apoptosis and injury of endothelial cells was obviously inhibited, achieved the protective effect of vascular endothelial cells.

CLINICAL STUDY OF THE NAOXINTONG CAPSULE IN ANTI ATHEROSCLEROSIS AND ENDOTHELIAL PROTECTION

Study progress of Naoxintong in the treatment of cardiovascular diseases

Wang.f.k27observed the effect of the Naoxintong Capsule on blood viscosity in patients with coronary heart disease and endothelial cell function in 126 cases, the result showed that in the treatment group after taking the Naoxintong Capsule, the blood viscosity, ET of patients decreased and NO were increased significantly, indicating that the Naoxintong Capsule has the protection of vascular endothelial, can significantly reduce coronary heart disease in patients with blood viscosity, protect and improve endothelial function, delay the progression of coronary atherosclerosis, is an ideal drug in the treatment of coronary heart disease (CHD); Liu.s.t28studied the NaoxintongCapsule on unstable type of angina pectoris vascular endothelial function in patients with hs-CRP and the effects of it. The results showed that the Naoxintong Capsules can significantly decrease plasma levels of ET in patients with UPA, decrease the level of hs-CRP, promote the release of NO, improve endothelial function and reduce the intravascular plaque inflammation; Gao. a.b29studied of the Naoxintong Capsule effect on coronary heart disease patients with blood lipid and endothelial pigment. The results indicated that Naoxintong can regulate blood lipid levels of patients with coronary heart disease, reduce endothelin and improve endothelial function, anti atherosclerosis inflammation; Chen.b.j30studied about the effect of the Naoxintong Capsule on acute myocardial infarction patients with vascular endothelial function and infarct size. The results of the study showed that the research subjects in Naoxintong therapy group, whose NO, FMD and NMD significantly increased, vWF and ET and infarct size was significantly lower, which suggested that the Naoxintong Capsules can reduce the area of infarction in patients with AMI. The mechanism may be related to the Naoxintong Capsule in improving the vascular endothelial function in patients with AMI.

Study progress of Naoxintong in the treatment of cerebrovascular disease

Wen.z.y31used a randomized, single blind method to observe the effect of the Naoxintong Capsule on carotid atherosclerosis in 100 cases. The result showed that the size, thickness and IMT of atherosclerotic plaque of people that taking the Naoxintong Capsule for 6 months, were significantly smaller than those of the control group, which suggested that the Naoxintong Capsule can effectively intervene the occurrence and development of carotid atherosclerosis, reduce the incidence rate of cerebral vascular disease, Xi.d.y32observed the clinical curative effect of the Naoxintong Capsule on acute cerebral infarction and its effect on vascular endothelial cells and platelet function in 62 patients. The result showed that, the Naoxintong Capsule can significantly improve neurological function, at the same time can significantly reduce TXB2, vWF and platelet aggregation rate, improve the role of platelet function, and increase the plasma PGI2, t-PA content, the vascular endothelialcells releaseing of anticoagulation and fibrinolysis of bioactive substances, increased vascular endothelial antithrombotic ability, has the protection of vascular endothelial, platelet aggregation.

DISCUSSION

Atherosclerosis is the pathological basis of coronary heart disease and stroke, AS starts in endothelial injury. Consisting of 16 types of traditional Chinese medicine, such as astragalus, salvia miltiorrhiza, pberetima, scorpion etc. The Naoxintong Capsule can reduce the blood viscosity of patients, promote the synthesis and release of vascular endothelial cells NO, adjust the ratio of endothelin ET/NO, improve the vascular endothelial function, protect the effect of vascular endothelium, thereby delaying the AS process. The Naoxintong Capsule is an ideal drug for treating cardiovascular and cerebrovascular diseases.

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(Accepted: February 20, 2016)

a: Department of Cardiovascular Internal Medicine, Bu-Chang Cardio-cerebrovascular Disease Hospital, Xi’an 710082, China

b: Dermatology Department, DongFang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China

＊ E-mail: songlinlin577@sohu.com