New research at The University of Texas Health Science Center at Houston suggests that ancient Chinese herbal formulas used primarily for cardiovascular indications including heart disease may produce large amounts of artery-widening nitric oxide. Findings of the preclinical study by scientists in the university’s Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) appear in the Sept. 15 print issue of the journal Free Radical Biology & Medicine.
Nitric oxide is crucial to the cardiovascular system because it signals the inner walls of blood vessels to relax, which facilitates the flow of blood through the heart and circulatory system. The messenger molecule also eliminates dangerous clots, lowers high blood pressure and reduces artery-clogging plaque formation.
The results from this study reveal that ancient Chinese herbal formulas “have profound nitric oxide bioactivity primarily through the enhancement of nitric oxide in the inner walls of blood vessels, but also through their ability to convert nitrite and nitrate into nitric oxide,” said Nathan S. Bryan, Ph.D., the study’s senior author and an IMM assistant professor.
Herbal formulas are a major component of traditional Chinese medicines (TCMs), which also include acupuncture and massage. “TCMs have provided leads to safe medications in cancer, cardiovascular disease and diabetes,” said C. Thomas Caskey, M.D., IMM director and CEO. “The opportunity for Dr. Bryan’s work is outstanding given that cardiac disease is the No. 1 cause of death in the United States.”
In the study, researchers performed laboratory tests on DanShen, GuaLou and other herbs purchased at a Houston store to assess their ability to produce nitric oxide. Ancient Chinese herbal formulas used primarily for cardiovascular indications are made up of three to 25 herbs. The formulas can be administered as tablets, elixirs, soups and teas.
Most Chinese herbal formulas marketed in the United States are not considered drugs by the U.S. Food and Drug Administration, said Yong-Jian Geng, M.D., Ph.D., study co-author and cardiology professor at The University of Texas Medical School at Houston. They are considered dietary supplements and are not regulated as strictly as drugs.
Scientists also tested the capacity of the store-bought TCMs to widen blood vessels in an animal model. “Each of the TCMs tested in the assays relaxed vessels to various degrees,” the authors stated. “Further studies should be considered in humans, particularly those with cardiac indications,” Geng said. “Hopefully, we will have more data to report in the near future.”
While fully integrated into the healthcare systems in some parts of Asia, ancient Chinese herbal formulas are often considered alternative medicines in Western nations. Part of the reason, according to Bryan, may be that until recently little was known about how they work.
“The next step is to identify the active components of the TCMs that are responsible for producing the NO. We are currently trying to isolate and identify the active component or components,” Bryan said.
Yaoping Tang, M.D., an IMM postdoctoral fellow, was the lead author of the study titled “Nitric oxide bioactivity of traditional Chinese medicines used for cardiovascular indications.” Also collaborating on the study was Harsha Garg, an IMM senior research assistant.
Bryan is the editor of a new book titled “Food, Nutrition and the Nitric Oxide Pathway: Biochemistry and Bioactivity” published by DesTech Publishing and works in the IMM Center for Cell Signaling directed by Ferid Murad, M.D., Ph.D., who won the 1998 Nobel Prize in Physiology and Medicine for his work with nitric oxide as a signaling molecule in the cardiovascular system. Bryan and Geng are on the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston.
Adapted from materials provided by HYPERLINK “http://www.uthouston.edu/”University of Texas Health Science Center at Houston.
Researchers in this study are apparently not aware of the vast amount of scientific and medical research conducted on Chinese herbs and herbal formulas over the past 50 years. It is as if they have only looked at the ancient formulas and not the modern research.
Researchers in China have conducted extensive studies on cardiovascular herbs because of the central concern about cardiovascular disease in the aging Chinese population. Formulas like Vital Cell are based on traditional formulations, but modified according to modern research. Dr. Dexin Yan, who developed Vital Cell, used contemporary scientific research over 25 years ago to begin his development of a modern formulation for enhanced blood circulation at his gerontology hospital in Shanghai.
One of the herbs investigated by the University of Houston researchers is Dan Shen, or Salvia miltiorrhizae root, an important circulatory herb included in Vital Cell and Herbal Boost. The US National Institutes of Health database of published scientific research, called Pub Med, cites 951 research reports on this herb. The earliest of these reports is from 1979 and most of the earlier studies were performed to identify active ingredients and mechanisms of action for cardiovascular disorders.
The Pub Med reports are only those in English and represent only a fraction of the actual research done on the herb at Chinese and Asian natural medicine research centers. Many of the reports are from Europe as many scientists there have long been aware of the value of the herb.
Because poor blood circulation is a component of many disorders, Salvia miltiorrhizae has taken a special place in Asian research for treating a wide variety of disorders, including heart disease, stroke, hepatitis, senile dementia and cancer.
And, because of the importance of the herb, much research is devoted to identification of active ingredients and their bioactivity. This type of research also extends to growing and harvesting, plus extraction and manufacturing techniques that enhance bioactivity.
Below is a small sampling of research summaries from Pub Med on Salvia miltiorrhizae as a cardiovascular herb. The first study is on the role of nitric oxide in eliciting arterial vasodilation, just the topic investigated by the University of Houston research group.
The technical nature of these studies also shows the extent of development of Chinese science and medicine in evaluating and improving their traditional formulations.
Department of Medicine, 2nd Xiangya Hospital of Central South University, Changsha, Hunan, PR China. firstname.lastname@example.org
Salvia miltiorrhiza has been widely used in the treatment of various cardiovascular diseases due to its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone II(A), the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was shown to induce vasodilation in coronary arteries. But its effects on coronary arterioles remain unknown. The purpose of this study was to investigate the effects of tanshinone II(A) on isolated rat coronary arteriole and the underlying mechanisms. Coronary arterioles were carefully dissected, cannulated and pressurized. Tanshinone II(A)-elicited vascular inner diameter change was recorded by a computerized diameter tracking system. To investigate the mechanisms governing the vasodilative effects of tanshinone II(A), the roles of endothelium, endothelium-derived vasoactive factors and potassium channels were assessed respectively. Endothelium denudation, inhibition of nitric oxide synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of the large conductance calcium(Ca(2+))-activated potassium channels (BKca) significantly decreased the vasodilation elicited by Tanshinone II(A). The results indicated that tanshinone II(A) induces an endothelium-dependent vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450 metabolites contribute to the vasodilation; activation of BKca channels plays an important role in the vasodilation.
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan 70101, ROC. email@example.com.
Tanshinone IIA is one of the active principles in danshen (Salvia miltiorrhiza Bge) widely used in treatment of cardiovascular disorders. We investigated the effect of danshen or tanshinone IIA on blood pressure and its possible mechanisms. An i.p. injection of danshen at 10 mg kg(-1) significantly lowered systolic blood pressure (SBP) of spontaneously hypertensive rats (SHRs) but failed to modify the SBP in normotensive Wistar-Kyoto rats (WKY). Oral administration of tanshinone IIA also decreased SBP in SHR but not in WKY. Tanshinone IIA produced a concentration-dependent relaxation in isolated SHR aortic rings precontracted with phenylephrine (10 nmol l(-1)) or potassium chloride (KCl) (40 mmol l(-1)). The relaxing effect of tanshinone IIA on tonic contraction of phenylephrine in isolated aortic rings without endothelium remained produced. Glibenclamide at concentration sufficient to block adenosine triphosphatase (ATP)-sensitive potassium (K(+)) channel attenuated this tanshinone IIA-induced relaxation that was not influenced by other inhibitors. We further investigated the effect of tanshinone IIA on the changes of intracellular calcium concentration ([Ca(2+)]i) in cultured aortic smooth muscle (A7r5) cells using fura-2 as indicator. Tanshinone IIA decreased [Ca(2+)]i elicited by phenylephrine (10 nmol l(-1)) or KCl (40 mmol l(-1)) in a concentration-dependent manner; glibenclamide, but not other inhibitors for K(+) channel, abated this effect. Our results suggest that tanshinone IIA acts as an active principle of danshen showing vasodilation through ATP-sensitive K(+) channel to lower [Ca(2+)]i.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Tanshinone IIA (Tan IIA), a derivative of phenanthrenequinone isolated from Salvia miltiorrhiza, has been widely used for treating cardiovascular diseases in China. In the present study, we assessed the effect of Tan IIA on cardiac function, vascular endothelial growth factor (VEGF) expression and angiogenesis on models of myocardial infarction (MI) in rats. The results demonstrated that TanIIA elicited a significantly cardioprotective effect by improving heart function, reducing infarct size, and increasing survival rate in MI rat. Our results offer, for the first time, further insight into Tan IIA promoting angiogenesis and up-regulating VEGF expression in MI rats due to the enhancement of hypoxia-inducible factor 1alpha mRNA expression, and provide a novel target for Tan IIA in the prevention and treatment of myocardial ischemia injury.
Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
Homocysteine (Hcy) is a by-product of methionine metabolism. An imbalance of Hcy in the body may lead to hyperhomocysteinemia, a condition with elevated Hcy concentration in blood that may be one of the risk factors responsible for the development of several vascular diseases (thromboembolism, atherosclerosis, stroke, vascular diseases and dementia). Radix Salvia miltiorrhiza (Danshen), a well-known Chinese medicinal herb that can activate and improve blood microcirculation, is noticeable for its beneficial effect in treating cardiovascular diseases. The present study is to demonstrate the protective effect of Danshen extract against the homocysteine-induced adverse effect on human umbilical vein endothelial cell (HUVEC). Homocysteine (5 mM) not only decreased the cell viability but also caused the disruption of capillary-like structure formation in vitro. The protective effect of Danshen aqueous extract and its active compounds on endothelial cell function were demonstrated through an in vitro tube formation assay, which mimics the new blood vessel formation. To identify the active components in the aqueous extract of Danshen, the content was characterized by instrumental analysis using high performance liquid chromatography with diode array detector (DAD) and electrospray tandem mass spectrometry (ESI-MS/MS). Interestingly, Danshen extract and its pure compounds showed different effectiveness in protecting HUVEC against Hcy-induced injury according to the following descending order: Danshen aqueous extract, 3-(3,4-dihydroxy-phenyl)-2-hydroxy-propionic acid (Danshensu), protocatechuic acid, catechin and protocatechualdehyde. We believed that such findings might provide evidence in understanding the beneficial effects of Danshen on the cardiovascular system.