Ecklonia Cava Extract - Super Antioxidant & Beyond
Ecklonia Cava Extract: Polyphenol / Phlorotannin Derived from Brown Algae
Ecklonia Cava Extract (ECE) is a standardized natural complex of unique marine molecules that originate from a specific species of brown algae (Ecklonia cava). ECE represents a unique category of polyphenols often called phlorotannins. Their unique polyphenolic structure endows them with biological activities that are not found in land-based plants.
ECE naturally occurs as high-molecular weight tannin (Mw> 2,000 Dalton) and low-molecular weight tannin (Mw=400-1000 Dalton). ECE can be classified into four types depending on the ratio of high molecular weight and low molecular weight tannins. Various physiological activities of ECE have been evaluated in vitro, in vivo and clinically as individual compounds (ECE1-ECE14) and complex forms (ECE, Type I-IV).
Millions on Research
Dr. Haengwoo Lee and his team of M.D.’s and Ph.D.’s have spent over thirty million dollars on research, from in vitro to animal and human studies. Much of the work was done in Korea, and some at the University of Washington. ECE has been found to be an impressive therapeutic agent in a wide array of clinical applications.
The power of an antioxidant is determined by its structure, which is made up of rings. These rings capture stray electrons from free radicals. Most flavonoids generally have three interconnected rings. ECE has up to eight interconnected rings, making its free-radical scavenging ability 10-100 times more powerful than other polyphenols. It is substantially more powerful than green tea catechins, which only have four rings.
Multiple Antioxidant Profiles of ECE
ECE’s antioxidant activities against various reactive oxygen species have been confirmed to be highly potent in physiologically relevant concentrations. The effective dose of ECE for free radical scavenging is in the 10-20 µg/mL range which belongs to most potent families of natural antioxidants. ECE itself and its individual compounds have demonstrated potent reducing power and radical scavenging activities against DPPH radical, oxidized LDL and peroxynitrite.*
Much Longer Half-Life
ECE is a unique polyphenol in that it has a very long half-life in the body. This is because ECE is a marine-based polyphenol which is 40% fat-soluble. Virtually all other polyphenols are derived from land-based plants and are water-soluble. The half-life of ECE is up to 12 hours, compared to 30 minutes for water-soluble, land-based polyphenols. ECE has the ability to cross the blood-brain barrier.
The Research of Martin Pall, Ph.D.
Peroxynitrite is the most notorious of the free radicals incriminated by Martin Pall, Ph.D.'s groundbreaking research on multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, post traumatic stress disorder, Gulf War syndrome, and fourteen other conditions. Peroxynitrite plays a main role in Dr. Pall’s mechanism, along with NF-kappaB and other inflammatory mediators. ECE also reduces tissue specific NF-kappaB.
*Peroxynitrate is a central reactive oxidant, which appears to play a major role in many disease processes.
ECE: Phase I Clinical Trial Results (Preliminary)
In an 8-week, double-blinded, placebo-controlled study of established fibromyalgia patients, ECE was used as an adjunct therapy to the patients’ current standard of physician care. The results established the general safety of ECE. ECE cut the time it took the participants to fall asleep by 47 minutes; it increased total nighttime sleep by 1.6 hours; it improved soundness of sleep by 80%; it boosted their energy levels by 71%; it gave them 2 1/4 more good days per week; it helped reduce their pain by 31%; and their general condition improved by 39%. Interestingly, these improvements were achieved at all doses. Patients given the placebo had no improvement during the study.
BRAIN FUNCTION: MEMORY, RELAXATION, ALERTNESS
Acetylcholine & Memory
Memory is dependent on the neurotransmitter acetylcholine (ACh). In an animal study, ECE increased rodent ACh by 140% in brain regions responsible for learning and memory in seven days. Memory enhancement increased by 100-200% at an oral dose as low as 0.2-1mg/kg.
With regard to mechanism, it is thought that the mild acetylcholinesterase inhibitory activity of two phlorotannin compounds found in ECE, dieckol (DE) and phlorofurofucoeckol (PFF), may be involved in the up-regulation of acetylcholine.
Increased Blood Flow
ECE crosses the blood-brain barrier and significantly improves blood flow, which is likely another way ECE improves memory. More specifically, Dr. Lee’s group found that ECE can increase the velocity of blood flow in the carotid artery from an average of 36.68 cm/sec. to 40.09 cm/sec., while the placebo showed no improvement.
Relaxation & Alpha-Waves
An EEG study on brain waves of healthy middle age volunteers found that ECE compounds increase alpha-waves. Alpha-waves are an indicator of relaxation.
Yet another study found that ECE compounds prevented sleepiness in bus drivers and in high school students during daytime activities. This is likely due to increased blood flow and oxygen delivery.
ECE demonstrated powerful neuroprotective effects owing to several features of its components. ECE compounds are both powerful antioxidants and anti-inflammatory agents capable of scavenging free radicals and suppressing excessive inflammatory reactions. Fucoidan in ECE has recently been found to protect neuronal cells from ischemia-induced inflammatory reactions which often occur in the aged and highly stressed brain. ECE compounds also neutralize the neurotoxic free-radical peroxynitrite.
Enhancement of Acetylcholine Levels in Mice
After 7 days oral administration of two ECE compounds (DE 10mg/kg and PFF 2mg/kg), mice under ethanol-induced cognitive impairment showed substantial enhancement of acetylcholine in three brain regions related to memory formation, as compared with non-treated mice. Especially, 140% enhancement was observed in the frontal cortex that is crucial in long-term memory and associative thinking.
Resistance of Stress-Induced Learning Deficit in Mice
In a 5-day study, ECE treated mice showed significant resistance to electric shock treatment-induced learning deficiency, as compared to non-treated mice whose learning process was significantly retarded during the test period.
Memory Enhancement in Mice
The beneficial effects of ECE compounds on memory enhancement were further demonstrated by measuring the latency time avoiding the previously experienced electric shock treatment in mice as passive-avoidance memory testing. After 7 days oral administration of two ECE compounds DE and PFF (as low as 1 and 0.2mg/kg), mice under ethanol-induced cognitive impairment showed 130-140% improvement, especially in the PFF group.
Beta-Amyloid Deposition Inhibition in Rats
Researchers at the National Institute of Health’s aging research labs in Baltimore studied ECE in rats, and found it to inhibit beta-amyloid deposition in the brain. Beta-amyloid is the same substance that accumulates in Alzheimer’s disease. The rats also learned maze challenges faster, which demonstrated improvement in short-term memory.
ARTHRITIS, INFLAMMATION, NEURALGIA
Dr. Lee and colleagues found ECE to naturally suppress inflammatory responses and neutralize inflammatory damage caused by reactive oxygen species. The optimal combination of ECE’s natural anti-inflammatory and tissue-protective properties appears to enable dramatic improvement in both arthritis and neuralgia. In a human trial, ECE significantly reduced pain in a group of knee arthritis patients compared with placebo.
Comparable to CelebrexÆ
ECE’s ability to treat arthritis was found to be comparable to CelebrexÆ, the prescription drug that reduces inflammatory cox enzymes.
The influence of ECE in lipopolysaccharide (LPS)-induced generation of prostaglandin E2 (PGE2) using RAW 246.7 cells was studied. While PGE2 was barely detectable in non-stimulated cells, more than one hundred times the amount of PGE2 was detected in the stimulated cells. ECE, celecoxib (CelebrexÆ) and aspirin all showed significant inhibition of PGE2 generation in the concentration range tested. ECE showed inhibition of 61%, 85%, 92% and 99% at concentrations of 10, 30, 60 and 100 µg/mL, showing similar activity to celecoxib which showed 65%, 79%, 85% and 96%.
Cartilage Protecting Activities
As demonstrated above, ECE compared almost identically to celecoxib in the ability to reduce PGE2 by slowing down the lipoxygenase (LOX) system. ECE compounds have more than double the ability of resveratrol to inhibit LOX. These results were demonstrated in a study on rabbit cartilage cells. Those cells treated with ECE had up to an 80% reduction in degeneration.
In an animal study, rabbit articular cartilage explant culture was treated with recombinant human interleukin 1 (rhIL-1) to induce proteoglycan degradation. The amount of glycosaminoglycan released into the medium was measured as an index of proteoglycan degradation. When the rabbit cartilage explants were treated with rhIL-1 for 60 hours, the amount of released glycosaminoglycan into the culture medium increased significantly compared to the vehicle group (1.44 ± 0.06µg/mg vs. 0.30 ± 0.01µg/mg). Diclofenac, which is known as a selective COX-2 inhibitor was used as a positive control at a dose of 10µM (3.2µg/mL). ECE significantly interfered with the rhIL-1-mediated degradation of proteoglycan in all concentrations tested (p <0.001). It showed 53%, 79%, 81% and 70% of inhibition at 1, 3, 10 and 30 µg/mL concentration.
Neuropathy: 4-Week Clinical Trial
Researchers recently studied ECE on 40 patients with neuropathy. ECE reduced nerve pain by 40% in four weeks. Overall, 80% of the patients responded favorably.
Speculation about Neuropathy Mechanism
The strong lipid and cholesterol reducing potential of ECE supports reduced vascular inflammation. Increasingly, the scientific literature supports the notion that many forms of nerve pain or neuropathy are caused by nerve pressure, as exerted by swollen, inflamed blood vessels adjacent to the nerves.
ALLERGIES / ASTHMA
Overall, ECE appears to significantly relieve allergic reactions without drowsiness, dizziness and other side effects of anti-histamine drugs.
Allergic Inflammation: Mouse Model
Dr. Lee and his team found that ECE significantly reduced allergic inflammation in mice. Specifically, ECE reduced the migration of eosinophils to the lungs by 75%. Inflammatory white blood cells (CD4+4 T Cells, resultant cytokines Il-4, 5, 13) were reduced by 50%. Mucus plugs in the airways were reduced by 75%. Airway epithelial hyperplasia reduced by 75%. Collagen-causing fibrosis in lung interstitium (fibrosis, airway remodeling) and smooth muscle cell thickness was reduced by 20% and 32%. These latter findings suggest that ECE compounds can prevent or reverse the progression of chronic lung disease such as asthma and Chronic Obstructive Pulmonary Disease (COPD).
5-Lipoxygenase (5-LOX) catalyzes the first step in the oxygenation of arachidonic acid, thus leading to the production of biologically active compounds such as leukotrienes and 5-hydroxyeicosatetraenoic acid. The peptidoleukotrienes (leukotriene C4, leukotriene D4 and leukotriene E4) are powerful spasmogens, which have been implicated in inflammatory and allergic responses. Therefore, inhibition of 5-LOX is a medicinal target for the treatment of inflammatory diseases. One of the ECE compounds (8,8-BE) significantly inhibits 5-LOX compared with other well-known natural medicinal compounds such as resveratrol and EGCG.
University of Washington Asthma Mouse Model
The efficacy of ECE for asthma was demonstrated in an allergen-induced murine asthma mouse model by Dr. Emil Chi, Chairman, Department of Histopathology, University of Washington.
The researchers tested an ECE product (KLS) in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal antigen sensitization on day 0 and day 14, were given weekly intranasal inhalations of antigen from day 14-60. The antigen-treated and challenged mice developed an extensive eosinophil and mononuclear cell inflammatory response, mucus cell hyperplasia and mucus occlusion of the airway.
KLS was found to be effective in reducing allergic reaction in inflammation. By feeding at a concentration of 5.4 mg/ml in the drinking water for 12 days, KLS reduced the airway mucus plugging, and sub-epithelial fibrosis in the antigen-sensitized / challenged mice. The reduced BAL fluid eosinophil indicated that KLS is effective in improving the asthmatic lung structures. No pathological alterations in the liver, kidney, spleen, or small intestine were found.
Coronary Artery Disease
ECE has been shown to improve coronary artery disease (CAD). Researchers found that ECE is even more potent at inhibiting the oxidation of LDL cholesterol than green tea catechins, and appears to scrub the plaque off the endothelial lining. ECE also reduces vascular inflammation by preventing oxidation, which also directly effects inflammatory mediators such as inflammatory prostaglandins, etc.
Coronary Artery Disease: 6-Week Clinical Trial
A clinical trial using ECE was conducted confirming its capacity to regenerate vascular endothelium and recover plasticity of blood vessels after 6 weeks of treatment by measuring flow-mediated dilation (FMD) & nitroglycerin-mediated dilation (NMD) of normal and CAD patients with narrowed coronary arteries by 50+%. FMD indicates nitric oxide (NO) releasing ability of endothelial cells to expand blood vessels by detecting shear stress caused by incoming blood flow (low FMD value can indicate endothelium damage).
After 6 weeks of treatment with ECE, clinical data showed that FMD, the endothelium-dependent dilation, was greatly enhanced in the CAD group, indicating its remarkable activity of inducing recovery of endothelial cells. NMD, the endothelium-independent dilation, which represents the vascular plasticity, also showed remarkable improvement in the CAD group, again supporting ECE’s ability to support restoration of vascular integrity by reversing atherosclerosis.
Cholesterol: 6-Week ClinicalTrial
Researchers gave 39 adults (average age 55.6) low dose (100 mg) ECE compounds for six weeks. Their average cholesterol dropped from 228 to 224. LDL dropped from 141 to 135. HDL rose from 46.5 to 50.7 (highly significant). Triglycerides fell from 215 to 195, and the atherogenic index dropped 12.5%.
Some of the parameters from the above study show very mild changes, which in themselves, may not be statistically significant. However, all parameters went in a health-positive direction, so taken together, the changes in LDL, HDL, triglycerides, blood pressure, and antioxidant protection are very significant. Also, endothelial cells were protected against oxidative damage, and were able to produce significantly more NO, which dilates blood vessels. Dramatic increases in blood flow were also found at this low dose.
Hypertension: 4-Week Animal Study
The remarkable effect of ECE on vasodilation was clearly demonstrated in renovascular clipping induced hypertensive rats. Renovascular clipping surgery is known to increase ACE activity via the renin-angiotensin-aldosterone system, which increased systolic blood pressure (SBP) from 140 to over 200 mm Hg after 4 weeks. Upon oral administration of phlorotannin (99.4%, 50 mg/kg) or enalapril (commercial hypotensive drug, 10 mg/kg) SBP dropped to as low as 160 and 140 mm Hg. Upon cessation of treatment, SBP increased again in both cases. Although ECE showed a similar pattern to the drugs, it also showed a slower rebounding of blood pressure during the no treatment period, which indicates its potential as a vascular protector with prolonged oral administration.
Angiotensin-converting enzyme (ACE), is responsible for conversion of angiotensin I to angiotensin II and degradation of bradykinin, and is a key component in the renin-angiotensin-aldosterone system. Angiotensin II regulates cellular proliferation, inflammation, and endothelial function, and is therefore important in the pathogenesis of atherosclerosis and its complications. Aging or various vascular risk factors tend to increase ACE levels resulting in excessive vasoconstriction and hypertension. Current hypotensive drugs block the action of ACE or its by-product angiotensin II.
ECE tannins have been found to be potent natural ACE inhibitors, demonstrating more than 15 times the power to inhibit ACE as the most powerful land-based polyphenols, including the natural hypotensive substance catechin found in green tea. One of the compounds found in ECE, THP-BE is comparable to the physiological vasodilative hormone bradykinin.
Plasmin (a fibrinolytic enzyme that breaks down blood clots) is rapidly blocked by a protein called antiplasmin. ECE compounds are natural potent inhibitors of anti-plasmin, capable of efficient promotion of plasmin that performs fibrinolysis. ECE compounds have shown remarkable activity which is 40-200 times greater than synthetic compounds Flufenamate and Chloramine T. One study on ECE compounds found a small but significant rise in prothrombin time and a fall in fibrinogen levels.
ERECTILE FUNCTION - ECE V. VIAGRAÆ
ECE can regenerate the vascular endothelium, the cells critical to the inner lining of the blood vessels. They generate the chemical nitric oxide (NO), which keeps the arterial walls relaxed and dilated. After a six-week study of ECE, flow mediated dilation and NO mediated dilation increased by 60% and 50%. In another study, coronary artery disease patients were given ECE for six weeks. Blood flow controlled by NO increased 50-60%. These results confirm that ECE can rejuvenate damaged endothelial cells to produce NO. This effect was further confirmed in a study on erectile dysfunction (see below). Interestingly, ViagraÆ works by increasing NO in the penile artery.
ECE v.ViagraÆ: 8-Week Clinical Trial
Scientists studied 31 men with erectile dysfunction (ED) for over six months. They compared eight weeks of ECE use to ViagraÆ. They looked at orgasmic function (OF), intercourse satisfaction (IS), overall satisfaction (OS), and erectile function (EF). Over those eight weeks, ECE scored 87%, 74%, 62%, and 66%. ViagraÆ scored 27%, 44%, 39%, and 66%. No side effects were reported with ECE:
Population with 25+% Improvement in IIEF (International Index of Erectile Function) score was as high as 81%. Total IIEF score significantly increased from 29.1 ± 13.1 to 47.0 ± 14.5 with 62% of improvement. When the IIEF scores were grouped into five separate domains, mean IIEF scores at the 8th week were significantly greater than those at week 0 for all domains (all p<0.01). The degree of improvement was significant in the following order: OF (87%), IS (74%), EF (66%), and OS (62%). Scores on key questions (asking frequency of penetration and asking frequency of maintaining an erection after penetration), which directly indicate the ability to achieve and maintain an erection sufficient for sexual activity, were improved up to 74% and 77%, respectively (p<0.01).
It is very important to note that despite the marginal improvement in sexual desire (20%) that is of psychological nature, great improvements were reported in the domains directly related with erection that is of physical nature and dependent on normal vascular function of the penile artery.
Also noteworthy, was a significant increase in the orgasmic function score (87%), intercourse satisfaction (74%) and overall satisfaction (62%) as well as erectile function (66%) in comparison with the results for sildenafil reported by Marks, et al. (Marks, et al., 1999) (27%, 44%, 39% and 66%, respectively), which indicates that ECE significantly contributed to the normalization of the general vascular conditions around the sexual organ.
These results strongly indicate that the long-term administration of ECE significantly contributes to the neutralization of oxidative risk factors, thereby improving peripheral blood circulation around muscles and nerves involved in sexual function as well as the penile artery. No side effects were reported.
Vasodilation & Erectile Function
It has been reported that vasculogenic ED patients have elevated levels of angiotensin II for the duration of the erection process. The demonstrated action of ECE on ACE and resulting vasodilation is thought to play an important role in inducing successful erectile function.
Long-Term Improvement Via Vascular Protection
As discussed, ECE phlorotanins have potent antioxidant and anti-inflammatory effects. Together with ECE's ACE inhibitory activity, which is also beneficial to vascular homeostasis, these activities, upon long-term oral administration, may all contribute to supporting a healthy vascular system, including the penile artery.
Diacylglycerol acetyl transferase (DGAT) is the enzyme involved in the final step of triglyceride synthesis. Triglycerides are circulating fat bodies that ultimately wind up in the fat cells, and are almost always elevated in diabetes. They also have emerged as a major risk factor in vascular disease.
Dr. Lee found that ECE compounds inhibited DGAT more than 50%. In genetically caused obese laboratory rats, ECE reduced body fat and increased physical activity. In another study, ECE caused leanness and fat-resistance in animals given a high fat diet.
ECE Beverage: 2-Week Clinical Trial
In a human study, 141 young adults were given a beverage containing ECE at 200 mg daily. In two weeks their average weight dropped nearly 2.5 pounds, muscle mass increased by nearly 2.5 pounds, and body fat dropped by 4 pounds, or 7.48%. ECE stimulates the body to burn fat by increasing muscle mass.
Obesity & Cardiovascular Disease
As discussed, ECE contains an optimal combination of natural compounds capable of suppressing triglyceride synthesis, while promoting cholesterol removal and cardiovascular protection. ECE provides additional cardiovascular protection for obese patients prone to CVD and CHD through lowering LDL cholesterol and scavenging free radicals.
DGAT Inhibition & Obesity
DGAT inhibition has recently been recognized as a novel and safe target for the treatment of obesity. DGAT is involved in intestinal fat absorption, lipoprotein assembly, regulation of plasma TG concentration, fat storage in adipocytes, and energy metabolism in muscle. DGAT knockout mice have been shown to have obesity resistance with a high-fat diet, the mechanism of which was confirmed to be through energy expenditure.
Aldose Reductase Inhibition
When blood sugar levels become elevated, aldose reductase is the enzyme that converts excess glucose into the sugar alcohol sorbitol. Sorbitol can build up in critical cells and cause damage. Recent research found that animals deficient in aldose reductase were protected from the retinal complications of diabetes. ECE compounds have been found to be potent aldose reductase inhibitors, which may be of benefit for patients with metabolic syndrome, syndrome X, or diabetes.
Reduced Fat in Liver & Pancreas
A mouse study showed that ECE reversed fat deposition in liver and pancreas cells. Furthermore, this same study showed that ECE served to markedly inhibit NF-kappaB inflammation in the pancreas. A recent Harvard (Joslin School of Diabetes) mouse study directly implicates excessive fat deposition in the mouse pancreas as turning on the NF-kappaB inflammation pathway, resulting in full-blown type II diabetes and insulin insensitivity in the mice.
ECE is manufactured from edible algae through food-compatible processes. Tens of thousands of people throughout the world have experienced ECE in various forms of product without side effects. To date, Dr. Lee’s team has not found any toxicity at any level. Several toxicity tests have been performed, and no adverse effects have been found at the effective human dose level of 1-10 mg/kg.
• “Composition For Prevention And Improvement Of Dementia And Promotion Of Memory, And Healthy Assistance Foodstuffs Containing The Composition” Korean Patent Application# 10-2003-88177 (Assigned To Haengwoo Lee).
• “Compound For Improving Hypertension Containing Inhibitors Of Angiotensin Converting Enzyme Activity Extracted From Marin Plants And Articles Comprising Thereof”, Korean Patent Application 10-2004-24347 (Livechem, Inc).
• “Compound For Improving Neuralgia Containing Dibenzo-P-Dioxine Derivatives Extracted From Marine Plants And Articles Comprising Thereof”. Korean Patent Application 10-2004-0028066 (Livechem, Inc).
• Ahn MJ, Yoon KD, Min SY, Lee JS, Kim JH, Kim TG, Kim SH, Kim NG, Huh H, Kim J. Inhibition of HIV-1 reverse transcriptase and protease by phlorotannins from the brown alga Ecklonia cava. Biol Pharm Bull. 2004 Apr;27(4):544-7.
• Aikawa, T., S. Shimura, H. Sasaki, M. Ebina, And T. Takishima. 1992. Marked Goblet Cell Hyperplasia With Mucus Accumulation In The Airways Of Patients Who Died Of Severe Acute Asthma Attack. Chest 101:916-921.
• Athukorala Y, Kim KN, Jeon YJ. Antiproliferative and antioxidant properties of an enzymatic hydrolysate from brown alga, Ecklonia cava. Food Chem Toxicol. 2006 Jul;44(7):1065-74. Epub 2006 Mar 3.
• Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Jonas U. Plasma levels of angiotensin II during different penile conditions in the cavernous and systemic blood of healthy men and patients with erectile dysfunction. Urology. 2001 Nov;58(5):805-10.
• Becker AJ, Uckert S, Stief CG, Truss MC, Machtens S, Scheller F, Knapp WH, Hartmann U, Jonas U. Possible role of bradykinin and angiotensin II in the regulation of penile erection and detumescence. Urology. 2001 Jan;57(1):193-8.
• Cases S, Smith SJ, Zheng YW, Myers HM, Lear SR, Sande E, Novak S, Collins C, Welch CB, Lusis AJ, Erickson SK, Farese RV Jr. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13018-23.
• Chapman VJ, Chapman DJ. (1980). Seaweeds and their uses. London: Chapman & Hall.
• De Angelis L, Marfella MA, Siniscalchi M, Marino L, Nappo F, Giugliano F, De Lucia D, Giugliano D. Erectile and endothelial dysfunction in Type II diabetes: a possible link. Diabetologia. 2001 Sep;44(9):1155-60.
• Djukanovic, R., J.W. Wilson, K.M. Britten, S.J. Wilson, A.F. Walls, W.R. Roche, P.H. Howarth, S.T. Holgate. 1990. Quantitation Of Mast Cells And Eosinophils In The Bronchial Mucosal Of Symptomatic Atopic Asthmatics And Healthy Control Subjects Using Immunohistochemistry. Am.Rev.Respir.Dis. 142:863-871.
• Dorrance AM, Lewis RW, Mills TM. “Captopril Treatment Reverses Erectile Dysfunction In Male Stroke Prone Spontaneously Hypertensive Rats.” Int J Impot Res. 2002 Dec;14(6):494-7
• Fukuyama Y, Kodama M, Miura I, Kinzyo Z, Mori H, Nakayama Y, Takahashi M. Anti-plasmin inhibitor. VI. Structure of phlorofucofuroeckol A, a novel phlorotannin with both dibenzo-1,4-dioxin and dibenzofuran elements, from Ecklonia kurome Okamura. Chem Pharm Bull (Tokyo). 1990 Jan;38(1):133-5.
• Fukuyama, Y., Kodama, M., Miura, I., Kinzyo, Z., Kido, M., Mori, H., Nakayama, Y., Takahashi, M. Structure Of An Anti-Plasmin Inhibitor, Eckol, Isolated From The Brown Alga Ecklonia Kurome Okamura And Inhibitory Activities Of Its Derivatives On Plasmin Inhibitors. Chem. Pharm. Bull. 37: 349-353 (1989)
• Glombitza, K.W., Gerstberger, G. Phlorotannins With Dibenzodioxin Structural Elements From The Brown Alga Eisenia Arborea. Phytochemistry 24: 543-551 (1985)
• Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, Sheppard D, Mohrs M, Donaldson DD, Locksley RM, Corry DB. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998 Dec 18;282(5397):2261-3.
• Hamed EA, Meki AR, Gaafar AA, Hamed SA. Role Of Some Vasoactive Mediators In Patients With Erectile Dysfunction: Their Relationship With Angiotensin-Converting Enzyme And Growth Hormone. Int J Impot Res. 2003 Dec;15(6):418-25.
• Henderson, W.R., E.Y. Chi. 1985. Ultrastructural Characterization And Morphometric Analysis Of Human Eosinophil Degranulation. J. Cell Sci. 73:33-48.
• Henderson, W.R., Jr., D.B. Lewis, R.K. Albert, Y. Zhang, W.J.E. Lamm, G.K.S. Chiang, F. Jones, P. Eriksen, Y. Tien, M. Jonas, E.Y. Chi. 1996. The Importance Of Leukotrienes In Airway Inflammation In A Mouse Model Of Asthma. J. Exp. Med. 184:1483-1494.
• Henderson, W.R., Jr., E.Y. Chi, C.R. Maliszewski. 2000. Soluble Interleukin-4 Receptor (Sil-4R) Inhibits Airway Inflammation Following Allergen Challenge In A Mouse Model Of Asthma. J. Immunol. 164:1086-1095.
• Hoppe HA. (1979). Marine algae and their products and constituents in pharmacy. In: Marine Algae in Pharmaceutical Science. Hoppe HA, Levring T, Tanaka Y, eds. Berlin & New York: Walter de Gruyter.
• Hoshino, M., Y. Nakamura, J.J. Sim. 1998. Expression Of Growth Factors And Remodeling Of The Airway Wall In Bronchial Asthma. Thorax 53:21-27.
• Kang K, Park Y, Hwang HJ, Kim SH, Lee JG, Shin HC. Antioxidative properties of brown algae polyphenolics and their perspectives as chemopreventive agents against vascular risk factors. Arch Pharm Res. 2003 Apr;26(4):286-93.
• Kang KA, Lee KH, Chae S, Koh YS, Yoo BS, Kim JH, Ham YM, Baik JS, Lee NH, Hyun JW. Triphlorethol-A from Ecklonia cava protects V79-4 lung fibroblast against hydrogen peroxide induced cell damage. Free Radic Res. 2005 Aug;39(8):883-92.
• Kang KA, Lee KH, Chae S, Zhang R, Jung MS, Ham YM, Baik JS, Lee NH, Hyun JW. Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation. J Cell Biochem. 2006 Feb 15;97(3):609-20.
• Kang KA, Lee KH, Chae S, Zhang R, Jung MS, Lee Y, Kim SY, Kim HS, Joo HG, Park JW, Ham YM, Lee NH, Hyun JW. Eckol isolated from Ecklonia cava attenuates oxidative stress induced cell damage in lung fibroblast cells. FEBS Lett. 2005 Nov 21;579(28):6295-304. Epub 2005 Oct 19.
• Kang KA, Zhang R, Lee KH, Chae S, Kim BJ, Kwak YS, Park JW, Lee NH, Hyun JW. Protective effect of triphlorethol-A from Ecklonia cava against ionizing radiation in vitro. J Radiat Res (Tokyo). 2006 Mar;47(1):61-8.
• Kang, K., Park, Y., Hwang, H. J., Kim, S. H., Lee, J. G., Shin, H.-C. (2003). Antioxidative Properties Of Brown Algae Polyphenolics And Their Perspectives As Chemopreventive Agents Against Vascular Risk Factors. Arch. Pharm. Res.. 26: 286-293
• Kang, K.J., Hwang, H.J., Hong, D.H., Park, Y.J., Kim, S,H., Lee, B.H., Shin, H.C. Anti-Oxidant And Anti-Inflammatory Activities Of Ventol, A Phlorotannin-Rich Natural Agent Derived From Ecklonia Cava, And Its Effect On Proteoglycan Degradation In Cartilage Explant Culture. Submitted To Molecular Pathology And Pharmacology
• Kay, A.B. 1997. T Cells As Orchestrators Of The Asthmatic Response. Ciba Found. Symp. 206:56-67.
• Kim MM, Ta QV, Mendis E, Rajapakse N, Jung WK, Byun HG, Jeon YJ, Kim SK. Phlorotannins in Ecklonia cava extract inhibit matrix metalloproteinase activity. Life Sci. 2006 Sep 5;79(15):1436-43. Epub 2006 May 7.
• Krug, N., J. Madden, A.E. Redington, P. Lackie, R. Djukanovic, U. Schauer, S.T. Holgate, A.J. Frew, P.H. Howarth. 1996. T-Cell Cytokine Profile Evaluated At The Single Cell Level In Bal And Blood In Allergic Asthma. Am. J. Respir. Cell Mol. Biol. 14:319-326.
• Lee, B.H., Stein, S. Improvement Of Learning Behavior Of Mice By An Antiacetylcholinesterase And Neuroprotective Agent Nx42, A Laminariales-Alga Extract. Presented To The Pharm. Soc. Kor., Spring Conference (2004); Manuscript Submitted To Korean Journal Of Food Science And Technology.
• Lee, S.H., Han, S.B., Baik, J.Y. The Influence Of VNP Intake On The Symptoms Of Osteoarthritis Of The Knee Joint. Clinical Report By Department Of Orthopedic Surgery, Anam Hospital, Korea University Medical Center
• Mcever, R.P. 1991. Selectins: Novel Receptors That Mediate Leukocyte Adhesion During Inflammation. Thromb. Haemost. 65:223-228.
• Myung CS, Shin HC, Bao HY, Yeo SJ, Lee BH, Kang JS. Improvement of memory by dieckol and phlorofucofuroeckol in ethanol-treated mice: possible involvement of the inhibition of acetylcholinesterase. Arch Pharm Res. 2005 Jun;28(6):691-8.
• Nakamura, T., Nagayama, K., Uchida, K., Tanaka, R. Antioxidant Activity Of Phlorotannins Isolated From The Brown Alga Eisenia Bicyclis. Fisheries Sci. 62: 923-926 (1996).
• Roche, W.R., R. Beasley, J.H. Williams, S.T. Holgate. 1989. Subepithelial Fibrosis In The Bronchi Of Asthmatics. Lance 1:520-524.
• Ruehl ML, Orozco JA, Stoker MB, Mcdonagh PF, Coull BM, Ritter LS. Protective Effects Of Inhibiting Both Blood And Vascular Selectins After Stroke And Reperfusion. Neurol Res. 2002 Apr;24(3):226-32.
• Sheehan, D.C., B.B. Hrapchak. 1980. Connective Tissue/Muscle Fiber Stains. In Theory And Practice Of Histotechnology. Battelle Press, Columbus, OH. 180-201.
• Shibata, T., Fujimoto, K., Nagayama, K., Yamaguchi, K., Nakamura, T. Inhibitory Activity Of Brown Algal Phlorotannins Against Hyaluronidase. Int. J. Food Sci. Tech. 37: 703-709 (2002)
• Shibata, T., Nagayama, K., Tanaka, R., Yamaguchi, K., Nakamura, T. Inhibitory Effects Of Brown Algal Phlorotannins On Secretory Phospholipase A2S, Lipoxygenases And Cycloxygenases. J. Appl. Phycol. 15: 61-66 (2003)
• Shin HC, Hwang HJ, Kang KJ, Lee BH. An antioxidative and antiinflammatory agent for potential treatment of osteoarthritis from Ecklonia cava. Arch Pharm Res. 2006 Feb;29(2):165-71.
• Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV Jr. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet. 2000 May;25(1):87-90.
• Temann UA, Prasad B, Gallup MW, Basbaum C, Ho SB, Flavell RA, Rankin JA. A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion. Am J Respir Cell Mol Biol. 1997 Apr;16(4):471-8.
• Tsukada H, Nishiyama S, Fukumoto D, Ohba H, Sato K, Kakiuchi T. Effects of acute acetylcholinesterase inhibition on the cerebral cholinergic neuronal system and cognitive function: Functional imaging of the conscious monkey brain using animal PET in combination with microdialysis. Synapse. 2004 Apr;52(1):1-10.
• Uhm CS, Kim KB, Lim JH, Pee DH, Kim YH, Kim H, Eun BL, Tockgo YC. Effective treatment with fucoidin for perinatal hypoxic-ischemic encephalopathy in rats. Neurosci Lett. 2003 Dec 15;353(1):21-4.
• Virag R, Floresco J, Richard C. Impairment Of Shear-Stress-Mediated Vasodilation Of Cavernous Arteries In Erectile Dysfunction. Int J Impot Res. 2004 Jan;16(1):39-42
• Wills-Karp, M., J. Luyimbazi, X. Xu, B. Schofield, T.Y. Neben, C.L. Karp, D.D. Donaldson. 1998. Interleukin-13: Central Mediator Of Allergic Asthma. Science 282:2258-2261.
• Zhu, Z., R.J. Homer, Z. Wang, Q. Chen, G.P. Geba, J. Wang, Y. Zhang, J.A. Elias. 1999. Pulmonary Expression Of Interleukin-13 Causes Inflammation, Mucus Hypersecretion, Subepithelial Fibrosis, Physiologic Abnormalities, And Eotaxin Production. J. Clin. Invest. 103:779-788.