Conformationally Restricted Glycopeptide Backbone Inhibits Gas-Phase H/D Scrambling between Glycan and Peptide Moieties.

Protein glycosylation is a common post-translational modification on extracellular proteins. The conformational dynamics of several glycoproteins have been characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS). However, it is, in most cases, not possible to extract information about glycan conformation and dynamics due to the general difficulty of separating the deuterium content of the glycan from that of the peptide (in particular, for O-linked glycans). Here, we investigate whether the fragmentation of protonated glycopeptides by collision-induced dissociation (CID) can be used to determine the solution-specific deuterium content of the glycan. Central to this concept is that glycopeptides can undergo a facile loss of glycans upon CID, thereby allowing for the determination of their masses. However, an essential prerequisite is that hydrogen and deuterium (H/D) scrambling can be kept in check. Therefore, we have measured the degree of scrambling upon glycosidic bond cleavage in glycopeptides that differ in the conformational flexibility of their backbone and glycosylation pattern. Our results show that complete scrambling precedes the glycosidic bond cleavage in normal glycopeptides derived from a glycoprotein; i.e., all labile hydrogens have undergone positional randomization prior to loss of the glycan. In contrast, the glycosidic bond cleavage occurs without any scrambling in the glycopeptide antibiotic vancomycin, reflecting that the glycan cannot interact with the peptide moiety due to a conformationally restricted backbone as revealed by molecular dynamics simulations. Scrambling is also inhibited, albeit to a lesser degree, in the conformationally restricted glycopeptides ristocetin and its pseudoaglycone, demonstrating that scrambling depends on an intricate interplay between the flexibility and proximity of the glycan and the peptide backbone.

Intratympanic Administration of Dieckol Prevents Ototoxic Hearing Loss.

OBJECTIVE: Systemic administration of dieckol reportedly ameliorates acute hearing loss. In this study, dieckol was delivered to the inner ear by the intratympanic route. The functional and anatomic effects and safety of dieckol were assessed using the rat ototoxicity model. MATERIALS AND METHODS: Dieckol in a high-molecular-weight hyaluronic acid vehicle (dieckol+vehicle group) or vehicle without dieckol (vehicle-only group) were randomly delivered into 12 ears intratympanically. Ototoxic hearing loss was induced by intravenous administration of cisplatin, gentamicin, and furosemide. The hearing threshold and surviving outer hair cells (OHC) were enumerated. Biocompatibility was assessed by serial endoscopy of the tympanic membrane (TM), and the histology of the TM and the base of bulla (BB) mucosa was quantitatively assessed. RESULTS: The hearing threshold was significantly better (difference of 20 dB SPL) in the dieckol+vehicle group than in the vehicle-only group. The number of surviving OHCs was significantly greater in the dieckol+vehicle group than in the vehicle-only group. There were no signs of inflammation or infection in the ear. The thickness of the TM and the BB mucosa did not differ between the two groups. CONCLUSION: Intratympanic local delivery of dieckol may be a safe and effective method to prevent ototoxic hearing loss.

Regioselective Synthesis of 6-O-Acetyl Dieckol and Its Selective Cytotoxicity against Non-Small-Cell Lung Cancer Cells.

Dieckol, a phlorotannin from Ecklonia cava, has shown potential for use as an anticancer agent that selectively kills cancer cells. However, it is necessary to amplify its potency without damaging its inherent safety in order to develop it as a competitive chemotherapeutic. Here, we explored the controlled O-acylations of dieckol. Acyl groups could be consistently introduced to the 6-O position of dieckol with a high regioselectivity, which was confirmed by NOESY, HMBC and HSQC spectroscopies. In cytotoxicity studies on the newly synthesized 6-O-acetyl, 6-O-benzoyl dieckols and previously synthesized 6-O-alkyl dieckols against A549 vs. normal cells, all of the derivatives showed low cytotoxicity in normal cells with an IC50 of 481-719 µM, and highly structure-dependent cytotoxicity in A549 cells with an IC50 of 7.02 (acetyl)-842.26 (benzyl) µM. The selectivity index also showed a large structure dependency in the range of 0.67 (benzyl)-68.58 (acetyl). An analysis of the structure-activity relationship indicated that the activity was dramatically reduced in the presence of a benzene ring and was highly increased in the presence of small polar substituents. Conclusions: Controlled mono-O-modifications of dieckol could be a powerful tool to enhance the anticancer activity of dieckol, thus contributing to the development strategy for dieckol-based chemotherapeutics.

Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

Multifunctional activity of polyphenolic compounds associated with a potential for Alzheimer's disease therapy from Ecklonia cava.

Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3 µM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol-A (PFF-A), showed a particularly potent inhibitory activity (IC50 0.95 µM), which is over 100-fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Aß. Bieckol and PFF-A inhibited amyloid precursor protein biosynthesis. PFF-A also showed very strong ß-secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease.

Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders.

Phlorotannins are natural polyphenolic compounds produced by brown marine algae and are currently found in nutritional supplements. Although they are known to cross the blood-brain barrier, their neuropharmacological actions remain unclear. Here we review the potential therapeutic benefits of phlorotannins in the treatment of neurodegenerative diseases. In mouse models of Alzheimer's disease, ethanol intoxication and fear stress, the phlorotannin monomer phloroglucinol and the compounds eckol, dieckol and phlorofucofuroeckol A have been shown to improve cognitive function. In a mouse model of Parkinson's disease, phloroglucinol treatment led to improved motor performance. Additional neurological benefits associated with phlorotannin intake have been demonstrated in stroke, sleep disorders, and pain response. These effects may stem from the inhibition of disease-inducing plaque synthesis and aggregation, suppression of microglial activation, modulation of pro-inflammatory signaling, reduction of glutamate-induced excitotoxicity, and scavenging of reactive oxygen species. Clinical trials of phlorotannins have not reported significant adverse effects, suggesting these compounds to be promising bioactive agents in the treatment of neurological diseases. We therefore propose a putative biophysical mechanism of phlorotannin action in addition to future directions for phlorotannin research.

Effects of 12-week oral supplementation of Ecklonia cava polyphenols on anthropometric and blood lipid parameters in overweight Korean individuals: a double-blind randomized clinical trial.

The effects of 12-week supplementation with a polyphenol extract from Ecklonia cava (ECP) on anthropometry, serum biochemistry and hematology have been investigated. Ninety-seven overweight male and female adults (average age 40.5 ± 9.2 yr and body mass index (BMI) of 26.5 ± 1.6 kg/m²) were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Subjects were randomly allocated into three groups designated as PC (placebo), LD (low-dose, 72 mg-ECP/day) and HD (high-dose, 144 mg-ECP/day). Both LD and HD groups showed significant decreases in BMI, body fat ratio, waist circumference, waist/hip ratio, total cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol/high-density lipoprotein (HDL) cholesterol and atherogenic index (AI) after 12 weeks, as compared with the placebo group. The HD group also showed a significant increase in serum HDL cholesterol as compared with the placebo group. Only the HD group showed significant decreases in serum glucose and systolic blood pressure after 12 weeks. There was no significant adverse event related with ingestion of ECP, and serum biochemical and hematological parameters were maintained within normal range during the intervention period. In conclusion, these results demonstrated that ECP supplementation significantly contributed to lowering body fat and serum lipid parameters such as total and LDL cholesterols with dose dependence. Further studies using different populations, dosages or biological markers are highly recommended to better understand the physiological features of this polyphenol.

Effects of marine oligomeric polyphenols on body composition and physical ability of elderly individuals with sarcopenia: a pilot study.

PURPOSE: We aimed to identify the effects of marine oligomeric polyphenol (MOP) intake in elderly individuals with sarcopenia. METHODS: Older adults (aged 65 years or older) were recruited based on the diagnostic criterion for sarcopenia and were randomly assigned to the MOP intake group (n=10) or the placebo (PBO) intake group (n=10). To determine the effect of MOP intake received for four weeks, the pre- and post-intake body composition (weight, skeletal muscle mass, and bone density) and senior fitness tests were assessed. RESULTS: Our results showed there were significant differences in the skeletal muscle mass (p=0.039), bone density (p=0.020), fat-free mass index (p=0.026), and 2.4 m up and go test (p=0.001) between pretest and post-test. There was a significant difference between the pre-test and post-test and an interaction effect for the one-leg stand test (p=0.010 and p=0.049, respectively). However, there were no significant differences in body fat percentage, calf circumference, grip strength, or the chair rise test. CONCLUSION: Some variables exhibited significant differences in the pre- and post-assessments, and there was an interaction effect for the one-leg stand. However, this was insufficient to prove the effectiveness of MOP intake in improving sarcopenia. Therefore, additional studies are essential to examine the effects of MOP intake and exercise intervention on the body composition and fitness of patients over a longer period.

Voltammetric, spectroscopic, and cellular characterization of redox functionality of eckol and phlorofucofuroeckol-A: A comparative study.

Interest in phlorotannins has increased in recent years largely due to antioxidant capacity, however, the redox mechanism of phlorotannins is still obscure. In the present study, the electrochemical oxidation mechanisms of eckol (EL) and phlorofucofuroeckol-A (PFF-A), two representative phlorotannin compounds, were comparatively analyzed in a wide pH range using cyclic and differential pulse voltammetry as well as spectroscopic assay. The voltammetric study revealed that EL and PFF-A were successively oxidized in three pH-dependent steps. Moreover, it was found that the PFF-A presented a stronger proton and electron transferring activity as compared to EL since PFF-A exhibited lower acid-base dissociation constant (pKa ) value and higher heterogeneous rate constant (kbh ) value in the first oxidation step. These property were further evidenced by comparison of direct antioxidant activity (i.e., superoxide anion and peroxide radicals) as well as indirect antioxidant activity (i.e., mRNA expression of two phase II enzymes) between EL and PFF-A. PRACTICAL APPLICATIONS: Phlorotannins from edible algae have been regarded as novel antioxidants those presented high application potential in food industry. Even though antioxidant activity of phlorotannin compounds have been widely investigated in both in vitro and in vivo studies, very few reports focused on electron transferring functionality which is chemical basis for antioxidant process. Herein, the oxidative mechanisms of two representative phlorotannins were comparatively analyzed using multiple electrochemical methods. This is hopefully to give information on the chemical meaning behind the antioxidant activity of dietary phlorotannins.

Comparative analysis of oxidative mechanisms of phloroglucinol and dieckol by electrochemical, spectroscopic, cellular and computational methods.

Numerous studies have been carried out on the redox activities of phenolic compounds from terrestrial plants, however, the redox pathway of phlorotannins, a type of marine algae-derived polyphenol, is far from clear. In the present study, the redox mechanisms of two phlorotannins, phloroglucinol (PL) and dieckol (DL), were comparatively scrutinized. Differential pulse voltammetry was conducted in the pH range 2.0-12.0 to determine the acid-base dissociation constant (pK a) and the number of electrons and protons involved in the redox reactions of two phlorotannins. Cyclic voltammetry was applied to obtain the heterogeneous electron transfer rate constant (k 0). By means of computational calculation, UV-vis spectroscopy, and electrochemical analysis, it is proposed that PL oxidation in the whole pH range undergoes two steps which are dominated by proton-coupled electron transfer (PCET) (pH ≤ 9) and sequential proton-loss electron transfer (SPLET) mechanisms (pH > 9), respectively. In contrast, the multiple steps taking place in the DL oxidation process rely on PCET (pH ≤ 5), mixed SPLET/PCET (5 < pH ≤ 10), and electron transfer (pH > 10) mechanisms, respectively. Also, the lower proton affinity and ionization potential values of DL, which are attributed to its conjugated Cπ-O-Cπ moieties, lead to relatively higher redox activity as compared to PL in various chemical and cellular models. These findings may provide useful insights into the oxidative conversion of phlorotannins in their biological and chemical processes.

Cardioprotective Effects of a Phlorotannin Extract Against Doxorubicin-Induced Cardiotoxicity in a Rat Model.

Long-term therapy with doxorubicin (DOX) is associated with high incidence of cumulative and irreversible dilated cardiomyopathy. The goal of this study was to evaluate the cardioprotective effects and safety of a phlorotannin extract from a brown algae Ecklonia cava (Seapolynol™, SPN) against DOX-induced cardiotoxicity in a rat model. A total of 42 rats were divided into six groups: control, low-dose SPN (LDS), high-dose SPN (HDS), DOX, DOX with low-dose SPN (DOX+LDS), and DOX with high-dose SPN (DOX+HDS). Echocardiography was performed at baseline and after 6 weeks. In left ventricular (LV) ejection fraction, DOX and DOX+LDS groups showed significant decreases (P < .001), while LDS, HDS, and DOX+HDS groups showed no significant change compared with control group. In LV mass index, DOX and DOX+LDS groups showed significant increases (P < .001 and P = .013), while LDS, HDS, and DOX+HDS groups showed no significant change compared with control group. In electron microscopy of the LV wall tissue, DOX+HDS group showed markedly less impaired myofibrils and mitochondria compared with both DOX and DOX+LDS groups. On the findings in echocardiography and electron microscopy, 6-week oral administration of SPN was safe and cardioprotective in a DOX-induced rat cardiotoxicity model in a dose-dependent manner.

An antioxidative and antiinflammatory agent for potential treatment of osteoarthritis from Ecklonia cava.

Osteoarthritis is thought to be induced by the ageing-related loss of homeostatic balance between degeneration and repair mechanism around cartilage tissue in which inflammatory mediators such as reactive oxygen species, cytokines and prostaglandins are prone to over-production under undesirable physiological conditions. Phlorotannins are unique polyphenolic compounds bearing dibenzo-1,4-dioxin skeleton which are not found in terrestrial plants but found only in some brown algal species such as Ecklonia and Eisenia families. Phlorotannin-rich extracts of Ecklonia cava including LAD103 showed significant antioxidant activities such as DPPH radical scavenging, ferric ion reduction, peroxynitrite scavenging, and inhibition of LDL oxidation, indicating their possible antioxidative interference both in onset and downstream consequences of osteoarthritis. LAD103 also showed significant down regulation of PGE2 generation in LPS-treated RAW 246.7 cells, and significant inhibition of human recombinant interleukin-1alpha-induced proteoglycan degradation, indicating its beneficial involvement in pathophysiological consequences of osteoarthritis, the mechanism of which needs further investigation. Since LAD103 showed strong therapeutic potentials in arthritic treatment through several in vitro experiments, it is highly encouraged to perform further mechanistic and efficacy studies.

Protective effects of the seaweed phlorotannin polyphenolic compound dieckol on gentamicin-induced damage in auditory hair cells.

OBJECTIVES: Drug-induced ototoxicity from compounds such as aminoglycosides and platinum can damage the inner ear resulting in hearing loss, tinnitus or balance problems and may be caused by the formation of reactive oxygen species (ROS). Dieckol is a phlorotannin polyphenolic compound with strong antioxidant effects found in edible brown algae. This study investigated the protective effects of dieckol on drug-induced ototoxicity in cochlear cultures obtained from neonatal mice. METHODS: Cochlear explants were pretreated with dieckol and exposed to gentamicin for 48h. The explants were then fixed and stained with fluorescein isothiocyanate-phalloidin and the intact hair cells counted. The free radical scavenging activity of dieckol was assessed using a 1,1-diphenyl-2-picrylhydrazyl assay. E. coli (Escherichia coli) cultures were used to evaluate the effect of dieckol on the antibiotic activity of gentamicin. RESULTS: Gentamicin treatment resulted in dose-dependent hair cell loss that was partially protected by dieckol. Moreover, at concentrations >67µM dieckol had significant radical scavenging activity. Dieckol did not compromise the antibiotic effect of gentamicin. CONCLUSIONS: These findings suggest that dieckol can be used as a therapeutic agent that reduces the damage caused by drug-induced ototoxicity.

Enhancement of Human Hair Growth Using Ecklonia cava Polyphenols.

BACKGROUND: Ecklonia cava is a brown alga that contains various compounds, including carotenoids, fucoidans, and phlorotannins. E. cava polyphenols (ECPs) are known to increase fibroblast survival. The human dermal papilla cell (hDPC) has the properties of mesenchymal-origin fibroblasts. OBJECTIVE: This study aims to investigate the effect of ECPs on human hair growth promotion in vitro and ex vivo. METHODS: MTT assays were conducted to examine the effect of ECPs on hDPC proliferation. Hair growth was measured using ex-vivo hair follicle cultures. Real-time polymerase chain reaction was performed to evaluate the mRNA expression of various growth factors in ECP-treated hDPCs. RESULTS: Treatment with 10 µg/ml purified polyphenols from E. cava (PPE) enhanced the proliferation of hDPCs 30.3% more than in the negative control (p<0.001). Furthermore, 0.1 µg/ml PPE extended the human hair shaft 30.8% longer than the negative control over 9 days (p<0.05). Insulin-like growth factor-1 (IGF-1) mRNA expression increased 3.2-fold in hDPCs following treatment with 6 µg/ml PPE (p<0.05). Vascular endothelial growth factor (VEGF) mRNA expression was also increased 2.0-fold by 3 µg/ml PPE (p<0.05). Treatment with 10 µg/ml PPE reduced oxidative stress in hDPCs (p<0.05). CONCLUSION: These results suggest that PPE could enhance human hair growth. This can be explained by hDPC proliferation coupled with increases in growth factors such as IGF-1 and VEGF. Reducing oxidative stress is also thought to help increase hDPCs. These favorable results suggest that PPE is a promising therapeutic candidate for hair loss.

Protective effect of a purified polyphenolic extract from Ecklonia cava against noise-induced hearing loss: Prevention of temporary threshold shift.

OBJECTIVE: Noise is one of the most common causes of hearing loss. Approximately 16% of American teenagers (12-19 years) have hearing loss caused by loud noise. The implication of noise-induced hearing loss (NIHL) in teenagers has received increasing attention. Although temporary threshold shift (TTS), a type of NIHL, is a transient hearing loss, it can accelerate age-related hearing loss. Reactive oxygen species are a primary cause of TTS. As the polyphenols from Ecklonia cava are known to have potent antioxidant effects, we investigated the protective effects of a purified polyphenolic extract of Ecklonia cava (PPEE) against TTS in mice. METHODS: The radical-scavenging activity of PPEE was evaluated using the 1,1-diphenyl-2-picrylhydrazyl assay. The PPEE + Noise and Saline + Noise groups were administered intraperitoneal PPEE (100 mg/kg) and saline, respectively, for 5 days before exposure to noise at 100 dB SPL for 60 min. Hearing ability was assessed following noise exposure using auditory brainstem responses and distortion product otoacoustic emissions. RESULTS: PPEE exhibited significant radical scavenging activity. The ABR threshold shifts 1 day after exposure to noise at 16 kHz and 1, 7, and 14 days after exposure to noise at 32 kHz, were significantly less in the PPEE + Noise than in the Saline + Noise group. One day after noise exposure, mice in the PPEE + Noise group showed a significant degree of protection in relation to their DPOAE level at f2, 17, and 28 kHz. CONCLUSIONS: These findings suggest that PPEE may be a potential preventive agent against TTS. In addition, as a food ingredient approved by the United States Food and Drug Administration, PPEE may be administered to those who are exposed to noise inevitably with little likelihood of adverse effects, thereby contributing to the prevention of TTS.

Improvement of memory by dieckol and phlorofucofuroeckol in ethanol-treated mice: possible involvement of the inhibition of acetylcholinesterase.

Phlorotannins, the polyphonic compounds found in brown Eisenia and Ecklonia algae, have several pharmacologically beneficial effects such as anti-inflammation. In addition, our recent data show that these compounds may improve the cognitive functions of aged humans suggesting the potential ability to enhance memory in several neurodegenerative disorders. To examine the experimental hypothesis that two effective components of Ecklonia cava, dieckol and phlorofucofuroeckol (PFF), have memory-enhancing abilities, both were administered orally to mice before a passive avoidance test. The repeated administration of either dieckol or PFF dose-dependently reduced the inhibition of latency by the administration of ethanol. To investigate the mode of memory-enhancing actions, the levels of major central neurotransmitters in three different regions (striatum, hippocampus, and frontal cortex) of the mouse brain were measured. The levels of some of the neurotransmitters were significantly changed by ethanol. Both dieckol and PFF altered the levels of some neurotransmitters modified by the ethanol treatment. It is noteworthy that both dieckol and PFF increased the level of acetylcholine, and they exerted anticholinesterase activities. Overall, the memory-enhancing abilities of dieckol and PFF may result from, at least in part, the increment of the brain level of acetylcholine by inhibiting acetylcholinesterase.

Blood-brain barrier-permeable fluorone-labeled dieckols acting as neuronal ER stress signaling inhibitors.

We studied the blood-brain barrier (BBB) permeability and intracellular localization of a fluorescein isothiocyanate (FITC)-labeled dieckol (1) and a rhodamine B-labeled dieckol (7), for exploring the possible therapeutic application of fluorone-labeled dieckols in neurodegenerative diseases. Both compounds (1 &7) were synthesized through a click reaction and were found to be localized in the endoplasmic reticulum (ER) of the two types of brain cell lines (SH-SY5Y and BV-2 cells) tested; they also reduced ER stress in the SH-SY5Y human neuroblastoma cells. In addition, 1 and 7 were shown to pass the BBB in rats upon intravenous administration. Altogether, our study demonstrates, for the first time, that targeted ER-stress reduction in brain cells can be achieved by introducing fluorone-dieckol conjugates into systemic circulation. Therefore, 1 and 7 provide a novel and promising ER-targeting therapeutic strategy for neurodegenerative diseases.

Antioxidative properties of brown algae polyphenolics and their perspectives as chemopreventive agents against vascular risk factors.

Several polyphenolic compounds and complex mixtures were isolated from brown algae species. The 1,1-diphenyl-2-picryhydarzyl (DPPH) radical scavenging activity and ferric reducing antioxidant power (FRAP) of these compounds were evaluated to determine their physiological usefulness as antioxidants for vascular protection. The antioxidative protection of low-density lipoprotein (LDL) was also evaluated and compared with that of catechin, because the generation of oxidized LDL is one of the most active and specific risk factors contributing to atherogenesis. Oral administration to rats of a commercially available sample (VNP) containing 30% of these polyphenolic compounds and 70% dietary fiber revealed that the serum reducing capacity measured in terms of FRAP value was significantly elevated 30 min after the treatment, but declined rather quickly thereafter, indicating the good oral absorption of the compounds and their fast binding to the lumenal surface of the blood vessels. An eight-week, human, clinical trial (n=31) of VNP showed significant improvement in erectile function measured by IIEF (international index of erectile function) score. These results collectively demonstrated the usefulness of these polyphenolic compounds as fundamental chemopreventive agents against vascular risk factors originating from oxidative stress.

Effects of Ecklonia cava polyphenol in individuals with hypercholesterolemia: a pilot study.

We evaluated the efficacy and safety of Ecklonia cava polyphenol (Seapolynol™, a polyphenol antioxidant and anti-inflammatory agent purified from E. cava) during a 12-week treatment period (400 mg orally once daily) in individuals with hypercholesterolemia and performed subgroup analysis for metabolic syndrome (MetS). As a noncomparative study, forty-six individuals (M:F=22:24, mean age=54±11 years) with fasting total cholesterol concentration >240 mg/dL or low-density lipoprotein cholesterol (LDL-C) concentration >130 mg/dL were enrolled. Hip circumference (100±7 cm vs. 98±7 cm, P<.01), total cholesterol (244±25 mg/dL vs. 225±37 mg/dL, P<.01), LDL-C (161±24 mg/dL vs. 146±34 mg/dL, P<.01), and C-reactive protein (2.51±3.55 mg/L vs. 1.37±1.32 mg/L, P<.05) were significantly decreased without significant adverse effect. A differential assessment according to the presence [MetS(+) group, n=18] and absence [MetS(-) group, n=28] of MetS showed that Hb(A1c) decreased significantly following 12-week Seapolynol treatment in the MetS(+) compared with the MetS(-) group (-0.3%±0.5% vs. 0.1%±0.3%, P<.01). In conclusion, although our results showed that Seapolynol treatment is effective and safe without significant adverse events or abnormal laboratory findings during a 12-week period in individuals with hypercholesterolemia, more research in a larger population with a longer-term follow-up period in a randomized placebo-controlled study is needed to confirm the results.