Mar Drugs. 2015 Apr 14;13(4):2327-46. doi: 10.3390/md13042327.
Fucoidan and cancer: a multifunctional molecule with anti-tumor potential.
Atashrazm F1, Lowenthal RM2, Woods GM3, Holloway AF4, Dickinson JL5.
There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed.
J Med Food. 2014 Jul;17(7):830-2. doi: 10.1089/jmf.2013.0053. Epub 2014 Mar 10.
Effect of fucoidan administration on insulin secretion and insulin resistance in overweight or obese adults.
Hernández-Corona DM1, Martínez-Abundis E, González-Ortiz M.
11 Cardiovascular Research Unit, Department of Physiology, Health Sciences University Center, University of Guadalajara , Guadalajara, Mexico .
The aim of this article is to evaluate the effect of fucoidan administration on insulin secretion and insulin sensitivity in overweight or obese adults. A randomized, double-blind, placebo-controlled clinical trial was carried out in 25 obese or overweight volunteers. Thirteen patients received an oral dose of 500 mg of fucoidan once daily before breakfast and 12 patients received placebo for 3 months. Before and after the intervention, fasting glucose and 2-h postload, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and insulin levels were measured. Low-density lipoprotein cholesterol (LDL-C) and homeostasis model analysis formulas (HOMA) for β-cell function and insulin resistance were calculated. The results showed a significant decrease in diastolic blood pressure (71.7 ± 12.2 vs. 67.8 ± 13.8 mmHg; P<.05) and LDL-C (3.1 ± 0.5 vs. 2.7 ± 0.6 mmol/l; P<.01) with increase in insulin levels (60.6 ± 24.0 vs. 78.6 ± 32.4 pmol/l; P<.05), HOMA β-cell (35.0 ± 20.8 vs. 50.6 ± 18.7; P<.05) and HOMA IR (1.9 ± 1.2 vs. 2.6 ± 1.8; P<.05) were observed after fucoidan administration. We conclude that fucoidan administration during a 3-month period in overweight or obese adults decreased diastolic blood pressure and LDL-C concentrations, increasing insulin secretion and insulin resistance.
fucoidan; insulin secretion; insulin sensitivity; obesity; overweight
J Surg Res. 2012 Aug;176(2):657-65. doi: 10.1016/j.jss.2011.11.1014. Epub 2011 Dec 22.
Progenitor cell mobilizing treatments prevent experimental transplant arteriosclerosis.
Roux N1, Brakenhielm E, Freguin-Bouillant C, Lallemand F, Henry JP, Boyer O, Thuillez C, Plissonnier D.
Vascular rejection after organ transplantation is characterized by an arterial occlusive lesion, resulting from intimal proliferation occurring in response to arterial wall immune aggression. Our hypothesis is that an early endothelial repair may prevent vascular graft rejection. The aim of the current study was to compare different pharmacologic progenitor cell mobilizing treatments for their protective effects against vascular rejection.
METHODS AND RESULTS:
Aortic transplants were made from balb/c donor to C57Bl/6 recipient mice. Three different mobilizing pharmacologic agents were used: low molecular weight fucoidan (LMWF), simvastatin, and AMD3100. The circulating levels of progenitor cells were found to be increased by all three treatments, as determined by flow cytometry. For each treatment, the design was: treated allografts, nontreated allografts, treated isografts, and nontreated isografts. After 21 d, morphometric and immunohistochemical analyses were performed. We found that the three treatments significantly reduced intimal proliferation, compared with nontreated allografts. This was associated with intimal re-endothelialization of the grafts. Further, in chimeric mice that had previously received GFP-transgenic bone marrow transplantation, GFP-positive cells were found in the vascular allograft intima, indicating that re-endothelialization was, at least partly, due to the recruitment of bone marrow-derived, presumably endothelial progenitor circulating cells.
In this aortic allograft model, three different mobilizing treatments were found to partially prevent vascular transplant rejection. Bone marrow-derived progenitor cells mobilized by the three treatments may play a direct role in the endothelial repair process and in the suppression of intimal proliferation.
Copyright © 2012 Elsevier Inc. All rights reserved.
Comment in Progenitor cell mobilizing treatments prevent experimental transplant arteriosclerosis. [J Surg Res. 2013]
US National Library of MedicineNational Institutes of Health
Mar Drugs. 2015 Apr 3;13(4):1882-900. doi: 10.3390/md13041882.
Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in Lewis tumor-bearing mice.
Huang TH1,2, Chiu YH3, Chan YL4, Chiu YH3,5, Wang H6,7, Huang KC8, Li TL9, Hsu KH10,11, Wu CJ12,13.
Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs.
Biomol Ther (Seoul). 2015 May;23(3):225-32. doi: 10.4062/biomolther.2014.136. Epub 2015 May 1.
Antitumor Effects of Fucoidan on Human Colon Cancer Cells via Activation of Akt Signaling.
Han YS1, Lee JH2, Lee SH1.
We identified a novel Akt signaling mechanism that mediates fucoidan-induced suppression of human colon cancer cell (HT29) proliferation and anticancer effects. Fucoidan treatment significantly inhibited growth, induced G1-phase-associated upregulation of p21WAF1 expression, and suppressed cyclin and cyclin-dependent kinase expression in HT29 colon cancer cells. Additionally, fucoidan treatment activated the Akt signaling pathway, which was inhibited by treatment with an Akt inhibitor. The inhibition of Akt activation reversed the fucoidan-induced decrease in cell proliferation, the induction of G1-phase-associated p21WAF1 expression, and the reduction in cell cycle regulatory protein expression. Intraperitoneal injection of fucoidan reduced tumor volume; this enhanced antitumor efficacy was associated with induction of apoptosis and decreased angiogenesis. These data suggest that the activation of Akt signaling is involved in the growth inhibition of colon cancer cells treated with fucoidan. Thus, fucoidan may serve as a potential therapeutic agent for colon cancer.
J Cardiovasc Pharmacol Ther. 2011 Mar;16(1):79-86. doi: 10.1177/1074248410378751. Epub 2010 Dec 30.
Sulfated polysaccharide fucoidan ameliorates experimental autoimmunemyocarditis in rats.
Tanaka K1, Ito M, Kodama M, Tomita M, Kimura S, Hoyano M, Mitsuma W, Hirono S, Hanawa H, Aizawa Y.
Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the initial pathologic event of experimental autoimmune myocarditis (EAM). Subsequently, various bystander inflammatory cells are recruited into the myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide fucoidanbinds selectin nonselectively and blocks its function. Therefore, this study was designed to evaluate whether in vivo fucoidan treatment can improve EAM. A 21-day infusion of physiological saline orfucoidan was administrated intraperitoneally to the rats with sham operation (sham-saline, n = 5; sham-fucoidan, n = 6) or those with cardiac myosin injection (EAM-saline, n = 10; EAM-fucoidan, n = 10). After 3 weeks, fucoidan treatment improved left ventricular ejection fraction (79.04 ± 2.81 vs 65.94% ± 3.22%; P < .01 vs EAM-saline) with a reduced ratio of heart weight to body weight (4.016 ± 0.239 vs 4.975 ± 0.252 mg/g; P < .05 vs EAM-saline) in EAM. Furthermore, fucoidan treatment decreased serum levels of BNP (292.0 ± 53.4 vs 507.4 ± 89.2 ng/mL; P < .05 vs EAM-saline) and the myocarditis area (31.66 ± 1.53 vs 42.51% ± 3.24%; P < .01 vs EAM-saline) in EAM. These beneficial effects of fucoidan were accompanied by inhibition of both macrophage and CD4-positive T-cell infiltration into the myocardium.Fucoidan, a nonselective selectin blocker, attenuates the progression of EAM. This observation may be explained, at least in part, by blocking the extravasation of inflammatory cells into the myocardium.
Int Immunopharmacol. 2008 Jan;8(1):109-16. Epub 2007 Nov 20.
Defensive effects of a fucoidan from brown alga Undaria pinnatifida against herpes simplex virus infection.
Hayashi K1, Nakano T, Hashimoto M, Kanekiyo K, Hayashi T.
Fucoidan, a sulfated polysaccharide isolated from an edible brown alga Undaria pinnatifida, was previously shown to be a potent inhibitor of the in vitro replication of herpes simplex virus type 1 (HSV-1). HSV-1 is a member of herpes viruses that cause infections ranging from trivial mucosal ulcers to life-threatening disorders in immunocompromised hosts. In the in vivo conditions, the replication of HSV-1 is controlled under the immunoresponse coordinated by both the innate and adaptive immune systems. In the present study, the effects of the fucoidan were examined on in vivo viral replication and the host's immune defense system. Oral administration of the fucoidan protected mice from infection with HSV-1 as judged from the survival rate and lesion scores. Phagocytic activity of macrophages and B cell blastogenesis in vitro were significantly stimulated by the fucoidan, while no significant change in the release of NO(2)(-) by macrophages was observed. In in vivo studies, oral administration of the fucoidan produced the augmentation of NK activity in HSV-1-infected mice immunosuppressed by 5-fluorouracil treatment. CTL activity in HSV-1-infected mice was also enhanced by oral administration of the fucoidan. The production of neutralizing antibodies in the mice inoculated with HSV-1 was significantly promoted during the oral administration of the fucoidan for 3 weeks. These results suggested that oral intake of the fucoidan might take the protective effects through direct inhibition of viral replication and stimulation of both innate and adaptive immune defense functions.
Carbohydr Polym. 2015 Jan 22;115:122-8. doi: 10.1016/j.carbpol.2014.08.068. Epub 2014 Sep 2.
Anti-HIV activity of fucoidans from three brown seaweed species.
Thuy TT1, Ly BM2, Van TT2, Quang NV3, Tu HC4, Zheng Y4, Seguin-Devaux C4, Mi B5, Ai U5.
Fucoidans are sulfated polysaccharides derived from marine brown algae. In the current work the anti-HIV activity of three fucoidans, extracted from three brown seaweeds Sargassum mcclurei, Sargassum polycystum and Turbinara ornata and collected from Nha Trang bay, Vietnam was investigated. Fucoidans extracted from the three species displayed similar antiviral activities with a mean IC50 ranging from 0.33 to 0.7 μg/ml while displaying no cell toxicity. Our results showed that the anti-HIVactivity of fucoidans is not primarily linked to the sulfate content and the appropriate position of sulfate groups in the fucoidanbackbones was also not associated with the antiviral activity. Fucoidans inhibited HIV-1 infection when they were pre-incubated with the virus but not with the cells, and not after infection, blocking the early steps of HIV entry into target cells. These data contribute to a better understanding of the influence of fucoidans structural characteristics on their biological activity.
Mar Drugs. 2013 Aug 19;11(8):3000-14. doi: 10.3390/md11083000.
Fucoidans as potential inhibitors of HIV-1.
Prokofjeva MM1, Imbs TI, Shevchenko NM, Spirin PV, Horn S, Fehse B, Zvyagintseva TN, Prassolov VS.
The antiviral activity of different structure fucoidans (α-l-fucans and galactofucans) was studied using two model viral systems based on a lentiviral vectors and a replication competent Moloney murine leukemia virus (Mo-MuLV). It was found that investigated fucoidans have no cytotoxic effects on Jurkat and SC-1cell at the concentration range of 0.001-100 µg/mL. Fucoidans with different efficiency suppressed transduction of Jurkat cell line by pseudo-HIV-1 particles carrying the envelope protein of HIV-1 and infection of SC-1 cells by Mo-MuLV. According to our data, all natural fucoidans can be considered as potential anti-HIV agents regardless of their carbohydrate backbone and degree of sulfating, since their activity is shown at low concentrations (0.001-0.05 µg/mL). High molecular weight fucoidans isolated from Saccharina cichorioides (1.3-α-l-fucan), and S. japonica (galactofucan) were the most effective inhibitors.
Helicobacter. 2003 Feb;8(1):59-65.
Preventive effects of Cladosiphon fucoidan against Helicobacter pylori infection in Mongolian gerbils.
Shibata H1, Iimuro M, Uchiya N, Kawamori T, Nagaoka M, Ueyama S, Hashimoto S, Yokokura T, Sugimura T, Wakabayashi K.
Recently, the acquisition by Helicobacter pylori of resistance to antibiotics has become a serious problem. Therefore, nonantibiotic substances are required to diminish H. pylori-induced gastric lesions. In the present study, the effects of Cladosiphon fucoidan were examined in terms of H. pylori attachment to porcine gastric mucin in vitro and Helicobacter pylori-induced gastritis in vivo.
The inhibitory effect of Cladosiphon fucoidan and other polysaccharides on H. pylori attachment to porcine gastric mucin was assayed in vitro with mucin-coated microtiter plates. The effect of Cladosiphon fucoidan on H. pylori-induced gastritis was examined in vivo using Mongolian gerbils. H. pylori-inoculated gerbils were given fucoidan in drinking water. Six weeks after H. pylori-inoculation, gerbils were sacrificed for macroscopic and microscopic examination of gastric lesions and counting of viable H. pylori in the gastric mucosa.
Cladosiphon fucoidan inhibited the H. pylori attachment to porcine gastric mucin at pH 2.0 and 4.0. Two other sulfated polysaccharides, Fucus fucoidan and dextran sulfate sodium, also inhibited the attachment but only at pH 2.0. Inhibitory effects of these three sulfated polysaccharides were not observed at pH 7.2 and nonsulfated polysaccharides, such as mannan and dextran, exerted no influence at any pH. In the in vivo experiment, the H. pylori-induced gastritis and the prevalence of H. pylori infected animals were markedly reduced by fucoidan in a dose-dependent manner, at doses of 0.05 and 0.5% in the drinking water.
Cladosiphon fucoidan may deserve particular attention as a safe agent that can prevent H. pylori infection and reduce the risk of associated gastric cancer.
Nutrients. 2014 Dec 31;7(1):239-52. doi: 10.3390/nu7010239.
Fucoidan supplementation improves exercise performance and exhibits anti-fatigue action in mice.
Chen YM1, Tsai YH2, Tsai TY3, Chiu YS1, Wei L4, Chen WC5, Huang CC6.
Fucoidan (FCD) is a well-known bioactive constituent of seaweed extract that possess a wide spectrum of activities in biological systems, including anti-cancer, anti-inflammation and modulation of immune systems. However, evidence on the effects of FCD on exercise performance and physical fatigue is limited. Therefore, we investigated the potential beneficial effects of FCD on ergogenic and anti-fatigue functions following physiological challenge. Male ICR mice from three groups (n = 8 per group) were orally administered FCD for 21 days at 0, 310 and 620 mg/kg/day, which were, respectively, designated the vehicle, FCD-1X and FCD-2X groups. The results indicated that the FCD supplementations increased the grip strength (p = 0.0002) and endurance swimming time (p = 0.0195) in a dose-depend manner. FCD treatments also produced dose-dependent decreases in serum levels of lactate (p < 0.0001) and ammonia (p = 0.0025), and also an increase in glucose level (p < 0.0001) after the 15-min swimming test. In addition, FCD supplementation had few subchronic toxic effects. Therefore, we suggest that long-term supplementation with FCD can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue.
February 16, 2006
I was very skeptical when I first heard about Limu – which was the end of January when Charlie and Letha got back from the conference in Little Rock. I was hurting so bad I decided what the heck, it is all natural and no hidden chemicals. I started drinking Limu just 2 oz. – (a shotglass) in the morning and another in the evening. After four days I realized I hadn’t needed to take any pain medicine in several days and what limp? (I am just be bopping around.) The painful symptoms of the neuropathy are better and I have never, ever felt more energy.
March 7, 2006
I went to my Neurologist and slhe was very pleased with how well I was doing. She is all for natural medicine and healing. I explained to her about Limu. Since I was doing so well, she reduced my seizure medicine for the diabetic neuropathy from 800mg to 600mg 4x a day. Instead of seeing her every 6 weeks now I see her every 6 months. I started doing so well after a week or so, I started taking the reduced dose of seizure medicine twice a day.
March 28, 2006
Back on February 1, 2006 I had ear reconstruction and mastoid surgery. The ear did not heal as fast as it should have – they said it was because diabetics take longer to heal. The ear canal and the incision behind the ear were inflamed and I possibly had an allergic reaction to the antiboiotic cream. When I went back to the surgeon after drinking Limu for several weeks he was surprised that it was healed like it should have been – if I wasn’t diabetic.
April 10, 2006
I went to my regular scheduled appointment with my pain management Dr who was shocked at how well I was doing. He could not get over how I could walk and not limp. He was even more shocked to know I had not had my usual migraines in weeks. He agreed with my decision to reduce the seizure medicine and now is reducing it to 1 1/2 pills a day, then 1 a day to see if we can wean off it completely. Even if it was reduced to a low dose I would be thrilled! I shared the Limu story and DVD with him.
May 1, 2006
What a way to start the new month! I went to the Endocrinologist who I hadn’t seen since January and was concerned because my cholesterol was 260. Today after drinking the Limu for six weeks my total cholesterol was 168! DOWN 92 points! My LDH (bad cholesterol) was 164 and it is now 81. My triglycerides went from 116 to 97. She sas in disbelief when she learned that I stopped my cholesterol meds when I started drinking the Limu. She said she has never seen someone do a healthy turnaround like I have done in such a short time. She was interested in researching the Limu on the pubmed.org site. The Dr checked my reflexes and then stuck my feet with a pin – and it hurt! It was so good to feel the pain – in January I could not feel the vibrations or the pins being stuck in my ankle and feet. I feel like a new person walking without a limp and the doctor said she was amazed at how well I was looking and doing health wise and to keep up the good work and the limu!
I thank God for Charlie and Letha every day for sharing Original Limu with me. If they had now shared with me, then “dripped on me” each time they saw how bad I was feeling – I know I never would have started drinking Original Limu and probably would not be walking today!
Limu is Pure Gold!
Limu testimony on MS, and autism on YouTube:
https://www.youtube.com/watch?v=D3SZP7UAeCQ&feature=youtu.be [Note: Copy and paste link into browser]
“LIMU products are not drugs and have not been evaluated by the FDA. They are simply dietary supplements and are not intended to diagnose, cure or treat any illness or disease. While your body may experience amazing positive health responses when you feed it the right nutritional building blocks, and there is indeed reliable scientific evidence supporting the beneficial effect key ingredients of LIMU products have on the immune system, there is insufficient scientific evidence to support some of the specific therapeutic results reported by users of the product. We therefore promote LIMU products for their benefit on the immune system but we do not, and you must not, promote the products on the basis that it will cure, prevent or treat any disease.”