Turn off the cytokine switch.
Known as HMGB1 (for "High Mobility Group Box-1"), this intriguing protein molecule triggers the release of the cytokines--a collection of chemical signals--that generate inflammation in your body. (1)
And as inflammation accumulates, aging accelerates, to the point that most scientists now speak about "inflammaging" as a single entity that underlies disorders that cause premature death, including conditions ranging from diabetes and atherosclerosis to lung disease and cancer, to name just a few. (2-4)
In an exciting new development, the discovery of HMGB1 as the switch that turns "on" accelerated aging has led to the development of a safe and effective means of turning "off" that switch and reducing premature senescence.
Research over the past few years has demonstrated that two natural ingredients can directly control HMGB1, switching off the massive cytokine flow that generates age-related inflammation and leads to disease and premature death.
Tested in prestigious hospital research laboratories, two plant extracts, mung bean seed coat and green tea, extended life spans and increased survival rate caused by inflammation in blood poisoning (sepsis) by up to 82%.5,6
This combination of natural ingredients can reduce total body exposure to the ravages of inflammation. By doing so, maturing individuals can protect themselves from accelerated aging, guard against inflammation-induced chronic disorders, and live a longer and more productive life.
HMGB1: THE "CYTOKINE SWITCH"
Inflammation is a helpful reaction when your body is under attack by germs, or following an injury. Under those circumstances, inflammation represents the first step in the healing process, bringing in white blood cells to clean up after the invaders have been destroyed and boosting blood supply to the injured or damaged area.
But ongoing, chronic inflammation is another matter entirely--it has been linked with many age-related, lifespan-shortening disorders, including heart disease, cancer, chronic obstructive pulmonary disease (COPD), diabetes, and others. (3), (4)
Scientists have now discovered that HMGB1 has been implicated in acute inflammation--and that sustained high levels of HMGB1 are responsible for maintaining the chronic inflammation that speeds the aging process. (1)
It turns out that HMGB1 inside your body cells is very much a good thing; it helps regulate the way your genes are expressed, acting as a kind of "general manager" of cellular processes. (7) But when a cell is damaged, its contents of HMGB1 leak out, and trouble begins. (8)
This released HMGB1 binds to receptor molecules on immune system cells, acting as a "danger signal" that triggers them to release cytokines. (1), (7) Cytokines, in turn, are chemical signaling molecules that call in still more white blood cells, which release still more cytokines, in a deadly frenzy of activity.
Taken to the extreme, such activity can result in a "cytokine storm," a massive, body-wide release of cytokines that can shut down your body's entire system. (9-11) During a cytokine storm, which can be potentially lethal, over 150 inflammatory mediators are released throughout the body. (12) We dealt with the prospect of a cytokine storm on a large scale during the 2003 outbreak of SARS ("severe acute respiratory syndrome") and more recently in 2009 during the H1N1 outbreak. (13-15)
Fortunately, most of us never have to face a true cytokine storm. Instead, we experience the cumulative effects of lower levels of cytokines, maintaining a steady and rising drumbeat of chronic inflammation that destroys our blood vessels, bones, and joints, promotes cancer development, and lays waste to our brain cells to rob us of memory and cognition. (1), (16-45)
Elevated HMGB1 levels have now been found to be associated with many acute and chronic inflammation-related disorders, including:
* Asthma and chronic obstructive pulmonary disease (COPD) (16-19)
* Atherosclerosis, lipid disturbances, and their consequences, coronary artery disease, heart attacks, strokes, and congestive heart failure (20-28)
* Autoimmune disorders, including lupus, multiple sclerosis, rheumatoid arthritis, type I diabetes, and others (29-34)
* Cancer (35), (36)
* Diabetes (27), (28), (31), (34), (37)
* Inflammatory bowel diseases (Crohn's disease and ulcerative colitis) (38), (39) Neurodegenerative disorders (21), (23), (29)
* Obesity (40)
* Surgical procedures, even those without obvious complications (43)
* Trauma, including hemorrhagic shock, traumatic brain injury, acute lung injury and bone fractures (41), (42), (44), (450
* Viral and other infections46,47
WHAT YOU NEED TO KNOW
Turn Off Your Cytokine Switch
* Your body ages more rapidly the more chronic inflammation you have.
* Many chronic diseases that cause premature death and disability are accelerated by higher levels of inflammation.
* The recent discovery of the ytokine switch, HMGB1, has allowed scientists for the first time to think about ways to quell chronic inflammation and help promote successful aging by controlling HMGB1 levels in your body.
* Drugs that fight HMGB1 are potentially years away from practical use; however, extracts from mung bean seed coat and green tea offer safe, natural anti-HMGB1 therapy--and they are available for oral use now.
* Studies show that mung bean seed coat extract and EGCG from green tea prevented death from acute inflammation by counteracting HMGB1, suggesting that their use will be effective in other inflammatory diseases, such as the chronic diseases of aging.
FIGHTING HMGB1 TO REDUCE INFLAMMATION
Impeding HMGB1 is turning out to be a powerful means of slowing and reversing inflammatory processes, with laboratory results showing an increase in survival rate in the face of ongoing inflammatory damage. (5), (6) Scientists are just now beginning to make strides in the fight against inflammation in asthma, in arthritis, in multiple sclerosis, and in inflammatory bowel diseases (Crohn's disease and ulcerative colitis), using specialized large molecules (antibodies) that bind HMGB1 and prevent its cytokine-mediated effects. (18), (48-55)
Don't expect to see these treatments available from Big Pharma any time soon, though. Therapies employing HMGB1-neutralizing antibodies have shown promise in animal models; however, they have not been tested in clinical trials. Moreover, neutralizing antibody treatments are faced with several challenges, including poor drug response and adverse side effects like acute hypersensitivity reactions. (56)
But there's hope for all of us who recognize the importance of suppressing inflammation in pursuit of a long and healthy life. The anti-HMGB1 properties of mung bean seed coat and EGCG from green tea leaf have now been harnessed to tamp down inflammation and slow the accelerated aging that accompanies chronic inflammatory processes. (5), (6)
Since these products are natural and have millenniums of human use to back their safety, you can use them as a daily supplement to gain protection from chronic, inflammation-induced diseases, and slow down certain aging processes in your body.
Both mung bean and green tea are components of traditional Asian cuisine and medicines. Mung bean is an excellent source of protein that, unlike most other beans, is virtually free of flatulence-inducing factors, making it a natural food for the ill. (57) And mung bean soup is credited with having "cooling" properties in traditional Chinese medicine, a prescient idea that accords perfectly with present-day discoveries about the bean's anti-inflammatory properties.58
Green tea has been consumed in China for millennia and has been used as a health aid since at least the 12th century for its many beneficial effects. Today, green tea is known to be one of the most prominent sources of plant polyphenols with anti-inflammatory actions. (59)
The sources of the anti-inflammatory properties of these two ancient health-promoting substances are becoming increasingly clear under the scrutiny of modern science. Both of these ingredients have been shown to interfere at several different points in the cascade of events that leads to HMGB1 release from stressed or damaged cells, making them especially potent in battling inflammation from several causes, infectious and non-infectious, acute and chronic. (5), (6), (60-63)
The HMGB1-lowering effect of mung bean is found mainly in the seed coat portion of the bean. Mung bean seed coat extract reduces HMGB1 levels both within and outside of immune cells stimulated by bacterial toxins. (5) Two flavonoid molecules in particular, vitexin and isovitexin, account for a large part of the anti-HMGB1 activity of the extract. Studies show, however, that these molecules are effective only in crude extracts of the bean; commercially purified versions are much less useful. (5)
Fed to rats both before and after exposure to heat stress (swimming in 104[degrees]F water), mung bean seed coat extract reduced blood markers of excessive oxidant stress, while also strengthening the body's natural antioxidant defense system. (58) These findings bear out the traditional view of mung bean as a "cooling" food.
Green tea extract dose-dependently attenuates HMGB1 release from cells exposed to bacterial toxins; this activity was later found to be produced by EGCG, the major beneficial component in green tea.6 And EGCG drives down HMGB1 release in immune cells even when given 2 to 6 hours after exposure of cells to the toxin. (6), (62)
Mung bean seed coat extract and EGCG are available in oral form, making their combination an effective HMGB1-blocking therapy. (5), (6)
MUNG BEAN AND GREEN TEA
The most dramatic illustration of how mung bean seed coat and EGCG from green tea leaves can save lives comes from two recent studies at the Department of Emergency Medicine, North Shore University Hospital on Long Island, New York; University School of Medicine, New York; and the Feinstein Institute for Medical Research, Manhasset, New York. (5), (6)
Researchers were interested in the therapeutic role of targeting HMGB1 in sepsis. Sepsis, commonly called blood poisoning, kills more than 225,000 Americans (mostly older adults)
every year in intensive care units, despite modern antibiotics and life-saving technologies. (64)
It is also a useful model for understanding the role of anti-HMGB1 therapies in the most extreme example of out-of-control inflammation. In sepsis, massive amounts of HMGB1 trigger an outpouring of cytokines. It is this resulting inflammation, and not the infecting germ, that ultimately kills the patient. (65), (66) And once those cytokines are on the loose, it's typically too late to fight
back with anti-cytokine therapies. (67-69)
Instead of turning to expensive and dangerous anti-HMGB1 antibodies, however, as other researchers had done, researchers at the North Shore University Hospital and Feinstein Institute for Medical Research chose to study mung bean seed coat extract and EGCG from green tea leaf extract, based on their known anti-HMGB1 activities.
The experiments were simple but dramatic. The researchers first induced sepsis in laboratory mice, dooming them to almost certain death without intervention. (5), (6) In half of the mice, however, the researchers did intervene--but not until 24 hours after the induction of sepsis.
In their first experiment, the scientists gave the mice EGCG from green tea, or a salt-water control, at 24, 48, and 72 hours following the onset of sepsis. (6)
There was no other intervention: no antibiotics, no IV fluids, no ICU drugs or equipment.
As described in Figure 1, repeated administration of EGCG conferred protection against lethal sepsis by significantly increasing the survival rate of
animals from 53% to 82%.6
Encouraged by this result, the researchers turned to mung bean seed coat extract. (5) You can see this outcome in Figure 2; using the same experimental design as in the previous study, the mice were given the extract (or saline control) beginning the day after induction of sepsis. Mung bean seed coat conferred a significant protection against lethal sepsis, increasing animal survival rates from nearly 30% to just over 70%. (5)
It's impossible to overstate the significance of these results. In unprecedented research, septic shock was significantly prevented, and animals were rescued from an otherwise likely death, using a simple, natural, oral treatment. The secret to their success was the sharp drop in HMGB1 levels induced by both EGCG and mung bean seed coat extract. (5), (6)
How does all this relate to you?
Most of us will, mercifully, never have to deal with sepsis or the out-of-control inflammation that it can produce. The combination of EGCG and mung bean seed coat that contain such potent HMGB1-suppressing activity means that we can all benefit from reduced levels of total-body chronic inflammation.
Chronic inflammation has recently been shown to reduce the length of telomeres, the "living fuses" in our chromosomes that shorten with age. (70), (71) Thus, reduced chronic inflammation might translate to a longer and healthier life. This is a very literal demonstration of how chronic inflammation acts as an aging accelerator, fueled by excessively high HMGB1 levels. Mung bean seed coat extract and EGCG might help you to literally slow down your aging processes and prolong your life.
Chronic inflammation accelerates aging, producing symptoms that we recognize as diseases that cause early death. Scientists have now discovered the accelerator switch, in the form of HMGB1, the molecule that triggers the release of inflammatory cytokines under a wide variety of circumstances.
Anti-HMGB1 therapies, therefore, are avidly sought-after by big pharma companies. While producing dramatic results in the laboratory, however, no anti-HMGB1 drug is anywhere near market-ready because treatments to date use large antibody molecules that can't be given orally and that have unacceptable side effects.
But mung beans and green tea, in use for thousands of years in traditional Chinese medicine, contain safe, powerful HMGB1-fighting substances. Extract s of mung bean seed coat and EGCG from green tea leaf extract can be given orally, and in preclinical studies have proven to be highly effective at shutting down HMGB1-induced inflammation in a life-saving fashion.
If you have any questions on the scientific content of this article, please call a Life Extension[R] Health Advisor at 1-866-864-3027.
(1.) Nogueira-Machado JA, de Oliveira Volpe CM. HMGB-1 as a target for inflammation controlling. Recent Pat Endocr Metab Immune Drug Discov. 2012 Sep;6(3):201-9.
(2.) Chilosi M, Carloni A, Rossi A, Poletti V. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema. Transl Res. 2013 Jul 2.
(3.) Liezmann C, Stock D, Peters EM. Stress induced neuroendocrine-immune plasticity: A role for the spleen in peripheral inflammatory disease and inflammaging? Dermatoendocrinol. 2012 Jul 1;4(3):271-9.
(4.) Yao H, Rahman I. Perspectives on translational and therapeutic aspects of SIRT1 in inflammaging and senescence. Biochem Pharmacol. 2012 Nov 15;84(10):1332-9.
(5.) Zhu S, Li W, Li J, Jundoria A, Sama AE, Wang H. It is not just folklore: The aqueous extract of mung bean coat is protective against sepsis. Evid Based Complement Alternat Med. 2012;2012:498467.
(6.) Li W, Ashok M, Li J, Yang H, Sama AE, Wang H. A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1. PLoS One. 2007;2(11):e1153.
(7.) Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A. HMGB1: endogenous danger signaling. Mol Med. 2008 Jul-Aug;14(7-8):476-84.
(8.) Zhu S, Li W, Ward MF, Sama AE, Wang H. High mobility group box 1 protein as a potential drug target for infection- and injury-elicited inflammation. Inflamm Allergy Drug Targets. 2010 Mar;9(1):60-72.
(9.) Kruttgen A, Rose-John S. Interleukin-6 in sepsis and capillary leakage syndrome. J Interferon Cytokine Res. 2012 Feb;32 (2):60-5.
(10.) Lotze MT, Buchser WJ, Liang X. Blocking the interleukin 2 (IL2)-induced systemic autophagic syndrome promotes profound antitumor effects and limits toxicity. Autophagy. 2012 Aug;8(8):1264-6.
(11.) Ye C, Choi JG, Abraham S, et al. Human macrophage and dendritic cell-specific silencing of high-mobility group protein B1 ameliorates sepsis in a humanized mouse model. Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21052-7.
(12.) Available at: http://www.omicsonline.org/2153-0645/2153-0645-3-e131.php?aid=10050#4. Accessed October 14, 2013.
(13.) Li Y, Chen M, Cao H, Zhu Y, Zheng J, Zhou H. Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response. Microbes Infect. 2013 Feb;15(2):88-95.
(14.) Theron M, Huang KJ, Chen YW, Liu CC, Lei HY. A probable role for IFN-gamma in the development of a lung immunopathology in SARS. Cytokine. 2005 Oct 7;32(1):30-8.
(15.) Available at: http://www.cidrap.umn.edu/news-perspective/2013/08/study-shows-cytokine-storm-fatal-2009-h1n1-cases. Accessed October 17, 2013.
(16.) Cheng Z, Kang Y, Wu QG, et al. Levels of HMGB1 in induced sputum from patients with asthma and chronic obstructive pulmonary disease. Zhonghua Yi Xue Za Zhi. 2011 Nov 15;91(42):2981-4.
(17.) Kanazawa H, Tochino Y, Asai K, Ichimaru Y, Watanabe T, Hirata K. Validity of HMGB1 measurement in epithelial lining fluid in patients with COPD. Eur J Clin Invest. 2012 Apr;42(4):419-26.
(18.) Shim EJ, Chun E, Lee HS, et al. The role of high-mobility group box-1 (HMGB1) in the pathogenesis of asthma. Clin Exp Allergy. 2012 Jun;42(6):958-65.
(19.) Zhou Y, Jiang YQ, Wang WX, et al. HMGB1 and RAGE levels in induced sputum correlate with asthma severity and neutrophil percentage. Hum Immunol. 2012 Nov;73(11):1171-4.
(20.) Andrassy M, Volz HC, Schuessler A, et al. HMGB1 is associated with atherosclerotic plaque composition and burden in patients with stable coronary artery disease. PLoS One. 2012;7(12):e52081.
(21.) He M, Zhang B, Wei X, et al. HDAC4/5-HMGB1 signalling mediated by NADPH oxidase activity contributes to cerebral ischaemia/reperfusion injury. J Cell Mol Med. 2013 Apr;17(4):531-42.
(22.) Jin D, Wu Y, Zhao L, Guo J, Zhang K, Chen Z. Atorvastatin reduces serum HMGB1 levels in patients with hyperlipidemia. Exp Ther Med. 2012 Dec;4(6):1124-26.
(23.) Mazarati A, Maroso M, Iori V, Vezzani A, Carli M. High-mobility group box-1 impairs memory in mice through both toll-like receptor 4 and Receptor for Advanced Glycation End Products. Exp Neurol. 2011 Dec;232(2):143-8.
(24.) Menini T, Ikeda H, Kimura S, Gugliucci A. Circulating soluble RAGE increase after a cerebrovascular event. Clin Chem Lab Med. 2013 Mar 13:1-8.
(25.) Moreno JA, Sastre C, Madrigal-Matute J, et al. HMGB1 expression and secretion are increased via TWEAK-Fn14 interaction in atherosclerotic plaques and cultured monocytes. Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):612-20.
(26.) Volz HC, Laohachewin D, Schellberg D, HMGB1 is an independent predictor of death and heart transplantation in heart failure. Clin Res Cardiol. 2012 Jun;101(6):427-35.
(27.) Volz HC, Seidel C, Laohachewin D, et al. HMGB1: the missing link between diabetes mellitus and heart failure. Basic Res Cardiol. 2010 Nov;105(6):805-20.
(28.) Zhao D, Wang Y, Tang K, Xu Y. Increased serum HMGB1 related with HbA1c in coronary artery disease with type 2 diabetes mellitus. Int J Cardiol. 2013 Jan 18.
(29.) Fang P, Schachner M, Shen YQ. HMGB1 in development and diseases of the central nervous system. Mol Neurobiol. 2012 Jun;45(3):499-506.
(30.) He Z, Shotorbani SS, Jiao Z, et al. HMGB1 promotes the differentiation of Th17 via up-regulating TLR2 and IL-23 of CD14+ monocytes from patients with rheumatoid arthritis. Scand J Immunol. 2012 Nov;76(5):483-90.
(31.) Morimoto-Yamashita Y, Ito T, Kawahara K, et al. Periodontal disease and type 2 diabetes mellitus: is the HMGB1-RAGE axis the missing link? Med Hypotheses. 2012 Oct;79(4):452-5.
(32.) Hwang CS, Liu GT, Chang MD, Liao IL, Chang HT. Elevated serum autoantibody against high mobility group box 1 as a potent surrogate biomarker for amyotrophic lateral sclerosis. Neurobiol Dis. 2013 Oct;58:13-8.
(33.) Wen Z, Xu L, Chen X, et al. Autoantibody induction by DNA-containing immune complexes requires HMGB1 with the TLR2/MicroRNA-155 pathway. J Immunol. 2013 Apr 24.
(34.) Zhang S, Zhong J, Yang P, Gong F, Wang CY. HMGB1, an innate alarmin, in the pathogenesis of type 1 diabetes. Int J Clin Exp Pathol. 2009;3(1):24-38.
(35.) Dong YD, Cui L, Peng CH, Cheng DF, Han BS, Huang F. Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep. 2013 Jan;29(1):87-94.
(36.) Li ML, Wang XF, Tan ZJ, et al. Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGB1-RAGE axis. Int J Immunopathol Pharmacol. 2012 Oct-Dec;25(4):955-65.
(37.) Skrha J, Jr., Kalousova M, Svarcova J, et al. Relationship of soluble RAGE and RAGE ligands HMGB1 and EN-RAGE to endothelial dysfunction in type 1 and type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2012 May;120(5):277-81.
(38.) McDonnell M, Liang Y, Noronha A, et al. Systemic Toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease. Inflamm Bowel Dis. 2011 Jan;17(1):298-307.
(39.) Vitali R, Stronati L, Negroni A, et al. Fecal HMGB1 is a novel marker of intestinal mucosal inflammation in pediatric inflammatory bowel disease. Am J Gastroenterol. 2011 Nov;106(11):2029-40.
(40.) Arrigo T, Chirico V, Salpietro V, et al. High-mobility group protein B1: a new biomarker of metabolic syndrome in obese children. Eur J Endocrinol. 2013 Apr;168(4):631-8.
(41.) Degos V, Maze M, Vacax S, et al. Bone fracture exacerbates murine eschemic cerebral injury. Anesthesiology. 2013 Feb 22.
(42.) Li Y, Xiang M, Yuan Y, et al. Hemorrhagic shock augments lung endothelial cell activation: role of temporal alterations of TLR4 and TLR2. Am J Physiol Regul Integr Comp Physiol. 2009 Dec;297(6):R1670-80.
(43.) Liu A, Dirsch O, Fang H, et al. HMGB1 translocation and expression is caused by warm ischemia reperfusion injury, but not by partial hepatectomy in rats. Exp Mol Pathol. 2011 Oct;91(2):502-8.
(44.) Guo F, Shi Y, Xu H, Ding J. High mobility group box 1 as a mediator of endotoxin administration after hemorrhagic shockprimed lung injury. Braz J Med Biol Res. 2009 Sep;42(9):804-11.
(45.) Okuma Y, Liu K, Wake H, et al. Anti-high mobility group box-1 antibody therapy for traumatic brain injury. Ann Neurol. 2012 Sep;72(3):373-84.
(46.) Ong SP, Lee LM, Leong YF, Ng ML, Chu JJ. Dengue virus infection mediates HMGB1 release from monocytes involving PCAF acetylase complex and induces vascular leakage in endothelial cells. PLoS One. 2012;7(7):e41932.
(47.) Moisy D, Avilov SV, Jacob Y, et al. HMGB1 protein binds to influenza virus nucleoprotein and promotes viral replication. J Virol. 2012 Sep;86(17):9122-33.
(48.) Andersson U, Tracey KJ. HMGB1 as a mediator of necrosis-induced inflammation and a therapeutic target in arthritis. Rheum Dis Clin North Am. 2004 Aug;30(3):627-37, xi.
(49.) Andersson U, Harris HE. The role of HMGB1 in the pathogenesis of rheumatic disease. Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):141-8.
(50.) Uzawa A, Mori M, Taniguchi J, Masuda S, Muto M, Kuwabara S. Anti-high mobility group box 1 monoclonal antibody ameliorates experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2013 Apr;172(1):37-43.
(51.) Robinson AP, Caldis MW, Harp CT, Goings GE, Miller SD. High-mobility group box 1 protein (HMGB1) neutralization ameliorates experimental autoimmune encephalomyelitis. J Autoimmun. 2013 Mar 17.
(52.) Maeda S, Hikiba Y, Shibata W, et al. Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer. Biochem Biophys Res Commun. 2007 Aug 24;360(2):394-400.
(53.) Andersson UG, Tracey KJ. HMGB1, a pro-inflammatory cytokine of clinical interest: introduction. J Intern Med. 2004 Mar;255(3):318-9.
(54.) Han J, Zhong J, Wei W, et al. Extracellular high-mobility group box 1 acts as an innate immune mediator to enhance autoimmune progression and diabetes onset in NOD mice. Diabetes. 2008 Aug;57(8):2118-27.
(55.) Yang H, Hreggvidsdottir HS, Palmblad K, et al. A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release. Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11942-7.
(56.) Cozzani E, Burlando M, Parodi A. Detection of antibodies to anti-TNF agents in psoriatic patients: a preliminary study. G Ital Dermatol Venereol. 2013 Apr;148(2):171-4.
(57.) Adsule RN, Kadam SS, Salunkhe DK. Chemistry and technology of green gram (Vigna radiata [L.] Wilczek). Crit Rev Food Sci Nutr. 1986;25(1):73-105.
(58.) Cao D, Li H, Yi J, et al. Antioxidant properties of the mung bean flavonoids on alleviating heat stress. PLoS One. 2011;6 (6):e21071.
(59.) Recio MC, Andujar I, Rios JL. Anti-inflammatory agents from plants: progress and potential. Curr Med Chem. 2012;19 (14):2088-103.
(60.) Chen X, Li W, Wang H. More tea for septic patients?--Green tea may reduce endotoxin-induced release of high mobility group box 1 and other pro-inflammatory cytokines. Med Hypotheses. 2006;66(3):660-3.
(61.) Kuang X, Huang Y, Gu HF, et al. Effects of intrathecal epigallocatechin gallate, an inhibitor of Toll-like receptor 4, on chronic neuropathic pain in rats. Eur J Pharmacol. 2012 Feb 15;676(1-3):51-6.
(62.) Li W, Zhu S, Li J, et al. EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages. Biochem Pharmacol. 2011 May 1;81(9):1152-63.
(63.) Saiwichai T, Sangalangkarn V, Kawahara K, et al. Green tea extract supplement inhibition of HMGB1 release in rats exposed to cigarette smoke. Southeast Asian J Trop Med Public Health. 2010 Jan;41(1):250-8.
(64.) Zhu S, Li W, Li J, Sama AE, Wang H. Caging a beast in the inflammation arena: Use of Chinese medicinal herbs to inhibit a late mediator of lethal sepsis, HMGB1. Int J Clin Exp Med. 2008;1(1):64-75.
(65.) Cai B, Deitch EA, Ulloa L. Novel insights for systemic inflammation in sepsis and hemorrhage. Mediators Inflamm.
(66.) Naglova H, Bucova M. HMGB1 and its physiological and pathological roles. Bratisl Lek Listy. 2012;113(3):163-71.
(67.) Khalil AA, Hall JC, Aziz FA, Price P. Tumour necrosis factor: implications for surgical patients. ANZ J Surg. 2006 Nov;76 (11):1010-6.
(68.) Qiu P, Cui X, Barochia A, Li Y, Natanson C, Eichacker PQ. The evolving experience with therapeutic TNF inhibition in sepsis: considering the potential influence of risk of death. Expert Opin Investig Drugs. 2011 Nov;20(11):1555-64.
(69.) Sama AE, D'Amore J, Ward MF, Chen G, Wang H. Bench to bedside: HMGB1-a novel proinflammatory cytokine and potential therapeutic target for septic patients in the emergency department. Acad Emerg Med. 2004 Aug;11(8):867-73.
(70.) Hohensinner PJ, Goronzy JJ, Weyand CM. Telomere dysfunction, autoimmunity and aging. Aging Dis. 2011 Dec;2(6):524-37.
(71.) Pedersen-Lane JH, Zurier RB, Lawrence DA. Analysis of the thiol status of peripheral blood leukocytes in rheumatoid arthritis patients. J Leukoc Biol. 2007 Apr;81(4):934-41.
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