Arthritis is a condition characterized by inflammation of one or more of your joints, leading to joint pain and stiffness.
Arthritis is the common autoimmune disorder affected over 50 millions world wide, according to the statistic.
According to the College of Pharmacy, green tea epigallocatechin 3-gallate (EGCG) in preclinical studies displayed a significant effect in treatment of arthritic disease(41).
In the study to evaluate the possible effects of the administration of green tea extract on the oxidative state of the liver and brain of adjuvant-induced arthritic rats(3), researchers indicated that rats treated with green tea EGCG showed a significant improvement in restored natural antioxidant glutathione (GSH) and protein thiol levels produced by the body, by exhibiting the activities of the antioxidant enzymes(3).
Green tea injection also normalized the activity of glucose 6-phosphate dehydrogenase, which is increased in the liver of arthritic patients and considered as a risk factor for the development of arthritis(6).
Additional differentiation of green tea EGCG immunomodulatory effects, researchers found that application of green tea EGCG at dose of 10 mg/kg demonstrated a strong effect in ameliorated clinical symptoms and reduced histological scores in arthritic mice, through modulated the immune activity by induced over expression of the Nrf-2 antioxidant pathway(6).
EGCG also ameliorated experimental arthritis in mice by eliciting indoleamine-2,3-dioxygenase (IDO) through inhibition of pro-inflammatory cytokine interferon-gamma, astrocytes and microglia in facilitated production of dendritic cells (DCs)(6) in activation of the immune system to attack the dendritic cell located on surface on the joint tissue.
In the study of adolescent male Wistar rats 12-week exposure to Cd and Pb (7mg Cd and 50mg Pb in 1kg of the diet randomly assigned to 12 to each group, as positive control received without Cd, Pb and teas, a negative control group received Cd and Pb, and groups supplemented additionally with green (GT), black (BT), red (RT), and white tea (WT), application of tea significant inhibited the decreased levels of the geometric(shape) and densitometric(density) parameters and total thickness of articular cartilage(1) caused by Cd and Pb in compared to the negative control group.
Tea injection group also displayed a huge improvement in mechanical endurance, growth plate thickness, and trabecular histomorphometry depending on the tea type(1).
Due to limitation of the study, Dr. Tomaszewska E, the lead researcher said, " It is difficult to indicate which tea has the best protective effects on bone and hyaline cartilage against heavy metal action".
Some scientists insisted that green tea with bioactive epigallocatechin-3-gallate, a green tea polyphenol, may be the ingredient in contributed to the cartilage protection against various types of influence(2).
Application of green tea EGCG in drinking water of mice was found to prevent collagen-induced arthritis through inhibiting the production of certain proinflammatory factors in association of damage of collagen such as tumor necrosis factor alpha (TNFα)(2), a cell signaling cytokine with pro inflammatory involvement in systemic inflammation and cyclooxygenase-2(2), an enzyme in response to inflammation and pain.
In EGCG treatment of human chondrocytes derived from OA cartilage, the application inhibited and modulated IL-1β cytokines(2) in induced activity and expression of cyclooxygenase-2(3) through its immune and inflammatory signalling and production of nitric oxide in contribution of T lymphocyte dysfunction and prostaglandin E2(2) in promotion of inflammation in chondrocytes.
According to the study, the inhibition of IL-1β by EGCG in human chondrocytes was also associated with its inhibitory effects on the activation of nuclear translocation of NF-κB(2) in expression of proinflammatory activity.
Dr. Santosh K Katiya, the lead author, after taking into account of other co founders said, "These data thus provide a mechanistic link in prevention of arthritis responses as well as potential therapeutic value for EGCG/GTPs inhibiting cartilage resorption in arthritic joints".
In investigated the effects of catechins found in green tea on cartilage extracellular matrix components using bovine nasal and metacarpophalangeal cartilage as well as human non diseased, osteoarthritic and rheumatoid cartilage cultured with and without reagents known to accelerate cartilage matrix breakdown in vitro, researchers found that catechins, containing gallate ester, were most effective in inhibited proteoglycan and type II collagen breakdown without inducing adverse effects(4).
These results suggested that some green tea catechins may have a significant effect in protected or delayed against cartilage reduction and joint damage through protection of chondrocytes.
Dr. Adcocks C, the lead author said, "green tea may be prophylactic for arthritis and may benefit the arthritis patient by reducing inflammation and slowing cartilage breakdown".
In the investigation of green tea EGCG effect on BALB/c mice induced psoriasis by topically treated with imiquimod (IMQ) for 6 consecutive days in psoriatic mouse model, researchers found that application of green tea bioactive compound demonstrates a significant effect in improved psoriasiform dermatitis, and the skin pathological structure by inhibited the proliferating cell nuclear antigen (PCNA)(5) which has been found in elevated levels in patient with psoriasis.
The levels of proliferating cell nuclear antigen (PCNA) considered as a bio marker and a abnormal proliferating cell pool in patient with skin cancer was also inhibited by EGCG injection
Administration of EGCG promoted caspase-14 expression(5) which has been altered in patients with psoriasis to orchestrate epidermal differentiation in decreased in inflammatory lesions in atopic dermatitis through its function as a novel regulator of skin cell differentiation and skin barrier formation to protect the skin cell against inflammation.
Treatment of EGCG also attenuated skin inflammation through reduced levels of inflammatory factors such as interleukin (IL)-17A(5), a pro-inflammatory cytokine, produced by a group of T helper cell and IL-17F a pro inflammatory cytokine and immune mediator in trigger the innate immune activity in the acute phase of infection.
Injection of green EGCG also inhibited the T helper (Th) cell subsets IL-22(5) in secreted cytokines in stimulated immune the defense against certain microbes and the development and maintenance of chronic inflammatory diseases and IL-23(5) in enhanced the expansion of T helper type 17 (Th17)(5) cells which have been found to associate to prevalence of many of the inflammatory autoimmune responses, including psoriasis.
Green tea also reduced infiltrations of T cells in facilitate inflammatory skin lesions caused by injection of imiquimod (IMQ).
Administration of EGCG ameliorated the production of malondialdehyde (MDA), an end product of lipid peroxidation in plasma obsevered by the protocol with colorimetric Diagnostic Reagent Kit(5), an indication of over production of reactive oxygen species (ROS) in precipitated free radical chain reaction to induce oxidative stress caused by psoriasis through expression of its antioxidants and induced production of natural antioxidants in the body.
The application of green tea compound increased percentages of CD4+ T cells(5) in immunocytes in activated a series of local immunologically mediated stimulatory events that produce further T cell activation and appearance against triggers conversion of symptomless (PN) skin into psoriatic plaques (PP skin).
Dr. Shuangshuang Zhang(5), the lead author after taking into account of other con founder said, " (
EGCG attenuates the IMQ-induced histological changes of skin) of marked hyperkeratosis, parakeratosis, modest acanthosis, elongated rete ridges, and modest dermal inflammation.... , increased parakeratosis, acanthosis and inflammatory cell infiltration (caused by IMQ)".
EGCG exerted anti-inflammatory, immune regulatory and antioxidant effects in ameliorated expression of psoriasis may also have strong implication in prevented psoriasis in induction of chronic inflammation of the joint in catalyzed psoriatic arthritis.
According to the statistic, the most common form of juvenile idiopathic arthritis (JIA), affects over 50,000 children in the United States alone.
In the investigation of the effect of green tea extract on the oxidative state of the liver and brain of adjuvant-induced arthritic rats, a model for human rheumatoid arthritis with daily doses of 250 mg kg(-1) (59.8 mg catechins per kg) for 23 days, researchers at the State University of Maringá, found that treatment group expessed a significant activity in reduced the protein and lipid damage in liver, brain and plasma, caused by ROS expression(6) in induction of oxidation in association of the progression of arthritis.
Injection of green tea extract also enhanced the over expression of antioxidant defenses, found in low levels in patients with arthritis through restoration of the glutathione (GSH)(6) with important function in preventing damage to important cellular components caused by reactive oxygen species and protein thiol levels in reduced cellular oxidation through chelative and detoxified activities and improved the natural antioxidant enzymes, produced by the body.
Green tea extract also inhibited the elevated levels of glucose 6-phosphate dehydrogenase(6) in the liver, one of major risk factor for the development of arthritis.
These results suggested that application of green tea exerted a significantly profound effect in the liver and brain of patients suffering from rheumatoid arthritis through reduced over expression of oxidative stress in precipitated injury to lipids and proteins.
Some researchers suggested that by modifying the metabolic function in lipid and protein, green tea extract exhibited a strong protective effect in reduced the symptoms and progression of arthritis.
According to the study of University of Health System of green tea effect in patient with rheumatoid
arthritis, injection of green tea extract demonstrated a therapeutic effect in patients synovial fibroblast
of the lining of the tissue(7) which surround the capsule of the joint by inhibited the production of IL-1B(7), a prototypic proinflammatory cytokines in response to acute and chronic inflammation. Over expression of IL-1B is associated in contribution of joint damage.
In the study of adolescent male Wistar rats 12-week exposure to Cd and Pb (7mg Cd and 50mg Pb in 1kg of the diet randomly assigned to 12 to each group, as positive control received without Cd, Pb and teas, a negative control group received Cd and Pb, and groups supplemented additionally with green (GT), black (BT), red (RT), and white tea (WT), researchers indicated that application of tea significant inhibits the decreased levels of the geometric(shape) and densitometric(density) parameters and total thickness of articular cartilage(1) caused by Cd and Pb in compared to the negative control group.
Tea injection group also displayed a huge improvement in mechanical endurance, growth plate thickness(1), and trabecular histomorphometry depending on the tea type.
More importantly, in the examine some major factors in contributed to the juvenile arthritis, green tea rich in catechins (Healthya green tea) in animal study restored these biomarkers of cytokine genes (IL-1A, IL-2, IFN-alpha, FGF-alpha, TNF-alpha)(1) to near normal levels, thus preventing or attenuating the development of a certain type of inflammatory arthritis.
In the study to evluate the effects of ingestion of green tea and green tea bioactive compounds in mitigating bone loss and risk of osteoporotic fractures in both elderly women and men, researchers found that application of green tea and its bioactive compounds exert significant activities in reduced onset of osteoporosis, through its antioxidants and its initiation of the production of natural antioxidant in the body such as glutathione and enzymes(8) (e.g., catalase and superoxide dismutase) in inhibited the levels of ROS in facilitated the chain reaction.
The over expression of free radicals has been associated to the change in balance between activities of osteoblasts and osteoclasts(8), leading to osteoclasts in destroyed the calcified tissue and induced bone remodeling.
These results demonstrated a significant decrease of risk of fracture by improving bone mineral density and preventing free radicals in damage the bone-forming osteoblasts while suppressing osteoclastic activities.
The review of the effect of green tea on bone health, researchers indicated that ingestion of green and its bioactive compound display an impressive osteo-protective impact on bone mass and microarchitecture in various bone loss models associated to aging, sex hormone deficiency, and chronic inflammation(9).
The implication of reduced onset and progression of osteoporosis in aging population due to sex hormone deficiency of the study may be attributed to green tea and its bioactive compound in increased the levels of osteocalcin(9), a bone formation marker, decreased serum of tartrate-resistant acid phosphatase (TRAP)(9), a bone resorption marker and improved the body in absorption of calcium.
Serum levels of osteocalcin (OC) and tartrate-resistant acid phosphatase (TRAP) are considered as an effective measurement in the rate of bone turn over in patients with osteoporosis.
Application of green tea and its bioactive compound also found to modulate the expression of proinflammatory cytokines in the regulation of osteoblasts and osteoclasts, through inhibited the production of C-reactive protein (CRP)(10) production in the liver in demonstrated of inflammation by reduced levels of interleukin-1 and 6(IL-1-6)(10) and tumor necrosis factor-alpha (TNF-α)(10), the sensitive markers of systemic inflammation.
These differentiation were supported by the study in evaluation of the efficacy of green tea polyphenols (GTPs) at mitigating bone loss and microstructure deterioration along with related mechanisms in 40 androgen-deficient aged male rats, a model of male osteoporosis, randomly assigned to received A 2 (sham vs. orchidectomy) × 2 (no GTP and 0.5% GTP in drinking water)(10) for 16 weeks.
At the end of experiment, researchers found that rats treated with GTP demonstrate an increased serum osteocalcin concentrations, bone mineral density, and trabecular volume, number, and strength of femur; increased trabecular volume and thickness and bone formation in both the proximal tibia and periosteal tibial shaft(10); decreased eroded surface in the proximal tibia and endocortical tibial shaft; and increased liver glutathione peroxidase activity(10).
These results indicated a strong implication of green tea polyphenols in decreased cortical and trabecular bone loss and increased both bone density by stimulated over expression of bone formation and reduced bone resorption via antioxidant capacity.
According to the joint study lead by Washington State University College of Pharmacy, green tea (EGCG, EGC, and EC) ameliorated the expression of pro-inflammatory mediators including (IL-6 and IL-8) and Cox-2(11) in primary human rheumatoid arthritis synovial fibroblasts (RASFs), through the effects of its phytochemical compounds of EGCG and EGC antioxidant activities.
Dr. Fechtner S, the lead researcher said," EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of (epicatechin) EC".
In the investigation of the anti-inflammatory activity of green versus black tea aqueous extract in a rat model with orally/daily distilled water as placebo, indomethacin (1.0 mg/kg body weight; a non-steroidal/anti-inflammatory drug), or tea aqueous extracts (for 28 or 14 consecutive days administrated from day 0 or 14 of arthritis induction, respectively), group treated with high dose of GTE (from day 0) significantly alleviated (P < 0.05-0.001) the progression and all complications induced by rheumatoid arthritis in compared to placebo(12).
Researchers also found that the expression of anti-arthritic activity of the high dose of GTE (from day 0) significantly decreased the systemic production of pro-inflammatory cytokines(12) and the expression of chemokine receptor-5(12), a protein in activated immune activities in the in synovial tissues, in comparable (P > 0.05) to those of indomethacin(12) (12.9-53.8 vs. 9.5-48.4%, respectively).
The anti-arthritic potency of tea aqueous extracts was doses dependent in the order of high dose of GTE > low dose of GTE ≥ high dose of BTE > low dose of BTE(12).
Other researchers suggested that green tea extract in reduced symptoms and risk of complications probably are the result in regulating chemokine(a family of cytokines secreted by cells)(13) production in immune reaction and chemokine receptor expression in interaction with proimflammatory cytokines of human RA synovial fibroblasts, according to rat adjuvant-induced arthritis (AIA).
In a randomized open-label active-controlled clinical trial of 50 adults with osteoarthritis of knee allocated to receive the green tea extract (in dosage form of tablet) plus diclofenac tablet as "intervention group"(14); or: diclofenac tablet alone as "control group" for a period of four weeks, combination treated group exerted a significant improvement of physical function in compared to control(14).
Treatment group also expressed a similar progress in pain reduction during knee joint physical function in adults with osteoarthritis as in control group.
In the compared the effect of curcuminoids extract, hydrolyzed collagen and green tea extract, in chondrocytes culture cell, researchers found that the combination scores an enormous expression in reduced production of pro inflammatory cytokins(15) through various mechanisms, including ameliorated free radical elucidation.
In the support of the above differentiation, the study in the investigation of a posttraumatic osteoarthritis (OA) mouse model tested with EGCG against progression of OA and OA-associated pain, researchers suggested that EGCG-treated mice promoted cartilage protection against Safranin O, staining(16) of knee joint cartilage loss and cartilage erosion in compared to control group with no treatment.
Cartilage of treated mice also displays a significant reduction of gene in regulated degeneration(16) of connective tissue as well as pathways involved promotional of tissues inflammation.
Pain score of treated mice also exhibited a significant enhancement in compared control group(16).
In animal study of inflammatory diseases induced by injection of LPS, application of green tea bioactive polyphenols EGCG improved antioxidant status(17) of the host and decreased production of inflammatory factors(17), including PMR through its antioxidant properties.
Application of EGCG reduced symptoms of inflammation such as pain, tension, stiffness, swelling(17) of the infectious site without affecting the function of immune system in protection against micro organisms invasion through inhibiting over-expression of tumor necrosis alpha(TNF-α)(17) involved in systematic inflammatory response to acute phase of infection.
The bioactive compound also inhibited reactive oxygen species (ROS)(17) in stimulated production of inflammatory cytokines through free radicals chain reactions in facilitated inflammation and precipitated skeletal muscle dysfunction(17) and degradation(17) by infiltrating immune cells to induce direct injury to muscle tissue or activating catabolic signaling.
In fact, over production of ROS increased continuously expression of mitochondria, NAD(P)H oxidases, xanthine oxidoreductases, and nitric oxide synthases(17)(19) caused imbalance of the free radicals and antioxidant ratio, in orchestrated oxidative stress to muscle cells..
Further evaluation suggested that green tea EGCG reduced expression of interleukin 6 (IL-6)(17), with function in response to infections and tissue injuries.
Long term over production of IL 6(17) due to the duo factors as a pro and anti inflammatory protein may increase high-level concentrations of serum amyloid A (SAA)(17), which has been found to induce serious complications of several chronic inflammatory diseases(18) through generated and deposited amyloid A amyloidosis into the extracellular space in an abnormal, insoluble, fibrillar form,
EGCG also attenuated levels of nuclear factor kappa B (NF-κB)(17) in regulated innate and adaptive immune functions and served as a pivotal mediator of inflammatory responses(17)(18) through deactivation of tumor necrosis factor alpha (TNF-α) in promoted muscle wasting, leading to muscle atrophy in induction of pain and stiffness and swelling.
Application of green tea EGCG enhanced the natural antioxidant enzymes in the host such as glutathione(19), an antioxidant enzyme produced naturally found in every cell and tissue of the body.
These actions together with antioxidant initiated by injection of green tea EGCG stimulated cell regeneration(17)(19), preserved the muscle cells and tissues and prevented muscle tension to precipitate polymyalgia arthritis.
Deficiency of glutathione levels was found to associate to the early development of Polymyalgia Arthritis in facilitated symptoms of pain, stiffness, achiness, fatigue and fever.
Differentiations of the above were supported by conventional medicine corticosteroids, a powerful anti-inflammatory drugs with function to target pro inflammation cytokines(18) in relieved stiffness and pain in patients with polymyalgia arthritis.
Application of biologically active polyphenol epigallocatechin 3-gallate (EGCG) demonstrated a significant effect in reduced back pain through facilitate anti inflammatory(20) and anti-catabolic activity(20) in patients with intervertebral disc (IVD) disease due to age-related changes in the adult disc in induction of back pain.
According to the study by the Institute for Biomechanics (D-HEST), ETH Zurich ingestion of green tea EGCG on back pain patients, human IVD cells isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D indicated that the phytochemicals inhibited levels of inflammatory response activated by IL-1β(20), a cytokine protein produced by macrophages, with function in contributed to the inflammatory pain hypersensitivity in the site of infection observed by the reverse transcription polymerase chain reaction (qRT-PCR)(20), western blotting, enzyme-linked immunosorbent assay (ELISA)(20), immunofluorescence and transcription factor assay(20).
Application also displayed a strong effect in reduced expression of
p38(20) mitogen-activated protein kinases in mediated inflammatory factors of IL-1β(20) in responded to stress stimuli.
Also, according to the Institute for Biomechanics (D-HEST), in the investigation of the analgesic properties of EGCG, by the von Frey filament test in Sprague-Dawley rats (n = 60), green tea EGCG injection also significantly inhibited the expression of pro-inflammatory mediators as expressed in above and reduced matrix metalloproteinases(21) which have been found to associate to pro-inflammatory cytokines, chemokines and other proteins to regulate various aspects of inflammation and immunity.
In the radiculopathic pain component, researchers also indicated that EGCG inhibited the inflammation in precipitated back pain through modulation of the activity of IRAK-1(21) in glucose metabolism and insulin sensitivity in skeletal muscle and p38, c-Jun N-terminal kinases (JNK)(21) and nuclear factor NF-κB(21) in responded to stress stimuli in mediated production of pain related pro inflammatory cytokines such as IL-1β(21).
Some researchers postulated that back pain may also induced by muscle degeneration and impairment nerve injury, leading to increased levels of reactive oxygen species in induced tissue apoptosis.
In crushing of the sciatic nerve induced back pain in tested animal, application of green tea EGCG improved motor function in the toe spread and foot positioning and gain in the percentage motor deficit(22).
EGCG expressed a significant effect in recovery of sensory innervation in neuropathic pain-like syndrome and improvement of muscle tissues from injured limb with severe histopathological alterations at the end of week 3 post-surgery in treated animals(22).
According to the RT-PCR assay, EGCG treatment also normalizing the Bax/Bcl-2 ratio(22), abnormal ratio of the Bax/Bcl-2 ratio has been found to associate in induction of nerve cell apoptosis as well as inhibited levels of p53(22) with function in regulated the cell death cycle at days 3 and 7 post-surgery.
These results demonstrated an important effect of green tea EGCG in enhanced functional recovery, protected muscle fibers from cellular death, and improved morphological recovery in skeletal muscle after nerve injuries.
However, in the study of caffeine activity in the modulation of pain perception in chronic pain states of 131 patients with chronic low back pain (64 men and 67 women; mean age = 42.1 years; mean duration of pain = 6.1 years) referred to a multidisciplinary pain clinic over a 2-year period, researchers found that regardless to concentration, caffeine is not related to the global experience of pain and disability in patients with chronic low back pain(23), although high caffeine use may be embedded in a context of other unhealthy life-style behaviors.
In other words, in herbal medicine, green tea is considered to have certain effect in reduced symptoms and treatment of such syndrome.
Some evidences in medical literature suggested that over production of ROS in induction of oxidative stress(25) may have a strong implication in the pathophysiology of FM.
In the investigation of the effect of green tea epigallocatechin-3-gallate (EGCG) in protection of oxidative stress to cardiac cells cultured in the conditions of control, 400 μM H2O2 exposure for 30 min with and/or without 10 to 20 μM EGCG pre-treatment, researchers at the National Tsing Hua University found that treatment of green tea in H(2)O(2) group demonstrated a significant reduction of levels of reactive oxygen species through its antioxidant and its ability(25) in induced production of natural antioxidant presented in the cardiac cells in compared to over expression of ROS in H2O2 treatment group without injection of EGCG.
Also, application of green tea reduced levels of cytosolic Ca2+ overload in the H(2)O(2) group in induced oxidative stress(25) through improved antioxidant protein.
EGCG inhibited H(2)O(2) expression in increased glycolytic protein in response to the degree of oxidative stress in the culture cells and α-enolase(25), a key glycolytic enzyme on the surface of several cell types in contribution of impaired glycolytic activity through oxidative and nitrative stress.
Additionally, green tea EGCG also increased levels of peroxiredoxin-4(25), an antioxidant with function in protection against oxidative stress by detoxifying peroxides and mitochondrial proteins with function of redox reactions of oxidative phosphorylation.
After taking into account of other con founders, researchers suggested that ingestion of green tea EGCG inhibited the damage of H(2)O(2) group through inhibition of the downstream signalling for Akt in expression glucose oxidation and cell apoptosis in cellular processes, and loss of phosphorylation of GSK-3β(25) and cyclin D1(25) depletion in facilitated oxidative stress.
These result postulated that green tea EGCG exerted the similar inhibited effect of those of GSK-3β inhibitor (SB 216763) in significantly improved H(2)O(2)-induced suppression on cell viability, phosphorylation of pAkt (S473) and pGSK-3β (S9), and level of cyclin D1 in cells(25).
The above differentiation was supported by the study conducted by the Universidad de Sevilla(26), in evaluated some evidences of green tea in reduced oxidative stress in facilitated pathophysiology of FM in initiated signs and symptoms of muscular alteration and mitochondrial dysfunction.
In primary rat model, administration of green tea EGCG in different concentrations for 24 h before being exposed to hydrogen peroxide (H(2)O(2)) for 2 h to induce oxidative stress, researchers found that pretreatment with 10, 25, and 50 µM EGCG significantly inhibited the expression of H2O2(26) in reduced substantial decrease in cell viability.
Further analysis also showed that green EGCG application dose of 50 µM ameliorated the proportion of propidium iodide (PI)-positive cells increased in cultures caused by H(2)O(2) injection(26), thus reducing H(2)O(2) in induced cell death.
In healthy participants, the study indicated that sleep deprivation can also cause fibromyalgia like symptoms such as myalgia, tenderness and fatigue(27) and suggested that sleep dysfunction might be not only a consequence of pain.
These results showed a strongly correlated condition of sleep disturbance in initiation of chronic fibromyalgia if sleep disorders are left untreated for a prolonged period of time.
According to the presentation, long time effect of sleep disturbance may influence and alter the pathophysiology of the central nervous system in abnormal pain processing and central sensitization(27), according to observation of the neuroimaging of patients with fibromyalgia neural activation in compared to lower pressure-pain threshold in healthy age-matched and gender-matched individuals(27).
After taking into account to other con founders, researchers said, " improving sleep quality can reduce pain and fatigue, further supporting the hypothesis that sleep dysfunction is a pathogenic stimulus of fibromyalgia"(27).
Green tea, bioactive polyphenols (-)-Epigallocatechin gallate (EGCG) in the evaluation of the the chick brain under an acute stressful condition in facilitated sleep disturbance, researchers found that EGCG attenuates stress behavior with special reference to gamma-aminobutyric acid (GABA)(28), a neurotransmitter with function in sending chemical messages through the brain and the nervous system, and involving the regulation of communication between brain cells in stress environment.
Deficiency of GABA is associated to many nervous conditions, including depression, anxiety, and sleep disorders.
Application of EGCG of doses of 50, 100 and 200 microg, intracerebroventricularly exerted a profound effect in suppressed the vocalization which normally occurs during social separation stress(28).
This illustration truly suggested that EGCG reduced the time spent in active wakefulness and induced sleep-like behavior in a dose-dependent manner.
Under influence and presence of the GABAA receptor antagonist picrotoxin but not by the GABAB receptor antagonist CGP 54626 (3-N-(1-(3,4-dichlorophenyl)ethylamino)-2-hydroxypropyl cyclohexylmethyl phosphinic acid hydrochloride)(28), a antidote in poisoning by CNS depressants, the effect of green tea EGCG is significantly decrease in attenuated the production of hormone corticosterone release under social separation stress.
These interaction opinionated that EGCG inducted sedation and hypnosis in reduced stress hormone production in precipitated sleep distance probably though GABAA receptors(28) in moderated and acute stress response.
Some researchers suggested that green tea improves symptoms of fibromyalgia by normalizing the levels of GABA (gamma-aminobutyric acid)(29), may have a therapeutic effect in reduced anxiety by relaxed the muscles and the brain. through increased production of dopamines, serotonin, and alpha waves within the brain in orchestrated the sleep pattern.
These improvements were associated to the interaction of the brain with chemical compounds found in green tea caffeine and L-theanine(29), suggested by the author.
According to the Cairo University, as many as 15-30% of patients with classic inflammatory rheumatic disorders also have a co-morbid fibromyalgia syndrome (FMS)(30) incompared to the rate of only 2% of the prevalence of FMS in the general population (2%)(30).
These results suggested that rheumatological syndromes have a strong implication in the development of fibromyalgia syndrome (FMS) in compared to other initiators such as stress.
Therefore, patients with chronic rheumatic diseases are capable of triggering condition of fibromyalgia syndrome (FMS).
Due to the highly correlated rheumatologic disease and FMS component, researchers postulated "Considerations of the FMS component in the management of rheumatologic diseases increase the likelihood of the success of the treatment" and "(prevented) FMS in misdiagnosed as an autoimmune disorder"(30).
In the study of the effect of green tea's active ingredient, epigallocatechin 3-gallate (EGCG) in risk of inflammatory rheumatic disorders in collagen-induced arthritis (CIA) in mice, researchers found that application of green tea demonstrates a substantially marked inhibition of the inflammatory mediators cyclooxygenase (COX) -2(31) in converting arachidonic acid in stimulated production of proinflammatory cytokine prostaglandin H2, in catalyzation(31) of symptoms of inflammation in the muscles.
Green tea EGCG oral ingestion also inhibited levels of interferon gamma in precipitated inflammation by modulating T-cells(31) and natural killer cells(31) activated by antigens, mitogens or alloantigens to the site of infection, and tumor necrosis factor alpha (TNFα)(31) involved in systemic inflammation, one of the cytokines that make up the acute phase reaction in mice was also inhibited by injection of green tea EGCG.
These results suggested that green tea ameliorated symptoms expression of inflammatory rheumatic disorders, through attenuating production pro inflammatory factors without reducing the healing progression of injure tissue.
The above differentiation were supported by the study of green tea extract GTE in modestly ameliorated rat adjuvant-induced arthritis.
According to researchers, a daily per oral administration of GTE (200 mg/kg) reduced expression of RA through reduced levels of MCP-1/CCL2(31) in expression (which can also be treated by biological agents, such as antibodies and inhibitory peptides) of a variety of diseases characterized by mononuclear cell infiltration involved substantial biological and genetic evidence, including RA.
and GROα/CXCL1(31) in the recruitment of inflammatory cells in the wound healing process after injury in angiogenesis(31) and in formation of granulation tissue of wounds.
Application of green tea beside attenuated the expression of proinflammatory factors, its also exhibited the production of chemokine receptors CCR-1, CCR-2, CCR-5(31) in reduced direct communication between the innate and adaptive immune responses in initiated the development of inflammatory responses. through inactivation of leukocytes(31) in inflamed tissues in contribution to the pathogenesis of inflammatory and autoimmune diseases.
And CXCR1 receptor in binding to IL-8 in reduced expression some infallmatory cytokines in initiated inflammation such as epidermal growth factor (EGF) and tumor necrosis factor-α (TNF-α)(31).
Some researchers suggested that application of green tea extract may also reduce the symptoms of arthritis through expression of IL-6 levels(31), as increased levels of Il-6 was associated to the presence and progression of rheumatoid arthritis (RA) found in conventional clinical and laboratory indices and MMP-2(31) activity in activated immune inflammatory response through inducing production of pro inflammatory factors.
In the study of the effect of serum of alpha1-Antitrypsin (AAT) and risk of fibromyalgia (FM), researchers at the Hospital Valle del Nalón found that deficiency of AAT has been found in numbers of patients with fibromyalgia (FM) with severe hereditary(32).
Functional magnetic resonance imaging of these patients revealed a significant greater activity in pain sensitive areas of the brain in response to cutaneous stimuli(32), which may be another evidence for a physiological explanation for FM pain.
Patients with FM also were found to consist an abnormal profile of inflammation markers in biopsies analysis(32).
The results suggested that these patients may have an imbalance levels of pro inflammatory and anti-inflammatory substances, in the soft body tissues caused by alpha1-Antitrypsin (AAT) deficiency.
Due to surprising findings, Dr. Blanco LE(32), the lead author, after taking into account of other confounders, said, "identification of genetic, familial, and environmental risk factors suspected to participate in the FM syndrome development (may be necessary) to determine the gene frequency of AAT deficiency alleles in FM patients".
Green tea, bioactive polyphenols EGCG, according to the Dr Helieh S in animal model induced by alpha1-Antitrypsin (AAT) (α1-antitrypsin) deficiency exerted a significant anti inflammatory effect in inhibited the PI3K/Akt signalling pathway(32) with function in activated proinflammaory factors(32) through the innate immune response involved in pathogen killing, antigen processing and immune cell survival.
Green tea EGCG application also enhanced antioxidant activity not only through its antioxidant profiles, but also stimulated production of the body natural antioxidants in reduced inflammatory response through nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression(32), observed by Griess reagent and western blotting.
These results indicated that green tea EGCG may have a profound effect in reduced serum alpha1-Antitrypsin (AAT) deficiency in initiated the onset of fibromyalgia
The above differentiations were supported by the review of Chronic Inflammatory Diseases and Green Tea Polyphenol, by Dr. Helieh S. Oz at the University of Kentucky Medical Center(33).
According to the authors, green tea polyphenols are potent antioxidants with important roles in regulating vital signaling pathways in activated inflammatory responses by attenuated nuclear factor (NF)-kappaB IKK, NF-κB933) in facilitated innate- and adaptive-immune responses, cell death and inflammation and cytokines like TNFα(33), inflammatory markers and cyclooxygenase-2(33) in elevated symptoms of inflammation and pain.
Dr. Helieh S. in summary said, "green tea polyphenols (GrTPs) are potent antioxidants with important roles in regulating vital signaling pathways" and "these comprise transcription nuclear factor-kappa B mediated I kappa B kinase complex pathways, programmed cell death pathways like caspases and B-cell lymphoma-2 (through regulating the cytochrome c release from the mitochondria) and intervention with the surge of inflammatory markers like cytokines and production of cyclooxygenase-2"(33).
According to the study, green tea and its bioactive compoud Epigallo catechin-O-gallate (EGCG) may be considered as a putative curative drug for various diseases of gout, through its properties in reduced vascular endothelial growth factor receptor 2 (VEGFR2)(34)(35) in response to vascular endothelial growth factor signal (VGFG)(35) for formation of gout through expression of levels of uric acid.
The study also emphasized that green tea with high levels of antioxidant and function in stimulated production of natural antioxidant in the body may also be used to reduce symptoms of recurrently inflammatory arthritis and inflammatory arthritis(37) such as gout, through inhibiting the oxidative stress in induced production of inflammatory cytokines to facilitate symptoms of inflammation(37).
The above differentiation were supported by the study of the effect of EGCG on monosodium urate monohydrate (MSU)-induced inflammation and cryopyrin (NLRP3 inflammasome)(36) activation in C57BL/6 mice received subcutaneous injection or oral gavage of EGCG before the intraperitoneal injection of MSU.
Application green tea EGCG decreased expression of gouty arthritis caused by injection of MSU-induced neutrophil infiltration with function in initiated inflammation in the acute phase of infection and IL-1β secretion(36), in response and resistance to pathogens in exacerbated damage during chronic disease and acute tissue injury.
The injection of green EGCG also decreased MSU-triggered neutrophil cytosolic factor 1(36), in activated inflammatory response to optimize healing and reduce injury to the body but the proteins has been found to cause severed damage to the infectious site and NLRP3 protein expression(36) in initiated systematic inflammatory expression.
The effect of green tea in protection against gout occurrence also limited pro-inflammatory mediator secretion interleukin 1 beta (IL1β)(36), a mediator of inflammation, in response to acute phase infection, interleukin 6 (IL-6) produced by large amount at sites of acute and chronic inflammation, monocyte chemoattractant protein-1 in regulated monocytes, memory T cells, and dendritic cells(36) to the sites of inflammation, and serum amyloid A(36), the serum was found to increase substantially in patient of chronic inflammatory disease.without limiting the function of the mediators in protect the infectious site against pathogens invasion.
The efficacy of green tea in reduced recurrent gout also extended to suppress NLRP3 inflammasome in stimulated caspase-1(38) in promoted secretion of others proinflammatory cytokines activation(38).
Dr. Jhang JJ, the lead author said, "EGCG treatment ameliorates MSU-induced inflammation, suggesting that EGCGexerts anti-inflammatory effect against MSU-induced acute gout attack."
Additionally to above study, the University of Pretoria suggested that polyphenols extracted from green tea also exhibit antioxidant effect in reduced pronounce of oxidative stress by their antioxidant properties(37).
Catechin (C) (Ki = 303.95, uncompetitive), epicatechin (EC) (Ki = 20.48, mixed), epigallocatechin (EGC) (Ki = 10.66, mixed), epicatechin gallate (ECg) (Ki = 2.86, mixed) and epigallocatechin gallate (EGCg) (Ki = 0.76, competitive) were found to have similar efficacy as allopurinol (Ki = 0.30, mixed), the drug used to inhibit the levels of xanthine oxidase (XO)(37) in gout patients, through reduced reactive oxygen species in initiated oxidative stress in induction of inflammatory symptoms.
According to the study of the effect of GT and/or glycine in the diet on tendinitis on Wistar rats, randomly divided into seven groups (G): control group (C); G1 and G4, tendinitis; G2 and G5, tendinitis supplied with GT; and G3 and G6, tendinitis supplied with GT and a glycine diet for 7 or 21 days, respectively, group with tendinitis treated with green tea demonstrated a significant effect in enhanced collagen stablility(40) through expression of hydroxyproline in compared to other groups.
GT and glycine alone treated groups showed an increased activity of metalloproteinase-2 MMP-2 levels(40) which has been associated to the healing process of the fibrous connective tissue in tendinitis patients.
In compared to control and non GT treatment groups, application of green tea or GT+ gyycine group displayed a statistical significance in the decreased muscle retardation(40).
After taking into account of other co founders, Dr. Vieira CP, the lead author said, " GT + a glycine diet has beneficial effects that aid in the recovery process of the tendon after tendinitis".
In the study investigated the remodeling effects of green tea and glycine in the myotendinous junction (MTJ) of male Wistar rats with tendinitis, randomly divided into five groups: animals without tendinitis and animals with tendinitis; animals with tendinitis supplied with green tea; animals with tendinitis supplied with a glycine diet; animals with tendinitis supplied with a green tea and glycine diet, researcher found that all treatment groups exerted a profound effect in regulated the activity of metalloproteinases (MMP)-2(39) with function in remodeling the tendon after tendinitis, MMP-8 and -9(99)in associated to remodeling tissue expression in the disease progression and induced the synthesis of type I collagen regulation by cell spreading, platelet-derived growth factor and interactions with collagen fibers.
Rats groups treated above applications also demonstrated an increase of glycosaminoglycans, in stimulated the regenerative processes(39), while maintaining host cell characteristics and function and non-collagenous proteins(39) in modulated the development of fine fibrils presented in collagen fibers of connective tissue
The combination of green tea and glycine also modulated the inflammatory process through stimulated production of anti inflammatory factors and induced the synthesis of the elements, such as extra cellular matrix involved in the post-lesion recovery of the tissue.
These results indicated an important recovery from injured tendon through improving the compaction of the collagen molecules and inducing assembly of early collagen fibers(39), in green tea and glycin treated groups.
After considering of all cofounders, researchers and colleagues at the Anat Rec said, " each region of the inflamed tendon can exhibit different responses during the treatment and therefore, modify its extracellular matrix components to facilitate recovery and repair".
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Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
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Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
(1) Alteration in bone geometric and mechanical properties, histomorphometrical parameters of trabecular bone, articular cartilage, and growth plate in adolescent rats after chronic co-exposure to cadmium and lead in the case of supplementation with green, black, red and white tea by Tomaszewska E1, Dobrowolski P2, Winiarska-Mieczan A3, Kwiecień M3, Tomczyk A4, Muszyński S5, Radzki R4.(PubMed)
(2) Green tea: a new option for the prevention or control of osteoarthritis by Santosh K Katiyar1,2 and Chander Raman(PMC)
(3) Green tea: a new option for the prevention or control of osteoarthritis by Santosh K Katiyar1,2 and Chander Raman(PMC)
(4) Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilageproteoglycan and type II collagen degradation in vitro by Adcocks C1, Collin P, Buttle DJ.(PubMed)
(5) Epigallocatechin-3-gallate (EGCG) inhibits imiquimod-induced psoriasis-like inflammation of BALB/c mice by Shuangshuang Zhang,#1 Xiangdong Liu,#2 Lihong Mei,1 Hongfeng Wang,1 and Fang Fang(PMC)
(6) Green tea extract improves the oxidative state of the liver and brain in rats with adjuvant-induced arthritis by de Almeida Gonçalves G1, de Sá-Nakanishi AB, Wendt MM, Comar JF, Bersani Amado CA, Bracht A, Peralta RM.(PubMed)
(7) (Alteration in bone geometric and mechanical properties, histomorphometrical parameters of trabecular bone, articular cartilage, and growth plate in adolescent rats after chronic co-exposure to cadmium and lead in the case of supplementation with green, black, red and white tea by Tomaszewska E1, Dobrowolski P2, Winiarska-Mieczan A3, Kwiecień M3, Tomczyk A4, Muszyński S5, Radzki R4.(PubMed)
(8) Green tea and bone metabolism by Shen CL1, Yeh JK, Cao JJ, Wang JS.(PubMed)
(9) Green tea and bone health: Evidence from laboratory studies by Shen CL1, Yeh JK, Cao JJ, Chyu MC, Wang JS.(PubMed)
(10) Supplementation with green tea polyphenols improves bone microstructure and quality in aged, orchidectomized rats by Shen CL1, Cao JJ, Dagda RY, Tenner TE Jr, Chyu MC, Yeh JK.(PubMed)
(11) Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts by Fechtner S1, Singh A1, Chourasia M2, Ahmed S3.(PubMed)
(12) Anti-inflammatory activity of green versus black tea aqueous extract in a rat model of human rheumatoid arthritis by Ramadan G1, El-Beih NM1, Talaat RM2, Abd El-Ghffar EA1.(PubMed)
(13) Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis by Marotte H1, Ruth JH, Campbell PL, Koch AE, Ahmed S.(PubMed)
(14)Green tea (Camellia sinensis) for patients with knee osteoarthritis: A randomized open-label active-controlled clinical trial by Hashempur MH1, Sadrneshin S2, Mosavat SH3, Ashraf A4.(PubMed)
(15) Curcuminoids extract, hydrolyzed collagen and green tea extract synergically inhibit inflammatory and catabolic mediator's synthesis by normal bovine and osteoarthritic human chondrocytes in monolayer by Comblain F1, Sanchez C1, Lesponne I2, Balligand M3, Serisier S2, Henrotin Y4.(PubMed)
(16) Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model by Leong DJ, Choudhury M, Hanstein R, Hirsh DM, Kim SJ, Majeska RJ, Schaffler MB, Hardin JA, Spray DC, Goldring MB, Cobelli NJ, Sun HB.(PubMed)
(17) Epigallocatechin-3-gallate attenuates lipopolysaccharide-induced mastitis in rats via suppressing MAPK mediated inflammatory responses and oxidative stress by Chen J1, Xu J1, Li J1, Du L1, Chen T2, Liu P1, Peng S1, Wang M1, Song H3.(PubMed)
(18) [Anti-inflammatory effects of tea-flavonoids].[Article in German] by Hoensch H1, Oertel R.(PubMed)
(19) Green tea polyphenol epigallocatechin-3-gallate: inflammation and arthritis. [corrected]. by Singh R1, Akhtar N, Haqqi TM.(PubMed)
(20) Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats by Krupkova O1, Sekiguchi M, Klasen J, Hausmann O, Konno S, Ferguson SJ, Wuertz-Kozak K.(PubMed)
(21) (-)-Epigallocatechin-3-gallate (EGCG) attenuates functional deficits and morphological alterations by diminishing apoptotic gene overexpression in skeletal muscles after sciatic nerve crush injury by Renno WM1, Al-Maghrebi M, Al-Banaw A.(PubMed)
(22) (-)-Epigallocatechin-3-Gallate Modulates Spinal Cord Neuronal Degeneration by Enhancing Growth-Associated Protein 43, B-Cell Lymphoma 2, and Decreasing B-Cell Lymphoma 2-Associated X Protein Expression after Sciatic Nerve Crush Injury(PMC)
(23) Caffeine and chronic low back pain by Currie SR1, Wilson KG, Gauthier ST.(PubMed)
(24) Use of complementary and alternative medical therapies by patients referred to a fibromyalgiatreatment program at a tertiary care center by Wahner-Roedler DL1, Elkin PL, Vincent A, Thompson JM, Oh TH, Loehrer LL, Mandrekar JN, Bauer BA.(PubMed)
(25) Oxidative stress and mitochondrial dysfunction in fibromyalgia by Cordero MD1, de Miguel M, Carmona-López I, Bonal P, Campa F, Moreno-Fernández AM(PubMed)Molecular identification for epigallocatechin-3-gallate-mediated antioxidant intervention on the H2O2-induced oxidative stress in H9c2 rat cardiomyoblasts by Chen WC, Hsieh SR, Chiu CH, Hsu BD1, Liou YM.(PubMed)
(26) Molecular identification for epigallocatechin-3-gallate-mediated antioxidant intervention on the H2O2-induced oxidative stress in H9c2 rat cardiomyoblasts by Chen WC, Hsieh SR, Chiu CH, Hsu BD1, Liou YM.(PubMed)
(27) The role of sleep in pain and fibromyalgia by Choy EH(PubMed)
(28) (-)-Epigallocatechin gallate attenuates acute stress responses through GABAergic system in the brain by Adachi N1, Tomonaga S, Tachibana T, Denbow DM, Furuse M.(research gate)
(29) Green Tea Health Benefits To Get You Drinking Healthy! by Abby Hannaford
(30) Fibromyalgia and Rheumatic Diseases by Gheita TA*, El-Rabbat SM and Mahmoud NK(Open Access)
(31) Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise by Salahuddin Ahmed(PMC)
(32) alpha1-Antitrypsin and fibromyalgia: new data in favour of the inflammatory hypothesis of fibromyalgia by Blanco LE1, de Serres FJ, Fernańdez-Bustillo E, Kassam DA, Arbesú D, Rodríguez C, Torre JC.(PubMed)
(33) Chronic Inflammatory Diseases and Green Tea Polyphenols by Helieh S. Oz(PubMed Central Canada)
(34) Association and interaction effect between VEGF receptor-2 (VEGFR-2) gene polymorphisms and dietary pattern on blood uric acid in Malays and Indians by Roseline YW1, Shidoji Y1, Hon WM2, Masaki M1.(PubMed)
(35) [Multiple actions of EGCG, the main component of green tea].[Article in French] by L'Allemain G1.(PubMed)
(36) Epigallocatechin gallate inhibits urate crystals-induced peritoneal inflammation in C57BL/6 mice by Jhang JJ1, Lu CC1, Yen GC2.(PubMed)
(37) Inhibition of xanthine oxidase by catechins from tea (Camellia sinensis) by Aucamp J1, Gaspar A, Hara Y, Apostolides Z.(PubMed)
(38) Beneficial Properties of Phytochemicals on NLRP3 Inflammasome-Mediated Gout and Complication by Jhang JJ1, Lin JH1, Yen GC1.(PubMed)
(39) Green Tea and Glycine Modulate the Activity of Metalloproteinases and Collagen in the Tendinitis of the Myotendinous Junction of the Achilles Tendon by Vieira CP1, De Oliveira LP2, Da Ré Guerra F3, Marcondes MC2, Pimentel ER2.(PubMed)
(40) Green tea and glycine aid in the recovery of tendinitis of the Achilles tendon of rats by Vieira CP1, Guerra Fda R, de Oliveira LP, Almeida MS, Marcondes MC, Pimentell ER.(PubMed)
(41) Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise by Ahmed S1.(PubMed)