Rheumatoid Arthritis (RA) and Phytochemicals

Rheumatoid Arthritis
Rheumatoid Arthritis is defined a chronic disorder as a result of inflammation, affecting mostly the flexible (synovial) joints and tissues and organs in the body. The disease affects more women than in men and generally occurs after the ages of 40 and diminishes the quality of life of many elders.
In conventional medicine, there is no known way to prevent rheumatoid arthritis, although progression of the disease usually can be stopped or slowed by early, aggressive treatment. Since  Rheumatoid Arthritis RA is caused by inflammation of flexible (synovial) joints and tissues and organs in the body, diet with high in anti inflammatory and immunity enhancing foods, antioxidants and phytochemicals may provide protection and reduced risk of the disease.
Phytochemicalx
1.  Curcumin is a phytochemical found abundant in
Curcumin is a phytochemical found abundantly in Turmeric, principal curcuminoid of the popular Indian spice,
a. Anti-inflammatory agent
According to the study of evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. by Satoskar RR, Shah SJ, Shenoy SG., poated in US National Library of Medicine National Institutes of Health, researchers wrote that In this model of postoperative inflammation, the anti-inflammatory activity of curcumin (diferuloyl methane) was investigated in comparison with phenylbutazone and placebo. Phenylbutazone and curcumin produced a better anti-inflammatory response than placebo.
b. Antioxidants
In a study of `Protective Role of Curcumin Against Oxidative Stress,Immunosuppressive and Cytotoxic Effects of Lead Exposure` by Mahmoud El-sherbiny, Azza Araffa, Mona Mantawy and Hany M. Hassan (Therapeutic Chemistry Department, National Research Centre – Dokki, Giza, Egypt. Immunology Department, Animal Reproduction Research Institute (ARRI), Giza, Egypt), posted in World Applied Sciences Journal 12 (10): 1832-1838, 2011, researchers found that ground, curcumin’s benefits on tumorigenesis are thought to be mediated by its antiinflammatory activity; however, these effects have not been well characterized in a mouse model of colon cancer. Briefly, curcumin is efficacious for chronic nonbacterial prostatitis in rats and the action mechanism may be associated with its decreasing effect on the proinflammatory cytokines IL-8 and TNF-alpha in the blood and tissues. Curcumin has protective effect on DNA of pulmonary cells. There was direct evidence for an involvement of curcumin in reducing arsenic and lead induced oxidative stress in Swiss albino mice by virtue of its antioxidant potential and trapping of free radicals. The current investigation concluded that curcumin has protective role against cytotoxic, immunosuppressive , oxidative and immunosuppressive profile that perform due to lead acetate exposure.
2. Gingerol
Gingerole, is also known as gingerol, a phytochemical of Flavonoids (polyphenols) found in fresh ginger.
a. Antioxidant and anti-inflammatory effects
In the investigation of the effectiveness of chemical constituents of Zingiber officinale Rosc. (Zingiberaceae)in treating oxidative stress found that compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol of the herb scavenges of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibitsof N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), lipopolysaccharide induced nitrite and prostaglandin E(2) production in RAW 264.7 cells, according to the study of “Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol” byDugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN(39)
b. Rheumatoid arthritis
In the investigation of the crude dichloromethane extract, which also contained essential oils and more polar compounds, was more efficacious (when normalized to gingerol content and it effects on rheumatoid arthritis found that there are very significant joint-protective effect of these ginger samples and suggest that nongingerol components are bioactive and can enhance the antiarthritic effects of the more widely studied gingerols, according to the study of ‘Comparative effects of two gingerol-containing Zingiber officinale extracts on experimental rheumatoid arthritis” by Funk JL, Frye JB, Oyarzo JN, Timmermann BN.(40)
3.  Quercetin
Quercetin is a member of flavonoids, found in fruits, vegetables, leaves and grains. Quercetin also inhibits the phosphorylation of ERK-1/2, p38, JNK and activation of NF-kB by IL-1ed. These results indicate that quercetin inhibits synovial fibroblasts proliferation and MMPs, COX-2, and PGE2 production, which involved joint destruction in rheumatoid arthritis (RA), and suggest that it might be a new therapeutic agent for management of RA(41).
4. Omega 3 fatty acid
a. Antioxidants
In the investigation of the hexane extract from different parts in several Hypericum species, found that The antioxidant activity of all hexane extracts was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The results indicate that hexane extracts from different parts of H. scabrum possess considerable antioxidant activity. The highest radical scavenging activity was detected in seed, which had an IC50 = 165 microg/mL. The antimicrobial activity of the extracts of those samples were determined against seven Gram-positive and Gram-negative bacteria (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, S. epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae), as well as three fungi (Candida albicans, Saccharomyces cerevisiae, and Aspergillus niger), according to “Antioxidant, antimicrobial activities and fatty acid components of flower, leaf, stem and seed of Hypericum scabrum” by Shafaghat A.(42)
b. Relieving inflammation
In the evaluation of the effects of lymphatic drainage and omega-3 polyunsaturated fatty acid (omega-3PUFA) on high mobility group box 1 (HMGB1), inflammatory cytokines and endotoxin in rats with intestinal ischemia-reperfusion (I/R) injury, found that Lymphatic drainage may reduce the levels of endotoxin, inflammatory cytokines and HMGB1 so as to alleviate the intestinal I/R injury. The intervention of omega-3PUFA has some protective effect through relieving inflammation, according to “[Effects of lymphatic drainage and omega-3 polyunsaturated fatty acids on intestinal ischemia-reperfusion injury in rats].[Article in Chinese]” by Zhou KG, He GZ, Zhang R, Chen XF.(43)
c. Suppression of inflammatory
In the determination of whether salmon (rich in n-3 LCPUFAs) consumption twice a week during pregnancy affected offspring umbilical vein EC CAM expression, showed that increased dietary salmon intake in pregnancy dampens offspring EC activation, which implicates a role for n-3 LCPUFAs in the suppression of inflammatory processes in humans. This trial was registered at clinicaltrials.gov as NCT00801502, according to “Salmon consumption by pregnant women reduces ex vivo umbilical cord endothelial cell activation” by van den Elsen LW, Noakes PS, van der Maarel MA, Kremmyda LS, Vlachava M, Diaper ND, Miles EA, Eussen SR, Garssen J, Willemsen LE, Wilson SJ, Godfrey KM, Calder PC.(44)
d. Neonatal immune responses
In thye assessment of whether an increased intake of oily fish in pregnancy modifies neonatal immune responses and early markers of atopy, showed that Oily fish intervention in pregnancy modifies neonatal immune responses but may not affect markers of infant atopy assessed at 6 mo of age, according to “Increased intake of oily fish in pregnancy: effects on neonatal immune responses and on clinical outcomes in infants at 6 mo” by Noakes PS, Vlachava M, Kremmyda LS, Diaper ND, Miles EA, Erlewyn-Lajeunesse M, Williams AP, Godfrey KM, Calder PC.(45)
5. Epigallocatechin-3-gallate (EGCG) and theaflavin-3,3′-digallate (TFDG)
In the study to investigate, Polyphenols in green tea, particularly epigallocatechin-3-gallate (EGCG), inhibit MMPs expression and activity and the effects of the black tea polyphenol, theaflavin-3,3′-digallate (TFDG), on osteoclast and MMP activity MMP-2 and MMP-9 activities were lower in TFDG- and EGCG-treated rat osteoclast precursor cells than in control cultures. MMP-9 mRNA levels declined significantly in TFDG-treated osteoclasts in comparison to control osteoclasts. TFDG and EGCG inhibited the formation and differentiation of osteoclasts via inhibition of MMPs. TFDG may suppress actin ring formation more effectively than EGCG. Thus, TFDG and EGCG may be suitable agents or lead compounds for the treatment of bone resorption diseases(46).
6. Resveratrol
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc.
a. Anti inflammatory effects
In the study of implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanism, found that resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion- and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells, according to “Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18″ by Salado C, Olaso E, Gallot N, Valcarcel M, Egilegor E, Mendoza L, Vidal-Vanaclocha F.(47)
b. Antioxidants
In the assessment of the effects of the antioxidants resveratrol and quercetin on frozen-thawed ram sperm, found that Semen samples (which exceeded minimum standards) from four mature crossbreed Santa Inês rams were pooled and aliquots of each pool were diluted in Tris-egg yolk-glycerol, with the addition of 0, 5, 10, 15, and 20 μg/mL of resveratrol and quercetin in Experiment 1 and Experiment 2, respectively. In Experiment 1, the proportion of sperm with a high mitochondrial membrane potential was greater (P < 0.02) in the control group than in resveratrol 20 μg/mL group. In Experiment 2, the proportion of sperm with high mitochondrial membrane potential was greater in the control group (P < 0.0001) than in the other experimental groups, and greater in the quercetin 5 μg/mL group (P < 0.05) than in the other quercetin-treated groups, according to “Effect of antioxidants resveratrol and quercetin on in vitro evaluation of frozen ram sperm” by Silva EC, Cajueiro JF, Silva SV, Soares PC, Guerra MM.(48)
7. Etc.

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Sources 

(39) http://www.ncbi.nlm.nih.gov/pubmed/19833188
(40)  http://www.ncbi.nlm.nih.gov/pubmed/19216559
(41) http://www.ncbi.nlm.nih.gov/pubmed/22592909
(42) http://www.ncbi.nlm.nih.gov/pubmed/22224301
(43) http://www.ncbi.nlm.nih.gov/pubmed/22093738
(44) http://www.ncbi.nlm.nih.gov/pubmed/22011457
(45) http://www.ncbi.nlm.nih.gov/pubmed/22218160
(46) http://www.ncbi.nlm.nih.gov/pubmed/22186621
(47) http://www.ncbi.nlm.nih.gov/pubmed/21569399
(48) http://www.ncbi.nlm.nih.gov/pubmed/22289215