Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by elevated oxidative stress and inflammatory biomarkers. The severe side effects of drug used during such disease necessitate the search for new and safe approaches. Food is a rich source of antioxidants and anti-inflammatory bioactive constituents including phenolic compounds, polyunsaturated fatty acids, phytosterols, toccopherols, and carotenoids. We have a series of publications dealing with the anti-inflammatory activity of different food extracts (as nutraceuticals) in experimental animals (acute and chronic inflammation model) and in clinical study (RA patients). Fish oil, primrose oil, extracts of black cumin, fenugreek, liquorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, and date in addition to the probiotic Bifidobacterium bifidum were the nutraceuticals studied. During these studies, changes in inflammatory biomarkers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), seromucoids, fibrinogen, tumor necrosis factor-α (TNF-α), prostaglandin E2), oxidative stress (malondialdehyde), antioxidant status (total antioxidant capacity, vitamin C, vitamin E, retinol, β-carotene), the level of copper (Cu) and zinc (Zn) and colonic microflora in response to the administration of nutraceuticals have been assessed.

Results of these studies showed that the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases, which might be due to the presence of one or more of the above-mentioned phytochemicals.

CONCLUSION:

Anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA.

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The constituents of Nigella sativa modulate the immune system. The aim of the present work was to study the effectiveness of Nigella sativa oil in RA patients. Data from 40 female RA patients diagnosed according to the 2010 ACR/EULAR were analysed and discussed. The patients took two placebo (starch filled) capsules daily for 1”‰month. This was followed by a month of Nigella sativa oil capsules 500”‰mg twice/day. The disease activity score (DAS-28) significantly decreased after receiving the Nigella sativa capsules (4.55”‰±”‰0.82) compared with before and after placebo (4.98”‰±”‰0.79 and 4.99”‰±”‰0.72, respectively) (p”‰=”‰0.017). Similarly, the number of swollen joints and the duration of morning stiffness improved. A marked improvement in the disease activity was shown by both the ACR20 and EULAR response criteria in 42.5% and 30% of the patients, respectively, after intake of Nigella. Supplementation with Nigella sativa during DMARD therapy in RA may be considered an affordable potential adjuvant biological therapy.

Thymoquinone (TQ) is the major active compound derived from the medicinal Nigella sativa. A few studies have shown that TQ exhibits anti-inflammatory activities in experimental models of rheumatoid arthritis (RA) through mechanisms that are not fully understood. The aim of this work was to evaluate the in vitro and in vivo effects of TQ and to investigate its influence on the major signalling pathways involved in pathophysiological RA changes. We used isolated human RA fibroblast-like synoviocytes (FLS) and a rat adjuvant-inducedarthritis model of RA. In isolated RA FLS, TQ (0-10”‰µM) was not cytotoxic and inhibited slightly lipopolysaccharide (LPS)-induced FLS proliferation and strongly H(2)O(2)-induced 4-hydroxynonenal (HNE) generation. By studying different inflammatory and catabolic factors, we determined that TQ significantly abolished LPS-induced interleukin-1beta (IL-1β), tumour necrosis factor-alpha (TNFα), metalloproteinase-13, cyclooxygenase-2, and prostaglandin E(2). Furthermore, LPS-induced the phosphorylation of p38 mitogen-activated protein kinase, extracellular-regulated kinases ½, and nuclear factor-kappaB-p65 were also blocked by TQ in time-dependent manner. In our experimental RA model, the oral administration of TQ 5”‰mg/kg/day significantly reduced the serum levels of HNE, IL-1β and TNFα as well as bone turnover markers, such as alkaline phosphatase and tartrate-resistant acid phosphatase. The protective effects of TQ against RA were also evident from the decrease in arthritis scoring and bone resorption. In conclusion, the fact that TQ abolishes a number of factors known to be involved in RA pathogenesis renders it a clinically valuable agent in the prevention of articular diseases, including RA.

Many studies have been carried out in recent years on the pharmacological effects of Nigella sativa seeds that have uncovered their antiinflammatory and immunological effects. The objective of this study was to explore the antiinflammatory effects of thymoquinone on arthritis in rat models. Rats with arthritis induced by Freund’s incomplete adjuvant were assigned to five groups: group 1: controls 0.9% NaCl (n = 7); group 2: 2.5 mg/kg thymoquinone (n = 7); group 3: 5 mg/kg thymoquinone (n = 7); group 4: Bacilli Chalmette Guerin (BCG) 6 x 105 CFU (n = 7); group 5: methotrexate 0.3 mg/kg (n = 7). Signs of inflammation on the claw and radiological signs were searched for and TNF-alpha and IL-1beta were measured. The results of the control and other groups were compared. As a result, thymoquinone, confirmed clinically and radiologically, suppressed adjuvant-induced arthritis in rats.

A larger number of medicinal plants and their purified constituents have been shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon of the Ranunculaceae family, have been employed for thousands of years as a spice and food preservative. The oil and seed constituents, in particular thymoquinine (TQ), have shown potential medicinal properties in traditional medicine. In view of the recent literature, this article lists and discusses different immunomodulatory and immunotherapeutic potentials for the crude oil of N.sativa seeds and its active ingredients. The published findings provide clear evidence that both the oil and its active ingredients, in particular TQ, possess reproducible anti-oxidant effects through enhancing the oxidant scavenger system, which as a consequence lead to antitoxic effects induced by several insults. The oil and TQ have shown also potent anti-inflammatory effects on several inflammation-based models including experimental encephalomyelitis, colitis, peritonitis, oedama, and arthritis through suppression of the inflammatory mediators prostaglandins and leukotriens. The oil and certain active ingredients showed beneficial immunomodulatory properties, augmenting the T cell- and natural killer cell-mediated immune responses. Most importantly, both the oil and its active ingredients expressed anti-microbial and anti-tumor properties toward different microbes and cancers. Coupling these beneficial effects with its use in folk medicine, N. sativa seed is a promising source for active ingredients that would be with potential therapeutic modalities in different clinical settings. The efficacy of the active ingredients, however, should be measured by the nature of the disease. Given their potent immunomodulatory effects, further studies are urgently required to explore bystander effects of TQ on the professional antigen presenting cells, including macrophages and dendritic cells, as well as its modulatory effects upon Th1- and Th2-mediated inflammatory immune diseases. Ultimately, results emerging from such studies will substantially improve the immunotherapeutic application of TQ in clinical settings.