The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats

Abstract

BackgroundRheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1) examining the therapeutic effect of CM administered via intravenous (iv) injection on RA and 2) formulating the drug into oil–water nanoemulsions (Ns) to overcome the low oral bioavailability of CM and achieve oral delivery of the drug.MethodsThe effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI) fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high performance liquid chromatography method and the pharmacokinetic parameters were calculated based on a statistical moment theory was also performed in rats.ResultsCM administered via iv injection had a therapeutic effect on RA similar to methotrexate. CM-Ns with a diameter of approximately 150 nm were successfully prepared, and the drug was well encapsulated into the Ns without degradation in simulated GI conditions. The area under the curve (AUC) and Cmax for the CM-Ns were more than threefold greater than those for the suspensions; moreover, similar decreases in the levels of TNF-α and interleukin-1β in both synovial fluid and blood serum were obtained from oral administration of CM-Ns and iv injection.ConclusionCM was an effective antiarthritic agent, and the present N formulation appeared to be a promising system that allowed RA therapy with CM to be converted from iv to oral administration.

The role of diet in rheumatoid arthritis

“…Results of a meta-analysis of randomized clinical trials (RCTs) concerning turmeric extracts containing curcumin in patients with arthritis suggested that turmeric extract (about 1000 mg/day of curcumin) alleviated pain symptoms connected with arthritis [ 35 ]. Moreover, in a study by Zheng et al [ 36 ], curcumin was shown to decrease the expression of NF-κB, TNF-α, and IL-1β in the synovial fluid and blood serum. Since the observed effects were similar to effects observed in a standard regimen with methotrexate, the authors of the study speculated that curcumin could be used as anti-rheumatic therapy either in monotherapy or as an adjuvant in RA patients.…”

Food-Derived Nanoscopic Drug Delivery Systems for Treatment of Rheumatoid Arthritis

“…A threefold increase in maximum plasma concentration and the area under the plasma drug concentration-time curve (AUC) was observed when comparing curcumin in NEs to curcumin suspensions. Oral administration of curcumin-NEs significantly decreased TNF-α and IL-1β levels in both synovial fluid and blood serum (Table 1) [13]. It is therefore concluded that the formulation of NEs significantly enhanced curcumin absorption.…”

“…The expansion of an emulsifier is necessary for producing droplets with smaller size because it reduces the interfacial tension and surface energy in unit range between the oil and water phases of the emulsion. NEs show advantages in high drug-loading capacity [12], core-shell protection of embedded drugs from physicochemical and enzymatic degradation [8], wide drug distribution along the GI tract, prolonged drug release due to large surface area [7], and ease of preparation [13]. A threefold increase in maximum plasma concentration and the area under the plasma drug concentration-time curve (AUC) was observed when comparing curcumin in NEs to curcumin suspensions.…”

“…Moreover, owing to the oxygen-containing groups of curcumin, polyphenol compounds tend to distribute evenly across the NE surface, thereby gaining the most access to the solvent [52]. Therefore, curcumin has been loaded on soybean-oil-based NEs to enhance its absorption after oral administration (Table 2) [13].…”

Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction

“…Monocytes can differentiate into macrophages, which play a pivotal role in the induction and progression of inflammatory processes (Liu et al, ). Paeoniflorin; astragaloside IV; esculentic acid; hesperidin; 7′‐(3′,4′‐dihydroxyphenyl)‐ N ‐[(4‐methoxyphenyl)ethyl]propenamide; sinomenine; tetrandrine; curcumin; methyl benzoate‐2‐ O ‐β‐ d ‐xylopyranosyl(1‐2)[ O ‐β‐ d ‐xylopyranosyl(1‐6)]‐ O ‐β‐ d ‐glucopyranoside; methyl benzoate‐2‐ O ‐β‐ d ‐xylopyranosyl(1‐6)‐ O ‐β‐ d ‐gluco‐pyranoside; polyphyllin I, 9,9′‐ O ‐di‐( E )‐feruloyl‐meso‐5,5′‐dimethoxysecoisolariciresinol; cimifugin; 1‐ethoxy‐3,7‐dihydroxy‐4,6‐dimethoxy‐9‐fluorenone; triptolide; celastrol; anhuienoside C; artemisinin; and (−)‐epicatechin‐3‐ O ‐β‐ d ‐allopyranoside can inhibit the macrophages‐mediated inflammatory processes in the joints of RA model (Cai, Zheng, Shang, & Zhao, ; Fan et al, ; Gao et al, ; Han et al, ; Hsiao, Wu, & Lin, ; Hu et al, ; Lee, Lee, Kim, & Lee, ; Li, Li, Cai, Hu, & Zhang, ; Lin et al, ; Lin et al, ; Liu et al, ; Liu et al, ; Matta et al, ; Niu et al, ; Wang et al, ; Wang et al, ; Wang & Chen, ; Yang et al, ; Yi et al, ; Zhang et al, ; Zhou et al, ). Following maturation, the lymphocytes enter the circulation and peripheral lymphoid organs (spleen and lymph nodes).…”