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

Zheng Z, Sun Y, Liu Z, Zhang M, Li C, Cai H - Drug Des Devel Ther (2015)

Bottom Line: 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.CM 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Dongying People's Hospital, Dongying, People's Republic of China.

ABSTRACT

Background: Rheumatoid 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.

Methods: The 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.

Results: CM 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.

Conclusion: CM 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.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of curcumin.
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f1-dddt-9-4931: Chemical structure of curcumin.

Mentions: Curcumin (CM) is a yellow hydrophobic polyphenol derived from the herb turmeric, the structure of which is presented in Figure 1. CM possesses various pharmacological activities against many chronic diseases, including cancer, type II diabetes, multiple sclerosis, Alzheimer’s disease, and atherosclerosis. The molecular mechanisms for these effects of the drug involve not only the suppression of cell proliferation and metastasis but also the downregulation of various factors, including nuclear factor kappa B (NF-κB), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, hypoxia-inducible factor-1α, and activator protein.4,5 In general, numerous cytokines are expressed and are functionally active in synovial tissues, and multiple factors, including TNF-induced NF-κB, IL-1β and TNF-α, are associated with the pathogenesis of RA.6 In particular, TNF is now targeted in the standard treatment of RA patients.7 Given the activity of CM and the pathogenesis of RA, we hypothesized that the drug could also exert a therapeutic effect on RA.


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

Zheng Z, Sun Y, Liu Z, Zhang M, Li C, Cai H - Drug Des Devel Ther (2015)

Chemical structure of curcumin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555965&req=5

f1-dddt-9-4931: Chemical structure of curcumin.
Mentions: Curcumin (CM) is a yellow hydrophobic polyphenol derived from the herb turmeric, the structure of which is presented in Figure 1. CM possesses various pharmacological activities against many chronic diseases, including cancer, type II diabetes, multiple sclerosis, Alzheimer’s disease, and atherosclerosis. The molecular mechanisms for these effects of the drug involve not only the suppression of cell proliferation and metastasis but also the downregulation of various factors, including nuclear factor kappa B (NF-κB), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, hypoxia-inducible factor-1α, and activator protein.4,5 In general, numerous cytokines are expressed and are functionally active in synovial tissues, and multiple factors, including TNF-induced NF-κB, IL-1β and TNF-α, are associated with the pathogenesis of RA.6 In particular, TNF is now targeted in the standard treatment of RA patients.7 Given the activity of CM and the pathogenesis of RA, we hypothesized that the drug could also exert a therapeutic effect on RA.

Bottom Line: 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.CM 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Dongying People's Hospital, Dongying, People's Republic of China.

ABSTRACT

Background: Rheumatoid 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.

Methods: The 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.

Results: CM 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.

Conclusion: CM 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.

No MeSH data available.


Related in: MedlinePlus