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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

Immunohistochemical localization of NF-κB in synovial sections stained by H&E in AIA rats (×200).Abbreviations: AIA, adjuvant-induced arthritis; CM, curcumin; H&E, hematoxylin and eosin; MTX, methotrexate; NF-κB, nuclear factor kappa B.
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f4-dddt-9-4931: Immunohistochemical localization of NF-κB in synovial sections stained by H&E in AIA rats (×200).Abbreviations: AIA, adjuvant-induced arthritis; CM, curcumin; H&E, hematoxylin and eosin; MTX, methotrexate; NF-κB, nuclear factor kappa B.

Mentions: It is well known that NF-κB regulates the expression of pro-inflammatory cytokines and osteoclast differentiation in RA.23 We therefore determined the expression of NF-κB in the synovial tissue using immunohistochemical analysis. As depicted in Figure 4, the positive areas of NF-κB in the model group were significantly higher than those of the normal group. In the animals treated with CM or MTX, the intensity and positivity were significantly reduced or eliminated. The expression level of NF-κB was further analyzed using a score scale according to the intensity and positivity in synovial tissue sections. As displayed in Figure 2D, the scores for NF-κB expression from both the CM and MTX groups were lower than that of the model group.


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)

Immunohistochemical localization of NF-κB in synovial sections stained by H&E in AIA rats (×200).Abbreviations: AIA, adjuvant-induced arthritis; CM, curcumin; H&E, hematoxylin and eosin; MTX, methotrexate; NF-κB, nuclear factor kappa B.
© Copyright Policy
Related In: Results  -  Collection

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

f4-dddt-9-4931: Immunohistochemical localization of NF-κB in synovial sections stained by H&E in AIA rats (×200).Abbreviations: AIA, adjuvant-induced arthritis; CM, curcumin; H&E, hematoxylin and eosin; MTX, methotrexate; NF-κB, nuclear factor kappa B.
Mentions: It is well known that NF-κB regulates the expression of pro-inflammatory cytokines and osteoclast differentiation in RA.23 We therefore determined the expression of NF-κB in the synovial tissue using immunohistochemical analysis. As depicted in Figure 4, the positive areas of NF-κB in the model group were significantly higher than those of the normal group. In the animals treated with CM or MTX, the intensity and positivity were significantly reduced or eliminated. The expression level of NF-κB was further analyzed using a score scale according to the intensity and positivity in synovial tissue sections. As displayed in Figure 2D, the scores for NF-κB expression from both the CM and MTX groups were lower than that of the model group.

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