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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

Histopathological changes in H&E-stained synovial sections in the AIA rats (×200).Abbreviations: AIA, adjuvant-induced arthritis; CM, curcumin; H&E, hematoxylin and eosin; MTX, methotrexate.
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f3-dddt-9-4931: Histopathological changes in H&E-stained synovial sections in the AIA rats (×200).Abbreviations: AIA, adjuvant-induced arthritis; CM, curcumin; H&E, hematoxylin and eosin; MTX, methotrexate.

Mentions: The effects of CM on the histopathological changes are presented in Figures 2C and 3. The rats were killed on day 14 after induction of AIA and subjected to histopathological examination. As shown in Figure 3, intense inflammatory cell infiltration consisting of lymphocyte plasma cells, macrophages and neutrophils; synovial thickening; and significant proliferation of synovial tissue and fibrous tissue were observed in the model group, whereas the normal group displayed no inflammatory cell infiltration. Treatment with CM or MTX resulted in a significant reduction in these symptoms, including inflammatory cell infiltration and MP. To confirm the histopathological examination, the changes in the IIC, MP, synovial tissue hyperplasia and fibrous tissue hyperplasia were scored. As indicated in Figure 2C, the scores for the four indicators in CM and MTX groups were less than those of the model group. In particular, the IIC and MP scores for the CM-treated group were less than those of the MTX group, thus indicating a better therapeutic effect of CM.


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)

Histopathological changes in H&E-stained synovial sections in the AIA rats (×200).Abbreviations: AIA, adjuvant-induced arthritis; CM, curcumin; H&E, hematoxylin and eosin; MTX, methotrexate.
© Copyright Policy
Related In: Results  -  Collection

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

f3-dddt-9-4931: Histopathological changes in H&E-stained synovial sections in the AIA rats (×200).Abbreviations: AIA, adjuvant-induced arthritis; CM, curcumin; H&E, hematoxylin and eosin; MTX, methotrexate.
Mentions: The effects of CM on the histopathological changes are presented in Figures 2C and 3. The rats were killed on day 14 after induction of AIA and subjected to histopathological examination. As shown in Figure 3, intense inflammatory cell infiltration consisting of lymphocyte plasma cells, macrophages and neutrophils; synovial thickening; and significant proliferation of synovial tissue and fibrous tissue were observed in the model group, whereas the normal group displayed no inflammatory cell infiltration. Treatment with CM or MTX resulted in a significant reduction in these symptoms, including inflammatory cell infiltration and MP. To confirm the histopathological examination, the changes in the IIC, MP, synovial tissue hyperplasia and fibrous tissue hyperplasia were scored. As indicated in Figure 2C, the scores for the four indicators in CM and MTX groups were less than those of the model group. In particular, the IIC and MP scores for the CM-treated group were less than those of the MTX group, thus indicating a better therapeutic effect of CM.

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