Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo
Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were eval...
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/16/5700 |
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| author | Rianthong Phumsuay Chawanphat Muangnoi Peththa Wadu Dasuni Wasana Hasriadi Opa Vajragupta Pornchai Rojsitthisak Pasarapa Towiwat |
| author_facet | Rianthong Phumsuay Chawanphat Muangnoi Peththa Wadu Dasuni Wasana Hasriadi Opa Vajragupta Pornchai Rojsitthisak Pasarapa Towiwat |
| author_sort | Rianthong Phumsuay |
| collection | DOAJ |
| description | Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (<i>p</i> < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (<i>p</i> < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (<i>p</i> < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent. |
| first_indexed | 2024-03-10T17:44:44Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:44:44Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-490407d4e9bc460da11cd553ec3f28192023-11-20T09:33:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116570010.3390/ijms21165700Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In VivoRianthong Phumsuay0Chawanphat Muangnoi1Peththa Wadu Dasuni Wasana2Hasriadi3Opa Vajragupta4Pornchai Rojsitthisak5Pasarapa Towiwat6Inter-Department Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok 10330, ThailandInstitute of Nutrition, Mahidol University, Salaya, Nakhon Pathom 73170, ThailandPharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandPharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandResearch Affairs, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandNatural Products for Ageing and Chronic Diseases Research Unit, Chulalongkorn University, Bangkok 10330, ThailandCurcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (<i>p</i> < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (<i>p</i> < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (<i>p</i> < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.https://www.mdpi.com/1422-0067/21/16/5700curcumincurcumin diglutaric acidinflammationcarrageenan-induced paw edema |
| spellingShingle | Rianthong Phumsuay Chawanphat Muangnoi Peththa Wadu Dasuni Wasana Hasriadi Opa Vajragupta Pornchai Rojsitthisak Pasarapa Towiwat Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo International Journal of Molecular Sciences curcumin curcumin diglutaric acid inflammation carrageenan-induced paw edema |
| title | Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo |
| title_full | Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo |
| title_fullStr | Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo |
| title_full_unstemmed | Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo |
| title_short | Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo |
| title_sort | molecular insight into the anti inflammatory effects of the curcumin ester prodrug curcumin diglutaric acid in vitro and in vivo |
| topic | curcumin curcumin diglutaric acid inflammation carrageenan-induced paw edema |
| url | https://www.mdpi.com/1422-0067/21/16/5700 |
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