Abstract:
Due to its several mechanisms of action, curcumin (CUR) has been employed as adjuvant therapy in treating psoriasis. Limited oral bioavailability was the problem for the development of CUR for therapeutic purposes. Therefore, many approaches, including the prodrug strategy, have been devised to address Cur's drawbacks. CUR was conjugated with mycophenolic acid (MPA) as a new prodrug in this research. Characterization of MPA-CUR structure was done by FT-IR, 1H-NMR, 13C-NMR, and MS. MPA-CUR showed water solubility at 0.73 μM and log P at 2.33, respectively. MPA-CUR was found more stable in buffer solutions than CUR and MPA. In vitro anti-psoriatic of MPA-CUR, namely antiproliferative and anti-inflammatory effect was investigated using TNF-alpha-induced HaCaT cells. The antiproliferation effect of direct treatment of MPA-CUR was lower than the parent drug. Therefore, the bioavailable fractions (BFs) of CUR, MPA, and MPA-CUR were used for further biological activity evaluation. Each BF was collected after CUR, MPA, and MPA-CUR across Caco-2 cells as an in vitro cellular transport model for oral administration. BF of MPA-CUR presented a better antiproliferation effect than CUR (p< 0.001). In the anti-inflammation assay, BF of MPA-CUR was also showed a reduction of inflammatory cytokines, including IL-6, IL-8, and IL-1β. An inhibited signaling cascade of MAPKs proteins, such as p38, ERK, and JNK, was the molecular mechanism of the anti-inflammatory effect of MPA-CUR. Our findings support the MPA-CUR conjugation as a promising antiproliferative and anti-inflammatory therapeutic agent for psoriasis treatment.
