Ellagic Acid Exerts Dual Action to Curb the Pathophysiological Manifestations of Sickle Cell Disease and Attenuate the Hydroxyurea-Induced Myelosuppression in Berkeley Mice

Theuse of adjuvant therapy is an attractive approachto managesickle cell disease (SCD) symptomatically. The present study aimedto investigate the potential of ellagic acid as an adjuvant therapywith hydroxyurea (HU), a key drug for SCD with myelosuppressive toxiceffects. A panel of experiments was performed using SCD patient'sblood (ex vivo) and transgenic mice model of SCD (in vivo). Ellagicacid exhibited the following beneficial pharmacological actions: (a)potent anti-sickling, polymerization inhibitory, and inherent non-hemolyticactivity; (b) pronounced action to abrogate HU-induced neutropeniaand to improve key hematological parameters during SCD (RBC, Hb, plateletlevels); (c) considerable action to foster vascular tone (L-proline);(d) marked attenuating effect against oxidative stress (nitrotyrosine,hypoxanthine, MDA, GSH); (e) substantial inhibitory role against inflammation(analgesic activity and regulation of hemin, TNF-alpha, IL-1 beta,NF-kappa B/I kappa B alpha); (f) remarkable outcome of decliningvaso-occlusive crisis (P-selectin, ERK1/2); (g) notable shieldingdeed against elevated biochemical marker for organ toxicity (creatinine);(h) noticeably prevented histopathological alterations of the spleen.Additionally, the pharmacokinetic study results of HU in the presenceand absence of ellagic acid using a mouse model demonstrate that ellagicacid could be safely co-administered with HU. Overall findings suggestthat ellagic acid is a promising candidate for adjuvant therapy inSCD based on its own significant ability against SCD and potentiatingcapability of HU action via targeting improvement at the various stagesof pathophysiological complications during SCD and minimizing HU-inducedtoxicological manifestations.

Automated summary

The present study investigated the potential of ellagic acid as an adjuvant therapy for managing sickle cell disease (SCD) symptoms. The results showed that ellagic acid exhibited numerous beneficial pharmacological actions, including anti-sickling, polymerization inhibition, and improvement of key hematological parameters. It also showed a protective effect against toxicological manifestations of the key drug hydroxyurea (HU) used for SCD treatment. Therefore, ellagic acid holds promise as a candidate for adjuvant therapy in SCD.