Andrographolide is one of the main active principles of
Andrographolide paniculata and has been extensively explored for its
therapeutic use. Current studies focus on phytotherapeutics-based adjuvant
therapy to symptomatically treat
sickle cell anemia (SCA) as there is no specific drug/gene therapy available to date. The present study aimed to explore the potential of
andrographolide as an adjuvant
therapy for SCA in the presence or absence of
hydroxyurea (HU), a key drug for SCA treatment. A panel of ex vivo and in vivo experimentations was performed to explore the antisickling activity of
andrographolide, followed by evaluating pharmacokinetic and pharmacodynamic (PK/PD) activities in the presence of HU.
Andrographolide showed significant antisickling activity using blood from SCA patients (ex vivo) and did not show any deleterious effect to cause
hemolysis using rat blood (ex vivo). It displayed a substantial decrease in HU-induced decline in splenic lymphocyte proliferation and
cytokine level (TNF-α and IFN-γ) using rat splenocytes (ex vivo). Concomitant
oral administration of
andrographolide with HU in rats for 15 days exhibited a noticeable improvement in the RBC count and
hemoglobin levels comparable to the efficacy of
l-glutamine (in vivo). Simultaneous administration of
andrographolide with HU caused no marked effect on any pharmacokinetic parameters of HU except the highest plasma concentration of HU and its corresponding time point, which significantly dropped and delayed, respectively (in vivo). No considerable effect of
andrographolide was observed on
urease and
horseradish peroxidase activity (in vitro). Overall, results suggest that
andrographolide has several beneficial actions to be an adjuvant
therapy to symptomatically manage SCA, but it should be avoided during the prescribed
therapy of HU.