Oroxylum indicum extract prevents chemotherapy‐induced cognitive impairment in mice

Abstract

Chemotherapy‐induced cognitive impairment (CICI) is an emerging concern among cancer patients undergoing chemotherapy treatment. Several mechanisms including neuronal oxidative stress and mitochondrial dysfunction have been proposed as the underlying mechanisms of CICI. While a few synthetic and natural compounds with different mechanisms of action have been proposed for targeting the CICI, their beneficial effects are outweighed by severe adverse effects including reduced efficacy of chemotherapy drugs. Therefore, search for novel and safer neuroprotective avenues to target CICI is needed. We sought to determine whether Oroxylum indicum extract (OIE, Sabroxy®) prevents CICI in a rodent model by suppressing chemotherapy induced neuronal oxidative stress and mitochondrial dysfunction. Male C57BL/6J mice were injected intraperitoneally with saline or doxorubicin (2mg/kg) and cyclophosphamide (50mg/kg) once a week for 4 weeks. While control mice received powdered rodent food alone, OIE treatment group received the powdered rodent food mixed with OIE (250 or 500mg/kg) daily for 4 weeks. After the treatment period, the mice were assessed for cognitive function using novel object recognition, Y‐maze, and Morris water maze analyses. Biochemical assays were performed using brain tissues to determine the underlying mechanisms of CICI. While the chemotherapy treatment impaired the performance of the mice in the novel object recognition, Y‐maze and Morris water maze tests, OIE significantly prevented the chemotherapy impaired performance in these tests. Additionally, OIE treatment prevented the chemotherapy‐induced changes in oxidative stress and mitochondrial dysfunction in the cortex and rest of the brain. Mechanistically, OIE enhanced mitochondrial function and counteracted chemotherapy‐increased reactive oxygen species formation and lipid peroxidation. Furthermore, OIE treatment increased the monoamine oxidase activity in the cortex and rest of the brain. Our results support the hypothesis that neuronal mitochondrial dysfunction induced by doxorubicin and cyclophosphamide treatment is an underlying cause of CICI, and that OIE may be offered as an adjuvant therapeutic strategy to treat CICI.Support or Funding InformationOIE (Sabroxy®) and funding was provided by Sabinsa Corporation.