Abstract
While chemotherapy is the most effective therapeutic approach for treating a variety of cancer patients, commonly used chemotherapeutic agents, often induce several adverse effects. Escalating evidence indicates that chemotherapeutics, particularly doxorubicin (DOX) and cyclophosphamide (CPS), induce cognitive impairment associated with central nervous system toxicity. This study was performed to determine neuroprotective effects of Oroxylum indicum extract (OIE) in regard to preventing chemotherapy induced cognitive impairment (CICI) occurring after 4 cycles of DOX (2mg/kg) and CPS (50mg/kg) combination chemotherapy in male C57BL/6J mice. OIE significantly prevented the chemotherapy impaired short-term cognitive performance, exploratory behavior associated with cognitive performance, cognitive performance, and spatial learning and memory in the Y-maze, Open-Field, Novel Object Recognition, and Morris Water Maze tests, respectively. These data suggest that OIE protects from the CICI. OIE decreased the reactive oxygen species and lipid peroxide generated by the chemotherapy treatment in the brain, while also blocking the chemotherapy-induced glutathione depletion. These results establish that OIE exhibits potent antioxidant activity in chemotherapy treated mice. Notably, OIE significantly increased the Complex-I and Complex-IV activities in the brain, indicating that OIE enhances mitochondrial function in the brain. In silico analysis of the major active chemical constituents (Oroxylin A, Baicalein and Chrysin) of OIE indicated that OIE has a favorable absorption, distribution, metabolism and excretion (ADME) profile. Taken together, our results are consistent with the conclusion that OIE prevents CICI by counteracting oxidative stress and perhaps by improving mitochondrial function.
Highlights
As per the American Cancer Society estimates, 1.8 million Americans will be diagnosed with cancer in 2020, in addition to 14.5 million cancer survivors
The mice (25–35 g) were administered with vehicle saline; chemotherapeutics (CT), doxorubicin (2 mg/kg) and cyclophosphamide (50 mg/kg) intraperitoneally with one injection per week for a total of four weeks; Oroxylum Indicum extract (OIE, Sabroxy1) prepared by Sabinsa Corporation [250 mg/kg Oroxylum indicum extract (OIE) low dose (LD) and 500 mg/kg OIE high dose (HD)] was mixed with powdered rodent food and fed daily for 4 weeks to mice treated with CT
OIE consumption did not result in any adverse events, major toxicity, or death
Summary
As per the American Cancer Society estimates, 1.8 million Americans will be diagnosed with cancer in 2020, in addition to 14.5 million cancer survivors. One example of a cognitive side effect is “mental fog,” which is measurable as difficulties with learning, memory, and executive functioning [3,4,5] This chemotherapeutics induced cognitive impairment (CICI) is known as “chemobrain,” frequently develops during chemotherapy and persists following termination of treatment, severely affecting the quality of life. Epidemiologic studies have validated that the consumption of botanicals significantly reduces the overall risk for cancer [7] It would prove highly beneficial if a novel botanical could be discovered to protect from CICI
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