Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Chemotherapy, while effective against cancer, can cause significant adverse effects, including central nervous system toxicity.
• Doxorubicin (DOX) and cyclophosphamide (CPS) are common chemotherapeutic agents linked to chemotherapy-induced cognitive impairment (CICI).
• There is a need for neuroprotective strategies to mitigate CICI in cancer patients.

Purpose of the Study:

• To investigate the neuroprotective effects of Oroxylum indicum extract (OIE) against CICI.
• To evaluate OIE's impact on cognitive function, oxidative stress, and mitochondrial activity in mice treated with DOX and CPS.

Main Methods:

• Male C57BL/6J mice received 4 cycles of combination chemotherapy (DOX and CPS).
• OIE was administered to assess its effects on cognitive performance using Y-maze, Open-Field, Novel Object Recognition, and Morris Water Maze tests.
• Biochemical analyses were performed to measure reactive oxygen species, lipid peroxide, glutathione levels, and mitochondrial Complex-I and Complex-IV activities in brain tissue.
• In silico analysis evaluated the ADME profile of OIE's major active constituents.

Main Results:

• OIE significantly prevented chemotherapy-induced deficits in short-term memory, exploratory behavior, and spatial learning and memory.
• OIE treatment reduced oxidative stress markers (reactive oxygen species, lipid peroxide) and prevented chemotherapy-induced glutathione depletion.
• OIE enhanced mitochondrial Complex-I and Complex-IV activities in the brain, indicating improved mitochondrial function.
• In silico analysis suggested a favorable ADME profile for OIE's key compounds (Oroxylin A, Baicalein, Chrysin).

Conclusions:

• Oroxylum indicum extract (OIE) demonstrates significant neuroprotective effects against chemotherapy-induced cognitive impairment (CICI).
• OIE's mechanism of action involves counteracting oxidative stress and potentially improving mitochondrial function in the brain.
• These findings suggest OIE as a potential therapeutic agent to mitigate cognitive side effects of chemotherapy.