Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment.
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), induc...
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2021
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oai:doaj.org-article:52b5bde371c24b3bac72c7874af7e8d32021-12-02T20:07:20ZOroxylum Indicum ameliorates chemotherapy induced cognitive impairment.1932-620310.1371/journal.pone.0252522https://doaj.org/article/52b5bde371c24b3bac72c7874af7e8d32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252522https://doaj.org/toc/1932-6203While 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.Satyanarayana R PondugulaMohammed MajrashiMohammed AlmaghrabiSindhu RameshKodye L AbbottManoj GovindarajuluKristina GillEddie FahouryNatasha NarayananDarshini DesaiJun RenRishi NadarTrey McElroyTimothy MooreMuhammed MajeedNagabhushanam KalyanamMuralikrishnan DhanasekaranPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0252522 (2021) |
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Medicine R Science Q Satyanarayana R Pondugula Mohammed Majrashi Mohammed Almaghrabi Sindhu Ramesh Kodye L Abbott Manoj Govindarajulu Kristina Gill Eddie Fahoury Natasha Narayanan Darshini Desai Jun Ren Rishi Nadar Trey McElroy Timothy Moore Muhammed Majeed Nagabhushanam Kalyanam Muralikrishnan Dhanasekaran Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment. |
| description |
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. |
| format |
article |
| author |
Satyanarayana R Pondugula Mohammed Majrashi Mohammed Almaghrabi Sindhu Ramesh Kodye L Abbott Manoj Govindarajulu Kristina Gill Eddie Fahoury Natasha Narayanan Darshini Desai Jun Ren Rishi Nadar Trey McElroy Timothy Moore Muhammed Majeed Nagabhushanam Kalyanam Muralikrishnan Dhanasekaran |
| author_facet |
Satyanarayana R Pondugula Mohammed Majrashi Mohammed Almaghrabi Sindhu Ramesh Kodye L Abbott Manoj Govindarajulu Kristina Gill Eddie Fahoury Natasha Narayanan Darshini Desai Jun Ren Rishi Nadar Trey McElroy Timothy Moore Muhammed Majeed Nagabhushanam Kalyanam Muralikrishnan Dhanasekaran |
| author_sort |
Satyanarayana R Pondugula |
| title |
Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment. |
| title_short |
Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment. |
| title_full |
Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment. |
| title_fullStr |
Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment. |
| title_full_unstemmed |
Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment. |
| title_sort |
oroxylum indicum ameliorates chemotherapy induced cognitive impairment. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/52b5bde371c24b3bac72c7874af7e8d3 |
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