Neuroprotective effect of Mulmina Mango against chemotherapy-induced cognitive decline in mouse model of mammary carcinoma

Abstract

The post-treatment status of breast cancer survivors has become a concern because of the toxicity induced by chemotherapeutic agents in the brain tissues resulting in cognitive deficits, which is generally referred as chemobrain. The aim of this study was to assess the effect of a proprietary ayurvedic formulation Mulmina Mango against chemotherapy-induced cognitive impairment (CICI). Mammary carcinoma was induced by subcutaneously inoculating 4T1 cells into the mammary fat pad of the animals. Intraperitoneal administration of Cyclophosphamide, Methotrexate, 5-Fluorouracil (CMF) regimen was carried out once a week for three weeks. Treatment of Mulmina began one week before chemotherapy and continued till the end of the chemotherapy cycle. After three cycles of chemotherapy, cognitive decline was assessed by Morris water maze task followed by assessment of locomotor activity by open-field test. Tumor progression was evaluated by measurement of tumor volume. Oxidative and neuroinflammatory markers were also evaluated from the isolated brain samples. CMF treatment resulted in a considerable reduction in tumour volume. We found chemotherapy negatively affected behavioral and biochemical parameters in animals and Mulmina treatment ameliorated these cognitive impairments by restoring antioxidant and maintaining cytokine levels. The combination of phytochemicals in Mulmina proved its possible ability to alleviate CICI without affecting chemotherapeutic efficiency and could pave the way for identifying treatment strategies to combat chemobrain.

Cognitive impairment after cancer treatment: mechanisms, clinical characterization, and management

“…Zinc sulfate prevented short term memory deficits in rats treated with the cytotoxic agent carmustine compared with controls 155. Interestingly, a study reported that mulmina mango ameliorated cognitive impairments and aided the maintenance of regular cytokine concentrations in rodents, with tumor size considerably reduced during cyclophosphamide, methotrexate, and 5-fluorouracil treatment 156. Phytochemical and antioxidant alkaloid piperlongumine prevented measurable social memory deficits in mice treated with a doxorubicin, cyclophosphamide, and docetaxel cancer regimen 157.…”

Chemotherapy-Mediated Neuronal Aberration

“…Recently, John et al demonstrated the neuroprotective effect of lumina mango, Mangifera indica fruit pulp, Curcuma longa rhizome, Centella asiatica, and nutrient and vitamins [ 107 ]. Various studies suggested the neuroprotective, anti-inflammatory, and antioxidant properties of mangiferin [ 108 , 109 ].…”

“…Various studies suggested the neuroprotective, anti-inflammatory, and antioxidant properties of mangiferin [ 108 , 109 ]. Mangiferin is a possible neuroprotective candidate against chemotherapy-induced neurotoxicity because of its ability to cross the blood-brain barrier [ 107 ]. In vivo studies revealed that combinatorial treatment of cyclophosphamide, Methotrexate, and 5-fluorouracil (CMF) reduced the burden of mammary cancer in mice and led to cognitive dysfunction.…”

“…In vivo studies revealed that combinatorial treatment of cyclophosphamide, Methotrexate, and 5-fluorouracil (CMF) reduced the burden of mammary cancer in mice and led to cognitive dysfunction. Daily oral administration of mulmina (40 mL/kg and 80 mL/kg) started one week before chemotherapy and continued till the end of chemotherapy cycle showed a remarkable reduction in tumor volume which revealed that mulmina did not impede the anti-cancer activity of CMF therapy [ 107 ]. Animals treated with 40 ml/kg mulmina display more learning behavior than animals treated with CMF.…”

“…It has been seen that CMF treatment enhances the IL-1β, IL-6, and TNF-α in the tumor-bearing animal. However, the augmented level of IL-1β, IL-6, and TNF-α was reversed after mulmina treatment [ 107 ]. In the quest of potential phytochemical for treatment of chemobrain, donepezil or rivastigmine, an acetylcholinesterase inhibitor, improves cognitive function [ 110 ].…”