From the clinical researcher’s desk

Introduction

Chemotherapy for cancer cure can lead to chemo brain which is its deleterious side effect that occurs in the cognitive domains of the brain. This affects the memory, learning ability, and ability to process information. The condition arises because of oxidative stress due to chemotherapy, apoptosis, chemotherapy-induced inhibition of neuronal proliferation and differentiation, activation of microglia, etc. This affects chromatin remodeling and causes aberrant expression of neurotrophic proteins in the brain. As the understanding of the chemo-brain has evolved in recent, significant efforts are being made to find preventive strategies.

Some promising natural products against the chemo brain are mangiferin from mango pulp, curcumin and Gotu kola. Mulmina® Mango is a combination of Mangiferaindica fruit pulp, Centella asiatica whole plant extract, Curcuma longa rhizome extract along with various vitamins and minerals that makes Mulmina® Mango a potential candidate for preventive care in case of chemo brain.

Objective

A study evaluated the effectiveness of Mulmina® Mango as preventive care for chemo brain.

Methodology

• Male swiss albino mice weighing 20-30 g were treated with food and water ad libitum to produce chemotherapy-induced cognitive impairment.
• A combination of three chemotherapeutic agents was used to induce cognitive impairment in mice, namely cyclophosphamide, methotrexate and 5-fluorouracil (CMF).
• Mulmina® Mango in selected doses was administered orally to the respective groups’ animals (excluding normal and disease control) every day from day 0 to day 21. The effect of the treatments was compared with the effect of the standard drug donepezil.
• They were evaluated for:

» Behavioural parameters: Open field test (OFT) for locomotor activity; Morris Water Maze (MWM) for learning and memory.

» Estimation of antioxidant parameters in brain homogenate: Catalase, lipid peroxidation (LPO).

» Estimation of hematological parameters: Total and differential WBC, RBC, platelet count and hemoglobin content.

» Parameters to understand the mechanism of Mulmina® Mango: Brain IL-6, Brain TNF-α, brain-derived neurotrophic factor (BDNF).

Observations of the study were-

• In the Morris Water Maze test, the mice treated with both doses of Mulmina® demonstrated a significant improvement in spatial memory of the animals, indicating the potential of Mulmina® to protect the hippocampus from the inflammation-induced damage.
• OFT concluded that all the animals were equal in cognitive abilities before the beginning of the water maze test.
• A lower dose of Mulmina® i.e. 40 mL/kg/day (24±4.0), higher dose i.e. 80 mL/kg/day (16±3.7) and donepezil (16±6.3) were found to be significant in terms of escape latency (ELT) as compared with CMF.
• Higher dose of Mulmina® (20±3.3) was found to be significantly different compared with CMF in terms of retention time (RT).
• Lower (7.8±1.9), as well as a higher dose of Mulmina® (2.9±0.46) and donepezil (5.9±1.2), significantly reduced the latency to first-line crossing (FLC) when compared to CMF (17±2.3).
• The test groups showed an increase in total leukocyte count and differential leukocyte count, except the normal control, which indicated an exacerbated inflammatory reaction in the body.
• A statistically significant elevation was noted in the monocyte count with a higher dose of Mulmina® (1.40±0.81) when compared to normal control (0.52±0.12).
• The higher dose of Mulmina® (2.10±0.15) and donepezil (2.22±0.22) showed a statistically significant increase in the granulocyte count when compared with the normal control (0.78±0.16).
• Higher dose of Mulmina® showed a significant fall in platelet count when compared to normal control.
• Higher dose of Mulmina® significantly restored the levels of pro-inflammatory cytokines (35±4.4).
• Lower dose of Mulmina® (26±1.6) and donepezil (26±2.4) significantly reduced the BDNF levels at p<0.05, whereas a higher dose of Mulmina® was significant at p<0.001.
• Lipid peroxidation was significantly increased in the CMF group. All the treatment groups were able to restore it.

CONCLUSION

• In chemo brain, which is characterized by cognitive dysfunction, Mulmina® can improve cognition, learning as well as memory.
• Mulmina®

» Reduced pro-inflammatory cytokines such as IL-6 and BDNF which are elevated in neuroinflammatory conditions.

» Improved endogenous antioxidant potential evident from its ability to decrease the levels of LPO.

• There were no adverse effects on locomotor activity and hematological parameters after Mulmina® administration which highlights the safety of the product.