Neuroprotective effect of Mulmina™ against chemotherapy-induced cognitive decline in normal mice.

Neuroprotective effect of Mulmina™ against chemotherapy-induced cognitive decline in normal mice.
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DOI:
10.3892/br.2020.1377
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发表时间:
2021-01
期刊:
影响因子:
2.3
通讯作者:
Nandakumar K
Nandakumar K
中科院分区:
其他
文献类型:
--
作者:
Kinra M;Ranadive N;Gourishetti K;Nayak PG;Jagdale RN;Ahmed SM;Raghavendra KV;Mudgal J;Nandakumar K

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本研究的目的是评估一种针对化疗引起的认知功能障碍的上市制剂。配方,Mulmina™,含有天然化合物,已知有助于改善功能,并防止认知能力下降。配方中的所有植物成分都经过了单独测试,但这是第一次在小鼠模型中评估这种配方对化疗诱导的认知衰退(CICD)的影响。采用环磷酰胺(50 mg/kg)、甲氨蝶呤(5 mg/kg)和5-氟尿嘧啶(5 mg/kg)灌胃诱导CICD。CMF分三个周期给药,每周注射一次,持续三周。通过运动活动测试(Open Field test)和空间记忆测试(Morris Water Maze)来评估小鼠认知能力的下降。生化参数评估包括脑细胞因子水平和BDNF水平通过ELISA。使用兽医血细胞计数器进行血液学计数以评估血液剖面的任何变化。氧化应激标志物的过氧化氢酶活性和脂质过氧化水平也用紫外分光光度法在大脑中进行了评估。与未治疗的动物相比,Mulmina™能够在化疗后表现出显著的认知功能改善。除了空间记忆的改善,生化指标也有所改善。在本初步研究中,Mulmina™植物化学物质的特殊组合证明了它们在缓解CICD方面的成功,并为未来的研究铺平了道路,这些研究可以为Mulmina™的作用机制建立坚实的分子和药理学基础。
The aim of the present study was to evaluate a marketed formulation against chemotherapy-induced cognitive dysfunction. The formulation, Mulmina™, contains natural compounds which are known to help in improving function as well as in preventing cognitive decline. All of the phytoconstituents in the formulation have been tested individually but this is the first study where such a formulation has been evaluated against chemotherapy-induced cognitive decline (CICD) in a mouse model. CICD was induced by cyclophosphamide (50 mg/kg), methotrexate (5 mg/kg), and 5-fluorouracil (5 mg/kg) (CMF), administered intraperitonially. CMF was administered in three cycles, with one injection per week for three weeks. The decline in cognition of the mice was evaluated by a test of locomotor activity (Open Field Test) followed by a test for spatial memory (Morris Water Maze). Biochemical parameters evaluated include brain cytokine levels and BDNF levels via ELISA. Hematological counts were also performed to evaluate any changes in blood profile using a veterinary blood cell counter. Levels of oxidative stress markers with respect to catalase activity and lipid peroxidation were also evaluated in the brain using UV-spectrophotometric analysis. Mulmina™ was able to show significant improvement in cognitive function post chemotherapy when compared to the untreated animals. Apart from improvement in spatial memory, there was also an improvement in biochemical parameters. The particular combination of phytochemicals in Mulmina™ proved themselves successful in alleviating the CICD in this preliminary study and pave a path for future studies which can establish the solid grounds with respect to molecular and pharmacological basis for the mechanism of action of Mulmina™.
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