SGT College of Pharmacy, SGT University, Gurugram, India.
Metab Brain Dis. 2022 Jan;37(1):173-183. doi: 10.1007/s11011-021-00858-6. Epub 2021 Nov 5.
The present study was designed to determine the antidepressant like effect of pyridoxine in mice. Pyridoxine (12.5, 25 and 50 mg/kg, i.p.) was administered to the mice and depression related behavioral and neurochemical alterations were determined. It was observed that pyridoxine (50 mg/kg, i.p.) treatment decreased the immobility period in tail suspension test (TST) and forced swim test (FST) significantly as compared to control. Pyridoxine (50 mg/kg, i.p.) treatment increased the level of serotonin (5-HT) and decreased the level of nitrite in the brain of mice significantly as compared to control. Pyridoxine thus confer antidepressant like effect by increasing the level of 5-HT and by decreasing the level of nitrite in the brain of mice. Further the influence of nitric oxide (NO)/ soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) in antidepressant-like effect of pyridoxine was studied. It was observed that the pretreatment of NO donor (i.e. L-Arginine) and cGMP modulator (i.e. sildenafil) counteracted while the pretreatment of NO/sGC inhibitor (i.e. methylene blue) potentiated the effect of pyridoxine in TST and FST. Pretreatment of NO donor did not influence, pretreatment of NO/sGC inhibitor decreased while the pretreatment of cGMP modulator increased the level of brain nitrite in pyridoxine treated mice. Further the pretreatment of NO donor and cGMP modulator decreased while the pretreatment of NO/sGC inhibitor increased the level of brain serotonin in pyridoxine treated mice. Pyridoxine thus exerted antidepressant like effect and NO-sGC-cGMP signaling modulated the antidepressant like effect of pyridoxine in mice.
本研究旨在确定吡哆醇对小鼠的抗抑郁作用。将吡哆醇（12.5、25 和 50mg/kg，ip）给予小鼠，并确定与抑郁相关的行为和神经化学改变。结果观察到，与对照组相比，吡哆醇（50mg/kg，ip）处理显著降低了悬尾试验（TST）和强迫游泳试验（FST）中的不动期。吡哆醇（50mg/kg，ip）处理显著增加了小鼠大脑中的 5-羟色胺（5-HT）水平，降低了亚硝酸盐水平。吡哆醇通过增加大脑中的 5-HT 水平和降低亚硝酸盐水平，从而发挥抗抑郁作用。此外，还研究了一氧化氮（NO）/可溶性鸟苷酸环化酶（sGC）/环鸟苷单磷酸（cGMP）对吡哆醇抗抑郁样作用的影响。结果观察到，NO 供体（即 L-精氨酸）和 cGMP 调节剂（即西地那非）的预处理可拮抗吡哆醇在 TST 和 FST 中的作用，而 NO/sGC 抑制剂（即亚甲蓝）的预处理则增强了其作用。NO 供体的预处理不影响，NO/sGC 抑制剂的预处理降低，而 cGMP 调节剂的预处理增加了吡哆醇处理小鼠大脑中亚硝酸盐的水平。进一步的研究发现，NO 供体和 cGMP 调节剂的预处理降低，而 NO/sGC 抑制剂的预处理增加了吡哆醇处理小鼠大脑中 5-羟色胺的水平。因此，吡哆醇发挥了抗抑郁作用，而 NO-sGC-cGMP 信号通路调节了吡哆醇在小鼠中的抗抑郁作用。
