Role of Nitric Oxide Modulators in Neuroprotective Effects of Mangiferin in 6-Hydroxydopamine-induced Parkinson's Disease in Rats

被引：1
作者：
Tiwari, Prafulla Chandra [1 ]
Chaudhary, Manju J. [2 ]
Pal, Rishi [1 ]
Nath, Rajendra [1 ]
机构：
[1] King Georges Med Univ, Dept Pharmacol & Therapeut, Lucknow 226003, Uttar Pradesh, India
[2] Govt Med Coll, Dept Physiol, Tirwa Rd, Kannauj, Uttar Pradesh, India
来源：
ANNALS OF NEUROSCIENCES | 2024年 / 31卷 / 03期
关键词：
6-OHDA; NF-kappa B; mangiferin; inflammation; Nitric Oxide; NF-KAPPA-B; TRANSCRIPTIONAL REGULATION; GENE; ACTIVATION; EXPRESSION; HEREDITARY; MUTATIONS; APOPTOSIS; PATHWAY; MODEL;
D O I：
10.1177/09727531231184698
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Background Parkinson's disease (PD) is typified by inflammation of dopaminergic neurons leading to the release of various inflammatory mediators. These mediators activate the transcription factor NF-kappa B, which in turn activates inducible nitric oxide synthase (iNOS), leading to increased inflammation.Purpose This study was intended to study the effect of combination of mangiferin, a specific inhibitor of NF-kappa B with low-dose nitric oxide (NO) modulators.Methods A total of eight Wistar rats weighing 200-250 g were used in each group. Stereotactic surgery was performed to induce 6-hydroxydopamine (6-OHDA) lesions. The treatment period extended from day 14 to day 42, during which time behavioral tests were performed to evaluate the effects of mangiferin and its combination with NO modulators. On day 42, the brains of the rats were removed for biochemical and molecular analyzes.Results Mangiferin significantly improved locomotor activity and decreased inflammatory chemokines levels in rats with 6-OHDA lesions. Mangiferin therapy decreased myeloperoxidase (MPO) levels and reduced oxidative stress. In particular, caspase-3, caspase-9 and COX-2 activities were significantly reduced after the mangiferin treatment. A combination of 45-mu g mangiferin and 10-mg/kg L-NAME showed the greatest improvement in locomotor, behavioral, biochemical, and molecular parameters impaired by 6-OHDA.Conclusion In this study, mangiferin was found to protect rats with 6-OHDA lesions by inhibiting inflammation causing chemokines such as TNF-alpha and IL-6. Besides, the grouping of iNOS inhibitor L-NAME at a dose of 10 mg/kg with 45-mu g mangiferin enhanced the anti-inflammatory and anti-Parkinsonian activity of mangiferin. Consequently, the combination therapy of mangiferin and L-NAME is promising for the treatment of PD. However, clinical trials will be required to evaluate the efficacy of this combination therapy in humans.
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页码：186 / 203
页数：18
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