Tiwari Prafulla Chandra, Chaudhary Manju J, Pal Rishi, Nath Rajendra
Department of Pharmacology & Therapeutics, King George's Medical University, Lucknow, Uttar Pradesh, India.
Department of Physiology, Government Medical College, Tirwa Road, Kannauj, Uttar Pradesh, India.
Ann Neurosci. 2024 Jul;31(3):186-203. doi: 10.1177/09727531231184698. Epub 2023 Aug 23.
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-κB, which in turn activates inducible nitric oxide synthase (iNOS), leading to increased inflammation.
This study was intended to study the effect of combination of mangiferin, a specific inhibitor of NF-κB with low-dose nitric oxide (NO) modulators.
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.
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-µg mangiferin and 10-mg/kg L-NAME showed the greatest improvement in locomotor, behavioral, biochemical, and molecular parameters impaired by 6-OHDA.
In this study, mangiferin was found to protect rats with 6-OHDA lesions by inhibiting inflammation causing chemokines such as TNF-α and IL-6. Besides, the grouping of iNOS inhibitor L-NAME at a dose of 10 mg/kg with 45-µg 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.
帕金森病（PD）的典型特征是多巴胺能神经元炎症，导致各种炎症介质释放。这些介质激活转录因子NF-κB，进而激活诱导型一氧化氮合酶（iNOS），导致炎症加剧。
本研究旨在探讨芒果苷（一种NF-κB特异性抑制剂）与低剂量一氧化氮（NO）调节剂联合使用的效果。
每组使用8只体重200 - 250 g的Wistar大鼠。进行立体定向手术以诱导6-羟基多巴胺（6-OHDA）损伤。治疗期从第14天延长至第42天，在此期间进行行为测试以评估芒果苷及其与NO调节剂联合使用的效果。在第42天，取出大鼠大脑进行生化和分子分析。
芒果苷显著改善了6-OHDA损伤大鼠的运动活性，并降低了炎症趋化因子水平。芒果苷治疗降低了髓过氧化物酶（MPO）水平并减轻了氧化应激。特别是，芒果苷治疗后半胱天冬酶-3、半胱天冬酶-9和COX-2活性显著降低。45μg芒果苷与10mg/kg L-精氨酸甲酯（L-NAME）联合使用对6-OHDA损伤所致的运动、行为、生化和分子参数损害改善最大。
在本研究中，发现芒果苷通过抑制引起趋化因子如肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的炎症来保护6-OHDA损伤的大鼠。此外，10mg/kg剂量的iNOS抑制剂L-NAME与45μg芒果苷联合使用增强了芒果苷的抗炎和抗帕金森病活性。因此，芒果苷与L-NAME联合治疗有望用于治疗帕金森病。然而，需要进行临床试验来评估这种联合治疗对人类的疗效。
