Pal Rishi, Chaudhary Manju J, Tiwari Prafulla Chandra, Nath Rajendra, Pant Kamlesh Kumar
Department of Pharmacology and Therapeutics, King George's Medical University, Lucknow, UP, 226003, India.
Department of Physiology, Government Medical College, Tirwa Road, Kannauj, UP, India.
Inflammopharmacology. 2018 Jun 22. doi: 10.1007/s10787-018-0507-8.
Current study was designed to evaluate protective effect of mangiferin and its interaction with low dose of nitric oxide (NO) modulators in complete Freund's adjuvant (CFA) inoculated rats. Male wistar rats (200-300 g, n = 8 per group) were used in the study. On day ''0'' of study arthritis was induced in rats by injecting 0.2 ml CFA in sub-planter region of right hind paw of animals. Treatment with methotrexate (5 mg/kg), mangiferin (10-30 mg/kg) alone and in combination with NO modulators was given (i.p.) from days 14 to 28. After 28 days, blood and joint synovial fluid was collected for biochemical analysis and rat paws were excised to estimate MDA and SOD in tissue (paw) homogenates. CFA inoculation significantly increases (1) arthritic index, (2) ankle diameter, (3) paw volume, and (4) serum TNF-α, IL-6, IL-1β, and synovial TNF-α levels (p < 0.001). The serum Th (IFN-γ) and Th (IL-4) cytokine levels, MDA levels in rat paw tissue homogenates and serum NF-κB levels were also found significantly increased. Significant decrease in serum IL-10 levels and SOD activity was found after CFA inoculation. These CFA-induced arthritic changes, cytokine profile, and oxidative stress markers were significantly reversed by mangiferin (10-30 mg/kg) treatment alone and in combination with L-arginine and L-NAME nitric oxide modulators (p < 0.05). Treatment with methotrexate (5 mg/kg) also significantly reversed these adjuvant changes (p < 0.05). However, effect of methotrexate was less marked as compared to mangiferin (30 mg/kg) alone and in combination with L-NAME (10 mg/kg), but was comparable or slightly better than mangiferin (10 and 20 mg/kg). Thus, on the basis of our findings, we can suggest that interaction of mangiferin with nitric oxide modulators may have therapeutic value for chronic inflammatory disease such as RA.
本研究旨在评估芒果苷的保护作用及其与低剂量一氧化氮（NO）调节剂在完全弗氏佐剂（CFA）接种大鼠中的相互作用。研究使用雄性Wistar大鼠（200 - 300克，每组n = 8）。在研究的第“0”天，通过在动物右后爪足底区域注射0.2毫升CFA诱导大鼠患关节炎。从第14天至28天腹腔注射甲氨蝶呤（5毫克/千克）、单独的芒果苷（10 - 30毫克/千克）以及与NO调节剂联合使用的药物。28天后，采集血液和关节滑液进行生化分析，并切除大鼠爪子以评估组织（爪子）匀浆中的丙二醛（MDA）和超氧化物歧化酶（SOD）。CFA接种显著增加了：（1）关节炎指数，（2）踝关节直径，（3）爪子体积，以及（4）血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和滑膜TNF-α水平（p < 0.001）。还发现大鼠爪子组织匀浆中的血清Th（干扰素-γ）和Th（白细胞介素-4）细胞因子水平、MDA水平以及血清核因子-κB（NF-κB）水平显著升高。CFA接种后血清白细胞介素-10水平和SOD活性显著降低。单独使用芒果苷（10 - 30毫克/千克）以及与L-精氨酸和L- NAME一氧化氮调节剂联合使用可显著逆转这些CFA诱导的关节炎变化、细胞因子谱和氧化应激标志物（p < 0.05）。甲氨蝶呤（5毫克/千克）治疗也显著逆转了这些佐剂诱导的变化（p < 0.05）。然而，与单独的芒果苷（30毫克/千克）以及与L- NAME（10毫克/千克）联合使用相比，甲氨蝶呤的效果不太明显，但与芒果苷（10和20毫克/千克）相当或略好。因此，根据我们的研究结果，我们可以认为芒果苷与一氧化氮调节剂的相互作用可能对类风湿性关节炎等慢性炎症性疾病具有治疗价值。
