Oral Nanocurcumin Alone or in Combination with Insulin Alleviates STZ-Induced Diabetic Neuropathy in Rats.
Oral Nanocurcumin Alone or in Combination with Insulin Alleviates STZ-Induced Diabetic Neuropathy in Rats.
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DOI：
10.1021/acs.molpharmaceut.2c00465
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发表时间：
2022-12-05
影响因子：
4.9
通讯作者：
Kumar, M. N. V. Ravi
中科院分区：
文献类型：
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作者：
Dwivedi, Subhash;Gottipati, Anuhya;Ganugula, Raghu;Arora, Meenakshi;Friend, Richard;Osburne, Robert;Rodrigues-Hoffman, Aline;Basu, Rita;Pan, Hui-Lin;Kumar, M. N. V. Ravi
关键词：
糖尿病（DM）是一种多方面的代谢紊乱，如果管理不当会导致继发性并发症。糖尿病周围神经病变（DPN）是一种由神经损伤引起的并发症，不能逆转，但可以延迟。最近，糖尿病患者正在使用膳食补充剂，尽管人们对这种做法普遍持怀疑态度。姜黄素（CUR），一种这样的补充剂可以帮助预防糖尿病中潜在的低度炎症，但它受到口服生物利用度差的困扰。为了更好地了解生物利用度在临床结果中的作用，我们测试了含有姜黄素（nCUR）的双头纳米系统对DPN的影响。由于CUR不影响血糖水平，我们还测试了nCUR与长效皮下胰岛素（INS）联合使用的效果。如后爪、坐骨神经、脾脏和L4-6脊髓的定性和定量分析所示，含或不含INS的nCUR以比未配制的CUR低两倍的剂量稀释DPN。此外，通过Bielschowsky银染色和通过免疫荧光测量的表皮内神经纤维（IENF）密度，nCUR和nCUR+INS可保护后爪神经轴突。机制研究进一步证实了结果，其中nCUR或nCUR+INS显示坐骨神经中TUNEL阳性细胞、NLRP 3、IL-1β的mRNA表达和巨噬细胞浸润显著减少，同时保留巢蛋白和NF 200表达。总之，数据证实CUR生物利用度与临床结局成比例，INS单独给药可能不是DM的解决方案之一。本研究强调了nCUR联合或不联合INS在缓解DPN方面的潜力，需要进一步研究。
Diabetes mellitus (DM), a multifaceted metabolic disorder if not managed properly leads to secondary complications. Diabetic peripheral neuropathy (DPN) is one such complication caused by nerve damage that cannot be reversed but can be delayed. Recently, diabetes patients are using dietary supplements, although there remains a general skepticism about this practice. Curcumin (CUR), one such supplement can help prevent underlying low-grade inflammation in diabetes, but it is plagued by poor oral bioavailability. To better understand the role of bioavailability in clinical outcomes, we have tested double-headed nanosystems containing curcumin (nCUR) on DPN. Because CUR does not influence glucose levels, we have also tested the effects of nCUR combined with long-acting subcutaneous insulin (INS). nCUR with or without INS alleviates DPN at two times lower dose than unformulated CUR, as indicated by qualitative and quantitative analysis of the hind paw, sciatic nerve, spleen, and L4–6 spinal cord. In addition, nCUR and nCUR+INS preserve hind paw nerve axons as evident by the Bielschowsky silver stain and intraepidermal nerve fibers (IENF) density measured by immunofluorescence. The mechanistic studies further corroborated the results, where nCUR or nCUR+INS showed a significant decrease in TUNEL positive cells, mRNA expression of NLRP3, IL-1β, and macrophage infiltration while preserving nestin and NF200 expression in the sciatic nerve. Together, the data confirms that CUR bioavailability is proportional to clinical outcomes and INS alone may not be one of the solutions for DM. This study highlights the potential of nCUR with or without INS in alleviating DPN and warrants further investigation.
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