Curcumin Analogs Reduce Stress and Inflammation Indices in Experimental Models of Diabetes

Abstract

Chronic inflammation and oxidative stress lead to a multitude of adverse cellular responses in target organs of chronic diabetic complications. Curcumin, a highly investigated phytochemical, has been shown to exhibit both anti-inflammatory and antioxidant activities. However, the clinical application of curcumin has been greatly limited due to a poor pharmacokinetic profile. To overcome these limitations, we have generated analogs of curcumin to enhance bioavailability and offer a preferable pharmacokinetic profile. Here, we explored the effects of two mono-carbonyl curcumin analogs, L2H21 and L50H46, in alleviating indices of inflammation and oxidative stress in cell culture and mouse model of diabetic complications. Our results show that L2H21 and L50H46 normalize inflammatory mediators (IL-6 and TNF-α), extracellular matrix proteins (FN and COL4α1), vasoactive factors (VEGF and ET-1) and a key transcriptional coactivator (p300) in cultured human retinal microvascular endothelial cells (HRECs) and dermal-derived microvascular endothelial cells (HMVECs) challenged with high levels of glucose. These curcumin analogs also reduced glucose-induced oxidative DNA damage as evidenced by 8-OHdG labeling. We further show that treatment of streptozotocin-induced diabetic mice with curcumin analogs prevents cardiac and renal dysfunction. The preservation of target tissue function was associated with normalization of pro-inflammatory cytokines and matrix proteins. Collectively, our results show that L2H21 and L50H46 offer the anti-inflammatory and antioxidant activities as has been reported for curcumin, and may provide a clinically applicable therapeutic option for the treatment of diabetic complications.

Exercise and Curcumin in Combination Improves Cognitive Function and Attenuates ER Stress in Diabetic Rats

“…However, other human studies have shown that single lifestyle factor changes, such as physical activity changes, have less effect on cognitive function in neurodegenerative diseases. Curcumin is a well-known natural antioxidant that reduces the inflammatory response in diabetes via Nrf2 and PI3K/AKT signaling pathways [27][28][29][30][31]. Evidence indicates that curcumin can ameliorate pathologies associated to amyloid-β and recover p-Tau-related pathologies in animal models [32,33].…”

The Evolving Role of Natural Compounds in the Medical Treatment of Uterine Fibroids

“…Lately, it was found that curcumin presents powerful anti-inflammatory and anti-oxidant activities. It stabilizes the levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), ECM proteins (fibronectin and collagen), as well as a vascular endothelial growth factor (VEGF) [124].…”

PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

“…Curcumin is a polyphenol and natural product isolated from root of turmeric rhizome [ 179 , 180 , 181 ]. It has pharmacological activities for the amelioration of cardiovascular disorders [ 182 ], improving blood lipids [ 183 ], reducing the risk of diabetes development [ 184 , 185 ], and so on. However, among them, antitumor activity of curcumin is of importance, since curcumin has been able to suppress proliferation of cancer cells, induce apoptosis, and inhibit their migration [ 167 , 186 , 187 ].…”