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A Synthetic Curcuminoid Analog, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone, Ameliorates Impaired Wound Healing in Streptozotocin-Induced Diabetic Mice by Increasing miR-146a

by Jingjuan Huang 1,2,3, Jia Fu 1,2,3, Bing Liu 2,3,4,5, Rui Wang 1,2,3,* and Tianhui You 1,2,3,*
1
School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
2
Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou 510006, China
3
Key Laboratory of New Drug Discovery and Evaluation of Ordinary Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China
4
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
5
Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China
*
Authors to whom correspondence should be addressed.
Molecules 2020, 25(4), 920; https://doi.org/10.3390/molecules25040920
Received: 28 December 2019 / Revised: 8 February 2020 / Accepted: 17 February 2020 / Published: 19 February 2020
The impairment in diabetic wound healing represents a significant clinical problem, with no efficient targeted treatments for these wound disorders. Curcumin is well confirmed to improve diabetic wound healing, however, its low bioavailability and poor solubility severely limit its clinical application. This study aims to provide the pharmacological basis for the use of (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66). The results showed that topically applied C66 improved cutaneous wound healing in vivo. Further studies showed that C66 treatment increased the level of microRNA-146a (miR-146a) in the wounds in streptozotocin (STZ)-induced diabetic mice, downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) and phosphorylated nuclear factor-κB (NF-κB) p65 subunit (p-p65) (both p < 0.05), and suppressed the mRNA expression of inflammation-related cytokines, tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6). The in vitro data obtained in human umbilical vein endothelial cells (HUVECs) showed that C66 could reverse high glucose (HG)-induced NF-κB activation due to upregulation of miR-146a expression, which matched the in vivo findings. In conclusion, the present study indicates that C66 exerts anti-inflammation activity and accelerates skin wound healing of diabetic mice, probably via increasing miR-146a and inhibiting the NF-κB-mediated inflammation pathway. Therefore, C66 may be a promising alternative for the treatment of diabetic wounds. View Full-Text
Keywords: curcuminoid; synthetic analog; wound healing; miR-146a; inflammation; NF-κB curcuminoid; synthetic analog; wound healing; miR-146a; inflammation; NF-κB
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MDPI and ACS Style

Huang, J.; Fu, J.; Liu, B.; Wang, R.; You, T. A Synthetic Curcuminoid Analog, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone, Ameliorates Impaired Wound Healing in Streptozotocin-Induced Diabetic Mice by Increasing miR-146a. Molecules 2020, 25, 920.

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