Inhibitory effect of curcumin on angiogenesis in a streptozotocin-induced diabetic rat model: An aortic ring assay

Mohammad Hossein Dehghan; Hossein Mirmiranpour; Sara Faghihi-Kashani; Kourosh Kabir; Mehrdad Larry; Ehsan Zayerzadeh; Salume Salehi

doi:10.1016/j.jtcme.2015.12.003

Inhibitory effect of curcumin on angiogenesis in a streptozotocin-induced diabetic rat model: An aortic ring assay

J Tradit Complement Med. 2016 Jan 27;6(4):437-441. doi: 10.1016/j.jtcme.2015.12.003. eCollection 2016 Oct.

Authors

Mohammad Hossein Dehghan¹, Hossein Mirmiranpour², Sara Faghihi-Kashani³, Kourosh Kabir⁴, Mehrdad Larry³, Ehsan Zayerzadeh⁵, Salume Salehi³

Affiliations

¹ Biochemistry Department, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
² Biochemistry Department, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran; Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
³ Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Social Medicine Department, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
⁵ Department of Biology, Faculty of Food Industry and Agriculture, Standard Research Institute, Karaj, Iran.

Abstract

Background: Curcumin (diferuloylmethane) has been associated with the inhibition of angiogenesis, as well as the prevention of cancers and inflammatory processes. The aim of this study was to assess the efficacy of curcumin in suppressing angiogenesis in the cultured endothelial cells of rat aortic rings.

Methods: Eight-week-old male Wistar rats were randomized into five groups each with a different treatment and cell culturing paradigm: controls cultured in the absence of VEGF (vascular endothelial growth factor) (C), controls cultured in the presence of VEGF (C-V), controls treated with curcumin and then cultured in media lacking VEGF (C-TC), diabetics cultured in media supplemented with VEGF (D-V) and diabetics treated with curcumin and then cultured in media supplemented with VEGF (D-V-TC). Each group consisted of 8 animals. Diabetes was induced in by streptozotocin (STZ; 60 mg/kg body weight, IV). After 8 weeks, animals were sacrificed and their aortas were excised. Ring-shaped explants were embedded in a 96-well culture plate. Angiogenesis response was measured by counting the number of primary microtubules in each well.

Results: Optic microscopy revealed that the D-V group had the highest number of microvessels, while angiogenesis was not observed in the C or C-TC groups. The number of primary microtubules was significantly lower in the D-V-TC group compared to the D-V group (P < 0.05). The D-V-TC group had a significantly higher number of microvessels compared to the C-TC group (P < 0.05).

Conclusion: Curcumin attenuates angiogenesis response in stertozotocin-induced diabetic rats.

Keywords: AP-1, activator protein 1; Angiogenesis; Aortic ring assay; C, controls in the absence of VEGF; C-TC, controls treated with curcumin cultured in the absence of VEGF; C-V, controls in the presence of VEGF; CPCSEA, Committee for the Purpose of Control and Supervision of Experiments on Animals; Curcumin; D-V, diabetics in a culture containing VEGF; D-V-TC, diabetics treated with curcumin in a culture containing VEGF; DM, diabetes mellitus; DMSO, dimethyl sulfoxide; Diabetes mellitus; MMP, matrix metalloproteinases; NF-kB, nuclear factor kappa; PBS, phosphate buffer saline; UPA, urokinase plasminogen activator; VEGF; VEGF, vascular endothelial growth factor.