Curcumin improves prostanoid ratio in diabetic mesenteric arteries associated with cyclooxygenase-2 and NF-κB suppression

Figures & data

Table 1 Bodyweight and mean arterial blood pressure, blood glucose, and percentage HbA_1c

Group	BW (g)	mABP (mmHg)	BG (mg/dL)	HbA1c (%)
CON-NSS	398.7 ± 12.3	103.1 ± 3.5	101.8 ± 4.89	3.68 ± 0.17
CON-CUR300	403.8 ± 17.0	106.1 ± 3.9	106.8 ± 0.92	4.08 ± 0.41
DM-NSS	285.3 ± 8.8a	151.6 ± 9.6a	459.0 ± 24.40a	10.73 ± 0.32a
DM-CUR30	292.7 ± 17.8a	128.3 ± 3.6c	360.8 ± 35.82a	8.20 ± 0.88a,c
DM-CUR300	325.7 ± 13.0b	122.2 ± 8.6c	310.00 ± 32.73a,c	7.90 ± 0.97a,c

a Notes: P < 0.01 significant difference compared with control;

b P < 0.05 significant difference compared with control;

c Significant difference compared with diabetic rat (P < 0.05). Values are means ±SEM (n =10 for each group).

Abbreviations: BG, blood glucose; BW, bodyweight; CON-NSS, control with 0.9% normal saline; CON-CUR300, control treated with 300 mg/kg; DM-CUR30, diabetestreated with curcumin 30 mg/kg; DM-CUR300, diabetes-treated with curcumin 300 mg/kg; DM-NSS, diabetes with 0.9% normal saline; HbA_1c, glycosylated hemoglobin; mABP, mean arterial blood pressure; SEM, standard error of the mean.

Figure 1 Co-immunofluorescent staining of protein kinase C (PKC)-βII and vascular smooth muscle cells in mesenteric arteries (diameter =100–120 μm) taken from control, diabetes mellitus (DM), and DM curcumin 300 (DM-CUR 300) groups. Double-immunofluorescent staining was performed to demonstrate PKC-βII in the mesenteric arteries (red fluorescence; A), α-smooth muscle actin (green fluorescence; B), and merged image (yellow; C). Magnification: ×400.

Figure 2 A) Immunostaining for cyclo-oxygenase (COX)-2 in small mesenteric arteries. Sections of arterial segment show the endothelial cell layer inwards. Positive immunoreactions are observed as a brown precipitate.

Notes: CON-NSS (left upper panel), DM-NSS (right upper panel), DM-CUR30 (left lower panel), and DM-CUR300 (right lower panel) rats. Magnification: ×400. B) Expression of COX-2 in the endothelium layer in small mesenteric arteriesusing image analysis (Global Lab Image/2 software) measurements in the DMNSS, DM-CUR30, and DM-CUR300 groups. Data are expressed as mean ±SEM. ***P < 0.001 significant difference compared with control arteries; ^†P <0.05 significant difference compared with diabetic arteries; ^††P < 0.01 significant difference compared with diabetic arteries.
Abbreviations: CON-NSS, control with 0.9% normal saline; DM-CUR30, diabetes-treated with curcumin 30 mg/kg; DM-CUR300, diabetes-treated with curcumin 300 mg/kg; DM-NSS, diabetes treated with 0.9% normal saline; SEM, standard error of the mean.

Figure 3 A) The expression of nuclear factor-κB p65 (NF-κB p65) in small mesenteric arteries in the control (left upper panel), DM (right upper panel), DM-CUR30 (left lower panel) and DM-CUR300 (right lower panel) rats. Positive immunoreactions are observed as a brown precipitate. Magnification: ×400. B) Expression of NF-κB in the endothelium layer in small mesenteric arteries using image analysis (Global Lab Image/2 software) measurement in the DM-NSS, DM-CUR30, and DM-CUR300 groups.

Notes: Data are expressed as mean ±SEM. NS, no significant difference compared with diabetic arteries. **P < 0.01 significant difference compared with control arteries. ^†P < 0.05 significant difference compared with diabetic arteries.
Abbreviations: DM-CUR30, diabetes-treated with curcumin 30 mg/kg; DM-CUR300, diabetes-treated with curcumin 300 mg/kg; DM-NSS, diabetes treated with 0.9% normal saline; NF-κB, nuclear factor-κB; SEM, standard error of the mean.

Table 2 Means ±SEM of basal levels of 6-keto-PGF_1α and TXB₂ together with the 6-keto-PGF_1α/TXB₂ ratios in the mesenteric arteriolar bed of CON-NSS, DM-NSS, and DM-CUR300 groups

Group	6-keto-PGF1α level (pg/mL)	TXB2 level (pg/mL)	6-keto-PGF1α/TXB2 ratio
CON-NSS	536.9 ± 53.3	29.4 ± 4.3	18.4 ± 0.6
DM-NSS	407.6 ± 37.1a	58.4 ± 5.8a	7.0 ± 0.06a
DM-CUR 300	502.3 ± 27.6b	47.4 ± 7.2b	10.7 ± 1.0b

a Note: P < 0.05 significant difference compared with control arterioles

b No significant difference compared with control arterioles. Values are means ±SEM (n = 10 for each group).

Abbreviations: CON-NSS, control with 0.9% normal saline; DM-CUR300, diabetes treated with curcumin 300 mg/kg; DM-NSS, diabetes treated with 0.9% normal saline; PGF_1α, prostaglandin F_1α; SEM, standard error of the mean; TXB₂, thromboxane B₂.

Figure 4 The beneficial effects of curcumin on diabetic vascular functions. Curcumin supplementation (300 mg/kg bodyweight) improved diabetes-induced vascular dysfunction associated with its potential to reduce blood sugar, COX-2 and NF-κB suppression, PKC inhibition, and improve the ratio of prostanoid products PGI₂ and TXA₂.

Abbreviations: COX-2, cyclooxygenase-2; DAG, diacylglycerol; NF-κB, nuclear factor-κB; PGI₂, prostaglandin I₂; PKC, protein kinase C; ROS, reactive oxygen species; TXA₂, thromboxane A₂.