Liposomal Curcumin Enhances the Effect of Naproxen in a Rat Model of Migraine

Abstract

BACKGROUND Curcumin is an antioxidant that reduces inflammation and pain. This study aimed to assess the effect of pretreatment with naproxen and liposomal curcumin compared with naproxen and curcumin solution on oxidative stress parameters and pain in a rat model of migraine. MATERIAL AND METHODS Sixty-three male Wistar rats included a control group (n=9) and a rat model of migraine (n=54) induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The rat model group was divided into an untreated control group (n=9), a group pretreated with naproxen alone (2.8 mg/kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (1 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (2 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (1 mg/0.1 kg) (n=9) a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (2 mg/0.1 kg) (n=9). Spectroscopy measured biomarkers of total oxidative status and nociception was tested using an injection of 1% of formalin into the rat paw. RESULTS Expression of biomarkers of oxidative stress and enhanced nociception were significantly increased following pretreatment with combined naproxen and liposomal curcumin compared with curcumin solution or naproxen alone (P<0.001). Combined curcumin solution and naproxen were more effective at a concentration of 2 mg/0.1kg for the first nociceptive phase (P<0.005). CONCLUSIONS In a rat model of migraine, combined therapy with liposomal curcumin and naproxen showed an improved antioxidant effect and anti-nociceptive effect.

Figure 1

The patterns of expression of the oxidative stress biomarkers malondialdehyde (MDA), nitric oxide (NO), and total oxidative status (TOS) in the pretreated groups in a rat model of migraine. The line represents the median, and the circles represent the individual values. The rat model of migraine (M) (n=54), was induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The groups include the untreated control group (M-C) (n=9), a group pretreated with naproxen (2.8 mg/kg) (M+NP) (n=9), a group pretreated with naproxen (2.8 mg/kg) and curcumin solution (1 mg/0.1 kg) (M +NP+CC₍₁₎) (n=9), a group pretreated with naproxen (2.8 mg/kg) and curcumin solution (2 mg/0.1 kg) (M +NP+CC₍₂₎) (n=9), a group pretreated with naproxen (2.8 mg/kg) and liposomal curcumin solution (1 mg/0.1 kg) (M+NP+CCl₍₁₎) (n=9) a group pretreated with naproxen (2.8 mg/kg) and liposomal curcumin solution (2 mg/0.1 kg) (M+NP+CCl₍₂₎) (n=9). The letters and numbers correspond to the P-values, as follows in the M-C compared with C: ^a1–a3 0.0003; M+NP compared with M-C: ^b1 0.0003, ^b2 0.0007, ^b3 0.0006; M+NP+CC₍₁₎ compared with M+NP: ^c1 0.0423, ^c2 0.1333, ^c3 0.0027; M+NP+CC₍₂₎ compared with M+NP: ^d10.0703, ^d2 0.0341, ^d30.0071; M+NP+CCl₍₁₎ compared with M+NP: ^e1–e30.0003; M+NP+CCl₍₂₎ compared with M+NP: ^f1–f3 0.0003; M+NP+CC₍₁₎ compared with M+NP+CC₍₂₎: ^A1 0.9296, ^A2 0.5660; ^A3 0.3772; M+NP+CCl₍₁₎ compared with M+NP+CCl₍₂₎: ^B10.0047, ^B20.1120; ^B30.2510; NTG+NP+CC₍₁₎ compared with NTG+NP+CCl₍₁₎: ^X1–X3 0.0003; NTG+NP+CC₍₂₎ compared with NTG+NP+CCl₍₂₎: ^Y1–Y3 0.0003.

Figure 2

Distribution of antioxidant status in the plasma, including the thiol and total antioxidative capacity (TAC), in the pretreated groups in a rat model of migraine. The line is given by the median, and the circles represent the individual values. The rat model of migraine (M) (n=54), was induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The groups include the untreated control group (M-C) (n=9), a group pretreated with naproxen (2.8 mg/kg) (M+NP) (n=9), a group pretreated with naproxen (2.8 mg/kg) and curcumin solution (1 mg/0.1 kg) (M+NP+CC₍₁₎) (n=9), a group pretreated with naproxen (2.8 mg/kg) and curcumin solution (2 mg/0.1 kg) (M +NP+CC₍₂₎) (n=9), a group pretreated with naproxen (2.8 mg/kg) and liposomal curcumin solution (1 mg/0.1 kg) (M+NP+CCl₍₁₎) (n=9) a group pretreated with naproxen (2.8 mg/kg) and liposomal curcumin solution (2 mg/0.1 kg) (M+NP+CCl₍₂₎) (n=9). The letters and numbers correspond to the P-values, as follows in the M-C compared with C: ^1a–2a 0.0003; M+NP compared with M: ^1b–2b 0.0003; M+NP+CC₍₁₎ compared with M+NP: ^1c0.1853, ^2c0.0193; M+NP+CC₍₂₎ compared with M+NP: ^1d0.0423, ^2d0.0003; M+NP+CCl₍₁₎ compared with M+NP: ^e1–e2 0.0003; M+NP+CCl₍₂₎ compared with M+NP: ^1f–2fr 0.0003; M+NP+CC₍₁₎ compared with M+NP+CC₍₂₎: ^1A0.0054, ^2A0.1223; M+NP+CCl₍₁₎ compared with M+NP+CCl₍₂₎: ^1B0.1451, ^2B0.5365; M+NP+CC₍₁₎ compared with M+NP+CCl₍₁₎: ^1X–2X 0.0003; M+NP+CC₍₂₎ compared with M+NP+CCl₍₂₎: ^1Y 0.0023, ^2Y0.0009.

Figure 3

The distribution of the number of flinches and shakes by groups as a test of nociception following the injection of 1% of formalin subcutaneously in the right paw of the rats. The first phase (left-hand graph), and the second phase (right-hand graph). The line represents the median, and the circles represent the individual values. C is the rat control group (no medication) (n=9). The rat model of migraine (M) (n=54), was induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The groups include the untreated control group (M-C) (n=9), a group pretreated with naproxen (2.8 mg/kg) (M+NP) (n=9), a group pretreated with naproxen (2.8 mg/kg) and curcumin solution (1 mg/0.1 kg) (M +NP+CC₍₁₎) (n=9), a group pretreated with naproxen (2.8 mg/kg) and curcumin solution (2 mg/0.1 kg) (M +NP+CC₍₂₎) (n=9), a group pretreated with naproxen (2.8 mg/kg) and liposomal curcumin solution (1 mg/0.1 kg) (M+NP+CCl₍₁₎) (n=9) a group pretreated with naproxen (2.8 mg/kg) and liposomal curcumin solution (2 mg/0.1 kg) (M+NP+CCl₍₂₎) (n=9). The P-values represent comparison with the M+NP group.