Liposomal Curcumin is Better than Curcumin to Alleviate Complications in Experimental Diabetic Mellitus

Abstract

Curcumin (CC) is known to have anti-inflammatory and anti-oxidative properties and has already been tested for its efficiency in different diseases including diabetes mellitus (DM). New formulations and route administration were designed to obtain products with higher bioavailability. Our study aimed to test the effect of intraperitoneal (i.p.) administration of liposomal curcumin (lCC) as pre-treatment in streptozotocin(STZ)-induced DM in rats on oxidative stress, liver, and pancreatic functional parameters. Forty-two Wistar-Bratislava rats were randomly divided into six groups (seven animals/group): control (no diabetes), control-STZ (STZ-induced DM -60 mg/100g body weight a single dose intraperitoneal administration, and no CC pre-treatment), two groups with DM and CC pre-treatment (1mg/100g bw-STZ + CC1, 2 mg/100g bw-STZ + CC2), and two groups with DM and lCC pre-treatment (1 mg/100g bw-STZ + lCC1, 2 mg/100g bw-STZ + lCC1). Intraperitoneal administration of Curcumin in diabetic rats showed a significant reduction of nitric oxide, malondialdehyde, total oxidative stress, and catalase for both evaluated formulations (CC and lCC) compared to control group (p < 0.005), with higher efficacy of lCC formulation compared to CC solution (p < 0.002, excepting catalase for STZ + CC2vs. STZ + lCC1when p = 0.0845). The CC and lCC showed hepatoprotective and hypoglycemic effects, a decrease in oxidative stress and improvement in anti-oxidative capacity status against STZ-induced DM in rats (p < 0.002). The lCC also proved better efficacy on MMP-2, and -9 plasma levels as compared to CC (p < 0.003, excepting STZ + CC2 vs. STZ + lCC1 comparison with p = 0.0553). The lCC demonstrated significantly better efficacy as compared to curcumin solution on all serum levels of the investigated markers, sustaining its possible use as adjuvant therapy in DM.

Keywords: catalase; curcumin; diabetes mellitus (DM); malondialdehyde (MDA); matrix metalloproteinases (MMP); nitric oxide (NOx); oxidative stress; streptozotocin (STZ).

Figure 1

Variability of oxidative stress intensity by groups: (a) MDA (malondialdehyde) and (b) NOx (nitric oxide). C = control; STZ-C = streptozotocin control; STZ + CC1 = STZ and 1 mg/100 g bw CC as pre-treatment; STZ + CC2 = STZ and 2 mg/100 g bw CC as pre-treatment; STZ + lCC1 = STZ and pre-treatment with 1 mg/100 g bw lCC; STZ + lCC2 = STZ and pre-treatment with 2 mg/100 g bw lCC. ^a p-values < 0.002 as compared to STZ-C group; ^b p-values < 0.002 as compared to STZ + CC1 group excepting ^b1 0.0073, ^b2 0.2502, and ^b3 0.6547; ^c p-values< 0.002 as compared to STZ + CC2 group excepting ^c1 0.0040; ^d p-values < 0.002 as compared to STZ + lCC1 group excepting ^d1 0.0181. (c) TOS (total oxidative status).

Figure 2

Variability of antioxidant capacity of plasma by groups: (a) total antioxidant capacity (TAC) and (b) catalase. C = control; STZ-C = streptozotocin control; STZ + CC1 = STZ and 1 mg/100 g bw CC as pre-treatment; STZ + CC2 = STZ and 2 mg/100 g bw CC as pre-treatment; STZ + lCC1 = STZ and pre-treatment with 1 mg/100 g bw lCC; STZ + lCC2 = STZ and pre-treatment with 2 mg/100 g bw lCC. ^a p-values < 0.002 as compared to STZ-C group and ^a1 0.0350, ^a2 0.0088, ^a3 0.2502, ^a4 0.0409, and ^a5 0.0060, respectively; ^b p-values < 0.002 as compared to STZ + CC1 group excepting ^b1 0.2248, ^b2 0.0049, ^b3 0.4433, ^b4 0.0253, and ^b5 0.0088; ^c p-values < 0.002 as compared to STZ + CC2 group excepting ^c1 0.0253, ^c2 0.0845, and ^c3 0.0060; ^d p-values as compared to STZ + lCC1 group: ^d1 0.0476, ^d2 0.2502.

Figure 3

Variability of (a) glycemia, (b) AST (aspartate aminotransferase) and (c) alanine aminotransferase (ALT) by groups. C = control; STZ-C = streptozotocin control; STZ + CC1 = STZ and 1 mg/100 g bw CC as pre-treatment; STZ + CC2 = STZ and 2 mg/100 g bw CC as pre-treatment; STZ + lCC1 = STZ and pre-treatment with 1 mg/100 g bw lCC; STZ + nCC2 = STZ and pre-treatment with 2 mg/100 g bw lCC. ^a p-values < 0.002 as compared to STZ-C group; ^b p-values < 0.002 as compared to STZ + CC1 group excepting ^b1 0.0152, ^b2 0.0027, and ^b3 0.0060; ^c p-values < 0.002 as compared to STZ + CC2 group excepting ^c1 0.0040; ^d p-values < 0.002 as compared to STZ + lCC1 group excepting ^d1 0.0040.

Figure 4

Variability of matrix metalloproteinases (MMP) by groups: (a) MMP-2, (b) MMP-C = control; STZ-C = streptozotocin control; STZ + CC1 = STZ and 1 mg/100 g bw CC as pre-treatment; STZ + CC2 = STZ and 2 mg/100 g bw CC as pre-treatment; STZ + lCC1 = STZ and pre-treatment with 1 mg/100 g bw lCC; STZ + lCC2 = STZ and pre-treatment with 2 mg/100 g bw lCC. ^a p-values < 0.002 as compared to STZ-C group excepting ^a1 0.0181 and ^a2 0.0088; ^b p-values as compared to STZ + CC1 group of 0.0017 excepting ^b1 0.1797 and^b2 0.0027; ^c p-values as compared to STZ + CC2 group < 0.002 excepting ^c1 0.0553 and ^c2 0.0027; ^d p-value as compared to STZ + lCC1 group of 0.0017 excepting ^d1 0.0845.