| Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin, or alternatively, when the body cannot effectively use the insulin it produces. Hyperglycaemia is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, which results in various vascular complications such as retinopathy, neuropathy, kidney failure, heart disease and stroke. Due to the huge medical expenditure and complicated pathobiology of diabetes, also adverse effect of diabetes drug, the research has directed to herb medicine to improve glucose control and lower the risk of its complications.Propolis, a resinous substance collected from the buds of certain trees by bees, is a traditional herb medicine in many countries. More than 300 components have been found in propolis, mainly composed of phenolic compounds, terpenes and essential oil. Propolis has been proved various bioactivities of antibacterial, antivirus, antifungal, immunoloregulatory, anti-oxidative, anti-inflammatory,hepatoprotective and anti-tumor, Our previous studies have shown that Chinese propolis helps to reduce fast blood glucose, improve oxidative stress and lipid metablisom in alloxan-induced diabetic rats. In addition, propolis intake by diabetic patients are proved to reduce blood glucose and glycosylated hemoglobin (HbAlc) level.Some reports suggested the chemistry of propolis varied with botonical source, geographical origins and collecting bees. The botanical difference is a key factor for chemical variability. Chinese propolis contains many kinds of flavonoids and phenolic acid esters.The major components in of Brazilian green propolis are terpenoids and prenylated derivatives of pcoumaric.To guarantees the quality, safety and efficacy of propolis, we compared the antidiabetic effect of Chinese propolis and Brazilian green propolis in this experiment. We induced type 1 diabetes mellitus (T1DM) rat model by injection of streptozotcin, and type 2 diabetes mellitus (T2DM) rat model by injection of streptozotcin plus high lipid diet feeding. By determination of urine, blood and hepatorenal biochemical indicators and biopsy, we analyzed the effect of propolis on glycometabolism, lipid metabolism, protein metabolism, oxidative stress and hepatorenal function in T1DM and T2DM rats. To reveal the possible protection mechanism of propolis on diabetic kidney injury in T2DM rats, we measured the expression of pro inflammatory cytokines IL-2, IL-6 and TNF-a protein by ELISA. The TGF-β1 expressions were measured using immunohistochemical staining and the MCP-1 mRNA and protein kinase C (PKC) mRNA was measured using RT-PCR. The results are as follows:1. Effects of propolis on TIDM ratsGrouping and Administration:TIDM rats were randomly divided into groups of model, A1, A2, B1, B2 and positive groups, eight rats each group. Additional 8 rats without STZ induction were selected as normal group. Each rat of Al group was received a dose of 10 mg Chinese propolis per 100 g body weight; Each rat of A2 group was received a dose of 5 mg Chinese propolis per 100 g body weight; Each rat of B1 group was received a dose of 10 mg Brazilian propolis per 100 g body; Each rat of B2 group was received a dose of 5 mg Brazilian propolis per 100 g body; Each rat of positive group was received a dose of 1 mg glucobay perl00 g body weight; Each rat of model group and normal group was received a dose of 1 ml physiological saline per100 g body weight. Administration last continuously eight weeks intragastrically twice daily.Results:1) Body weight and glycometabolism:Chinese propolis and Brazilian green propolis obviously inhibited weight loss and blood glucose increment in TIDM rats in a dose-dependent effect, and Chinese propolis had a slightly better effect than Brazilian green propolis; China Propolis can significantly lower HbAlc levels in a dose-dependent effect; 2) Lipid metabolism:Compared with normal rats, model rats had an obviously elevated serum TC and TG level. High dose Chinese propolis obviously reduced serum TC levels in T1DM rats; 3) Serum oxidative stress: Compared with normal rats, model rats had an obviously elevated MDA, NO and NOS level and reduced SOD and CAT level. Chinese propolis and Brazilian green propolis improved serum oxidative damage in TIDM rats by a dose-independent effect. High dose Chinese propolis significantly reduced serum MDA level, whereas low dose Chinese propolis markedly raise serum SOD level. Brazilian propolis increased serum SOD level significantly. In addition, Brazilian green propolis can apparently reduce serum NOS level; 4) Hepatic function and histological injury: The content of AST and ALT in model rats increased significantly compared with normal rats. Chinese propolis and Brazilian green propolis can significantly reduced AST and ALT level. As to hepatic oxidative damage, Chinese propolis suppressed the hepatic MDA level and showed no effect on antioxidant enzyme, whereas Brazilian green propolis inhibited lipid peroxidation and improve the activity of antioxidant enzyme. By histological observation, model rats showed mild hepatic injury, and both Propolis and glucobay helped to recover hepatic injury.5) Renal function andhistological injury:The level of BUN, urine albumin and urine protein in model group were significantly higher than those in normal group. Treated with Chinese propolis and Brazilian propolis reduced urine albumin. Brazilian green propolis also reduced serum BUN and urine protein level significantly. As to renal oxidative stress, propolis can reduce renal MDA and GSH-px level and raise CAT markedly. By histological observation, model rats showed moderate renal injury, and both Propolis and acarbose helped to recover hepatic injury.2. Effects of propolis on T2DM ratsGrouping and Administration:T2DM rats were randomly divided into groups of model, A, B and positive groups, eight rats each group. Additional 8 rats without STZ induction were selected as normal group. Each rat of A group was received a dose of 5 mg Chinese propolis per 100 g body weight; Each rat of B group was received a dose of 5 mg Brazilian propolis per 100 g body; Each rat of positive was received a dose of 1 mg pioglitazonehcl per100 g body weight; Each rat of model group and normal group was received a dose of 1 ml physiological saline per100 g body weight. Administration last continuously eight weeks intragastrically twice daily.Results:1) Body weight:Chinese propolis and Brazilian green propolis had an indistinctive inhibition on weight loss of T2DM rats. A group rats (treated with Chinese propolis) is obviously heavier than model rats at Week 8; 2) Glycometabolism:Chinese propolis lowered FBG of T2DM significantly during the previous four weeks and showed no marked effect during the following four weeks, whereas Brazilian green propolis had no obvious effect. China Propolis can significantly lower HbAlc levels at Week 4 and Week 8, whereas Brazilian green propolis reduced HbAlc levels at Week 4; 3) Lipid metabolism:Compared with normal rats, model rats had an obviously elevated serum TC, LDL-C and TG level, Chinese propolis obviously reduced serum TG and LDL-C levels in early phase of T2DM rats; 4) Serum oxidative stress:Compared with normal rats, model rats had an obviously elevated serum MDA level and reduced GSH-px level. Chinese propolis increased serum GSH-px level and reduced serum MDA level significantly, whereas Brazilian green propolis improved serum CAT level and reduced serum MDA level significantly; 5) Insulin and protein metabolism:Compared with normal rats, T2DM rats had a normal insulin level and reduced serum protein and albumin level. Propolis showed no effect on insulin. Chinese propolis can raise serum protein and albumin level, whereas Brazilian propolis can raise serum albumin level; 6)Hepaticfunction and histological injury:Obviously reduced serum AST level and increased ALT level of model rats meant damaged hepatic function, propolis-treated rats had a significantly reduced ALT level. By histological observation, model rats liver showed severe adipose infiltration. Propolis and positive drug helped to recover hepatic injury.7) Renal function and histological injury:The level of serum BUN, CCR and urine albumin in model group were significantly higher than those in normal group. Propolis treating can reduce serum BUN and urine albumin. As to renal oxidative stress, Chinese propolis can reduce renal MDA and increase CAT level significantly, whereas Brazilian propolis can reduce renal MDA and increase GSH-px level. By histological observation, model rats showed moderate renal injury and propolis and acarbose helped to recover hepatic injury.3. Protection mechanism of propolis on T2DM rat kidneyAt Week 8 we measured kidney hemodynamics of T2DM rats by laser Doppler flowmetery. Once rats were sacrificed, kidney was removed to determine relevant indicators. 1) Inflammation:Compared with normal rats, model rats had an obviously increased serum CRP level and renal proinflammatory cytokines. Brazilian green propolis can reduce serum CRP levels significantly. As to renal inflammation, Chinese propolis can markedly reduce renal IL-2, IL-6 and TNF-a levels, whereas the Brazilian green propolis can effectively inhibit the expression of TNF-a protein and MCP-1 mRNA; 2) Renal hemodynamics:Diabetes/high glucose can change rats renal hemodynamics. Chinese propolis can significantly improve the abnormal renal hemodynamics in T2DM rats by increasing renal blood flow and reducing renal vascular resistance and filtration fraction, whereas Brazilian propolis showed little effect; 3) Expression of renal PKC mRNA:Both Chinese propolis and Brazilian green propolis inhibit the PKC mRNA expression in T2DM rat kidney; 4) Expression of renal TGF-β1:Immunohistochemical staining and image analysis showed that model rats had a significantly higher renal TGF-β1 expression compared with normal group. Brazilian green propolis and positive drug can improve total optical density, taverage optical density and positive index in rat kidneys, whereas Chinese propolis showed an inapparent improvement.In summary, Chinese propolis and Brazilian green propolis can effectively alleviate the diabetes-induced metabolism disorders in rats. Propolis can improve weight loss, glycometabolism, lipid metabolism, protein metabolism and serum, liver and kidney oxidative stress in diabetic rats. Determination of relevant indicators and histological observation suggested the protection effect of propolis on hepatorenal function in diabetic rats. In comparison, Chinese propolis showed a better hypoglycemic and hepatic-protection effect than Brazilian propolis, whereas Brazilian green propolis had a more comprehensive antioxidant effect. By measuring the renal proinflammatory cytokines, hemodynamics, PKC mRNA, and TGF-β1 protein, we analyzed a possible protection mechanism of propolis on diabetic nephropathy.
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