| Purpose：Present therapy for diabetes mellitus (DM) comprehend insulin and someoral hypoglycemic medications including sulphonylurea derivatives, α glucosidaseinhibitors, biguanides as well as thiazolidinediones. Although efficient, theses drugsgenerally have many undesirable adverse reactions such as constipation, obesity, drymouth, valvular heart disease and high blood pressure, etc, and some agents like thefirst-generation and second-generation sulphonylurea derivatives even destroy β cellof Langerhans islands when producing glycemic efffect, all of these side effectsgreatly limit their utilization in the treatment of DM. To date, traditional herbal agentshave received increased attention due to their well-known limited adverse effects.Therefore current work was carried out to examine the beneficial effects ofSchizandrae Fructus oil (SFO), an oily extract of Schisandra chinensis (Turcz.) Baill.,on the serological indicators of rats with type2diabetes, and furtherly, explore itspotential mechanism on two major grounds, i.e., insulin resistance and pancreatictissue apoptosis.Materials and Methods: Part I: Effects of Schizandrae Fructus oil on theserological indicators of rats with type2diabetes. Through high-fat diet plus low-dosetail vein injection of streptozotocin (STZ), type2diabetic rats were developed andwere divided into the following groups: model group, low-dose SFO group, high-doseSFO group and rosiglitazone group. Additionally, control group and SFO controlgroup, in which high dose of SFO was applied on normal rat were establishedaccordingly.8rats were included in each group and treated according to the protocolas belows: control group received a normal chow diet; SFO control group were treatedwith SFO when fed with a normal chow diet; model group continued on its high-fatdiet; low-dose SFO group and high-dose SFO group were treated with0.5and1.0mg/kg SFO, respectively; and rosiglitazone group recived30mg/kg rosiglitazone.SFO and rosiglitazone were both administered via epi-gastric route using a feeding needle. All the treatment was given daily for6weeks and subsequently,6rats pergroup were sampled and fasted up to12h for the examination of diverse serologicalindicators, including fasting blood glucose (FBG), lipidemic and insulinemic level.Furthermore, index of insulin resistance was estimated and calculated by thehomeostasis model assessment (HOMA). Part II: Effects of Schizandrae Fructus oilon the expresion of insulin resistance related adipokines and inflammatory markers inthe adipose tissue. Procedures including rat feeding, model developing, grouping andtreatment protocol were all in agreement with Part I. After6week treatment,6ratsper group were sampled and peritoneal adipose tissue were taken and subsequentlyreverse transcript polymerase chain reaction (RT-PCR) and westen blotting were usedto examine the expression of diverse insulin resistance related adipokines andinflammatory markers at the transcription and translation level, respectively. Thosesadipokines include glucose transporter-4(GLUT-4), adiponectin and retinal bindingprotein-4(RBP-4), and inflammatory makers are interleukin-6(IL-6), nuclear factorκB (NF-κB), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), C-reactiveprotein (CRP) and monocyte chemoattanctant protein-1(MCP-1). Part III: Effects ofSchizandrae Fructus oil on the pancreatic tissue morphology and its apoptosis relatedprotein expression, including cleaved caspase-3, Bcl-2and Bax. Procedures includingrat feeding, model developing, grouping and treatment protocol were all in agreementwith Part I. After6week treatment,6rats per group were sampled and pancreatictissue was removed for the subsequent test of pancreatic mophorlogy. Meanwhile,Gene expression of cleaved caspase-3, Bcl-2and Bax was also carried out by usingwestern blotting.Results:1Effects of Schizandrae Fructus oil on the serological indicators of rats withtype2diabetes.1.1Effects of Schizandrae Fructus oil on the general status of type2diabetic rats.Rats in control group were in great form with silky coats, quick reflex and bodyweight steadily creeping up. Rats in Schizandrae Fructus oil control group shared similar status with those in control group. Compared with control group, model grouprats exhibited such classical symptoms of DM as polyuria, polydipsia, polyphagia andweight loss. Moreover, these rats were slouchy, slow on the draw and had dim anddark fur. Compared with control group, the performance of rats in low-dose orhigh-dose Schizandrae Fructus oil was greatly improved, with high-dose group muchbetter than low-dose. The effect of high-dose Schizandrae Fructus oil treatment wascomparable to rosigilitazone treatment.1.2Effects of Schizandrae Fructus oil on fasting blood glucose of type2diabetic rats.Compared with control group, model group had markedly elevated fasting bloodglucose, which was significantly decreased by Schizandrae Fructus oil dosedependently. The fasting blood glucose level in high-dose Schizandrae Fructus oilgroup was similar to rosigilitazone group, almost declined to the normal level.1.3Effects of Schizandrae Fructus oil on lipidemic level of type2diabetic rats.Compared with control group, model group had markedly elevated levels of totalcholesterol, triglyceride, low density lipoprotein cholesterol as well as decreased levelof high density lipoprotein cholesterol, which were significantly reversed bySchizandrae Fructus oil dose dependently. The fasting lipidemic level in high-doseSchizandrae Fructus oil group was comparable to rosigilitazone group.1.4Effects of Schizandrae Fructus oil on FINS and HOMA-IR of type2diabetic rats.Compared with control group, while no significant changes of FINS and HOMA-IRwere observed in Schizandrae Fructus oil group, model group exhibited markablelyelevated FINS and HOMA-IR. These abnormal changes were significantlyameliorated, to varying degrees, by application of low or high dose of SchizandraeFructus oil or resiglitazone. The effects of high-dose Schizandrae Fructus oil werecomparable to resiglitazone and better than low-dose Schizandrae Fructus oil.2Effects of Schizandrae Fructus oil on the expression of insulin resistancerelated adipokines and inflammatory markers in the peritoneal adipose tissue.Reverse transcriptional polymerase chain reaction (RT-PCR) was introduced toexamine the influence of Schizandrae Fructus oil on the expression of variousadipokines and inflammatory markers in the gene (mRNA) transcription level. The results revealed that peritoneal adipose tissue from diabetic model group rats hadhigher mRNA expression of all inflammatory markers including IL-6, CRP, MCP-1,IL1β, TNF-α and NF-κB. Meanwhile, the expression Adipoctokines including andGLUT-4and Adiponectin were also decreased in mRNA level in the peritonealadipose tissue of diabetic model rats, whose expression in RBP-4were, however,lower than that from the control group. These abnormal changes were significantlyreversed, to varying degrees, by application of resiglitazone or low or high dose ofSchizandrae Fructus oil, which itself had no any influence on various geneexpressions. The effects of high-dose Schizandrae Fructus oil on the mRNAexpression were comparable to resiglitazone, oral hypoglycemic agent belonging tothiazolidinediones, and better than low-dose Schizandrae Fructus oil.Subsequently, Western blot was employed to examine the influence of SchizandraeFructus oil on the expression of various adipokines and inflammatory markers in theprotein translation level. The results demonstrate that all the alteration of theadipokines and inflammatory markers in protein (translation) were reconcilable withtheir changes in mRNA (transcription) level. That is, peritoneal adipose tissue fromdiabetic model group rats had higher protein expression of all inflammatory markersincluding IL-6, CRP, MCP-1, IL1β, TNF-α and NF-κB. Meanwhile, the expressionsof adipoctokines including GLUT-4and Adiponectin were also decreased in proteinlevel in the peritoneal adipose tissue of diabetic model rats, whose expression inRBP-4was, however, lower than that from the control group. These abnormalchanges were significantly reversed, to varying degrees, by application ofresiglitazone or low or high dose of Schizandrae Fructus oil, which itself had no anyinfluence on various gene expressions. The effects of high-dose Schizandrae Fructusoil on the protein expression were comparable to resiglitazone, oral hypoglycemicagent belonging to thiazolidinediones, and better than low-dose Schizandrae Fructusoil. 3Effects of Schizandrae Fructus oil on the pancreatic tissue morphology and itsapoptosis related protein expression.Application of Schizandrae Fructus oil could take a series of positive influence on thepathological changes including restore shrinked pancrease tissue and decreasednumber of β cells. Besides, Schizandrae Fructus oil greatly protected pancrease fromapoptotic damage, as demonstrated by diverse apoptosis relavant protein expression.Although Bax protein expression was unchanged, model group rats had higher proteinexpression of cleaved caspase-3and lower Bcl-2than control group. Both weregreatly corrected by application of low or high dose of Schizandrae Fructus oil orresiglitazone. The effects of high-dose Schizandrae Fructus oil were comparable toresiglitazone and better than low-dose Schizandrae Fructus oil. Schizandrae Fructusoil itself had no effect on caspase-3and lower Bcl-2expression.Conclusion:1. Schizandrae Fructus oil treatment could improve insulin resisrance, attenuatehyperglycemia and hyperlipidemia, and hyperinsulinemia in fat-fed stepzotocininduced type2diabetic rat model.2. Schizandrae Fructus oil treatment could produce beneficical effects on diabetes bycorrecting insulin resisrance associated gene expression.3. Schizandrae Fructus oil treatment could preserve pancreatic morphology, decreasepancreatic apoptosis by reducing cleaved caspase-3expressin and increasing Bcl-2. |
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