Rats In Normal Control Group Research Articles

Therapeutic Potential of Curcumin, a Bioactive Compound of Turmeric, in Prevention of Streptozotocin-Induced Diabetes through the Modulation of Oxidative Stress and Inflammation.

This study evaluates the anti-diabetic potential and underlying mechanisms of curcumin in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were randomly divided into four groups: normal control, negative control (diabetic group), diabetic group receiving glibenclamide (positive control group), and curcumin plus STZ (treatment group). The anti-diabetic activities of curcumin were examined at a dose of 50 mg/kg body weight through physiological, biochemical, and histopathological analysis. Compared to the normal control group rats, elevated levels of glucose, creatinine, urea, triglycerides (TG), and total cholesterol (TC) and low levels of insulin were found in the negative control rats. Curcumin treatment showed a significant decrease in these parameters and an increase in insulin level as compared to negative control rats. In negative control rats, a reduced level of antioxidant enzymes and an increased level of lipid peroxidation and inflammatory marker levels were noticed. Oral administration of curcumin significantly ameliorated such changes. From histopathological findings, it was noted that diabetic rats showed changes in the kidney tissue architecture, including the infiltration of inflammatory cells, congestion, and fibrosis, while oral administration of curcumin significantly reduced these changes. Expression of IL-6 and TNF-α protein was high in diabetic rats as compared to the curcumin treatment groups. Hence, based on biochemical and histopathological findings, this study delivers a scientific suggestion that curcumin could be a suitable remedy in the management of diabetes mellitus.

Reduced circulating growth hormone and insulin-like growth factor-1 and delayed growth of premature rats are aggravated by longer daily duration of chronic intermittent hypoxia exposure.

This study mainly aimed to investigate the effect of daily duration of chronic intermittent hypoxia (CIH) exposure on circulating growth hormone (GH)/insulin-like growth factor-1 (IGF-1) concentrations and body weight changes of premature rats. 40 healthy male SD rats aged six weeks were enrolled in this study. These rats were randomly divided into four groups (n = 10 per group), including normal control (NC) group (normal oxygen exposure every day), CIH-1 group (daily CIH exposure for 2 h), CIH-2 group (daily CIH exposure for 4 h), and CIH-3 group (daily CIH exposure for 8 h). The serum GH/IGF-1 concentrations and body weights in all rats were determined after 30 days of normal oxygen or CIH exposure. No significant difference was found with respect to the baseline body weight among the four groups of rats. After establishments of animal models with a duration of 30 days, significant differences were found respect to body weight, body weight changes, and serum GH/IGF-1 concentrations among the four groups of rats with a same trend (all P < 0.05): the highest values were all in NC group rats, followed CIH-1 group, CIH-2 group, and CIH-3 group rats. Among all the rats, the body weight changes correlated significantly with both serum GH and IGF-1 concentrations (both P < 0.05). CIH decreases circulating GH/IGF-1 concentrations and causes growth delay in premature rats. Such effects could be aggravated by increased daily duration of CIH exposures.

Effects of SIRT1 in amygdala on chronic restraint stress-induced depression-like behaviors in rats

To investigate the effects of silent information regulator 1 (SIRT1) in amygdala on depression-like behaviors in rats using chronic restraint stress (CRS) as a model of depression. Sixty male SD rats were randomly divided into six groups (n=10 per group): control group (Control), chronic restraint stress group (CRS), CRS + fluoxetine-treated group (CRS + FLU), CRS + saline-treated group (CRS + NaCl), CRS + SIRT1-overexpression group (CRS + AAV-SIRT1), and CRS + empty vector group (CRS + AAV-EGFP). Except for the control group, rats from the other groups were exposed to chronic restraint stress for 21 days. After the modeling, rats in fluoxetine-treated group and saline-treated group were, respectively, treated with fluoxetine (10 mg/kg) or saline (10 mg/kg) by gavage every day for 3 weeks; AAV-SIRT1 or AAV-EGFP was, respectively, stereotaxically injected into the amygdala of rats in SIRT1-overexpression group and empty vector group, and the virus was expressed for 3 weeks. Rats in normal control group and CRS model group were not given any drug treatment. The depression-like behaviors of rats in each group were evaluated by sugar preference test (SPT), open field test (OFT) and forced swimming test (FST). SIRT1 expression in amygdala of rats was assessed by using immunoblot blotting. The number of SIRT1-positive cells in amygdala of rats was detected by immunofluorescence technique. Compared with the normal control group, the level of SIRT1 protein and the number of SIRT1+ cells in amygdala of the CRS-exposed rats were decreased significantly (P＜0.01), and CRS-exposed rats showed a significant decrease in sucrose preference (P＜0.01), less total horizontal distance (P＜0.01) and less time entered the center field (P＜0.01) in the OFT, a significant increase in the immobility time of the FST (P＜0.01). Fluoxetine treatment (P＜0.05, P＜0.01) or SIRT1 overexpression (P＜0.01) partially reversed the down-regulation of SIRT1 protein and SIRT1+ cells in amygdala of CRS-exposed rats and significantly improved the depression-like behaviors of CRS rats. Fluoxetine treatment partially reversed the down-regulation of SIRT1 level and the number of SIRT1+ in CRS rats, and significantly improved the depression-like behaviors. The antidepressant effect of fluoxetine treatment may be related to the up-regulation of SIRT1 in the amygdala of CRS-exposed rats.

Mechanistic Research into the Effects of the Jianpi Xiaozhi Formula on Liver Injury in Diabetic Rats.

Objective The purpose of this study was to explore the mechanism of Jianpi Xiaozhi Formula (JPXZF) action in attenuating liver injury in a rat model of type 2 diabetes mellitus (T2DM). Methods A rat model of T2DM was established. Forty-eight male Sprague–Dawley (SD) rats were randomly allocated to six groups: healthy untreated rats (normal control (NC)), rats with diabetes mellitus (DM), diabetic rats treated with low-dosage JPXZF (DM + JL), diabetic rats treated with an intermediate JPXZF dosage (DM + JM), diabetic rats treated with high-dosage JPXZF (DM + JH), and diabetic rats treated with 4-phenylbutyric acid (PBA) (DM + PBA). The rats in each group were given the indicated drugs for 8 weeks, and pathological changes in the liver tissues of each rat group were observed by haematoxylin-eosin (HE) staining. Reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting (WB) were performed to determine the expression of glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), family with sequence similarity 134, member B (FAM134B), P62, Beclin-1, and light chain 3II/I (LC3II/I) genes and proteins in the liver tissues of the rats in each group. Immunofluorescence was used to observe changes in FAM134B expression. Results After successfully establishing the rat model, RT-PCR assays revealed that, compared with those in the NC group rats, the expression levels of GRP78, ATF6, and P62 mRNA in the livers of the DM group rats were significantly increased, and the relative expression levels of FAM134B and Beclin-1 mRNA were significantly decreased. Compared with that in the DM group, the relative expression of GRP78, ATF6, and P62 mRNA in the liver of the rats in each JPXZF intervention group was decreased in a dosage-dependent manner, and the relative expression of FAM134B and Beclin-1 mRNA was increased significantly (p < 0.05). WB indicated that, compared with that in the NC group rats, the LC3II/I protein expression ratio in the liver of the DM group rats was significantly reduced, and the LC3II/I protein expression ratio in the liver of the rats in each JPXZF intervention group was significantly increased. In addition, the expression of the other measured proteins was consistent with that of the corresponding mRNA measured by RT-PCR (p < 0.05). The immunofluorescence assay results showed that FAM134B changes were consistent with the results obtained by RT-PCR and WB (p < 0.05). Conclusion Jianpi Xiaozhi Formula may be effective in treating liver injury in diabetic rats by regulating autophagy induced by endoplasmic reticulum stress (ERS).

Maternal Deprivation Increased Vulnerability to Depression in Adult Rats Through DRD2 Promoter Methylation in the Ventral Tegmental Area.

ObjectiveEarly life adversity is a risk factor for depression in adulthood; however, the underlying mechanisms are not well understood. This study aims to investigate the effect of DNA methylation of DRD2 gene on early life stress–induced depression in adult rats.MethodsNewborn Sprague–Dawley rats were randomly assigned to four groups: maternal deprivation group (MD), chronic unpredictable stress (CUS) group, maternal deprivation plus chronic unpredictable stress (MD/CUS) group, and normal control group (NOR). Behaviors were measured by open field test (OFT), sucrose preference test (SPT), and Original Research Article forced swimming test (FST). Fecal CORT level was detected by ELISA. Bisulfite amplicon sequencing PCR was used to assess methylation levels of DRD2 promoter.ResultsCUS and MD/CUS rats had a significantly shorter total distance, longer immobility time, and higher CORT level, while MD and MD/CUS rats had a significantly lower percentage of central distance, more feces, lower rate of sucrose preference, and lower levels of DRD2 protein and mRNA in the VTA than NOR rats. CUS rats showed a significantly higher DRD2 mRNA and protein levels in the VTA than NOR rats. CUS, MD, and MD/CUS rats showed a significantly higher level of DRD2 promoter methylation than NOR rats. CORT level was significantly correlated with the sucrose preference rate in SPT, the immobility time in FST, the total distance, and the number of fecal pellets in OFT. DRD2 protein level was significantly correlated with the sucrose preference rate and the number of fecal pellets. DRD2 mRNA level was significantly correlated with the percentage of central distance and the number of fecal pellets in OFT. The level of DRD2 promoter methylation was significantly correlated with the sucrose preference rate, immobility time, total distance, the percentage of central distance, and the number of fecal pellets.ConclusionsEarly life MD increased vulnerability to stress-induced depressive-like behavior in adult rats. Enhanced DRD2 promoter methylation in the VTA may increase the susceptibility to depression.

Venlafaxine inhibits neuronal apoptosis in a depression rat model via ERK1/ERK2 pathway

Purpose: To investigate the effects and mechanism of action of venlafaxine on neuronal apoptosis of depressed rats.&#x0D; Methods: Rats were randomly divided into normal control (NC) group, depressed rats (depression) group or venlafaxine-treatment group. Changes in body weight and sucrose preference ratio were recorded and behaviors in open field test (OFT) were observed in each group. Pathological changes in and the apoptosis rate of the cerebral neurons, and the activity of extracellular signal-regulated kinase 1 (ERK1)/ERK2 pathway were observed under a microscope.&#x0D; Results: At weeks 2 and 4, the body weight and water consumption of rats in depression group dropped below those of rats in NC group. On the other hand, at week 2, the body weight and water consumption of rats in venlafaxine-treatment group were significantly higher than those of rats in depression group (p &lt; 0.05). Besides, depression group had randomly arranged neuron cells and a thinner cell layer, while venlafaxine-treatment group had a relatively regular hippocampal neural cell arrangement and a thicker cell layer. Moreover, cell apoptosis rate was higher in depression group than in that NC group, and lower in venlafaxine-treatment group than that in depression group (p &lt; 0.05). Finally, the protein expressions of phosphorylated (p)-ERK1 and p-ERK2 were significantly higher in depression group than those in NC group (p&lt;0.05), and distinctly lower in venlafaxine-treatment group than those in depression group (p &lt;0.05).&#x0D; Conclusion: By suppressing the activity of ERK1/ERK2 pathway, venlafaxine relieves the symptoms of depression and repairs neuronal injuries in rats, thereby suppressing neuronal apoptosis. Thus, these findings provide a novel approach for the development of new antidepressants.

Ameliorative effect of piracetam on emamectin benzoate induced perturbations in the activity of lactate dehydrogenase in murine system

Emamectin benzoate (4´-deoxy-4´-epimethylaminoavermectin B1) is a macrocyclic lactone developed for the control of insect pests in edible plant crops. The current study was taken to assess the possible ameliorative effect of piracetam (P) on emamectin benzoate (EMB) induced alterations in energy metabolism in liver, kidney, testis, heart, cerebral cortex, cerebellum and muscle of rats. Rats of normal control group (N) received water and normal diet ad libitum and (EMB as well as EMB+P) group received 5 mg/kg bw emamectin benzoate via drinking water for 4 weeks. After four weeks of EMB treatment, rats of (EMB+P) received piracetam (500 mg/kg bw, iv) for 15 days. The results demonstrate that emamectin benzoate caused a significant increase in lactate dehydrogenase activity and the level of lactate indicating organ damage in treated animals. Piracetam, the so-called ‘nootropic’ drug is mainly used to treat cognitive impairment in aging, brain injuries, as well as dementia. In the present study piracetam treatment caused a significant inhibition of lactate dehydrogenase activity in liver, kidney, testis, heart, cerebral cortex, cerebellum and muscle of rats. The amelioration of toxic effects by piracetam treatment in EMB treated rats indicate that this drug has the potential to mitigate emamectin benzoate induced toxicity in mammalian systems.

Reliability study on establishing a rat tuberculosis wound model using Bacillus Calmette-Guérin

Objective: To evaluate the reliability of a rat tuberculous wound model established by injecting Bacillus Calmette-Guérin (BCG). Methods: The experimental research was conducted. According to the random number table, fifteen 6-week-old male Sprague-Dawley rats were divided into normal control group and infection group, with 3 rats in normal control group and 12 rats in infection group. Rats in infection group were injected with Freund's complete adjuvant, 3 weeks later, they were injected subcutaneously with BCG bacterial solution to establish a model of tuberculous wounds in rats; rats in normal control group did not receive any treatment. On the 8th, 15th, 32nd, and 43rd day of infection, the skin condition at the injection sites of the rats in infection group was observed roughly. Skin tissue at the injection sites of 3 rats in infection group at each corresponding time point stated above and skin tissue at the corresponding sites of the rats in normal control group were stained with hematoxylin-eosin to observe the cell arrangement, necrosis and inflammation. On 43rd day of infection, acid-fast staining was performed on the skin tissue at the injection sites of the rats in infection group to observe the distribution of bacteria. Results: On the 8th, 15th, 32nd, and 43rd day of infection, tuberculous wound lesions were gradually developed at the skin tissues at the injection sites of the rats in infection group. The cells of the diseased tissue of the rats in infection group arranged disorderly or concentrically, and the number of granulomas and necrotic cells gradually increased, while the skin tissue cells in the corresponding parts of the rats in normal control group arranged regularly with no inflammatory cell infiltration. On the 43rd day of infection, a large number of rod-shaped bacteria were observed in the skin tissue at the injection sites of the rats in infection group. Conclusions: The rat tuberculous wound model established using BCG is stable and reliable, which can meet the experimental requirements.

Effects of unification medication of glycyrrhizinate and 5‐ASA on expression of TNF‐α,IL‐8 and NF‐κB in rats model with ulcerative colitis

Objective To explore mechanism of molecule of glycyrrhizinate and 5-aminosalicylic acid(5-ASA) treating ulcerative colitis（UC） through observing expression of TNF-α,IL-8 and NF-κB in rats with UC induced by 2,4-dinitro-chlorobenzene and acetic acid. Method 50 male Wistar rats were randomly divided into 5 groups: normal control group, UC model group,5-ASA group, glycyrrhizinate group and unification medication group.(10 rats in each group). The rats in normal control group and UC model group were given normal saline, the rats in 5-ASA group were given 5-ASA (1ml/200g weight), the rats in glycyrrhizinate group were given glycyrrhizinate(1ml/200g weight), the rats in unification medication group were given 5-ASA(1ml/200g weight) and glycyrrhizinate(1ml/200g weight). Symptom of bowel complaint and hemafecia in rats was observed and the change of body weight was recorded every day.After 7 days, blood of rats were got, the level of TNF-α、IL-8 in the blood serum was evaluated by ELISA. Colons(8cm) of rats were got, score of colonic damage was determined, the level of NF-κB in colonic mucosa was determined by immunohistochemistry． Result In the stage of UC, score of colonic damage advanced obviously, the level of TNF-α，IL-8 in the blood serum and expression of NF-κB in colonic mucosa advanced obviously, and those were correlated with change of state of the illness; After using glycyrrhizinate or 5-ASA, score of colonic damage in every group degraded obviously, the level of TNF-α，IL-8 in the blood serum and expression of NF-κB in colonic mucosa descended obviously; The effects of unification medication of glycyrrhizinate and 5-ASA lowering the level of TNF-α，IL-8 in the blood serum and expression of NF-κB in colonic mucosa were more excellent than that of single sentero clyster by using 5-aminosalicylic acid or glycyrrhizinate (P<0.05) . Conclusion Unification utilizing glycyrrhizinate and 5-ASA had a good therapeutic action for rats with ulcerative colitis evoked by 2,4-Dinitro-chlorobenzene and acetic acid. Its mechanism of action might be to reduce damage of inflammation by suppressing of expression of TNF-α，IL-8 and NF-κB in rats .

Therapeutic effect of ursolic acid on fetal development in pregnant rats with gestational diabetes mellitus via AGEs-RAGE signaling pathway.

To investigate the effect of ursolic acid on the fetal development of gestational diabetes mellitus (GDM) caused by streptozotocin (STZ) and explore the potential mechanism for it. For the current experimental research, SD rats (pregnant animal) were used. STZ has been used to cause the diabetes mellitus in pregnant rats. Rats with evolved GDM were randomly divided and ursolic acid was given to pregnant rats in the experimental period up to 19days in a dose-dependent manner. Blood samples and fetal rats of all group rats were collected at 19days (pregnant rats), fetal rats and placental rats were weighted and the blood glucose, plasma insulin, C-peptide, and lipid parameters of pregnant women were estimated prior to delivery. Advanced serum glycation end-products (AGEs) were estimated at regular intervals in the heart and brain of pregnant rats. Monocyte Chemoattractant Protein-1 (MCP-1), NADPH oxidase 2 (Nox2), Role of advanced glycation end product (RAGE), Vascular endothelial growth factor (VEGF), p65, and vascular cell adhesion molecule 1 (VCAM-1) mRNA expression were estimated in the placenta. STZ-induced GDM pregnant rats showed significantly decreased placental weight and weight of fetal rats and dose-dependent ursolic acid treatment (p<.001) improved placental weight and weight of fetal rats at dose-dependent levels. After the ursolic acid treatment, serum blood glucose and lipid level were improved especially fasting blood glucose (FBG), high density lipoprotein (HDL), hepatic glycogen, fasting insulin (FINS), and serum insulin level and reached near to the normal control group rats. The antioxidant level of pancreas and liver were significantly (p<.001) reduced by the dose-dependent treatment of ursolic acid. Treatment with Ursolic acid moderately but not significantly decreases the risk of fetal development defects relative to the GDM group. The potential effect on fetal development in Pregnant Rats with Gestational Diabetes Mellitus via AGEs-RAGE signaling pathway was shown by Ursolic acid. PRACTICAL APPLICATIONS: As we know that the gestational diabetes mellitus increases worldwide day by day. In the current experimental study, we try to examine the gestational diabetic effect of ursolic acid. The finding of the current study showed the gestational diabetic protective effect in the female rats via AGEs-RAGE signaling pathway. The result showed the antioxidant, anti-inflammatory, and biochemical parameters. On the basis of the result, we can say that the ursolic acid can be the protective drug for treatment of gestational diabetes mellitus.

Effects of Catalpa Alcohol From Rehmannia glutinosa on Calcium-Binding Protein, Interleukin-1β, and Galectin-3 in Synovial Tissues of Rats With Knee Osteoarthritis

Objectives We aimed to evaluate the effects of catalpa alcohol from Rehmannia glutinosa on the expressions of calcium-binding protein (S100A12), interleukin-1β (IL-1β), and galectin-3 in the synovium of rats with early knee osteoarthritis (KOA). Methods Fifty-two adult male Wistar rats aged 3 to 8 weeks were divided into normal control (n = 16), model (n = 12), low-dose (n = 12), and high-dose groups (n = 12). On the 10th day after modeling, 6 rats in normal control group and 6 in the other 3 groups were randomly selected. X-ray and 3-dimensional computed tomography (3D CT) images of the left knee joint were taken under live anesthesia. The joint cavity of sacrificed rats was opened to observe cartilage surface. After 28 consecutive days of administration, the synovial tissue of left knee joint was collected. Results The S100A12, IL-1β, and galectin-3 levels in synovial tissue were detected by immunohistochemistry and ELISA. There were articular cartilage defects in left knees. Radiologic examination showed significant joint space narrowing and hyperplasia, and 3D CT joint space value decreased (P &amp;lt; 0.05). The Mankins and OARSI scores of synovial histopathology were significantly different (P &amp;lt; 0.05). The S100A12, IL-1β, and galectin-3 levels in synovial tissue of the model group significantly exceeded those of the normal control group (P &amp;lt; 0.01). Compared with the model group, such levels of low-dose (P &amp;lt; 0.05) and high-dose groups (P &amp;lt; 0.01) were significantly lower. Conclusions The S100A12, IL-1β and galectin-3 levels in synovium tissue decreased with rising concentration of catalpa alcohol from R. glutinosa. Therefore, this drug is potentially suitable for inhibiting an inflammatory response to delay the progression of KOA.

Effects of Dingkun Dan combined with Western medicine on endometrial β-catenin, VEGF and MMP-9 mRNA expression in rats with multiple lesions

The aim of this paper was to investigate the effect of Dingkun Dan on endometrial receptivity in rats with multiple lesions. Forty SD female rats with regular sexual cycle were randomly divided into 5 groups, control group, model group, progynova group, Dingkun Dan group and combination group. The thin endometrium model of kidney-yang deficiency was established in all the other rats except normal control group. The rats in normal control group were free to drink and eat; the rats in the model group were administered with distilled water; the rats in the progynova group were treated with progynova; rats in Dingkun Dan group were treated with Dingkun Dan, and the rats in combination group were treated with Dingkun Dan and progynova. After 15 days, serum levels of OPN, VEGF and MMP-9 were measured by ELISA. HE staining, immunohistochemistry and RT-PCR were used to analyze endome-trial morphology, endometrial thickness and the treatment mechanism of Dingkun Dan. As compared with the control group, the serum levels of OPN, VEGF and MMP-9 in the model group were significantly increased(P&lt;0.01). As compared with the model group, the serum levels of OPN and MMP-9 were decreased in Dingkun Dan group(P&lt;0.05, P&lt;0.01). As compared with the control group, endometrial stromal cells were fewer, the endometrium glands and blood vessels were sparse, and the endometrium was thinner significantly in the model group(P&lt;0.01). As compared with the model group, there were more endometrial glands, rich intimal vessels, and dense stromal cells in various treatment groups, and the endometrium were thickened significantly in the treatment groups(P&lt;0.01). As compared with the control group, the expression area of CK19 in the model group was decreased significantly(P&lt;0.01). As compared with the model group, the expression area of CK19 in each treatment group was increased significantly(P&lt;0.05). As compared with the control group, endometrial β-catenin and MMP-9 mRNA expression levels were increased significantly in the model group(P&lt;0.05), while VEGF mRNA expression was decreased(P&lt;0.05). As compared with the model group, MMP-9 mRNA expression was decreased significantly in the progynova group and the combination group(P&lt;0.05). Dingkun Dan combined with progynova can improve endometrial receptivity by up-regulating expression of β-catenin, VEGF mRNA and down-regulating the expression of MMP-9 mRNA in the injury rats.

Effects of resveratrol on bone metabolism and bone turnover related indexes in ovariectomized osteoporosis rats

This study aimed to investigate the effects of resveratrol (RES) on bone metabolism and bone turnover related indexes in ovariectomized osteoporosis rats. 48 clean grade adult healthy unmated female SD rats were randomly divided into 6 groups, including normal control group (NCG), osteoporosis model group (OP MG), estrogen treatment group (17β-E2 group), RES low dose group (RES-L), RES medium-dose group (RES-M) and RES high dose group (RES-H). The rats in NCG and OP MG were given distilled water once a day and the rats in the other two groups were given 17β-E2 and resveratrol respectively. The levels of serum calcium (S-Ca), serum phosphorus (S-P), urinary calcium (U-Ca/Cr) and urinary phosphorus (U-P/Cr) were measured with an automatic biochemistry analyzer. The levels of serum osteocalcin (BGP), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), type I amino front-end peptide (PINP), type I collagen strong carboxyl peptide (CTX-I), urine deoxypyridinoline (DPD) and serum estrogen were detected by enzyme-linked immunosorbent assay (ELISA). In the OP group, the serum estrogen levels, S-Ca and S-P decreased significantly and the expression of U-Ca/Cr and U-P/Cr increased significantly (P&lt; 0.05). Compared with the OP group, the expression of S-Ca and S-P increased significantly and the expression of U-Ca/Cr and U-P/Cr decreased significantly (p&lt; 0.05) after treatment. The levels of TRAP, BGP, DPD and CTX-I in the OP group increased significantly (P&lt; 0.05). Compared with the OP group, the levels of TRAP decreased significantly (P&lt; 0.05). The levels of PINP and ALP in OP MG increased significantly (P&lt; 0.05). IP and ALP increased in the middle and lower levels (P&lt; 0.05). The bone mineral density of the OP group decreased significantly (P&lt; 0.05). Resveratrol can affect the changes in bone turnover in ovariectomized rats, promote bone formation in low estrogen state and inhibit bone resorption. Resveratrol may have a protective effect on the bone of ovariectomized rats.

Protective effect of Basella alba leaf against diabetic nephropathy in rats

Chronic hyperglycemic condition leads to development of diabetic nephropathy (DN). Basella alba is an important edible vegetable in India. Present study was conducted to inquire the effects of methanol extract from Basella alba leaf (MEBA) against diabetic nephropathy in rats. A single intraperitoneal injection of streptozotocin (55 mg/kg) was given to Wistar albino rats to induce diabetes. After 4 weeks of diabetes induction, the rats were divided into normal control group, disease DN group, MEBA treatment groups (200 and 400 mg/kg), metformin treatment group (150 mg/kg) and the treatment was continued for next 3 weeks. In MEBA treated groups there were marked improvements in blood glucose, ALP, ALT, total protein, serum lipid profile such as total cholesterol, triglyceride, HDL levels and renal functions such as urine volume, urinary protein excretion, serum creatinine, blood urea nitrogen, creatinine clearance as compared to non-treated DN group. There was significant rise in malonaldehyde level, and decline in acivites of superoxide dismutase and reduced Glutathione (GSH) of kidney in diabetic rats as compared to normal control group rats. The MEBA treated groups showed dose dependent restoration of altered oxidative stress parameters. Moreover, from renal histopathology it was evident that the abnormal thickening of Glomerular basement membrane in kidney of diabetic rats were improved in MEBA treated rats. From the present study it can be concluded that, Basella alba leaf has marked protective effect against diabetic nephropathy and proteinuria in rats.

Picroside-I attenuated isoproterenol-induced heart damage via modification of cardio-morphology, infarct size and inflammatory cascade

Purpose: To study the effect of picroside-I (PIC-I) on isoproterenol (ISO)-induced heart damage in rats through determination of infarct size, antioxidant enzymes, cardiac/inflammatory and apoptotic markers, as well as cardio-morphology.Methods: A total of 32 rats were divided equally into 4 groups. Rats in normal control group were treated with saline only, while myocardial infarction (MI) rat model was prepared by intraperitoneal (i.p.) injection of ISO at a concentration of 100 mg/kg. Rats pretreated with PIC-Iat dose 10 mg/kg (i.p) for 28 days and administered with isoproterenol. Another group of rats was administered only with PIC-I (10 mg/kg) for 28 days.Results: After 28 days of pretreatment with PIC-I, there were significant increases in arterial blood pressure and cardiac antioxidants, as well as marked decreases in infarct size, cardiac markers, inflammatory markers and apoptotic markers in rats with ISO-induced heart damage, when compared with rats given ISO alone. Rats administered PIC-I showed better histology, with reduced necrosis and prominent cardiac fibers.Conclusion: PIC-1 pre-treatment for 28 days significantly reversed elevations in infarct size, cardiac/inflammatory and apoptotic markers, and also improved antioxidant status and cardiacmorphology in rats with ISO-induced heart damage.&#x0D; Keywords: Picroside-I, Isoproterenol, Infarct size, Inflammation, Apoptosis

Adiponectin ameliorated pancreatic islet mitochondrial injury induced by chronic intermittent hypoxia

Objective: To explore the effect of adiponectin (APN) on islet injury induced by chronic intermittent hypoxia (CIH). Methods: Thirty-six SD rats were randomly divided into three groups: Normal control (NC), CIH, and CIH + APN groups. The rats in the CIH and CIH+APN groups received an intermittent hypoxia exposure while the rats in NC group received the room air only. The rats in CIH+APN group received the intravenous injection of APN. The intermittent hypoxia events persisted 8 hours a day and last for 35 days. The fasting blood glucose and fasting insulin were detected at the time of 0, 7, 14, 21, 28, and 35 day. After 35 days, the level of serum adiponectin, and adenosine triphosphate (ATP) level, superoxide dismutase (SOD), malondialdehyde (MDA), the mRNA levels of mitochondrial oxidative phosphorylation function and mitochondrial synthesis gene, and the protein level of mitochondrial and cytoplasmic cytochrome C of pancreatic islet were detected. Results: The glucose and insulin level had no statistically differences among three groups at different time points (all P>0.05). However, compared with NC and CIH+APN groups, CIH reduced the serum adiponectin [(7 265±2 209) ng/ml, (6 536±1 678) ng/ml vs (4 923±1 742) ng/ml, both P<0.05], ATP levels [(30.92±1.12) nmol/mg, (26.55±0.72) nmol/mg vs (20.22±1.47) nmol/mg, both P<0.05], mRNA levels of mitochondria oxidative phosphorylation function and mitochondrial synthesis gene, the activity of SOD, and the rate of mitochondrial/cytoplasmic cytochrome C protein level while increased the MDA level in pancreatic islet. Compared with NC group, the MDA level increased (P<0.05) and the APN level had no statistically difference, while the level of other indicators decreased in CIH+APN group (all P<0.05). Conclusion: APN ameliorates the pancreatic islet injury induced by CIH through inhibition of oxidative stress.

Comparative studies on the regulatory effects of raw and charred hawthorn on functional dyspepsia and intestinal flora

Purpose: To compare the effects of raw hawthorn (RH) and charred hawthorn (CH) on functional dyspepsia (FD) and intestinal flora (IF).Methods: A rat model of FD was established through use of a chronic stimulator. Rat models were evaluated by the rat’s physical state, body weight, diet, and histopathological examination. After RH or CH administration, the digestive function of the rats was evaluated by determining gastric emptying and intestinal propulsion rate, diversity of intestinal flora.Results: RH and CH both improved gastric emptying and intestinal propulsion rate in FD group when compared to control group (p &lt; 0.05). CH yielded higher treatment effectiveness than RH. Sixteen phyla of microbiomes were recognized from all samples. After FD model establishment, the relative abundance of Lactobacillus, Lachnospiraceae and Bacteroidales decreased compared to normal control rats. On the other hand, the relative abundance of Helicobacter and Bacteroides in the model control group increased compared to normal control. After RH and CH treatment, the relative abundance of all dysregulated phyla was restored to varying degrees, but the levels after CH treatment were similar to those of the normal control group.Conclusion: The relative abundance of intestinal flora of FD model rats is significantly different from that of rats in normal control group. Thus, RH and CH intervention improves digestive function, and the mechanisms may be related to adjustment of gut dysbacteriosis.Keywords: Raw Hawthorn, Charred Hawthorn, Functional dyspepsia, Intestinal flora

Design and Discovery of Novel 1,3,5-Triazines as Dipeptidyl Peptidase-4 Inhibitor against Diabetes

This study aims at synthesizing novel di-morpholine 1,3,5-triazine derivatives as antidiabetic agent via inhibition of dipeptidyl peptidase-4 (DPP-4). The molecules were developed via sequential nucleophilic reaction to afford target derivatives 5(a–f) and subsequently tested for inhibitory potency against DPP iso-enzymes, such as DPP-4, DPP-8, and DPP-9. The in vitro inhibition assay suggested that these derivatives prominently and selectively inhibit DPP-4 over ­DPP-8 and DPP-9. These molecules also showed no presence of cardiotoxicity, as confirmed by no activity against human Ether-à-go-go related gene channel. The study disclosed compound 5c as the most potent inhibitor of DPP-4 with IC₅₀ of 1.10 nmol/L as compared to the standard. Compound 5c was further evaluated for oral glucose tolerance test (OGTT) and antidiabetic activity in ICR mice and Wistar rats, respectively. In OGTT, compound 5c showed dose-dependent ­improvement of glucose tolerance with a maximum at 30 mg/kg. It also showed reduction in area under the curve from 0 to 120 min, similar to alogliptin (standard). In Wistar rats, compound 5c causes reduction in the blood glucose level, total cholesterol, triglyceride, low density lipoprotein (LDL) and very LDL level as compared to the diabetic control group, whereas the level of high-density lipoprotein was found to be increased. Compound 5c causes improvement in antioxidant defense mechanism, as confirmed via improving superoxide dismutase, catalase, glutathione peroxidase and reducing the malondialdehyde level as compared to normal control group rats.

Effect of TLR2 monoclonal antibody on new blood vessels and immune rejection response after keratoplasty

Purpose : To investigate the effect of TLR2 (toll-like receptor 2) monoclonal antibody on formation of new blood vessels and immune rejection response after keratoplasty. Methods : The rats were randomly divided into negative control group consisting of 16 rats from allogeneic corneal transplantation, and TLR2 monoclonal antibody group (study group) made up of 16 rats from allogeneic corneal transplantation treated with TLR2 monoclonal antibody. A group of 8 rats served as normal control. The study group was treated with 0.5 g·L-1 TLR2 monoclonal antibody through sub-conjunctival injection once daily for 5 days, while the normal control and negative control groups were given an equivalent volume of normal saline in place of TLR2. Corneal transparency and neovascularization were observed under slit lamp daily after operation, and scored using rejection index. Results : In the TLR2 monoclonal antibody group, the corneal structure was still clear, and only a few inflammatory cells infiltrated the stromal layer. There were trace amounts of TLR2 expression in the corneal epithelium of rats in normal control group, negative control group and TLR2 monoclonal antibody group. In the negative control group, the expression of TLR2 in the corneal epithelium and stromal cells significantly increased, especially in the stromal layer. Conclusion : TLR2 monoclonal antibody exerts a significant effect on neovascularization and immune rejection after corneal transplantation in rats. Thus, it may be clinically suitable for the prevention and treatment of rejection arising from corneal transplantation. Keywords : TLR2 monoclonal antibody, Corneal transplantation, Neovascularization, Immune rejection

Alterations of DNA Methylation at GDNF Gene Promoter in the Ventral Tegmental Area of Adult Depression-Like Rats Induced by Maternal Deprivation

Objective: To study the expression and DNA methylation of the Glial cell line-derived neurotrophic factor (GDNF) gene in the development of depression-like behaviors in rats experiencing maternal deprivation stress in early life.Methods: Newborn SD rats were randomly assigned to a normal control group (NOR) or maternal deprivation group (MD). An open field test (OPT), sucrose preference test (SPT), and a forced swimming test (FST) were used to evaluate rats' behaviors. Protein, mRNA, and methylation levels were measured by ELISA/Western blot, real-time PCR, and BiSulfte Amplicon sequencing PCR, respectively.Results: MD rats had significantly shorter total distance and more fecal pellets in OPT, a lower sucrose preference rate in SPT, and a longer immobility time in FST than NOR rats. Compared with NOR rats, MD rats showed a significantly higher plasma corticosterone (CORT) level. The levels of plasma dopamine (DA) and the GDNF were significantly lower in the MD rats than in NOR rats. In the ventral tegmental area (VTA) tissues, MD rats had a significantly higher level of methylation at the GDNF gene promoter than NOR rats. The expression of the GDNF mRNA and protein were significantly lower in MD rats than in NOR rats. The total distance was significantly correlated with plasma DA and GDNF, the DNA methylation level at the GDNF promoter and the GDNF mRNA level in the VTA. Fecal pellets showed a significant correlation with plasma CORT. The sucrose preference rate was significantly correlated with plasma DA, the DNA methylation level at the GDNF promoter and the GDNF mRNA level in the VTA. Immobility time showed a significant correlation with the plasma DA, the plasma GDNF and the GDNF mRNA level in the VTA.Conclusion: up-regulation of DNA methylation at the GDNF gene promotor and the subsequent down-regulation of the GDNF gene expression in the VTA, may be involved in the development of depression-like behaviors in rats experiencing MD in early life.