[Effect of salvia miltiorrhiza combined with roxadustat on wound healing of full-thickness skin defects in diabetic rats and its mechanism].

Objective: To explore the effect of salvia miltiorrhiza combined with roxadustat on wound healing of full-thickness skin defects in diabetic rats and its mechanism. Methods: This study was an experimental study. Twenty male 8-week-old Sprague-Dawley rats were used to successfully establish diabetic model, then full-thickness skin defect wounds on their backs were made. The rats were divided into normal saline group, roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group according to the random number table, with 5 rats in each group. Immediately after injury, the rats in normal saline group were given 5 mL normal saline by gavage, the rats in roxadustat alone group were given 1.5 mg/mL roxadustat suspension by gavage at 25 mg/kg, the rats in salvia miltiorrhiza alone group were given 18 mg/mL salvia miltiorrhiza suspension by gavage at 300 mg/kg, and the rats in roxadustat+salvia miltiorrhiza group were given 19.5 mg/mL roxadustat and salvia miltiorrhiza suspension at roxadustat 25 mg/kg and salvia miltiorrhiza 300 mg/kg. All were administered once a day for 2 weeks. The wounds at 0 (immediately), 4, 8, and 12 d after injury were observed, and the wound healing rates at 4, 8, and 12 d after injury were calculated (n=5). At 14 d after injury, abdominal aortic blood was collected, and hemoglobin, red cell count, and white blood cell count were detected (n=5). The wound tissue was collected for hematoxylin-eosin staining to observe inflammatory infiltration, skin tissue structure, and neovascularization, for Masson staining to observe the proportion of collagen fiber (n=3), for Western blotting to detect the protein expression levels of vascular endothelial growth factor (VEGF), CD31, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1ß (n=3), and for immunohistochemical staining to determine the protein expression levels of epidermal growth factor receptor (EGFR), hypoxia-inducible factor 1α (HIF-1α), and proliferating cell nuclear antigen (PCNA), with sample number of 3. Results: From 0 to 12 d after injury, the wound areas of rats in 4 groups were gradually decreased. At 4 d after injury, the wound healing rates of rats in salvia miltiorrhiza alone group and roxadustat+salvia miltiorrhiza group were significantly higher than those in normal saline group and roxadustat alone group (P<0.05). At 8 d after injury, the wound healing rates of rats in roxadustat alone group and salvia miltiorrhiza alone group were significantly higher than the rate in normal saline group (P<0.05), and the wound healing rate of rats in roxadustat+salvia miltiorrhiza group was significantly higher than the rates in the other 3 groups (with P values all <0.05). At 12 d after injury, the wound healing rates of rats in roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group were significantly higher than the rate in normal saline group (P<0.05). At 14 d after injury, there were no statistically significant differences in the hemoglobin or red blood cell count of rats in 4 groups (P<0.05). The white blood cell count of rats in roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group were respectively (24.3±1.2)×109/L, (26.3±2.4)×109/L, and (15.0±0.7)×109/L, which were significantly lower than (33.8±2.7)×109/L in normal saline group (P<0.05); the white blood cell count of rats in roxadustat+salvia miltiorrhiza group was significantly lower than that in roxadustat alone group and salvia miltiorrhiza alone group (with P values both <0.05). At 14 d after injury, a large number of inflammatory cell infiltration, disordered skin tissue structure, and few new blood vessels were observed in the wounds of rats in normal saline group; while a small amount of inflammatory cell infiltration, tight skin tissue structure, and rich neovascularization were observed in the wounds of rats in the other 3 groups. There were no statistically significant differences in the proportion of collagen fiber of wounds in rats among the 4 groups (P>0.05). At 14 d after injury, the protein expression levels of VEGF and CD31 in the wound tissue of rats in roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group were significantly higher than those in normal saline group (P<0.05), the protein expression level of CD31 in the wound tissue of rats in roxadustat+salvia miltiorrhiza group was significantly higher than the levels in roxadustat alone group and salvia miltiorrhiza alone group (with P values both <0.05). At 14 d after injury, the protein expression levels of IL-6, TNF-α, and IL-1ß in the wound tissue of rats in roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group were significantly lower than those in normal saline group (P<0.05); the protein expression levels of IL-6 and IL-1ß in the wound tissue of rats in roxadustat+salvia miltiorrhiza group were significantly lower than those in roxadustat alone group and salvia miltiorrhiza alone group (P<0.05); the protein expression level of TNF-α in the wound tissue of rats in roxadustat+salvia miltiorrhiza group was significantly lower than that in salvia miltiorrhiza alone group (P<0.05). At 14 d after injury, the protein expression level of EGFR in the wound tissue of rats in roxadustat+salvia miltiorrhiza group was significantly higher than the levels in the other 3 groups (with P values all <0.05); the protein expression levels of HIF-1α in the wound tissue of rats in roxadustat alone group and roxadustat+salvia miltiorrhiza group were significantly higher than the level in normal saline group (P<0.05), and the protein expression level of HIF-1α in the wound tissue of rats in roxadustat+salvia miltiorrhiza group was significantly higher than that in salvia miltiorrhiza alone group (P<0.05); there were no statistically significant differences in the protein expression level of PCNA in the wound tissue of rats in 4 groups (P>0.05). Conclusions: Roxadustat combined with salvia miltiorrhiza can promote the wound healing of full-thickness skin defects in diabetic rats by promoting blood vessel regeneration and reducing inflammatory response.

Antidiabetic Effect of Combined Leaf Extracts of Portulaca oleracea L., Beta vulgaris L., and Cichorium intybus L. in Streptozotocin-Induced Diabetic Rats.

Purslane (P), chard (CHA), and chicory (CHI) leaf extracts are individually and traditionally used in the treatment of diabetes mellitus. Polyphenols, flavonoids, the polyphenolic profile of the extracts, and their antioxidant activity were determined. This study evaluated the antidiabetic activity of combinations of these extracts in streptozotocin-induced diabetic rats. Diabetic groups were administered orally and daily for 40 days with the investigated extracts at 250 mg/kg body weight (b.w.) or metformin (100 mg/kg b.w.) as a drug. Fasting blood glucose, oral glucose tolerance, insulin, and fructosamine were assessed. The combined extracts with high levels of P or CHI exerted potent hypoglycemic activity compared with metformin in addition to the restoration of the histopathological changes in the liver and pancreas of diabetic rats to a near-normal state. Therefore, these combined extracts could be developed as natural drugs for diabetes.

Chromium Picolinate Protects against Testicular Damage in STZ-Induced Diabetic Rats via Anti-Inflammation, Anti-Oxidation, Inhibiting Apoptosis, and Regulating the TGF-ß1/Smad Pathway.

Chromium picolinate (CP) is an organic compound that has long been used to treat diabetes. Our previous studies found CP could relieve diabetic nephropathy. Thus, we speculate that it might have a positive effect on diabetic testicular injury. In this study, a diabetic rat model was established, and then the rats were treated with CP for 8 weeks. We found that the levels of blood glucose, food, and water intake were reduced, and body weight was enhanced in diabetic rats after CP supplementation. Meanwhile, in CP treatment groups, the levels of male hormone and sperm parameters were improved, the pathological structure of the testicular tissue was repaired, and testicular fibrosis was inhibited. In addition, CP reduced the levels of serum inflammatory cytokines, and decreased oxidative stress and apoptosis in the testicular tissue. In conclusion, CP could ameliorate testicular damage in diabetic rats, as well as being a potential testicle-protective nutrient in the future to prevent the testicular damage caused by diabetes.

The essential role of glutamine metabolism in diabetic cardiomyopathy: A review.

Diabetic cardiomyopathy (DCM) is a pathophysiological condition caused by diabetes mellitus and is the leading cause of diabetes mellitus-related mortality. The pathophysiology of DCM involves various processes, such as oxidative stress, inflammation, ferroptosis, and abnormal protein modification. New evidence indicates that dysfunction of glutamine (Gln) metabolism contributes to the pathogenesis of DCM by regulating these pathophysiological mechanisms. Gln is a conditionally essential amino acid in the human body, playing a vital role in maintaining cell function. Although the precise molecular mechanisms of Gln in DCM have yet to be fully elucidated, recent studies have shown that supplementing with Gln improves cardiac function in diabetic hearts. However, excessive Gln may worsen myocardial injury in DCM by generating a large amount of glutamates or increasing O-GlcNacylation. To highlight the potential therapeutic method targeting Gln metabolism and its downstream pathophysiological mechanisms, this article aims to review the regulatory function of Gln in the pathophysiological mechanisms of DCM.

Histologic and Biochemical Effect of Balanite aegyptiaca Fruit Extract on Alloxan-Induced Diabetes in Wistar Rats.

Background: Diabetes mellitus is among the most prevalent and costly chronic diseases in the world. Unfortunately, immediate prospects for a cure are not available. We aimed to determine the in vivo antidiabetic activity, histologic, and biochemical effect of Balanites aegyptiaca fruit extract on alloxan-induced diabetes in Wistar rats. Methods: Thirty-six Wistar rats were allotted into six groups (n=6). Group I was normal control. Group II was induced with diabetes but not treated.Groups III-V were induced with diabetes and treated with 100, 200, and 300 mg/kg extracts while Group VI was treated with Metformin once daily for 14 days. Animals were euthanized, and blood samples were collected for biochemical assays. The liver, kidney, pancreas, and testis were excised and processed by the paraffin wax method. Result: Oral administration of BA extract significantly (P<0.05) reduced blood glucose, liver enzymes, and creatinine levels in diabetic animals. The extract also improved the body weights of diabetic animals and microscopic anatomy of the pancreas, testis, liver, and kidney parenchyma compared to the control. Conclusion: Balanites aegyptiaca phytochemicals reduced blood glucose level and improved the histology of the liver, kidney, pancreas, and testis. Further study is recommended to identify the phytochemicals and mechanism of action.

Photobiomodulation, alone or combined with adipose-derived stem cells, reduces inflammation by modulation of microRNA-146a and interleukin-1ß in a delayed-healing infected wound in diabetic rats.

Diabetic wounds are categorized by chronic inflammation, leading to the development of diabetic foot ulcers, which cause amputation and death. Herewith, we examined the effect of photobiomodulation (PBM) plus allogeneic diabetic adipose tissue-derived stem cells (ad-ADS) on stereological parameters and expression levels of interleukin (IL)-1ß and microRNA (miRNA)-146a in the inflammatory (day 4) and proliferation (day 8) stages of wound healing in an ischemic infected (with 2×107 colony-forming units of methicillin-resistant Staphylococcus aureus) delayed healing wound model (IIDHWM) in type I diabetic (TIDM) rats. There were five groups of rats: group 1 control (C); group 2 (CELL) in which rat wounds received 1×106 ad-ADS; group 3 (CL) in which rat wounds received the ad-ADS and were subsequently exposed to PBM(890 nm, 80 Hz, 3.5 J/cm2, in vivo); group 4 (CP) in which the ad-ADS preconditioned by the PBM(630 nm + 810 nm, 0.05 W, 1.2 J/cm2, 3 times) were implanted into rat wounds; group 5 (CLP) in which the PBM preconditioned ad-ADS were implanted into rat wounds, which were then exposed to PBM. On both days, significantly better histological results were seen in all experimental groups except control. Significantly better histological results were observed in the ad-ADS plus PBM treatment correlated to the ad-ADS alone group (p<0.05). Overall, PBM preconditioned ad-ADS followed by PBM of the wound showed the most significant improvement in histological measures correlated to the other experimental groups (p<0.05). On days 4 and 8, IL-1 ß levels of all experimental groups were lower than the control group; however, on day 8, only the CLP group was different (p<0.01). On day 4, miR-146a expression levels were substantially greater in the CLP and CELL groups correlated to the other groups, on day 8 miR-146a in all treatment groups was upper than C (p<0.01). ad-ADS plus PBM, ad-ADS, and PBM all improved the inflammatory phase of wound healing in an IIDHWM in TIDM1 rats by reducing inflammatory cells (neutrophils, macrophages) and IL-1ß, and increasing miRNA-146a. The ad-ADS+PBM combination was better than either ad-ADS or PBM alone, because of the higher proliferative and anti-inflammatory effects of the PBM+ad-ADS regimen.

Evaluation of Antidiabetic Effect of Combined Leaf and Seed Extracts of Moringa oleifera (Moringaceae) on Alloxan-Induced Diabetes in Mice: A Biochemical and Histological Study.

Moringa oleifera (Moringaceae) is a medicinal plant rich in biologically active compounds. The aim of the present study was to screen M. oleifera methanolic leaf (L) extract, seed (S) extract, and a combined leaf/seed extract (2L : 1S ratio) for antidiabetic and antioxidant activities in mice following administration at a dose level of 500 mg/kg of body weight/day. Diabetes was induced by alloxan administration. Mice were treated with the extracts for 1 and 3 months and compared with the appropriate control. At the end of the study period, the mice were euthanized and pancreas, liver, kidney, and blood samples were collected for the analysis of biochemical parameters and histopathology. The oral administration of the combined L/S extract significantly reduced fasting blood glucose to normal levels compared with L or S extracts individually; moreover, a significant decrease in cholesterol, triglycerides, creatinine, liver enzymes, and oxidant markers was observed, with a concomitant increase in antioxidant biomarkers. Thus, the combined extract has stronger antihyperlipidemic and antioxidant properties than the individual extracts. The histopathological results also support the biochemical parameters, showing recovery of the pancreas, liver, and kidney tissue. The effects of the combined L/S extracts persisted throughout the study period tested. To the best of our knowledge, this is the first study to report on the antidiabetic, antioxidant, and antihyperlipidemic effects of a combined L/S extract of M. oleifera in an alloxan-induced diabetic model in mice. Our results suggest the potential for developing a natural potent antidiabetic drug from M. oleifera; however, clinical studies are required.

Potential therapeutic effect of medium chain triglyceride oil in ameliorating diabetic liver injury in a streptozotocin-induced diabetic murine model.

OBJECTIVE: Diabetes mellitus is one of the most commonly arising endocrine conditions. The disorder gives rise to enduring damage to a number of body tissues and viscera as a result of related macrovascular and microvascular complications. In patients who are unable to maintain their nutritional status independently, medium-chain triglyceride (MCT) oil is frequently added as a supplement to parenteral nutrition. The aim of the present research is to establish whether MCT oil has a therapeutic influence on the hepatic damage occurring in male albino rats as a result of streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: 24 male albino rats were randomized into four cohorts, i.e., controls, STZ-diabetic, metformin-treated and MCT oil-treated. The rodents were fed a high-fat diet for 14 days; a low dose of intraperitoneal STZ was then administered in order to induce diabetes. The rats were subsequently treated for 4 weeks with metformin or MCT oil. Analysis included an appraisal of liver histology and biochemical indices, i.e., fasting blood glucose (FBG), hepatic enzymes and glutathione (GSH), the latter obtained from hepatic tissue homogenate. RESULTS: A rise in FBG and hepatic enzymes was observed, but in the STZ-diabetic cohort, hepatic GSH levels were diminished. Treatment with either metformin or MCT oil led to a decline in FBG and hepatic enzyme titers whereas GSH concentrations increased. Liver histology findings were notable amongst rodents within control, STZ-diabetic and metformin-treated groups. The majority of histological changes were resolved following therapy with MCT oil. CONCLUSIONS: The anti-diabetic and antioxidant characteristics of MCT oil have been substantiated by this work. MCT oil led to a reversal of the hepatic histological changes seen in STZ-induced diabetes in rats.

Arabic gum ameliorates systemic modulation in Alloxan monohydrate-induced diabetic rats.

Medicinal plants are considered an alternative therapy for diabetes mellitus as they regulate glucose levels. Moreover, a variety of plants offer a rich source of bioactive compounds that have potent pharmacological effects without any negative side effects. The present study aimed to clarify the effects of Arabic gum/Gum Acacia (GA) on the biochemical, histopathological, and immunohistochemical changes observed in diabetic rats. Further, the anti-inflammatory activity of GA in response to diabetes, through inflammatory mediators analysis. Male rats were divided into four groups: untreated control, diabetic, Arabic gum-treated, and Arabic gum-treated diabetic rats. Diabetes was induced using alloxan. Animals were sacrificed after 7 and 21 days of treatment with Arabic gum. Body weight, blood and pancreas tissue samples were collected for analysis. Alloxan injection significantly decreased body weight, increased glucose levels, decreased insulin levels, and caused depletion of islets of Langerhans and ß-cell damage in the pancreas. Arabic gum treatment of diabetic rats significantly increased body weight, decreased serum glucose levels, increased insulin levels, exerts anti-inflammatory effect, and improved the pancreas tissue structure. Arabic gum has beneficial pharmacological effects in diabetic rats; therefore, it might be employed as diabetic therapy to reduce the hyperglycemic damage and may be applicable for many autoimmune and inflammatory diseases treatment. Further, the new bioactive substances, such as medications made from plants, have larger safety margins, and can be used for a longer period of time.

Influence of Murraya koenigii extract on diabetes induced rat brain aging.

Food supplements are used to improve cognitive functions in age-related dementia. This study was designed to determine the Murraya koenigii leaves' effect on Alloxan-induced cognitive impairment in diabetic rats and the contents of oxidative stress biomarkers, catalase, reduced glutathione, and glutathione reductase in brain tissue homogenates. Wistar rats were divided into seven groups (six rats per group). Group I received saline water (1 ml, p.o.), Diabetes was induced in Groups II-VII with Alloxan (120 mg/kg/p.o). Group III was provided with Donepezil HCl (2.5 mg/kg/p.o.), Group IV, V, VI, and VII with Murraya koenigii ethanol extract (200 and 400 mg/kg/p.o.) and aqueous extract (200 and 400 mg/kg/p.o.), respectively, for 30 days. Behavior, acetylcholinesterase (AChE) activity, oxidative stress status, and histopathological features were determined in the hippocampus and cerebral cortex. Administration of Murraya koenigii ethanolic and aqueous extracts significantly (P<0.05, P<0.001) increased the number of holes crossed by rats from one chamber to another. There was an increase in the (1) latency to reach the solid platform, (2) number of squares traveled by rats on the 30th day, and (3) percentage of spontaneous alternation behavior compared to the control group. Administration for successive days markedly decreased AChE activity (P<0.05), decreased TBARS level, and increased catalase, GSH, and GR levels. Murayya koenigii could be a promising food supplement for people with dementia. However, more research into sub-chronic toxicity and pharmacokinetic and pharmacodynamics interactions is essential.

Antidiabetic potential of Gymnemic acid mediated gold nanoparticles (Gym@AuNPs) on Streptozotocin-induced diabetic rats-An implication on in vivo approach.

Gymnemic acid is glycosides of triterpene with recognized and valuable applications for several chronic diseases, mainly diabetics. Despite this, it requires a delivery system in order to range its therapeutic target due to its limited solubility and bioavailability. Therefore, the Gymnemic acid mediated gold nanoparticles (Gym@AuNPs) was synthesised by eco-friendly approach. The synthesised Gym@AuNPs was confirmed by the colour change from light yellow to a deep ruby red. UV - visible spectroscopy results showed a strong narrow peak at 530 nm, confirming the controlled synthesis of monodispersed Gym@AuNPs. The reduction potential of standard Gymnemic acid (Gym) on synthesis of Gym@AuNPs was confirmed by using HPLC analysis. The spherical shaped Gym@AuNPs was observed by FESEM and HR-TEM studies with average size of 48.52 ± 5.53 nm. The XRD analysis exhibited a face-centered cubic (FCC) crystalline nature of Gym@AuNPs. The in vivo antidiabetic activity of Gym and Gym@AuNPs were validated using Streptozotocin induced diabetic Albino wistar rats. The Gym@AuNPs and Gym were regulates the glucose and lipid levels in experimental animals. The histopathology outcomes shown that the Gym@AuNPs were restoration of pancreatic islets cells in the animals. This investigation demonstrated that the Gym@AuNPs had the potential anti-diabetic properties.

Systemic Anti-Inflammatory Therapy Aided by Curcumin-Laden Double-Headed Nanoparticles Combined with Injectable Long-Acting Insulin in a Rodent Model of Diabetes Eye Disease.

Therapeutic interventions that counter emerging targets in diabetes eye diseases are lacking. We hypothesize that a combination therapy targeting inflammation and hyperglycemia can prevent diabetic eye diseases. Here, we report a multipronged approach to prevent diabetic cataracts and retinopathy by combining orally bioavailable curcumin-laden double-headed (two molecules of gambogic acid conjugated to terminal carboxyl groups of poly(d,l-lactide-co-glycolide)) nanoparticles and injectable basal insulin. The combination treatment led to a significant delay in the progression of diabetic cataracts and retinopathy, improving liver function and peripheral glucose homeostasis. We found a concurrent reduction in lens aggregate protein, AGEs, and increased mitochondrial ATP production. Importantly, inhibition of Piezo1 protected against hyperglycemia-induced retinal vascular damage suggesting possible involvement of Piezo1 in the regulation of retinal phototransduction. Histologic evaluation of murine small intestines revealed that chronic administration of curcumin-laden double-headed nanoparticles was well tolerated, circumventing the fear of nanoparticle toxicity. These findings establish the potential of anti-inflammatory and anti-hyperglycemic combination therapy for the prevention of diabetic cataracts and retinopathy.

Pharmacological Studies on the Antidiabetic, Antioxidant, and Antimicrobial Efficacies of Commiphora myrrha Resin in Streptozotocin-Induced Diabetes in Rats: A Preclinical Study.

Results: The aqueous extracts of MAE were phytochemically analyzed, and the results revealed the presence of high concentrations of tannins, sterols, and isoprenoids (terpenoids), while steroids and flavonoids were found in moderate concentrations. The plant extract showed promising inhibition of the growth of gram-positive and gram-negative pathogens. It also showed that MAE has potential antihyperglycemic and antioxidant activities. Microscopic examination of the pancreas showed degenerative changes and atrophy associated with dilatation of the exocrine ducts in the STZ-induced diabetic rats, while the treatment revealed that the Langerhans islets were close to normal without any histopathological alteration. Conclusion: The present results suggested that an aqueous extract of MAE could be considered an efficient antidiabetic, antioxidant, and antimicrobial treatment in the future.

The protective effect of green tea on diabetes-induced hepato-renal pathological changes: a histological and biochemical study.

We investigated the protective effect of green tea on diabetic hepato-renal complications. Thirty male Wistar rats were randomly divided into five equal groups: normal control, diabetic control, glibenclamide-treated, green tea-treated, and combined therapy-treated groups; ethical approval number "BERC-014-01-20." After eight weeks, animals were sacrificed by CO2 euthanasia method, liver and kidney tissues were processed and stained for pathological changes, and blood samples were collected for biochemical analysis. Diabetic rats showed multiple hepato-renal morphological and apoptotic changes associated with significantly increased some biochemical parameters, while serum albumin and HDL decreased significantly compared to normal control (p < .05). Monotherapy can induce significant improvements in pathological and biochemical changes but has not been able to achieve normal patterns. In conclusion, green tea alone has a poor hypoglycaemic effect but can reduce diabetic complications, whereas glibenclamide cannot prevent diabetic complications. The addition of green tea to oral hypoglycaemic therapy has shown a potent synergistic effect.

Effect of S-allylcysteine against diabetic nephropathy via inhibition of MEK1/2-ERK1/2-RSK2 signalling pathway in streptozotocin-nicotinamide-induced diabetic rats.

OBJECTIVE: In the current study, we evaluated the ameliorative effect of S-allylcysteine (SAC) against streptozotocin (STZ)-nicotinamide (NAD)-induced diabetic nephropathy (DN) in rats and also an attempt was made to establish the molecular mechanism of SAC. METHODS: DN rats were orally supplemented with SAC (150 mg/kg body weight) for a period of 45 days and the effect of SAC on urinary albumin excretion, metabolic parameters, and tubular injury biomarkers by ELISA, total levels and phosphorylation of MEK1/2, ERK1/2, and RSK2 by western blotting analysis in control and experimental rats were assessed. RESULTS: From this study, we observed that SAC considerably decreased polydipsia, poly urea, polyphagia, albuminuria and the levels of urinary N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, transforming growth factor-ß1 and SAC effectively altered the pathological changes in DN rats. SAC also reserved renal cortical phosphorylation of MEK1/2, ERK1/2 and RSK2. CONCLUSION: Hence this study recommended that SAC can successfully protect the DN through regulation of MEK1/2-ERK1/2-RSK2 signalling.

Bridelia ferruginea inhibits key carbohydrate digesting enzyme and intestinal glucose absorption and modulates glucose metabolism in diabetic rats.

The antidiabetic potentials of the dichloromethene, ethyl acetate, butanol and aqueous fractions of Bridelia ferruginea leaves were investigated using in vitro, ex vivo and in vivo models. In vitro and ex vivo antidiabetic activities revealed the butanol (BFBF) to be the most active of the fractions, and thus selected for in vivo study. Diabetes was induced using the fructose-streptozotocin model. Treatments with BFBF significantly reduced blood glucose level and improved glucose tolerance, serum insulin level and sensitivity as well as suppressed hyperlipidaemia and serum nephropathy markers. Histopathological analysis revealed the ability of BFBF to protect and regenerate pancreatic ß-cells. BFBF significantly elevated glutathione level, catalase and superoxide dismutase activities, while depleting MDA level in serums and kidney of diabetic rats. Phenols, steroids, terpenoids, aliphatic and aromatic compounds were identified in the fractions following GC-MS analysis. Overall, results from this study propose that BFBF possess potent antidiabetic activity.

Long-Term Alpha-Lipoic Acid (ALA) Antioxidant Therapy Reduces Damage in the Cardiovascular System of Streptozotocin-Induced Diabetic Rats.

Cellular damage, lipid oxidation and the action of inflammatory cytokines are implicated in the evolution of vascular complications associated with diabetes mellitus (DM) hyperglycemia. In contrast, alpha-lipoic acid (ALA) is a supplement with antioxidant and anti-inflammatory effects. This study aims to evaluate the overall effects of ALA supplementation by assessing its long-term systemic action on the vascular morphology of rats with induced diabetes. A total of 28 male rats were divided into 4 groups with seven animals each. For diabetes induction, two groups received streptozotocin. The animals in the lipoic and diabetic lipoic groups received ALA supplement. After 8 weeks the animals were anesthetized and blood collected was for hematological, biochemical and serological analyses. The thoracic aorta was removed, processed for paraffin and histological sections were stained for morphometric analysis. In diabetic groups, an improvement in hematological profile was observed, with platelet reduction in the diabetic lipoic group. ALA addition to the diet attenuated the negative effects in lipid profile; moreover, renal, hepatic and inflammatory parameters reduced or displayed values close to the values of the normal control. The anti-inflammatory effect of ALA was observed in diabetic animals, with a reduction of inflammatory citokines, accompanied by the improvement of morphological parameters in the aorta. In conclusion, long-term supplementation with ALA promoted systemic improvement, thus reducing the risk of vascular diseases. The changes in the renal and hepatic parameters without any negative impact in the hematological profile also show that ALA can be indicated as a low-risk prophylaxis or complementary therapy.

Stink bean (Parkia speciosa) empty pod: a potent natural antidiabetic agent for the prevention of pancreatic and hepatorenal dysfunction in high fat diet/streptozotocin-induced type 2 diabetes in rats.

The present study investigated the effect of polyphenol-rich extract of Parkia speciosa (PPS) against pancreatic and hepatorenal dysfunction in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes. Diabetic rats were treated with PPS (100 and 400 mg/kg) and glibenclamide. The results revealed that diabetic rats displayed marked hyperglycaemia, hyperlipidaemia, hypoinsulinemia as well as alterations in serum renal and kidney function markers. Furthermore, diabetic rats showed significant increase in hepatorenal level of malonaldehyde as well as suppression of antioxidant enzyme activities. Whereas, diabetic rats that received PPS displayed marked attenuation in most of the aforementioned parameters compared to the untreated diabetic rats. Additionally, histological examination revealed restoration of histopathological alterations of the pancreas, liver, and kidney of PPS treated diabetic rats. In conclusion, the results demonstrated that PPS could decrease serum lipids and blood glucose level, enhance insulin level and hepatorenal antioxidant capacity, as well as ameliorate hepatorenal dysfunction in rats.

Regulation of glucose transporter-4 intervention with S. saman leaves extract in streptozotocin-induced diabetic rats.

Diabetes mellitus is the leading disorder and affects more than millions of people worldwide. Nowadays, the usage of herbal drugs is said to control adiposity and hyperglycemia. The current research investigated the anti-adiposity and antidiabetic activity of S. saman leaf extract and bioactive compounds. Therefore, the results lower the sugar absorption into the blood and reveal the extract's antidiabetic properties. STZ-induced diabetic rats, Samanea saman methanolic extract show improvement in the parameters like fasting blood glucose levels, body weight, other biochemical parameters supported by the histopathological analysis, and an increase in serum levels in the experimental groups. The antioxidant plays a vital role by increasing SOD and catalase activity levels and decreasing lipid peroxidation levels. The methanolic extract protects the tissue from oxidation stress, which is responsible for the glycemic properties. According to the findings, diabetic-treated rats had overnight blood glucose levels lower and near standard biochemical markers. Histopathology of the liver, pancreas, kidneys, and adipose tissues supported the pharmacological observations. Further, we screened and documented S. saman extract used for in vitro and in vivo methods. In terms of effectiveness, the crude extracts exhibit 0.8-fold GLUT4 down-regulation. Consequently, this result contributes to clinical trials and develops antidiabetic therapy as a substitute for synthetic pharmaceuticals.

Investigation of the Chemical Composition, Antihyperglycemic and Antilipidemic Effects of Bassia eriophora and Its Derived Constituent, Umbelliferone on High-Fat Diet and Streptozotocin-Induced Diabetic Rats.

This study was designed to investigate the chemical profile, antihyperglycemic and antilipidemic effect of total methanolic extract (TME) of Bassia eriophora and isolated pure compound umbelliferone (UFN) in high-fat diet (HFD)- and streptozotocin (STZ)- induced diabetic rats. TME was subjected to various techniques of chromatography to yield UFN. Diabetes was induced after eight weeks of HFD by administration of STZ (40 mg/kg) intraperitoneally, and experimental subjects were divided into five groups. The diabetic control showed an increase in levels of blood glucose throughout the experiment. Treatments were initiated in the other four groups with glibenclamide (GLB) (6 mg/kg), TME (200 mg/kg and 400 mg/kg) and isolated UFN (50 mg/kg) orally. The effect on blood glucose, lipid profile and histology of the pancreatic and adipose tissues was assessed. Both 200 and 400 mg/kg of TME produced a comparably significant decrease in blood glucose levels and an increase in insulin levels with GLB. UFN began to show a better blood sugar-lowering effect after 14 days of treatment, comparatively. However, both 400 mg/kg TME and UFN significantly returned blood glucose levels in diabetic rats compared to normal rats. Analysis of the lipid profile showed that while HFD + STZ increased all lipid profile parameters, TME administration produced a significant decrease in their levels. Histopathological examinations showed that treatment with TME and UFN revealed an improved cellular architecture, with the healthy islets of Langerhans and compact glandular cells for pancreatic cells distinct from damaged cells in non-treated groups. Conversely, the adipose tissue displayed apparently normal polygonal fat cells. Therefore, these results suggest that TME has the potential to ameliorate hyperglycemia conditions and control lipid profiles in HFD + STZ-induced diabetic rats.