STZ-induced Damage Research Articles

Antihyperglycemic activity of a novel polyherbal formula (HF344), a mixture of fifteen herb extracts, for the management of type 2 diabetes: Evidence from in vitro, ex vivo, and in vivo studies

Antihyperglycemic effects of a novel polyherbal formula (HF344), comprising fifteen Thai herbal extracts, were elucidated for pharmacological mechanisms and potential for managing type 2 diabetes mellitus, by employing in vitro, ex vivo, and in vivo approaches. LC/MS analysis of HF344 extract revealed several phytoconstituents, with piperine identified as the major active compound. HF344 extract significantly enhanced insulin secretion in RINm5F cells in vitro and inhibited glucose uptake into the everted sacs of the mouse small intestine ex vivo in a concentration-dependent manner compared to the control (p < 0.05). It exhibited potent α-glucosidase inhibition in vitro, with an IC50 of 96.74 μg/mL. Moreover, HF344 extract upregulated mRNA levels of GLUT1 in L6 skeletal myoblasts, suggesting increased glucose uptake into skeletal muscle. In addition, in vivo antihyperglycemic effects were assessed in streptozotocin (STZ)-nicotinamide (NA)-induced diabetic mice. Acute oral toxicity testing confirmed the HF344 extract's safety, with an LD50 exceeding 2000 mg/kg. Oral administration of HF344 extract (500 and 1000 mg/kg) in STZ-NA-induced diabetic mice significantly reduced the area under the fasting blood glucose (FBG)-time curve (AUC) in the oral glucose tolerance test (OGTT) model and treatment for 28-day reduced the FBG levels as compared with control (p < 0.05). This was accompanied by increased serum insulin levels and improved insulin resistance. HF344 extract also demonstrated a concentration-dependent inhibitory effect on malondialdehyde (MDA) production in vitro, with an IC50 of 7.24 μg/mL. Oral treatment with HF344 extract decreased MDA production in the homogenized muscle ex vivo collected from STZ-NA-induced mice. Furthermore, pretreatment with HF344 extract effectively restored the survival of RINm5F cells from STZ-induced damage. These findings suggest that HF344 is a promising polyherbal formula for managing blood glucose levels, enhancing insulin production, and providing antioxidant benefits in T2DM. Further research is required to evaluate the clinical efficacy and safety profiles of HF344.

Moringa oleifera gum effect on blood sugar levels and rat pancreas histology induced by Streptozotocin

Moringa gum is a product that people can use as an anti-hyperglycemic agent. This study aimed to determine the effectiveness of Moringa gum in reducing blood sugar levels and improving the histology structure of the rat pancreas induced by streptozotocin (STZ). This study used 21 male rats divided into 3 groups including control, diabetes (STZ), and diabetes (STZ + 3% Moringa gum). STZ treatment at a single dose (45 mg/kg BW) was given intraperitoneally, while Moringa gum was given through drinking water for 2 weeks. Blood sugar levels were measured on days 0, 7th, 14th, 21st, and 28th. The results showed that STZ administration induced diabetes in rats with blood sugar levels of 487 mg/dL on the 14th day. Moringa gum administration was able to reduce blood sugar levels on days 21st and 28th respectively to 306 and 234 mg/dl. The histology structure of the pancreas of rats treated with gum also showed improvement. This study concludes that Moringa gum is effective in lowering blood sugar levels in rats even though it still does not show normal blood sugar levels, and can repair STZ-induced damage to the histology structure of the rat pancreas.

Effects of Caraway and (S)-(+)-carvone Extract on the Expression of Genes Coding Key Glycolytic Enzymes in Streptozotocin-induced Diabetic Rats

Background: Diabetes mellitus is a metabolic disorder causing dysfunctional regulation of carbohydrate metabolism and contributing to multiple serious health challenges worldwide. Aims: This research explores the effect of caraway hydroalcoholic extract and (S)-(+)-carvone on the transcription of genes coding for key glycolytic enzymes in the liver of the diabetic rat treated with streptozotocin (STZ). Methods: In this experimental study, diabetes was established in four groups of rats by injecting 45 mg/kg of STZ intraperitoneally. Further normal rats that were not injected formed the control group. Over four weeks, the effects of caraway hydroalcoholic extract (150 and 250 mg/kg) and carvone (100 mg/kg) were evaluated using PCR and histopathological evaluation, specifically in the form of effects on the transcription process of genes coding key glycolytic enzymes in the liver of the diabetic rats. Results: Over the four-week assessment period, rats’ food intake, and therefore blood glucose levels, were decreased through the daily oral administration of carvone and caraway extract (150 mg/kg) when compared to those administered with further STZ. The expression of key glycolytic enzymes, including glucokinase, pyruvate kinase, and phosphofructokinase 1 in the liver of diabetic rats was restored to near-normal levels by carvone and caraway extract, especially at the 150 mg/kg dose. Histopathological evaluation of diabetic rat liver demonstrated that administration of caraway extract and carvone decreased the STZ-induced damage to liver tissue. Conclusion: 150 mg/kg of caraway extract strongly regulates glycolysis by regulating the gene expression of key glycolytic enzymes in diabetic rats.

Rosemarinic acid protects β-cell from STZ-induced cell damage via modulating NF-κβ pathway

Rosmarinic acid (RA), a natural ester phenolic compound, is known to have antioxidant and anti-inflammatory properties. RA has also been reported to exhibit a hypoglycemic effect; however, the mechanisms underlying this effect have yet to be investigated. Therefore, the present study focused on the anti-diabetic effects and mechanism of RA in INS-1 cells using in vitro model. Streptozotocin (STZ) at a concentration of 3 mM was applied to INS-1 cells for 4 h to create a diabetic model. The cells were pretreated for 24 h with various concentrations (1 and 2.5 μM) of RA. The Cell viability, glucose-stimulated insulin secretion (GSIS), glucose uptake, lipid peroxidation, reactive oxygen species (ROS), apoptosis, and protein expression of Bcl-2, NF-κB, 1L-1β, and PARP were assessed. Results showed that STZ-treated INS-1 cells exhibited reduced cell viability, insulin release, insulin content, glucose uptake, and elevated MDA and ROS levels. Cells pretreated with RA maintained the function and morphology of β-cells against STZ-induced damage. Moreover, RA sustained high protein expression levels of Bcl-2 and low expression levels of NF-κB, IL-1β, and PARP. In conclusion, RA preserved β-cells function against STZ-induced damage by altering NF-κB and Bcl-2 pathways.

Dose-dependent progression of multiple low dose streptozotocin-induced diabetes in mice.

This study investigated the effects of different multiple low doses of streptozotocin (STZ), namely 35 and 55 mg/kg, on the onset and progression of diabetes in mice. Both doses are commonly used in research, and while both induced a loss of beta cell mass, they had distinct effects on whole glucose tolerance, beta cell function and gene transcription. Mice treated with 55 mg/kg became rapidly glucose intolerant, whereas those treated with 35 mg/kg had a slower onset and remained glucose tolerant for up to a week before becoming equally glucose intolerant as the 55 mg/kg group. Beta cell mass loss was similar between the two groups, but the 35 mg/kg-treated mice had improved glucose-stimulated insulin secretion in gold-standard hyperglycemic clamp studies. Transcriptomic analysis revealed that the 55 mg/kg dose caused disruptions in nearly five times as many genes as the 35 mg/kg dose in isolated pancreatic islets. Pathways that were downregulated in both doses were more downregulated in the 55 mg/kg-treated mice, whereas pathways that were upregulated in both doses were more upregulated in the 35 mg/kg treated mice. Moreover, we observed a differential downregulation in the 55 mg/kg-treated islets of beta cell characteristic pathways, such as exocytosis or hormone secretion. On the other hand, apoptosis was differentially upregulated in 35 mg/kg-treated islets, suggesting different transcriptional mechanisms in the onset of STZ-induced damage in the islets. This study demonstrates that the two STZ doses induce distinctly mechanistic progressions for the loss of functional beta cell mass.

Effect of Hesperidin on Sciatic Nerve Damage in STZ-Induced Diabetic Neuropathy: Modulation of TRPM2 Channel.

Diabetic neuropathy (DNP) is a severe complication of diabetes mellitus. In this study, we examined the potential of hesperidin (HES) to attenuate DNP and the involvement of the TRPM2 channel in this process. The rats were given a singledose of 45mg/kg of streptozotocin (STZ) intraperitoneally to induce diabetic neuropathic pain. On the third day, we confirmed the development of diabetes in the DNP and DNP + HES groups. The HES groups were treated with 100mg/kg and intragastric gavage daily for 14days. The results showed that treatment with HES in diabetic rats decreased STZ-induced hyperglycemia and thermal hyperalgesia. Furthermore, in the histopathological examination of the sciatic nerve, HES treatment reduced STZ-induced damage. The immunohistochemical analysis also determined that STZ-induced increased TRPM2 channel, type-4 collagen, and fibrinogen immunoactivity decreased with HES treatment. In addition, we investigated the TRPM2 channel activation in the sciatic nerve damage mechanism of DNP model rats created by STZ application using the ELISA method. We determined the regulatory effect of HES on increased ROS, and PARP1 and TRPM2 channel activation in the sciatic nerves of DNP model rats. These findings indicated that hesperidin treatment could attenuate diabetes-induced DNP by reducing TRPM2 channel activation.

Isolated fractions of Aloe vera carbohydrate ameliorate streptozotocin-induced pancreatic β-cell damage and bidirectionally regulated AMPK activity

The present study was to evaluate the effect of isolated fractions of enriched Aloe vera carbohydrate through diethylaminoethyl cellulose (DEAE-sephacel) on pancreatic β-cell protective effect in streptozotocin (STZ) induced Rin-m5F cells and the induction of AMPK activity in HepG2 cells. The isolated fractions were analyzed using Dionex-ion exchange chromatography for their sugar composition. The six isolated fractions of enriched Aloe vera carbohydrate (IFEAC) F1, F4, F5 and F6, F9, F10 exhibited significant inhibition of α-amylase and α-glucosidase activity and increased glucose uptake in yeast cells. Moreover, in these six fractions, F1, F4 and F9 showed a significant increase in BrdU and insulin levels and decreased inflammatory mediators in STZ-induced RIN-m5F cells. These fractions also exhibited significant bidirectional regulation of AMPK activity based on alteration in glucose concentrations in HepG2 cells. These results conclude that the IFEAC exhibited a potential pancreatic β-cell protective effect against STZ-induced damage in RIN-m5F cells. Further, the induction of AMPK activity in HepG2 cells supports glucose homeostasis maintenance in the liver. It is concluded that the sugar composition (arabinose, rhamnose, mannose, glucosamine and N-acetyl neuraminic acid) present in the IFEAC may play a major role in the antidiabetic effect which needs further to be explored for its therapeutic value in the management of diabetes.

The Potential Protective Role of Neoeriocitrin in a Streptozotocin-Induced Diabetic Model in INS-1E Pancreatic ß-Cells

HIGHLIGHTS The potential protective effect of Neo in the STZ-induced damage in INS-1E cells was evaluated. The protective role of Neo on cell viability and reactive oxygen species formation were evaluated. Neo prevented ROS formation and elevated insulin levels in high glucose conditions. Pretreatment of Neo might be a candidate agent to prevent ROS in STZ-induced diabetes.

Carnosic Acid Protects INS-1 β-Cells against Streptozotocin-Induced Damage by Inhibiting Apoptosis and Improving Insulin Secretion and Glucose Uptake.

Carnosic acid (CA), a natural polyphenolic diterpene derived from Rosmarinus officinalis, has been proven to possess a broad spectrum of medicinal properties. Nevertheless, no studies on its impact on pancreatic β-cells have been conducted to date. Herein, clonal rat INS-1 (832/13) cells were pretreated with CA for 24 h and then incubated with streptozotocin (STZ) for 3 h. Several functional experiments were performed to determine the effect of CA on STZ-induced pancreatic β-cell damage, including cell viability assay, apoptosis analysis, and measurement of the level of insulin secretion, glucose uptake, malondialdehyde (MDA), reactive oxygen species (ROS), and proteins expression. STZ treatment decreased cell survival, insulin secretion, glucose uptake, and increased apoptosis, MDA, and ROS production in INS-1 cells. Furthermore, protein expression/phosphorylation analysis showed significant down-regulation in insulin, PDX-1, PI3K, AKT/p-AKT, and Bcl2. On the other hand, expression of BAX and BAD and cleaved PARP were significantly increased. Interestingly, preincubation with CA reversed the adverse impact of STZ at the cellular and protein expression levels. In conclusion, the data indicate that CA protects β-cells against STZ-induced damage, presumably through its modulatory effect on the different pathways, including the Pi3K/AKT/PDX-1/insulin pathway and mitochondria-mediated apoptosis.

Hypoglycemic effects of Fu-Pen-Zi (Rubus chingii Hu) fruit extracts in streptozotocin-induced type 1 diabetic mice

• FPZ alleviated hyperglycemia in STZ-induced diabetic mice. • FPZ increased antioxidant response and protected pancreatic islet against STZ-induced damage. • FPZ inhibited Atrogin-1 and Trim63 expression and prevented muscle atrophy. To explore the effects of Chinese raspberry (Fu-Pen-Zi) on diabetes, a polyphenol-enriched extract (FPZ) was prepared. Streptozotocin (STZ)-induced diabetic mice were daily administered FPZ (30 mg/kg body weight) for 18 days, the anti-diabetic effects were evaluated. Compared to STZ alone mice, FPZ-treatment ameliorated STZ-induced type 1 diabetes, reduced body weight loss (by 71.61%), hyperglycemia (fasting blood glucose reduced by 19.23%), hyperlipidemia (hepatic triglycerides reduced by 15.50%) and skeletal muscle atrophy (quadriceps mass increased by 21.46%). FPZ protected pancreatic β-cells from STZ-induced damage and promoted insulin secretion, preserved insulin signaling in liver tissues and skeletal muscles. FPZ improved glucose tolerance, modulated liver glycogen metabolism, and inhibited hepatic gluconeogenesis via activating insulin/Akt/Gsk3β and LKB1/AMPK signaling. Moreover, FPZ reduced liver oxidative stress and steatosis, reduced Atrogin-1 and Trim63 expression, contributes to muscle atrophy inhibition. This study highlights the potential usage of FPZ as nutritional interventions for type 1 diabetes and muscle atrophy management.

IL-17 deficiency aggravates the streptozotocin\u2010induced diabetic nephropathy through the reduction of autophagosome formation in mice

BackgroundDiabetic nephropathy (DN) is one of the most important medical complications of diabetes mellitus. Autophagy is an important mediator of pathological response and plays a critical role in inflammation during the progression of diabetic nephropathy. Interleukin (IL)-17A favorably modulates inflammatory disorders including DN. In this study, we examined whether IL-17A deficiency affected the autophagy process in the kidneys of mice with streptozotocin (STZ)-induced DN.MethodsThe autophagic response of IL-17A to STZ-induced nephrotoxicity was evaluated by analyzing STZ-induced functional and histological renal injury in IL-17A knockout (KO) mice.ResultsIL-17A KO STZ-treated mice developed more severe nephropathy than STZ-treated wild-type (WT) mice, with increased glomerular damage and renal interstitial fibrosis at 12 weeks. IL-17A deficiency also increased the up-regulation of proinflammatory cytokines and fibrotic gene expression after STZ treatment. Meanwhile, autophagy-associated proteins were induced in STZ-treated WT mice. However, IL-17A KO STZ-treated mice displayed a significant decrease in protein expression. Especially, the levels of LC3 and ATG7, which play crucial roles in autophagosome formation, were notably decreased in the IL-17A KO STZ-treated mice compared with their WT counterparts.ConclusionsIL-17 deficiency aggravates of STZ-induced DN via attenuation of autophagic response. Our study demonstrated that IL-17A mediates STZ-induced renal damage and represents a potential therapeutic target in DN.

Lack of insulin resistance in response to streptozotocin treatment in neuronal SH-SY5Y cell line

Recently, it is suggested that brain insulin resistance may contribute to the development of Alzheimer’s disease; therefore, there is a high interest in its investigation. Streptozotocin (STZ) is often used to induce dysregulation of glucose and insulin metabolism in animal and cell culture models. Alteration in insulin sensitivity however, has not yet been assessed in neuronal cells after STZ treatment. We aimed at studying the concentration dependence of the protective effect of insulin on STZ-induced damage using SH-SY5Y cell line. Cells were treated with STZ and cell viability was assessed by resazurin reduction and lactate dehydrogenase release assays. Low serum (LS) medium was used as control damage. The effect of various concentrations (30, 100, 300, 1000 nM) of insulin was studied on cell viability and glycogen synthase kinase-3 (GSK-3) phosphorylation, an indicator of insulin signaling. STZ induced dose- and time-dependent cytotoxicity, its 1 mM concentration exerted a low, gradually developing damage. The cytoprotective effect of insulin was demonstrated in both STZ and LS groups. Its maximal effect was lower in the STZ-treated cells; however, its effective concentration remained largely unaltered. Insulin-induced GSK-3 phosphorylation was similar in the STZ- and LS-treated cells suggesting unchanged insulin signaling. Our present results indicate that STZ does not induce significant impairment in insulin sensitivity in SH-SY5Y cells, thus in this cell line it is not a good tool for studying the role of insulin resistance in neurodegeneration and to examine protective agents acting by improving insulin signaling.

Melatonin Affects Mitochondrial Fission/Fusion Dynamics in the Diabetic Retina.

Mitochondrial fission and fusion are dependent on cellular nutritional states, and maintaining this dynamics is critical for the health of cells. Starvation triggers mitochondrial fusion to maintain bioenergetic efficiency, but during nutrient overloads (as with hyperglycemic conditions), fragmenting mitochondria is a way to store nutrients to avoid waste of energy. In addition to ATP production, mitochondria play an important role in buffering intracellular calcium (Ca2+). We found that in cultured 661W cells, a photoreceptor-derived cell line, hyperglycemic conditions triggered an increase of the expression of dynamin-related protein 1 (DRP1), a protein marker of mitochondrial fission, and a decrease of mitofusin 2 (MFN2), a protein for mitochondrial fusion. Further, these hyperglycemic cells also had decreased mitochondrial Ca2+ but increased cytosolic Ca2+. Treating these hyperglycemic cells with melatonin, a multifaceted antioxidant, averted hyperglycemia-altered mitochondrial fission-and-fusion dynamics and mitochondrial Ca2+ levels. To mimic how people most commonly take melatonin supplements, we gave melatonin to streptozotocin- (STZ-) induced type 1 diabetic mice by daily oral gavage and determined the effects of melatonin on diabetic eyes. We found that melatonin was not able to reverse the STZ-induced systemic hyperglycemic condition, but it prevented STZ-induced damage to the neural retina and retinal microvasculature. The beneficial effects of melatonin in the neural retina in part were through alleviating STZ-caused changes in mitochondrial dynamics and Ca2+ buffering.

Paeoniflorin protects pancreatic β cells from STZ-induced damage through inhibition of the p38 MAPK and JNK signaling pathways

Pancreatic β-cells are responsible for insulin secretion and control of plasma glucose levels. Accumulating evidences indicate a relationship between β-cell dysfunction/death and diabetes onset. Paeoniflorin (PF), a natural glycoside, has antihyperglycemic effect. However, the role of PF in pancreatic β-cells has not been examined. The aim of this study was to evaluate the protective effect of PF on streptozotocin (STZ)-induced β-cell damage. Our results showed that PF improved STZ-caused inhibitory effect on cell viability and insulin secretion ability in INS-1 cells. PF reduced caspase-3 activity and bax expression, and induced bcl-2 expression in STZ-treated INS-1 cells. PF resulted in a decrease in production of reactive oxygen species and MDA, and an increase in SOD activity in STZ-treated INS-1 cells. Furthermore, PF inhibited the phosphorylation of p38 and JNK, which is induced by STZ in INS-1 cells. The results suggested that PF protected INS-1 cells from STZ-induced cell damage. Meanwhile, PF suppressed the activation of p38 MAPK and JNK pathways in STZ-treated INS-1 cells. These results indicated that PF might be a natural anti-diabetic agent by improving pancreatic β-cells injury through inhibition of the p38 MAPK and JNK signaling pathways.

Treatment With Naringenin Elevates the Activity of Transcription Factor Nrf2 to Protect Pancreatic β-Cells From Streptozotocin-Induced Diabetes in vitro and in vivo.

Chronic hyperglycemia and unusually high oxidative stress are the key contributors for diabetes in humans. Since nuclear factor E2-related factor 2 (Nrf2) controls the expression of antioxidant- and detoxification genes, it is hypothesized that targeted activation of Nrf2 using phytochemicals is likely to protect pancreatic β-cells, from oxidative damage, thereby mitigates the complications of diabetes. Naringenin is one such activator of Nrf2. However, it is currently not known whether the protective effect of naringenin against streptozotocin (STZ) induced damage is mediated by Nrf2 activation. Hence, the potential of naringenin to activate Nrf2 and protect pancreatic β-cells from STZ-induced damage in MIN6 cells is studied. In MIN6 cells, naringenin could activate Nrf2 and its target genes GST and NQO1, thereby inhibit cellular apoptosis. In animals, administration of 50 mg/kg body weight naringenin, for 45 days, significantly decreased STZ-induced blood glucose levels, normalized the lipid profile, and augmented the levels of antioxidants in pancreatic tissues. Immunohistochemical analysis measuring the number of insulin-positive cells in pancreas showed restoration of insulin expression similar to control animals. Furthermore, naringenin promoted glycolysis while inhibiting gluconeogenesis. In conclusion, naringenin could be a good anti-diabetic agent, which works by promoting Nrf2 levels and by decreasing cellular oxidative stress.

Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway.

Trichosanthes kirilowii lectin (TKL) has been reported to exert hypoglycemic effects in alloxan-induced diabetic mice. However, there is no evidence showing that it helps to prevent diabetic nephropathy (DN). We used a high glucose (HG)-induced HK-2 cell model and a streptozocin (STZ)-induced Wistar rat model to investigate the effects of TKL on DN, as well as the mechanisms for those effects. Our results showed that TKL significantly increased the viability of HG-treated HK-2 cells and inhibited cell apoptosis. In vivo experiments demonstrated that TKL attenuated STZ-induced histopathological damage and the inflammatory response in rat kidney tissues. Pre-treatment of HK-2 cells or STZ-treated rats with polyinosinic acid (Poly IC), an inhibitor of lectin-like oxLDL receptor 1 (LOX1), blocked the protective effect of TKL against HG- or STZ-induced damage to kidney tissue, indicating that TKL might exert its effect via LOX1-mediated endocytosis. Additional results suggested that TKL inhibits the phosphorylation of IκB kinase β (IKKβ) and the nuclear factor-κB (NF-κB) inhibitor protein (IκBα), and thereby reduces the nuclear translocation of NF-κB (p65). ChIP assay data indicated that TKL markedly inhibits the binding of p65 to the CASP9 gene in HG-treated HK-2 cells, subsequently suppressing transcription of the CASP9 gene. In the dual-luciferase reporter assay, TKL significantly inhibited luciferase activity in cells co-transfected with p65 and a wild-type capase-9 construct instead of mutated caspase-9 constructs.Taken together, our results show that TKL helps to protect against DN by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway, suggesting TKL as a promising agent for treating DN.

Protective effects of dietary polyphenols from black soybean seed coats on islet and renal function in streptozotocin-induced diabetic rats.

The aim of this study was to investigate the antidiabetic effects of the crude polyphenol extract (BSCP) from black soybean seed coats (BSC) and the whole flour of BSC and illustrate the mechanism in terms of islet and renal protection. BSCP and BSC effectively controlled the increased blood glucose level and impaired glucose tolerance in streptozotocin (STZ)-induced diabetic rats after 8 weeks of treatment. They increased the concentrations of serum insulin, C-peptide and Glp-1 (P < 0.05) by improving the STZ-induced damage of islet β-cells and increasing their insulin expression (P < 0.05). Lipid profiles and antioxidant activities were also improved. Moreover, BSCP and BSC tended to decrease serum creatinine (0.05 < P < 0.1), and blood urea nitrogen was decreased by BSC significantly (P < 0.05). They also led to significantly lower glomerular volume (P < 0.05). Long-term intervention with BSC at a low dose of polyphenols plays a role in controlling blood glucose and lipids levels by promoting insulin secretion and restoring islet β-cell function, the same as BSCP. These benefits are accompanied by their potential protection of diabetic renal dysfunction. BSCP is mainly responsible for the antidiabetic effect of BSC. © 2017 Society of Chemical Industry.

Protective effect of cirsimaritin against streptozotocin-induced apoptosis in pancreatic beta cells

Maintaining glucose homoeostasis is essential for the survival of cells. Despite the various health benefits of Korean thistle (Cirsium japonicum var. maackii), their effects on pancreatic β-cell apoptosis in type 1 diabetes mellitus and the underlying mechanisms remain unclear, and experimentally investigated in this study. The effects of C. japonicum var. maackii and its active component cirsimaritin against streptozotocin (STZ)-induced cytotoxicity were assessed in INS-1 cells. By Western blotting analysis, protein expressions related to apoptosis were evaluated. The involvement of apoptosis was also confirmed with image-based cytometric assay and caspase activity tests. Cirsium japonicum var. maackii extract and cirsimaritin in non-toxic concentrations improved cell viability to near normal levels and protected INS-1 cells against STZ-induced damage. In addition, cirsimaritin reduced the intracellular oxidative stress induced by STZ. Cirsimaritin effectively suppressed apoptosis in pancreatic β cells by decreasing the activation of caspase-8 and caspase-3, BID and the DNA repair protein poly (ADP-ribose) polymerase (PARP) and increasing anti-apoptotic BCL-2 protein expression. This study demonstrates the therapeutic potential and action mechanism of cirsimaritin for the prevention and treatment of type 1 diabetes mellitus.

Orcinol derivative compound with antioxidant properties protects Langerhans islets against streptozotocin damage

To design and synthesize an orcinol derivative compound, 3-formyl-2,4-dihydroxy-5,6-dimethyl sodium benzoate (A4), as an antioxidant molecule and to test its effects on oxidative stress in an in-vitro model of apoptosis of pancreatic rat beta cells induced by streptozotocin (STZ). Scavenger properties of A4 were assessed using its capacity to capture the DPPH radical in vitro. Antiapoptotic properties of A4 were analysed by electron microscopy and TUNEL assay in rat pancreatic islets in a streptozotocin model. The results show that A4 displays antioxidant activity in in-vitro assays and induced a significant reduction in STZ-induced beta cell apoptosis and low ultrastructural damage to cellular organelles in the rat pancreatic islets as evidenced by electronic microscopy, this effect could be attributed to its antioxidant activity in a similar manner than resveratrol. The overall results indicate that the new orcinol derivative molecule displays both antioxidant and antiapoptotic effects and protect pancreatic beta cells against STZ damage.

Beneficial effect of carvone, a dietary monoterpene ameliorates hyperglycemia by regulating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats.

Diabetes mellitus is a common metabolic/endocrine disorder characterized by inadequate control of carbohydrate metabolism and causes serious health issues. This study evaluates the effect of carvone, a novel monoterpene ketone, on carbohydrate metabolic enzymes in the liver of normal and streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (40mg/kg b.w). STZ intoxication led to a significant increase in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and decrease in the levels of insulin and hemoglobin (Hb). The activities of carbohydrate metabolic enzymes, glycogen, enzymatic antioxidants in pancreas and hepatic markers content were also altered. The daily oral administration of carvone (50mg/kg b.w) to diabetic rats for 30days resulted a significant decline in the levels of plasma glucose, HbA1c and significant improve in the levels of Hb and insulin. The reversed activities of carbohydrate metabolic enzymes, enzymic antioxidants and hepatic marker enzymes in diabetic rats were renovated to near normal level by the administration of carvone. The obtained results were compared with glyclazide, a standard oral hypoglycemia drug. Histopathological analysis of liver and pancreas and immunohistochemistry of pancreas revealed that treatment with carvone reduced the STZ-induced damage to hepatic and β-cells of the pancreas. From our results, carvone regulates carbohydrate metabolism by ameliorating the key enzymes in the hepatic tissues of STZ-induced diabetic rats however further studies and safety studies are needed to validate the effects of carvone.