Pancreatic Tissue Damage Research Articles

Curative role of mesenchymal stromal cells in chronic pancreatitis: Modulation of MAPK and TGF-β1/SMAD factors.

Background and objective: Living organisms respond to physical, chemical, and biological threats with a potent inflammatory response which alters organ cell signaling and leads to dysfunction. We evaluated the therapeutic effect of bone marrow-based mesenchymal stromal cell (BM-MSC) transplanted in rats to preserve tissue integrity and to restore homeostasis and function in the pancreatitis experimental pattern. Methods: This study involved 40 adult male Wister rats. Repeated L-arginine injections caused chronic pancreatitis (CP), leading to the development of pancreatic damage and shifting the intracellular signaling pathways. Rats were then infused with BM-MSC labeled with PKH26 fluorescent linker dye for 12 weeks. Results: Cell-surface indicators of BM-MSCs such as CD 90 and CD29 were expressed with the lack of CD34 expression. BM-MSC treatment considerably improved the alterations induced in a series of inflammatory markers, including IL-18, TNF-α, CRP, PGE2, and MCP-1. Furthermore, improvement was found in digestive enzymes and lipid profile with amelioration in myeloperoxidase activity. BM-MSC treatment also regulated the (TGF-/p-38MPAK/SMAD2/3) signaling factors that enhances repair of damaged pancreatic tissue, confirmed by reversed alteration of histopathological examination. Conclusion: our results further bring to light the promise of cell transplant therapy for chronic pancreatitis.

Indonesian plants with potential as an anti-diabetes mellitus agent

Diabetes Mellitus (DM) is a degenerative disease that continues to increase in numberin Indonesia and is a disease that is spread throughout the world due to unbalancednutritional conditions. Treatment of diabetes mellitus is a chronic and lifelongtreatment. Treatment of diabetes mellitus, such as the use of insulin and oralantihyperglycemia drugs, is relatively expensive, is used for a long time and can causeunwanted side effects. There are many plants that have potential as antihyperglycemiadrugs. One of the active compounds that act as antihyperglycemia isflavonoids.Flavonoids derived from various types of plants studied are thought to actas antihyperglycemic agents. Flavonoids are known to have the ability to scavenge freeradicals or act as natural antioxidants. The antioxidant activity of flavonoids is relatedto phenolic –OH groups which can capture or neutralize free radicals (such as ROS orRNS). Flavonoids can play a role in pancreatic tissue damage caused by DNA alkylationdue to alloxan induction as a result of improving the morphology of the rat pancreas(Prameswari and Widjanarko, 2014).

The Role of TLR-4 and Galectin-3 Interaction in Acute Pancreatitis

Abstract Toll-like receptor-4 (TLR-4) is a member of evolutionarily conserved type I transmembrane proteins that can initiate sterile inflammatory cascade in the pancreas. Expression of TLR-4 is up-regulated in pancreatic tissue, as well as, on peripheral blood innate immune cells in human and experimental models of acute pancreatitis. TLR-4 plays important pro-inflammatory roles during development of acute pancreatitis: it recognize alarmins released from injured acinar cells and promotes activation and infiltration of innate immune cells after the premature and intraacinar activation of tripsinogen. Galectin-3 is β-galactoside-binding lectin that plays pro-inflammatory roles in a variety autoimmune diseases, acute bacterial infections and during tumorigenesis. It is reported that Galectin-3 is alarmin in experimental models of neuroinflammation and binds to TLR-4 promoting the pro-inflammatory phenotype of microglia. Also, in experimental model of acute pancreatitis Galectin-3 is colocalized with TLR-4 on innate inflammatory cells resulted in enhanced production of inflammatory cytokines, TNF-α and IL-1β, increased infiltration of pro-inflammatory N1 neutrophils, macrophages and dendritic cells and increased damage of pancreatic tissue. This review paper discusses the role of TLR-4/Gal-3 axis in the pathogenesis of acute pancreatitis.

Hyperlipasemia and Potential Pancreatic Injury Patterns in COVID-19: A Marker of Severity or Innocent Bystander?

Hyperlipasemia and Potential Pancreatic Injury Patterns in COVID-19: A Marker of Severity or Innocent Bystander?

Duration-dependent effects induced by titanium dioxide nanoparticles on pancreas of adult male albino rats (histological and biochemical study)

ABSTRACT Titanium dioxide nanoparticles (TiO2NPs) have been widely used in numerous applications and enter the human body through different routes. This study aimed to investigate the effect of intraperitoneal TiO2NPs on the histological and biochemical structure of rat pancreas. Fifty adult male albino rats were divided into four groups. Group I (control) was equally divided into two subgroups. Groups II, III, and IV: rats received intraperitoneal TiO2NPs for 7, 14, and 45 days, respectively. Blood samples were taken for the estimation of blood glucose, serum insulin, serum α-amylase, and lipase activity levels. Sections of the pancreas were processed for light, electron microscope examination, and immunohistochemical detection of insulin protein. Other parts were exposed to Real-Time Polymerase Chain Reaction for Bax, Bcl-2, SOD, and GST mRNA gene expression. Results showed pancreatic tissue damage, including acinar and islet cells, which became worse with increased duration of exposure to TiO2NPs. Decreased immune expression of the insulin protein together with decreased serum insulin and increased blood glucose levels indicated the alteration of β cells. Decreased serum α-amylase and lipase activities indicated alteration of acinar cells. Increased Bax and decreased Bcl-2 mRNA expression levels showed the apoptotic effect of TiO2NPs caused by oxidative stress and evidenced by a significant reduction in the mRNA expression of SOD and GST in a duration-dependent manner. In conclusion: the present study stated that TiO2NPs exposure for long durations had toxic effects on both exocrine and endocrine pancreas mediated by apoptotic and oxidative stress pathways.

Pengaruh Ekstrak Daun Sirsak Terhadap Gambaran Histopatologi Pankreas Rattus Norvegicus Jantan yang Diinduksi Aloksan

<p><strong>ABSTRACT</strong></p><p> Diabetes melitus is a metabolic disorder characterized by an increase in blood glucose levels caused by disruption of the pancreas in producing insulin. Alloxan is a substrate that can trigger the condition of hyperglycemia which can cause diabetes because of its toxic nature to pancreatic beta cells. Damage to pancreatic beta cells is caused by Reactive Oxygen Species (ROS) which causes necrosis in the pancreatic beta cells. Soursop leaf extract (Annona muricata L.) has antioxidants such as flavonoids and tannins which can inhibit ROS increase.</p><p> The aim of this study to find out about the effect of soursop leaf (Annona muricata Linn) extract in repaired to pancreatic tissue damage of male wistar rats (Rattus norvegicus) induced by alloxan. This study used 24 male Wistar rats, divided into 3 groups : K(-) group that no treatment, K(+) group that induced by alloxan dose 150mg/kgBW and K(p) group that induced by alloxan dose 150mg/kgBW and given soursop leaf extract dose 150mg/kgBW. The result of this study showed that there was significant difference (p = 0.001) of pancreatic tissue damage measured by histopathologic score between group of no treatment rats compared to the group of rats induced by alloxan. There was a significant difference of pancreatic tissue damage measured by histopatology score group of rats induced by alloxan compared to group of rats induced by alloxan and given soursop leaf extract So it can be concluded that the administration of alloxan significantly increases the pancreatic tissue damage and the administration of soursop leaf extract can improve pancreatic tissue damage measured by histopathology score because soursop leaf extract contains flavonoids and tannins which function as antioxidants.</p><p> </p><p><strong>Keywords </strong>: Diabetes Melitus, Alloxan, Annona muricata Linn, Pancreatic Histopathology.</p>

Hypoglycemic potential of selenium nanoparticles capped with polyvinyl-pyrrolidone in streptozotocin-induced experimental diabetes in rats

This study was aimed to evaluate the efficacy of synthesized selenium nanoparticles (SeNPs) capped with glucose and polyvinyl-pyrrolidone (PVP) on the hyperglycemia and prooxidants/antioxidants imbalance present in model streptozotocin (STZ)-induced diabetic rats. SeNPs were synthesized and characterized. Twenty-four albino male rats were grouped into four different groups. After the rats were induced to have type 2 diabetes by STZ, the SeNPs-treated groups received a dose of 0.5 mg/ml of SeNPs for seven days. Plasma glucose and insulin levels, pancreatic insulin expression, the levels of lipid peroxidation (LPO), nitric oxide (NO), glutathione peroxidase (GPx) and glutathione (GSH) were evaluated. TEM images revealed the formation of semispherical particles with average size between 40 and 50 nm. SeNPs administration successfully reduced the hyperglycemia, raised the levels of insulin in both the pancreas and the plasma and restored the damaged pancreatic tissue. SeNPs also showed enhancement of the elimination of the diabetes-induced oxidative stress injuries by decreasing the pancreatic LPO and NO levels. Furthermore, the activities of the antioxidant enzyme GPx and GSH levels of the diabetic rats were increased. In conclusion, SeNPs capped with PVP could be used in the future as an agent that could manage Diabetes mellitus.

Inhibition of Matrix Metalloproteinase with BB-94 Protects against Caerulein-Induced Pancreatitis via Modulating Neutrophil and Macrophage Activation.

Methods AP was induced in Balb/C mice by ten hourly intraperitoneal injections of caerulein (100 μg/kg) and LPS (5 mg/kg). The MMP inhibitor, BB-94 (20 mg/kg) was intraperitoneally administered 30 min before AP induction. Pancreatitis was confirmed by histology and serum amylase and lipase. Expression of pancreatic proinflammatory mediators and NF-κB activation were assessed. Bone marrow-derived neutrophils (BMDNs) and macrophages (BMDMs) were isolated. BMDNs were activated by phorbol 12-myristate 13-acetate (PMA, 50 ng/ml) and neutrophil reactive oxygen species (ROS) production was recorded. BMDMs were stimulated with 10 ng/ml IFN-γ and 100 ng/ml LPS to induce M1 macrophage polarization. Results Pancreatic MMP-9 was markedly upregulated and serum MMP-9 was increased in caerulein-induced pancreatitis. Inhibition of MMP with BB-94 ameliorated pancreatic tissue damage and decreased the expression of proinflammatory cytokines (TNFα and IL-6) or chemokines (CCL2 and CXCL2) and NF-κB activation. Furthermore, using isolated BMDNs and BMDMs, we found that inhibition of MMP with BB-94 markedly decreased neutrophil ROS production, inhibited inflammatory macrophage polarization and NF-κB activation. Conclusions Our results showed that inhibition of MMP with BB-94 protected against pancreatic inflammatory responses in caerulein-induced pancreatitis via modulating neutrophil and macrophage activation.

The Immunomodulatory Effects and Mechanisms of Tim-3 Action in the Early Stage of Mice with Severe Acute Pancreatitis.

Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well. To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice. Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group. Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA method. Quantitative RT-PCR was performed to detect the transcripts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis. The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0). Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway. Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response.

Deletion of macrophage migration inhibitory factor ameliorates inflammation in mice model severe acute pancreatitis

BackgroundMacrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine implicated in sepsis, rheumatoid arthritis and other diseases. However, the role of MIF in acute pancreatitis (AP) remains unclear. This study aims to explore the role of MIF in the pathogenesis of AP using MIF−/− mice (referred to as KO) and the biological effects of pharmacological inhibition of MIF in l-arginine induced AP. MethodsAP was induced in C57BL/6 wild-type (referred to as WT) and KO mice by administration of l-arginine. The severity of AP was assessed by serum analysis of amylase and lipase, and of these pro-inflammatory cytokines TNF-α and IL-1β. Histological hematoxylin and eosin (H&E) and immunohistochemical staining of pancreatic tissues were examined for inflammation and expression of pro-inflammatory mediators. We also investigated the biological effects of pharmacological inhibition of MIF activity using ISO-1((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester). ResultsAt 72 h after the induction of AP with l-arginine, significantly lower levels of serum amylase, lipase, TNF-α, and IL-1β were observed in KO mice when compared with WT controls. Histological examination further showed protective effects against pancreatic tissue damage and inflammation, with pancreatic expression of TNF-α, IL-1β and NF-κB p65 markedly reduced. Pharmacological inhibition of MIF activity with ISO-1 markedly mirrored the protective effect seen in the KO AP model providing further evidence that MIF is involved in the pathogenesis of AP. ConclusionOur data provided strong evidence for the participation of MIF in the pathogenesis of AP and subsequent inflammatory response. The genetic ablation of MIF or its inhibition with pharmacological agents significantly ameliorated the severity of AP.

Loss of RE-1 silencing transcription factor accelerates exocrine damage from pancreatic injury

Regulation of pancreas plasticity is critical for preventing injury and promoting regeneration upon tissue damage. The intricate process of pancreatic differentiation is governed by an orchestrated network of positive and negative transcription factors for appropriate gene expression. While the transcriptional repressor REST is well characterized as a silencer of neuronal genes in non-neuronal cells, the role of REST in regulating exocrine pancreas cell identity remains largely unexplored. Rest expression is increased upon injury in the mouse pancreas, such as induced acute and chronic pancreatitis and ductal adenocarcinoma. At the cellular level, Rest expression is lower in mature acinar cells compared with pancreas progenitor and ductal cells. To investigate the role of REST activity in pancreatic transdifferentiation and homeostasis, we developed a novel mouse model (Cre/RESTfl/fl) with conditional knockout (KO) of Rest expression within pancreas cells. The high Cre-mediated excision efficiency of Rest exon two KO caused decreased Rest expression and activity within the pancreas. Short-term organoid cultures of pancreatic acini to undergo acinar-to-ductal metaplasia (ADM) showed that loss of REST impedes induced ADM, while overexpression of REST increases ADM. Interestingly, REST ablation accelerated acute pancreatitis in mice treated with the cholecystokinin analog caerulein, as indicated by cellular morphology, elevated serum amylase levels and pancreatic edema. Furthermore, Cre/RESTfl/fl mice were more sensitive to acute pancreatitis injury and displayed augmented tissue damage and cellular lesions. These results suggest REST has a novel protective role against pancreatic tissue damage by acting as a regulator of exocrine cell identity.

Crassocephalum rubens (Juss. Ex Jacq.) S. Moore improves pancreatic histology, insulin secretion, liver and kidney functions and ameliorates oxidative stress in fructose-streptozotocin induced type 2 diabetic rats

Crassocephalum rubens (C. rubens) is a traditional leafy vegetables (TLV) eaten in parts of Africa for the management of symptoms of diabetes mellitus. This study was done to investigate the in vivo anti-diabetic activity of the aqueous extract of C. rubens aerial parts (CRAQ). Type 2 diabetes (T2D) was induced in male Sprague Dawley (SD) rats by feeding them with a 10% fructose solution for two weeks followed by single dose (40 mg/kg body weight) intraperitoneal injection of streptozotocin. After confirmation of T2D, animals were treated with a low and a high dose (150 and 300 mg/kg body weight) of extract for five weeks. Parameters used as markers of hyperglycemia were analyzed in the samples collected from rats. Hematoxylin-eosin staining was used in analyzing the morphological changes of the pancreas. Treatment with high dose of the extract significantly (p < 0.05) lowered blood glucose level, increased oral glucose tolerance level and pancreatic β-cell function, while restoring the morphology of the pancreatic tissue damage. The high dose also increased insulin secretion, liver glycogen, antioxidant enzyme activities in serum and organs, and prevented liver and renal damages compared to the untreated diabetic animals. Data from this study suggest that C. rubens possesses impressive anti-diabetic activity and could be useful in ameliorating some complications associated with T2D therefore this plant can be exploited in finding new alternative therapies for the treatment of T2D.

Caffeic acid phenethyl ester attenuates changes in pancreatic tissue damage biomarkers induced by cisplatin.

Application of cisplatin (CP) for the treatment of different cancers is known to cause pancreatitis through an increase in reactive oxygen species production and promotion of inflammation. Caffeic acid phenethyl ester (CAPE), the main activity carrier of propolis extracts, was previously found to possess numerous beneficial properties. This study aims to determine for the first time the potential of CAPE in preventing CP-induced pancreatic tissue damage by studying the changes occurring on both biochemical and microscopic levels. The levels of serum α-amylase and a panel of pancreatic tissue biomarkers related to tissue injury (reduced glutathione, xanthine oxidase, malondialdehyde, and protein carbonylated concentration) and inflammation (myeloperoxidase, nitric oxide, and umor necrosis factor alpha) were studied in male Wistar rats treated with either CP alone or with CP and CAPE. Additionally, microscopic analysis of pancreatic tissue would be conducted as well. Application of CAPE together with CP statistically significantly prevented the disturbance in all here-studied pancreatic tissue damage and inflammation-related biomarkers. The changes in pancreas biochemical status was followed by morphological disturbance. The results of the present study suggest that CAPE could act as a protective agent in pancreatic damage that arises after CP application.

Protective Effect of Alprostadil on Acute Pancreatitis in Rats via Inhibiting Janus Kinase 2 (JAK2)/STAT3 Signal Transduction Pathway.

BackgroundAlprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of alprostadil in decreasing acute pancreatitis (AP) injury remains unknow. This study aimed to investigate the possible protective effects and mechanism of alprostadil against AP in rats.Material/MethodsForty healthy Sprague-Dawley rats were randomly divided into a control group, an AP group, an AP-alprostadil group, an AP-AG490 group, and an AP-(alprostadil+AG490) group. An animal model of acute pancreatitis was established. The pathological changes of the pancreases in each group were observed. We assessed levels of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO), as well as serum IL-1β, IL-6, IL-10, and TNF-α. TUNEL assay was used to detect apoptosis of pancreatic cells. The proteins p-Jak2 and p-Stat3 were investigated by Western blot.ResultsCompared with the control group, pancreatic pathological score, pancreatic apoptosis, MDA, MPO, serum IL-1β, IL-6, and TNF-α levels were significantly higher in the AP group, and SOD levels were significantly decreased. Compared with the AP group, after treatment with alprostadil, AG490, and alprostadil+AG490, respectively, the pancreatic pathological score, apoptosis, MDA, MPO, serum IL-1β, IL-6, and TNF-α were significantly decreased in AP rats, while SOD levels were significantly increased. The protein levels of p-JAK2 and p-STAT3 were significantly upregulated in the AP group compared with the control group, and the protein levels of p-JAK2 and p-STAT3 after treatment with alprostadil, AG490, and alprostadil+AG490 were significantly decreased, and the effect of alprostadil+AG490 was the strongest.ConclusionsAlprostadil can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas.

NQDI-1 protects against acinar cell necrosis in three experimental mouse models of acute pancreatitis

NQDI-1, an inhibitor of ASK1, has been reported to have protective effects in several experimental human disease models. However, the role of NQDI-1 in acute pancreatitis (AP) has not been reported. In this study, we found that NQDI-1 could attenuate histological damage of pancreatic tissue as well as the levels of serum amylase and lipase in a mouse model of AP induced by caerulein. Moreover, the production of reactive oxygen species (ROS) and the expression of necrosis-related proteins (RIP3 and p-MLKL) were also reduced after NQDI-1 administration. Correspondingly, we elucidated the effect of NQDI-1 in vitro and found that NQDI-1 protected against pancreatic acinar cells necrosis via decreasing the ROS production and RIP3 and p-MLKL expression. In addition, we identified the protective effect of NQDI-1 on AP through two other mouse models induced by l-arginine and pancreatic duct ligation. Taken together, these findings showed that NQDI-1 could reduce the acinar cells necrosis and alleviate the severity of AP, which may afford a new therapeutic target on pancreatic necrosis in AP clinically.

Iguratimod (T-614) attenuates severe acute pancreatitis by inhibiting the NLRP3 inflammasome and NF-κB pathway

Severe acute pancreatitis (SAP) is an acute abdominal disease that can develop locally to the multiple organs. It is characterized by pancreatic tissue self-digestion, and the rapid release of inflammatory cytokines, which play a dominant role in local or even systemic inflammation. In this study, we investigate the protective effect of T-614 against SAP induced by cerulein plus LPS in mice. Biochemical markers associated with pancreatitis in serum such as inflammatory cytokines, amylase and lipase activities were measured. Related proteins of NLRP3 inflammasome and NF-κB signaling pathway were evaluated by western blotting. Hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) were used to evaluate changes of inflammation in pancreatic tissue. T-614 significantly alleviated the elevation markers of pancreatitis and suppresses the pancreatic tissue damage, including histopathological and molecular manifestations. In conclusion, T-614 plays a protective role in experimental SAP mice model via anti-inflammatory effects.

Transgenic Expression of PRSS1R122H Sensitizes Mice to Pancreatitis

Mutations in the trypsinogen gene (PRSS1) cause human hereditary pancreatitis. However, it is not clear how mutant forms of PRSS1 contribute to disease development. We studied the effects of expressing mutant forms of human PRSS1 in mice. We expressed forms of PRSS1 with and without the mutation encoding R122H (PRSS1R122H) specifically in pancreatic acinar cells under control of a full-length pancreatic elastase gene promoter. Mice that did not express these transgenes were used as controls. Mice were given injections of caerulein to induce acute pancreatitis or injections of lipopolysaccharide to induce chronic pancreatitis. Other groups of mice were fed ethanol or placed on a high-fat diet to induce pancreatitis. Pancreata were collected and analyzed by histology, immunoblots, real-time polymerase chain reaction, and immunohistochemistry. Trypsin enzymatic activity and chymotrypsin enzymatic activity were measured in pancreatic homogenates. Blood was collected and serum amylase activity was measured. Pancreata from mice expressing transgenes encoding PRSS1 or PRSS1R122H had focal areas of inflammation; these lesions were more prominent in mice that express PRSS1R122H. Pancreata from mice that express PRSS1 or PRSS1R122H had increased levels of heat shock protein 70 and nuclear factor (erythroid-derived 2)-like 2, and reduced levels of chymotrypsin C compared with control mice. Increased expression of PRSS1 or PRSS1R122H increased focal damage in pancreatic tissues and increased the severity of acute pancreatitis after caerulein injection. Administration of lipopolysaccharide exacerbated inflammation in mice that express PRSS1R122H compared to mice that express PRSS1 or control mice. Mice that express PRSS1R122H developed more severe pancreatitis after ethanol feeding or a high-fat diet than mice that express PRSS1 or control mice. Pancreata from mice that express PRSS1R122H had more DNA damage, apoptosis, and collagen deposition and increased trypsin activity and infiltration by inflammatory cells than mice that express PRSS1 or control mice. Expression ofa transgene encoding PRSS1R122H in mice promoted inflammation and increased the severity of pancreatitis compared with mice that express PRSS1 or control mice. These mice might be used as a model for human hereditary pancreatitis and can be studied to determine mechanisms of induction of pancreatitis by lipopolysaccharide, ethanol, or a high-fat diet.

Exploration of the Effect and Mechanism of ShenQi Compound in a Spontaneous Diabetic Rat Model.

Type 2 Diabetes Mellitus (T2DM) is a world-wide metabolic disease with no cure from drugs and treatment. In China, The Traditional Chinese Medicine (TCM) herbal formulations have been used to treat T2DM for centuries. In this study, we proposed a formula called ShenQi Compound (SQC), which has been used in clinical therapeutics in China for several years. We evaluated the effect of SQC in a spontaneous diabetic rat model (GK rats) by detecting a series of blood indicators and performing histological observations. Meanwhile, the gene microarray and RT-qPCR experiments were used to explore the molecular mechanism of SQC treatment. In addition, western medicine, sitagliptin was employed as a comparison. The results indicated that SQC and sitagliptin could effectively improve the serum lipid (blood Total Cholesterol (TC) and blood Triglycerides (TG)), hormone levels (serum insulin (INS), Glucagon (GC) and Glucagon-Like Peptide-1 (GLP-1)), alleviated the inflammatory response (hypersensitive C-Reactive Protein (hsCRP)), blood glucose fluctuation (Mean Blood Glucose (MBG), standard deviation of blood glucose (SDBG) and Largest Amplitude of plasma Glucose Excursions (LAGE)), pancreatic tissue damage and vascular injury for T2DM. Compared with sitagliptin, SQC achieved a better effect on blood glucose fluctuation (p<0.01). Meanwhile, the gene microarray and RT-qPCR experiments indicated that SQC and sitagliptin may improve the T2DM through affecting the biological functions related to apoptosis and circadian rhythm. Moreover, SQC might be able to influence the mTOR signaling pathway by regulating Pik3r1, Ddit4 expression. All these results indicate that SQC is an effective therapeutic drug on T2DM. Notably, SQC presents an obvious blood glucose fluctuation-preventing ability, which might be derived from the regulation of the mTOR signaling pathway.

Synthesis of new antidiabetic agent by complexity between vanadyl (II) sulfate and vitamin B1: Structural, characterization, anti‐DNA damage, structural alterations and antioxidative damage studies

Complexity between thiamine (vitamin B1) and VSO4.xH2O salt with the suggest formula, [VO (vitB1)2] has been synthesized by the chemical reaction in neutralization media pH = 7.5 at 70 °C. The assignments of the elemental analysis, conductivity measurements, FT‐IR, UV–Vis, ESR spectroscopy, thermal analyses (TGA‐DTA) and magnetic moment data visualize the stoichiometry, formula and chelation of the vanadyl (II) complex. The spectroscopic analyses revealed that vitamin B1 reacted with vanadyl (II) ions as a bidentate ligand via hydroxyl ethyl‐oxygen and sulfur of the thiazole group. New vanadyl (II) complex has the protective effect against pancreatic toxicity induced by STZ. The target of this investigation was to assess the enhancement effect of new vanadyl (II)complex in two doses on pancreatic toxicity, oxidative stress, DNA damage and hyperglycemia persuade by STZ. The rats were divided into 7 groups; control group, STZ (diabetic untreated group) (50 mg/kg), STZ plus thiamine (10 mg/Kg) (Low dose), STZ plus thiamine (50 mg/Kg) (High dose), STZ plus VSO4. xH2O (15 mg/kg), STZ + vanadyl (II) complex (10 mg/Kg) (Low dose), STZ+ vanadyl (II) complex (50 mg/Kg) (High dose). Vanadyl (II) complex in high dose afforded a significant decline in MDA level parallel to significant elevation in antioxidant enzymes (SOD, CAT, MPO and XO) in pancreas homogenates. It may be due to the capturing activities of reactive oxygen species by the new complex, which reduces oxidative damage and enhance antioxidant capacities. The novel complex succeeded in the restoration of lipid parameters to its normal levels beside lowering TNF‐α and CRP levels. The new complex also reduces hyperglycemia induced by STZ greatly and improve histological and ultrastructure of pancreas and has a high potency in reducing DNA damage in pancreatic tissues.

Bone marrow–derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1–mediated anti-oxidant and anti-inflammatory effects

Background and aimsIt has been previously verified that mesenchymal stromal cells (MSCs) have a good therapeutic effect on severe acute pancreatitis (SAP) and the potential for regeneration of damaged pancreatic tissue, but the exact molecular mechanism remains unclear. In this study, we demonstrated the therapeutic effect of bone morrow MSCs (BMSCs) on SAP, probably by targeting heme oxygenase-1 (HO-1). MethodsSix hours after SAP induction, either phosphate-buffered saline (PBS) or BMSCs were transfused into the caudal vein of rats, zinc protoporphyrin (ZnPP) was administered intraperitoneally. Pancreatic pathological scoring, serum levels of amylase and inflammatory factors, as well as levels of reactive oxygen species (ROS), malondialdehyde (MDA) and myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) activity in the pancreas were evaluated. ResultsOur data showed that BMSCs significantly reduce inflammation and oxidative stress, reduce apoptosis and promote angiogenesis of damaged pancreas. Moreover, BMSCs increased the level of HO-1 in the serum and pancreatic tissue in rats with SAP. In addition, the protective effect of BMSCs was partially neutralized by the HO-1 activity inhibitor ZnPP, suggesting a key role of HO-1 in the therapeutic effect of BMSCs on SAP. ConclusionsBMSCs ameliorated SAP, probably by inducing expression of HO-1, which can exert anti-inflammatory and anti-oxidant effects, reduce apoptosis and promote angiogenesis.