Streptozotocin-induced Diabetic Rat Model Research Articles

Therapeutic Effects of Liposomal Resveratrol in the Mitigation of Diabetic Nephropathy via Modulating Inflammatory Response, Oxidative Stress, and Apoptosis.

An important factor in the development of diabetes and its associated consequences is prolonged chronic hyperglycemia, which weakens the antioxidant defense system and produces reactive oxygen species. Phytochemicals have been found to scavenge free radicals and exhibit antioxidant effects necessary to increase insulin sensitivity and reduce the development of diabetes-related complications. Current treatments for managing diabetes and diabetic nephropathy are often not very effective and come with several limitations and side effects. Resveratrol, for example, has shown therapeutic potential in mitigating kidney damage induced by high glucose levels, but its short bioavailability is a significant limitation. This accentuates the need for alternatives that not only improve the disease but also reduce the side effects associated with treatment. To enhance the therapeutic efficacy of resveratrol, we investigated the protective effects of liposomal resveratrol (LR) in a streptozotocin-induced diabetic rat model at doses of 20 and 40mg/kg. We compared the impact of LR to that of resveratrol alone (at a dose of 40mg/kg) on various parameters, including serum levels of biochemical markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress indices, and apoptotic markers. LR, as a highly absorbable and metabolized form of resveratrol, has demonstrated beneficial effects in diabetic rats. Administered at both 20mg/kg and 40mg/kg dosages over a 5-week period, it demonstrated notable efficacy in alleviating inflammation. This was accomplished by diminishing the levels of pro-inflammatory mediators, TNF-α and IL-6, through the inhibition of NF-κB translocation. Additionally, LR influenced apoptotic markers, specifically caspase, BCL-2, and BAX. Furthermore, it enhanced the expression of key antioxidant enzymes such as catalase and glutathione peroxidase while significantly lowering malondialdehyde levels. These significant biochemical and immunological protective effects correlated with improved histological integrity and overall kidney architecture. Notably, resveratrol alone was not as effective as LR in restoring kidney function, highlighting its potential as a therapeutic candidate for the treatment of diabetic nephropathy. However, more in-depth studies are needed to explore its mechanism of action and improved bioavailability.

A Tissue-Engineered Construct Based on a Decellularized Scaffold and the Islets of Langerhans: A Streptozotocin-Induced Diabetic Model.

Producing a tissue-engineered pancreas based on a tissue-specific scaffold from a decellularized pancreas, imitating the natural pancreatic tissue microenvironment and the islets of Langerhans, is one of the approaches to treating patients with type 1 diabetes mellitus (T1DM). The aim of this work was to investigate the ability of a fine-dispersed tissue-specific scaffold (DP scaffold) from decellularized human pancreas fragments to support the islets' survival and insulin-producing function when injected in a streptozotocin-induced diabetic rat model. The developed decellularization protocol allows us to obtain a scaffold with a low DNA content (33 [26; 38] ng/mg of tissue, p < 0.05) and with the preservation of GAGs (0.92 [0.84; 1.16] µg/mg, p < 0.05) and fibrillar collagen (273.7 [241.2; 303.0] µg/mg, p < 0.05). Rat islets of Langerhans were seeded in the obtained scaffolds. The rats with stable T1DM were treated by intraperitoneal injections of rat islets alone and islets seeded on the DP scaffold. The blood glucose level was determined for 10 weeks with a histological examination of experimental animals' pancreas. A more pronounced decrease in the recipient rats' glycemia was detected after comparing the islets seeded on the DP scaffold with the control injection (by 71.4% and 51.2%, respectively). It has been shown that the DP scaffold facilitates a longer survival and the efficient function of pancreatic islets in vivo and can be used to engineer a pancreas.

Cardioprotective effects of liposomal resveratrol in diabetic rats: unveiling antioxidant and anti-inflammatory benefits

ABSTRACT As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.

Anti-diabetic and anti-inflammatory activities of Marrubiin isolated from Marrubium vulgare: Indications of its interaction with PPAR γ

BackgroundThe aerial parts of Marrubium vulgare L. were used for many ailments like catarrh to diabetes in many parts of Latin America and Asia. PurposeIdentifying the active principle responsible for anti-diabetic activity of methanol extract of M. vulgare leaves and to predict the possible targets. Study designAll the activity investigations were conducted simultaneously for the extract, fraction, and isolated compounds to decipher the activity profile in comparison to each other which allowed the identification of an active principle followed by use of in silico methods to identify the possible target/s. MethodsThe aerial parts of M. vulgare were extracted using methanol. A chloroform fraction was prepared. Marrubiin and marrubinone B were isolated from this fraction. The anti-hyperglycemic, hypoglycemic, and postprandial blood glucose lowering activities were investigated using streptozotocin-induced diabetic and non-diabetic rat models. Pro-inflammatory cytokine inhibitory potential was investigated using LPS induced acute-inflammatory mouse model and RAW 264.7 cells. Further, antioxidant activity was investigated using a DPPH assay. The in silico analysis, using the Swiss-target prediction tool, was carried out to predict the probable targets of the isolated molecules. ResultsMarrubiin exhibited anti-hyperglycemic effect in diabetic rats followed by hypoglycemia, and postprandial blood glucose lowering in non-diabetic rats. Methanol extract (Mv extract) and chloroform fraction (Mv fraction) showed anti-hyperglycemic and hypoglycemic effects. Moderate inhibition of IL-1β, TNF-α, and IL-6 was observed for marrubiin, marrubinone B, Mv extract, and Mv fraction, in vitro and in vivo. Neither marrubiin nor marrubinone B could quench the DPPH free radicals while Mv extract and Mv fraction could show 80 % suppression. In silico analysis has predicted that marrubiin can interact with PPAR γ but not marrubinone B. ConclusionsMarrubiin and marrubinone B were responsible for the anti-inflammatory effect of Mv extract and Mv fraction while not contributing to the antioxidant effect. Marrubiin was found to be responsible for the anti-diabetic activity of Mv extract. The predicted interaction propensity of marrubiin with PPAR γ could explain its dual activity observed in the experimental setup.

The potential therapeutic role of Ginkgo biloba extracts on ventral prostate in a rat model of streptozotocin-induced diabetes: A histomorphometric study

The potential therapeutic role of Ginkgo biloba extracts on ventral prostate in a rat model of streptozotocin-induced diabetes: A histomorphometric study

Implications for Clinical Practice, Mechanisms, and Efficacy of Ageratum conyzoides Leaf Extracts in Streptozotocin-Induced Diabetes Rats: An Investigation into Their Antidiabetic, Hypolipidemic, and Antiatherogenic Activities

Ageratum conyzoides, a perennial herb native to tropical and subtropical regions, has been utilized in traditional medicine for centuries due to its diverse therapeutic properties. This review consolidates current research on the antidiabetic, hypolipidemic, and antiatherogenic effects of Ageratum conyzoides leaf extracts, specifically in streptozotocin-induced diabetic rat models. The review explores the plant’s potential mechanisms of action, including enhancement of insulin sensitivity, improvement of lipid profiles, and reduction of atherosclerotic plaque formation. Ageratum conyzoides extracts have demonstrated significant antidiabetic effects by lowering blood glucose levels, enhancing insulin secretion, and improving insulin sensitivity. They also exhibit hypolipidemic effects by reducing total cholesterol, LDL cholesterol, and triglycerides, while increasing HDL cholesterol. Additionally, these extracts show antiatherogenic properties by inhibiting plaque formation and reducing oxidative stress, thereby supporting cardiovascular health. The review examines the pharmacokinetics and bioavailability of Ageratum conyzoides bioactive compounds, emphasizing the need for further research to optimize their therapeutic potential. Comparative studies highlight its efficacy relative to other natural remedies and pharmaceuticals, noting its favorable safety profile. The review underscores the importance of integrating Ageratum conyzoides into both traditional and modern medicine practices and explores its role in dietary supplements and functional foods. Ongoing translational research and clinical trials are essential to validate the efficacy and safety of these extracts for broader clinical application. Keywords: Ageratum conyzoides, Leaf Extracts, Streptozotocin, Diabetes, Rats

Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo. Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.

Isorhamnetin improves diabetes-induced erectile dysfunction in rats through activation of the PI3K/AKT/eNOS signaling pathway

Erectile dysfunction is a complex and common complication of diabetes mellitus, which lacks an effective treatment. The repairing role of vascular endothelium is the current research hotspot of diabetic mellitus erectile dysfunction (DMED), and the activation of PI3K/AKT/eNOS pathway positively affects the repair of vascular endothelium. The herbal extract isorhamnetin has significant vasoprotective effects and has great potential in treating DMED. This study aimed to clarify whether isorhamnetin has an ameliorative effect on DMED and to investigate the modulation of the PI3K/AKT/eNOS signaling pathway by isorhamnetin to discover its potential mechanism of action. In vivo experiments were performed using a streptozotocin-induced diabetic rat model, and efficacy was assessed after 4 weeks of isorhamnetin gavage administration at 10 mg/kg or 20 mg/kg. Erectile function in rats was assessed by maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), and changes in corpus cavernosum (CC) fibrosis, inflammation levels, oxidative stress levels, and apoptosis were assessed by molecular biology techniques. In vitro experiments using high glucose-induced corpus cavernosum endothelial cells were performed to further validate the anti-apoptotic effect of isorhamnetin and its regulation of the PI3K/AKT/eNOS pathway. The findings demonstrated that isorhamnetin enhanced erectile function, decreased collagen content, and increased smooth muscle content in the CC of diabetic rats. In addition, isorhamnetin decreased the serum levels of pro-inflammatory factors IL-6, TNF-α, and IL-1β, increased the levels of anti-inflammatory factors IL-10 and IL-4, increased the activities of SOD, GPx, and CAT as well as the levels of NO, and decreased the levels of MDA in corpus cavernosum tissues. Isorhamnetin also increased the content of CD31 in CC tissues of diabetic rats, activated the PI3K/AKT/eNOS signaling pathway, and inhibited apoptosis. In conclusion, isorhamnetin exerts a protective effect on erectile function in diabetic rats by reducing the inflammatory response, attenuating the level of oxidative stress and CC fibrosis, improving the endothelial function and inhibiting apoptosis. The mechanism underlying these effects may be linked to the activation of the PI3K/AKT/eNOS pathway.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

Co-Delivery of Dragon's Blood and Alkanna tinctoria Extracts Using Electrospun Nanofibers: In Vitro and In Vivo Wound Healing Evaluation in Diabetic Rat Model.

The increasing prevalence of diabetic wounds presents a significant challenge due to the difficulty of natural healing and various obstacles. Dragon's blood (DB) and Alkanna tinctoria (AT) are well recognized for their potent healing abilities, which include potent antibacterial and anti-inflammatory activities. In this study, electrospun nanofibers (NFs) based on polyvinyl pyrrolidone (PVP) were co-loaded with both DB and AT, aiming to magnify their efficacy as wound-dressing applications for diabetic wound healing. The evaluation of these NFs as wound dressings was conducted using a streptozotocin-induced diabetic rat model. Electrospun NFs were prepared using the electrospinning of the PVP polymer, resulting in nanofibers with consistent, smooth surfaces. The loading capacity (LC) of AT and DB into NFs was 64.1 and 70.4 µg/mg, respectively, while in the co-loaded NFs, LC was 49.6 for AT and 57.2 µg/mg for DB. In addition, X-ray diffraction (XRD) revealed that DB and AT were amorphously dispersed within the NFs. The loaded NFs showed a dissolution time of 30 s in PBS (pH 7.4), which facilitated the release of AT and DB (25-38% after 10 min), followed by a complete release achieved after 180 min. The antibacterial evaluation demonstrated that the DB-AT mixture had potent activity against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). Along with that, the DB-AT NFs showed effective growth inhibition for both P. aeruginosa and S. aureus compared to the control NFs. Moreover, wound healing was evaluated in vivo in diabetic Wistar rats over 14 days. The results revealed that the DB-AT NFs improved wound healing within 14 days significantly compared to the other groups. These results highlight the potential application of the developed DB-AT NFs in wound healing management, particularly in diabetic wounds.

Investigation of diabetes-related molecular changes in embryo-endometrium crosstalk

The primary aim of this study was to explore the impact of diabetes on matrix metalloproteases and tissue inhibitors, crucial factors for successful implantation, and to elucidate the molecular mechanisms that undergo changes in the endometrium and the embryo during diabetic pregnancies. In this investigation, we established a streptozotocin-induced diabetic pregnant rat model. Microarray analysis followed by RT-PCR was utilized to identify gene regions exhibiting expression alterations. Subsequently, we assessed the effects of MMPs and tissue inhibitors using ELISA and immunohistochemistry techniques, in addition to analyzing changes at the genetic level. Diabetes led to the upregulation of MMP3, MMP9, and MMP20 on the 6.5th day of pregnancy, while causing the downregulation of MMP3, MMP9, and MMP11 on the 8.5th day of pregnancy. TIMP1 expression was downregulated on the 8.5th day compared to the control group. No statistically significant differences were observed between the groups regarding other TIMP expressions. KEGG pathway analysis revealed that diabetes induced alterations in the expression of genes associated with certain microRNAs, as well as signaling pathways such as cAMP, calcium, BMP, p53, MAPK, PI3K-Akt, Jak-STAT, Hippo, Wnt, and TNF. Additionally, gene ontology analysis unveiled changes in membrane structures, extracellular matrix, signaling pathways, ion binding, protein binding, cell adhesion molecule binding, and receptor-ligand activity. This study serves as a valuable guide for investigating the mechanisms responsible for complications in diabetic pregnancies. By revealing the early-stage effects of diabetes, it offers insight into the development of new diagnostic and treatment approaches, ultimately contributing to improved patient care.

Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic β-cells

Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of β-cell dysfunction induced by glucotoxicity. We employed three pancreatic β-cell lines, namely INS-1, 1.2B4, and NIT-1, as well as a streptozotocin-induced diabetes rat model. We demonstrate that after high glucose treatment, RAP1 is increased, probably through induction by AKT, allowing RAP1 to shuttle from the nucleus to the cytoplasm and activate NF-κB signaling. Furthermore, non-enzymatic post-translational modifications of RAP1, such as advanced glycation end products and carbonylation may affect the function of RAP1, such as activation of the NF-κB signaling. Taken together, we showed that RAP1 is a new player in the mechanism of glucotoxicity in pancreatic β-cells.

Assessment of Cyperus articulatus for Antidiabetic Effects in a Streptozotocin-Induced Diabetic Rat Model

Assessment of Cyperus articulatus for Antidiabetic Effects in a Streptozotocin-Induced Diabetic Rat Model

Hepatic and renal effects of oral stingless bee honey in a streptozotocin-induced diabetic rat model.

Diabetes is known damage the liver and kidney, leading to hepatic dysfunction and kidney failure. Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications. However, the effect of stingless bee honey (SBH) administration in relieving liver and kidney damage in diabetes has not been well-studied. To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced (STZ; 55 mg/kg) diabetic Sprague Dawley rats. The rats were grouped as follows (n = 6 per group): non-diabetic (ND), untreated diabetic (UNT), metformin-treated (MET), and SBH+metformin-treated (SBME) groups. After successful diabetic induction, ND and UNT rats were given normal saline, whereas the treatment groups received SBH (2.0 g/kg and/or metformin (250 mg/kg) for 12 d. Serum biochemical parameters and histological changes using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were evaluated. On H&E and PAS staining, the ND group showed normal architecture and cellularity of Bowman's capsule and tubules, whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane. The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining, but the two were similar on PAS staining. Likewise, the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining, but it was comparable to the SBH and ND groups on PAS staining. UNT diabetic rats had tubular hydropic tubules, which were smaller than other groups. Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group. Conversely, the UNT group had high glucose levels, which subsequently increased MDA levels, ultimately leading to liver damage. SBH treatment reduced this damage, as evidenced by having the lowest fasting glucose, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase levels compared to other groups, although the levels of liver enzymes were not statistically significant. The cellularity of the Bowman's capsule, as well as histological alteration of kidney tubules, glomerular membranes, and liver tissues in diabetic rats after oral SBH resembled those of ND rats. Therefore, SBH exhibited a protective hepatorenal effect in a diabetic rat model.

Ocimum gratissimum L. leaf flavonoid-rich extracts reduced the expression of p53 and VCAM in streptozotocin-induced cardiomyopathy rats

BackgroundThis study aimed to investigate the potential cardioprotective effects of flavonoid-rich extracts from Ocimum gratissimum leaves in a streptozotocin-induced diabetic rat model by assessing redox stress biomarkers, ATPase activities, gene expression levels, enzyme activities, and histopathological changes. MethodsDiabetic rats were administered low (LDOGFL) and high (HDOGFL) doses of O. gratissimum leaf flavonoid-rich extracts, metformin (MET), or served as diabetic (DC) and normal (NC) controls for twenty-one days. Various cardiac parameters were evaluated, including redox stress biomarkers, ATPase activities, relative gene expression of p53 and VCAM, phosphatase activities, transaminase activities, serum creatine kinase-MB (CKMB) activities, cardiac troponin levels, and natriuretic peptide levels. Additionally, heart histoarchitecture was also examined using hematoxylin and eosin (H&E) staining. ResultsFlavonoid-rich extracts of O. gratissimum significantly (p < 0.05) mitigated redox stress by decreasing malondialdehyde (MDA) levels and increasing reduced glutathione (GSH), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities in diabetic treated rats. The extracts also notably (p < 0.05) improved ATPase activities and significantly (p < 0.05) modulated the relative gene expression of p53 and VCAM in diabetic treated rats. Furthermore, diabetic rat administered flavonoid-rich extracts markedly (p < 0.05) attenuated phosphatase activities, transaminase activities, CKMB activities, cardiac troponin levels, and natriuretic peptide levels. Histopathological examination of the diabetic rats revealed improved cardiac histoarchitecture in extract-treated groups compared to diabetic controls. ConclusionThese findings suggest that O. gratissimum leaf flavonoid-rich extracts confer cardioprotective effects in STZ-induced diabetic rats by ameliorating redox imbalance, modulating gene expression, regulating enzyme activities, and preserving cardiac histoarchitecture. These results highlight the potential therapeutic application of O. gratissimum flavonoids in managing diabetes-induced cardiomyopathy.

Hypoglycemic and hypolipidemic activity of a catfish oil and Andrographis paniculata herb extract combination in diabetic rat model

The single use of natural ingredients for the treatment of diabetes mellitus is considered less optimal compared to the combination of several ingredients which is expected to produce a synergistic effect. Therefore, this study aimed to investigate the combined effect of catfish oil (CFO) and Andrographis paniculata ethanolic extract (APE) in reducing blood glucose levels and hyperlipidemia in a diabetic rat model. A total of 30 male Wistar rats were used while diabetes was induced using 50 mg/kg streptozotocin. The rats were randomly divided into six groups consisting of the control, diabetes, and drug control group treated with metformin 120 mg/kg; as well as treatments I, II, and III given CFO 1000 mg/kg, CFO 1000 mg/kg + APE 200 mg/kg, and CFO 1000 mg/kg + APE 400 mg/ kg, respectively. The test was carried out for 28 days, then on the 29th day, all the test animals were examined for observation of blood glucose levels and lipid profiles. In the fourth week of testing, all groups showed a significantly different blood glucose profile compared to the diabetes control group with p&lt;0.05. The combined administration of 1000 mg/kg CFO and 400 mg/kg APE showed a better reduction in blood glucose compared to the single dose of CFO (p&lt;0.05). Furthermore, the lipid profiles showed a significant reduction compared with the diabetes control (p&lt;0.05). Except for LDL values, the combination of both doses of CFO+APE showed a better reduction in lipid profile compared to the single CFO. A single dose of CFO and a combination dose of APE provided a beneficial effect by inhibiting the increase in blood glucose levels and lipid profiles in a streptozotocin-induced diabetic rat model. Based on the results, the combined dose of 1000 mg/kg CFO+400 mg APE produced a better effect on most of the blood biochemical parameters than the single administration of CFO

Cardioprotective and Hypolipidemic Effect of Cardamom Oil-Loaded Lipid Carrier Nanoparticles in a Rat Model of Streptozotocin-Induced Diabetes

Background: Diabetic cardiomyopathy (DCM) is a serious complication of poorly managed diabetes. Inflammation, hyperglycemia, oxidative stress, hyperlipidemia, and other factors all play a role in DCM pathogenesis. Objective: To investigate the cardioprotective effects of cardamom oil-loaded lipid carrier nanoparticles (CEO-LC NPs) on streptozotocin (STZ)-induced diabetes in rats. Methods: Twenty-four male rats were randomly divided into four groups of six each. STZ (50 mg/kg) caused diabetes in all groups but the negative control. The diabetic control group (G1) received a normal saline solution. For 28 days, group G2 received CEO-LC NPs (600 mg/kg), group G3 received empagliflozin (10 mg/kg), and group G4 (no diabetes) received normal saline as a negative control. On day 29, blood samples were taken to determine blood glucose, cholesterol, LDL, HDL, and triglyceride levels, as well as oxidative stress markers. Additionally, atherogenic indices were calculated. Heart tissue was sent for histopathological examination. Results: In diabetic rats treated with CEO-LC NPs, serum glucose, cholesterol, LDL, and triglyceride levels were significantly reduced, while HDL levels increased. The CEO-LC NP treatment also reduced oxidative stress by increasing total antioxidant capacity while decreasing malondialdehyde (MDA). Furthermore, diabetic rats treated with CEO-LC NP had significantly lower AIP, CRI-I, and CRI-II ratios. Conclusions: CEO-LC NPs improve cardioprotection in STZ-induced diabetic rats by lowering plasma lipid levels and oxidative stress.

Omentum Extracellular Matrix-Silk Fibroin Hydroscaffold Promotes Wound Healing through Vascularization and Tissue Remodeling in the Diabetic Rat Model.

Nonhealing diabetic wounds are often associated with significant mortality and cause economic and clinical burdens to the healthcare system. Herein, a biomimetic hydroscaffold is developed using omentum tissue-derived decellularized-extracellular matrix (dECM) and silk fibroin (SF) proteins that associate the behavior of a collagenous fibrous scaffold and a hydrogel to reproduce all aspects of the provisional skin tissue matrix. The chemical cross-linker-free in situ gelation property of the two types of SF proteins from Bombyx mori and Antheraea assamensis ensures the adherence of dECM with surrounding tissue on the wound bed, circumventing further suturing. The physicochemical and mechanical properties of the composite hydroscaffold (SF-dECM) were thoroughly evaluated. The hydroscaffolds were found to support the growth and proliferation of human dermal fibroblasts and influence the angiogenic potential of endothelial cells under in vitro conditions. Furthermore, the healing efficacy of the composites was evaluated by generating full-thickness wounds on a streptozotocin-induced diabetic rat model. The presence of dECM components in the composite facilitated the rate of wound closure, granulation tissue formation, and re-epithelialization by providing intrinsic cues to advance the inflammatory stage and stimulating angiogenesis. Collectively, as an off-the-shelf wound dressing requiring only a single topical administration, the SF-dECM hydroscaffold is a promising, cost-effective dressing for the management of chronic diabetic wounds.

Amorphophallus campanulatus tuber extract protects diabetic nephropathy in streptozotocin-induced diabetic nephropathy rat model by regulating oxidative stress and TNF-α inflammatory pathway.

To assess the effect of Amorphophallus campanulatus tuber (Ac) extract in the protection of diabetic nephropathy in streptozotocin (STZ) induced diabetic nephropathy (DN) rat model. Diabetes was induced with STZ (60 mg/kg, i.p.), and DN was confirmed after six weeks of STZ administration with the estimation of kidney function test. Further rats were treated with Ac 250 and 500 mg/kg p.o. for next four week. Oxidative stress and level of inflammatory cytokines were estimated in the kidney tissue of DN rats. Histopathology of kidney tissue was performed using hematoxylin and eosin staining. There was improvement in the body weight of Ac treated groups than DN group of rats. Blood glucose level was observed to be reduced in Ac treated groups than DN group on 42nd and 70th day of protocol. Treatment with Ac ameliorated the altered level of kidney function tests (creatinine and BUN), enzymes of liver function (aspartate aminotransferase and alanine aminotransferase), and lipid profile in the serum of DN rats. Oxidative stress parameters (malondialdehyde and reactive oxygen species enhances and reduction in the level of glutathione and superoxide dismutase) and inflammatory cytokines such as interleukin-6, tumour necrosis factor-α, and monocyte chemoattractant protein-1 reduces in the tissue of Ac treated group than DN group. Treatment with Ac also attenuates the altered histopathological changes in the kidney tissue of DN rats. The report suggests that Ac protects renal injury in DN rats by regulating inflammatory cytokines and oxidative stress.

Multifunctional alginate/polydeoxyribonucleotide hydrogels for promoting diabetic wound healing

A multifunctional alginate/PDRN hydrogel system by ionic crosslinking and the Schiff base reaction between oxidized alginate (OA) and PDRN was developed in the present study. Biocompatibility assessment of the PDRN-loaded OA hydrogels showed a significant enhancement in cell viability in human dermal fibroblast (HDF) cells. In addition, hydrogels showed migratory, anti-inflammatory, intracellular reactive oxygen species scavenging, and anti-apoptotic activities. In vivo studies using a streptozotocin-induced diabetic Wister rat model indicated that OA-4PDRN had the highest percentage of wound closure (96.1 ± 2.6 %) at day 14 compared to the control (79.0 ± 2.3 %) group. This was accompanied by up-regulation of vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-β) accompanied by down-regulation of pro-inflammatory markers (IL-6, IL-1β). Following histopathological observations, PDRN-loaded OA hydrogel ensured tissue safety and induced wound healing with granular tissue formation, collagen deposition, re-epithelialization, and regeneration of blood vessels and hair follicles. The downregulation of inflammatory cytokines (CD68) and expression of angiogenesis-related cytokines (CD31) in wound sites revealed the suppression of inflammation and increased angiogenesis, ensuring skin tissue regeneration in diabetic wound healing. In conclusion, the findings suggest that PDRN-loaded OA hydrogel has enormous therapeutic potential as a diabetic wound dressing.