Therapeutic effect of ginger garlic powder in rats with induced diabetes.

The purpose of this study was to examine the potential hypoglycemic effects of administering ginger (Zingiber officinale) and garlic (Allium sativum) to rats with induced type 2 diabetes. A total of forty-five male adult albino rats were randomly assigned to five groups. The groups were named Normal Control, Diabetic Control, Ginger group, Garlic group and a combination group of ginger and garlic. Diabetes was produced in all groups, except the normal control group, using an intraperitoneal injection of streptozotocin at a dosage of 60 mg/body weight. During the course of two months, rats were administered varying amounts of ginger and garlic powders as part of their treatment After the experiment concluded, measurements were taken for glycated hemoglobin, serum glucose, insulin, cholesterol, high density protein, low density protein and liver glycogen levels. These groups exhibited considerably greater serum insulin and high-density lipoprotein concentrations (P<0.05) compared to the diabetic control group. Conversely, body weight, fasting blood glucose, total cholesterol, low density lipoprotein, and glycated hemoglobin levels were significantly lower (P<0.05) in all groups compared to the diabetic control group. A statistically significant increase (P<0.05) increase shown in liver glycogen levels. This study proposes that the utilization of ginger and garlic powders improve the condition of type 2 diabetes and maybe reduce the risk of subsequent diabetic complications.

Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice.

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.

A graminan type fructan from Achyranthes bidentata prevents the kidney injury in diabetic mice by regulating gut microbiota.

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and few therapeutic options are available. The root of Achyranthis bidentatae (AB) is commonly used for DKD treatment in Traditional Chinese medicine. However, its mechanisms are still unclear. Here, a graminan type fructan ABPW1 with molecular weight of 3998 Da was purified from AB. It was composed of ß-1,2-linked Fruf, ß-2,6-linked-Fruf and ß-1,2,6-linked-Fruf backbone, and terminated with T-Glcp and 2-Fruf residues. ABPW1 protected against kidney injuries and intestinal barrier disruption in Streptozotocin (STZ)/High fat diet (HFD) mice. It could modulate gut microbiota composition, evidenced by a rise in the abundance of Bacteroide and decreases of Rikenella, Alistipes, Laedolimicola and Faecalibaculum. ABPW1 intervention promoted short chain fatty acids (SCFAs) production in STZ/HFD mice, especially propionate and isobutyric acid. Antibiotic treatment further demonstrated the key role of gut microbiota in the renal protective action of ABPW1. In addition, in vitro simulated digestion and fermentation together with in vivo fluorescent labeling studies demonstrated ABPW1 was indigestible in upper digestive tract but could reach the colon and be degraded into SCFAs by gut microbiota there. Overall, these data suggested ABPW1 has the potential application on DKD prevention.

Rosa canina extract relieves methylation alterations of pancreatic genes in STZ-induced diabetic rats : Gene methylation in diabetic rats treated with an extract.

BACKGROUND: Diabetes is a chronic metabolic disease that affects many parts of the body. Considering diabetes as a beta cells' defect and loss, the focus is on finding mechanisms and compounds involved in stimulating the function and regeneration of pancreatic ß-cells. DNA methylation as an epigenetic mechanism plays a pivotal role in the ß-cells' function and development. Considering the regenerative and anti-diabetic effects of Rosa canina extract, this study aimed to assess the methylation levels of Pdx-1, Pax-4, and Ins-1 genes in diabetic rats treated with Rosa Canina extract. METHODS AND RESULTS: Streptozotocin-induced diabetic rats were used to evaluate the frequency of Pdx-1, Pax-4, and Ins-1 gene methylation. Treatment groups were exposed to Rosa canina as spray-dried and decoction extracts. Following blood glucose measurement, pancreatic DNA was extracted and bisulfited. Genes' methylation was measured using MSP-PCR and qRT-PCR techniques. Oral administration of Rosa canina extracts significantly reduced blood sugar levels in diabetic rats compared to the control group. The methylation levels of the Pdx-1, Pax-4, and Ins-1 genes promoter in streptozotocin-induced diabetic rats increased compared to the control rats while, the treatment of diabetic rats with Rosa canina extracts, spray-dried samples especially, led to a decreased methylation in these genes. CONCLUSION: The results of this study showed that Rosa canina extract as a spray-dried sample could be effective in treating diabetes by regulating the methylation of genes including Pdx-1, Pax-4, and Ins-1 involved in the activity and regeneration of pancreatic islet cells.

Fosfenopril Attenuates Inflammatory Response in Diabetic Dry Eye Models by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway.

Purpose: The purpose of this study was to investigate the involvement of the TLR4/NF-κB/NLRP3 signaling pathway and its underlying mechanism in diabetic dry eye. Methods: Two models of diabetic dry eye were established in high glucose-induced human corneal epithelial (HCE-T) cells and streptozotocin (STZ)-induced C57BL/6 mice, and the TLR4 inhibitor fosfenopril (FOS) was utilized to suppress the TLR4/NF-κB/NLRP3 signaling pathway. The expression changes in TLR4, NF-κB, NLRP3, and IL-1ß, and other factors were detected by Western blot and RT‒qPCR, the wound healing rate was evaluated by cell scratch assay, and the symptoms of diabetic mice were evaluated by corneal sodium fluorescein staining and tear secretion assay. Results: In the diabetic dry eye model, the transcript levels of TLR4, NF-κB, NLRP3, and IL-1ß were raised, and further application of FOS, a TLR4 inhibitor, downregulated the levels of these pathway factors. In addition, FOS was found to be effective in increasing the wound healing rate of high glucose-induced HCE-T cells, increasing tear production, and decreasing corneal fluorescence staining scores in diabetic mice, as measured by cell scratch assay, corneal sodium fluorescein staining assay, and tear production. Conclusions: The current study found that the TLR4/NF-κB/NLRP3 signaling pathway regulates diabetic dry eye in an in vitro and in vivo model, and that FOS reduces the signs of dry eye in diabetic mice, providing a new treatment option for diabetic dry eye.

Oridonin ameliorates renal fibrosis in diabetic nephropathy by inhibiting the Wnt/ß-catenin signaling pathway.

Diabetic nephropathy (DN) is one of the most serious and frequent complications among diabetes patients and presently constitutes vast the cases of end-stage renal disease worldwide. Tubulointerstitial fibrosis is a crucial factor related to the occurrence and progression of DN. Oridonin (Ori) is a diterpenoid derived from rubescens that has diverse pharmacological properties. Our previous study showed that Ori can protect against DN by decreasing the inflammatory response. However, whether Ori can alleviate renal fibrosis in DN remains unknown. Here, we investigated the mechanism through which Ori affects the Wnt/ß-catenin signaling pathway in diabetic rats and human proximal tubular epithelial cells (HK-2) exposed to high glucose (HG) levels. Our results revealed that Ori treatment markedly decreased urinary protein excretion levels, improved renal function and alleviated renal fibrosis in diabetic rats. In vitro, HG treatment increased the migration of HK-2 cells while reducing their viability and proliferation rate, and treatment with Ori reversed these changes. Additionally, the knockdown of ß-catenin arrested cell migration and reduced the expression levels of Wnt/ß-catenin signaling-related molecules (Wnt4, p-GSK3ß and ß-catenin) and fibrosis-related molecules (α-smooth muscle actin, collagen I and fibronectin), and Ori treatment exerted an effect similar to that observed after the knockdown of ß-catenin. Furthermore, the combination of Ori treatment and ß-catenin downregulation exerted more pronounced biological effects than treatment alone. These findings may provide the first line of evidence showing that Ori alleviates fibrosis in DN by inhibiting the Wnt/ß-catenin signaling pathway and thereby reveal a novel therapeutic avenue for treating tubulointerstitial fibrosis.

Antidiabetic Effect of Fig Seed Oil in Rats with Diabetes Induced by Streptozotocin.

The anti-diabetic effect of Ficus carica (Fig) seed oil was investigated. 4 groups with 6 rats in each group were used in the experiment as control, diabetes (45 mg/kg streptozotocin), fig seed oil (FSO) (6 mL/ kg/day/rat by gavage) and diabetes+FSO groups. Glucose, urea, creatinine, ALT, AST, GSH, AOPP and MDA analyses were done. Pancreatic tissues were examined histopathologically. When fig seed oil was given to the diabetic group, the blood glucose level decreased. In the diabetes+FSO group, serum urea, creatinine, AOPP, MDA levels and ALT and AST activities decreased statistically significantly compared to the diabetes group, while GSH levels increased significantly, histopathological, immunohistochemical, and immunofluorescent improvements were observed. It has been shown for the first time that FSO has positive effects on blood glucose level and pancreatic health. It can be said that the protective effect of fig seed oil on tissues may be due to its antioxidant activity.

Cinnamaldehyde ameliorates STZ-induced diabetes through modulation of autophagic process in adipocyte and hepatic tissues on rats.

Type 2 diabetes mellitus is a worldwide public health issue. In the globe, Egypt has the ninth-highest incidence of diabetes. Due to its crucial role in preserving cellular homeostasis, the autophagy process has drawn a lot of attention in recent years, Therefore, the purpose of this study was to evaluate the traditional medication metformin with the novel therapeutic effects of cinnamondehyde on adipocyte and hepatic autophagy in a model of high-fat diet/streptozotocin-diabetic rats. The study was conducted on 40 male albino rats, classified into 2 main groups, the control group and the diabetic group, which was subdivided into 4 subgroups (8 rats each): untreated diabetic rats, diabetic rats received oral cinnamaldehyde 40 mg/kg/day, diabetic rats received oral metformin 200 mg/kg/day and diabetic rats received a combination of both cinnamaldehyde and metformin daily for 4 weeks. The outcomes demonstrated that cinnamaldehyde enhanced the lipid profile and glucose homeostasis. Moreover, Cinnamaldehyde had the opposite effects on autophagy in both tissues; by altering the expression of genes that control autophagy, such as miRNA 30a and mammalian target of rapamycin (mTOR), it reduced autophagy in adipocytes and stimulated it in hepatic tissues. It may be inferred that by increasing the treatment efficacy of metformin and lowering its side effects, cinnamaldehyde could be utilized as an adjuvant therapy with metformin for the treatment of type 2 diabetes.

Inulin Reduces Kidney Damage in Type 2 Diabetic Mice by Decreasing Inflammation and Serum Metabolomics.

This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic ß-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor ß1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1ß), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Effects of metformin, saxagliptin and repaglinide on gut microbiota in high-fat diet/streptozocin-induced type 2 diabetic mice.

INTRODUCTION: There has been increasing evidence that the gut microbiota is closely related to type 2 diabetes (T2D). Metformin (Met) is often used in combination with saxagliptin (Sax) and repaglinide (Rep) for the treatment of T2D. However, little is known about the effects of these combination agents on gut microbiota in T2D. RESEARCH DESIGN AND METHODS: A T2D mouse model induced by a high-fat diet (HFD) and streptozotocin (STZ) was employed. The T2D mice were randomly divided into six groups, including sham, Met, Sax, Rep, Met+Sax and Met+Rep, for 4 weeks. Fasting blood glucose level, serum biochemical index, H&E staining of liver, Oil red O staining of liver and microbiota analysis by 16s sequencing were used to access the microbiota in the fecal samples. RESULTS: These antidiabetics effectively prevented the development of HFD/STZ-induced high blood glucose, and the combination treatment had a better effect in inhibiting lipid accumulation. All these dosing regimens restored the decreasing ratio of the phylum Bacteroidetes: Firmicutes, and increasing abundance of phylum Desulfobacterota, expect for Met. At the genus level, the antidiabetics restored the decreasing abundance of Muribaculaceae in T2D mice, but when Met was combined with Rep or Sax, the abundance of Muribaculaceae was decreased. The combined treatment could restore the reduced abundance of Prevotellaceae_UCG-001, while Met monotherapy had no such effect. In addition, the reduced Lachnospiraceae_NK4A136_group was well restored in the combination treatment groups, and the effect was much greater than that in the corresponding monotherapy group. Therefore, these dosing regimens exerted different effects on the composition of gut microbiota, which might be associated with the effect on T2D. CONCLUSIONS: Supplementation with specific probiotics may further improve the hypoglycemic effects of antidiabetics and be helpful for the development of new therapeutic drugs for T2D.

Effect of pegagan (Centella asiatica) nanoparticle coated with chitosan on the cytokine profile of chronic diabetic mice.

Diabetes is closely related to immune response problems when it occurs chronically. Pegagan (Centella asiatica) is a medicinal plant with active compounds. Madecassoside is beneficial in treating diabetes, and nanoparticle technology is expected to enhance the medicinal potential and availability of pegagan compounds. The aim of this study was to determine the effect of chitosan-coated pegagan nanoparticles on the cytokine profile of chronic diabetic mice, which included CD4+TNF-α+, CD8+TNF-α+, CD4+IFN-γ+, CD8+IFN-γ+ and IL-6+. An experimental study with a randomized complete block design (CRD) consisting of six treatments with seven replicates was conducted. The groups were: healthy mice as negative control; diabetic mice treated with distilled water as positive control and diabetic mice treated with nanoparticle coated with chitosan (NPC) 20 mg/kg, 30 mg/kg, 40 mg/kg, and metformin 130 mg/kgBW. The data were tested using one-way analysis of variance (ANOVA) with a significance level of 5% and continued with the Duncan's multiple range test. The results showed that pegagan NPC could significantly reduce the relative number of CD4+TNF-α+, CD8+TNF-α+, CD4+IFN-γ+ and CD8+IFN-γ+ and IL-6 in the dose of 20 mg/kg, 30 mg/kg and 40 mg/kg (p<0.05). The treatment dose of 20 mg/kg reduced CD4+TNF-α+, CD8+TNF-α+, CD4+IFN-γ+, CD8+IFN-γ+ to the levels of healthy mice and a dose of 30 mg/kg could reduce IL-6 as in healthy mice. These findings suggest that chitosan-coated pegagan nanoparticles are a promising therapy for diabetes, as they have the potential to modulate the immune response associated with chronic diabetes.

Integrated Network Pharmacology Analysis and Experimental Validation to Elucidate the Mechanism of Acteoside in Treating Diabetic Kidney Disease.

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.

Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats.

Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.

Effect of Ducrosia anethifolia methanol extract against methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms on excision wound in diabetic mice.

Background: Ducrosia anethifolia is an aromatic desert plant used in Saudi folk medicine to treat skin infections. It is widely found in Middle Eastern countries. Methods: A methanolic extract of the plant was prepared, and its phytoconstituents were determined using LC-MS. In-vitro and in-vivo antibacterial and antibiofilm activities of the methanolic extract were evaluated against multidrug-resistant bacteria. The cytotoxic effect was assessed using HaCaT cell lines in-vitro. Diabetic mice were used to study the in-vivo antibiofilm and wound healing activity using the excision wound method. Results: More than 50 phytoconstituents were found in the extract after LC-MS analysis. The extract exhibited antibacterial activity against both the tested pathogens. The extract was free of irritant effects on mice skin, and no cytotoxicity was observed on HaCaT cells with an IC50 value of 1381 µg/ml. The ointment formulation of the extract increased the healing of diabetic wounds. The microbial load of both pathogens in the wounded tissue was also reduced after the treatment. The extract was more effective against methicillin-resistant Staphylococcus aureus (MRSA) than MDR-P. aeruginosa in both in vitro and in vivo experiments. Further, skin regeneration was also observed in histological studies. Conclusions: The results showed that D. anethifolia methanol extract supports wound healing in infected wounds in diabetic mice through antibacterial, antibiofilm, and wound healing activities.

Dietary menhaden fish oil supplementation suppresses lipopolysaccharide-induced neuroinflammation and cognitive impairment in diabetic rats.

CONTEXT: Menhaden fish oil (FO) is widely recognized for inhibiting neuroinflammatory responses and preserving brain function. Nevertheless, the mechanisms of FO influencing brain cognitive function in diabetic states remain unclear. OBJECTIVE: This study examines the potential role of FO in suppressing LPS-induced neuroinflammation and cognitive impairment in diabetic animals (DA). MATERIALS AND METHODS: Thirty male Wistar rats were divided into 5 groups: i) DA received LPS induction (DA-LPS); ii) DA received LPS induction and 1 g/kg FO (DA-LPS-1FO); iii) DA received LPS induction and 3 g/kg FO (DA-LPS-3FO); iv) animals received normal saline and 3 g/kg FO (NS-3FO) and v) control animals received normal saline (CTRL). Y-maze test was used to measure cognitive performance, while brain samples were collected for inflammatory markers and morphological analysis. RESULTS: DA received LPS induction, and 1 or 3 g/kg FO significantly inhibited hyperglycaemia and brain inflammation, as evidenced by lowered levels of pro-inflammatory mediators. Additionally, both DA-LPS-1FO and DA-LPS-3FO groups exhibited a notable reduction in neuronal damage and glial cell migration compared to the other groups. These results were correlated with the increasing number of entries and time spent in the novel arm of the Y-maze test. DISCUSSION AND CONCLUSION: This study indicates that supplementation of menhaden FO inhibits the LPS signaling pathway and protects against neuroinflammation, consequently maintaining cognitive performance in diabetic animals. Thus, the current study suggested that fish oil may be effective as a supporting therapy option for diabetes to avoid diabetes-cognitive impairment.

Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment.

Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.

Chlorogenic acid ameliorates intestinal inflammation via miRNA-microbe axis in db/db mice.

Chlorogenic acid improves diabetic symptoms, including inflammation, via the modulation of the gut microbiota. However, the mechanism by which the microbiota is regulated by chlorogenic acid remains unknown. In this study, we firstly explored the effects of chlorogenic acid on diabetic symptoms, colonic inflammation, microbiota composition, and microRNA (miRNA) expression in db/db mice. The results showed that chlorogenic acid decreased body weight, improved glucose tolerance and intestinal inflammation, altered gut microbiota composition, and upregulated the expression level of five miRNAs, including miRNA-668-3p, miRNA-467d-5p, miRNA-129-1-3p, miRNA-770-3p, and miRNA-666-5p in the colonic content. Interestingly, the levels of these five miRNAs were positively correlated with the abundance of Lactobacillus johnsonii. We then found that miRNA-129-1-3p and miRNA-666-5p promoted the growth of L. johnsonii. Importantly, miRNA-129-1-3p mimicked the effects of chlorogenic acid on diabetic symptoms and colonic inflammation in db/db mice. Furthermore, L. johnsonii exerted beneficial effects on db/db mice similar to those of chlorogenic acid. In conclusion, chlorogenic acid regulated the gut microbiota composition via affecting miRNA expression and ameliorated intestinal inflammation via the miRNA-microbe axis in db/db mice.

Ziyin Bushen Fang improves Diabetic Osteoporosis by Inhibiting Autophagy and Oxidative Stress In vitro and In vivo.

OBJECTIVE: Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress. METHODS: Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels. RESULTS: After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK. CONCLUSION: ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.

Paris polyphylla Sm. characterized extract infused ointment accelerates diabetic wound healing in In-vivo model.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried rhizome of Paris polyphylla Sm. is extensively used by traditional healers in India, China, and Vietnam to treat skin inflammation, cut wounds, uterine and traumatic bleeding, and cancer. AIM OF THE STUDY: The traditional use of P. polyphylla rhizomes for treating wounds and bleeding has been reported previously. However, the potential of P. polyphylla in the treatment of diabetic wounds has not yet been explored. Our present study focused on the investigation of the wound-healing activity of P. polyphylla infused ointment in streptozotocin (STZ)-induced diabetic rats to validate the traditional claim. MATERIALS AND METHODS: Hydroalcoholic extract of the dried rhizomes of P. polyphylla were quantified by validated and optimized HPTLC (High-performance thin layer chromatography) method for Paris saponin VII, Dioscin and Polyphyllin V. The extract was used to prepare P. polyphylla ointments (5 and 10%). P. polyphylla ointment was subjected to physiochemical analysis and skin irritation test. Thirty STZ-induced diabetic adult male Wistar albino rats were divided into five groups (n = 6) and a circular excision wound was created. P. polyphylla ointment, ointment base (OB), and standard (STD) (Povidone Iodine 10%) were administered topically. The wound area of all groups were recorded every six days and compared with that of control. The epithelization period of each group was recorded. On day 18, the histopathological study of skin tissues of all groups was performed using hematoxylin and eosin (H&E) and Mallory's trichrome (MT). RESULTS: Marker analysis and quantification of phytomolecules in hydroalcoholic extract ofP. Polyphylla were found to be of paris saponin VII (3.28 ± 0.08% w/w), dioscin (1.94 ± 0.12% w/w), and polyphyllin V (1.87 ± 0.84% w/w). A physiochemical study of P. polyphylla ointment showed that the prepared ointment was within an acceptable range and was not irritable to the skin. Daily topical administration of 10% P. polyphylla ointment (PP10) for 18 days completely healed the STZ-induced diabetic wounds. On day 18, the 5% P. polyphylla ointment (PP5) showed 99.1 ± 2.9% wound closure, while that of the standard and control was 78.4 ± 7.3% and 18.5 ± 5.9%, respectively. The epithelialization period of PP10 was 18 days, whereas that of the control was 28 days. Histopathological analysis of the progression of PP10 and PP5 wounds showed a decrease in inflammatory cells, regenerated epithelial layer, keratosis layer, hair follicles, fibroblasts, and collagen. Upon collagen intensity quantification of MT stained sections, an increase in collagen density of PP10 and PP5 treated groups was observed, showing accelerated wound healing potential of P. polyphylla extract in diabetic wounds compared to the standard ointment. CONCLUSION: This study suggested the potential of P. polyphylla rhizomes derived formulation to treat diabetic wounds, although the plant is traditionally used to treat normal wounds. The results indicate the validation of traditional claim, which has been explored commercially in industrial aspect.