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.

Protective effect of a hydromethanolic extract from Fraxinus excelsior L. bark against a rat model of aluminum chloride-induced Alzheimer's disease: Relevance to its anti-inflammatory and antioxidant effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Fraxinus excelsior L. (FE), commonly known as the ash, belongs to the Oleaceae family and has shown several pharmacological and biological properties, such as antioxidant, immunomodulatory, neuroprotective, and anti-inflammatory effects. It has also attracted the most attention toward neuroinflammation. Moreover, FE bark and leaves have been used to treat neurological disorders, aging, neuropathic pain, urinary complaints, and articular pain in traditional and ethnomedicine. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder resulting from the involvement of amyloid-beta, metal-induced oxidative stress, and neuroinflammation. AIM OF THE STUDY: The objective of the current study was to assess the neuroprotective effects of hydromethanolic extract from FE bark in an AlCl3-induced rat model of AD. MATERIALS AND METHODS: The maceration process was utilized to prepare the hydromethanolic extract of FE bark, and characterized by LC-MS/MS. To assess the anti-AD effects of the FE extract, rats were categorized into five different groups, AlCl3; normal control; FE-treated groups at 50, 100, and 200 mg/kg. Passive avoidance learning test, Y-maze, open field, and elevated plus maze behavioral tests were evaluated on days 7 and 14 to analyze the cognitive impairments. Zymography analysis, biochemical tests, and histopathological changes were also followed in different groups. RESULTS: LC-MS/MS analysis indicated the presence of coumarins, including isofraxidin7-O-diglucoside in the methanolic extract of FE as a new isofraxidin derivative in this genus. FE significantly improved memory and cognitive function, maintained weight, prevented neuronal damages, and preserved the hippocampus's histological features, as demonstrated by behavioral tests and histopathological analysis. FE increased anti-inflammatory MMP-2 activity, whereas it decreased that of inflammatory MMP-9. Moreover, FE increased plasma antioxidant capacity by enhancing CAT and GSH while decreasing nitrite levels in the serum of treated groups. In comparison between the treated groups, the rats that received high doses of the FE extract (200 mg/kg) showed the highest therapeutic effect. CONCLUSION: FE rich in coumarins could be an effective anti-AD adjunct agent, passing through antioxidant and anti-inflammatory pathways. These results encourage further studies for the development of this extract as a promising agent in preventing, managing, or treating AD and related diseases.

Targeted protein modification as a paradigm shift in drug discovery.

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases.

Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways.

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

Anti-diabetic Effects of Macronutrients via Modulation of Angiogenesis: A Comprehensive Review on Carbohydrates and Proteins.

BACKGROUND: Diabetes is a major global health concern, manifesting the symptoms of chronic hyperglycemia. Either insufficient or excessive angiogenesis is generally involved in the pathogenesis of diabetes and its complications. OBJECTIVE: Given that macronutrients are important dietary players in global health issues, we aimed to review the role of macronutrients, including carbohydrates and proteins, to manage diabetes via angiogenesis modulation. METHODS: Sixteen studies regarding the effects of macronutrients, including carbohydrates and proteins derived from plants, fungus, bacteria, and their derivatives, on angiogenesis in diabetes were included in our study. RESULTS: Reviewing these studies suggests that carbohydrates, including low molecular weight fucoidan (LMWF), Astragalus polysaccharide (APS), and Ganoderma lucidum polysaccharide (Gl-PS), as well as oligopeptides, like sea cucumber-isolated small molecule oligopeptides (SCCOPs), can induce angiogenesis in the process of wound healing. Considering retinopathy, carbohydrates, including Diphlorethohydroxycarmalol (DPHC), Lyciumbarbarum (LBP), Sulfated K5 Escherichia coli polysaccharide (K5-N, OS (H)), and carnosine suppressed retinal angiogenesis. Furthermore, rice bran protein (RBP) ameliorated angiogenesis in diabetic nephropathy. Carbohydrates, including DPHC, Anoectochilus roxburghii polysaccharide (ARP), and LMWF, showed beneficial effects on endothelial cell dysfunction. CONCLUSION: In conclusion, data suggest that a number of macronutrients, including proteins and carbohydrates, could have protective effects against complications of diabetes via modulation of angiogenesis.

Notch signaling-induced cyclin d1 in diabetes ameliorating effects of the isolated polysaccharide from Rosa canina: In vitro and in vivo studies.

Notch signaling has a role in the expansion of the pancreas and the pathogenesis of diabetes. Modulation of Notch signaling by natural products seems to pave the way for treating diabetes. This research aimed to scrutinize the involvement of the Notch cascade in the diabetes-ameliorating effects of an isolated polysaccharide from Rosa canina. The isolated polysaccharide was characterized using Fourier transform infrared, nuclear magnetic resonance, high-performance gel-permeation chromatography, and liquid chromatography with tandem mass spectrometry techniques. Rat pancreatic ß cells and STZ-induced diabetic rats were treated with the isolated polysaccharide. MTT assay, cell cycle analysis, quantative realtime-polymerase chain reaction, immunohistochemistry, and immunoblotting were used to reveal the growth and the expression levels of Notch1, DLL4, Jagged-1, hes1, Ins-1, Pdx-1, and cyclin d1 in treated and untreated pancreatic cells and tissues. The ameliorating effect of the polysaccharide in STZ-treated cells was accomplished by upregulation of cyclin d1 and hes1 as well as cell cycle progression. Notch inhibition by LY-411575 was associated with the downregulation of cyclin d1 which upregulates with polysaccharide treatment. The significant expression of cyclin d1 (90%) and nuclear expression of hes1 in the pancreas of the polysaccharide group were accompanied by improvement of hyperglycemia and associated biochemical factors as well as regeneration of islet cells as compared to untreated diabetic rats. Based on these findings, upregulation of Notch signaling-induced cyclin d1 could be proposed as the underlying diabetes-reducing effects of the isolated polysaccharide derivative implying that cyclin d1 actuation through activation of the Notch-DLL4 circuit may play the causal role in the treatment of diabetes.

Neuroprotective effect of naringenin-loaded solid lipid nanoparticles against streptozocin-induced neurotoxicity through autophagy blockage.

Autophagy is a pivotal contributing factor to modulate the progression of neurodegenerative diseases. Although naringenin (Nar) has shown beneficial effects against neurodegenerative diseases, its poor solubility and bioavailability have limited its application. The present research aimed to design a nanostructured formulation of Nar to achieve an enhanced therapeutic effect. Herein, Nar-loaded solid lipid nanoparticles (Nar-SLNs) were prepared and characterized. Then, PC12 cells were exposed to streptozocin (STZ) and/or Nar and Nar-SLNs in vitro to clarify the protective effect of Nar and its nanoformulation against STZ-stimulated neurotoxicity. The empty SLNs and Nar-SLNs indicated a narrow polydispersity index value with a negative zeta potential. As determined by the scanning electron microscopy images, the nanoparticles had a spherical shape and were less than 20 nm in size. FTIR results demonstrated the interaction between Nar and SLNs and supported the presence of Nar in the nanoparticle. The nanoformulation revealed an initial burst release followed by a sustained release manner. Treatment of PC12 cells with STZ resulted in mitochondrial dysfunction and increased autophagic markers, including LC3-II, Beclin1, Akt, ATG genes, and accumulation of miR-21 and miR-22. Both Nar and Nar-SLNs pre-treatment improved cell survival and augmented mitochondrial membrane potential, accompanied by reduced autophagic markers expression. However, Nar-SLNs were more effective than free Nar. As a result, our findings suggested that SLNs effectively enhance the neuroprotective effect of Nar, and Nar-SLNs may be a promising candidate to suppress or prevent STZ-elicited neurotoxicity. PRACTICAL APPLICATIONS: According to the beneficial effect of Nar in the management of neurodegenerative diseases, we evaluated the protective effect of Nar and Nar-SLNs against STZ-stimulated neurotoxicity and analyzed the role of autophagy in STZ-stimulated neurotoxicity. Our results proposed that Nar-SLNs could be a promising option for neurological disorders prevention through autophagy suppression.

Evaluation of the Cytotoxicity of Aqueous Extract and Oleo-Essential Oil of Dorema ammoniacum Plant Oleo-Gum Resin in Some Human Cancer Cell Lines.

Results: Aqueous extract and essential oil reduced the viability of A549 cancer cells in a concentration-dependent manner. The lowest inhibitory concentrations (IC50) for both samples of D. ammoniacum oleo-gum resin were 10 and 2.5 µg/ml for 24 hours in A549 cell line, respectively. After treatment with extract and essential oil of D. ammoniacum oleo-gum resin, ROS increased significantly compared to the control group. Although changes in caspase-3 did not show a significant increase in extract, the caspase-3 was found to be increased after exposure to essential oil and caspase-9 was downregulated after exposure to essential oil. Also, exposure to essential oil of D. ammoniacum caused a reduction in MMP level. Conclusion: Based on results, the cytotoxic effect of essential oil of D. ammoniacum can induce apoptosis toward A549 cell line via induction of oxidative stress, MMP depletion, and caspase-3 activation, which is independent to mitochondrial cytochrome c release and caspase-9 function.

Improving Animal Model of Induced Colitis by Acetic Acid in Terms of Fibrosis and Inflammation Incidence in the Colon.

METHODS: Fifty rats were randomly separated into five groups (n = 10) with different durations (30 s, 5, 10, and 20 min) of exposure of the colon to 4% acetic acid and colitis was investigated for 0-9 days. The extent of the mucosal ulcers, colon tissue thickening, and mucosal bleeding were scored by the Gerald classification system score. Slides of tissues were prepared for pathologic assay using the modified Wallace method. RESULTS: In all groups, inflammation was severe three days after the colitis induction, but no inflammation was observed in the 30 s group after five days. Acid contact with the colon surface did not result in fibrosis for the 30 s and the colon fibrosis was mild in 5 min group and severe in 10 and 20 min groups. The tissue damage was higher in groups of 20, 10, 5 min, and 30 s, respectively. Over time, the recovery rates in the 30 s and 5 min groups were higher than other groups. CONCLUSION: Our results showed that the evaluation of the disease process from 3 days to nine days after a 10 min contact of acid to the colon is a suitable model that mimics the histological features of the disease.

Immunoengineering Biomaterials in Cell-Based Therapy for Type 1 Diabetes.

Type 1 diabetes (T1D) is caused by low insulin production and chronic hyperglycemia due to destruction of pancreatic ß-cells. Cell transplantation is an attractive alternative approach compared to insulin injection. However, cell therapy has been limited by major challenges, including life-long requirement for immunosuppressive drugs to prevent host immune responses. Encapsulation of the transplanted cells can solve the problem of immune rejection, by providing a physical barrier between the transplanted cells and the recipient's immune cells. Despite current disputes in cell encapsulation approaches, thanks to recent advances in the fields of biomaterials and transplantation immunology, extensive effort has been dedicated to immunoengineering strategies, in combination with encapsulation technologies, to overcome the problem of host's immune responses. This review summarizes the most commonly used encapsulation and immunoengineering strategies combined with cell therapy, which have been applied as a novel approach to improve cell replacement therapies for management of T1D. Recent advances in the fields of biomaterial design, nanotechnology, as well as deeper knowledge about immune modulation had significantly improved cell encapsulation strategies. However, further progress requires combined application of novel immunoengineering approaches and islet/ß-cell transplantation. Impact statement Cell encapsulation shows promising potential in preventing host's immune responses and rejection of islets or ß-cells by providing a selectively permeable barrier between the host and the transplanted cells. Innovative materials, conformal nanocoatings, and immunomodulation have provided promising approaches in the field of encapsulation technology. Novel nanocarriers have been synthesized to release and deliver immunosuppressive agents to islets/ß-cells within the capsules in a controlled manner. The immunoengineering approach (immunosuppressive and immunomodulatory agents) could overcome the challenges of cell replacement therapy in type 1 diabetes.

Anti-Diabetic Effects of Isolated Lipids from Natural Sources through Modulation of Angiogenesis.

BACKGROUND: Aberrant angiogenesis plays a fateful role in the development of diabetes and diabetic complications. Lipids, as a diverse group of biomacromolecules, are able to relieve diabetes through the modulation of angiogenesis. OBJECTIVES: Owing to the present remarkable anti-diabetic effects with no or few side effects of lipids, the aim of this study was to assess the state-of-the-art research on anti-diabetic effects of lipids via the modulation of angiogenesis. METHODS: To study the effects of lipids in diabetes via modulation of angiogenesis, we have searched the electronic databases including Scopus, PubMed, and Cochrane. RESULTS: The promising anti-diabetic effects of lipids were reported in several studies. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil (FO) were reported to significantly induce neovasculogenesis in high glucose (HG)-mediated endothelial progenitor cells (EPCs) with neovasculogenesis dysfunction in type 2 diabetic mice. Linoleic acid, mono-epoxy-tocotrienol- α (MeT3α), and ginsenoside Rg1 facilitate wound closure and vessel formation. N-Palmitoylethanolamine (PEA), α-linolenic acid (ALA), omega-3 (ω3) lipids from flaxseed (FS) oil, ω-3 polyunsaturated fatty acids (PUFA), lipoic acid, taurine, and zeaxanthin (Zx) are effective in diabetic retinopathy via suppression of angiogenesis. Lysophosphatidic acid, alkyl-glycerophosphate, crocin, arjunolic acid, α-lipoic acid, and FS oil are involved in the management of diabetes and its cardiac complications. Furthermore, in two clinical trials, R-(+)-lipoic acid (RLA) in combination with hyperbaric oxygenation therapy (HBOT) for treatment of chronic wound healing in DM patients, as well as supplementation with DHA plus antioxidants along with intravitreal ranibizumab were investigated for its effects on diabetic macular edema. CONCLUSION: Proof-of-concept studies presented here seem to well shed light on the anti-diabetic effects of lipids via modulation of angiogenesis.

Modulation of Notch signaling and angiogenesis via an isolated polysaccharide from Momordica charantia in diabetic rats.

Given the impact of notch signaling in the modulation of metabolic diseases and normal tissue homeostasis, this study aimed to evaluate whether notch signaling has a role in anti-diabetic and islet regenerative effects of the isolated polysaccharide from Momordica charantia in diabetic rats. The polysaccharide was isolated from M. charantia (MCP) and was characterized by using FTIR and LC-MS/MS. The diabetic model was established by intraperitoneal administration of streptozotocin in male Wistar rats and grouped into control, diabetic, metformin (500 mg kg-1  day-1 ), and treatment (10 mg kg-1  day-1 ) groups. The levels of Hes1, Notch 1, DLL4, Jagged1, Pdx1, CD34, CD31, and VEGF were analyzed by using immunohistochemistry and real-time PCR. Structural analyses have revealed the polysaccharide structure of the isolated fraction. High blood glucose was normalized by MCP treatment in diabetic rats. MCP scaled up the mRNA levels of Ins1, jagged1, Pdx1, and Hes1 while it scaled down the levels of Notch1, Dll4, and the ratio of Bax/Bcl2 in diabetic rats. Furthermore, the immunohistochemistry staining levels of hes1, cyclin d1, and VEGF proteins were increased in the pancreas of MCP-treated diabetic rats compared to the diabetic group. These findings provide insights into the anti-diabetic potential of MCP through modulation of islets' regeneration and suggest that modulation of notch and angiogenesis pathways may play a pivotal role in the restoration of the islets to relieve diabetes. PRACTICAL APPLICATIONS: Polysaccharides extracted from Momordica charantia could normalize the level of blood glucose in STZ-induced type 2 diabetic rats through modulation of notch and angiogenesis singling pathways. Given that this effect was associated with the increased expression of Pdx-1 and Insulin in the pancreas, the isolated polysaccharide is expected to be introduced as a convenient medicine in the treatment of diabetes through modulation of ß-cell regeneration.

Dissolving microneedle-assisted long-acting Liraglutide delivery to control type 2 diabetes and obesity.

Integrating nanoparticles (NPs) as a smart and targeted tool for drug delivery with dissolving microneedle (DMN) patch, the non-invasive device for drug delivery, is a promising for future therapeutic delivery applications. Liraglutide (Lira) encapsulation in poly (lactic-co-glycolic acid) (PLGA) NPs provides a sustained release of Lira to 15 days in a biphasic profile which 80% of released content happens in the first 8 days. Embedding such sustained release NPs in the DMN comprising poly vinyl pyrrolidone (PVP) 50% w/v, eliminates the need for Lira subcutaneous injection. Additionally, NPs containing DMN enhance mechanical strength of needles to 5.31 N compared to DMN with pure Lira content which was 4.32 N. The flexible backing layer of the DMN was obtained via blending of PVP and poly vinyl alcohol (PVA) in 10% w/v. Circular dichroism (CD) analysis showed that Lira encapsulated in NPs maintained its native secondary structure even after solidification in DMN. In this study, the capacity of 2 kinds of 500 µm and 1000 µm needles to deliver the desired dose of drug was obtained based on experimental and mathematical methods.

Wound-Healing Potential of Cucurbita moschata Duchesne Fruit Peel Extract in a Rat Model of Excision Wound Repair.

MATERIALS AND METHODS: Hydroalcoholic extractions of pumpkin fruit peel were obtained and used to prepare two different cold cream-based formulations, namely, 10% and 20% pumpkin peel extracts (PPEs). These formulations, phenytoin cream, and cold cream were topically used once daily for 14 days to compare their wound-healing effects in a rat model of excision wound repair. Wound sizes were monitored at different intervals. Skin tissue samples were subject to H&E staining for histopathological analysis. Blood samples were also taken on day 14 to measure serum levels of nitrite. RESULTS: Both 10% and 20% PPE formulations resulted in a significant reduction of wound sizes compared to positive and negative controls. Wound closure rate was estimated to be higher in 20% PPE-treated rats. According to histopathological analysis, treatment with 20% PPE improved parameters associated with efficient wound repair, including better regeneration of epidemic layer, higher density of dermis collagen fibers, and lower presence of inflammatory cells. Also, both formulations lowered serum concentrations of nitrite. CONCLUSION: Given the obtained data from our study, the hydroalcoholic extract of Cucurbita moschata Duchesne fruit peel is proposed to be effective in accelerating the process of excision wound repair partly due to its antioxidant effect in terms of decreasing nitrite concentration.

The effects of co-administration of artichoke leaf extract supplementation with metformin and vitamin E in patients with nonalcoholic fatty liver disease: A randomized clinical trial.

Medicinal plants are widely used as a complementary therapy to treat complex diseases, such as nonalcoholic fatty liver disease (NAFLD). Therefore, this study was done to investigate the effect of co-administration of artichoke leaf extract supplement (ALES) with conventional medicines on patients with NAFLD. The clinical trial was based on patients randomly divided into three groups involving metformin-vitamin E (ME), metformin-ALES (MA), and vitamin E-ALES (EA). The effectiveness of treatment in the treated groups was evaluated using liver ultrasonography and biochemical markers. After 12 weeks of treatment, the results showed that the rate of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was significantly reduced within all the study groups (p < .05). Liver ultrasonographic findings revealed that the rate of fat accumulation in liver of patients was decreased significantly within all the study groups and it was increased in the subjects with grade 0 fatty liver (without fat accumulation) in the MA and EA groups by 23.3 and 17.2%, respectively. In summary, the results of the present study showed that the concomitant use of ALES with metformin and vitamin E can have beneficial effects on amelioration of complications in patients with NAFLD. However, larger-scale clinical trial studies are required in this regard.

Antidiabetic potential of the isolated fractions from the plants of Rosaceae family in streptozotocin-induced diabetic rats.

BACKGROUND AND PURPOSE: Diabetes is a group of multifactorial disorders characterized by chronic-elevated blood glucose levels (hyperglycemia). Natural remedies are used as alternative medications to treat diabetes. Here, we tested the protective effect of the plant extracts of the Rosaceae family on improving insulin secretion and repairing the pancreatic beta cells in diabetic rats. EXPERIMENTAL APPROACH: The oligosaccharide fraction was isolated from the Rosaceae family of herbs. LC-MS/MS was applied to characterize the isolated fractions. The male Wistar rats were randomly divided into six groups, 10 each, including the control group with no intervention, diabetic rats without treatment, diabetic rats that received the extract of Malus domestica (apple), Cydonia oblonga (quince), Prunus persica (nectarine), and Prunus persica (peach), separately. Rats were monitored for the weight, fasting plasma glucose, and insulin levels. The effect of extracts in streptozotocin (STZ)-induced diabetic rats on the pancreatic islets was evaluated by morphometric analysis. FINDINGS/RESULTS: LC-MS/MS results indicated a similar mass spectrum of isolated fractions from nectarine and peach with Rosa canina. Oral administration of nectarine and peach extracts to STZ-induced diabetic rats showed restoration of blood glucose levels to normal levels with a concomitant increase in insulin levels. Morphometric analysis of pancreatic sections revealed the increase in number, diameter, volume, and area of the pancreatic islets in the diabetic rats treated with extracts compared to the untreated diabetic rats. CONCLUSION AND IMPLICATIONS: Nectarine and peach extracts' anti-diabetic properties improved insulin secretion and pancreatic beta-cell function and subsequently led to restoring pancreatic islet mass in STZ-induced diabetic rats.

Targeting Common Signaling Pathways for the Treatment of Stroke and Alzheimer's: a Comprehensive Review.

Neurodegenerative diseases such as stroke and Alzheimer's disease (AD) are two inter-related disorders that affect the neurons in the brain and central nervous system. Alzheimer's is a disease by undefined origin and causes. Stroke and its most common type, ischemic stroke (IS), occurs due to the blockade of cerebral blood vessels. As an important feature, both of disorders are associated with irreversible damages to the brain and nervous system. In this regard, finding common signaling pathways and the same molecular origin between these two diseases may be a promising way for their solution. On the basis of literature appraisal, the most common signaling cascades implicated in the pathogenesis of AD and stroke including notch, autophagy, inflammatory, and insulin signaling pathways were reviewed. Furthermore, current therapeutic strategies including natural and synthetic pharmaceuticals aiming modulation of respective signaling factors were scrutinized to ameliorate neural deficits in AD and stroke. Taken together, digging deeper in the common connections and signal targeting can be greatly helpful in understanding and unified treating of these disorders.

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms.

Since its inception, the coronavirus disease 2019 (COVID-19) pandemic has infected millions of people around the world. Therefore, it is necessary to find effective treatments against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), as it is the viral source of COVID-19. Alkaloids are one of the most widespread plant-derived natural compounds with prominent antiviral effects. Accordingly, these phytochemicals have been promising candidates towards discovering effective treatments for COVID-19. Alkaloids have shown potential anti-SARS-CoV activities via inhibiting pathogenesis-associated targets of the Coronaviridae family that are required for the virus life cycle. In the current study, the chemistry, plant sources, and antiviral effects of alkaloids, as well as their anti-SARS-CoV-2 effect with related mechanisms, are reviewed towards discovering an effective treatment against COVID-19.

Characterization and optimization of de-esterified Tragacanth-chitosan nanocomposite as a potential carrier for oral delivery of insulin: In vitro and ex vivo studies.

Oral administration of insulin is one of the most challenging topics within this area, because insulin is degraded in stomach before it enters the bloodstream. In this study, for the first time, a nano-carrier for controlled and targeted oral delivery of insulin was developed using de-esterified Tragacanth and chitosan. The fabricated nanoparticles were synthesized using coacervation technique and their properties were optimized using response surface methodology. The effect of experimental variables on the particle size and loading efficiency was examined. In addition, the interactions between components were analyzed using Fourier transform infrared. The thermal stability of nanoparticles was studied by thermal gravimetric analysis. The insulin loading efficiency was measured and in vitro release profile and ex vivo insulin permeability was determined. Optimized nanoparticles showed spherical shape with a size less than 200 nm and zeta potential of +17 mV. Owing to their nanoscale dimensions and mucoadhesiveness, nanoparticles were synthesized using medium molecular weight of Chitosan. The insulin loading efficacy for the system was 6.4%, released under simulated gastrointestinal conditions in a pH-dependent manner. Based on all of the obtained results, it can be concluded that these nanoparticles can potentially be utilized as a carrier for the oral insulin delivery.

Co-electrospun nanofibrous mats loaded with bitter gourd (Momordica charantia) extract as the wound dressing materials: in vitro and in vivo study.

BACKGROUND: Interactive dressings are innovatively designed to interact with the wound surface and alter the wound environment to promote wound healing. In the current study, we integrated the physicochemical properties of Poly (caprolactone)/ Poly (vinyl alcohol)/Collagen (PCL/PVA/Col) nanofibers with the biological activities of Momordica charantia pulp extract to develop an efficient wound dressing. The electrospinning method was applied to fabricate the nanofibers, and the prepared wound dressings were thoroughly characterized. RESULTS: SEM imaging showed that the nanofibers were uniform, straight, without any beds with a diameter in the range of 260 to 480 nm. Increasing the concentration of the extract increased the diameter of the nanofibers and also the wettability characteristics while reduced the ultimate tensile strength from 4.37 ± 0.90 MPa for PCL/PVA/Col to 1.62 ± 0.50 MPa for PCL/PVA/Col/Ex 10% (p < 0.05). The in vivo studies showed that the application of the wound dressings significantly enhanced the healing process and the highest wound closure, 94.01 ± 8.12%, was obtained by PCL/PVA/Col/Ex 10% nanofibers (p < 0.05). CONCLUSION: The incorporation of the extract had no significant effects on nanofibers' porosity, water vapor permeability, and swelling characteristics. The in vitro evaluations showed that the fabricated nanofibers were hemocompatible, cytocompatible, and prevent bacterial penetration through the dressing. These findings implied that the PCL/PVA/Col/Ex nanofibers can be applied as the wound dressing materials.