Unlocking the potential of flavonoid-infused drug delivery systems for diabetic wound healing with a mechanistic exploration.

Diabetes is one of the common endocrine disorders generally characterized by elevated levels of blood sugar. It can originate either from the inability of the pancreas to synthesize insulin, which is considered as an autoimmune disorder, or the reduced production of insulin, considered as insulin resistivity. A wound can be defined as a condition of damage to living tissues including skin, mucous membrane and other organs as well. Wounds get complicated with respect to time based on specific processes like diabetes mellitus, obesity and immunocompromised conditions. Proper growth and functionality of the epidermis gets sustained due to impaired diabetic wound healing which shows a sign of dysregulated wound healing process. In comparison with synthetic medications, phytochemicals like flavonoids, tannins, alkaloids and glycosides have gained enormous importance relying on their distinct potential to heal diabetic wounds. Flavonoids are one of the most promising and important groups of natural compounds which can be used to treat acute as well as chronic wounds. Flavonoids show excellent properties due to the presence of hydroxyl groups in their chemical structure, which makes this class of compounds different from others. Based on the novel principles of nanotechnology via utilizing suitable drug delivery systems, the delivery of bioactive constituents from plant source amplifies the wound-healing mechanism, minimizes complexities and enhances bioavailability. Hence, the encapsulation and applicability of flavonoids with an emphasis on mechanistic route and wound-healing therapeutics have been highlighted in the subsequent study with focus on multiple drug delivery systems.

Comprehensive investigations for a potential natural prophylaxis-A cellular and murine model for apple cider vinegar against hydrogen peroxide and scopolamine induced oxidative stress.

Oxidative stress is the critical marker of neurological complications such as Alzheimer's disease (AD). Apple cider vinegar (ACV) is known to have health benefits due to its antidiabetic, anti-inflammatory, and high antioxidant properties. Therefore, we hypothesized that regular consumption of ACV would protect against AD-like neurological diseases via inhibition of oxidative stress. Authors have compared the efficacy of ACV with that of Chrysin and Rivastigmine in cellular and animal studies. In the cellular study, oxidative stress was induced in Neuro2A cells (1 × 107 ) via H2 O2 (50 µM) treatment. Subsequently, acetylcholinesterase (AChE) activity was performed, and cell viability, SOD, GSH, lipid peroxidation (MDA) levels were measured. Similarly, in the animal study, oxidative stress was introduced in Swiss albino mice (10-11 weeks old, 20-25 g, n = 30) via scopolamine (1 mg/kg). Subsequently, histopathological experiments were performed; cognitive ability, AChE activity, and SOD, GSH, and MDA levels were measured. The in vitro results indicated that ACV (2 µM) provided better protection than Chrysin and Rivstigmine in cell viability. ACV has also performed better in restoring the antioxidants markers (SOD, GSH levels) and reducing MDA and AChE levels. In the in vivo study, test compounds (ACV, Chrysin, and Rivastigmine) improved cognitive impairment, increased the SOD and GSH level, reduced the MDA level and AChE activity, and protected the cortex-hippocampal neurons from degeneration. Here also, ACV (0.7%) showed better neuroprotection than the other two compounds. Therefore, these results supported our hypothesis that moderate consumption of ACV might prove to be beneficial prophylaxis against AD-like neurological diseases.

High fat diet administration leads to the mitochondrial dysfunction and selectively alters the expression of class 1 GLUT protein in mice.

Metabolic syndrome is an agglomeration of disorders including obesity, diabetes and cardiovascular diseases and characterized as chronic mild inflammation which elevates the circulatory inflammatory markers. This could be due to mitochondrial dysfunction, oxidative stress and hypoxia as a consequence of high fat diet (HFD) intake. The present study focuses on the effects of HFD on lactate and mitochondrial metabolism as well as tissue dependent changes in glucose transporter (GLUT) expression in liver, skeletal muscles and adipose tissue of mouse. Lactate dehydrogenase (LDH) and mitochondrial dysfunction established the link between the occurrences of metabolic stress due to HFD. In this work, it was observed that chronic HFD administration aggravated the metabolic alterations by causing reduced ATP production, imbalanced oxidative stress and altered class 1 GLUTs expression. Chronic HFD significantly reduced (p < 0.001) the superoxide dismutase (SOD), catalase (CAT) activities alongside elevated liver injury markers AST and ALT. This in turn causes decreased ATP/ADP ratio, mitochondrial dysfunction and exacerbated LDH levels. This imbalance further led to altered GLUT expression in hepatic cells, adipose tissue and skeletal muscles. HFD significantly (p < 0.001) upregulated the GLUT 1 and 3 expressions while significant downregulated (p < 0.001) GLUT 2 and 4 expression in liver, skeletal muscles and white adipose tissue. These results revealed the link between class 1 GLUTs, mitochondrial dysfunction and HFD-induced metabolic disorder. It can be concluded that HFD impacts mitochondrial metabolism and reprograms tissue-dependent glucose transporter.

Assessment of efficacy of chrysin in diabetes-associated cardiac complications in chick embryo and murine model.

OBJECTIVES: Patients with type 2 diabetes or prolonged diabetic condition are webbed into cardiac complications. This study aimed to ascertain the utility of chick embryo as an alternative to the mammalian model for type 2 diabetes-induced cardiac complications and chrysin as a protective agent. METHODS: Diabetes was activated in ovo model (chick embryo) using glucose along with ß-hydroxybutyric acid. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Alamar, and Kenacid blue assay were used to compare with chrysin-administered group. Blood glucose level, total cholesterol, triglyceride, and high-density lipoprotein were considered as endpoints. Diabetes was induced in Wistar albino rats by administering a high-fat diet and a subdued dose of streptozotocin (35 mg/kg, b.w). Percentage of glycated hemoglobin, creatinine kinase-MB, tumor necrosis factor-α, and C-reactive protein were evaluated and compared with chrysin administered group. KEY FINDINGS: Chrysin treatment improved elevated blood glucose levels and dyslipidemia in a diabetic group of whole embryos. Condensed cellular growth and protein content as well as enhanced cytotoxicity in ovo were shielded by chrysin. Chrysin reduced cardiac and inflammatory markers in diabetic rats and provided cellular protection to damage the heart of diabetic rats. CONCLUSION: The protective action of chrysin in ovo model induced a secondary complication associated with diabetes, evidenced that the ovo model is an effective alternative in curtailing higher animal use in scientific research.

Saccharomyces boulardii ameliorates gut dysbiosis associated cognitive decline.

Saccharomyces boulardii, a probiotic yeast is well prescribed for various gastrointestinal disorders accompanied by gut dysbiosis such as inflammatory bowel disease, bacterial diarrhea and antibiotic associated diarrhea. Gut dysbiosis has been associated with central nervous system via gut brain axis primarily implied in the modulation of psychiatric conditions. In the current study we use Saccharomyces boulardii as a therapeutic agent against gut dysbiosis associated cognitive decline. In mice, gut dysbiosis was induced by oral Ampicillin Na (250 mg/kg twice-daily) for 14 days. While in the treatment group S. boulardii (90 mg/kg once a day) was administered orally for 21 days along with 14 days of antibiotic treatment. Gene expression studies revealed antibiotic mediated decrease in the Lactobacillus, Bifidobacterium, Firmicutes and Clostridium which were restored by S. boulardii treatment. Cognitive behavioral studies showed a parallel reduction in fear conditioning, spatial as well as recognition memory which were reversed upon S. boulardii treatment in these animals. S. boulardii treatment reduced myeloperoxidase enzyme, an inflammatory marker, in colon as well as brain which was increased after antibiotic administration. Similarly, S. boulardii reduced the brain acetylcholine esterase, oxidative stress and inflammatory cytokines and chemokines which were altered due to antibiotic treatment. S. boulardii treatment also protected hippocampal neuronal damage and restored villus length and crypt depth thus normalizing gut permeability in antibiotic treated animals. Hence, we conclude that S. boulardii prevented antibiotic associated gut dysbiosis leading to reduced intestinal and brain inflammation and oxidative stress thus preventing hippocampal neuronal damage and eventually reversing gut dysbiosis associate cognitive decline in mice.

Ameliorative effects of apple cider vinegar on neurological complications via regulation of oxidative stress markers.

Dementia linked with cognitive impairments is the most prominent indication of Alzheimer's disease (AD). In the current investigation, we have examined the streptozotocin- (STZ) induced cellular toxicity in mouse neuroblastoma (N2A) cells, and Zn with the high-fat diet- (HFD) induced neurotoxicity in mouse brain. These cells and animals were pretreated with apple cider vinegar (ACV), Chrysin, and Rivastigmine to examine their protection against cellular toxicity and neurotoxicity. Experiments have affirmed that pretreatment of ACV, Chrysin, and Rivastigmine has displayed protective outcomes in MTT reduction, tau phosphorylation, amyloid aggregation, attenuated memory impairment as well as oxidative stress, and protected cholinergic hippocampal neurons from degeneration. ACV showed better antioxidant and neuroprotection potential as compared with Chrysin and Rivastigmine. So the existence of excitatory/inhibitory enzymatic activity and higher antioxidant potential indicate that ACV, as a food beverage in a regular diet, could be promising and effective against neurological complications such as AD. PRACTICAL APPLICATIONS: In the Urban lifestyle, HFD and stress are the critical factors of various chronic and prevalent diseases, including diabetes, obesity, cardiovascular, and neurodegenerative disorders like AD. We are already familiar with the multiple benefits of ACV, such as weight loss, antimicrobial activity, diabetes, skin disorders. So in the current research work, we have gauged the effectiveness of ACV against neurological complications in comparison with a synthetic flavonoid (Chrysin) and an anti-Alzheimer's drug (Rivastigmine). To enhance the pragmatic orientation of our results, we have used the ACV in our study, which is readily available in the market for domestic consumption. All the cellular, biochemical, behavioral, and histopathological data revealed that ACV had high antioxidant potential. Our findings suggest that the addition of ACV as a food additive in the daily diet may reduce the threat of multiple neurodegenerative diseases. Therefore, our study could be the precursor of a new pharmacological therapeutic approach via ACV toward cognitive impairments associated with Alzheimer's disease.

Probiotics protect against gut dysbiosis associated decline in learning and memory.

Gut-Brain-Axis imbalance due to gut dysbiosis by antibiotics may lead to neurobehavioral changes. Here we determine neuroprotective effect of probiotic against gut dysbiosis associated decline in learning and memory. Oral Ampicillin was used to induce gut dysbiosis while probiotic was administered along with antibiotic as treatment in Swiss albino mice. Antibiotic decreased Lactobacillus, Bifidobacterium, Firmicutes and Clostridium level. This was followed by reduced cognition, hippocampal neuronal density, intestinal crypt depth, villus length and increased corticohippocampal acetylcholinesterase, myeloperoxidase activity and oxidative stress which were partially reversed by probiotic treatment. Probiotic protected hippocampal neurons from gut dysbiosis associated inflammatory and oxidative damage in mice.

Ixora coccinea Enhances Cutaneous Wound Healing by Upregulating the Expression of Collagen and Basic Fibroblast Growth Factor.

Background. Ixora coccinea L. (Rubiaceae) has been documented for traditional use in hypertension, menstrual irregularities, sprain, chronic ulcer, and skin diseases. In the present study, I. coccinea was subjected to in vitro and in vivo wound healing investigation. Methods. Petroleum ether, chloroform, methanol, and water sequential I. coccinea leaves extracts were evaluated for in vitro antioxidant, antimicrobial, and fibroblast proliferation activities. The promising I. coccinea methanol extract (IxME) was screened for in vivo wound healing activity in Wistar rat using circular excision model. Wound contraction measurement, hydroxyproline quantification, and western blot for collagen type III (COL3A1), basic fibroblast growth factor (bFGF), and Smad-2, -3, -4, and -7 was performed with 7-day postoperative wound granulation tissue. Gentamicin sulfate (0.01% w/w) hydrogel was used as reference standard. Results. IxME showed the potent antimicrobial, antioxidant activities, with significant fibroblast proliferation inducing activity, as compared to all other extracts. In vivo study confirmed the wound healing accelerating potential of IxME, as evidenced by faster wound contraction, higher hydroxyproline content, and improved histopathology of granulation tissue. Western blot analysis revealed that the topical application of I. coccinea methanol extract stimulates the fibroblast growth factor and Smad mediated collagen production in wound tissue.