The misfolding mystery: α-syn and the pathogenesis of Parkinson's disease.

Neurodegenerative diseases such as Parkinson's disease (PD) are characterized by the death of neurons in specific areas of the brain. One of the proteins that is involved in the pathogenesis of PD is α-syn (α-syn). α-Syn is a normal protein that is found in all neurons, but in PD, it misfolds and aggregates into toxic fibrils. These fibrils can then coalesce into pathological inclusions, such as Lewy bodies and Lewy neurites. The pathogenic pathway of PD is thought to involve a number of steps, including misfolding and aggregation of α-syn, mitochondrial dysfunction, protein clearance impairment, neuroinflammation and oxidative stress. A deeper insight into the structure of α-syn and its fibrils could aid in understanding the disease's etiology. The prion-like nature of α-syn is also an important area of research. Prions are misfolded proteins that can spread from cell to cell, causing other proteins to misfold as well. It is possible that α-syn may behave in a similar way, spreading from cell to cell and causing a cascade of misfolding and aggregation. Various post-translational alterations have also been observed to play a role in the pathogenesis of PD. These alterations can involve a variety of nuclear and extranuclear activities, and they can lead to the misfolding and aggregation of α-syn. A better understanding of the pathogenic pathway of PD could lead to the development of new therapies for the treatment of this disease.

Diabetes Warriors from Heart Wood: Unveiling Dalbergin and Isoliquiritigenin from Dalbergia latifolia as Potential Antidiabetic Agents in-vitro and in-vivo.

Diabetes mellitus is a serious and complex metabolic disorder characterized by hyperglycemia. In recent years natural products has gained much more interest by researchers as alternative sources for diabetes treatment. Though many potential agents are identified so far but their clinical utility is limited because of their adverse effects. Therefore, there is a keen interest in discovering natural compounds to treat diabetes efficiently with less side effects. Dalbergia latifolia is well explored because of its diverse pharmacological activities including diabetes. Therefore, the present research work aimed to identify and isolate the potential antidiabetic agents from the heart wood of Dalbergia latifolia. We successfully extracted DGN and ISG from the heartwood and evaluated their antidiabetic potential both in-vivo and in-vitro. Alpha amylase activity inhibition of ISG and DGN was found to be 99.05 ± 8.54% (IC50 = 0.6025 µg/mL) and 84.68 ± 5.2% (IC50 = 0.0216 µg/mL) respectively. Glucose uptake assay revealed DGN (158%) promoted maximum uptake than ISG (77%) over control. In vivo anti diabetic activity was evaluated by inducing diabetes in SD rats with the help of HFD and STZ (35 mg/kg body weight). After the continuous administration of DGN (5 mg/kg, 10 mg/kg) and ISG (5 mg/kg, 10 mg/kg) for 14 days, we observed the reduction in the blood glucose levels, body weight, total cholesterol, low density lipoprotein, very low-density lipoprotein, blood urea, serum creatinine, serum glutamate oxaloacetic transaminase, serum glutamate pyruvate transaminase and alkaline phosphatase levels than vehicle group indicates the potency of ISG and DGN against diabetes.

Enhancing the oral bioavailability of fisetin: polysaccharide-based self nano-emulsifying spheroids for colon-targeted delivery.

Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.

Screening of natural epigenetic modifiers for managing glycemic memory and diabetic nephropathy.

Short hyperglycaemic episodes trigger metabolic memory (MM) in which managing hyperglycaemia alone is not enough to tackle the progression of Diabetic nephropathy on the epigenetic axis. We used a structural similarity search approach to identify phytochemicals similar to natural epigenetic modifiers and docked with SIRT1 protein and did ADME studies. We found that UMB was 84.3% similar to esculetin. Upon docking, we found that UMB had a binding energy of -9.2 kcal/mol while the standard ligand had -11.8 kcal/mol. ADME showed UMB to be a good lead. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed it to be a good antioxidant with IC50 of 107 µg/mL and MTT stands for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) showed that it does not promote cell death. Oxidative biomarkers in vitro showed UMB was able to ameliorate glycemic memory induced by high glucose. Western blot revealed decreased histone acetylation under hyperglycaemic conditions and upon treatment with UMB along with DR, its levels increased. This led us to check our hypothesis of whether concomitant diet reversal (DR) together with UMB can alleviate high-fat diet-induced metabolic memory and diabetic nephropathy (DN) in SD rats. UMB was able to decrease blood glucose, lipid, renal, and liver profile concluding UMB was able to ameliorate DN and MM by increasing the histone acetylation level.

Nephro-protective effects of alpha-lipoic acid in type I diabetes.

Type 1 diabetes (T1D) is an insulin-dependent autoimmune condition. Short chain fatty acids (SCFAs) are volatile fatty acids with 1-6 carbon atoms that influence glucose storage in the body and can reduce appetite, potentially decreasing T1D risk. Alpha-lipoic acid (α-LA), a type of SCFA, has previously been used to treat diabetic neuropathy and inflammation due to its antioxidant properties. This study aims to assess α-LA's protective effects against T1D and associated kidney damage in rats induced with streptozotocin. Diabetic rats were treated with α-LA orally for 15 days, resulting in improved blood glucose (56% decrease) and kidney function markers like blood urea nitrogen, creatinine and uric acid. α-LA also showed significant antioxidant effects by decreasing LPO as well as improving activities of antioxidant enzymes like superoxide dismutase, catalase and glutathione-S transferase and alleviated kidney damage caused by diabetes. Docking experiments suggest that α-LA may regulate diabetes-related changes at the epigenetic level through interactions with the SIRT1 protein, indicating its potential as a target for future antidiabetic drug development.

PPAR gamma agonistic activity of dillapiole: protective effects against diabetic nephropathy.

Using structural similarity approach we identified dillapiole, a phenylpropanoid, the main component of Piper aduncum L. and Anethum graveolens L. essential oils as potential PPARγ agonist. Molecular docking revealed that dillapiole binds to the active site of PPARγ, similar to pioglitazone binding. In silico ADME studies showed that dillapiole has high water solubility and GI absorption. Dillapiole was also observed to be partial agonist of PPARγ receptors with EC50 of 43.95 µM. In BHK-21 cells cultured under hyperglycaemic conditions, dillapiole administration reduced oxidative stress and prevented decrease in histone H3 acetylation (k9/14) levels. In HFD + STZ induced diabetic mice, dillapiole treatment for 7 days was able to improve renal functions and decrease plasma glucose level to 138.39 ± 12.36 mg/dl along with decreasing total cholesterol (29%), triglycerides (48.8%), LDL (24.7%), and VLDL (65%) levels in serum. These results show that dillapiole is a potential PPARγ-agonist and thus needs to explore further.

Prevalence of self-medication practices among pregnant women in India: A systematic review and meta-analysis.

BACKGROUND: Self-medication practice among pregnant women is a global concern. However, its understanding in the Indian context is limited due to a lack of comprehensive studies. PURPOSE: This study aimed to comprehensively assess the prevalence of self-medication, the medications used for self-medication, diseases/conditions associated with self-medication, and the reasons for self-medication among Indian pregnant women. METHODS: This study was carried out following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A thorough search was done in PubMed, Embase, and Google Scholar to find articles that were published up until May 2023. Inclusion criteria comprised observational studies reporting self-medication prevalence among pregnant women in India. Data were extracted using a standardized sheet, and a random-effects model was applied to determine the overall prevalence of self-medication using R software. The I2 statistic was employed to assess the heterogeneity among the studies. RESULTS: This study analyzed eight studies with a collective sample size of 2208 pregnant women. The pooled prevalence of self-medication among pregnant Indian women was 19.3% (95% CI: 7.5%-41.3%; I2 = 99%; p < 0.01). Common self-treated conditions were cold, cough, fever, headache, and stomach disorders. Antipyretics, analgesics, antihistamines, and antacids were frequently used for self-medication. The perception of mild ailment, immediate alleviation, convenience, time savings, and advice from family, friends, or the media were all reasons for self-medication. Local pharmacies were the most usual source for obtaining drugs, and pharmacists, family, friends, and past prescriptions were common sources of medicine information. CONCLUSIONS: A low yet substantial number of pregnant women in India are engaged in self-medication practices. Appropriate strategies need to be planned to reduce self-medication practices to attain sustainable developmental goals for maternal health in India.

Osteomyelitis and non-coding RNAS: A new dimension in disease understanding.

Osteomyelitis, a debilitating bone infection, presents considerable clinical challenges due to its intricate etiology and limited treatment options. Despite strides in surgical and chemotherapeutic interventions, the treatment landscape for osteomyelitis remains unsatisfactory. Recent attention has focused on the role of non-coding RNAs (ncRNAs) in the pathogenesis and progression of osteomyelitis. This review consolidates current knowledge on the involvement of distinct classes of ncRNAs, including microRNAs, long ncRNAs, and circular RNAs, in the context of osteomyelitis. Emerging evidence from various studies underscores the potential of ncRNAs in orchestrating gene expression and influencing the differentiation of osteoblasts and osteoclasts, pivotal processes in bone formation. The review initiates by elucidating the regulatory functions of ncRNAs in fundamental cellular processes such as inflammation, immune response, and bone remodeling, pivotal in osteomyelitis pathology. It delves into the intricate network of interactions between ncRNAs and their target genes, illuminating how dysregulation contributes to the establishment and persistence of osteomyelitic infections. Understanding their regulatory roles may pave the way for targeted diagnostic tools and innovative therapeutic interventions, promising a paradigm shift in the clinical approach to this challenging condition. Additionally, we delve into the promising therapeutic applications of these molecules, envisioning novel diagnostic and treatment approaches to enhance the management of this challenging bone infection.

Serum Zinc Level and Efficacy of Zinc Therapy in Cutaneous Leishmaniasis: a Systematic Review and Meta-analysis.

Cutaneous leishmaniasis is a parasitic skin disease prevalent in many parts of the world. Zinc has been investigated for its potential role in the immune response against Leishmania parasites. This study aimed to systematically review the literature and conduct meta-analyses to evaluate the serum zinc level and efficacy of zinc therapy in cutaneous leishmaniasis. A comprehensive search of electronic databases was performed to find studies reporting serum zinc levels and the efficacy of zinc therapy in cutaneous leishmaniasis. Meta-analyses were conducted using RevMan software (version 5.4), calculating the mean difference for serum zinc levels and risk ratio for the efficacy of zinc therapy. A total of 11 studies with 1009 participants were evaluated. Five of these studies, comprising 637 participants, examined serum zinc levels; the remaining six, involving 372 individuals, examined the effectiveness of zinc therapy in treating cutaneous leishmaniasis. The results showed that the serum zinc level was significantly lower in cutaneous leishmaniasis patients compared to controls (MD: - 26.65; 95% CI: [- 42.74, - 10.57]; p = 0.001). However, zinc therapy did not demonstrate a significant clinical improvement compared to standard treatment (RR: 0.96; 95% CI: [0.74, 1.23], p = 0.73).

Artificial viruses: A nanotechnology based approach.

OBJECTIVES: The main objective of this work was to review and summarise the detailed literature available on viral nanoparticle and the strategies utilised for their manufacture along with their applications as therapeutic agents. DATA ACQUISITION: The reported literature related to development and application of virus nanoparticles have been collected from electronic data bases like ScienceDirect, google scholar, PubMed by using key words like "viral nanoparticles", "targeted drug delivery" and "vaccines" and related combinations. RESULT: From the detailed literature survey, virus nanoparticles were identified as carriers for the targeted delivery. Due to the presence of nanostructures in virus nanoparticles, these protect the drugs from the degradation in the gastrointestinal tract and in case of the delivery of gene medicine, they carry the nucleic acids to the target/susceptible host cells. Thus, artificial viruses are utilised for targeted delivery to specific organ in biomedical and biotechnological areas. CONCLUSION: Thus, virus nanoparticles can be considered as viable option as drug/gene carrier in various healthcare sectors especially drug delivery and vaccine and can be explored further in future for the development of better drug delivery techniques.

Novel Approaches for the Management of Type 2 Diabetes Mellitus: An Update.

Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the ß cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication's traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin.

Significant Advancement in Various Synthetic Strategies and Pharmacotherapy of Piperine Derivatives: A Review.

BACKGROUND: Piperine is a natural compound found in black pepper that has been traditionally used for various therapeutic purposes. In the ayurvedic system of medication there is a lot of evidence which shows that the piperine is widely used for different therapeutic purpose. In recent years, there has been an increasing interest in the pharmacological and therapeutic potential of piperine and its derivatives in modern medicine. In order to increase the bioavailability and therapeutic effectiveness of piperine and its analogs, researchers have been looking at various extraction methods and synthesis approaches. Many studies have been conducted in this area because of the promise of piperine as a natural substitute for synthetic medications. OBJECTIVES: The objective of this review article is to provide an up-to-date analysis of the literature on the synthesis of piperine analogs, including their extraction techniques and various biological activities such as antihypertensive, antidiabetic, insecticidal, antimicrobial, and antibiotic effects. Additionally, the review aims to discuss the potential of piperine in modern medicine, given its traditional use in various medicinal systems such as Ayurveda, Siddha, and Unani. The article also provides a comprehensive analysis of the plant from which piperine is derived. CONCLUSION: This review article provides a thorough examination of piperine and the source plant. The best extraction technique for the extraction of piperine and the synthesis of its analogs with various biological activities, including antihypertensive, antidiabetic, insecticidal, antibacterial, and antibiotic properties, are covered in the article. This review aims to provide an updated analysis of the literature on the synthesis of piperine analogs.

The multifactorial role of vanillin in amelioration of aluminium chloride and D-galactose induced Alzheimer's disease in mice.

The onset and progression of Alzheimer's disease (AD) are influenced by a variety of factors. These include oxidative stress, overexpression of acetylcholinesterase (AChE), depletion of acetylcholine levels, increased beta-secretase mediated conversion of Amyloid Precursor Protein (APP) to Amyloid Beta (Abeta), accumulation of Abeta oligomers, decrease in Brain Derived Neurotrophic factor (BDNF) and accelerated neuronal apoptosis due to elevated levels of caspase-3. The currently available therapeutic approaches are inadequate in affecting these pathological processes except maybe the overexpression of AChE (AChE inhibitors like donepezil, rivastigmine). There is an urgent need to develop disease modifying pharmacotherapeutic interventions which have appreciable safety and cost effectiveness. From previously reported in vitro studies and a preliminary assessment of neuroprotective effect in scopolamine induced dementia-like cognitive impairment in mice, vanillin has been used as the compound of interest in the present study. Vanillin, a phytoconstituent, has been used in humans, safely, in the form of a flavouring agent for various foods, beverages, and cosmetics. Owing to its chemical nature i.e. being a phenolic aldehyde, it has an additional antioxidant property that is congruent to the desirable characteristics that are sought in a suitable novel anti-AD agent. In our study, vanillin proved to have a nootropic effect in healthy Swiss albino mice as well as an ameliorative effect in aluminium chloride and D-galactose induced AD model in mice. Apart from tackling oxidative stress, vanillin was found to reduce the levels of AChE, beta secretase, caspase-3, enhance degradation of Abeta plaques and elevate the levels of BDNF, in cortical and hippocampal regions. Vanillin is a promising candidate for being incorporated into the search for safe and effective anti-AD molecules. However, further research might be needed to warrant its application clinically.

Aspects of Nanotechnology for COVID-19 Vaccine Development and Its Delivery Applications.

Coronavirus, a causative agent of the common cold to a much more complicated disease such as "severe acute respiratory syndrome (SARS-CoV-2), Middle East Respiratory Syndrome (MERS-CoV-2), and Coronavirus Disease 2019 (COVID-19)", is a member of the coronaviridae family and contains a positive-sense single-stranded RNA of 26-32 kilobase pairs. COVID-19 has shown very high mortality and morbidity and imparted a significantly impacted socioeconomic status. There are many variants of SARS-CoV-2 that have originated from the mutation of the genetic material of the original coronavirus. This has raised the demand for efficient treatment/therapy to manage newly emerged SARS-CoV-2 infections successfully. However, different types of vaccines have been developed and administered to patients but need more attention because COVID-19 is not under complete control. In this article, currently developed nanotechnology-based vaccines are explored, such as inactivated virus vaccines, mRNA-based vaccines, DNA-based vaccines, S-protein-based vaccines, virus-vectored vaccines, etc. One of the important aspects of vaccines is their administration inside the host body wherein nanotechnology can play a very crucial role. Currently, more than 26 nanotechnology-based COVID-19 vaccine candidates are in various phases of clinical trials. Nanotechnology is one of the growing fields in drug discovery and drug delivery that can also be used for the tackling of coronavirus. Nanotechnology can be used in various ways to design and develop tools and strategies for detection, diagnosis, and therapeutic and vaccine development to protect against COVID-19. The design of instruments for speedy, precise, and sensitive diagnosis, the fabrication of potent sanitizers, the delivery of extracellular antigenic components or mRNA-based vaccines into human tissues, and the administration of antiretroviral medicines into the organism are nanotechnology-based strategies for COVID-19 management. Herein, we discuss the application of nanotechnology in COVID-19 vaccine development and the challenges and opportunities in this approach.

Ameliorative effect of vanillin on scopolamine-induced dementia-like cognitive impairment in a mouse model.

Background: Alzheimer's disease (AD) is the most common form of dementia, which is among the top five causes of death in the United States. It is a neurodegenerative disorder that causes permanent loss of memory and cognition. The current pharmacotherapy for AD is based on providing symptomatic relief only and has many side effects. There is a need for a safer, disease-modifying drug for the treatment of AD. Experimental approach: The PASS online software was used to screen phytoconstituents based on their predicted effects on various AD-related targets. Vanillin was selected as the compound of interest, as it has not been researched elaborately on any animal model of AD. The acetylcholinesterase inhibitory activity of vanillin was established in vitro. Thereafter, ameliorative effect of vanillin was evaluated using the exteroceptive memory model in scopolamine-induced cognitive impairment mice model. Results: Vanillin showed an acetylcholinesterase inhibitory activity in vitro, and the IC50 value was calculated to be 0.033 mM. Vanillin significantly reversed the memory and behavioral deficits caused by scopolamine as demonstrated by significant improvement in memory in negative reinforcement, elevated plus maze, and spatial learning paradigms. Vanillin also proved to have a nootropic effect. Also, vanillin proved to have significantly better antioxidant and acetylcholinesterase inhibitory effects in vivo than donepezil hydrochloride. The potential anti-AD activity of vanillin was also confirmed by the reduction in IL-6 levels and TNF-α levels. Conclusion: Our results suggest that vanillin is a safe and effective natural drug candidate having a great potential for the treatment of AD. However, more research is required to evaluate its effect on A beta plaques and Tau neurofibrillary tangles in vivo.

Development, optimization, and validation of Inflammatory Bowel Disease rat model using isotretinoin.

BACKGROUND: and Purpose: Inflammatory Bowel Disease (IBD) is a persistent bio-psychological disorder with the absence of actual pathological reason. Association between IBD and isotretinoin has been reported by many human and in vitro studies. However, in this study, our focus is on finding the causal relationship between IBD and isotretinoin for the development of a new animal model. METHODS: Twenty-eight Sprague Dawley rats were taken for this study and divided into five groups (i.e. Group 1: Normal control, Group 2: Standard IBD Model Group (Indomethacin treated), Group 3: Isotretinoin low dose (7 mg/kg), Group 4: Isotretinoin medium dose (35 mg/kg), Group 5: Isotretinoin high dose (70 mg/kg). The rats were treated according to assigned treatment and observed on different days to evaluate the severity of IBD with the help of symptomatical (nausea, diarrhea, stool consistency, etc.) activity, biochemical parameters, macroscopy, and histological analyses. KEY RESULTS: During the entire study period, body weight, stool consistency and frequency of the animals had been observed daily. No significant reduction in body weight was observed between the disease induced and normal control animals; however, it was observed that the stool consistency of the animals became less (mucus in stool) day by day and stool frequency increased (frequent defecation) in the different isotretinoin groups compared to the control group. There was statistically significant increase in TBARS levels of isotretinoin low (p < 0.05), medium (p < 0.001) and high dose (p < 0.01) treated group was observed, as compared to control group. Similarly, statistically significant effects of isotretinoin on GSH level (p < 0.01), CAT activity (p < 0.01), and SOD (p < 0.01) were also observed. Increase in TNF-α levels found significantly higher in isotretinoin medium dose (35 mg/kg) treated group (p < 0.001) as compared with control group as well as standard IBD model group. All the three-isotretinoin treated groups (Isotretinoin low dose: p < 0.001; Isotretinoin medium dose: p < 0.001; Isotretinoin high dose: p < 0.001) depicted significant difference in macroscopic scores as compared with control group; these results are comparable with standard IBD model group. Histological analyses revealed that, among three-dose groups of isotretinoin, there was excessive amount of crypt abscesses, infiltration of inflammatory cells, and formation of ulceration observed in isotretinoin medium dose treated group. CONCLUSION: As standard indomethacin treated group, isotretinoin also caused significant damage to intestinal mucosa, and form ulceration in gastrointestinal tract. Compared to control group, isotretinoin significantly worsens the disease condition, which were comparable to the indomethacin-treated group; however, isotretinoin at the dose of 35 mg/kg caused maximum severe damage to the intestinal mucosa.

Improved neuroprotective activity of Fisetin through SNEDDS in ameliorating the behavioral alterations produced in rotenone-induced Parkinson's model.

Fisetin is a polyphenolic flavonoid reported to have antioxidant, anti-inflammatory, and anti-cancer activities. However, it loses its importance as an effective phytochemical due to its poor water solubility and lower bioavailability. In the present study, the self-nanoemulsifying drug delivery system (SNEDDS) of fisetin was developed in order to improve its pharmacological activity. The developed SNEDDS of fisetin was evaluated for improving the rotenone-induced behavioral changes in the rats, and its efficacy was compared with naïve fisetin. It was noticed that fisetin loaded in the SNEDDS formulation significantly (p < 0.001) ameliorated the rotenone-induced alteration in the body weight, grip strength, beam walk, postural instability, etc., in rats when compared to the effect of naïve fisetin. Naïve fisetin significantly (p < 0.05) ameliorated the effect of rotenone on the level of dopamine only at a higher dose. Whereas, SNEDDS of fisetin produced a significant (p < 0.05) effect at both dose levels when compared with the diseased group as well as also produced a significant (p < 0.05) effect when compared with the naïve fisetin group. The results of histopathological examination revealed about the neuroprotective effect of SNEDDS loaded with fisetin as observed through the protection of neuronal damage. From this study, it was concluded that SNEDDS improved the anti-Parkinsonian activity of fisetin by improving the behavioral alteration produced by rotenone due to enhancement in its solubility and bioavailability.

Pharmacological evaluation of bromelain in mouse model of Alzheimer's disease.

The current study elucidates pharmacological evaluation of bromelain as a bioactive compound obtain from pineapple stem belongs to family Bromeliaceae in AlCl3 and D - galactose induced mice. In mice, co-administration of AlCl3 at dose 5 mg/kg b.w., via the oral route, and D - galactose at dose 60 mg/kg b.w., via intraperitoneal route for 90 days resulted in cognitive impairment, spatial learning, and memory deficits, as well as neurotoxicity. However, 30 consecutive days, treatments via an intraperitoneal route with bromelain low dose (Brm L) at dose 10 mg/kg b.w., bromelain high dose (Brm H) at dose 20 mg/kg b.w., donepezil (Dnpz) at dose 2 mg/kg b.w., and Brm L + Dnpz at doses 10, 2 mg/kg b.w. were considerably reversed the effect of AlCl3 and D - galactose induced AD mice. Consequences of behavioral parameters (Morris water maze, elevated plus maze and locomotor), biochemical estimation (MDA, GSH, SOD, CAT, Nitrite and AChE), and ELISA tests (mouse BACE, Aß1 - 42, TNF-α, IL-6, and BDNF) confirmed significant (p < 0.05) neuroprotective effect of treatments in AlCl3 and D - galactose induced mice. Additionally, hematoxylin and eosin staining of the cerebral cortex and the hippocampus exposed eosinophilic lesions and hyperchromatic nuclei in AD mice, but these neurodegenerative effects were eliminated by Brm L, Brm H, Dnpz, and Brm L + Dnpz treatments. Thus, bromelain alone and in combination with donepezil prevent AlCl3 and D - galactose induced spatial learning and memory deficits, as well as cognitive impairment, by increasing cholinergic activity and synaptic plasticity, as well as reducing oxidative damage, neuroinflammation, Aß 1-42 aggregations, and histopathological damage, according to our findings. The present study consequences indicate that bromelain alone and in combination with donepezil appears to have neuroprotective properties. Henceforward, this may be a promising treatment option for Alzheimer's disease.

p-Coumaric acid attenuates high-fat diet-induced oxidative stress and nephropathy in diabetic rats.

The prevalence of persistent hyperglycaemia during diabetes, impair antioxidant defence system and generate reactive oxygen species, which majorly contribute to its progression and associated complications. Phytochemicals were suggested to scavenge-free radicals and exert antioxidant effects required to improve insulin sensitivity and reduce the occurrence of diabetes-associated complications. We hypothesise that a phenolic phytochemical p-coumaric can reduce diabetes-induced oxidative stress and improve diabetes-associated nephropathy in rats. The aim of this study is to analyse the protective effects of p-coumaric acid against diabetes-induced oxidative stress and nephropathy in high-fat diet-induced diabetic rats. The oral feeding of p-coumaric acid (20 mg/kg for 12 weeks) was found to significantly decrease the elevated levels of blood glucose in high-fat diet-induced type 2 diabetic rats. p-Coumaric acid treatment also decreases the kidney weight whilst increasing the total body weight of diabetic rats. Furthermore whilst evaluation of the different renal functioning tests, p-coumaric acid significantly improves histopathological changes and the levels of urea, creatinine and uric acid in serum of diabetic rats, which was otherwise elevated under diabetic conditions. Our results also highlight that p-coumaric acid is an efficient compound with antioxidant properties and improves the diabetes-induced change in lipid peroxidation and activities of antioxidant enzymes: catalase, glutathione-S-transferase and superoxide dismutase. p-Coumaric acid thus possesses the potential to prevent diabetic nephropathy by reducing oxidative stress and can thus serve as a potential drug target for pharmaceutical companies.