Naringenin, a flavonoid with potent antioxidant properties, faces low bioavailability, limiting its clinical application in Alzheimer's disease. This study developed naringenin-loaded chitosan nanoparticles (NAR-CNPs) for nose-to-brain delivery using the ionic gelation method. The NAR-CNPs exhibited an average particle size of 112.35 ± 1.55 nm, zeta potential of 15.36 ± 2.05 mV, and entrapment efficiency of 69.49 ± 1.88 %, with a sustained release profile (65.80 % over 8 h). Ex vivo permeation studies showed a 1.91-fold higher steady-state flux for NAR-CNPs compared to naringenin suspension, indicating enhanced brain penetration. The NAR-CNPs were safe for goat nasal mucosa and improved cognitive function in scopolamine-induced demented mice, whereas significantly reducing acetylcholinesterase activity (p < 0.001) and increasing antioxidant enzyme activities in the brain of experimental mice. Concurrently, the level of malondialdehyde was decreased in the brain, indicating reduced lipid peroxidation. Histopathological analysis showed a significant increase in neuronal count in NAR-CNPs treated animals compared to control group. These findings suggest that intranasally administered NAR-CNPs hold promise for treating cognitive impairment, though further studies are needed for clinical translation.

BACKGROUND:Ageing is a complex process characterized by the gradual deterioration of physiological functions, often leading to a diminished quality of life. Dementia is among the prominent indicators of ageing characterized by cognitive impairment. Animal studies employing D-galactose have provided insights into the mechanisms underlying cognitive decline and neuronal degeneration, resembling features of human brain ageing while Vitamin K2, known for its diverse physiological functions, also have neuroprotective potential. Here we study the effect of Vitamin K2 in D-galactose induced ageing in mice. METHODS:Ageing was induced in adult Swiss albino mice using D-galactose via subcutaneous (SC) route for 45 days while one group of animals received Vitamin K2 (MK-7) via oral gavage during last 21 days. Then different behavioral studies, including the elevated plus maze, Morris water maze, passive avoidance and novel object recognition test were performed to measure cognitive changes, followed by measuring AChE, corticosterone (plasma), oxidative stress parameters (SOD, GSH, MDA) and pro-inflammatory markers (TNFα, IL1β) in hippocampal homogenates. Histopathology of the hippocampal sections were performed to measure neuronal density. RESULTS:Vitamin K2, treatment reversed D-galactose associated memory changes. In the biochemical studies, plasma corticosterone was reduced while hippocampal AChE, MDA and pro-inflammatory cytokines were reduced after Vitamin K2 treatment. The antioxidants like SOD and GSH were improved in Vitamin K2 treated animal brain. The hippocampal neuronal density increased in treatment group compared to D-galactose induced aged animals. CONCLUSION:Treatment with Vitamin K2 (MK-7) partially reversed cognitive decline associated with ageing, highlighting its potential as a therapeutic intervention for age associated cognitive decline.

Central nervous system-related disorders have become a continuing threat to human life and the current statistic indicates an increasing trend of such disorders worldwide. The primary therapeutic challenge, despite the availability of therapies for these disorders, is to sustain the drug's effective concentration in the brain while limiting its accumulation in non-targeted areas. This is attributed to the presence of the blood–brain barrier and first-pass metabolism which limits the transportation of drugs to the brain irrespective of popular and conventional routes of drug administration. Therefore, there is a demand to practice alternative routes for predictable drug delivery using advanced drug delivery carriers to overcome the said obstacles. Recent research attracted attention to intranasal-to-brain drug delivery for promising targeting therapeutics in the brain. This review emphasizes the mechanisms to deliver therapeutics via different pathways for nose-to-brain drug delivery with recent advancements in delivery and formulation aspects. Concurrently, for the benefit of future studies, the difficulties in administering medications by intranasal pathway have also been highlighted.

Background Honey has been used for centuries for its medicinal benefits, where topical treatments in the folklore literature reported its beneficial role in treating different types of wounds. Despite its immense use in wound care, honey’s exact mechanism remains unclear. Purpose The present study aimed to explore and abridge the gap between honey and its molecular wound healing mechanism. Methodology An extensive literature study has been performed where these activities can be explained due to phenolic compounds, nitric oxide, non-peroxide factors, low pH, high osmolarity, and hydrogen peroxide in honey. Besides that, honey also contains carbohydrates, proteins, amino acids, lipids, minerals, and vitamins, contributing to the wound healing potential to some extent. However, these metabolites and constituents differ among different honey varieties due to the distinct nutritional requirements of different species of bees and their collection of nectar from varied sources containing different natural actives. Results The revival of honey-based wound care research has identified a few probable mechanistic pathways of honey primarily due to its anti-inflammatory, antioxidant, antimicrobial, and immunomodulatory potentials. It also promotes angiogenesis, facilitates reepithelialization, stimulates proliferation of extracellular matrix, reduces neutrophil formation, modulates production of TNF-α, IL-1β, and IL-6, and prevents secondary infection at the wound site. Conclusion The varieties of honey vary in their qualities, phenolic compounds, and safety for human use. A few of these are currently clinically employed for wound dressings. Moreover, honey can be effective for managing complicated and chronic wounds; more extensive molecular research and safety profiling would be necessary.

Diabetes, a chronic metabolic disease, affects approximately 422 million people and leads to 1.5 million deaths every year, It is found that 45

•ACV and p-CA combination has been assessed for its antioxidant, antimicrobial, and wound-healing properties in two different doses.•This combination has also been compared with individual raw ACV and p-CA to confirm if the overall dosage of the ACV can be reduced to avoid side effects.•The combination drug therapy had a better effect than the individual component itself.

Vitamin K2/ Menaquinones produced predominantly by the gut microbiome improve bone health and prevent coronary calcification. The central nervous system has been linked with gut microbiota via the gut-brain axis and is strongly associated with psychiatric conditions. In the present study, we show the role of Vitamin K2 (MK-7) in gut dysbiosis-associated cognitive decline. Gut dysbiosis was induced in mice by administering Ampicillin (250 mg/kg twice a day orally) for 14 days and Vitamin K2 (0.05 mg/kg) for 21 days with or without antibiotic treatment and altered gene expression profile of intestinal microbes determined. This was followed by behavioural studies to determine cognitive changes. The behavioural observations are then correlated with proinflammatory, oxidative, and brain and intestinal histopathological changes in antibiotic-treated animals with or without vitamin K2 administration. With the use of antibiotics, Lactobacillus, Bifidobacterium, Firmicutes, and Clostridium's relative abundance reduced. When vitamin K2 was added to the medication, their levels were restored. Cognitive impairment was observed in behavioural trials in the antibiotic group, but this drop was restored in mice given both an antibiotic and vitamin K. Myeloperoxidase levels in the colon and brain increased due to gut dysbiosis, which vitamin K2 prevented. The acetylcholine esterase and oxidative stress markers brought on by antibiotics were also decreased by vitamin K2. Additionally, vitamin K2 guarded against alterations in intestine ultrastructure brought on by antibiotic use and preserved hippocampus neurons. So, it can be concluded that vitamin K2 improved cognitive skills, avoided hippocampus neuronal damage from antibiotics, and lowered intestine and brain inflammation and oxidative stress.

Multidrug salts represent more than one drug in a crystal lattice and thus could be used to deliver multiple drugs in a single dose. It showcases unique physicochemical properties in comparison to individual components, which could lead to improved efficacy and therapeutic synergism. This study presents the preparation and scale-up of sulfamethoxazole-piperazine salt, which has been thoroughly characterized by X-ray diffraction and thermal and spectroscopic analyses. A detailed mechanistic study investigates the impact of piperazine on the microenvironmental pH of the salt and its effect on the speciation profile, solubility, dissolution, and diffusion profile. Also, the improvement in the physicochemical properties of sulfamethoxazole due to the formation of salt was explored with lattice energy contributions. A greater ionization of sulfamethoxazole (due to pH changes contributed by piperazine) and lesser lattice energy of sulfamethoxazole-piperazine contributed to improved solubility, dissolution, and permeability. Moreover, the prepared salt addresses the stability issues of piperazine and exhibits good stability behavior under accelerated stability conditions. Due to the improvement of physicochemical properties, the sulfamethoxazole-piperazine salt demonstrates better pharmacokinetic parameters in comparison to sulfamethoxazole and provides a strong suggestion for the reduction of dose. The following study suggests that multidrug salts can concurrently enhance the physicochemical properties of drugs and present themselves as improved fixed-dose combinations.

Exposing the hydrated-soft-starch matrix of intact grain or reconstituted flour dough to a high-temperature-short-time (HTST) leads to rapid vapor generation that facilitates high-pressure build-up in its elastic matrix linked to large deformation and expansion. The expanded starch matrix at high temperatures dries up quickly by flash vaporization of water, which causes loss of its structural flexibility and imparts a porous and rigid structure of the expanded porous starch matrix (EPSM). EPSM, with abundant pores in its construction, offers adsorptive effectiveness, solubility, swelling ability, mechanical strength, and thermal stability. It can be a sustainable and easy-to-construct alternative to porous starch (PS) in food and pharmaceutical applications. This review is a comparative study of PS and EPSM on their preparation methods, structure, and physicochemical properties, finding compatibility and addressing challenges in recommending EPSM as an alternative to PS in adsorbing, dispersing, stabilizing, and delivering active ingredients in a controlled and efficient way.

Recent studies have shown that, coupled with other environmental factors, aluminium exposure may lead to neurodegeneration resulting in cognitive impairment resembling Alzheimer's disease. Menaquinone, a form of vitamin K2, aids in maintaining healthy bones and avoids coronary calcification. It also has anti-inflammatory and antioxidant properties. Here, we study the neuroprotective effects of vitamin K2 (MK-7) using the animal model of Alzheimer's disease (AD). Aluminium chloride (AlCl3; 100 mg/kg for 3 weeks orally) was administered to Swiss albino mice to induce neurodegeneration and Vitamin K2 (100 g/kg for 3 weeks orally) was applied as treatment. This was followed by behavioural studies to determine memory changes. The behavioural observations correlated with proinflammatory, oxidative, and brain histopathological changes in AlCl3-treated animals with or without vitamin K2 treatment. AlCl3 administration led to memory decline which was partially restored in Vitamin K2 treated animals. Myeloperoxidase levels in the brain increased due to AlCl3-mediated inflammation, which Vitamin K2 prevented. The acetylcholine esterase and oxidative stress markers induced by AlCl3 were reversed by Vitamin K2. Also, Vitamin K2 helps to restore hippocampal BDNF levels and reduced the amyloid β accumulation in AlCl3-administered animals. Additionally, Vitamin K2 protected the hippocampal neurons against AlCl3-mediated damage as observed in histopathological studies. We conclude that Vitamin K2 could partially reverse AlCl3-mediated cognitive decline. It increases acetylcholine and BDNF levels while reducing oxidative stress, neuroinflammation, and β-amyloid deposition, thus protecting the hippocampal neurons from AlCl3-mediated damage.

Neurodegeneration, a progressive disease due to the arrested development of atrophy and regression of neuron function, is the most common disorder people go through. The treatment of the disease is generally symptomatic, and after a certain time, the effectivity of the drug decreases. A less toxic compound, vitamin K, a lipophilic (fat-soluble) vitamin, shows some promising results. Generally, vitamin K is found in three different forms: phylloquinone (vitamin K1) from green vegetables, menaquinone (vitamin K2) from anaerobic bacteria, and synthetic analog menadione (vitamin K3). The biological activities of each form of vitamin K differ from each other. Vitamin K1 is mainly stored in the liver and has a more prominent role in forming coagulation proteins. On the other hand, vitamin K2 is widely dispersed throughout the human body. Here in this review, the therapeutic role of vitamin K in different disorders, mainly focusing the neurological disorders, including neuroinflammation, Parkinson's disease, Alzheimer's disease, and multiple sclerosis, is discussed. As a limited number of laboratories are involved in understanding vitamin K as a neuroprotective agent, the review will encourage further exploration in validating the neuroprotective effects of vitamin K among the pharmacognostic community.

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.

The microbiome is the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space (Medical and Health Genomics, 2016, page 15-28). The human gut is the location where the maximum number of microorganisms can be found. Among the different microorganisms they can be broadly classified into two groups: the beneficial and harmful. In the human gut there is always a balance between the beneficial and the opportunistic microorganism which maintains human health. However, if the balance is not maintained and homeostasis is disturbed, with an increase in opportunistic microorganisms, it may result in various diseases like inflammatory bowel disease, irritable bowel disease, ulcerative colitis, Crohn's disease, colorectal cancer, metabolic disorders and neurodegenerative diseases including motor neuron diseases. In the present chapter we discuss the role of gut bacteria in motor neuron diseases like multiple sclerosis, Parkinson's disease and amyotrophic lateral sclerosis.