Mesoporous Silica-Based Nanoplatforms Are Theranostic Agents for the Treatment of Inflammatory Disorders.

Complete recovery from infection, sepsis, injury, or trauma requires a vigorous response called inflammation. Inflammatory responses are essential in balancing tissue homeostasis to protect the tissue or resolve harmful stimuli and initiate the healing process. Identifying pathologically important inflammatory stimuli is important for a better understanding of the immune pathways, mechanisms of inflammatory diseases and organ dysfunctions, and inflammatory biomarkers and for developing therapeutic targets for inflammatory diseases. Nanoparticles are an efficient medical tool for diagnosing, preventing, and treating various diseases due to their interactions with biological molecules. Nanoparticles are unique in diagnosis and therapy in that they do not affect the surroundings or show toxicity. Modern medicine has undergone further development with nanoscale materials providing advanced experimentation, clinical use, and applications. Nanoparticle use in imaging, drug delivery, and treatment is growing rapidly owing to their spectacular accuracy, bioavailability, and cellular permeability. Mesoporous silica nanoparticles (MSNs) play a significant role in nano therapy with several advantages such as easy synthesis, loading, controllability, bioavailability over various surfaces, functionalization, and biocompatibility. MSNs can be used as theranostics in immune-modulatory nano systems to diagnose and treat inflammatory diseases. The application of MSNs in the preparation of drug-delivery systems has been steadily increasing in recent decades. Several preclinical studies suggest that an MSN-mediated drug-delivery system could aid in treating inflammatory diseases. This review explains the role of nanoparticles in medicine, synthesis, and functional properties of mesoporous silica nanoparticles and their therapeutic role against various inflammatory diseases.

Comparative study of zinc oxide nanoparticles synthesized through biogenic and chemical route with reference to antibacterial, antibiofilm and anticancer activities.

The present focused on comparative study on synthesis of ZnO nanoparticles (ZnO NPs) using chemical method via alkaline precipitation method (ZnO(A) NPs) using NaOH and biogenic method using termite mound extract (ZnO(B) NPs). GC-MS analysis revealed that D-limonene present in termite mound extract might be responsible for the synthesis of ZnO(B) NPs. XRD patterns confirmed hexagonal crystalline structure of ZnO(A) and (B) NPs. Results of antibacterial activity illustrated that ZnO(B) NPs showed its potential against Pseudomonas aeruginosa, ESBL-1, ESBL-2 and EBSL-3. Antibiofilm studies revealed that ZnO(B) NPs exhibited optimum decline in MRSA biofilm formation than ZnO(A) NPs. In addition, ZnO(B) NPs showed potent cytotoxic effect against lung cancer cell lines A549 with IC50 of 35.16 ± 0.10 µg/mL in comparison with ZnO(A) NPs (IC50- 55.09 ± 0.30 µg/mL). Overall, the results revealed that biogenic synthesis of ZnO NPs ensures its biosafety level and enhanced biological activity when compared to chemical synthesis method.

Biosynthesis of zirconium nanoparticles (ZrO2 NPs) by Phyllanthus niruri extract: Characterization and its photocatalytic dye degradation activity.

The present study focused on microwave assisted synthesis of zirconium nanoparticles (ZrO2NPs) using leaf extract of Phyllanthus niruri as ecofriendly approach and assessed its antimicrobial and bioremediation efficiency. Visual color transition from yellow to brown indicates the formation of ZrO2NPs which was further substantiated by UV-Visible absorption peak at 300 nm. Dynamic Light Scattering (DLS) analysis revealed that the average particle size of ZrO2NPs as 121.5 nm with negative zeta potential of -22.6 mv. Scanning electron microscopic analysis showed spherical shaped nanoparticles with an average size of 125.4 nm. Results of photocatalytic studies revealed that ZrO2NPs exhibited 74%, 62% and 57%, dye degradation for methyl red, methyl orange, and methyl blue respectively. Antimicrobial studies depicted that ZrO2NPs exhibited bactericidal activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Aspergillus niger at dose of 200 µg/mL. Overall results of the present study revealed biogenic synthesis of ZrO2 NPs with potent bioremediation and antimicrobial properties.

Anticancer Potential of L-Histidine-Capped Silver Nanoparticles against Human Cervical Cancer Cells (SiHA).

This study reports the synthesis of silver nanoparticles using amino acid L-histidine as a reducing and capping agent as an eco-friendly approach. Fabricated L-histidine-capped silver nanoparticles (L-HAgNPs) were characterized by spectroscopic and microscopic studies. Spherical shaped L-HAgNPs were synthesized with a particle size of 47.43 ± 19.83 nm and zeta potential of -20.5 ± 0.95 mV. Results of the anticancer potential of L-HAgNPs showed antiproliferative effect against SiHa cells in a dose-dependent manner with an IC50 value of 18.25 ± 0.36 µg/mL. Fluorescent microscopic analysis revealed L-HAgNPs induced reactive oxygen species (ROS) mediated mitochondrial dysfunction, leading to activation of apoptotic pathway and DNA damage eventually causing cell death. To conclude, L-HAgNPs can act as promising candidates for cervical cancer therapy.

Alzheimer's Disease: A Molecular View of ß-Amyloid Induced Morbific Events.

Amyloid-ß (Aß) is a dynamic peptide of Alzheimer's disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by ß- and γ-secretases and engenders the Aß. In addition, externally produced Aß gets inside the cells by receptors mediated internalization. An elevated amount of Aß yields spontaneous aggregation which causes organelles impairment. Aß stimulates the hyperphosphorylation of tau protein via acceleration by several kinases. Aß travels to the mitochondria and interacts with its functional complexes, which impairs the mitochondrial function leading to the activation of apoptotic signaling cascade. Aß disrupts the Ca2+ and protein homeostasis of the endoplasmic reticulum (ER) and Golgi complex (GC) that promotes the organelle stress and inhibits its stress recovery machinery such as unfolded protein response (UPR) and ER-associated degradation (ERAD). At lysosome, Aß precedes autophagy dysfunction upon interacting with autophagy molecules. Interestingly, Aß act as a transcription regulator as well as inhibits telomerase activity. Both Aß and p-tau interaction with neuronal and glial receptors elevate the inflammatory molecules and persuade inflammation. Here, we have expounded the Aß mediated events in the cells and its cosmopolitan role on neurodegeneration, and the current clinical status of anti-amyloid therapy.

Decoding the Neuroprotective Potential of Methyl Gallate-Loaded Starch Nanoparticles against Beta Amyloid-Induced Oxidative Stress-Mediated Apoptosis: An In Vitro Study.

Alzheimer's disease (AD) is a multifaceted neuronal disorder and a challenge to medical practitioners, as the blood-brain barrier (BBB) acts as a major obstacle for drug delivery to the brain. Development of a nanomaterial-based drug delivery system (DDS) paved a way to penetrate the BBB. Starch, a ubiquitous natural biopolymer, has received much attention as a DDS due to its biocompatibility, biodegradability and eco-friendly nature. The present study focuses on encapsulating methyl gallate (MG) within starch nanoparticles (starch-encapsulated MG (SEMG)) and assesses its neuroprotective potential against ß-amyloid (Aß)-induced toxicity, the key factor for AD pathogenesis in Neuro2A cells. SEMG showed potent acetylcholinesterase inhibitory, antioxidant activity and anti-amyloidogenic activity by attenuating the fibrillation of Aß and destabilizing the preformed mature fibrils. Furthermore, SEMG also attenuated the cytotoxic effect induced by Aß in Neuro2A cells (50% inhibitory concentration 18.25 ± 0.025 µg/mL) by mitigating reactive oxygen species (ROS)-mediated macromolecular damage, restoring mitochondrial membrane potential and attenuating apoptosis. Characterization of SEMG revealed amorphous rock-shaped structure with average particle size of 264.6 nm, exhibiting 83% loading efficiency and sustained release of drug, with 73% release within 24 h at physiological pH. Overall, the outcome of the present study signifies starch as a promising nanocarrier for the delivery of drugs for the treatment of AD.

Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease.

Gut microbiota represents a diverse and dynamic population of microorganisms harboring the gastrointestinal tract, which influences the host health and disease. Gut microbiota communicates with the brain and vice versa through complex bidirectional communication systems - the gut-brain axis, which integrates the peripheral intestinal function with emotional and cognitive brain centers via neuro-immuno-endocrine mediators. Aging alters the gut microbial population, which not only leads to gastrointestinal disturbances but also causes central nervous system (CNS) disorders such as dementia. Alzheimer's disease (AD) is the most common form of dementia affecting the older person, characterized by beta-amyloid (Aß) plaques and neurofibrillary tangles leading to the cognitive deficit and memory impairment. Multiple experimental and clinical studies revealed the role of gut microbiota in host cognition, and its dysbiosis associated with aging leads to neurodegeneration. Gut microbial dysbiosis leads to the secretion of amyloid and lipopolysaccharides (LPS), which disturbs the gastrointestinal permeability and blood-brain barrier. Thereby modulates the inflammatory signaling pathway promoting neuroinflammation, neuronal injury, and ultimately leading to neuronal death in AD. A recent study revealed the antimicrobial property of Aß peptide as an innate immune response against pathogenic microbes. Another study showed that bacterial amyloid shares molecular mimicry with Aß peptide, which elicits misfolding and aggregation of Aß peptide, it's seeding, and propagation through the gut-brain axis followed by microglial cell activation. As aging together with poor diet and gut-derived inflammatory response due to dysbiosis contributes to the pathogenesis of AD, modification of gut microbial composition by uptake of probiotic-rich food can act as a preventive/therapeutic option for AD. The objective of the present review is to summarize the recent findings on the role of gut microbiota in the development of AD. Understanding the relationship between gut microbiota and CNS will help identify novel therapeutic strategies, especially probiotic-based supplementation, for the treatment of AD.

The Role of Microbiome, Dietary Supplements, and Probiotics in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by the impairment of the cognitive function of a child. Studies suggested that the intestinal microbiota has a critical role in the function and regulation of the central nervous system, neuroimmune system and neuroendocrine system. Any adverse changes in the gut-brain axis may cause serious disease. Food preferences and dietary patterns are considered as key in influencing the factors of ASD development. Several recent reviews narrated the importance of dietary composition on controlling or reducing the ASD symptoms. It has been known that the consumption of probiotics confers several health benefits by positive amendment of gut microbiota. The influence of probiotic intervention in children with ASD has also been reported and it has been considered as an alternative and complementary therapeutic supplement for ASD. The present manuscript discusses the role of microbiota and diet in the development of ASD. It also summarizes the recent updates on the influence of dietary supplements and the beneficial effect of probiotics on ASD symptoms. An in-depth literature survey suggested that the maternal diet and lifestyle are greatly associated with the development of ASD and other neurodevelopmental disorders. Mounting evidences have confirmed the alteration in the gut microbial composition in children suffering from ASD. However, the unique profile of microbiome has not yet been fully characterized due to the heterogeneity of patients. The supplementation of probiotics amended the symptoms associated with ASD but the results are inconclusive. The current study recommends further detailed research considering the role of microbiome, diet and probiotics in the development and control of ASD.

A Review on Role of Microbiome in Obesity and Antiobesity Properties of Probiotic Supplements.

Probiotics are now recognized for several health benefits and they have been recommended as a complementary therapeutic agent for metabolic disorders. Obesity is an altered health condition, which is a resultant of irregular energy intake and energy balance, changes in gut microbiota, and improper diet with the influence of genetic makeup and environmental factors. Several studies revealed the influence of probiotic supplementation on obesity-associated consequences in vitro, in vivo, and in human clinical studies. The current manuscript discussed the factors influencing the occurrence of obesity, the interplay between microbiome and obesity, the effect of the probiotic intervention on the health status of obese people, and possible mechanism of antiobesity activity of probiotics. The literature survey revealed that the antiobese activity of probiotics might be associated with their ability to alter the intestinal microbiota, remodeling of energy metabolism, alter the expression of genes related to thermogenesis, glucose metabolism, and lipid metabolism, and change the parasympathetic nerve activity. Further intense research is necessary to figure out the best probiotic or synbiotic mixture and optimum dosage and duration of the intervention to reduce obesity and prevent the recurring of obese condition.

Biogenic synthesis of gold nanoparticles from Terminalia arjuna bark extract: assessment of safety aspects and neuroprotective potential via antioxidant, anticholinesterase, and antiamyloidogenic effects.

The development of neuroprotective drugs through eco-friendly production routes is a major challenge for current pharmacology. The present study was carried out to synthesize gold nanoparticles (AuNPs) through biogenic route using ethanolic bark extract of Terminalia arjuna, a plant of high interest in Asian traditional medicine, and to evaluate its neuroprotective effects. The synthesized AuNPs were characterized by UV-Vis spectroscopy, FTIR spectroscopy, XRD, FESEM, EDX, HRTEM, DLS, and zeta potential analyses. UV-Vis spectroscopy showed a characteristics SPR absorption band at 536 nm specific for AuNPs. XRD, TEM, and FESEM analyses revealed the formation of face-centered cubic crystalline, spherical and triangular shaped AuNPs, with size ranging between 20 and 50 nm. DLS and ZP analysis illustrated that the average size of AuNPs was 30 nm, which was found to be stable at 45 mv. The neuroprotective potential of AuNPs was evaluated by assessing its antioxidant, cholinesterase inhibitory, and antiamyloidogenic activities. AuNPs showed dose-dependant inhibition of acetylcholinesterase and butyrylcholinesterase with IC50 value of 4.25 ± 0.02 and 5.05 ± 0.02 µg/ml, respectively. In vitro antioxidant assays illustrated that AuNPs exhibited the highest reducing power and DPPH radical scavenging activity. In addition, AuNPs also efficiently suppressed the fibrillation of Aß and destabilized the preformed mature fibrils. Results of toxicity studies in PBMC and adult zebra fish illustrated that AuNPs are non-toxic and biocompatible. Overall, our results highlighted the AuNPs promising potential in terms of antioxidant, anticholinesterase, antiamyloidogenic effects, and non-lethality allowing us to propose these nanomaterials as a suitable candidate for the development of drugs helpful in the treatment of neurodegenerative disorders like Alzheimer's disease. Graphical abstract ᅟ.

In vitro antiaggregation and deaggregation potential of Rhizophora mucronata and its bioactive compound (+)- catechin against Alzheimer's beta amyloid peptide (25-35).

OBJECTIVE: Amyloid hypothesis states that endogenous ß-amyloid peptides (Aß), especially its aggregated oligomers and fibrils are the key pathogenic factors leading to Alzheimer's disease (AD). Therefore, inhibition of Aß fibrillation rather than blocking its production is considered promising therapeutic intervention. Hence, the present study was carried out to assess the effect of methanolic leaf extract of R. mucronata (MERM) and its bioactive compound catechin on in vitro fibrillation of Aß (25-35). METHODOLOGY: Antiaggregation and disaggregation effect by MERM and (+)- catechin against Aß (25-35) were assessed in three different phases by thioflavin T (ThT) fluorescence assay and confocal microscopic analysis. The conformational changes in the aggregated Aß fibrils in the presence and absence of MERM and catechin were analysed by Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and CD spectroscopy. RESULTS: Results of ThT and confocal microscopic studies showed decrease in fluorescence intensity in MERM and catechin-treated groups illustrating that both MERM and catechin effectively inhibited fibril aggregation as well as destabilized preformed Aß fibril. TEM revealed that MERM incubated samples were virtually devoid of structured fibrils but had an amorphous-like consistency, whereas the control contained structured fibrils of various width and length. FTIR analysis showed decrease in absorbance at 1630 cm-1 (amide I region) in MERM-treated groups substantiating the results of ThT assay. Circular dichroism data indicate that catechin prevents the formation of ß-structured aggregates of Aß peptide. CONCLUSION: Results suggest that MERM and catechin might have direct interaction with Aß peptide preventing its fibrillation.

Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions.

Quercetin, a ubiquitous flavonoid that is widely distributed in plants is classified as a cognitive enhancer in traditional and oriental medicine. The protective effects of quercetin for the treatment of neurodegenerative disorders and cerebrovascular diseases have been demonstrated in both in vitro and in vivo studies. The free radical scavenging activity of quercetin has been well-documented, wherein quercetin has been observed to exhibit protective effects against oxidative stress mediated neuronal damage by modulating the expression of NRF-2 dependent antioxidant responsive elements, and attenuation of neuroinflammation by suppressing NF-κB signal transducer and activator of transcription-1 (STAT-1). Several in vitro and in vivo studies have also shown that quercetin destabilizes and enhances the clearance of abnormal protein such as beta- amyloid peptide and hyperphosphorlyated tau, the key pathological hallmarks of Alzheimer's disease. Quercetin enhances neurogenesis and neuronal longevity by modulating a broad number of kinase signaling cascades such as phophoinositide 3- kinase (P13-kinase), AKT/PKB tyrosine kinase and Protein kinase C (PKC). Quercetin has also been well reported for its ability to reverse cognitive impairment and memory enhancement during aging. The current review focuses on summarizing the recent findings on the neuroprotective effect of quercetin, its mechanism of action and its possible roles in the prevention of neurological disorders.

Rhizophora mucronata attenuates beta-amyloid induced cognitive dysfunction, oxidative stress and cholinergic deficit in Alzheimer's disease animal model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by accumulation and deposition of Aß peptide in human brain. The present study aimed to determine the protective effect of catechin rich extract of MERM (methanolic extract of Rhizophora mucronata) on Aß (25-35) induced cognitive impairment and neuronal toxicity in mice. In the present study AD characteristics were induced by intracerberoventricular administration of aggregated Aß (25-35) in the Swiss albino mice. Learning and memory deficits were assessed using behavioral assays such as Morris water maze, Y-maze and step down avoidance tasks. Oxidative stress mediated impairment were assessed by measuring the activities of enzymatic and non-enzymatic antioxidants, level of apoptotic protein and oxidative markers in the hippocampus and frontal cortex region. Histolopathological analysis of brain was also carried out. Results illustrated that oral treatment of MERM (200 and 400 mg/kg bw) significantly attenuated Aß (25-35) induced memory impairment as evaluated by behavioral tests. In addition treatment with MERM attenuated the elevation of ß-secretase activity accompanying the reduced level of Aß (25-35) in the cortex and hippocampus of brain. MERM also enhanced the cognitive function by significantly inhibiting AChE, BuChE and MAO-B. Furthermore, MERM attenuated lipid peroxidation, protein oxidation, restored the antioxidant status and inhibited neuronal apoptosis by down-regulating the level of caspase 3 and Bax protein. These data suggest that MERM rich in catechin can act as promising drug for AD treatment because of its antioxidant, anti-apoptotic and reducing Aß oligomer activities.

Mangrove plant extracts: radical scavenging activity and the battle against food-borne pathogens.

AIMS: The present study was carried out to evaluate the radical scavenging and antibacterial activity of methanolic leaf extracts of mangrove plants. 8 mangrove plants, which are used as folk medicine in various tropical countries, were collected in Pichavaram and Thondi, Tamil Nadu, India. METHODS: The antioxidant properties of methanolic leaf extracts were assessed under in vitro conditions using different antioxidant tests, including DPPH, nitric oxide, hydrogen peroxide, hydroxyl radical scavenging assay, reducing power, ferrous ion chelating, and lipid peroxidation inhibition assay. RESULTS AND CONCLUSION: Of the 8 mangrove plants screened, Rhizophora mucronata (100 microg/ml) showed significantly higher (p < 0.05) activities for all antioxidant assays, and its IC50 values were 43.17, 116, 60.06, and 46.76 microg/ml for DPPH, hydrogen peroxide, nitric oxide, and hydroxyl radical scavenging activity, respectively. Butylated hydroxytoluene, ascorbic acid and alpha-tocopherol were used as positive controls. Methanolic extracts of R. mucronata were also found to be effective in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals in a Fenton's reaction mixture. Moreover, the total phenolic content of R. mucronata (720.79 mg/gm of dry leaves) was very high and a strong positive correlation was observed between its phenolic content and its antioxidant activity. Methanolic leaf extracts of mangrove plants exhibited no antibacterial activity against seven food-borne pathogens studied.

Cholinesterase inhibitory effects of Rhizophora lamarckii, Avicennia officinalis, Sesuvium portulacastrum and Suaeda monica: Mangroves inhabiting an Indian coastal area (Vellar Estuary).

Alzheimer's disease is a progressive neurodegenerative illness accounting for approximately 50% of all types of dementia in elderly people. The only symptomatic treatment proven effective to date is the use of cholinesterase inhibitors to augment surviving cholinergic activity. The purpose of this study is to investigate cholinesterase inhibitory activity of mangroves as an alternative medicine for the treatment of Alzheimer's disease. About nine mangrove plants, which were used as folk medicine in tropical countries, were collected from Parangipettai, Vellar estuary, Tamilnadu, India. Nile Tilapia muscle homogenate was used as source of enzyme. Inhibitory effect of methanolic leaf extract was assessed under in vitro condition by incubating various concentration of the extract with total cholinesterase and butyryl cholinesterase and assessing their residual activities by Ellman's colorimetric method. The results showed that of the nine plants screened Rhizophora lamarckii, Suaeda monica, Avicennia officinalis and Sesuvium portulacastrum showed 50% inhibitory activity to both TChE and BChE at concentrations less than 2 mg/mL when compared to other plant extracts, which was comparable to the standard drug Donepezil. Phytochemical analysis showed the presence of alkaloids in high concentration which might be correlated to its cholinesterase inhibitory activity.

Bioprotective properties of seaweeds: in vitro evaluation of antioxidant activity and antimicrobial activity against food borne bacteria in relation to polyphenolic content.

BACKGROUND: For many years chemical preservatives have been used in food, to act as either antimicrobials or antioxidants or both. In general, consumers regard additive-free foods as safer since preservatives can cause health hazards like asthma and cancer and are suspected to be mutagenic and neurotoxic. The present study was carried out to evaluate the antimicrobial and antioxidant activity of methanolic extracts of seaweeds, with a view to developing safer food preservatives. METHODS: Ten edible seaweeds, which have wide pharmaceutical application, were collected from Central Marine Fisheries Research Institute, Tamil Nadu, India and evaluated for antioxidant and antimicrobial activity against food borne pathogens. RESULTS: The results indicate that Gelidiella acerosa has the highest antioxidant activity while Haligra sps exhibited antibacterial activity against Staphylococcus aureus (MTCC 96). CONCLUSION: Quantitative analysis of the total phenolic content of the seaweeds indicated that Gelidella acerosa and Haligra sps have high phenolic contents, which correlated to their respective antioxidant and antimicrobial activity.