Microglia in Alzheimer's Disease: A Favorable Cellular Target to Ameliorate Alzheimer's Pathogenesis.

Microglial cells serve as molecular sensors of the brain that play a role in physiological and pathological conditions. Under normal physiology, microglia are primarily responsible for regulating central nervous system homeostasis through the phagocytic clearance of redundant protein aggregates, apoptotic cells, damaged neurons, and synapses. Furthermore, microglial cells can promote and mitigate amyloid ß phagocytosis and tau phosphorylation. Dysregulation of the microglial programming alters cellular morphology, molecular signaling, and secretory inflammatory molecules that contribute to various neurodegenerative disorders especially Alzheimer's disease (AD). Furthermore, microglia are considered primary sources of inflammatory molecules and can induce or regulate a broad spectrum of cellular responses. Interestingly, in AD, microglia play a double-edged role in disease progression; for instance, the detrimental microglial effects increase in AD while microglial beneficiary mechanisms are jeopardized. Depending on the disease stages, microglial cells are expressed differently, which may open new avenues for AD therapy. However, the disease-related role of microglial cells and their receptors in the AD brain remain unclear. Therefore, this review represents the role of microglial cells and their involvement in AD pathogenesis.

Anti-Alzheimer's Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential.

Alzheimer's disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aß) aggregation, glutamate excitotoxicity, and cholinergic deficit. Still, there is no available therapy that can cure AD. Available therapies only manage some of the AD symptoms at the early stages of AD. Various studies have revealed that bioactive compounds derived from marine organisms and plants can exert neuroprotective activities with fewer adverse events, as compared with synthetic drugs. Furthermore, marine organisms have been identified as a source of novel compounds with therapeutic potential. Thus, there is a growing interest regarding bioactive compounds derived from marine sources that have anti-AD potentials. Various marine drugs including bryostatin-1, homotaurine, anabaseine and its derivative, rifampicins, anhydroexfoliamycin, undecylprodigioisin, gracilins, 13-desmethyl spirolide-C, and dictyostatin displayed excellent bioavailability and efficacy against AD. Most of these marine drugs were found to be well-tolerated in AD patients, along with no significant drug-associated adverse events. In this review, we focus on the drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat AD.

A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer's Disease, Aging, Cancer, Inflammation, and Diabetes.

Natural products have long been used as drugs to treat a wide array of human diseases. The lead compounds discovered from natural sources are used as novel templates for developing more potent and safer drugs. Natural products produce biological activity by binding with biological macromolecules, since natural products complement the protein-binding sites and natural product-protein interactions are already optimized in nature. Sirtuin 6 (SIRT6) is an NAD+ dependent histone deacetylase enzyme and a unique Sirtuin family member. It plays a crucial role in different molecular pathways linked to DNA repair, tumorigenesis, glycolysis, gluconeogenesis, neurodegeneration, cardiac hypertrophic responses, etc. Thus, it has emerged as an exciting target of several diseases such as cancer, neurodegenerative diseases, aging, diabetes, metabolic disorder, and heart disease. Recent studies have shown that natural compounds can act as modulators of SIRT6. In the current review, a list of natural products, their sources, and their mechanisms of SIRT6 activity modulation has been compiled. The potential application of these naturally occurring SIRT6 modulators in the amelioration of major human diseases such as Alzheimer's disease, aging, diabetes, inflammation, and cancer has also been delineated. Natural products such as isoquercetin, luteolin, and cyanidin act as SIRT6 activators, whereas vitexin, catechin, scutellarin, fucoidan, etc. work as SIRT6 inhibitors. It is noteworthy to mention that quercetin acts as both SIRT6 activator and inhibitor depending on its concentration used. Although none of them were found as highly selective and potent modulators of SIRT6, they could serve as the starting point for developing selective and highly potent scaffolds for SIRT6.

Multifarious roles of mTOR signaling in cognitive aging and cerebrovascular dysfunction of Alzheimer's disease.

Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood-brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aß Therapeutics to Auspicious New Ways for Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-ß (Aß), a peptide of 40-42 amino acids. The conversion of Aß into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aß accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aß monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aß and antagonize Aß aggregation, or raise Aß clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aß which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aß oligomers have exhibited exciting findings. Nevertheless, Aß oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aß monomer or Aß plaques ought to have displayed valuable clinical benefits. In this article, Aß-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.

Combination Drug Therapy for the Management of Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Even though the number of AD patients is rapidly growing, there is no effective treatment for this neurodegenerative disorder. At present, implementation of effective treatment approaches for AD is vital to meet clinical needs. In AD research, priorities concern the development of disease-modifying therapeutic agents to be used in the early phases of AD and the optimization of the symptomatic treatments predominantly dedicated to the more advanced AD stages. Until now, available therapeutic agents for AD treatment only provide symptomatic treatment. Since AD pathogenesis is multifactorial, use of a multimodal therapeutic intervention addressing several molecular targets of AD-related pathological processes seems to be the most practical approach to modify the course of AD progression. It has been demonstrated through numerous studies, that the clinical efficacy of combination therapy (CT) is higher than that of monotherapy. In case of AD, CT is more effective, mostly when started early, at slowing the rate of cognitive impairment. In this review, we have covered the major studies regarding CT to combat AD pathogenesis. Moreover, we have also highlighted the safety, tolerability, and efficacy of CT in the treatment of AD.

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer's Disease.

Alzheimer's disease (AD) is one of the utmost chronic neurodegenerative disorders, which is characterized from a neuropathological point of view by the aggregates of amyloid beta (Aß) peptides that are deposited as senile plaques and tau proteins which form neurofibrillary tangles (NFTs). Even though advancement has been observed in order to understand AD pathogenesis, currently available therapeutic methods can only deliver modest symptomatic relief. Interestingly, naturally occurring dietary flavonoids have gained substantial attention due to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties as alternative candidates for AD therapy. Experimental proof provides support to the idea that some flavonoids might protect AD by interfering with the production and aggregation of Aß peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aß peptides and inhibit tau phosphorylation by the mTOR/autophagy signaling pathway. Moreover, due to their cholinesterase inhibitory potential, flavonoids can represent promising symptomatic anti-Alzheimer agents. Several processes have been suggested for the aptitude of flavonoids to slow down the advancement or to avert the onset of Alzheimer's pathogenesis. To enhance cognitive performance and to prevent the onset and progress of AD, the interaction of flavonoids with various signaling pathways is proposed to exert their therapeutic potential. Therefore, this review elaborates on the probable therapeutic approaches of flavonoids aimed at averting or slowing the progression of the AD pathogenesis.

Intranasal Epitope-Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus.

Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP366, a nucleoprotein-derived epitope and PA224, a polymerase acidic subunit derived epitope, are bioengineered. These BP-NP366/PA224 can be manufactured at a high yield and are obtained at ≈93% purity, exhibiting ambient-temperature stability. Immunological characterization includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunization. Immunization with BP-NP366/PA224 without adjuvant triggers influenza-specific CD8+ T cell priming and memory CD8+ T cell development. Co-delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza-specific pulmonary resident memory CD8+ T cell pool. Intranasal, but not intramuscular delivery of BP-NP366/PA224 with poly(I:C), provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.

Precision-engineering of subunit vaccine particles for prevention of infectious diseases.

Vaccines remain the best approach for the prevention of infectious diseases. Protein subunit vaccines are safe compared to live-attenuated whole cell vaccines but often show reduced immunogenicity. Subunit vaccines in particulate format show improved vaccine efficacy by inducing strong immune responses leading to protective immunity against the respective pathogens. Antigens with proper conformation and function are often required to induce functional immune responses. Production of such antigens requiring post-translational modifications and/or composed of multiple complex domains in bacterial hosts remains challenging. Here, we discuss strategies to overcome these limitations toward the development of particulate vaccines eliciting desired humoral and cellular immune responses. We also describe innovative concepts of assembling particulate vaccine candidates with complex antigens bearing multiple post-translational modifications. The approaches include non-covalent attachments (e.g. biotin-avidin affinity) and covalent attachments (e.g. SpyCatcher-SpyTag) to attach post-translationally modified antigens to particles.

Unveiling the Potential of Polyphenols as Anti-Amyloid Molecules in Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease that mostly affects the elderly population. Mechanisms underlying AD pathogenesis are yet to be fully revealed, but there are several hypotheses regarding AD. Even though free radicals and inflammation are likely to be linked with AD pathogenesis, still amyloid-beta (Aß) cascade is the dominant hypothesis. According to the Aß hypothesis, a progressive buildup of extracellular and intracellular Aß aggregates has a significant contribution to the AD-linked neurodegeneration process. Since Aß plays an important role in the etiology of AD, therefore Aß-linked pathways are mainly targeted in order to develop potential AD therapies. Accumulation of Aß plaques in the brains of AD individuals is an important hallmark of AD. These plaques are mainly composed of Aß (a peptide of 39-42 amino acids) aggregates produced via the proteolytic cleavage of the amyloid precursor protein. Numerous studies have demonstrated that various polyphenols (PPHs), including cyanidins, anthocyanins, curcumin, catechins and their gallate esters were found to markedly suppress Aß aggregation and prevent the formation of Aß oligomers and toxicity, which is further suggesting that these PPHs might be regarded as effective therapeutic agents for the AD treatment. This review summarizes the roles of Aß in AD pathogenesis, the Aß aggregation pathway, types of PPHs, and distribution of PPHs in dietary sources. Furthermore, we have predominantly focused on the potential of food-derived PPHs as putative anti-amyloid drugs.

GC-MS-employed phytochemical characterization, synergistic antioxidant, and cytotoxic potential of Triphala methanol extract at non-equivalent ratios of its constituents.

Triphala is a famous triherbal drug, comprising three herb fruits, including Terminalia chebula (Haritaki), Terminalia bellirica (Bibhitaki), and Phyllanthus emblica (Amalaki). It is enriched with vitamin C, polyphenols, flavonoids, sterols, saponins, etc., and is well-documented for its potent antioxidant, anticancer, chemoprotective, antimicrobial, and anti-inflammatory effects. This research was conducted to evaluate the synergistic antioxidative and cytotoxic potential of mixtures of the individual constituents of Triphala at their nonequivalent ratios along with the chemical characterization of individual constituents of Triphala to identify and quantify individual compounds. The antioxidative potential was measured using total antioxidant capacity (TAC), DPPH free radical scavenging assay, and total phenolic content (TPC) tests. The cytotoxic potential was assessed on brain cancer cells (N4X4) using MTT assay, and phytochemical characterization was performed by GS-MS analysis. Nonequivalent ratios of Triphala constituents exhibited significantly higher synergistic antioxidant and cytotoxic potential than the equivalent ratios of them. Moreover, the nonequivalent ratio where the quantity of Amalaki was doubled than the other two constituents showed the highest synergistic antioxidant and cytotoxic effect. GC-MS analysis of individual constituents of Triphala identified and quantified the presence of a wide array of compounds, and fatty acid, fatty acid ester, triterpene, and aminoglycoside remained the predominant class of compounds. Thus, it can be inferred that the observed bioactivities can be attributed to the phytocompounds characterized and extracts at the nonequivalent ratio of Triphala constituents where Amalaki is doubled can be more effective in treating oxidative degenerative diseases and glioblastoma.

A Comprehensive Review on Hydrogels.

The conventional drug delivery systems have a long list of repeated dosing and toxicity issues. The hydrogels solve these issues as they minimize such activities and optimize therapeutic benefits. The hydrogels possess tunable properties that can withstand degradation, metabolism, and control release moieties. Some areas of applications of hydrogels involve wound healing, ocular systems, vaginal gels, scaffolds for tissue and bone engineering, etc. They comprise about 90% of the water that makes them suitable bio-mimic moiety. Here, we present an extensive review of various perspectives of hydrogels, along with their applications.

Therapeutic potential of dopamine agonists in the treatment of type 2 diabetes mellitus.

Diabetes is a global health concern that has affected almost 415 million people globally. Bromocriptine is a dopamine D2 agonist, which is a Food and Drug Administration (FDA)-approved drug to treat type 2 diabetes mellitus (T2DM) patients. However, it is considered that a novel treatment therapy is required which can be used in the treatment of diabetes with or without other antidiabetic agents. Dopamine agonists are usually used in neurological disorders like Parkinson's disease (PD), restless leg syndrome, and hyperprolactinemia. However, dopamine agonists including bromocriptine and cabergoline are also effective in reducing the glycemic level in T2DM patients. Bromocriptine was formerly used for the treatment of PD, hyperprolactinemia, and restless leg syndrome, but now it is used for improving glycemic levels as well as reducing free fatty acids and triglycerides. In addition, cabergoline has been found to be effective in glycemic control, but this drug is yet to be approved by the FDA due to its limitations and lack of study. Findings of the clinical trials of bromocriptine have suggested that it reduces almost 0.4-0.8% glycated hemoglobin and cardiovascular risk by 40% in insulin-resistant patients. Moreover, the safe use of bromocriptine in obese T2DM patients makes it a more attractive option as it causes weight loss. Indeed, bromocriptine is a novel therapy for T2DM patients, as its mechanism of action is unique in T2DM patients with minimal adverse effects. This review summarizes the potential of dopamine agonists in the treatment of T2DM.

Neuroinflammatory Signaling in the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can, in turn, induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.

Unravelling the photoprotective effects of freshwater alga Nostoc commune Vaucher ex Bornet et Flahault against ultraviolet radiations.

Several studies have suggested the direct relationship between skin complications, air pollution, and UV irradiation. UVB radiations cause various skin complications such as skin aging, skin inflammation, and skin cancer. The current study is designed to develop an ultraviolet (UV) absorbing MAA-loaded topical gel and to evaluate its UVA and UVB screening potential. MAA was extracted from the Nostoc commune Vaucher ex Bornet et Flahault (N. commune) and characterized by HPLC-PDA (with a retention time 2.6 min), UV-Visible (absorption maximum 334 nm), and mass spectrometry (m/z 346.2) techniques. The methanolic (10%) solution of MAA (50-150 µl) was dissolved in propylene glycol and mixed with hydrated gel (1.5 % of carbopol 934) by using EDTA (0.3%). Eight (F1-F8) formulations were evaluated for their physico-chemical characters. F7 retained its physio-chemical characters for 90 days. Further selected formulation (F7) was evaluated for its gelling strength (GSg), gelling temperature (GT), melting temperature (MT), apparent viscosity (cp), molecular mass (MMS), pH, physical appearance, homogeneity, and spreading diameter (SD). The stability study of the fabricated gel formulation was done as per International Committee on Harmonization guidelines and sunscreen potential was determined by in vitro sunscreen UV method. Findings revealed that GSg (337 ± 1.7 g/cm2), GT (22.8 ± 0.2 °C), cp (71.1 ± 0.2), MMS (424.177 ± 0.7), pH (6.2 ± 0.04), and SD (56 ± 0.2). For in vitro sunscreen potential determination, different concentrations of F7 (50-150 µl) were prepared. Topical application of the F7 displayed UV-A/UV-B photoprotection with SPF 1.13 folds greater then marketed formulation (Lotus herbals UV screen gel). Based on these findings, it was concluded that methanolic extract derived from N. commune contains Porphyra-334 which can be potentially used as photo protective compound in several cosmetic preparations. Development of sunscreen gel from Nostoc commune The current investigation is designed to develop ultraviolet (UV) absorbing MAA (mycosporine amino acid)-loaded topical gel from Nostoc commune to evaluate its UVA and UVB screening potential. LCMS characterization of HPLC-PDA purified MAA from N. commune methanolic extract demonstrated a prominent ion peak of a protonated molecule ([M + H]+) at m/z 346.2 [M+H]+ value confirmed the presence of Porphyra-334. Porphyra-334 is a broad-spectrum sun-protective compound evidenced for its potential in blocking UVA and UVB (Bhatia et al. 2010). Prepared sunscreen formulations remain stable for prolonged period and provide broad-spectrum protection against harmful UV range.

Anti-migraine activity of freeze-dried latex obtained from Calotropis gigantea Linn.

Migraine which is characterized by a pulsating headache affected an estimated population of 12% worldwide. Herbal products like latex derived from Calotropis gigantea R. Br. (Asclepiadaceae) are a representative intervention to treat migraine traditionally. However, post-harvesting stability issues of latex affect its biological potential. Freeze-drying has been successfully employed for the encapsulation of herbal bioactive compounds resulting in stable dried preparations. Latex derived from Calotropis gigantea (C. gigantea) was microencapsulated using chitosan by freeze-drying (FDCG) method and compared with sun ray-dried latex (ADCG). Current investigation was aimed to improve the shelf life of latex by freeze-drying microencapsulation technique and evaluation of its anti-migraine potential. Dried latex powders (ADCG and FDCG) were evaluated in terms of phenolic content, coloring strength, first-order kinetic, color parameters (L*, a*, b*, C*, and E*), moisture, water activity, solubility, and hygroscopicity. Additionally, apomorphine-induced climbing behavior, L-5-HTP-induced syndrome, and MK-801-induced hyperactivity were used to evaluate the anti-migraine potential of powdered latex. FDCG showed good physicochemical properties due to its higher concentration of phenolic and flavonoid contents. Moreover, FDCG significantly reduced the apomorphine-induced climbing behavior, L-5-HTP-induced syndrome, and MK-801-induced hyperactivity in a dose-dependent manner through an interaction of dopaminergic and serotonergic receptors. In conclusion, the method developed for shelf life improvement of latex offered maximum protection over a period of 10 weeks with retaining its natural biological potential; thus, it can be effectively utilized in the treatment or management of migraine. Anti-migraine effect of Calotropis gigantea freeze-dried latex by inhibition of dopamine and serotonin receptors (D1 and D2: dopamine receptors; 5-HT: serotonin receptors); yellow color represents serotonergic, and blue color indicates dopaminergic neurons.

Therapeutic promise of carotenoids as antioxidants and anti-inflammatory agents in neurodegenerative disorders.

Neurodegenerative disorders (NDs) including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis have various disease-specific causal factors and pathological features. A very common characteristic of NDs is oxidative stress (OS), which takes place due to the elevated generation of reactive oxygen species during the progression of NDs. Furthermore, the pathological condition of NDs including an increased level of protein aggregates can further lead to chronic inflammation because of the microglial activation. Carotenoids (CTs) are naturally occurring pigments that play a significant role in averting brain disorders. More than 750 CTs are present in nature, and they are widely available in plants, microorganisms, and animals. CTs are accountable for the red, yellow, and orange pigments in several animals and plants, and these colors usually indicate various types of CTs. CTs exert various bioactive properties because of its characteristic structure, including anti-inflammatory and antioxidant properties. Due to the protective properties of CTs, levels of CTs in the human body have been markedly linked with the prevention and treatment of multiple diseases including NDs. In this review, we have summarized the relationship between OS, neuroinflammation, and NDs. In addition, we have also particularly focused on the antioxidants and anti-inflammatory properties of CTs in the management of NDs.

Nutraceuticals and Bio-inspired Materials from Microalgae and their Future Perspectives.

Nutraceuticals are food or component of food that do not only promote health but also help in recovering and combating health disorders. Algae are microorganisms that are used as supplements used in treating health disorders. They are rich in essential fatty acids, antioxidant pigments, and other micronutrients. These algae are gaining importance as functional components in the green synthesis of metal nanoparticles and applications in fabrics incorporated antimicrobial agents and pharmaceuticals. The present review focus on the distinctive algal components that are beneficial in biomedical applications. It also focuses on the research techniques to enrich the macronutrients and micronutrients by altering growth conditions and susceptible nutritional factors. A diagram model for a systematic review is utilized for this search. The research is conducted through the following databases: PubMed, Web of Science, Scopus, and Science Direct. Results: Here in this review, current reviewers put forward the importance of microalgae and other algae as alternative marine nutrient sources of dietary supplements for human consumption. In this context, extrinsic and intrinsic environmental parameter manipulative studies by eminent research groups to enhance the nutrient composition of these marine creatures are focused on in this study. Some costeffective approach-based techniques for industrial output have also been manifested. The role of algae as bio-inspired material for the production of biosynthetic metal nanoparticles, water-soluble polymers, bioplastic, antimicrobials, antifouling agents has been incurred as research interests in the past decades. In spite of being so impressive as nutraceuticals and bio-inspired material components, research gaps still exist. The purpose of the manuscript is to cover such gaps and show a new paradigm of biomedical applications.

Effect of natural leaf extracts as phytomedicine in curing geriatrics.

Old age is viewed as an unavoidable, undesirable, and problem-ridden phase of life. As people age, they become more susceptible to disease and disability due to various factors like low immunity, decreased functionality of cells, DNA damage, higher incidence of inflammation, etc. Healthy aging is very important. The nutrition and health of the elderly is often neglected. Nutritional interventions could play an important part in the prevention of degenerative conditions of the elderly and an improvement of their quality of life. The medicinal properties of plants are always believed for its therapeutic effect and its efficiency in treating many without adverse effects. The role of phytomedicine in aging is very crucial as it possesses important bioactive compounds and constituents (such as polyphenols, flavonoids, phenolic acids, and others) which are considered to provide anti-aging properties as well as helps in reducing age-associated problems. Some natural leaves such as Moringa oleifera, curry leaves, guava leaves, green tea, olive leaves, Ginkgo biloba, thankuni leaves, grape leaves, vasaka leaves, and kulekhara leaves are found to have therapeutic effects against diseases like cancer, diabetes, immunosuppression, hepatic damage, and neurodegenerative disorders. Hence, this review aims at understanding the effectiveness of these natural products in curing the geriatric population and the mechanism by which the therapeutic effects are exerted by them.

Exploring the Anti-Neuroinflammatory Potential of Steroid and Terpenoid-Derived Phytochemicals to Combat Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that significantly affects cognitive functions in a way that causes loss of memory, thinking, and behavior. Multiple studies revealed that neuroinflammation associated with AD is linked with the amyloid-beta deposition in the brain. Elevated levels of expression of cytokines, microglial activation, nuclear factor kappa B, and reactive oxygen species play roles in AD-related inflammatory processes. Indeed, effective therapeutic approaches are urgently required to develop therapeutic agents to prevent and treat AD. So far, many anti-AD drug candidates have failed in the clinical stages and currently available drugs only provide symptomatic treatment. In recent times, pharmacologically active phytochemicals have been found to possess promising anti-neuroinflammatory effects; therefore, these natural products can be useful in AD treatment. In this review, we have comprehensively discussed the role of neuroinflammation and the molecular processes altered by multiple steroid and terpenoid-derived phytochemicals in various AD-related neuroinflammatory pathways. Indeed, steroid and terpenoid-derived phytochemicals show important therapeutic activities, which can be useful in ameliorating and treating AD-related neurodegeneration.