Probing the anti-Aß42 aggregation and protective effects of prenylated xanthone against Aß42-induced toxicity in transgenic Caenorhabditis elegans model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-ß (Aß) protein aggregates, leading to synaptic dysfunction and neuronal cell death. In this study, we used a comprehensive approach encompassing in vitro assays, computational analyses, and an in vivo Caenorhabditis elegans model to evaluate the inhibitory effects of various xanthones, focusing on Garcinone D (GD), on Aß42 oligomer formation. Dot blot analysis revealed concentration-dependent responses among xanthones, with GD consistently inhibiting Aß42 oligomer formation at low concentrations (0.1 and 0.5 µM, inhibitions of 84.66 ± 2.25% and 85.06 ± 6.57%, respectively). Molecular docking and dynamics simulations provided insights into the molecular interactions between xanthones and Aß42, highlighting the disruption of key residues involved in Aß42 aggregation. The neuroprotective potential of GD was established using transgenic C. elegans GMC101, with substantial delays in paralysis reported at higher concentrations. Our findings show that GD is a potent suppressor of Aß42 oligomer formation, suggesting its potential as a therapeutic candidate for AD. The concentration-dependent effects observed in both in vitro and in vivo models underscore the need for nuanced dose-response assessments. These findings contribute novel insights into the therapeutic landscape of xanthones against AD, emphasizing the multifaceted potential of GD for further translational endeavors in neurodegenerative disorder research.

Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.

The human gastrointestinal tract is populated with a diverse microbial community. The vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology, including health maintenance, development, aging, and disease. The advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome-host interactions. Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the "microbiota-gut-brain axis". The microbiota-gut-brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases. In this review, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases. As the gut microbiome provides essential cues to microglia, astrocytes, and oligodendrocytes, we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative diseases. Subsequently, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases using a metabolite-centric approach, while also examining the role of gut microbiota-related neurotransmitters and gut hormones. Next, we examine the potential of targeting the intestinal barrier, blood-brain barrier, meninges, and peripheral immune system to counteract glial dysfunction in neurodegeneration. Finally, we conclude by assessing the pre-clinical and clinical evidence of probiotics, prebiotics, and fecal microbiota transplantation in neurodegenerative diseases. A thorough comprehension of the microbiota-gut-brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.

Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation.

Hydroxychloroquine (HCQ) is a unique class of medications that has been widely utilized for the treatment of cancer. HCQ plays a dichotomous role by inhibiting autophagy induced by the tumor microenvironment (TME). Preclinical studies support the use of HCQ for anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they sensitize tumor cells to drugs, potentiating the therapeutic activity. However, clinical evidence has suggested poor outcomes for HCQ due to various obstacles, including non-specific distribution, low aqueous solubility and low bioavailability at target sites, transport across tissue barriers, and retinal toxicity. These issues are addressable via the integration of HCQ with nanotechnology to produce HCQ-conjugated nanomedicines. This review aims to discuss the pharmacodynamic, pharmacokinetic and antitumor properties of HCQ. Furthermore, the antitumor performance of the nanoformulated HCQ is also reviewed thoroughly, aiming to serve as a guide for the HCQ-based enhanced treatment of cancers. The nanoencapsulation or nanoconjugation of HCQ with nanoassemblies appears to be a promising method for reducing the toxicity and improving the antitumor efficacy of HCQ.

Calcium food sources in primary school children with low calcium intakes in Kuala Lumpur.

Background: Adequate calcium intake at an early age is crucial to achieving peak bone mass. Nevertheless, low calcium intake is common in Malaysian children. Aim: This study examined the calcium food sources and factors associated with low calcium intake among 243 children aged 9-11 years in Kuala Lumpur. Methods: Diet histories and bone density were measured. Results: The mean calcium intake was 370 ± 187 mg/day. The main contributors to calcium intake were beverages (19.2%), cereal (18.6%), milk and dairy (13.0%), meat and poultry (12.9%), and fish and seafood (10.1%). Within each food group, calcium-contributing foods tend to be from low bioavailability sources such as rice, cocoa-based and malted drinks, and chicken rather than milk. Children who practised regular meals, ate breakfast and snacks and consumed milk more than one serving daily have a higher calcium intake. Conclusion: In conclusion, public health strategies to improve the status of low calcium intake and poor choices of calcium-rich foods are needed to optimise bone health in this population.

13C NMR-based dereplication using MixONat software to decipher potent anti-cholinesterase compounds in Mesua lepidota bark.

A bio-assay guided fractionation strategy based on cholinesterase assay combined with 13C NMR-based dereplication was used to identify active metabolites from the bark of Mesua lepidota. Eight compounds were identified with the aid of the 13C NMR-based dereplication software, MixONat, i.e., sitosterol (1), stigmasterol (2), α-amyrin (3), friedelin (6), 3ß-friedelinol (7), betulinic acid (9), lepidotol A (10) and lepidotol B (11). Further bio-assay guided isolation of active compounds afforded one xanthone, pyranojacareubin (12) and six coumarins; lepidotol A (10), lepidotol B (11), lepidotol E (13), lepidotin A (14), and lepidotin B (15), including a new Mammea coumarin, lepidotin C (16). All the metabolites showed strong to moderate butyrylcholinesterase (BChE) inhibition. Lepidotin B (15) exhibited the most potent inhibition towards BChE with a mix-mode inhibition profile and a Ki value of 1.03 µM. Molecular docking and molecular dynamics simulations have revealed that lepidotin B (15) forms stable interactions with key residues within five critical regions of BChE. These regions encompass residues Asp70 and Tyr332, the acyl hydrophobic pocket marked by Leu286, the catalytic triad represented by Ser198 and His438, the oxyanion hole (OH) constituted by Gly116 and Gly117, and the choline binding site featuring Trp82. To gauge the binding strength of lepidotin B (15) and to pinpoint pivotal residues at the binding interface, free energy calculations were conducted using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) approach. This analysis not only predicted a favourable binding affinity for lepidotin B (15) but also facilitated the identification of significant residues crucial for the binding interaction.

N-Methyl Costaricine and Costaricine, Two Potent Butyrylcholinesterase Inhibitors from Alseodaphne pendulifolia Gamb.

Studies have been conducted over the last decade to identify secondary metabolites from plants, in particular those from the class of alkaloids, for the development of new anti-Alzheimer's disease (AD) drugs. The genus Alseodaphne, comprising a wide range of alkaloids, is a promising source for the discovery of new cholinesterase inhibitors, the first-line treatment for AD. With regard to this, a phytochemical investigation of the dichloromethane extract of the bark of A. pendulifolia Gamb. was conducted. Repeated column chromatography and preparative thin-layer chromatography led to the isolation of a new bisbenzylisoquinoline alkaloid, N-methyl costaricine (1), together with costaricine (2), hernagine (3), N-methyl hernagine (4), corydine (5), and oxohernagine (6). Their structures were elucidated by the 1D- and 2D-NMR techniques and LCMS-IT-TOF analysis. Compounds 1 and 2 were more-potent BChE inhibitors than galantamine with IC50 values of 3.51 ± 0.80 µM and 2.90 ± 0.56 µM, respectively. The Lineweaver-Burk plots of compounds 1 and 2 indicated they were mixed-mode inhibitors. Compounds 1 and 2 have the potential to be employed as lead compounds for the development of new drugs or medicinal supplements to treat AD.

Natural Corynanthe-Type Cholinesterase Inhibitors from Malaysian Uncaria attenuata Korth.: Isolation, Characterization, In Vitro and In Silico Studies.

The Uncaria genus is notable for its therapeutic potential in treating age-related dementia, such as Alzheimer's disease. A phytochemical study of the leaves of Malaysian Uncaria attenuata Korth., afforded an undescribed natural corynanthe-type oxindole alkaloid, isovillocarine D (1) together with two known indole alkaloids, villocarine A (2) and geissoschizine methyl ether (3), and their structural identification was performed with extensive mono- and bidimensional NMR and MS spectroscopic methods. The isolated alkaloids were evaluated for their acetylcholinesterase (AChE)- and butyrylcholinesterase (BChE)-inhibitory activity. The results indicated that compound (2) was the most potent inhibitor against both AChE and BChE, with IC50 values of 14.45 and 13.95 µM, respectively, whereas compounds (1) and (3) were selective BChE inhibitors with IC50 values of 35.28 and 17.65 µM, respectively. In addition, molecular docking studies revealed that compound (2) interacts with the five main regions of AChE via both hydrogen and hydrophobic bonding. In contrast to AChE, the interactions of (2) with the enzymatic site of BChE are established only through hydrophobic bonding. The current finding suggests that U. attenuata could be a good source of bioactive alkaloids for treating age-related dementia.

Linking Diabetes to Alzheimer's Disease: Potential Roles of Glucose Metabolism and Alpha-Glucosidase.

Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) are more prevalent with ageing and cause a substantial global socio-economic burden. The biology of these two conditions is well elaborated, but whether AD and type 2 DM arise from coincidental roots in ageing or are linked by pathophysiological mechanisms remains unclear. Research findings involving animal models have identified mechanisms shared by both AD and type 2 DM. Deposition of ß-amyloid peptides and formation of intracellular neurofibrillary tangles are pathological hallmarks of AD. Type 2 DM, on the other hand, is a metabolic disorder characterised by hyperglycaemia and insulin resistance. Several studies show that improving type 2 DM can delay or prevent the development of AD, and hence, prevention and control of type 2 DM may reduce the risk of AD later in life. Alpha-glucosidase is an enzyme that is commonly associated with hyperglycaemia in type 2 DM. However, it is uncertain if this enzyme may play a role in the progression of AD. This review explores the experimental evidence that depicts the relationship between dysregulation of glucose metabolism and AD. We also delineate the links between alpha-glucosidase and AD and the potential role of alpha-glucosidase inhibitors in treating AD.

Insights into Carbapenem Resistance in Vibrio Species: Current Status and Future Perspectives.

The increasing prevalence of resistance in carbapenems is an escalating concern as carbapenems are reserved as last-line antibiotics. Although indiscriminate antibiotic usage is considered the primary cause for resistance development, increasing evidence revealed that inconsequential strains without any direct clinical relevance to carbapenem usage are harboring carbapenemase genes. This phenomenon indirectly implies that environmental microbial populations could be the 'hidden vectors' propelling carbapenem resistance. This work aims to explore the carbapenem-resistance profile of Vibrio species across diverse settings. This review then proceeds to identify the different factors contributing to the dissemination of the resistance traits and defines the transmission pathways of carbapenem resistance. Deciphering the mechanisms for carbapenem resistance acquisition could help design better prevention strategies to curb the progression of antimicrobial resistance development. To better understand this vast reservoir selecting for carbapenem resistance in non-clinical settings, Vibrio species is also prospected as one of the potential indicator strains for carbapenem resistance in the environment.

Metabolomics Analysis and Antioxidant Potential of Endophytic Diaporthe fraxini ED2 Grown in Different Culture Media.

Endophytic fungi are a promising source of bioactive metabolites with a wide range of pharmacological activities. In the present study, MS-based metabolomics was conducted to study the metabolomes variations of endophytic Diaporthe fraxini ED2 grown in different culture media. Total phenolic content (TPC), total flavonoid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays were conducted to assess the antioxidant potential of the fungal extracts. Multivariate data analysis (MVDA) was employed in data analysis and interpretation to elucidate the complex metabolite profile. The supplemented culture medium of D. fraxini fungal extract stimulated the production of metabolites not occurring in the normal culture medium. Antioxidant activity studies revealed the potential of supplemented cultured fungal extract of D. fraxini as a source of antioxidants. The present findings highlight that fungal culture medium supplementation is an effective approach to unravelling the hidden metabolome in plant-associated fungal diversity.

Natural HSP90 inhibitors as a potential therapeutic intervention in treating cancers: A comprehensive review.

Heat shock protein 90 (Hsp90) has evolved as a cancerous cell growth regulator by stabilising various oncogenic kinases. Upon the Hsp90 inhibition, the expression of its client proteins is downregulated and thus leads to denaturation of cellular proteins and cancer cell death. Hsp90 inhibitors, particularly those naturally derived from plants, fungi and bacteria, have gained substantial interest as a feasible therapeutic approach for cancer treatment due to their diverse pharmacological properties. In order to gain insights into the potential development of more efficacious Hsp90 inhibitors for cancer treatment, this review is conducted to analyse both in vitro and in vivo data on the chemical and biological activities of natural Hsp90 inhibitors. The systematic search was conducted in databases (PubMed, Scopus and Web of Science) with terms "Hsp90 inhibitor" and "cancer", prompting a total of 61 articles after screening with inclusion criteria. This comprehensive review systematically summarised the efficacy of 14 different classes of naturally derived Hsp90 inhibitors in cancerous cell and animal tumour models by consolidating the primary outcomes in terms of IC50, reduction of tumour size and physicochemical properties. The detailed pharmacodynamic (the structure-activity relationship, mechanism of action) and pharmacokinetics (toxicity, oral bioavailability) of these Hsp90 inhibitors together with the study limitations were discussed. Collectively, these findings emphasise the necessity of comprehending the molecular mechanisms as well as the correlation of Hsp90 and its relative client proteins to drive the generation of viable Hsp90 inhibitors with improved pharmacodynamic and pharmacokinetic profiles.

Plant Terpenoids as the Promising Source of Cholinesterase Inhibitors for Anti-AD Therapy.

Plant-derived terpenes are the prolific source of modern drugs such as taxol, chloroquine and artemisinin, which are widely used to treat cancer and malaria infections. There are research interests in recent years on terpene-derived metabolites (diterpenes, triterpenes and sesquiterpenes), which are believed to serve as excellent cholinesterase inhibitors. As cholinesterase inhibitors are the current treatment for Alzheimer's disease, terpene-derived metabolites will have the potential to be involved in the future drug development for Alzheimer's disease. Hence, a bibliographic search was conducted by using the keywords "terpene", "cholinesterase" and "Alzheimer's disease", along with cross-referencing from 2011 to 2020, to provide an overview of natural terpenes with potential anticholinesterase properties. This review focuses on the extraction, chemical structures and anti-cholinesterase mechanisms of terpenes, which support and encourage future research on drug discovery and development in treating Alzheimer's disease.

Anticancer activities of dietary benzyl isothiocyanate: A comprehensive review.

Benzyl isothiocyanate (BITC) is one of the common isothiocyanates found in cruciferous vegetables such as broccoli, cabbage or watercress. Preclinical studies report of its effectiveness in the prevention and treatment against several cancers. This review aims to report and discuss findings on anticancer activities of BITC and its modes of action against 14 types of cancer. A literature search was conducted using the keywords "BITC" and "anticancer" from PubMed, Google Scholar and CINAHL Plus to obtain relevant research articles. This review highlights the anticancer efficacy of BITC through modulation of various signaling pathways involved in apoptosis, cell proliferation, cell cycle arrest, metastasis, angiogenesis, autophagy and the effects of BITC in combination with other drugs. With the available pharmacology evidence, we conclude that further studies are needed to validate its effectiveness in humans for further development and translation into prophylaxis or therapy by promoting optimal therapeutic effects and minimizing toxicity in cancer treatment.

In vitro evaluation of the involvement of Nrf2 in maslinic acid-mediated anti-inflammatory effects in atheroma pathogenesis.

AIMS: Maslinic acid (MA) is a naturally occurring pentacyclic triterpene known to exert cardioprotective effects. This study aims to investigate the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) for MA-mediated anti-inflammatory effects in atheroma pathogenesis in vitro, including evaluation of tumor necrosis factor-alpha (TNF-α)-induced monocyte recruitment, oxidized low-density lipoprotein (oxLDL)-induced scavenger receptors expression, and nuclear factor-kappa B (NF-ĸB) activity in human umbilical vein endothelial cells (HUVECS) and human acute monocytic leukemia cell line (THP-1) macrophages. MATERIALS AND METHODS: An in vitro monocyte recruitment model utilizing THP-1 and HUVECs was developed to evaluate TNF-α-induced monocyte adhesion and trans-endothelial migration. To study the role of Nrf2 for MA-mediated anti-inflammatory effects, Nrf2 inhibitor ML385 was used as the pharmacological inhibitor. The expression of Nrf2, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 36 (CD36), and scavenger receptor type A (SR-A) in HUVECs and THP-1 macrophages were investigated using RT-qPCR and Western blotting. The NF-κB activity was determined using NF-κB (p65) Transcription Factor Assay Kit. KEY FINDINGS: The results showed opposing effects of MA on Nrf2 expression in HUVECs and THP-1 macrophages. MA suppressed TNF-α-induced Nrf2 expression in HUVECs, but enhanced its expression in THP-1 macrophages. Combined effects of MA and ML385 suppressed MCP-1, VCAM-1, and SR-A expressions. Intriguingly, at the protein level, ML385 selectively inhibited SR-A but enhanced CD36 expression. Meanwhile, ML385 further enhanced MA-mediated inhibition of NF-κB activity in HUVECs. This effect, however, was not observed in THP-1 macrophages. SIGNIFICANCE: MA attenuated foam cell formation by suppressing VCAM-1, MCP-1, and SR-A expression, as well as NF-κB activity, possibly through Nrf2 inhibition. The involvement of Nrf2 for MA-mediated anti-inflammatory effects however differs between HUVECs and macrophages. Future investigations are warranted for a detailed evaluation of the contributing roles of Nrf2 in foam cells formation.

Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review.

Oxidative stress is a result of disruption in the balance between antioxidants and pro-oxidants in which subsequently impacting on redox signaling, causing cell and tissue damages. It leads to a range of medical conditions including inflammation, skin aging, impaired wound healing, chronic diseases and cancers but these conditions can be managed properly with the aid of antioxidants. This review features various studies to provide an overview on how Carica papaya help counteract oxidative stress via various mechanisms of action closely related to its antioxidant properties and eventually improving the management of various oxidative stress-related health conditions. Carica papaya is a topical plant species discovered to contain high amounts of natural antioxidants that can usually be found in their leaves, fruits and seeds. It contains various chemical compounds demonstrate significant antioxidant properties including caffeic acid, myricetin, rutin, quercetin, α-tocopherol, papain, benzyl isothiocyanate (BiTC), and kaempferol. Therefore, it can counteract pro-oxidants via a number of signaling pathways that either promote the expression of antioxidant enzymes or reduce ROS production. These signaling pathways activate the antioxidant defense mechanisms that protect the body against both intrinsic and extrinsic oxidative stress. To conclude, Carica papaya can be incorporated into medications or supplements to help manage the health conditions driven by oxidative stress and further studies are needed to investigate the potential of its chemical components to manage various chronic diseases.

Chemical Composition, Antioxidant and Cytoprotective Potentials of Carica papaya Leaf Extracts: A Comparison of Supercritical Fluid and Conventional Extraction Methods.

The leaves of Carica papaya (CP) are rich in natural antioxidants. Carica papaya has traditionally been used to treat various ailments, including skin diseases. This study aims to decipher the antioxidant effects and phytochemical content of different CP leaf extracts (CPEs) obtained using supercritical carbon dioxide (scCO2) and conventional extraction methods. The antioxidant activities of CPEs were evaluated by cell-free (1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric-reduced antioxidative power (FRAP)) and cell-based (H2O2) assay. Both C. papaya leaf scCO2 extract with 5% ethanol (CPSCE) and C. papaya leaf scCO2 extract (CPSC) exhibited stronger DPPH radical scavenging activity than conventional extracts. In the FRAP assay, two hydrophilic extracts (C. papaya leaf ethanol extract (CPEE) and C. papaya freeze-dried leaf juice (CPFD)) showed relatively stronger reducing power compared to lipophilic extracts. Cell-based assays showed that CPFD significantly protected skin fibroblasts from H2O2-induced oxidative stress in both pre-and post-treatment. CPEE protected skin fibroblasts from oxidative stress in a dose-dependent manner while CPSCE significantly triggered the fibroblast recovery after treatment with H2O2. GC-MS analysis indicated that CPSCE had the highest α-tocopherol and squalene contents. By contrast, both CP hydrophilic extracts (CPEE and CPFD) had a higher total phenolic content (TPC) and rutin content than the lipophilic extracts. Overall, CPEs extracted using green and conventional extraction methods showed antioxidative potential in both cell-based and cell-free assays due to their lipophilic and hydrophilic antioxidants, respectively.

Licorice: A Potential Herb in Overcoming SARS-CoV-2 Infections.

The management of the global pandemic outbreak due to the coronavirus disease (COVID-19) has been challenging with no exact dedicated treatment nor established vaccines at the beginning of the pandemic. Nonetheless, the situation seems to be better controlled with the recent COVID-19 vaccines roll-out globally as active immunisation to prevent COVID-19. The extensive usage and trials done in recent outbreak in China has shown the effectiveness of traditional Chinese Medicines (TCM) in improving the wellbeing of COVID-19 patients. Therefore, COVID-19 Prevention and Treatment guidelines has listed a number of recommended concoctions meant for COVID-19 patients. Licorice, more commonly known as Gancao in Chinese Pinyin, is known as one of the most frequently used ingredients in TCM prescriptions for treatment of epidemic diseases. Interestingly, it is deemed as food ingredient as well, where it is normally used in Western cuisines' desserts and sweets. The surprising fact that licorice appeared in the top 10 main ingredients used in TCM prescriptions in COVID-19 has drawn great attention from researchers in revealing its biological potential in overcoming this disease. To date, there are no comprehensive review on licorice and its benefits when used in COVID-19. Thus, in this current review, the possible benefits, mechanism of actions, safety and limitations of licorice were explored in hope to provide a quick reference guide for its preclinical and clinical experimental set-up in this very critical moment of pandemic.

Focused Review: Potential Rare and Atypical Symptoms as Indicator for Targeted COVID-19 Screening.

The global pandemic of the coronavirus disease 2019 is a known consequence of infection of severe respiratory syndrome coronavirus-2 (SARS-CoV-2). It has affected nations worldwide with soaring number of cases daily. Symptoms such as fever, cough, and shortness of breath, diarrhea, nausea and vomiting are commonly presented in COVID-19 patients. This focused review aims to discuss these uncommon and atypical COVID-19 symptoms that may be presented which might affect neurological, cardiovascular, cutaneous and ocular systems and their possible mode of actions. Nonetheless, there are some cases of reported uncommon or atypical symptoms which may warrant healthcare professionals to be aware of, especially when in contact with patients. The knowledge and information concerning these symptoms might be able to provide additional cues for healthcare professional by subjecting patients to COVID-19 screening. Meanwhile, it might be able to further enhance the alertness and additional precautions being taken by healthcare personnel, which eventually lead to reduced risk of infections.

Potential of Naturally Derived Alkaloids as Multi-Targeted Therapeutic Agents for Neurodegenerative Diseases.

Alkaloids are a class of secondary metabolites that can be derived from plants, fungi and marine sponges. They are widely known as a continuous source of medicine for the management of chronic disease including cancer, diabetes and neurodegenerative diseases. For example, galanthamine and huperzine A are alkaloid derivatives currently being used for the symptomatic management of neurodegenerative disease. The etiology of neurodegenerative diseases is polygenic and multifactorial including but not limited to inflammation, oxidative stress and protein aggregation. Therefore, natural-product-based alkaloids with polypharmacology modulation properties are potentially useful for further drug development or, to a lesser extent, as nutraceuticals to manage neurodegeneration. This review aims to discuss and summarise recent developments in relation to naturally derived alkaloids for neurodegenerative diseases.