Medicinal Plants and Natural Compounds for Potential Use in Aging-Related Disorders

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 19377

Special Issue Editors


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Guest Editor
1. Faculties of Sciences and Medicine, University of Chile, Santiago, Chile
2. International Center for Biomedicine-ICC, Santiago, Chile
Interests: Alzheimer; tau protein; neuroimmunomodulation theory; disease prevention; nutraceutical compounds; multi target compounds; non-pharmacological treatment

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Guest Editor
International Center for Biomedicine ICC, Vitacura, Santiago, Chile
Interests: nutraceuticals; nutritional supplements; bioactive compounds; preventive actions

Special Issue Information

Dear Colleagues,

Aging is a progressive physiological change in an organism that leads to senescence or a decline in biological functioning. Occasionally, this is manifested by its close association with an increased incidence of human diseases and higher vulnerability to death. Currently, diseases such as diabetes, cancer, and cardiovascular and neurodegenerative disorders have been related to aging, without successful treatment. However, natural products have been shown to prevent or delay the onset of those aging-associated diseases through various action mechanisms. Natural products, and many nutraceuticals, have played essential roles in aging research due to their chemical structure diversity and the rich obtaining sources documented in different countries or cultures. We aim to develop a Special Issue for Pharmaceuticals that identifies the molecular pathways underlying novel natural products in aging, and establishes their biotechnological uses as anti-aging treatments, and eventually provide a solution to aging-associated diseases.

Prof. Dr. RICARDO B. MACCIONI
Dr. Camila Calfio
Guest Editors

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Keywords

  • nutraceuticals
  • bioactive molecules
  • mechanisms of action
  • non-pharmacological therapies
  • disease prevention
  • human aging
  • natural products-based formulations

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Published Papers (5 papers)

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Research

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13 pages, 3994 KiB  
Article
Effect of Lampaya medicinalis Phil. (Verbenaceae) and Palmitic Acid on Insulin Signaling and Inflammatory Marker Expression in Human Adipocytes
by Gabriela Yuri, Mariana Cifuentes, Pedro Cisternas, Adrián Paredes and Paulina Ormazabal
Pharmaceuticals 2024, 17(5), 566; https://doi.org/10.3390/ph17050566 - 29 Apr 2024
Viewed by 1656
Abstract
Background: Aging and obesity are associated with insulin resistance (IR) and low-grade inflammation. Molecularly, IR is characterized by a reduction in glucose uptake and insulin signaling (IRS-1/Akt/AS160 pathway), while inflammation may result from upregulated NF-κB pathway after low Tyr-IκBα phosphorylation. Upregulated phosphatase activity [...] Read more.
Background: Aging and obesity are associated with insulin resistance (IR) and low-grade inflammation. Molecularly, IR is characterized by a reduction in glucose uptake and insulin signaling (IRS-1/Akt/AS160 pathway), while inflammation may result from upregulated NF-κB pathway after low Tyr-IκBα phosphorylation. Upregulated phosphatase activity of PTP1B is associated with impaired insulin signaling and increased inflammation. Plasma levels of palmitic acid (PA) are elevated in obesity, triggering inflammation and disruption of insulin signaling. Traditional medicine in Northern Chile uses oral infusions of Lampaya medicinalis Phil. (Verbenaceae) to treat inflammatory conditions. Significant amounts of flavonoids are found in the hydroethanolic extract of Lampaya (HEL), which may account for its biological activity. The aim of this work was to study the effect of HEL and PA on insulin signaling and glucose uptake as well as inflammatory marker expression in human adipocytes. Methods: We studied HEL effects on PA-induced impairment on insulin signaling, glucose uptake and inflammatory marker content in human SW872 adipocytes. HEL cytotoxicity was assessed in adipocytes at different concentrations (0.01 to 10 g/mL). Adipocytes were incubated or not with PA (0.4 mM, 24 h) with or without HEL (2 h pre-incubation), and then stimulated with insulin (10 min, 100 mM) or a vehicle. Phospho-IRS-1, phospho-Akt, phospho-AS160, phospho-NF-κB and phospho-IκBα, as well as protein levels of PTP1B, were assessed using Western blotting, and glucose uptake was evaluated using the 2-NBDG analogue. Results: At the assessed HEL concentrations, no cytotoxic effects were observed. PA decreased insulin-stimulated phospho-Akt and glucose uptake, while co-treatment with HEL increased such markers. PA decreased phospho-IRS-1 and phospho-Tyr-IκBα. On the other hand, incubation with HEL+PA decreased phospho-AS160 and phospho-NF-κB compared with cells treated with PA alone. Conclusion: Our results suggest a beneficial effect of HEL by improving PA-induced impairment on molecular markers of insulin signaling, glucose uptake and inflammation in adipocytes. Further studies are necessary to elucidate whether lampaya may constitute a preventive strategy for people whose circulating PA levels contribute to IR and inflammation during aging and obesity. Full article
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19 pages, 5091 KiB  
Article
Scaling the Andean Shilajit: A Novel Neuroprotective Agent for Alzheimer’s Disease
by Víctor Andrade, Maylin Wong-Guerra, Nicole Cortés, Gabriela Pastor, Andrea González, Camila Calfío, Leonardo Guzmán-Martínez, Leonardo P. Navarrete, Nicolas Ramos-Escobar, Inelia Morales, Rocío Santander, Juan Andrades-Lagos, Mitchell Bacho, Leonel E. Rojo and Ricardo Benjamín Maccioni
Pharmaceuticals 2023, 16(7), 960; https://doi.org/10.3390/ph16070960 - 4 Jul 2023
Cited by 2 | Viewed by 5967
Abstract
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder without a cure, despite the enormous number of investigations and therapeutic approaches. AD is a consequence of microglial responses to “damage signals”, such as aggregated tau oligomers, which trigger a neuro-inflammatory reaction, promoting the misfolding [...] Read more.
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder without a cure, despite the enormous number of investigations and therapeutic approaches. AD is a consequence of microglial responses to “damage signals”, such as aggregated tau oligomers, which trigger a neuro-inflammatory reaction, promoting the misfolding of cytoskeleton structure. Since AD is the most prevalent cause of dementia in the elderly (>60 years old), new treatments are essential to improve the well-being of affected subjects. The pharmaceutical industry has not developed new drugs with efficacy for controlling AD. In this context, major attention has been given to nutraceuticals and novel bioactive compounds, such as molecules from the Andean Shilajit (AnSh), obtained from the Andes of Chile. Primary cultures of rat hippocampal neurons and mouse neuroblastoma cells were evaluated to examine the functional and neuroprotective role of different AnSh fractions. Our findings show that AnSh fractions increase the number and length of neuronal processes at a differential dose. All fractions were viable in neurons. The AnSh fractions inhibit tau self-aggregation after 10 days of treatment. Finally, we identified two candidate molecules in M3 fractions assayed by UPLC/MS. Our research points to a novel AnSh-derived fraction that is helpful in AD. Intensive work toward elucidation of the molecular mechanisms is being carried out. AnSh is an alternative for AD treatment or as a coadjuvant for an effective treatment. Full article
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11 pages, 1610 KiB  
Article
Angelica keiskei Impacts the Lifespan and Healthspan of Drosophila melanogaster in a Sex and Strain-Dependent Manner
by Mahtab Jafari, Samuel E. Schriner, Yun-Seo Kil, Sally T. Pham and Eun Kyoung Seo
Pharmaceuticals 2023, 16(5), 738; https://doi.org/10.3390/ph16050738 - 12 May 2023
Cited by 3 | Viewed by 1870
Abstract
Angelica keiskei is a perennial plant, belonging to the Apiaceae family and originating from Japan. This plant has been reported to act as a diuretic, analeptic, antidiabetic, hypertensive, tumor, galactagogue, and laxative. The mechanism of action of A. keiskei is not known, but [...] Read more.
Angelica keiskei is a perennial plant, belonging to the Apiaceae family and originating from Japan. This plant has been reported to act as a diuretic, analeptic, antidiabetic, hypertensive, tumor, galactagogue, and laxative. The mechanism of action of A. keiskei is not known, but previous studies have suggested that it may act as an antioxidant. In this work, we used Drosophila melanogaster to evaluate the impact of A. keiskei on lifespan and healthspan and its potential anti-aging mechanism by conducting multiple assays on three fly strains: w1118, chico, and JIV. We observed that the extract extended lifespan and improved healthspan in a sex- and strain-dependent manner. A. keiskei extended lifespan and improved reproductive fitness in female flies and either had no effect or decreased survival and physical performance in males. The extract protected against the superoxide generator paraquat in both sexes. These sex-specific effects suggest that A. keiskei may act through age-specific pathways such as the insulin and insulin-like growth factor signaling (IIS) pathways. Upon examination, we found that the increased survival of A. keiskei-fed females was dependent on the presence of the insulin receptor substrate chico, supporting the role of IIS in the action of A. keiskei. Full article
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16 pages, 2100 KiB  
Article
Effects of Fisetin, a Plant-Derived Flavonoid, on Response to Oxidative Stress, Aging, and Age-Related Diseases in Caenorhabditis elegans
by Suhyeon Park, Bo-Kyoung Kim and Sang-Kyu Park
Pharmaceuticals 2022, 15(12), 1528; https://doi.org/10.3390/ph15121528 - 8 Dec 2022
Cited by 20 | Viewed by 5618
Abstract
Fisetin (3,3′,4′,7-tetrahydroxyflavone), a flavonoid abundant in various fruits and vegetables, including apple, strawberry, and onion, shows several beneficial effects such as anti-oxidant, anti-inflammatory, and anti-tumor effects. The free radical theory of aging suggests that age-related accumulation of oxidative damage is the major cause [...] Read more.
Fisetin (3,3′,4′,7-tetrahydroxyflavone), a flavonoid abundant in various fruits and vegetables, including apple, strawberry, and onion, shows several beneficial effects such as anti-oxidant, anti-inflammatory, and anti-tumor effects. The free radical theory of aging suggests that age-related accumulation of oxidative damage is the major cause of aging and that decreasing cellular oxidative stress can regulate aging. Here, we investigated the effects of dietary supplementation with fisetin on the stress response, aging, and age-related diseases. Fisetin reduced the cellular ROS levels and increased the resistance to oxidative stress. However, the response to UV irradiation was not affected by fisetin. Both the mean and maximum lifespans were significantly extended by fisetin; lifespan extension by fisetin was accompanied by reduced fertility as a trade-off. Age-related decline in motility was also delayed by supplementation with fisetin. Amyloid beta-induced toxicity was markedly decreased by fisetin, which required DAF-16 and SKN-1. Reduced motility induced by a high-glucose diet was completely recovered by supplementation with fisetin, which was dependent on SKN-1. Using a Parkinson’s disease model, we showed that degeneration of dopaminergic neurons was significantly inhibited by treatment with fisetin. Genetic analysis revealed that lifespan extension by fisetin was mediated by DAF-16-induced stress response and autophagy. These findings support the free radical theory of aging and suggest that fisetin can be a strong candidate for use in novel anti-aging anti-oxidant nutraceuticals. Full article
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Review

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17 pages, 1531 KiB  
Review
Pomegranate: A Source of Multifunctional Bioactive Compounds Potentially Beneficial in Alzheimer’s Disease
by Lidia Ciccone, Susanna Nencetti, Armando Rossello and Elisabetta Orlandini
Pharmaceuticals 2023, 16(7), 1036; https://doi.org/10.3390/ph16071036 - 21 Jul 2023
Cited by 3 | Viewed by 3429
Abstract
Pomegranate fruit (PF) is a fruit rich in nutraceuticals. Nonedible parts of the fruit, especially peels, contain high amounts of bioactive components that have been largely used in traditional medicine, such as the Chinese, Unani, and Ayurvedic ones, for treating several diseases. Polyphenols [...] Read more.
Pomegranate fruit (PF) is a fruit rich in nutraceuticals. Nonedible parts of the fruit, especially peels, contain high amounts of bioactive components that have been largely used in traditional medicine, such as the Chinese, Unani, and Ayurvedic ones, for treating several diseases. Polyphenols such as anthocyanins, tannins, flavonoids, phenolic acids, and lignans are the major bioactive molecules present in PF. Therefore, PF is considered a source of natural multifunctional agents that exert simultaneously antioxidant, anti-inflammatory, antitumor, antidiabetic, cardiovascular, and neuroprotective activities. Recently, several studies have reported that the nutraceuticals contained in PF (seed, peel, and juice) have a potential beneficial role in Alzheimer’s disease (AD). Research suggests that the neuroprotective effect of PF is mostly due to its potent antioxidant and anti-inflammatory activities which contribute to attenuate the neuroinflammation associated with AD. Despite the numerous works conducted on PF, to date the mechanism by which PF acts in combatting AD is not completely known. Here, we summarize all the recent findings (in vitro and in vivo studies) related to the positive effects that PF and its bioactive components can have in the neurodegeneration processes occurring during AD. Moreover, considering the high biotransformation characteristics of the nutraceuticals present in PF, we propose to consider the chemical structure of its active metabolites as a source of inspiration to design new molecules with the same beneficial effects but less prone to be affected by the metabolic degradation process. Full article
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