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1.
Molecules ; 29(5)2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38474465

ABSTRACT

The pharmacological activity and medicinal significance of Amauroderma rugosum (AR) have rarely been documented. We examined the antioxidant and neuroprotective effects of AR on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in an SH-SY5Y human neuroblastoma cell model of Parkinson's disease (PD) and explored the active ingredients responsible for these effects. The results showed that the AR aqueous extract could scavenge reactive oxygen species and reduce SH-SY5Y cell death induced by 6-OHDA. In addition, the AR aqueous extract increased the survival of Caenorhabditis elegans upon juglone-induced toxicity. Among the constituents of AR, only polysaccharides and gallic acid exhibited antioxidant and neuroprotective effects. The AR aqueous extract reduced apoptosis and increased the expression of phospho-Akt, phospho-mTOR, phospho-MEK, phospho-ERK, and superoxide dismutase-1 in 6-OHDA-treated SH-SY5Y cells. The polysaccharide-rich AR extract was slightly more potent than the aqueous AR extract; however, it did not affect the expression of phospho-Akt or phospho-mTOR. In conclusion, the AR aqueous extract possessed antioxidant and neuroprotective properties against 6-OHDA-induced toxicity in SH-SY5Y cells. The mechanism of action involves the upregulation of the Akt/mTOR and MEK/ERK-dependent pathways. These findings indicate the potential utility of AR and its active ingredients in preventing or treating neurodegenerative disorders associated with oxidative stress such as PD.


Subject(s)
Neuroblastoma , Neuroprotective Agents , Parkinson Disease , Polyporaceae , Humans , Oxidopamine/pharmacology , Neuroprotective Agents/pharmacology , Antioxidants/pharmacology , Gallic Acid/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Cell Line, Tumor , Neuroblastoma/drug therapy , Apoptosis , Reactive Oxygen Species/metabolism , Parkinson Disease/drug therapy , TOR Serine-Threonine Kinases , Mitogen-Activated Protein Kinase Kinases
2.
Foods ; 12(21)2023 Oct 29.
Article in English | MEDLINE | ID: mdl-37959074

ABSTRACT

Nam Wah banana (Musa paradisiaca L.) is the most common banana cultivar in Thailand. Large amounts of its non-consumable byproducts are considered undervalued and thrown as waste. Exploring the potential utilization and application of banana byproducts for human benefit can add to their value and minimize the risk of threats. This study aimed to investigate phytochemicals, antioxidant and anti-inflammatory activities, and toxicity of Nam Wah banana byproducts. Five banana plant parts, including the midrib, leaf, peduncle, unripe and ripe peels, were extracted using hexane, ethyl acetate, ethanol, and water. Among the extracts tested, the ethyl acetate leaf extract showed the strongest antioxidant capacity and anti-inflammatory activity, probably through the inhibition of inducible nitric oxide synthase (iNOS) and 15-lipoxygenase (15-LOX). Positive correlations existed between the activities and the total phenolic/flavonoid content of banana byproducts. An in silico docking analysis demonstrated that flavonoid glycosides in banana byproducts, such as kaempferol-3-O-rutinoside and rutin, may bind to inducible iNOS, whereas omega-3-polyunsaturated fatty acids, such as eicosapentaenoic acid, may bind to 15-LOX and cyclooxygenase-2 (COX-2). The extracts showed either low or no toxicity. These findings suggest that banana byproducts are a natural source of antioxidant and anti-inflammatory compounds. It is recommended that additional investigations be conducted to explore their potential therapeutic applications in treating disorders linked with oxidative stress or inflammation. This research has the potential to enhance the value of banana byproducts.

3.
Sci Rep ; 13(1): 16707, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37794096

ABSTRACT

Achieving healthy aging and providing protection from aging-related diseases is a major global concern. Probiotics, are a safer and more natural alternative. Moreover, identifying novel probiotics can help develop a new therapeutic approach and may help in personalized probiotic-formulations for individual's unique gut microbiome. In this study, we evaluated the benefits of our novel probiotic strains in promoting healthy aging and whether they protect against Amyloid ß toxicity of Alzheimer's disease. Henceforth, we analyzed the impact of four different probiotics (Lactobacillus paracasei HII01, L. rhamnosus, L. reuteri, L. salivarius) on the lifespan extension of Caenorhabditis elegans model. Our results determine that L. paracasei HII01 provided the most positive effect on longevity and antiaging effects on C. elegans. The qPCR data and mutant-based studies indicated that L. paracasei HII01-mediated lifespan extension could be modulated by DAF-16 mediated pathway. The probiotic strains also protected the worms from the toxicity induced by ß-Amyloid-expressing (Aß) transgenic C. elegans strains, and L. paracasei HII01 provided the most significant protection. Overall, identifying novel probiotics is an important area of research that can improve health outcomes. Our study showed that L. paracasei HII01 could be considered a dietary supplement for providing healthy aging and preventing aging-related diseases.


Subject(s)
Lacticaseibacillus paracasei , Probiotics , Animals , Caenorhabditis elegans/metabolism , Longevity , Amyloid beta-Peptides/metabolism , Neuroprotection , Probiotics/pharmacology , Probiotics/metabolism
4.
Nutrients ; 15(18)2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37764767

ABSTRACT

Aquilaria crassna (AC) is a beneficial plant widely used to alleviate various health ailments. Nevertheless, the neuroprotection, antiaging, and xenobiotic detoxification against high benzo[a]pyrene induction have not been investigated. This study aimed to investigate the effects of ethanolic extract of AC leaves (ACEE) in vitro using SH-SY5Y cells and in vivo using Caenorhabditis elegans (C. elegans). Neuroprotective activities and cell cycle progression were studied using SH-SY5Y cells. Additionally, C. elegans was used to determine longevity, health span, and transcriptional analysis. Furthermore, ACEE possible active compounds were analyzed by gas chromatograph-mass spectrometry (GC-MS) analysis and the possible active compounds were evaluated using a molecular docking study. First, ACEE possessed neuroprotective effects by normalizing cell cycle progression via the regulation of AhR/CYP1A1/cyclin D1 pathway. Next, ACEE played a role in xenobiotic detoxification in high B[a]P-induced C. elegans by the amelioration of lifespan reduction, and body length and size decrease through the reduction in gene expression in hexokinase (hxk) and CYP35 pathway. Finally, phytochemicals of ACEE were identified and we uncovered that clionasterol was the possible active constituent in powerfully inhibiting both CYP1A1 and hexokinase II receptor. Essentially, ACEE was recognized as a potential alternative medicine to defend against high B[a]P effects on neurotoxicity and xenobiotic detoxification.

5.
Foods ; 12(13)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37444267

ABSTRACT

Ergosterol is an important sterol commonly found in edible mushrooms, and it has important nutritional value and pharmacological activity. Ergosterol is a provitamin. It has been well established that edible mushrooms are an excellent food source of vitamin D2 because ergosterol is a precursor that is converted to vitamin D2 under ultraviolet radiation. The pharmacological effects of ergosterol, which include antimicrobial, antioxidant, antimicrobial, anticancer, antidiabetic, anti-neurodegenerative, and other activities, have also been reported. This review aims to provide an overview of the available evidence regarding the pharmacological effects of ergosterol and its underlying mechanisms of action. Their potential benefits and applications are also discussed.

6.
Molecules ; 28(10)2023 May 12.
Article in English | MEDLINE | ID: mdl-37241795

ABSTRACT

Our early work indicated that methanolic extracts from the flowers, leaves, bark, and isolated compounds of Acacia saligna exhibited significant antioxidant activities in vitro. The overproduction of reactive oxygen species (ROS) in the mitochondria (mt-ROS) interfered with glucose uptake, metabolism, and its AMPK-dependent pathway, contributing to hyperglycemia and diabetes. This study aimed to screen the ability of these extracts and isolated compounds to attenuate the production of ROS and maintain mitochondrial function via the restoration of mitochondrial membrane potential (MMP) in 3T3-L1 adipocytes. Downstream effects were investigated via an immunoblot analysis of the AMPK signalling pathway and glucose uptake assays. All methanolic extracts effectively reduced cellular ROS and mt-ROS levels, restored the MMP, activated AMPK-α, and enhanced cellular glucose uptake. At 10 µM, (-)-epicatechin-6 (from methanolic leaf and bark extracts) markedly reduced ROS and mt-ROS levels by almost 30% and 50%, respectively, with an MMP potential ratio 2.2-fold higher compared to the vehicle control. (-)-Epicatechin 6 increased the phosphorylation of AMPK-α by 43%, with an 88% higher glucose uptake than the control. Other isolated compounds include naringenin 1, naringenin-7-O-α-L-arabinopyranoside 2, isosalipurposide 3, D-(+)-pinitol 5a, and (-)-pinitol 5b, which also performed relatively well across all assays. Australian A. saligna active extracts and compounds can reduce ROS oxidative stress, improve mitochondrial function, and enhance glucose uptake through AMPK-α activation in adipocytes, supporting its potential antidiabetic application.


Subject(s)
Acacia , Catechin , Hypoglycemic Agents , Animals , Mice , 3T3-L1 Cells , Acacia/chemistry , Adipocytes/metabolism , AMP-Activated Protein Kinases/metabolism , Australia , Catechin/chemistry , Catechin/pharmacology , Glucose/metabolism , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism
7.
Sci Rep ; 13(1): 7225, 2023 05 04.
Article in English | MEDLINE | ID: mdl-37142620

ABSTRACT

Glutamate-induced neurotoxicity in the HT22 mouse hippocampal neuronal cell line has been recognized as a valuable cell model for the study of neurotoxicity associated with neurodegenerative diseases including Alzheimer's disease (AD). However, the relevance of this cell model for AD pathogenesis and preclinical drug screening remains to be more elucidated. While there is increasing use of this cell model in a number of studies, relatively little is known about its underlying molecular signatures in relation to AD. Here, our RNA sequencing study provides the first transcriptomic and network analyses of HT22 cells following glutamate exposure. Several differentially expressed genes (DEGs) and their relationships specific to AD were identified. Additionally, the usefulness of this cell model as a drug screening system was assessed by determining the expression of those AD-associated DEGs in response to two medicinal plant extracts, Acanthus ebracteatus and Streblus asper, that have been previously shown to be protective in this cell model. In summary, the present study reports newly identified AD-specific molecular signatures in glutamate-injured HT22 cells, suggesting that this cell can be a valuable model system for the screening and evaluation of new anti-AD agents, particularly from natural products.


Subject(s)
Alzheimer Disease , Glutamic Acid , Mice , Animals , Glutamic Acid/toxicity , Glutamic Acid/metabolism , Oxidative Stress/physiology , Transcriptome , Neurons/metabolism , Cell Line , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Hippocampus/metabolism
8.
Heliyon ; 9(4): e15233, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37035364

ABSTRACT

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has been affecting people globally, and the Philippines is one of the countries greatly struck by the virus. The continued rise of new positive cases has drawn attention to the urgent need for healthcare management to cope with this challenge. Severity prediction could help improve medical decision-making and optimise the patient's treatment plan with a good clinical outcome. This study aimed to identify the determinants of COVID-19 disease severity. Methods: Demographic characteristics and laboratory findings were collected from electronic medical records and paper forms of all confirmed COVID-19 cases reported by the University of Perpetual Help DALTA Medical Center between the September 1, 2020 and the October 31, 2021. We performed statistical analyses and interpretation of data to compare severe and non-severe groups. Results: 5,396 confirmed cases were examined. Most of the severe cases were elderly, male, had blood type A, and with comorbidities. Cycle threshold (Ct) values were lower in the severe group. Most patients had higher-than-normal levels of all blood parameters except platelet, white blood cell (WBC), neutrophil, and lymphocyte counts. Age, sex, ABO blood groups, comorbidities, open reading frame 1 ab (ORF1ab) and nucleocapsid (N) gene Ct values, ferritin, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, white blood cell (WBC) count, neutrophil count, and lymphocyte count were significantly associated with disease severity. In multivariate analysis, age groups >60 and 30-59 years, presence of comorbidities, CRP level >5 ng/mL, and PCT >0.05 ng/mL were identified as disease severity predictors. Conclusions: Based on our results, age, comorbidities, CRP, and PCT level may be utilised as primary assessment factors for possible hospital admission and close monitoring upon testing. Early detection of these risk factors may provide strategic interventions that help reduce mortality, hospital admissions, and more expensive and extensive treatments.

9.
Molecules ; 28(3)2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36770694

ABSTRACT

Acacia saligna growing in Australia has not been fully investigated for its bioactive phytochemicals. Sequential polarity-based extraction was employed to provide four different extracts from individual parts of A. saligna. Bioactive extracts were determined using in vitro antioxidant and yeast α-glucosidase inhibitory assays. Methanolic extracts from barks, leaves, and flowers are the most active and have no toxicity against 3T3-L1 adipocytes. Compound isolation of bioactive extracts provided us with ten compounds. Among them are two novel natural products; naringenin-7-O-α-L-arabinopyranoside 2 and (3S*,5S*)-3-hydroxy-5-(2-aminoethyl) dihydrofuran-2(3H)-one 9. D-(+)-pinitol 5a (from barks and flowers), (-)-pinitol 5b (exclusively from leaf), and 2,4-di-t-butylphenol 7 are known natural products and new to A. saligna. (-)-Epicatechin 6, quercitrin 4, and myricitrin 8 showed potent antioxidant activities consistently in DPPH and ABTS assays. (-)-Epicatechin 6 (IC50 = 63.58 µM),D-(+)-pinitol 5a (IC50 = 74.69 µM), and naringenin 1 (IC50 = 89.71 µM) are the strong inhibitors against the α-glucosidase enzyme. The presence of these compounds supports the activities exerted in our methanolic extracts. The presence of 2,4-di-t-butylphenol 7 may support the reported allelopathic and antifungal activities. The outcome of this study indicates the potential of Australian A. saligna as a rich source of bioactive compounds for drug discovery targeting type 2 diabetes.


Subject(s)
Acacia , Catechin , Diabetes Mellitus, Type 2 , Humans , Plant Extracts/chemistry , Antioxidants/chemistry , alpha-Glucosidases , Australia , Phytochemicals/pharmacology
10.
WIREs Mech Dis ; 15(2): e1591, 2023 03.
Article in English | MEDLINE | ID: mdl-36494193

ABSTRACT

Alzheimer's disease (AD) is one of the progressive neurodegenerative disorders and the most common cause of dementia in the elderly worldwide causing difficulties in the daily life of the patient. AD is characterized by the aberrant accumulation of ß-amyloid plaques and tau protein-containing neurofibrillary tangles (NFTs) in the brain giving rise to neuroinflammation, oxidative stress, synaptic failure, and eventual neuronal cell death. The total cost of care in AD treatment and related health care activities is enormous and pharmaceutical drugs approved by Food and Drug Administration have not manifested sufficient efficacy in protection and therapy. In recent years, there are growing studies that contribute a fundamental understanding to AD pathogenesis, AD-associated risk factors, and pharmacological intervention. However, greater molecular process-oriented research in company with suitable experimental models is still of the essence to enhance the prospects for AD therapy and cell lines as a disease model are still the major part of this milestone. In this review, we provide an insight into molecular mechanisms, particularly the recent concept in gut-brain axis, vascular dysfunction and autophagy, and current models used in the study of AD. Here, we emphasized the importance of therapeutic strategy targeting multiple mechanisms together with utilizing appropriate models for the discovery of novel effective AD therapy. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.


Subject(s)
Alzheimer Disease , United States , Humans , Aged , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Neurofibrillary Tangles/metabolism , Brain/metabolism , Autophagy
11.
Nutrients ; 14(17)2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36079924

ABSTRACT

Hyperglycemia is one of the important causes of neurodegenerative disorders and aging. Aquilaria crassna Pierre ex Lec (AC) has been widely used to relieve various health ailments. However, the neuroprotective and anti-aging effects against high glucose induction have not been investigated. This study aimed to investigate the effects of hexane extract of AC leaves (ACH) in vitro using human neuroblastoma SH-SY5Y cells and in vivo using nematode Caenorhabditis elegans. SH-SY5Y cells and C. elegans were pre-exposed with high glucose, followed by ACH treatment. To investigate neuroprotective activities, neurite outgrowth and cell cycle progression were determined in SH-SY5Y cells. In addition, C. elegans was used to determine ACH effects on antioxidant activity, longevity, and healthspan. In addition, ACH phytochemicals were analyzed and the possible active compounds were identified using a molecular docking study. ACH exerted neuroprotective effects by inducing neurite outgrowth via upregulating growth-associated protein 43 and teneurin-4 expression and normalizing cell cycle progression through the regulation of cyclin D1 and SIRT1 expression. Furthermore, ACH prolonged lifespan, improved body size, body length, and brood size, and reduced intracellular ROS accumulation in high glucose-induced C. elegans via the activation of gene expression in the DAF-16/FoxO pathway. Finally, phytochemicals of ACH were analyzed and revealed that ß-sitosterol and stigmasterol were the possible active constituents in inhibiting insulin-like growth factor 1 receptor (IGFR). The results of this study establish ACH as an alternative medicine to defend against high glucose effects on neurotoxicity and aging.


Subject(s)
Caenorhabditis elegans , Plant Extracts , Thymelaeaceae , Animals , Caenorhabditis elegans/drug effects , Cell Line, Tumor , Forkhead Transcription Factors/metabolism , Glucose/adverse effects , Humans , Longevity , Molecular Docking Simulation , Plant Extracts/chemistry , Thymelaeaceae/chemistry
12.
Nutrients ; 14(18)2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36145217

ABSTRACT

Phenanthrene (Phe) exposure is associated with skin ageing, cardiotoxicity and developmental defects. Here, we investigated the mode of Phe toxicity in human keratinocytes (HaCaT cells) and the attenuation of toxicity on pre-treatment (6 h) with ethanol extract of Hibiscus sabdariffa calyxes (HS). Cell viability, reactive oxygen species (ROS) generation, mitochondrial membrane potential (ΔΨm) alteration, changes in the transcriptional activity of selected genes involved in phase I and II metabolism, antioxidant response and gluconeogenesis, western blot and docking studies were performed to determine the protective effect of HS against Phe. Phe (250 µM) induced cytotoxicity in HaCaT cells through AhR-independent, CAR/PXR/RXR-mediated activation of CYP1A1 and the subsequent alterations in phase I and II metabolism genes. Further, CYP1A1 activation by Phe induced ROS generation, reduced ΔΨm and modulated antioxidant response, phase II metabolism and gluconeogenesis-related gene expression. However, pre-treatment with HS extract restored the pathological changes observed upon Phe exposure through CYP1A1 inhibition. Docking studies showed the site-specific activation of PXR and CAR by Phe and inhibition of CYP1A1 and CYP3A4 by the bioactive compounds of HS similar to that of the positive controls tested. Our results conclude that HS extract can attenuate Phe-induced toxicity in HaCaT cells through CAR/PXR/RXR mediated inhibition of CYP1A1.


Subject(s)
Hibiscus , Phenanthrenes , Plant Extracts/pharmacology , Receptors, Steroid , Antioxidants/pharmacology , Constitutive Androstane Receptor , Cytochrome P-450 CYP1A1 , Cytochrome P-450 CYP3A , Ethanol , HaCaT Cells , Humans , Pregnane X Receptor , Reactive Oxygen Species , Receptors, Cytoplasmic and Nuclear , Receptors, Steroid/metabolism
13.
Saudi J Biol Sci ; 29(7): 103330, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35721231

ABSTRACT

Diabetic foot ulcer (DFU) is a common and devastating complication in diabetic patients and is associated with an elevated risk of amputation and mortality. DFU remains a major therapeutic challenge due to poor understanding of its underlying pathogenesis. This complication is characterized by impaired wound healing; however, mechanisms causing this impairment are complicated and involve interactions between many different cell types and infections. In addition to other conventional DFU treatments, herbal foot baths are also common, although little is known about their mechanisms of action, and they contain a wide variety of herbal ingredients. In this study, we aimed to examine the effects of three polyherbal formulations consisting of medicinal plants used in traditional Thai herbal foot baths on wound healing, anti-inflammation, angiogenesis, and extracellular matrix modulation using high-concentration glucose-treated human keratinocytes, in addition to antibacterial evaluation. Our results showed that formulation 3 (F3) possessed the greatest potential to restore the impairment of keratinocytes caused by high glucose concentrations. We found that F3 could inhibit the growth of Staphylococcus aureus, accelerate wound healing, and upregulate the expression of TIMP-1, VEGF, and TGF-ß, and downregulate the expression of TNF-α, IL-6, and MMP-9. Collectively, these data support the potential of F3 for therapeutic development in the treatment of DFU.

14.
Nutrients ; 15(1)2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36615695

ABSTRACT

The tea plant (C. sinensis) has traditionally been consumed worldwide as "tea" for its many health benefits, with the potential for the prevention and therapy of various conditions. Regardless of its long history, the use of tea plants in modern times seems not to have changed much, as the beverage remains the most popular form. This review aimed to compile scientific information about the role and action of tea plants, as well as their status concerning clinical applications, based on the currently available evidence, with a focus on metabolic syndrome, mainly covering obesity, diabetes, and cardiovascular disease. It has been recognized that these diseases pose a significant threat to public health, and the development of effective treatment and prevention strategies is necessary but still challenging. In this article, the potential benefits of tea plants and their derived bioactive components (such as epigallocatechin-3-gallate) as anti-obesity, anti-diabetic, and anti-cardiovascular agents are clearly shown and emphasized, along with their mechanisms of action. However, according to the status of the clinical translation of tea plants, particularly in drug development, more substantial efforts in well-designed, randomized, controlled trials are required to expand their applications in treating the three major metabolic disorders and avoiding the toxicity caused by overconsumption.


Subject(s)
Camellia sinensis , Cardiovascular Diseases , Catechin , Diabetes Mellitus , Metabolic Syndrome , Cardiovascular Diseases/prevention & control , Diabetes Mellitus/drug therapy , Diabetes Mellitus/prevention & control , Obesity , Catechin/pharmacology
15.
Plants (Basel) ; 12(1)2022 Dec 22.
Article in English | MEDLINE | ID: mdl-36616194

ABSTRACT

The skin is the largest organ that performs a variety of the body's essential functions. Impairment of skin structure and functions during the aging process might severely impact our health and well-being. Extensive evidence suggests that reactive oxygen species play a fundamental role in skin aging through the activation of the related degradative enzymes. Here, the 16 Thai medicinal plant species were screened for their potential anti-skin aging properties. All extracts were investigated for total phenolic and flavonoid contents, antioxidant, anti-elastase, and anti-tyrosinase activities, as well as the binding ability of compounds with target enzymes by molecular docking. Among all the plants screened, the leaves of A. occidentale and G. zeylanicum exhibited strong antioxidants and inhibition against elastase and tyrosinase. Other potential plants include S. alata leaf and A. catechu fruit, with relatively high anti-elastase and anti-tyrosinase activities, respectively. These results are also consistent with docking studies of compounds derived from these plants. The inhibitory actions were found to be more highly positively correlated with phenolics than flavonoids. Taken together, our findings reveal some Thai plants, along with candidate compounds as natural sources of antioxidants and potent inhibitors of elastase and tyrosinase, could be developed as promising and effective agents for skin aging therapy.

16.
Pharmaceuticals (Basel) ; 14(10)2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34681206

ABSTRACT

Polyphenols are a family of naturally occurring organic compounds, majorly present in fruits, vegetables, and cereals, characterised by multiple phenol units, including flavonoids, tannic acid, and ellagitannin. Some well-known polyphenols include resveratrol, quercetin, curcumin, epigallocatechin gallate, catechin, hesperetin, cyanidin, procyanidin, caffeic acid, and genistein. They can modulate different pathways inside the host, thereby inducing various health benefits. Autophagy is a conserved process that maintains cellular homeostasis by clearing the damaged cellular components and balancing cellular survival and overall health. Polyphenols could maintain autophagic equilibrium, thereby providing various health benefits in mediating neuroprotection and exhibiting anticancer and antidiabetic properties. They could limit brain damage by dismantling misfolded proteins and dysfunctional mitochondria, thereby activating autophagy and eliciting neuroprotection. An anticarcinogenic mechanism is stimulated by modulating canonical and non-canonical signalling pathways. Polyphenols could also decrease insulin resistance and inhibit loss of pancreatic islet ß-cell mass and function from inducing antidiabetic activity. Polyphenols are usually included in the diet and may not cause significant side effects that could be effectively used to prevent and treat major diseases and ailments.

17.
Pharmaceuticals (Basel) ; 14(9)2021 Sep 04.
Article in English | MEDLINE | ID: mdl-34577601

ABSTRACT

Alzheimer's disease (AD) is implicated in the imbalance of several proteins, including Amyloid-ß (Aß), amyloid precursor protein (APP), and BACE1. APP overexpression interferes with neurite outgrowth, while BACE1 plays a role in Aß generation. Medicinal herbs with effects on neurite outgrowth stimulation and BACE1 inhibition may benefit AD. This study aimed to investigate the neurite outgrowth stimulatory effect, along with BACE1 inhibition of Caesalpinia mimosoides (CM), using wild-type (Neuro2a) and APP (Swedish mutant)-overexpressing (Neuro2a/APPSwe) neurons. The methanol extract of CM leaves stimulated neurite outgrowth in wild-type and APP-overexpressing cells. After exposure to the extract, the mRNA expression of the neurite outgrowth activation genes growth-associated protein-43 (GAP-43) and teneurin-4 (Ten-4) was increased in both Neuro2a and Neuro2a/APPSwe cells, while the mRNA expression of neurite outgrowth negative regulators Nogo receptor (NgR) and Lingo-1 was reduced. Additionally, the extract suppressed BACE1 activity in the APP-overexpressing neurons. Virtual screening demonstrated that quercetin-3'-glucuronide, quercetin-3-O-glucoside, clausarinol, and theogallin were possible inhibitors of BACE1. ADMET was analyzed to predict drug-likeness properties of CM-constituents. These results suggest that CM extract promotes neurite outgrowth and inhibits BACE1 activity in APP-overexpressing neurons. Thus, CM may serve as a source of drugs for AD treatment. Additional studies for full identification of bioactive constituents and to confirm the neuritogenesis in vivo are needed for translation into clinic of the present findings.

18.
Nutrients ; 13(7)2021 Jul 10.
Article in English | MEDLINE | ID: mdl-34371875

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) have been recognized to cause neurobehavioral dysfunctions and disorder of cognition and behavioral patterns in childhood. Momordica charantia L. (MC) has been widely known for its nutraceutical and health-promoting properties. To date, the effect of MC for the prevention and handling of PAHs-induced neurotoxicity has not been reported. In the current study, the neuroprotective effects of MC and its underlying mechanisms were investigated in mouse hippocampal neuronal cell line (HT22); moreover, in silico analysis was performed with the phytochemicals MC to decipher their potential function as neuroprotectants. MC was demonstrated to possess neuroprotective effect by reducing reactive oxygen species' (ROS') production and down-regulating cyclin D1, p53, and p38 mitogen-activated protein kinase (MAPK) protein expressions, resulting in the inhibition of cell apoptosis and the normalization of cell cycle progression. Additionally, 28 phytochemicals of MC and their competence on inhibiting cytochrome P450 (CYP: CYP1A1, CYP1A2, and CYP1B1) functions were resolved. In silico analysis of vitamin E and stigmasterol revealed that their binding to either CYP1A1 or CYP1A2 was more efficient than the binding of each positive control (alizarin or purpurin). Together, MC is potentially an interesting neuroprotectant including vitamin E and stigmasterol as probable active components for the prevention for PAHs-induced neurotoxicity.


Subject(s)
Hippocampus/drug effects , Momordica charantia , Neurons/drug effects , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Polycyclic Aromatic Hydrocarbons/toxicity , Stigmasterol/pharmacology , Vitamin E/pharmacology , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Cell Cycle/drug effects , Cell Cycle Proteins/metabolism , Cell Line , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A2/metabolism , Hippocampus/metabolism , Hippocampus/pathology , Mice , Momordica charantia/chemistry , Neurons/metabolism , Neurons/pathology , Oxidative Stress/drug effects , Plant Extracts/isolation & purification , Protein Binding , Reactive Oxygen Species/metabolism , Stigmasterol/isolation & purification , Vitamin E/isolation & purification
19.
Nutrients ; 13(7)2021 Jun 23.
Article in English | MEDLINE | ID: mdl-34201882

ABSTRACT

Tea is one of the most popular and widely consumed beverages worldwide, and possesses numerous potential health benefits. Herbal teas are well-known to contain an abundance of polyphenol antioxidants and other ingredients, thereby implicating protection and treatment against various ailments, and maintaining overall health in humans, although their mechanisms of action have not yet been fully identified. Autophagy is a conserved mechanism present in organisms that maintains basal cellular homeostasis and is essential in mediating the pathogenesis of several diseases, including cancer, type II diabetes, obesity, and Alzheimer's disease. The increasing prevalence of these diseases, which could be attributed to the imbalance in the level of autophagy, presents a considerable challenge in the healthcare industry. Natural medicine stands as an effective, safe, and economical alternative in balancing autophagy and maintaining homeostasis. Tea is a part of the diet for many people, and it could mediate autophagy as well. Here, we aim to provide an updated overview of popular herbal teas' health-promoting and disease healing properties and in-depth information on their relation to autophagy and its related signaling molecules. The present review sheds more light on the significance of herbal teas in regulating autophagy, thereby improving overall health.


Subject(s)
Autophagy , Cells/metabolism , Health , Homeostasis , Teas, Herbal , Animals , Humans
20.
J Tradit Complement Med ; 11(2): 144-157, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33520683

ABSTRACT

BACKGROUND AND AIM: The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now become a worldwide pandemic bringing over 71 million confirmed cases, while the specific drugs and vaccines approved for this disease are still limited regarding their effectiveness and adverse events. Since virus incidences are still on rise, infectivity and mortality may also rise in the near future, natural products are highly considered to be valuable sources for the discovery of new antiviral drugs against SARS-CoV-2. This present review aims to comprehensively summarize the up-to-date scientific literatures on biological activities of plant- and mushroom-derived compounds relevant to mechanistic targets involved in SARS-CoV-2 infection and inflammatory-associated pathogenesis, including viral entry, replication and release, and the renin-angiotensin-aldosterone system (RAAS). EXPERIMENTAL PROCEDURE: Data were retrieved from a literature search available on PubMed, Scopus and Google Scholar databases and collected until the end of May 2020. The findings from in vitro cell and non-cell based studies were considered, while the results of in silico studies were excluded. RESULTS AND CONCLUSION: Based on the previous findings in SARS-CoV studies, except in silico molecular docking analysis, herein, we provide a total of 150 natural compounds as potential candidates for development of new anti-COVID-19 drugs with higher efficacy and lower toxicity than the existing therapeutic agents. Several natural compounds have showed their promising actions on multiple therapeutic targets, which should be further explored. Among them, quercetin, one of the most abundant of plant flavonoids, is proposed as a lead candidate with its ability on the virus side to inhibit SARS-CoV spike protein-angiotensin-converting enzyme 2 (ACE2) interaction, viral protease and helicase activities, as well as on the host cell side to inhibit ACE activity and increase intracellular zinc level.

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