Transcriptomic analysis of glutamate-induced HT22 neurotoxicity as a model for screening anti-Alzheimer's drugs.

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.

Stigmasterol isolated from Azadirachta indica flowers attenuated glutamate-induced neurotoxicity via downregulation of the Cdk5/p35/p25 signaling pathway in the HT-22 cells.

BACKGROUND: Glutamate, an excitatory neurotransmitter, was elevated in the brain of neurodegenerative disease (ND) patients. The excessive glutamate induces Ca2+ influx and reactive oxygen species (ROS) production which exacerbates mitochondrial function, leading to mitophagy aberration, and hyperactivates Cdk5/p35/p25 signaling leading to neurotoxicity in ND. Stigmasterol, a phytosterol, has been reported for its neuroprotective effects; however, the underlying mechanism of stigmasterol on restoring glutamate-induced neurotoxicity is not fully investigated. PURPOSE: We investigated the effect of stigmasterol, a compound isolated from Azadirachta indica (AI) flowers, on ameliorating glutamate-induced neuronal apoptosis in the HT-22 cells. STUDY DESIGN: To further understand the underlying molecular mechanisms of stigmasterol, we investigated the effect of stigmasterol on Cdk5 expression, which was aberrantly expressed in glutamate-treated cells. Cell viability, Western blot analysis, and immunofluorescence are employed. RESULTS: Stigmasterol significantly inhibited glutamate-induced neuronal cell death via attenuating ROS production, recovering mitochondrial membrane depolarization, and ameliorating mitophagy aberration by decreasing mitochondria/lysosome fusion and the ratio of LC3-II/LC3-I. In addition, stigmasterol treatment downregulated glutamate-induced Cdk5, p35, and p25 expression via enhancement of Cdk5 degradation and Akt phosphorylation. Although stigmasterol demonstrated neuroprotective effects on inhibiting glutamate-induced neurotoxicity, the efficiency of stigmasterol is limited due to its poor water solubility. We conjugated stigmasterol to soluble soybean polysaccharides with chitosan nanoparticles to overcome the limitations. We found that the encapsulated stigmasterol increased water solubility and enhanced the protective effect on attenuating the Cdk5/p35/p25 signaling pathway compared with free stigmasterol. CONCLUSION: Our findings illustrate the neuroprotective effect and the improved utility of stigmasterol in inhibiting glutamate-induced neurotoxicity.

Identification of Phytochemicals in Bioactive Extracts of Acacia saligna Growing in Australia.

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.

Health benefits of astaxanthin against age-related diseases of multiple organs: A comprehensive review.

Age-related diseases are associated with increased morbidity in the past few decades and the cost associated with the treatment of these age-related diseases exerts a substantial impact on social and health care expenditure. Anti-aging strategies aim to mitigate, delay and reverse aging-associated diseases, thereby improving quality of life and reducing the burden of age-related pathologies. The natural dietary antioxidant supplementation offers substantial pharmacological and therapeutic effects against various disease conditions. Astaxanthin is one such natural carotenoid with superior antioxidant activity than other carotenoids, as well as well as vitamins C and E, and additionally, it is known to exhibit a plethora of pharmacological effects. The present review summarizes the protective molecular mechanisms of actions of astaxanthin on age-related diseases of multiple organs such as Neurodegenerative diseases [Alzheimer's disease (AD), Parkinson's disease (PD), Stroke, Multiple Sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Status Epilepticus (SE)], Bone Related Diseases [Osteoarthritis (OA) and Osteoporosis], Cancers [Colon cancer, Prostate cancer, Breast cancer, and Lung Cancer], Cardiovascular disorders [Hypertension, Atherosclerosis and Myocardial infarction (MI)], Diabetes associated complications [Diabetic nephropathy (DN), Diabetic neuropathy, and Diabetic retinopathy (DR)], Eye disorders [Age related macular degeneration (AMD), Dry eye disease (DED), Cataract and Uveitis], Gastric Disorders [Gastritis, Colitis, and Functional dyspepsia], Kidney Disorders [Nephrolithiasis, Renal fibrosis, Renal Ischemia reperfusion (RIR), Acute kidney injury (AKI), and hyperuricemia], Liver Diseases [Nonalcoholic fatty liver disease (NAFLD), Alcoholic Liver Disease (AFLD), Liver fibrosis, and Hepatic Ischemia-Reperfusion (IR) Injury], Pulmonary Disorders [Pulmonary Fibrosis, Acute Lung injury (ALI), and Chronic obstructive pulmonary disease (COPD)], Muscle disorders (skeletal muscle atrophy), Skin diseases [Atopic dermatitis (ATD), Skin Photoaging, and Wound healing]. We have also briefly discussed astaxanthin's protective effects on reproductive health.

Oolonghomobisflavans exert neuroprotective activities in cultured neuronal cells and anti-aging effects in Caenorhabditis elegans.

Potential health benefits of tea has attracted significant scientific and public attention worldwide. Tea polyphenols are considered as natural promising complementary therapeutical agents for neurodegenerative diseases. However, the anti-neurodegeneration or anti-aging activities of oolong tea polyphenols have not been investigated. The current study aims to document beneficial effects of oolong tea polyphenols [dimers of epigallocatechin gallate (EGCG), oolonghomobisflavan A (OFA), and oolonghomobisflavan B (OFB)] with neuroprotective and neuritogenesis properties in cultured neuronal (Neuro-2a and HT22) cells and Caenorhabditis elegans models. In vitro, we found that the compounds (EGCG, OFA, and OFB) protect against glutamate-induced neurotoxicity via scavenging radical activity, suppression intracellular ROS and up-regulation of antioxidant enzymes. Moreover, the compounds induce neurite outgrowth via up-regulate Ten-4 gene expression. Interestingly, OFA and OFB exert stronger neuroprotective and neurite outgrowth properties than EGCG known as an excellent antioxidant agent in tea. In vivo, we found that the compounds protect against C. elegans Aß-induced paralysis, chemotaxis deficiency and α-synuclein aggregation. Moreover, the compounds are capable of extending the lifespan of C. elegans. OFA and OFB possess both anti-neurodegeneration and anti-aging activities, supporting its therapeutic potential for the treatment of age-related neurodegenerative diseases which need to be studied in more detail in intervention studies.

Aquilaria crassna Leaf Extract Ameliorates Glucose-Induced Neurotoxicity In Vitro and Improves Lifespan in Caenorhabditis elegans.

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.

Hibiscus sabdariffa Extract Protects HaCaT Cells against Phenanthrene-Induced Toxicity through the Regulation of Constitutive Androstane Receptor/Pregnane X Receptor Pathway.

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.

Cleistocalyx nervosum var. paniala Berry Promotes Antioxidant Response and Suppresses Glutamate-Induced Cell Death via SIRT1/Nrf2 Survival Pathway in Hippocampal HT22 Neuronal Cells.

Excessive glutamate neurotransmitters result in oxidative neurotoxicity, similar to neurodegeneration. An indigenous berry of Thailand, Cleistocalyx nervosum var. paniala (CNP), has been recognized for its robust antioxidants. We investigated the effects and mechanisms of CNP fruit extracts on antioxidant-related survival pathways against glutamate-induced neurotoxicity. The extract showed strong antioxidant capability and had high total phenolic and flavonoid contents, particularly resveratrol. Next, the protective effects of the CNP extract or resveratrol on the glutamate-induced neurotoxicity were examined in HT22 hippocampal cells. Our investigation showed that the pretreatment of cells with the CNP extract or resveratrol attenuated glutamate-induced neuronal death via suppression of apoptosis cascade by inhibiting the levels of cleaved- and pro-caspase-3 proteins. The CNP extract and resveratrol suppressed the intracellular ROS by increasing the mRNA expression level of antioxidant enzymes (SODs, GPx1, and CAT). We found that this extract and resveratrol significantly increased SIRT1 expression as a survival-related protein. Moreover, they also promoted the activity of the Nrf2 protein translocation into the nucleus and could bind to the promoter containing the antioxidant response element, inducing the expression of the downstream GPx1-antioxidant protein. Our data illustrate that the CNP extract and resveratrol inhibit apoptotic neuronal death via glutamate-induced oxidative neurotoxicity in HT22 cells through the activation of the SIRT1/Nrf2 survival mechanism.

Polyherbal formulation exerts wound healing, anti-inflammatory, angiogenic and antimicrobial properties: Potential role in the treatment of diabetic foot ulcers.

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.

HydroZitLa inhibits calcium oxalate stone formation in nephrolithic rats and promotes longevity in nematode Caenorhabditis elegans.

Low fluid intake, low urinary citrate excretion, and high oxidative stress are main causative factors of calcium oxalate (CaOx) nephrolithiasis. HydroZitLa contains citrate and natural antioxidants and is developed to correct these three factors simultaneously. Antioxidants theoretically can prolong the lifespan of organisms. In this study, we preclinically investigated the antilithogenic, lifespan-extending and anti-aging effects of HydroZitLa in HK-2 cells, male Wistar rats, and Caenorhabditis elegans. HydroZitLa significantly inhibited CaOx crystal aggregation in vitro and reduced oxidative stress in HK-2 cells challenged with lithogenic factors. For experimental nephrolithiasis, rats were divided into four groups: ethylene glycol (EG), EG + HydroZitLa, EG + Uralyt-U, and untreated control. CaOx deposits in kidneys of EG + HydroZitLa and EG + Uralyt-U rats were significantly lower than those of EG rats. Intrarenal expression of 4-hydroxynonenal in EG + HydroZitLa rats was significantly lower than that of EG rats. The urinary oxalate levels of EG + HydroZitLa and EG + Uralyt-U rats were significantly lower than those of EG rats. The urinary citrate levels of EG + HydroZitLa and EG + Uralyt-U rats were restored to the level in normal control rats. In C. elegans, HydroZitLa supplementation significantly extended the median lifespan of nematodes up to 34% without altering feeding ability. Lipofuscin accumulation in HydroZitLa-supplemented nematodes was significantly lower than that of non-supplemented control. Additionally, HydroZitLa inhibited telomere shortening, p16 upregulation, and premature senescence in HK-2 cells exposed to lithogenic stressors. Conclusions, HydroZitLa inhibited oxidative stress and CaOx formation both in vitro and in vivo. HydroZitLa extended the lifespan and delayed the onset of aging in C. elegans and human kidney cells. This preclinical evidence suggests that HydroZitLa is beneficial for inhibiting CaOx stone formation, promoting longevity, and slowing down aging.

Tea Plant (Camellia sinensis): A Current Update on Use in Diabetes, Obesity, and Cardiovascular Disease.

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.

Antioxidant and Anti-Skin Aging Potential of Selected Thai Plants: In Vitro Evaluation and In Silico Target Prediction.

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.

Caesalpinia mimosoides Leaf Extract Promotes Neurite Outgrowth and Inhibits BACE1 Activity in Mutant APP-Overexpressing Neuronal Neuro2a Cells.

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.

Momordica charantia L. Extract Protects Hippocampal Neuronal Cells against PAHs-Induced Neurotoxicity: Possible Active Constituents Include Stigmasterol and Vitamin E.

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.

Role of Herbal Teas in Regulating Cellular Homeostasis and Autophagy and Their Implications in Regulating Overall Health.

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.

Anti-COVID-19 drug candidates: A review on potential biological activities of natural products in the management of new coronavirus infection.

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.

Mushroom-derived bioactive compounds potentially serve as the inhibitors of SARS-CoV-2 main protease: An in silico approach.

BACKGROUND AND AIM: Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become the world pandemic. There is a race to develop suitable drugs and vaccines for the disease. The anti-HIV protease drugs are currently repurposed for the potential treatment of COVID-19. The drugs were primarily screened against the SARS-CoV-2 main protease. With an urgent need for safe and effective drugs to treat the virus, we have explored natural products isolated from edible and medicinal mushrooms that have been reported to possess anti-HIV protease. EXPERIMENTAL PROCEDURES: We have examined 36 compounds for their potential to be SARS-CoV-2 main protease inhibitors using molecular docking study. Moreover, drug-likeness properties including absorption, distribution, metabolism, excretion and toxicity were evaluated by in silico ADMET analysis. RESULTS: Our AutoDock study showed that 25 of 36 candidate compounds have the potential to inhibit the main viral protease based on their binding affinity against the enzyme's active site when compared to the standard drugs. Interestingly, ADMET analysis and toxicity prediction revealed that 6 out of 25 compounds are the best drug-like property candidates, including colossolactone VIII, colossolactone E, colossolactone G, ergosterol, heliantriol F and velutin. CONCLUSION: Our study highlights the potential of existing mushroom-derived natural compounds for further investigation and possibly can be used to fight against SARS-CoV-2 infection. TAXONOMY CLASSIFICATION BY EVISE: Disease, Infectious Disease, Respiratory System Disease, Covid-19, Traditional Medicine, Traditional Herbal Medicine, Phamaceutical Analysis.

The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data.

Bacopa monnieri (Linn.) Wettst. has been used in traditional medicine as a drug to enhance and improve memory. In this regard, this study aims to provide B. monnieri's efficacy as a neuroprotective drug and as a nootropic against various neurological diseases. Literatures were collected, following Prisma guidelines, from databases, including Scopus, PubMed, Google Scholar, and Science Direct and were scrutinized using a quality scoring system. Means, standard deviations and 'n' numbers were extracted from the metrics and analyzed. Jamovi computer software for Mac was used to carry out the meta-analysis. The selected studies suggested that the plant extracts were able to show some improvements in healthy subjects which were determined in Auditory Verbal Learning Task, digit span-reverse test, inspection time task and working memory, even though it was not significant, as no two studies found statistically significant changes in the same two tests. B. monnieri was able to express modest improvements in subjects with memory loss, wherein only a few of the neuropsychological tests showed statistical significance. B. monnieri in a cocktail with other plant extracts were able to significantly reduce the effects of Alzheimer's disease, and depression which cannot be solely credited as the effect of B. monnieri. Although in one study B. monnieri was able to potentiate the beneficial effects of citalopram; on the whole, currently, there are only limited studies to establish the memory-enhancing and neuroprotective effects of B. monnieri. More studies have to be done in the future by comparing the effect with standard drugs, in order to establish these effects clinically in the plant and corroborate the preclinical data.

Neuroprotective Effects of Extracts from Tiger Milk Mushroom Lignosus rhinocerus Against Glutamate-Induced Toxicity in HT22 Hippocampal Neuronal Cells and Neurodegenerative Diseases in Caenorhabditis elegans.

Despite the Tiger Milk Mushroom Lignosus rhinocerus (LR) having been used as a traditional medicine, little is known about the neuroprotective effects of LR extracts. This study aims to investigate the neuroprotective effect of three extracts of LR against glutamate-induced oxidative stress in mouse hippocampal (HT22) cells as well as to determine their effect in Caenorhabditis elegans. In vitro, we assessed the toxicity of three LR extracts (ethanol extract (LRE), cold-water extract (LRC) and hot-water extract (LRH)) and their protective activity by MTT assay, Annexin V-FITC/propidium iodide staining, Mitochondrial Membrane Potential (MMP) and intracellular ROS accumulation. Furthermore, we determined the expression of antioxidant genes (catalase (CAT), superoxide dismutase (SOD1 and SOD2) and glutathione peroxidase (GPx)) by qRT-PCR. In vivo, we investigated the neuroprotective effect of LRE, not only against an Aß-induced deficit in chemotaxis behavior (Alzheimer model) but also against PolyQ40 formation (model for Morbus Huntington) in transgenic C. elegans. Only LRE significantly reduced both apoptosis and intracellular ROS levels and significantly increased the expression of antioxidant genes after glutamate-induced oxidative stress in HT22 cells. In addition, LRE significantly improved the Chemotaxis Index (CI) in C. elegans and significantly decreased PolyQ40 aggregation. Altogether, the LRE exhibited neuroprotective properties both in vitro and in vivo.

Rhinacanthus nasutus "Tea" Infusions and the Medicinal Benefits of the Constituent Phytochemicals.

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) (Rn) is an herbaceous shrub native to Thailand and much of South and Southeast Asia. It has several synonyms and local or common names. The root of Rn is used in Thai traditional medicine to treat snake bites, and the roots and/or leaves can be made into a balm and applied to the skin for the treatment of skin infections such as ringworm, or they may be brewed to form an infusion for the treatment of inflammatory disorders. Rn leaves are available to the public for purchase in the form of "tea bags" as a natural herbal remedy for a long list of disorders, including diabetes, skin diseases (antifungal, ringworm, eczema, scurf, herpes), gastritis, raised blood pressure, improved blood circulation, early-stage tuberculosis antitumor activity, and as an antipyretic. There have been many studies investigating the roles of Rn or compounds isolated from the herb regarding diseases such as Alzheimer's and other neurodegenerative diseases, cancer, diabetes and infection with bacteria, fungi or viruses. There have, however, been no clinical trials to confirm the efficacy of Rn in the treatment of any of these disorders, and the safety of these teas over long periods of consumption has never been tested. This review assesses the recent research into the role of Rn and its constituent compounds in a range of diseases.