Leaf extract of Caesalpinia mimosoides enhances oxidative stress resistance and prolongs lifespan in Caenorhabditis elegans

Background: Caesalpinia mimosoides, a vegetable consumed in Thailand, has been reported to exhibit in vitro antioxidant properties. The in vivo antioxidant and anti-aging activities have not been investigated. The aim of this research was to study the antioxidant activity of C. mimosoides extracts in Caenorhabditis elegans, a widely used model organism in this context. Methods: C. elegans were treated with C. mimosoides extracts in a various concentrations. To investigate the protective effects of the extract against oxidative stress, wild-type N2 were used to determine survival rate under oxidative stress and intracellular ROS. To study underlying mechanisms, the mutant strains with GFP reporter gene including TJ356, CF1553, EU1 and LD4 were used to study DAF-16, SOD-3, SKN-1 and GST-4 gene, respectively. Lifespan and aging pigment of the worms were also investigated. Results: A leaf extract of C. mimosoides improved resistance to oxidative stress and reduced intracellular ROS accumulation in nematodes. The antioxidant effects were mediated through the DAF-16/FOXO pathway and SOD-3 expression, whereas the expression of SKN-1 and GST-4 were not altered. The extract also prolonged lifespan and decreased aging pigments, while the body length and brood size of the worms were not affected by the extract, indicating low toxicity and excluding dietary restriction. Conclusions: The results of this study establish the antioxidant activity of C. mimosoides extract in vivo and suggest its potential as a dietary supplement and alternative medicine to defend against oxidative stress and aging, which should be investigated in intervention studies

A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and long-COVID complications

There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out to date, with seven of those being randomized placebo-controlled studies. This systematic review and meta-analysis covers the literature from the outbreak of SARS-CoV-2 in late 2019 until January 2024. Search terms related to fluvoxamine, such as its trade names and chemical names, along with words related to COVID-19, such as SARS-CoV-2 and coronavirus, were used in literature databases including PubMed, Google Scholar, Scopus, and the ClinicalTrials.gov database from NIH, to identify the trials used in the subsequent analysis. Clinical deterioration and death data were extracted from these studies where available and used in the meta-analysis. A total of 7153 patients were studied across 14 studies (both open-label and double-blind placebo-controlled). 681 out of 3553 (19.17%) in the standard care group and 255 out of 3600 (7.08%) in the fluvoxamine-treated group experienced clinical deterioration. The estimated average log odds ratio was 1.087 (95% CI 0.200 to 1.973), which differed significantly from zero (z = 2.402, p = 0.016). The seven placebo-controlled studies resulted in a log odds ratio of 0.359 (95% CI 0.1111 to 0.5294), which differed significantly from zero (z = 3.103, p = 0.002). The results of this study identified fluvoxamine as effective in preventing clinical deterioration, and subgrouping analysis suggests that earlier treatment with a dose of 200 mg or above provides the best outcomes. We hope the outcomes of this study can help design future studies into respiratory viral infections and potentially improve clinical outcomes

Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells

Serotonin (5-HT) is a monoamine neurotransmitter and plays important roles in several of the human body’s systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT) plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR). It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR), lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L) allele as compared to short (S) allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05) as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5-HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells

Acanthus ebracteatus leaf extract provides neuronal cell protection against oxidative stress injury induced by glutamate

Abstract Background Acanthus ebracteatus (AE), an herb native to Asia, has been recognized in traditional folk medicine not only for its antioxidant properties and various pharmacological activities but also as an ingredient of longevity formulas. However, its anti-neurodegenerative potential is not yet clearly known. This work aimed to evaluate the protective effect of AE leaf extract against glutamate-induced oxidative damage in mouse hippocampal HT22 cells, a neurodegenerative model system due to a reduction in glutathione levels and an increase in reactive oxygen species (ROS). Methods Cell viability, apoptosis, and ROS assays were performed to assess the protective effect of AE leaf extract against glutamate-induced oxidative toxicity in HT22 cells. The antioxidant capacity of AE was evaluated using in vitro radical scavenging assays. The subcellular localization of apoptosis-inducing factor (AIF) and the mRNA and protein levels of genes associated with the nuclear factor erythroid 2–related factor 2 (Nrf2) antioxidant system were determined to elucidate the mechanisms underlying the neuroprotective effect of AE leaf extract. Results We demonstrated that AE leaf extract is capable of attenuating the intracellular ROS generation and HT22 cell death induced by glutamate in a concentration-dependent manner. Co-treatment of glutamate with the extract significantly reduced apoptotic cell death via inhibition of AIF nuclear translocation. The increases in Nrf2 levels in the nucleus and gene expression levels of antioxidant-related downstream genes under Nrf2 control were found to be significant in cells treated with the extract. Conclusions The results suggested that AE leaf extract possesses neuroprotective activity against glutamate-induced oxidative injury and may have therapeutic potential for the treatment of neurodegenerative diseases associated with oxidative stress

Amyloidosis in Alzheimer’s Disease: The Toxicity of Amyloid Beta (Aβ), Mechanisms of Its Accumulation and Implications of Medicinal Plants for Therapy

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to memory deficits and death. While the number of individuals with AD is rising each year due to the longer life expectancy worldwide, current therapy can only somewhat relieve the symptoms of AD. There is no proven medication to cure or prevent the disease, possibly due to a lack of knowledge regarding the molecular mechanisms underlying disease pathogenesis. Most previous studies have accepted the “amyloid hypothesis,” in which the neuropathogenesis of AD is believed to be triggered by the accumulation of the toxic amyloid beta (Aβ) protein in the central nervous system (CNS). Lately, knowledge that may be critical to unraveling the hidden pathogenic pathway of AD has been revealed. This review concentrates on the toxicity of Aβ and the mechanism of accumulation of this toxic protein in the brain of individuals with AD and also summarizes recent advances in the study of these accumulation mechanisms together with the role of herbal medicines that could facilitate the development of more effective therapeutic and preventive strategies

Ethanolic extract of Streblus asper leaves protects against glutamate-induced toxicity in HT22 hippocampal neuronal cells and extends lifespan of Caenorhabditis elegans

Abstract Background Although such local herb as Streblus asper (family Moraceae) has long been recognized for traditional folk medicines and important ingredient of traditional longevity formula, its anti-neurodegeneration or anti-aging activity is little known. This study aimed to investigate the neuroprotective effect of S. asper leaf extracts (SA-EE) against toxicity of glutamate-mediated oxidative stress, a crucial factor contributing to the neuronal loss in age-associated neurodegenerative diseases and the underlying mechanism as well as to evaluate its longevity effect. Methods Using mouse hippocampal HT22 as a model for glutamate oxidative toxicity, we carried out MTT and LDH assays including Annexin V-FITC/propidium iodide staining to determine the SA-EE effect against glutamate-induced cell death. Antioxidant activities of SA-EE were evaluated using the radical scavenging and DCFH-DA assays. To elucidate the underlying mechanisms, SA-EE treated cells were analyzed for the expressions of mRNA and proteins interested by immunofluorescent staining, western blot analysis and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) techniques. The longevity effect of SA-EE was examined on C. elegans by lifespan assay. Results We demonstrate that a concentration-dependent reduction of glutamate-induced cytotoxicity was significant after SA-EE treatment as measured by MTT and LDH assays. Annexin V-FITC/propidium iodide and immunofluorescent staining showed that co-treatment of glutamate with SA-EE significantly reduced apoptotic-inducing factor (AIF)-dependent apoptotic cell death. DCFH-DA assay revealed that this extract was capable of dose dependently attenuating the ROS caused by glutamate. Western blot analysis and qRT-PCR showed that nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels in the nucleus, as well as mRNA levels of antioxidant-related genes under Nrf2 regulation were significantly increased by SA-EE. Furthermore, this extract was capable of extending the lifespan of C. elegans. Conclusions SA-EE possesses both longevity effects and neuroprotective activity against glutamate-induced cell death, supporting its therapeutic potential for the treatment of age-associated neurodegenerative diseases

Age, comorbidities, c-reactive protein and procalcitonin as predictors of severity in confirmed COVID-19 patients in the Philippines

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

Identification of Phytochemicals in Bioactive Extracts of <i>Acacia saligna</i> 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

<i>Hibiscus sabdariffa</i> 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

Exploring the In Vitro Antioxidant, Anti-Aging, and Cytotoxic Properties of <i>Kaempferia galanga</i> Linn. Rhizome Extracts for Cosmeceutical Formulations

Kaempferia galanga Linn. (KG), a member of the family Zingiberaceae, is native to India, and commonly found in China, Indonesia, and Thailand. It has been used as a food condiment, folk medicine, and to relieve skin diseases due to its biological activities. However, its anti-aging effect has not yet been investigated. In this study, the rhizome of Kaempferia galanga Linn was extracted with solvents of different polarities (deionized water, absolute ethanol, ethyl acetate, and hexane). Phytochemical screening assay, total flavonoid and total phenolic contents, antioxidant activity (DPPH•, FRAP, ABTS +• assay), anti-aging activity (anti-collagenase, anti-elastase), and cell cytotoxicity on human dermal fibroblasts were investigated. The outcomes revealed that the extraction in highly polar solvents resulted in a high extract yield. Flavonoids, phenolic, and terpenoid compounds were detected in KG extracts using all extraction solvents. However, deionized water as a solvent exhibited the lowest level of flavonoids and phenolics, as compared to the other solvents. The highest total flavonoid and phenolic contents were achieved through extraction with absolute ethanol and ethyl acetate, respectively. Interestingly, the extract obtained with absolute ethanol exhibited the most potent antioxidant activities (the IC50 value of DPPH• was 0.612 mg/mL, the FRAP value was 62.79 mmol of Fe2+/g of extract, and TEAC value was 9.21 mg TE/g of extract in ABTS+• assay) and anti-aging properties (the percentages of collagenase inhibitory and elastase were 71.83%, and 66.35%, respectively). Regarding cell cytotoxicity, both KG extracts obtained with deionized water and absolute ethanol showed lower toxicity on human dermal fibroblasts compared to those obtained with ethyl acetate and hexane. Ethanol-based KG extract demonstrated a good antioxidant, anti-aging capacity and is considered safe for cosmeceutical products focused on anti-aging applications