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.

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.

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.

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.

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.

Bacopa monnieri (L.) wettst. Extract protects against glutamate toxicity and increases the longevity of Caenorhabditis elegans.

BACKGROUND: Neurodegenerative diseases, such as Alzheimer's disease, cause a great deal of suffering for both patients and carers. Bacopa monnieri (L.) wettst. Is known for its memory-enhancing properties, and is of great interest in treating neurodegenerative disease. AIMS: This study aimed to evaluate B.monnieri against glutamate toxicity, and identify whether B.monnieri reduces mitochondrial and ER stress, as well as to measure B.monnieri's effect on the life span and aging of Caenorhabditis elegans. We hypothesized that B.monnieri would prevent cellular oxidative stress, prevent mitochondrial/ER stress, and increase the life span while reducing signs of aging in C.elegans. EXPERIMENTAL PROCEDURES: Glutamate toxicity was measured using viable cell staining assays and the MTT assay. ROS and mitochondrial stress were assessed by H2DCFDA and Rodamine123 staining, with fluorescence/confocal microscopy. C.elegans' median and maximum life span were measured, in response to B.monnieri treatment, along with lipofuscin imaging to measure the health of the C.elegans population. RESULTS: B.monnieri hexane extract (but not ethanol extract) prevented the toxicity of 5 mM glutamate in HT-22 cells. We found that the mechanism involves the reduction of ROS production and the prevention of mitochondrial and ER stress. Furthermore, we showed that B.monnieri could increase the median and maximal lifespan of wild type C.elegans, maintain a younger appearing phenotype in the aged C.elegans. CONCLUSIONS: In conclusion, B.monnieri prevents mitochondrial, and oxidative stress in the cultured cells. Furthermore, it can prolong the healthy lifespan of C.elegans, indicating that B.monnieri the potential for therapeutic and preventative use in neurodegenerative disease.

Neuroprotective Properties of Green Tea (Camellia sinensis) in Parkinson's Disease: A Review.

Neurodegenerative disease is a collective term given for the clinical condition, which results in progressive degeneration of neurons and the loss of functions associated with the affected brain region. Apart from the increase in age, neurodegenerative diseases are also partly affected by diet and lifestyle practices. Parkinson's disease (PD) is a slow onset neurodegenerative disorder and the second most common neurodegenerative disease, which affects the motor system. Although there is no prescribed treatment method to prevent and cure PD, clinical procedures help manage the disease symptoms. Green tea polyphenols are known for several health benefits, including antioxidant, anti-inflammatory, and neuroprotective activity. The current manuscript summarizes the possible mechanisms of neuroprotective potential of green tea with a special focus on PD. Studies have suggested that the consumption of green tea protects against free-radicals, inflammation, and neuro-damages. Several in vivo studies aid in understanding the overall mechanism of green tea. However, the same dose may not be sufficient in humans to elicit similar effects due to complex physiological, social, and cultural development. Future research focused on more clinical trials could identify an optimum dose that could impart maximum health benefits to impart neuroprotection in PD.

Paper-Based Analytical Device for Real-Time Monitoring of Egg Hatching in the Model Nematode Caenorhabditis elegans.

Caenorhabditis elegans is an in vivo model known for its easy handling and maintenance and lack of associated ethical issues. The release of chitinase can be used to monitor the egg-laying stage in C. elegans. The aim of this study was to develop a simple and cost-effective device to monitor the activity of chitinase in embryos of C. elegans. Colloid chitin azure (CCA), a substrate for chitinase, was preimmobilized on the detection area of paper, forming a purple region, to generate a CCA paper-based analytical device (CCA-PAD). The degradation of CCA by chitinase could be observed as the purple color became faint and the filter paper eventually became colorless. Under the optimum conditions, the proposed device quantified the chitinase enzyme in the range of 15.625-125 mU/mL within 48 h (R2 = 0.993). In this work, 10 young adult-staged wild-type C. elegans (Bristol N2) worms were analyzed on the CCA-PAD, which was supplemented with the laboratory food source E. coli OP50 on a gauze layer. The same strain treated with 5-fluoro-2'-deoxyuridine was used to prevent egg production in C. elegans. A significant difference in the color intensity was observed between these two groups at the end of the experiment (P = <0.001, independent t-test, n = 3). We successfully developed a simple and effective method for monitoring chitinase activity. The device may have potential applications in drug-screening studies as it efficiently distinguishes drugs that can impact egg laying.

Analyzing the Synergistic Effects of Antioxidants in Combating Photoaging Using Model Nematode, Caenorhabditis elegans.

Aging, a universal and unique process, occurs both intrinsically (chronological) and extrinsically (photoaging). Ultraviolet-A (UV-A)-mediated stress is a growing health hazard to mankind as it is the major cause of photoaging, which could lead to much damage of skin cells and tissues ranging from tan, burn, or even cancer. The present study focuses on the role of antioxidants and other natural compounds which have been widely used in oral/topical applications to combat and delay the effects of photoaging using model nematode Caenorhabditis elegans. Compounds like green tea extract, naringenin, and naringin, which are known for their antioxidant properties, were able to extend life span and healthspan of the nematode in normal as well as under UV-A-mediated stress conditions. Regulation of both the stress-responsive genes (skn-1 and sir-2.1) and the aging-regulating genes (daf-2 and age-1) was attributable for these conditions. Interestingly, it was observed that these compounds when combined in equal ratios by weight worked synergistically to combat the aging process. Pronounced synergistic effects were observed during UV-A-mediated stress conditions, suggesting that these could be used as potential antiphotoaging compounds which will be of greater significance for health-based research.

Antiaging, Stress Resistance, and Neuroprotective Efficacies of Cleistocalyx nervosum var. paniala Fruit Extracts Using Caenorhabditis elegans Model.

Plant parts and their bioactive compounds are widely used by mankind for their health benefits. Cleistocalyx nervosum var. paniala is one berry fruit, native to Thailand, known to exhibit various health benefits in vitro. The present study was focused on analyzing the antiaging, stress resistance, and neuroprotective effects of C. nervosum in model system Caenorhabditis elegans using physiological assays, fluorescent imaging, and qPCR analysis. The results suggest that the fruit extract was able to significantly extend the median and maximum lifespan of the nematode. It could also extend the healthspan by reducing the accumulation of the "age pigment" lipofuscin, inside the nematode along with regulating the expression of col-19, egl-8, egl-30, dgk-1, and goa-1 genes. Further, the extracts upregulated the expression of daf-16 while downregulating the expression of daf-2 and age-1 in wild-type nematodes. Interestingly, it could extend the lifespan in DAF-16 mutants suggesting that the extension of lifespan and healthspan was dependent and independent of DAF-16-mediated pathway. The fruit extract was also observed to reduce the level of Reactive Oxygen Species (ROS) inside the nematode during oxidative stress. The qPCR analysis suggests the involvement of skn-1 and sir-2.1 in initiating stress resistance by activating the antioxidant mechanism. Additionally, the fruit could also elicit neuroprotection as it could extend the median and maximum lifespan of transgenic strain integrated with Aß. SKN-1 could play a pivotal role in establishing the antiaging, stress resistance, and neuroprotective effect of C. nervosum. Overall, C. nervosum can be used as a nutraceutical in the food industry which could offer potential health benefits.

Protective effect of neglected plant Diplocyclos palmatus on quorum sensing mediated infection of Serratia marcescens and UV-A induced photoaging in model Caenorhabditis elegans.

Plants are considered to be a leading source for possible human therapeutic agents. This holistic study has investigated the anti-quorum sensing (anti-QS), anti-infection, antioxidant and anti-photoaging properties of neglected plant Diplocyclos palmatus. The results showed that D. palmatus methanolic leaf extract (DPME) effectively inhibited the quorum sensing (QS) regulated virulence factor production as well as biofilm formation in Serratia marcescens. The transcriptomic analysis revealed that DPME significantly downed the expression of QS-regulated genes such as fimA, fimC, flhC, bsmB, pigP and shlA in S. marcescens, which supports the outcome of in vitro bioassays. Further, the docking study revealed that the presence of active compounds, namely tocopherols and phytol, DPME exhibited its anti-QS activity against S. marcescens. In addition, DPME treatment extended the lifespan of S. marcescens infected C. elegans by the action of dropping the internal accumulation. Further, qPCR analysis clearly revealed that DPME treatment significantly up-regulated the expression of the lifespan-related gene (daf-16) and immune-related genes (clec-60, clec-87, lys-7 and bec-1) in S. marcescens infected C.elegans. On the other hand, DPME extensively reduced the UV-A induced ROS stress, thereby, extended the lifespan in UV-A photoaged C. elegans. Further, the qPCR analysis also confirmed the up-regulation of daf-16, clec-60, clec-87 and col-19 genes which advocated the improvement of the lifespan, healthspan and collagen production in UV-A photoaged C. elegans. Further bioassays evidenced that that the lifespan extension of photoaged C. elegans was accomplished by the actions of antioxidants such as tocopherols and phytol in DPME.

A Review of the Role of Green Tea (Camellia sinensis) in Antiphotoaging, Stress Resistance, Neuroprotection, and Autophagy.

Tea is one of the most widely consumed beverages worldwide, and is available in various forms. Green tea is richer in antioxidants compared to other forms of tea. Tea is composed of polyphenols, caffeine, minerals, and trace amounts of vitamins, amino acids, and carbohydrates. The composition of the tea varies depending on the fermentation process employed to produce it. The phytochemicals present in green tea are known to stimulate the central nervous system and maintain overall health in humans. Skin aging is a complex process mediated by intrinsic factors such as senescence, along with extrinsic damage induced by external factors such as chronic exposure to ultraviolet (UV) irradiation-A process known as photoaging-Which can lead to erythema, edema, sunburn, hyperplasia, premature aging, and the development of non-melanoma and melanoma skin cancers. UV can cause skin damage either directly, through absorption of energy by biomolecules, or indirectly, by increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Green tea phytochemicals are a potent source of exogenous antioxidant candidates that could nullify excess endogenous ROS and RNS inside the body, and thereby diminish the impact of photoaging. Several in vivo and in vitro studies suggest that green tea supplementation increases the collagen and elastin fiber content, and suppresses collagen degrading enzyme MMP-3 production in the skin, conferring an anti-wrinkle effect. The precise mechanism behind the anti-photoaging effect of green tea has not been explored yet. Studies using the worm model have suggested that green tea mediated lifespan extension depends on the DAF-16 pathway. Apart from this, green tea has been reported to have stress resistance and neuroprotective properties. Its ROS scavenging activity makes it a potent stress mediator, as it can also regulate the stress induced by metal ions. It is known that tea polyphenols can induce the expression of different antioxidant enzymes and hinder the DNA oxidative damage. Growing evidence suggests that green tea can also be used as a potential agent to mediate neurodegenerative diseases, including Alzheimer's disease. EGCG, an abundant catechin in tea, was found to suppress the neurotoxicity induced by Aß as it activates glycogen synthase kinase-3ß (GSK-3ß), along with inhibiting c-Abl/FE65-the cytoplasmic nonreceptor tyrosine kinase which is involved in the development of the nervous system and in nuclear translocation. Additionally, green tea polyphenols induce autophagy, thereby revitalizing the overall health of the organism consuming it. Green tea was able to activate autophagy in HL-60 xenographs by increasing the activity of PI3 kinase and BECLIN-1. This manuscript describes the reported anti-photoaging, stress resistance, and neuroprotective and autophagy properties of one of the most widely known functional foods-green tea.

A Mini Review on Antidiabetic Properties of Fermented Foods.

In general, fermented foods (FFs) are considered as functional foods. Since the awareness about the health benefits of FFs has increased, the consumption of FF also improved significantly in recent decades. Diabetes is one of the leading threats of the health span of an individual. The present manuscript details the general methods of the production of FFs, and the results of various studies (in vitro, in vivo, and clinical studies) on the antidiabetic properties of FFs. The fermentation method and the active microbes involved in the process play a crucial role in the functional properties of FFs. Several in vitro and in vivo studies have been reported on the health-promoting properties of FFs, such as anti-inflammation, anticancer, antioxidant properties, improved cognitive function and gastrointestinal health, and the reduced presence of metabolic disorders. The studies on the functional properties of FFs by randomized controlled clinical trials using human volunteers are very limited for several reasons, including ethical reasons, safety concerns, approval from the government, etc. Several scientific teams are working on the development of complementary and alternative medicines to improve the treatment strategies for hyperglycemia.

Grewia tiliaefolia and its active compound vitexin regulate the expression of glutamate transporters and protect Neuro-2a cells from glutamate toxicity.

AIM: Glutamate is a major neurotransmitter involved in several brain functions and glutamate excitotoxicity is involved in Alzheimer's disease (AD). In the current study, the neuroprotective effect of the Indian medicinal plant Grewia tiliaefolia (GT) and its active component vitexin was evaluated in Neuro-2a cells against glutamate toxicity. MATERIALS AND METHODS: Neuro-2a cells were exposed to glutamate to cause excitotoxicity and the neuroprotective effect of GT and vitexin were evaluated using biochemical studies (estimation of reactive oxygen species, reactive nitrogen species, protein carbonyl content, lipid peroxidation level, mitochondrial membrane potential and caspase-3 activity), molecular docking studies, gene expression and western blot analysis. KEY FINDINGS: Glutamate exposure to Neuro-2a cells induced oxidative stress, loss of membrane potential, suppressed the expression of antioxidant response genes (Nrf-2, HO-1, NQO-1), glutamate transporters (GLAST-1, GLT-1) and induced the expression of NMDAR, Calpain. However, pre-treatment of cells with GT/vitexin inhibited oxidative stress mediated damage by augmenting the expression of Nrf-2/HO-1 pathway, inducing the expression of glutamate transporters and downregulating Calpain, NMDAR. Molecular docking showed that vitexin effectively binds to NMDAR and GSK-3ß and thereby can inhibit their activation. GT/vitexin also inhibited glutamate induced Bax expression. SIGNIFICANCE: Methanol extract of G. tiliaefolia and its active component vitexin can act in an antioxidant dependent mechanism as well as by regulating glutamate transporters in mitigating the toxicity exerted by glutamate in Neuro-2a cells. Our results conclude that GT/vitexin can act as potential drug leads for the therapeutic intervention of AD.