Plant Polyphenols for Aging Health: Implication from Their Autophagy Modulating Properties in Age-Associated Diseases.

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.

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.

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.

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.

Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by depolarizing the mitochondrial membrane potential.

In the present study, the antiproliferative activity of phytol and its mechanism of action against human lung adenocarcinoma cell line A549 were studied in detail. Results showed that phytol exhibited potent antiproliferative activity against A549 cells in a dose and time-dependent manner with an IC50 value of 70.81 ±â€¯0.32 µM and 60.7 ±â€¯0.47 µM at 24 and 48 h, respectively. Phytol showed no adverse toxic effect in normal human lung cells (L-132), but mild toxic effect was observed when treated with maximum dose (67 and 84 µM). No membrane-damaging effect was evidenced by PI staining and SEM analysis. The results of mitochondrial membrane potential analysis, cell cycle analysis, FT-IR and Western blotting analysis clearly demonstrated the molecular mechanism of phytol as induction of apoptosis in A549 cells, as evidenced by formation of shrinked cell morphology with membrane blebbing, depolarization of mitochondrial membrane potential, increased cell population in the sub-G0 phase, band variation in the DNA and lipid region, downregulation of Bcl-2, upregulation of Bax and the activation of caspase-9 and -3. In addition, phytol inhibited the CAM vascular growth as evidenced by CAM assay, which positively suggests that phytol has anti-angiogenic potential. Taken together, these findings clearly demonstrate the mode of action by which phytol induces cell death in A549 lung adenocarcinoma cells.

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.

Vitexin inhibits Aß25-35 induced toxicity in Neuro-2a cells by augmenting Nrf-2/HO-1 dependent antioxidant pathway and regulating lipid homeostasis by the activation of LXR-α.

Amyloid beta (Aß) formation is one of the neuropathological hallmarks of Alzheimer's disease (AD), which induces the generation of reactive oxygen species (ROS), further leading to the alteration of several signalling pathways. In the present study, vitexin has been evaluated for its neuroprotective activity against Aß25-35 induced toxicity in Neuro-2a cells. Results of cell free studies indicated that vitexin significantly inhibited the aggregation of Aß25-35. Studies in Neuro-2a cells revealed that Aß25-35 significantly affected the cell viability by inducing ROS mediated toxicity and apoptosis. However, pre-treatment of Neuro-2a cells with vitexin (50 µM) significantly restored the cell viability up to 92.86 ±â€¯5.57%. Vitexin has been found to inhibit the production of free radicals and suppress ROS mediated lipid peroxidation, protein oxidation and loss of membrane potential. Also, vitexin modulated the expression of genes involved in antioxidant response mechanisms (Nrf-2, HO-1), cholesterol metabolism (LXR-α, APOE, ABCA-1, Seladin-1), and endoplasmic reticulum stress (Grp78, Gadd153) to offer neuroprotection. Aß25-35 induced caspase-3 activation, and Bax protein expression was also found to be significantly inhibited by vitexin. Taken together, our results indicate that vitexin offers neuroprotection to cells in part via augmenting the antioxidant mechanisms, maintaining lipid homeostasis and inhibiting apoptosis induced by Aß.

Kaempferol and inflammation: From chemistry to medicine.

Inflammation is an important process of human healing response, wherein the tissues respond to injuries induced by many agents including pathogens. It is characterized by pain, redness and heat in the injured tissues. Chronic inflammation seems to be associated with different types of diseases such as arthritis, allergies, atherosclerosis, and even cancer. In recent years natural product based drugs are considered as the novel therapeutic strategy for prevention and treatment of inflammatory diseases. Among the different types of phyto-constituents present in natural products, flavonoids which occur in many vegetable foods and herbal medicines are considered as the most active constituent, which has the potency to ameliorate inflammation under both in vitro and in vivo conditions. Kaempferol is a natural flavonol present in different plant species, which has been described to possess potent anti-inflammatory properties. Despite the voluminous literature on the anti-inflammatory effects of kaempferol, only very limited review articles has been published on this topic. Hence the present review is aimed to provide a critical overview on the anti-inflammatory effects and the mechanisms of action of kaempferol, based on the current scientific literature. In addition, emphasis is also given on the chemistry, natural sources, bioavailability and toxicity of kaempferol.