Search Results (88)

Alzheimer’s disease (AD) is considered one of the main pathologies of our time, whose incidence and prevalence are suggested to be strongly underestimated. AD presents as a complex neurodegenerative condition characterized by marked neuroinflammation and a significant decline in the cognitive and mnemonic functions of affected patients. Recognized AD pathological hallmarks include amyloid beta plaque and neurofibrillary tangle formation, synaptic dysfunction with considerable apoptosis of cholinergic and dopaminergic neurons, and high levels of oxidative stress and neuroinflammation. The available pharmacological treatments are represented by acetylcholinesterase inhibitors to treat the mild to moderate form of the disease and N-methyl-D-aspartate inhibitors alone or in combination with the previously cited ones in the late stage of the neurodegenerative condition. Furthermore, emerging drug therapies such as monoclonal antibodies are promising agents in AD management. Although scientific evidence highlights these chemicals as effective in slowing down disease progression, significant limitations behind their employment derive from the notable dose-dependent side effects and the single-target mechanism of action. In this context, two well-studied phytotherapeutics, W. somnifera (W. somnifera) and fungi belonging to the genus Cordyceps, have gained attention for their chemical composition regarding their neuroprotective and anti-inflammatory effects. Ashwagandha (obtained principally from the roots of W. somnifera) is an adaptogen that relieves stress and anxiety. It contains several ergostane-type steroidal lactones—such as withanolides and withaferin A—and various alkaloids, contributing to its antioxidant and neuroprotective effects. Likewise, cordycepin is the main bioactive principle found in Cordyceps fungi. This natural nucleoside has been reported to possess therapeutic potential as an anti-cancer, immunomodulatory, and anti-inflammatory agent, with some studies suggesting a beneficial role in AD treatment. The purpose of the present review is to investigate the pharmacological properties of W. somnifera and Cordyceps species in the context of AD treatment and explore the therapeutic potential of the constitutive bioactive molecules in preclinical models mimicking this neurodegenerative condition. Full article

Withanolides are a class of naturally occurring C-28 ergostane steroidal lactones with an abundance of biological activities, and their members are promising candidates for antineoplastic drug development. The ADMET properties of withanolides are still largely unknown, and in silico predictions can play a crucial role highlighting these characteristics for drug development, shortening time and resources spent on the development of a drug lead. In this work, ADMET properties of promising antitumoral withanolides were assessed. Each chemical structure was submitted to the prediction tools: SwissADME, pkCSM–pharmacokinetics, admetSAR v2.0, and Molinspiration Cheminformatics. The results indicate a good gastrointestinal absorption rate, inability to cross the blood–brain barrier, CYP3A4 metabolization, without inhibition of other P450 cytochromes, high interaction with nuclear receptors, and a low toxicity. It was also predicted for the inhibition of pharmacokinetics transporters and some ecotoxicity. This demonstrates a viability for oral drug development, with low probabilities of side effects. Full article

The highly conserved Wnt signaling pathway, a complex network critical for embryonic development and adult tissue homeostasis, regulates diverse cellular processes, ultimately influencing tissue organization and organogenesis; its dysregulation is implicated in numerous diseases, and it is known to be affected by oxidative pathways. This report reviews the recent literature on major classes of natural products with pronounced anti-oxidant properties, such as cardiac glycosides, steroid saponins, ecdysteroids, withanolides, cucurbitacins, triterpenes, flavonoids, and iridoids, that modulate its activity in various pathological conditions, summarizing and critically analyzing their effects on the Wnt pathway in various therapeutically relevant experimental models and highlighting the role of ROS-mediated crosstalk with Wnt signaling in these studies. Models reviewed include not only cancer but also stroke, ischemia, bone or kidney diseases, and regenerative medicine, such as re-epithelialization, cardiac maintenance, and hair loss. It highlights the paramount importance of modulating this signaling by natural products to define future research directions. We also discuss controversies identified in the mode of action of several compounds in different models and directions on how to further improve the quality and depth of such studies. Full article

Ashwagandha (Withania somnifera) is a well-known adaptogenic herb traditionally used to enhance sleep quality and mitigate stress-induced cognitive decline. This study investigated the effects of different doses of ashwagandha root extract (AE) formulations on cognitive function, oxidative stress, and neuronal plasticity in a rat model of sleep deprivation (SD). Forty-nine rats were randomly assigned to seven groups: control, wide platform (WP), SD, SD + A1 (15 mg/kg AE 1.5%), SD + A2 (30 mg/kg AE 1.5%), SD + A3 (5.5 mg/kg AE 8.0%), and SD + A4 (11 mg/kg AE 8.0%). The extract was administered orally for four weeks. SD induced via a modified wide platform model significantly impaired spatial memory, increased oxidative stress, and suppressed GABA receptor activity. Treatment with all AE doses, except 15 mg/kg AE 1.5%, considerably reduced serum corticosterone (12% for SD + A2, 15% for SD + A3, and 32% for SD + A4), CRH (11% for SD + A2, 14% for SD + A3, and 17% for SD + A4), ACTH (22% for SD + A2, 26% for SD + A3, and 38% for SD + A4), and MDA levels (31% for SD + A2, 34% for SD + A3, and 46% for SD + A4) (p < 0.05). All doses improved antioxidant enzyme activity and memory performance, while AE 8.0% doses notably increased serotonin (19% for SD + A3 and 33% for SD + A4) and dopamine levels (40% for SD + A3 and 50% for SD + A4). Moreover, AE treatment enhanced markers of neuronal plasticity and partially improved GABAergic function. These findings suggest that AE formulations, particularly at higher concentrations, exert neuroprotective effects against SD-induced cognitive impairment by modulating oxidative stress, neurotransmitter balance, and neuroplasticity, indicating their potential application in managing stress-related neurological disorders. Full article

Physalis peruviana is a native evergreen plant from the Andean region. It is also commonly known as goldenberry and gooseberry in English-speaking countries. P. peruviana fruit is a globose berry, yellowish in color, which has a pleasant smell and taste. In addition, fruits of this plant have been identified as a priority part for commercialization (also for their food products: wine, jam, and juice). The health benefits of P. peruviana are related to the content of various bioactive chemical compounds, including withanolides, phenolic compounds (especially flavonoids), alkaloids, sucrose ester, and others such as vitamins, especially carotenoids, and physalins. The aim of the present mini-review is to provide an overview of the beneficial potential of P. peruviana fruits and their food products, especially fruit juice, as important components of functional foods. Full article

In the Mediterranean and Himalayan regions, the genus Mandragora (family Solanaceae), sometimes called mandrake, is widely utilized in herbal therapy and is well-known for its mythical associations. Objective: To compile up-to-date information on M. autumnalis’s therapeutic properties. Its pharmacological properties and phytochemical composition are particularly covered in managing several illnesses, including diabetes, cancer, and heart disease. Methods: Articles on the review topic were found by searching major scientific literature databases, such as PubMed, Scopus, ScienceDirect, SciFinder, Chemical Abstracts, and Medicinal and Aromatic Plants Abstracts. Additionally, general online searches were conducted using Google Scholar and Google. The time frame for the search included items released from 1986 to 2023. Results:Mandragora has been shown to contain a variety of phytochemicals, including coumarins, withanolides, and alkaloids. The pharmacological characteristics of M. autumnalis, such as increasing macrophage anti-inflammatory activity, free radicals inhibition, bacterial and fungal growth inhibition, cytotoxic anticancer activities in vivo and in vitro against cancer cell lines, and enzyme-inhibitory properties, are attributed to these phytochemicals. Furthermore, M. autumnalis also inhibits cholinesterase, tyrosinase, α-amylase, α-glucosidase, and free radicals. On the other hand, metabolic risk factors, including the inhibition of diabetes-causing enzymes and obesity, have been treated using dried ripe berries. Conclusions: Investigations into the pharmacological and phytochemical characteristics of M. autumnalis have revealed that this plant is a rich reservoir of new bioactive substances. This review aims to provide insight into the botanical and ecological characteristics of Mandragora autumnalis, including a summary of its phytochemical components and antioxidant, antimicrobial, antidiabetic, anticancer, enzyme-inhibitory properties, as well as toxicological implications, where its low cytotoxic activity against the normal VERO cell line has been shown. More research on this plant is necessary to ensure its efficacy and safety. Still, it is also necessary to understand the molecular mechanism of action behind the observed effects to clarify its therapeutic potential. Full article

Physalis angulata is a plant of great value in traditional medicine known for its content of bioactive compounds, such as physalins and withanolides, which possess diverse biological activities. In this study, the chemical profile, antioxidant activity, and enzyme inhibition capacity of aqueous and ethanolic extracts obtained from the root, stem, leaves, calyx, and fruits of P. angulata collected in Peru were evaluated. A total of forty-two compounds were detected in the extracts using UHPLC-ESI-QTOF-MS analysis. In vitro analyses revealed that leaf extracts contained the highest concentration of phenolic compounds, while leaf and fruit extracts showed the best results in FRAP, DPPH, and ABTS antioxidant tests; on the other hand, inhibition of AChE, BChE, α-glucosidase, and α-amylase enzymes was variable, but calyx and fruit extracts showed higher effectiveness. In silico analyses indicated that the compounds physagulin A, physagulin F, physagulide P, physalin B, and withaminimin showed stable interactions and favorable binding affinities with the catalytic sites of the enzymes studied. These results confirm the pharmacological potential of extracts and compounds derived from different organs of P. angulata, suggesting their promising use in treating diseases related to the central nervous system and metabolic syndrome. Full article

Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit its application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, and anticancer activities. This study investigates the preventative benefits of a standardized WIT extract against DOX-induced renal damage in vivo. We also investigate the synergistic effects of combining WIT and DOX to improve therapeutic efficacy in breast cancer cells (MCF7-ADR). Methods: This study employed an animal model where rats were administered 300 mg/kg/day of WIT orally for a duration of 14 days. Rats received DOX injections at a dose of 5 mg/kg, for a total of 15 mg, on the 6th, 8th, and 10th days. Results: Present results revealed that WIT reduced DOX-induced increase levels of blood urea and creatinine and the activity of kidney injury molecule-1. WIT also reduced renal tissue damage, oxidative stress, and levels of pro-inflammatory markers. WIT alleviated the effects of DOX on nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and sirtuin 1 in the renal tissues. WIT modulated nuclear factor-κB activity and decreased apoptotic indicators. Furthermore, WIT improves DOX’s capacity to kill drug-resistant MCF7-ADR cells by arresting the cell cycle and promoting apoptosis. Chemical analysis of WIT root extract revealed 34 distinct compounds, including alkaloids, withanolides, flavanones, and fatty acids. Conclusions: These constituents synergistically contribute to WIT’s antioxidant, anti-inflammatory, and anti-apoptotic properties. In addition, they confirm its ability to reduce systemic toxicity while improving treatment efficacy. Full article

This study provides a comprehensive characterization of Physalis peruviana L., covering the nutritional composition of the fruit and the phytochemical profiles and in vitro bioactive properties of berry and calyx extracts. The fresh fruit stood out as a source of dietary fiber (5.16 g/100 g) and is low in fat (0.49 g/100 g). A 100-g serving also contained notable amounts of ascorbic acid (32.0 mg), tocopherols (2.34 mg), potassium (253 mg), phosphorus (45 mg), and magnesium (20 mg). HPLC-DAD-ESI/MS analysis tentatively identified five physalin derivatives and one withanolide in the fruit extract, which showed significant antiproliferative activity against human colorectal adenocarcinoma (Caco-2) and non-small-cell lung carcinoma (NCI-H460) cells. The calyx extracts contained three phenolic acids and four flavonoids, demonstrating high antioxidant activity through physiologically relevant cell-based assays, the ability to inhibit advanced glycation end products (AGEs) formation and nitric oxide production, and also antiproliferative properties. These findings highlight goldenberry as a nutrient-dense fruit rich in vitamins and functional compounds with potential health benefits, supporting its recognition as a “superfruit”. Furthermore, the fruit calyx emerged as a valuable source of bioactive secondary metabolites with potential applications in food and pharmaceutical industries and related sectors. Full article

The rise in antibiotic-resistant Staphylococcal infections necessitates innovative approaches to identify new therapeutic agents. This study investigates the application of machine learning models to identify potential phytochemical inhibitors against BacA, a target related to Staphylococcal infections. Active compounds were retrieved from BindingDB while the decoy was generated from DUDE. The RDKit was utilized for feature engineering. Machine learning models such as k-nearest neighbors (KNN), the support vector machine (SVM), random forest (RF), and naive Bayes (NB) were trained on an initial dataset consisting of 226 active chemicals and 2550 inert compounds. Accompanied by an MCC of 0.93 and an accuracy of 96%, the RF performed better. Utilizing the RF model, a library of 9000 phytochemicals was screened, identifying 300 potentially active compounds, of which 192 exhibited drug-like properties and were further analyzed through molecular docking studies. Molecular docking results identified Ergotamine, Withanolide E, and DOPPA as top inhibitors of the BacA protein, accompanied by interaction affinities of −8.8, −8.1, and −7.9 kcal/mol, respectively. Molecular dynamics (MD) was applied for 100 ns to these top hits to evaluate their stability and dynamic behavior. RMSD, RMSF, SASA, and Rg analyses showed that all complexes remained stable throughout the simulation period. Binding energy calculations using MMGBSA analysis revealed that the BacA_Withanolide E complex exhibited the most favorable binding energy profile with significant van der Waals interactions and a substantial reduction in gas-phase energy. It also revealed that van der Waals interactions contributed significantly to the binding stability of Withanolide E, while electrostatic interactions played a secondary role. The integration of machine learning models with molecular docking and MD simulations proved effective in identifying promising phytochemical inhibitors, with Withanolide E emerging as a potent candidate. These findings provide a pathway for developing new antibacterial agents against Staphylococcal infections, pending further experimental validation and optimization. Full article

Objectives: This study investigates the effectiveness of an herbal formulation, STRESSLESS (ST-65), which combines ashwagandha (Withania somnifera) and bacopa (Bacopa monnieri), on SH-SY5Y human neuroblastoma cells. Given the rising interest in natural compounds for neuroprotection and stress alleviation, we aimed to explore the cellular and molecular effects of this formulation. Methods: Utilizing a nuclear magnetic resonance (NMR) metabolomic approach and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS), we identified key bioactive compounds in ST-65, including withanolides from ashwagandha and bacosides from bacopa. Results: Our findings indicate that ST-65 treatment significantly alters the metabolic profile of SH-SY5Y cells. Key changes included increased levels of metabolites linked to neuroprotection, energy metabolism, and antioxidant defense. Notable enhancements were observed in specific amino acids and neuroprotective compounds, suggesting activation of neuroprotective mechanisms and mitigation of stress-induced damage. Conclusions: The study reveals a complex phyto-chemical profile of ST-65 and underscores its potential as a natural active agent for addressing stress-related neurodegenerative conditions. These insights into neuronal mechanisms provide a foundation for further exploration of herbal formulations in neuroprotection. Full article

We investigated the effect of purified withanolides and extracts derived from Ashwagandha on steatosis, the abnormal accumulation of fat that can lead to non-alcoholic fatty liver disease (NAFLD). Collaborator of ARF (CARF, also known as CDKN2AIP, a protein that regulates hepatic lipid metabolism, fat buildup, and liver damage) was used as an indicator. Six withanolides (Withaferin A, Withanone, Withanolide B, Withanoside IV, Withanoside V, and Withanostraminolide-12 deoxy) reversed the decrease in CARF caused by exposure to free fatty acids (FFAs) in liver-derived cells (HepG2 hepatocytes). After analyzing the effects of these withanolides on CARF mRNA and protein levels, FFA accumulation, protein aggregation, and oxidative and DNA damage stresses, we selected Withaferin A and Withanone for molecular analyses. Using the palmitic-acid-induced fatty acid accumulation stress model in Huh7 cells, we found a significant reduction in the activity of the key regulators of lipogenesis pathways, including sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and peroxisome proliferator-activated receptors (PPARγ and PPARα). This in vitro study suggests that low, non-toxic doses of Withaferin A, Withanone, or Ashwagandha extracts containing these withanolides possess anti-steatosis and antioxidative-stress properties. Further in vivo and clinical studies are required to investigate the therapeutic potential of these Ashwagandha-derived bioactive ingredients for NAFLD. Full article

Withania somnifera (common name: ashwagandha; WS) is an Ayurvedic botanical that has become popular for its reputed effects on stress and insomnia. Research into the bioactive compounds responsible for the biological effects of WS has largely focused on withanolides, a group of steroidal lactones commonly found in the Solanaceae family. Until recently, however, it was unclear which, if any, withanolides were present in the plasma after the ingestion of WS products. The aim of this review is to summarize current knowledge regarding the plasma pharmacokinetics of withanolides found in WS and the analytical methods developed to detect them in plasma. Twenty studies (sixteen animal, four human) were identified in which isolated withanolides or withanolide-containing products were administered to animals or humans and quantified in plasma. Withanolides were commonly analyzed using reversed-phase liquid chromatography coupled to mass spectrometry. Plasma concentrations of withanolides varied significantly depending on the substance administered, withanolide dose, and route of administration. Plasma pharmacokinetics of withaferin A, withanolide A, withanolide B, withanoside IV, 12-deoxywithastramonolide, and withanone have been reported in rodents (C_max range: 5.6–8410 ng/mL), while withaferin A, withanolide A, 12-deoxywithastramonolide, and withanoside IV pharmacokinetic parameters have been described in humans (C_max range: 0.1–49.5 ng/mL). Full article

Athenaea fasciculata belongs to the Solanaceae family and is a promising source of cytotoxic withanolides known as aurelianolides A and B. In the last years, the pharmacological studies of these aurelianolides on different leukemia cell lines have stimulated new studies on their potential as alternative candidates for new lead anticancer drugs. However, the obtention of these two pure compounds by traditional preparative is a costly and long time-consuming process, which is performed in several steps. This study aimed to propose a straightforward approach for isolating aurelianolides A and B using high-speed countercurrent chromatography (HSCCC). In this study, among 10 different solvent systems, the system composed of n-hexane/ethyl acetate/methanol/water 3:6:2:1 (v/v/v/v) was chosen for optimization. This HEMWat system was optimized to 4:8:2:4 (v/v/v/v) and chosen for HSCCC separation in a tail-to-head elution mode. After the HSCCC scale-up procedure, a withanolides mixture (200.0 mg) was separated within 160 min in a single-step purification process. In total, 78.9 mg of aurelianolide A (up to 95.0% purity) and 54.3 mg of aurelianolide B (up to 88.5% purity) was obtained by this fast sequential liquid–liquid partition process. The isolated withanolides were identified by ¹H and ¹³C NMR spectroscopy (this method has proven to be faster and more efficient than classical procedures (CC and Prep-TLC)). Full article

Physalis floridana Rydb., a member of the Solanaceae family, is renowned for its diverse secondary metabolites, including physalins and withanolides. The 28-spotted ladybird beetle (Henosepilachna vigintioctopunctata) is a notorious pest severely damaging Solanaceous crops. This study demonstrates that P. floridana Rydb. significantly impacts on the development and reproductive suppression of H. vigintioctopunctata. A comparative transcriptome analysis was performed by feeding H. vigintioctopunctata larvae on P. floridana Rydb., Solanum nigrum L., Solanum tuberosum L., and Solanum lycopersicum L. The results reveal that larvae fed on P. floridana Rydb. exhibit numerous differentially expressed genes, which are notably enriched in pathways related to energy metabolism, immunity, and detoxification. These functions and pathways are less enriched in larvae fed by other hosts. Weighted Gene Co-expression Network Analysis (WGCNA) indicates that feeding on P. floridana Rydb. influences the expression of specific genes involved in the Toll and IMD signaling pathways, impacting the immune system of H. vigintioctopunctata larvae. This study provides transcriptomic insights into larval responses to different diets and suggests that the effect of P. floridana Rydb. on the immune system of H. vigintioctopunctata is a key defense mechanism against herbivores. Full article