Exploring Medicinal Plants and Phytochemicals for Telomere Maintenance and Anti-aging: Insights into Telomerase Activation and Longevity

Revista Brasileira de Farmacognosia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Language: Английский

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An open-label, single dose, safety and pharmacokinetic study of Withania somnifera root extract in healthy volunteers

Drug Metabolism and Personalized Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Objectives Withania somnifera (WS), also known as Ashwagandha, is a health-beneficial Ayurvedic medicinal plant with great potential an adaptogen rejuvenating and anti-aging effects. However, studies investigating pharmacokinetics (PK), safety, tolerability of WS on humans are limited. The present study evaluated PK, root extract (2.5 % total withanolides) capsules upon oral administration two 200 mg each (total 400 mg) in healthy male female volunteers. Methods An open label, single dose, clinical design comprising volunteers was employed. PK parameters the four bioactive constituents viz. withanoside IV, withaferin A, 12-deoxy-withastramonolide, withanolide A after analysis plasma using validated UHPLC-MS/MS method. Further, safety assessment for vital signs, testing organ function, urine examination, X-ray, ECG, well adverse events profile were investigated. Results After 2 (200 each), participants reported normal physical, hematological, biochemical no abnormalities metrics. For bioactives, exposure range between 0.472 4.468 ng/mL (C max ), 1.000–1.416 h (T 2.051–13.319 ng/mL*h (AUC 0-t). t 1/2 (1.696–4.377 h), lambda_z (0.141–0.282 L/h), Cl/F (0.065–0.954 mg/(ng/ml)/h), AUMC 0-inf_obs (21.720–80.485 ng/mL*hˆ2) MRT (3.680–7.516 h) differed bioactive. Conclusions elucidated showed that may safely consume at dose (2 without any harmful

Language: Английский

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Effects of a natural ingredients-based intervention targeting the hallmarks of aging on epigenetic clocks, physical function, and body composition: a single-arm clinical trial

Aging, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Aging interventions have progressed in recent years due to the growing curiosity about how lifestyle impacts longevity. This study assessed effects of SRW Laboratories' Cel System nutraceutical range on epigenetic methylation patterns, inflammation, physical performance, body composition, and biomarkers aging. A 1-year was conducted with 51 individuals, collecting data at baseline, 3 months, 6 12 months. Participants were encouraged walk 10 minutes practice 5 mindfulness daily. Significant improvements muscle strength, function, composition metrics observed. Epigenetic clock analysis showed a decrease biological age significant reductions stem cell division rates. Immune subset indicated changes, increases eosinophils CD8T cells decreases B memory, CD4T T-regulatory cells. Predicted biomarker proxies (EBPs) changes retinol/TTHY, regulator growth, proliferation, differentiation, deoxycholic acid glucuronide levels, metabolite generated liver. Gene ontology revealed CpG genes involved critical processes related aging, such as oxidative stress-induced premature senescence, pyrimidine deoxyribonucleotide metabolic process, TRAIL binding, hyaluronan biosynthetic neurotransmitter loading into synaptic vesicles, pore complex assembly, collagen protein phosphatase 2A binding activity, activation transcription factor binding. Our findings suggest that supplement may effectively reduce improve health metrics, warranting further investigation its mechanistic pathways long-term efficacy.

Language: Английский

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Systems pharmacology of phytochemical anacardic acid in the chemoprevention of hepatocellular carcinoma

Drug Metabolism and Personalized Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract Objectives Hepatocellular carcinoma (HCC) is a common type of liver cancer that progresses quickly and has limited treatment options. Nutraceutical anacardic acid (AA), bioactive compound derived from cashew nut shell, emerged as potential candidate for HCC owing to its reported anti-inflammatory, anticancer diverse pharmacological properties. In the present study, we investigate AA an inhibitor using molecular docking, gene ontology, network pharmacology. Methods The pharmacokinetic physicochemical properties were assessed Swiss ADME. SuperPred, Similarity Ensemble Approach, ChEMBL Target Prediction online tools used determining targets AA. addition, GeneCards, NCBI, DisGeNET UniProt ID search top 25 hub genes determined Cytohubba plugin. A protein interaction (PPI) was constructed through STRING database. Gene Ontology (GO) biological process Kyoto Encyclopaedia Genes (KEGG) pathway enrichment analysis performed FunRich ShinyGO 0.77. Moreover, docking studies on NF-κB GSK-3β. expression levels also validated by western blotting. Results Comprehensive data identified 375 11,333 HCC, with 264 in common. Network key targets, including caspase-3, NF-κB. ontology topology highlighted essential pathways implicated progression such renin-angiotensin system, VEGF signalling, apoptosis. Molecular revealed strong binding affinity proteins Upregulation p-NRF2 p-GSK-3β, downregulation p-NF-κB caspase-1 Conclusions Taken together, our study highlights promising chemopreventive agent because significant modulatory effects important regulatory linked cell division, inflammation, apoptosis, antioxidant response.

Language: Английский

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The Impact of a Natural Ingredients based Intervention Targeting the Nine Hallmarks of Aging on DNA methylation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Aging interventions have progressed in recent years due to the growing curiosity about how lifestyle impacts longevity. This study assessed effects of SRW Laboratories Cel1, Cel2, and Cel3 (Cel System) nutraceutical range on epigenetic methylation patterns, inflammation, physical performance, body composition, biomarkers aging. A 1-year was conducted with 51 individuals, collecting data at baseline, 3 months, 6 12 months. Participants were encouraged walk 10 minutes practice 5 mindfulness daily. Significant improvements muscle strength, function, composition metrics observed. Epigenetic clock analysis showed a decrease biological age significant reductions stem cell division rates. Immune subset indicated changes, increases eosinophils CD8T cells decreases B memory, CD4T T-regulatory cells. Predicted biomarker proxies (EBPs) changes retinol/TTHY, regulator growth, proliferation, differentiation, deoxycholic acid glucuronide levels, metabolite generated liver. Gene ontology revealed CpG genes involved critical processes related aging, such as oxidative stress-induced premature senescence, pyrimidine deoxyribonucleotide metabolic process, TRAIL binding, hyaluronan biosynthetic neurotransmitter loading into synaptic vesicles, pore complex assembly, collagen protein phosphatase 2A binding activity, activation transcription factor binding. Our findings suggest that Cel System supplement may effectively reduce improve health metrics, warranting further investigation its mechanistic pathways long-term efficacy.

Language: Английский

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Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats

Drug Metabolism and Personalized Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Abstract Objectives Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The properties of WS are ascribed to existence secondary metabolites which in great demand herbal nutraceutical industry. Despite well-known therapeutic effects WS, it necessary assess preclinical toxicity on rats and further explore its potential application treatment various disorders humans. existing study assessed oral acute sub-chronic toxicities root extract Sprague Dawley (SD) (male female) for 14 90 days, respectively under OECD-423 -408 guidelines as well GLP compliance. Methods In toxicity, either sex were orally fed dose 2,000 mg/kg. animals administered repeated doses at 250, 500, 1,000 mg/kg days with an additional 14-day recovery period. Two more groups (n=5 each) receiving vehicle also observed. Results the results revealed LD 50 SD was higher than administration showed no significant toxicological changes rats. Haematological serum chemistry markers found within normal range. Terminal necropsy gross or histopathological outcomes. Conclusions no-observed-adverse-effect level (NOAEL) body weight, safe use this

Language: Английский

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Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats

Drug Metabolism and Personalized Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract Objectives Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The properties of WS are ascribed to existence secondary metabolites which in great demand herbal nutraceutical industry. Despite well-known therapeutic effects WS, it necessary assess preclinical toxicity on rats and further explore its potential application treatment various disorders humans. existing study assessed oral acute sub-chronic toxicities root extract Sprague Dawley (SD) (male female) for 14 90 days, respectively under OECD-423 -408 guidelines as well GLP compliance. Methods In toxicity, either sex were orally fed dose 2,000 mg/kg. animals administered repeated doses at 250, 500, 1,000 mg/kg days with an additional 14-day recovery period. Two more groups (n=5 each) receiving vehicle also observed. Results the results revealed LD 50 SD was higher than administration showed no significant toxicological changes rats. Haematological serum chemistry markers found within normal range. Terminal necropsy gross or histopathological outcomes. Conclusions no-observed-adverse-effect level (NOAEL) body weight, safe use this

Language: Английский

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Molecular Insights into the Inhibition of Lipid Accumulation in Hepatocytes by Unique Extracts of Ashwagandha

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12256 - 12256

Published: Nov. 14, 2024

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

Language: Английский

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