Phytochemicals And Herbs: Neem Leaf Extract Exhibits Anti-Aging Properties

Phytochemicals And Herbs: Neem, scientifically known as Azadirachta indica, is a medicinal plant renowned for its extensive use in traditional medicine across India and Africa. Belonging to the mahogany family, neem has been utilized for centuries to treat various acute and chronic diseases. Its applications range from skincare to serious ailments such as cancer and diabetes. Recent scientific investigations have begun to unravel the potential of neem leaf extract (NLE) in promoting longevity and combating the effects of aging. This Phytochemicals And Herbs report delves into the comprehensive study conducted by researchers from Sichuan University and Chengdu University, which unveils the anti-aging properties of neem leaf extract and explores the underlying mechanisms at play.


Neem Leaf Extract Exhibits Anti-Aging Properties
 
Neem Leaf Extract: A Promising Candidate for Longevity
Neem leaves have been traditionally acclaimed for their role in promoting longevity. However, the precise scientific mechanisms behind these benefits remained largely unexplored until now. The study in question employed a model organism, Saccharomyces cerevisiae (budding yeast), to investigate the anti-aging effects of neem leaf extract (NLE). Extracted using a 50% ethanol solution, NLE demonstrated a significant extension of the chronological lifespan of yeast cells. This remarkable finding was accompanied by heightened oxidative stress resistance and a reduction in reactive oxygen species (ROS) levels.
 
Identifying Active Compounds
To pinpoint the active compounds responsible for these effects, researchers utilized liquid chromatography-mass spectrometry (LC/MS) and the Global Natural Products Social Molecular Networking (GNPS) platform. The analysis revealed that the majority of active compounds in NLE were flavonoids, a class of polyphenolic compounds known for their antioxidant properties. The predominant flavonoids identified included quercetin, kaempferol, and L-epicatechin.
 
Constructing Pharmacological Networks
Understanding the multifaceted nature of aging, the study employed network pharmacology approaches to map out the interactions between the identified compounds and their potential targets. Using the STITCH and Swiss Target Prediction (STP) platforms, compound-target networks were constructed for both yeast and human cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these targets highlighted “oxidoreductase activity” as a key enriched term in both yeast and human cells. This suggested a regulatory role for NLE in oxidative stress response (OSR).
 
Mechanisms of Action: Insights from Yeast Models
The initial experiments demonstrated that NLE significantly extended the lifespan of the yeast strain BY4742. Further investigations revealed that the benefits were also observed in another commonly used laboratory strain, BY4741, albeit to a lesser extent. This indicated that while there might be strain-specific differences in response to NLE, the extract generally promotes longevity across different yeast strains.
 
Enhancing Oxidative Stress Response
The extension of lifespan in yeast cells was closely linked to an improved oxidative stress response. When yeast cells were pre-incubated with NLE and subsequently exposed to hydrogen peroxide (H2O2), a significant increase in survival was observed. This suggested that NLE enhances the cells’ ability to withstand oxidative stress, a key factor in aging.
 
Active Compounds and Target Prediction
The detailed LC/MS analysis identified 80 compounds in NLE, with flavonoids being the predominant constituents. The STITCH platform predicted 378 potential gene targets for 28 of these compounds in yeast. Enrichment analyses of these targets reinforced the importance of “oxidoreductase activity” and “longevity-regulating pathways,” supporting the observed effects of NLE.
 
Transcriptome Changes
To further elucidate the mechanisms, RNA sequencing (RNA-seq) was conducted on NLE-treated yeast cells. The analysis identified 1092 differentially expressed genes (DEGs), with significant upregulation in genes related to oxidative stress response. Notably, the gene CTT1, encoding catalase, was the most significantly upregulated gene within the “oxidoreductase activity” cluster. This finding was pivotal as CTT1 plays a crucial role in counteracting oxidative stress.
Implications for Human Cells
 
Antioxidative Effects
The study extended its investigations to human cells, specifically HeLa cells, to determine if the benefits of NLE observed in yeast were conserved in humans. Pretreatment with NLE resulted in a notable decrease in ROS levels and senescence-associated β-galactosidase activity under oxidative stress conditions. This indicated that NLE not only enhances oxidative stress resistance but also mitigates cellular senescence, pointing to its potential anti-aging properties in human cells.
 
Network Pharmacology in Human Cells
In human cells, the STITCH and STP platforms predicted 621 potential gene targets for 53 compounds found in NLE. Similar to yeast, enrichment analyses highlighted “oxidoreductase activity” and pathways related to reactive oxygen species. These findings suggest that the antioxidative mechanisms of NLE are likely conserved across different organisms.
 
Discussion: The Path to Pharmacological Interventions
The findings from this study underscore the potential of neem leaf extract as a pharmacological intervention to extend lifespan and enhance oxidative stress resistance. The straightforward preparation method of NLE, involving crushing, soaking, and ultrasound treatment, makes it a practical candidate for further development. The identification of active compounds and their targets through network pharmacology provides a comprehensive understanding of the extract's multifaceted effects.
 
Challenges and Future Directions
While the study offers valuable insights, it also highlights the complexity of aging as a biological process. The network pharmacology approach, although informative, has limitations in fully capturing the intricate interactions at play. Further experimental validation, particularly in animal models, is necessary to confirm the findings and explore the clinical potential of NLE.
 
CTT1 and Beyond
The identification of CTT1 as a key gene in mediating the effects of NLE is a significant milestone. However, the precise regulatory mechanisms leading to its upregulation remain to be fully understood. Future studies should focus on exploring the role of other regulatory factors and pathways involved in NLE's action.
 
Conclusion: Neem Leaf Extract as a Fountain of Youth
In conclusion, this comprehensive study sheds light on the anti-aging and antioxidative properties of neem leaf extract. By extending the lifespan of yeast cells and enhancing oxidative stress resistance, NLE demonstrates its potential as a natural remedy for aging. The conservation of these effects in human cells further bolsters the promise of neem as a therapeutic agent. As research progresses, neem leaf extract could emerge as a valuable component in the arsenal against aging, offering a natural and accessible means to promote longevity and well-being.
 
The study findings were published in the peer reviewed journal: Nutrients.
https://www.mdpi.com/2072-6643/16/10/1506
 
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