The reorientation of Callisia fragrans (Lindl.) Woodson, from therapeutic to ornamental use, exemplifies a broader domestication trend, favoring aesthetics over medicinal properties. Renewed phytomedicinal interest and the rise of plant extract markets drive demand for organic, sustainable consumer products, heightening the competition for superior cultivars. Synthetic polyploidization using oryzalin was conducted to obtain high-quality cultivars of C. fragrans, facilitating enhanced phenotypic and biological traits without genetic modification. This study aimed to explore the metabolic spectrum and biological activities of oryzalin-induced polyploid C. fragrans for its advanced medicinal application. Flow cytometric analysis confirmed the ploidy level of the plants. Consequently, GC-FID and 1H NMR analyses revealed distinct metabolite profiles, with increased ethyl stearate, malic acid, gallic acid, fumaric acid, and unique compounds like (Z)-11-eicosenoic acid and dodecan-1-ol in polyploids. Polyploid extracts demonstrated exceptional antioxidant capacity, with DPPH, ORAC, and ABTS assays showing higher radical scavenging and oxygen absorbance abilities than diploid extracts. The polyploid extract showed enhanced antimicrobial activity against skin pathogens, including Methicillin-resistant Staphylococcus aureus (MRSA). Callisia extracts, meticulously at a low concentration of 25 µg/mL, showed cytoprotective effects on HT-29 cells, mitigating H₂O₂-induced oxidative stress. Furthermore, treatment with polyploid extract was associated with the downregulation of the expression of pro-inflammatory enzymes COX-1 and COX-2, suggesting a potentially greater anti-inflammatory effect compared to the diploid extract. These findings depict enhanced metabolite accumulation and biological activities in polyploid compared than diploid progenitor, highlighting the potential of the novel polyploid C. fragrans variety for future therapeutic applications, particularly in pharmaceutical and cosmetic industries.

• Keywords
• Anti-inflammatory activity, Antioxidant activity, GC-FID, NMR, Polyploidization, Skin infection,
• MeSH
• Antioxidants pharmacology   metabolism   MeSH
• Cyclooxygenase 1 metabolism   MeSH
• Cyclooxygenase 2 metabolism   genetics   MeSH
• Genotype MeSH
• Humans MeSH
• Polyploidy * MeSH
• Plant Extracts * pharmacology   chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants MeSH
• Cyclooxygenase 1 MeSH
• Cyclooxygenase 2 MeSH
• Plant Extracts * MeSH

Neurodegenerative disorders (NDs) are typically characterized by progressive loss of neuronal function and the deposition of misfolded proteins in the brain and peripheral organs. They are molecularly classified based on the specific proteins involved, underscoring the critical role of protein-processing systems in their pathogenesis. Alpha-synuclein (α-syn) is a neural protein that is crucial in initiating and progressing various NDs by directly or indirectly regulating other ND-associated proteins. Therefore, reducing the α-syn aggregation can be an excellent option for combating ND initiation and progression. This study presents an in silico phytochemical-based approach for discovering novel neuroprotective agents from bioactive compounds of the Lamiaceae family, highlighting the potential of computational methods such as functional networking, pathway enrichment analysis, molecular docking, and simulation in therapeutic discovery. Functional network and enrichment pathway analysis established the direct or indirect involvement of α-syn in various NDs. Furthermore, molecular docking interaction and simulation studies were conducted to screen 85 major bioactive compounds of the Lamiaceae family against the α-syn aggregation. The results showed that five compounds (α-copaene, γ-eudesmol, carnosol, cedryl acetate, and spathulenol) had a high binding affinity towards α-syn with potential inhibitory activity towards its aggregation. MD simulations validated the stability of the molecular interactions determined by molecular docking. In addition, in silico pharmacokinetic analysis underscores their potential as promising drug candidates, demonstrating excellent blood-brain barrier (BBB) permeability, bioactivity, and reduced toxicity. In summary, this study identifies the most suitable compounds for targeting the α-syn aggregation and recommends these compounds as potential therapeutic agents against various NDs, pending further in vitro and in vivo validation.

• Keywords
• MD simulation, functional network analysis, molecular docking, neuroprotective agent, pathway enrichment analysis, phytochemical,
• Publication type
• Journal Article MeSH