Systems Pharmacology and Pharmaco-Transcriptomic Insights into Bauhinia variegata for Polycystic Ovary Syndrome...

Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine disorder affecting 8-13% of reproductive-aged women, often accompanied by comorbidities such as insulin resistance, cardiovascular disease, and infertility. Current pharmacological therapies primarily manage symptoms and usually cause adverse effects, highlighting the need for safer, multi-target treatments.

This study employs a multi-omics systems-level approach, combining differentially expressed genes (DEGs) and exosomal microRNAs (miRNAs) of PCOS to explore the therapeutic potential of Bauhinia variegata towards PCOS and its comorbidities. A comprehensive phytochemical dataset of Bauhinia variegata (BVPCs) (n=111) was compiled from publicly available databases and subjected to target prediction, ADMET screening, chemical clustering, drug-similarity analysis, molecular interaction, and multilayered network analysis.

Transcriptomic profiling identified 571 DEGs and exosomal miRNAs, revealing 92 key BVPCs, including hesperidin, apigenin, naringenin, and podophyllotoxin derivatives, as regulatory bridges linking miRNA dysregulation and gene expression. Toxicity and drug-similarity analysis confirmed that most BVPCs have low predicted toxicity and possess structural similarities to 50 FDA-approved drugs. Protein-protein interaction, network pathway enrichment, and molecular docking revealed strong interactions of BVPCs, viz., hesperidin, Bauhiniastansin, and bauhinols, with the neprilysin enzyme, a key PCOS-related comorbid protein. Their therapeutic effects may be attributed to their ability to modulate inflammation, insulin resistance, neuroendocrine imbalance, and oxidative stress.

The binding affinities of BVPCs (range -5.4 to -9.6kcal/mol) with PCOS and its comorbid protein targets, indicating a potential role in PCOS metabolic regulation, like Diabetes and Cancer. Moreover, Bauhinia- specific phytochemicals have shown potential as bioactive scaffolds for PCOS targets, which may raise their nutraceutical hope, as they are present in flowers and buds consumed in traditional diets.

The results identify BVPCs as promising multi-target agents for PCOS and its associated comorbidities, offering new insights into Bauhinia's therapeutic journey.