Harnessing Boerhavia
diffusa’s Phytocompounds to combat Cisplatin - induced Renal Damage: Insights from
Systems Pharmacology Analysis
Soora Sudarsanan Priyadharshini, Jaya Kumar Arun Kumar, Hari Rajeswary and Rajendran
Kowsalya
Res. J. Biotech.; Vol. 21(1); 177-189;
doi: https://doi.org/10.25303/211rjbt1770189; (2026)
Abstract
Cisplatin-induced nephrotoxicity (DIN) restricts the clinical utility of this frontline
chemotherapeutic, creating an urgent need for nephroprotective agents. Boerhavia
diffusa (Punarnava) is a reputed drug for renal benefits in traditional medicine,
but its molecular potential in drug induced nephrotoxicity DIN is yet to be elucidated.
Chloroform and ethanol extracts of Boerhavia diffusa leaves underwent GC-MS profiling,
revealing 40 phyto compounds (26 chloroform, 14 ethanol). Drug-likeness and specificity
were evaluated using Swiss ADME, narrowing the list to 20 compounds. Network pharmacology
mapped these phytoconstituents to 80 genes implicated in cisplatin nephrotoxicity,
identifying six key hub proteins: AKT1, AMPK, BCL2, CASP3, NLRP3 and OCT, enriched
in apoptotic, pyroptotic and drug transport pathways (FDR < 1 × 10⁻³⁶). Auto Dock
Vina-based molecular docking screened all actives against these targets and top
interactions were structurally characterized.
Five leads (DHP, HMPFP, BTDMP, Methylenebis, Flavone) displayed high binding affinities
(≤ –10.5 kcal/mol) to multiple targets. DHP and HMPFP exhibited robust hydrogen
bonding and π-stacking within AKT1 and NLRP3 pockets, blocking key sites (e.g. Gln179,
Trp80, Arg298) and impeding ATP access. BTDMP further bridged AKT1 and plugged NLRP3
and OCT channels. These multi-target interactions indicate modulation of autophagy
(via AKT1/AMPK), attenuation of inflammasome-driven pyroptosis (NLRP3) and inhibition
of cisplatin uptake (OCT). DHP, HMPFP and BTDMP from B. diffusa emerge as orally
bioavailable, multi-target nephroprotective candidates, meriting further in vivo
validation against cisplatin nephrotoxicity.
