β-carboline alkaloids from Stellaria dichotoma as anti-fibrotic therapeutics against chronic kidney disease

β -Carboline alkaloids possess significant industrial value and considerable potential for drug development. In pursuit of potential therapeutic agents for chronic kidney disease (CKD), twenty-one β -carboline alkaloids ( 1 – 21 ), including seven new β -carbolines, dichotomides J–M ( 1 – 4 ), 15-hydroxystellarine B ( 5 ), 8-hydroxydichotomide III ( 6 ) and dichotomoside F ( 20 ), were isolated from Stellaria dichotoma . HPLC analysis revealed that dichotomine B (DB) was the most abundant β -carboline alkaloid in the medicinal material, accounting for 0.31 % of the total content, suggesting its potential for industrial production. Using a cost-effective acid–base extraction combined with recrystallization, DB can be rapidly and efficiently obtained in large quantities, markedly reducing both experimental cost and complexity compared with conventional chromatographic methods. In vitro , DB downregulated key fibrosis-related markers in HK-2 cells exposed to TGF- β 1. In vivo , DB attenuated renal fibrosis in CKD mice and significantly improved kidney injury in 5/6 nephrectomy mice. Mechanistic analyses both in vitro and in vivo indicate that DB inhibits activation of TGF- β /Smad pathway, thereby mitigating extracellular matrix deposition and pathological indices of CKD. With remarkable abundance and potent bioactivity, DB holds strong potential as a natural lead compound for renoprotective drug development, while also indicating its feasibility for future industrial-scale production and application. • Twenty-one β -carbolines were isolated from Stellaria dichotoma . • High-yield DB obtained economically via acid–base extraction and recrystallization. • In CKD mice, DB treatment improved renal function and mitigated renal fibrosis. • DB reduced ECM deposition by inhibiting TGF- β /Smad pathways.