Organ fibrosis in older adults with obesity represents one of the most clinically underserved intersections of aging biology and metabolic disease. Conditions like metabolic dysfunction-associated steatohepatitis, fibrotic kidney disease, and heart failure with preserved ejection fraction share a common molecular driver — dysregulated TGF-β signaling — yet most pharmacological strategies target single pathways rather than the multi-tissue fibrotic cascade. A traditional Japanese herbal compound may offer a different approach.
Bofutsushosan (BTS), a multi-herb Kampo formulation historically prescribed for weight management, was tested in 63-week-old mice fed a high-fat diet — an age that more closely mirrors late-middle-aged human metabolic physiology than the young rodents used in most obesity research. Over two months of dietary BTS supplementation, treated animals showed a 14.8% reduction in body weight, decreased adipose depot size, and measurable attenuation of hepatic steatosis. More notably, expression of Col1a1, the gene encoding type I collagen and a sentinel marker of fibrotic remodeling, dropped 60.6% in adipose tissue and 46.2% in liver. Mechanistically, BTS suppressed TGF-β-induced SMAD2/3 phosphorylation in preadipocytes — the canonical intracellular cascade that drives fibroblast activation and extracellular matrix deposition. Of the 18 constituent herbs screened, Sal Mirabilis emerged as the primary anti-fibrotic component.
This work is notable for its translational architecture: combining an aged animal model with component-resolved in vitro screening allows attribution of effect to specific botanical fractions rather than the whole formula — a methodological step that most phytomedicine research skips entirely. Still, significant limitations apply. Mouse fibrosis models frequently overpredict human therapeutic responses, and the aged obese mouse, while more relevant than young animals, still does not fully recapitulate human MASH or cardiorenal fibrosis. The study is also preclinical and single-institution, with no pharmacokinetic data on how BTS components are absorbed or metabolized in aged mammals. The finding is incremental but scientifically credible — it narrows a broad traditional formula to a mechanistically testable active fraction worth pursuing in human tissue or early-phase trials.