Mechanistic insights into andrographolide-mediated cardioprotective action through mitochondrial homeostasis: a network pharmacology and in vivo approach.

Cardiovascular aging is the progressive deterioration of heart and blood vessel function with advancing age. Despite advances in cardiovascular research, no specific therapy is currently available to prevent cardiac aging. Andrographolide, a bioactive diterpenoid, has shown cardioprotective potential, but its role in cardiac aging remains inadequately explored. To evaluate the mechanistic role of andrographolide in attenuating cardiac aging, with a particular focus on mitochondrial homeostasis. Cardiac aging was induced in male C57BL/6J mice by intraperitoneal administration of D-galactose (50 mg/kg/day). Mice were divided into control, andrographolide (50 mg/kg), D-galactose, and D-galactose + andrographolide (50 mg/kg). Andrographolide was administered orally for 8 weeks. Cardiac tissues were analyzed for oxidative stress, inflammation, apoptosis, and mitochondrial biogenesis-related markers TFAM, PGC-1α, and SIRT-1. Andrographolide treatment significantly improved cardiac function in D-galactose-induced aged mice. It enhanced antioxidant defenses while reducing inflammation and apoptosis. Immunohistochemical analysis demonstrated increased expression of SIRT1, PGC-1α, TFAM, and Nrf2, suggesting that andrographolide may promote mitochondrial biogenesis and antioxidant defense. Andrographolide confers significant cardioprotection against induced cardiac aging by modulating oxidative, inflammatory, and mitochondrial regulatory pathways. Thus, andrographolide can act as an ameliorative therapeutic drug for management of cardiac aging, warranting further mechanistic and translational investigations.