Cardiovascular injury caused by fine particulate matter (PM2.5) exposure is an escalating public health concern due to its role in triggering systemic inflammation and oxidative stress. This study elucidates the sirtuin 1 (SIRT1)-mediated epigenetic mechanisms underlying the protective effects of phytosome-encapsulated L. var. tassel extract (PZT) in a rat model of PM2.5-induced cardiovascular inflammation. Male Wistar rats were pretreated with PZT (100, 200, and 400 mg/kg body weight) for 21 days before and throughout a 27-day PM2.5 exposure period. SIRT1 expression and associated inflammatory and oxidative stress markers were evaluated in cardiac and vascular tissues. The findings revealed that PZT significantly upregulated SIRT1 expression, a key epigenetic regulator known to modulate inflammatory and antioxidant pathways. The activation of SIRT1 inhibited the nuclear factor-kappa B (NF-κB) signaling pathway, leading to a reduction in pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) within cardiac tissue. In vascular tissue, treatment with PZT reduced the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β), thereby mitigating inflammatory and fibrotic responses. Furthermore, SIRT1 activation by PZT enhanced the antioxidant defense system by upregulating superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), which was associated with a decrease in malondialdehyde (MDA), a marker of lipid peroxidation. Collectively, these results demonstrate that PZT confers cardiovascular protection through SIRT1-dependent epigenetic modulation, mitigating PM2.5-induced inflammation, oxidative stress, and tissue remodeling. The dual anti-inflammatory and antioxidant actions of PZT via SIRT1 activation highlight its potential as a functional food-based preventative agent for reducing cardiovascular risk in polluted environments.