SIRT1-Mediated Epigenetic Protective Mechanisms of Phytosome-Encapsulated Zea mays L. var. ceratina Tassel Extract in a Rat Model of PM2.5-Induced Cardiovascular Inflammation

Abstract

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 Zea mays L. var. ceratina 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.

Keywords: Zea mays L. var. ceratina; cardiovascular diseases; inflammation; oxidative stress; phytosome; purple waxy corn; tassel.

Figure 1

Chromatographic fingerprint of rutin, quercetin, and kaempferol in Zea mays L. var. ceratina tassel extract and its phytosome formulation (PZT). PZT refers to phytosome-encapsulated Zea mays L. var. ceratina tassel extract.

Figure 2

Effects of PZT on SIRT1 expression in cardiac tissue. (A) Representative Western blot image showing the expression levels of SIRT1 protein. (B) Bar graph presenting the relative protein expression of SIRT1, normalized to β-actin. Data are expressed as mean ± SEM. ^# p < 0.05, compared to the naïve control group. * p < 0.05, compared to the PM2.5-exposed+vehicle group. Prednisolone refers to treatment with prednisolone at 1 mg/kg BW; PZT100, PZT200, and PZT400 refer to treatment with phytosome-encapsulated Zea mays L. var. ceratina tassel extract at 100, 200, and 400 mg/kg BW, respectively; and SIRT1 refers to sirtuin 1.

Figure 3

Effects of PZT on SIRT1 expression in vascular tissue. (A) Representative Western blot image showing the expression levels of SIRT1 protein. (B) Bar graph presenting the relative protein expression of SIRT1, normalized to β-actin. Data are expressed as mean ± SEM. ^### p < 0.001, compared to the naïve control group. *, **, and *** indicate p < 0.05, 0.01, and 0.001, respectively, compared to the PM2.5-exposed+vehicle group. Prednisolone refers to treatment with prednisolone at 1 mg/kg BW; PZT100, PZT200, and PZT400 refer to treatment with phytosome-encapsulated Zea mays L. var. ceratina tassel extract at 100, 200, and 400 mg/kg BW, respectively; and SIRT1 refers to sirtuin 1.

Figure 4

Effects of PZT on inflammatory markers, including NF-κB, TNF-α, and IL-6 expressions in cardiac tissue. (A) Representative Western blot image showing the expression levels of NF-κB, TNF-α, and IL-6 protein. (B) Bar graph presenting the relative protein expression of NF-κB, TNF-α, and IL-6, normalized to β-actin. Data are expressed as mean ± SEM. ^### p < 0.001, compared to the naïve control group. *, **, and *** indicate p < 0.05, 0.01, and 0.001, respectively, compared to the PM2.5-exposed+vehicle group. Prednisolone refers to treatment with prednisolone at 1 mg/kg BW; PZT100, PZT200, and PZT400 refer to treatment with phytosome-encapsulated Zea mays L. var. ceratina tassel extract at 100, 200, and 400 mg/kg BW, respectively; NF-κB refers to nuclear factor-kappa B; TNF-α refers to tumor necrosis factor-alpha; and IL-6 refers to interleukin-6.

Figure 5

Effects of PZT on inflammatory markers, including NF-κB, TNF-α, and TGF-β expressions in vascular tissue. (A) Representative Western blot image showing the expression levels of NF-κB, TNF-α, and TGF-β protein. (B) Bar graph presenting the relative protein expression of NF-κB, TNF-α, and TGF-β, normalized to β-actin. Data are expressed as mean ± SEM. ^### p < 0.001, compared to the naïve control group. *, **, and *** indicate p < 0.05, 0.01, and 0.001, respectively, compared to the PM2.5-exposed+vehicle group. Prednisolone refers to treatment with prednisolone at 1 mg/kg BW; PZT100, PZT200, and PZT400 refer to treatment with phytosome-encapsulated Zea mays L. var. ceratina tassel extract at 100, 200, and 400 mg/kg BW, respectively; NF-κB refers to nuclear factor-kappa B; TNF-α refers to tumor necrosis factor-alpha; and TGF-β refers to transforming growth factor-beta.

Figure 6

Effects of PZT on antioxidant enzyme activities in cardiac tissue. Data are presented as mean ± SEM. ^### p < 0.001, compared to the naïve control group. * and *** indicate p < 0.05 and 0.001, respectively, compared to the PM2.5-exposed vehicle group. Prednisolone refers to treatment with prednisolone at 1 mg/kg BW; PZT100, PZT200, and PZT400 refer to treatment with phytosome-encapsulated Zea mays L. var. ceratina tassel extract at 100, 200, and 400 mg/kg BW, respectively; CAT refers to catalase; SOD refers to superoxide dismutase; and GSH-Px refers to glutathione peroxidase.

Figure 7

Effects of PZT on antioxidant enzyme activities in vascular tissue. Data are presented as mean ± SEM. ^### p < 0.001, compared to the naïve control group. *, ** and *** indicate p < 0.05, 0.01, and 0.001, respectively, compared to the PM2.5-exposed vehicle group. Prednisolone refers to treatment with prednisolone at 1 mg/kg BW; PZT100, PZT200, and PZT400 refer to treatment with phytosome-encapsulated Zea mays L. var. ceratina tassel extract at 100, 200, and 400 mg/kg BW, respectively; CAT refers to catalase; SOD refers to superoxide dismutase; and GSH-Px refers to glutathione peroxidase.

Figure 8

Effects of PZT on malondialdehyde levels in cardiac and vascular tissues. Data are presented as mean ± SEM. ^### p < 0.001, compared to the naïve control group. * and *** indicate p < 0.05 and 0.001, respectively, compared to the PM2.5-exposed vehicle group. Prednisolone refers to treatment with prednisolone at 1 mg/kg BW; PZT100, PZT200, and PZT400 refer to treatment with phytosome-encapsulated Zea mays L. var. ceratina tassel extract at 100, 200, and 400 mg/kg BW, respectively; and MDA refers to malondialdehyde.

Figure 9

Schematic representation of the experimental procedures. (A) Overview of the protocol detailing PZT administration and the assessment of key parameters. (B) Timeline depicting the induction of PM2.5-induced systemic inflammation and the corresponding schedule for PZT treatment. PZT refers to phytosome-encapsulated Zea mays L. var. ceratina tassel extract.

Figure 10

Schematic diagram summarizing the pathophysiology of PM2.5-induced cardiovascular injury and the potential mechanisms underlying PZT treatment. PZT refers to phytosome-encapsulated Zea mays L. var. ceratina tassel extract; PM2.5 refers to fine particulate matter <2.5 µm; NF-κB refers to nuclear factor kappa B; IL-6 refers to interleukin-6; TNF-α refers to tumor necrosis factor-alpha; TGF-β: refers to transforming growth factor-beta; ROS refers to reactive oxygen species; SOD refers to superoxide dismutase; CAT refers to catalase; GSH-Px refers to glutathione peroxidase; and MDA: refers to malondialdehyde.