MEDICINAL PLANT-DERIVED THERAPY VERSUS ATORVASTATIN IN CARDIOVASCULAR DISEASE COMPARATIVE PHARMACOLOGICAL AND MOLECULAR ANALYSIS OF CARDIOPROTECTIVE PATHWAYS

Abstract

Background: Dyslipidemia, oxidative stress, inflammation, and endothelial dysfunction are all linked to cardiovascular disease (CVD) and there is a need to develop therapies with complementary cardioprotective properties. Objective: To compare the effects of standardized Nigella sativa (N. sativa) seed oil and atorvastatin on lipid parameters, oxidative stress, inflammation, endothelial function, and selected cardioprotective molecular pathways over 12 weeks. Methodology: A comparative parallel-group clinical study was conducted at Shifa International Hospital, Islamabad, Pakistan, from January 2024 to December 2025. A total of 428 adults with cardiovascular disease were recruited and allocated equally to receive standardized N. sativa seed oil (2 g/day) or atorvastatin (20 mg/day) for 12 weeks. Participants were assessed at baseline and at 4, 8, and 12 weeks for clinical, biochemical, oxidative stress, inflammatory, endothelial-function, molecular, and safety parameters. Comparative and longitudinal analyses were performed to assess changes over time and between treatment groups, while correlation and multivariable regression analyses were used to examine associations between molecular markers and pharmacological outcomes. Statistical significance was set at p<0.05. Results: Of 428 participants, 412 (96.26%) completed follow-up, including 204 (95.33%) in the N. sativa group and 208 (97.20%) in the atorvastatin group. At 12 weeks, N. sativa reduced total cholesterol by 33.6 mg/dL versus 48.4 mg/dL with atorvastatin (p<0.001), and LDL-C by 24.1 versus 46.0 mg/dL (p<0.001). N. sativa produced greater improvements in MDA (−1.11 vs. −0.82 nmol/mL, p=0.006), SOD (+15.1 vs. +10.3 U/mL, p<0.001), GSH (+1.33 vs. +1.03 µmol/L, p=0.005), hs-CRP (−1.27 vs. −0.97 mg/L, p=0.031), and nitric oxide (+8.2 vs. +6.5 µmol/L, p=0.019). Molecular markers including AMPK, Nrf2, HO-1, and eNOS showed greater modulation with N. sativa. Conclusion: N. sativa demonstrated multidimensional cardioprotective effects, although atorvastatin produced greater lipid-lowering efficacy.