Holy Basil (Ocimum sanctum L.) Flower and Fenofibrate Improve Lipid Profiles in Rats with Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD): The Role of Choline Metabolism

Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to choline metabolism. The present study investigated the effect of holy basil (<i>Ocimum sanctum</i> L.) flower water extract (OSLY) on MASLD with choline metabolism as an underlying mechanism. Rats with high-fat diet (HFD)-induced MASLD received 250-1000 mg/kg bw of OSLY, fenofibrate, or fenofibrate + 1000 mg/kg OSLY combination. Biochemical parameters, choline metabolites, and one-carbon gene transcription were analyzed. OSLY and fenofibrate independently reduced serum LDL cholesterol (<i>p</i> < 0.02), liver cholesterol (<i>p</i> < 0.001), and liver triglyceride levels (<i>p</i> < 0.001) in HFD-fed rats. Only OSLY reduced signs of liver injury and increased serum HDL. Fenofibrate influenced choline metabolism by decreasing liver glycerophosphocholine (GPC; <i>p</i> = 0.04), as well as increasing betaine (<i>p</i> < 0.001) and the betaine:choline ratio (<i>p</i> = 0.02) in HFD-fed rats. Fenofibrate (vs. HFD) increased the expression of one-carbon metabolism genes <i>Mthfd1l</i>, <i>Pemt</i>, <i>Smpd3</i>, and <i>Chka</i> (<i>p</i> < 0.04). The OSLY treatment decreased liver GPC (500 mg dose; <i>p</i> = 0.03) and increased <i>Smpd3</i> expression (1000 mg dose; <i>p</i> = 0.04). OSLY and fenofibrate showed weak synergistic effects on lipid and choline metabolism. Collectively, OSLY and fenofibrate independently improve lipid profiles in MASLD rats. The benefits of fenofibrate are partially mediated by choline/one-carbon metabolism, while those of OSLY are not mediated by this pathway. Holy basil flower extract merits further development as an alternative medicine for MASLD.