Nine-Week Co-Supplementation with Sugarcane Wax Alcohol (Policosanol), Phosphatidylserine, and Ginkgo biloba Leaf Extract Attenuates the Metabolic Dysfunction and Oxidative Stress in Blood and Vital Organs of Hyperlipidemic/Hyperglycemic Zebrafish

Policosanol (sugarcane wax alcohol), phosphatidylserine, and Ginkgo biloba leaf extract are Ministry of Food and Drug Safety (MFDS), Republic of Korea-listed functional foods for health-promoting effects. Herein, a combination of policosanol, phosphatidylserine, and G. biloba leaf extract (hereafter PPG) was investigated against metabolic stress induced by a high-cholesterol, high-galactose (HCHG) diet in hyperlipidemic and hyperglycemic zebrafish. After 9 weeks of feeding, the zebrafish following the HCHG diet co-supplemented with PPG exhibited a significant 14.1% (p < 0.02) reduction in body weight and higher zebrafish survivability compared to the HCHG-supplemented group. Significantly reduced total cholesterol (TC, 1.2-fold), triglycerides (TG, 1.4-fold), low-density lipoprotein cholesterol (LDL-C, 1.3-fold), and glucose levels (1.2-fold), along with a 1.5-fold (p = 0.003) elevated high-density lipoprotein cholesterol (HDL-C), were observed in the PPG co-supplemented group relative to the HCHG group. In addition, the HCHG-elevated plasma malondialdehyde (MDA), diminished ferric ion reduction activity (FRA), and paraoxonase (PON)-like activity significantly (p < 0.001) reverted by 1.6-fold, 1.4-fold, and 1.6-fold, respectively, by co-supplementation with PPG. Consistently, the plasma from the PPG-supplemented group showed greater ability to prevent carboxymethyllysine (CML)-induced apoptotic death, altered heart rate, and developmental deformities in zebrafish embryos. Moreover, PPG exerted significant protective effects against HCHG-induced hepatomegaly and fatty liver, accompanied by marked inhibition of hepatic interleukin (IL)-6 and reactive oxygen species (ROS) generation. Consistently, PPG supplementation inhibits ROS generation and senescence in the liver, intestine, brain, kidney, testis and ovary and protects the organ damage caused by exposure to HCHG. Similarly, in intestinal tissue, HCHG-induced fibrosis and oxidative stress were mitigated by the co-supplementation of PPG. The findings indicate that PPG is an effective combination for preventing dyslipidemia, oxidative stress, inflammation, and multi-organ damage associated with HCHG-mediated metabolic stress in zebrafish.