Synergistic combinatorial antihyperlipidemic study of selected natural antioxidants; modulatory effects on lipid profile and endogenous antioxidants.
BACKGROUND
Hyperlipidemia, a major pathological condition associated with disrupted lipid levels and physiological redox homeostasis. The excessive release of reactive oxygen species (ROS) leads to enhanced lipid peroxidation, aggravated atherosclerosis and oxidative stress. Integration of natural antioxidant blends in alone or with conventional treatments can alleviate these issues synergistically contributing least side effects. Published literature reported the efficacy of natural antioxidants as individual and in combinations in various conditions but less data is available on their evaluation in low dose ratio blends particularly in hypercholesterolemic diet.


METHODS
Antihyperlipidemic effects of selected natural antioxidants; the phenolic oligomeric proanthocyanidins (OPC) and pterostilbene (PT) with niacin (NA) were investigated in current study. Their effects on lipid profile, lipid peroxidation and their aptitude to establish redox state between oxidants and antioxidants in body were evaluated in high cholesterol diet fed animal model. Male albino rabbits (n = 6) weighing 1.2-1.6 kg, supplemented with high cholesterol diet (400 mg/kg) for 12 weeks were used in the experiment. Antioxidants were administered individual high (100 mg/kg) and in low dose combinations (total dose = 100 mg/kg). Student's t test and one way analysis of variance (ANOVA) followed by Dunnet's test were used as statistical tools for evaluation.


RESULTS
The results showed synergistic effects of low dose antioxidant blends. Therapies retarded elevation in blood lipid levels, lipid peroxidation and blood antioxidant depletion and consequently contributed in reestablishing redox homeostasis. The LDL/HDL ratio and atherogenic index were suppressed significantly in blend therapies with maximum effects of 59.3 and 25 % (p >0.001) observed in 50:30:20 ratios of OPC, NA and PT, compared to individual therapies 37 and 18 % max respectively. Moreover the results were also in close proximity with the statin therapy (52.66, 26.28 %).


CONCLUSIONS
This study provides an evidence for natural antioxidants blends superiority over individual therapy in chronic diseases like hyperlipidemia. Such therapies in human equivalent doses can help in mitigating chronic illnesses in general populations.
Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan.
Peer Abdul
PA
Hannan
Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. jamshaidkhan@upesh.edu.pk.
Jamshaid Ali
JA
Khan
Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan.
Irfan
I
Ullah
Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan.
Safi
S
Ullah
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism*; D050197:Atherosclerosis / Q000178:diet therapy* / Q000188:drug therapy / Q000473:pathology; D001688:Biological Products / Q000008:administration & dosage*; D004357:Drug Synergism; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D009525:Niacin / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects*; D044945:Proanthocyanidins / Q000008:administration & dosage; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage
D000975:Antioxidants; D001688:Biological Products; D000960:Hypolipidemic Agents; D008055:Lipids; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D013267:Stilbenes; D009525:Niacin; C107773:pterostilbene
Atherosclerosis; Hyperlipidemia; Lipid peroxidation; Redox homeostasis; Synergism