RETRACTED: Spirulina Unleashed: A Pancreatic Symphony to Restore Glycemic Balance and Improve Hyperlipidemia and Antioxidant Properties by Transcriptional Modulation of Genes in a Rat Model

Abstract

Hyperlipidemia is the root cause of numerous chronic conditions, leading to high mortality rates around the globe. Spirulina (Arthrospira platensis) microalgae serve as a promising reservoir of bioactive compounds with diverse pharmacological properties. The current study examined the nutritional profile of spirulina powder in relation to strict glycemic control, specifically focusing on its potential to lower lipid levels. In an in vivo investigation, normal healthy male Wistar albino rats (n = 60) were divided into two groups: a negative control group (NC) of ten rats and a high-fat diet group (n = 50) that were fed a cholesterol-rich diet until their cholesterol levels reached or exceeded 250 mg/dL. Subsequently, the hypercholesterolemic rats were then randomly allocated to several treatment groups: a positive control (PC); a standard treatment diet (STD) involving fenofibrate at a dose of 20 mg/kg body weight; and three experimental groups (T1, T2, and T3) that received spirulina powder supplementation at doses of 300, 600, and 900 mg per kg body weight, respectively, for the period of 12 weeks. Blood samples were analyzed for oxidative stress biomarkers, insulin levels, lipid profiles, liver function, and expression of gene levels in the diabetogenic pathway. The study utilized spectrophotometric colorimetric methods to identify oxidative stress biomarkers, serum kit methods to measure lipid profiles and liver enzymes, and the assessment of qPCR for mRNA quantity. According to the research findings, spirulina powder has certain noteworthy features. It had the greatest quantity of chlorogenic acid (4052.90 µg/g) among seven phenolics and two flavonoid compounds obtained by HPLC-UV analysis. Furthermore, the proximate analysis demonstrated that spirulina is high in protein (16.45 ± 0.8%) and has a significant energy yield of 269.51 K-calories per 100 g. A maximal spirulina dose of 900 mg/kg/wt significantly lowered oxidative stress, cholesterol, triglyceride, low-density lipoproteins (LDL), and insulin levels (p ≤ 0.05). In contrast, high-density lipoprotein (HDL) and total antioxidant capacity (TAC) levels increased significantly (p ≤ 0.05) compared to all other groups, except the NC group. The study provides remarkable proof about the pharmacological impact of spirulina powders. Significant reductions (p ≤ 0.05) in liver enzymes {alanine aminotransferase (ALT) and aspartate aminotransferase (AST)} were observed across all treatment groups, with the exception of the NC, compared to the positive control. The treatment groups had significantly greater gene expression levels of INS-1, PDX-1, IGF-1, and GLUT-2 than the positive control group (p ≤ 0.05). These findings highlight spirulina's potential as a long-term regulator of hyperglycemia in rat models with induced hyperlipidemia, owing to its phenolic bioactive components that serve as antioxidants.

Keywords: gene expression; hyperlipidemia; qPCR; spirulina.

Figure 1

Quantitative analysis of various phenolic and flavonoid compounds in spirulina powder by HPLC-UV chromatogram.

Figure 2

Oxidative stress biomarkers. (a) Total oxidative stress (TOS), (b) total antioxidant capacity (TAC), (c) malondialdehyde, and (d) catalase levels in the NC (normal control), PC (positive control), STD group (Fenoget oral dose of 20 mg/kg), and different spirulina-powder-treated groups: T1 (300 mg/kg body weight), T2 (600 mg/kg body weight), and T3 (900 mg/kg body weight), for a 12 week period in high-fat-diet-induced dyslipidemic rats. This means values with different superscripts are significantly different from each other (p ≤ 0.05). ^a–d Different superscripts on bars show a significant difference between different groups (Duncan’s test). Various bars represent concentration gradient variations; higher concentrations correlate with higher percent inhibition.

Figure 3

Lipid profile showing (a) cholesterol (mg/dL), (b) triglycerides (TG) (mg/dL), (c) low-density lipoprotein (LDL) (mg/dL), and (d) high-density lipoprotein (HDL) (mg/dL) levels in the NC (normal control), PC (positive control), STD group (Fenoget oral dose of 20 mg/kg body weight), and different spirulina-powder-treated groups: T1 (300 mg/kg body weight), T2 (600 mg/kg body weight), and T3 (900 mg/kg body weight), for a 12 week period in high-fat-diet-induced hyperlipidemic rats considering p ≤ 0.05. Positive partial correlation—orange color, negative partial correlation—black color.

Figure 4

Serum insulin in the NC (normal control), PC (positive control), STD group (Fenoget oral dose of 20 mg/kg body weight), and different spirulina-powder-treated groups: T1 (300 mg/kg body weight), T2 (600 mg/kg body weight), and T3 (900 mg/kg body weight), for a three-month period in high-fat-diet-induced hyperlipidemic rats. ^a–e Different superscripts on bars show a significant difference between different groups (Duncan’s test).

Figure 5

Histo-micrograph of pancreatic tissues collected from the NC, PC, STD, and different spirulina-powder-treated groups: T1 (300 mg/kg body weight), T2 (600 mg/kg body weight), and T3 (900 mg/kg body weight), for three months in high-fat-diet-induced dyslipidemic rats. Blue stars show the beta cells, the yellow arrow shows the exocrine portion, and the straight line shows the length of islets of Langerhans.

Figure 6

Histo-micrograph of liver tissues collected from the NC, PC, STD, and different spirulina-powder-treated groups: T1 (300 mg/kg body weight), T2 (600 mg/kg body weight), and T3 (900 mg/kg body weight), for three months in high-fat-diet-induced dyslipidemic rats.

Figure 7

Gene expression of INS-1 (a), IGF-1 (b), PDX-1 (c), and GLUT-2 (d) (mRNA expression levels ± SEM) in the NC (normal control), PC (positive control), STD group (Fenoget oral dose of 20 mg/kg body weight), and different spirulina-powder-treated groups: T1 (300 mg/kg body weight), T2 (600 mg/kg body weight), and T3 (900 mg/kg body weight), for the three-month period in high-fat-diet-induced dyslipidemic rats. ^a–f Different superscripts on bars show a significant difference between different groups (Duncan’s test). Various bars represent concentration gradient variations; higher concentrations correlate with higher percent inhibition.

Figure 8

Principal component analysis showing the relation among various attributes studied over 12-week periods in high-fat-diet-induced dyslipidemic rats treated with spirulina powder.