Consumption of Terpenoids-Rich Padina pavonia Extract Attenuates Hyperglycemia, Insulin Resistance and Oxidative Stress, and Upregulates PPARγ in a Rat Model of Type 2 Diabetes

Abstract

Seaweeds are rich in structurally diverse bioactive compounds with promising therapeutic effects. This study aimed to isolate and identify terpenes from the brown alga Padina pavonia and to investigate its antidiabetic activity, pointing to the possible involvement of peroxisome proliferator-activated receptor (PPAR)γ. Type 2 diabetes was induced by feeding rats a high fat diet (HFD) for 4 weeks followed by injection of 35 mg/kg streptozotocin (STZ). The diabetic rats received P. pavonia extract (PPE; 50, 100 and 200 mg/kg) for 4 weeks and samples were collected for analyses. HFD/STZ-induced rats showed hyperglycemia, dyslipidemia, impaired glucose tolerance, decreased insulin, and increased HbA1c and HOMA-IR. PPE ameliorated hyperglycemia and dyslipidemia, and improved glucose tolerance and insulin sensitivity in diabetic rats. Treatment with PPE increased hepatic hexokinase activity and glycogen, suppressed glucose-6-phosphatase, fructose-1,6-biphosphatase, and glycogen phosphorylase, and attenuated oxidative stress, inflammation, and liver injury and lipid infiltration in HFD/STZ-induced rats. In addition, PPE boosted antioxidants and upregulated PPARγ gene and protein expression in the liver of diabetic rats. Phytochemical investigation resulted in the isolation of six terpenes from PPE and in silico analysis revealed their binding affinity toward PPARγ. In conclusion, P. pavonia-derived terpenes attenuated hyperglycemia, dyslipidemia, oxidative stress, and inflammation, and improved insulin sensitivity and carbohydrate metabolism in type 2 diabetic rats. These beneficial effects are mediated via PPARγ activation. However, further studies to explore the exact mechanisms underlying the antidiabetic effect of PPE are recommended.

Effects of hyperglycemia on the TGF-β pathway in trabecular meshwork cells

“…Malik et al stated that oxidative stress caused by hyperglycemia due to the overproduction of mitochondrial reactive oxygen species (ROS) is involved in this process (Brownlee, 2001;Czajka & Malik, 2016;Nishikawa et al, 2000). Excessive ROS production mediates oxidative stress in DM by high glucose and/or fatty acid oxidation (Germoush et al, 2019). Lu et al demonstrated that the main mediator against diabetic complications is oxidation stress (Wang et al, 2019).…”

Lactobacillus plantarumTWK10‐fermented soymilk improves cognitive function in type 2 diabetic rats

“…Increasing evidence has suggested that oxidative stress plays a pivotal role in the development of diabetes-induced behavioral and cognitive defects. [3][4][5] The brain is highly sensitive to oxidation because of the presence of large amounts of unsaturated fatty acids and oxygen, which serve as a substrate for lipid peroxidation. The peroxidation products are the biomarkers of oxidative stress in neurodegenerative diseases.…”

“…However, cognitive decline is also one of the complications associated with such a lifestyle and habits but it has been studied relatively less. Increasing evidence has suggested that oxidative stress plays a pivotal role in the development of diabetes‐induced behavioral and cognitive defects 3–5 . The brain is highly sensitive to oxidation because of the presence of large amounts of unsaturated fatty acids and oxygen, which serve as a substrate for lipid peroxidation.…”

“…2 Moreover, excess ROS can directly lead to an increase in oxidative stress in various tissues and organs, therefore altering cell function, inflammation, and apoptosis in the kidney, liver, nerves, and vasculature. 3,4 In addition to these, T2D can cause cognitive decline. The consumption of diets high in fat is also associated with altered cognitive function, including impairment in learning and memory.…”

“…ROS initiate a chain reaction leading to reduced nitric oxide (NO) availability 2 . Moreover, excess ROS can directly lead to an increase in oxidative stress in various tissues and organs, therefore altering cell function, inflammation, and apoptosis in the kidney, liver, nerves, and vasculature 3,4 . In addition to these, T2D can cause cognitive decline.…”