Diabetes mellitus, a metabolic syndrome characterized by insulin deficiency or resistance, poses a significant global health concern. Current treatments often have limitations such as reduced efficacy over time, toxicity, and side effects. There's increasing interest in exploring natural alternatives with fewer side effects. Wheatgrass (*Triticum aestivum*), known for its nutritional value, exhibits elevated antioxidant compound concentrations upon germination. This study hypothesized that wheatgrass grown under simulated microgravity would exhibit enhanced antioxidant and antidiabetic properties compared to that grown under normal gravity. This is due to the potential impact of microgravity on plant growth and metabolite production. No previous research has explored the therapeutic potential of microgravity-grown wheatgrass.

Existing literature supports the antidiabetic and antioxidant potential of wheatgrass grown under normal gravity conditions. Studies show that germinated wheatgrass improves metabolic and lipid profiles and restores plasma glucose, insulin, and liver glycogen levels. However, the nutrient value of germinated grains is influenced by various factors, including the growth environment. The impact of microgravity on plant growth and content is well-documented, prompting this study to investigate the effects of microgravity on wheatgrass's therapeutic potential.

Simulated microgravity was achieved using a three-dimensional clinostat rotating at 4 rotations/min for 7 days. Wheatgrass seeds were sterilized and germinated under both microgravity (WGM) and normal gravity (WGG) conditions. Ethanolic extracts were prepared using a Soxhlet apparatus. Total phenolic content (TPC), total flavonoid content (TFC), and vitamin C content were determined using standard assays. Antioxidant activity was assessed using hydrogen peroxide and nitric oxide scavenging assays. Thirty-five male albino Wistar rats were used, with diabetes induced via streptozotocin injection. Diabetic rats were divided into four groups: a diabetic control group, a group treated with WGM extract, a group treated with WGG extract, and a group treated with metformin. A normal control group was also included. Oral glucose tolerance tests (OGTT) and fasting blood glucose monitoring were conducted over 30 days. At the end of the study, rats were sacrificed, and blood samples were collected to analyze HbA1c, insulin, C-peptide, lipid profile, liver enzymes (AST, ALT), urea, and creatinine. Pancreatic tissue was analyzed histopathologically to assess β-cell count. Statistical analysis was performed using two-way ANOVA followed by Tukey's multiple comparison test.

The WGM extract exhibited significantly higher TPC, TFC, and vitamin C content compared to the WGG extract. WGM extract demonstrated significantly greater hydrogen peroxide and nitric oxide scavenging activities. In the OGTT, diabetic rats treated with WGM extract showed significantly lower blood glucose levels than the diabetic control and WGG extract groups. Over 30 days, WGM extract significantly reduced fasting blood glucose levels compared to the diabetic control, showing an even more pronounced effect than WGG extract. WGM treatment resulted in significantly lower HbA1c levels, reduced serum urea and creatinine, and improved lipid profiles (decreased TC, TG, LDL-C, and increased HDL-C). Liver enzyme levels (AST, ALT) were significantly reduced with WGM treatment compared to the diabetic control. Importantly, the number of β-cells in the pancreatic islets was significantly higher in the WGM group compared to the diabetic control and even higher than that in the metformin-treated group.

The findings demonstrate that simulated microgravity significantly enhances the antioxidant and antidiabetic properties of wheatgrass. The increased TPC, TFC, and vitamin C content in WGM likely contribute to its superior antioxidant activity. The observed reduction in blood glucose, HbA1c, and improvements in lipid profile and liver and kidney function strongly suggest the antidiabetic effects of WGM. The significant increase in β-cell count indicates that WGM extract may stimulate β-cell regeneration or protect them from damage, leading to enhanced insulin secretion and improved glucose homeostasis. These results suggest that WGM extract's effects may involve multiple mechanisms including enhancing antioxidant defense, improving insulin sensitivity, and promoting β-cell function.

This study provides strong evidence that wheatgrass grown under simulated microgravity conditions possesses superior antioxidant and antidiabetic properties compared to wheatgrass grown under normal gravity. The enhanced therapeutic potential of WGM offers a promising natural alternative for diabetes management, potentially providing a cost-effective treatment with minimal side effects. Future research should focus on identifying the specific bioactive compounds responsible for these effects and conducting clinical trials to validate these preclinical findings.

The study utilized a simulated microgravity environment. While the 3D clinostat effectively reduces the effects of gravity, it doesn't perfectly replicate the conditions of actual spaceflight. The sample size, while adequate for statistical analysis, could be increased for enhanced power. Further studies investigating long-term effects and the underlying molecular mechanisms are needed before WGM can be considered for widespread clinical application.