International Journal of Clinical Case Reports 2024, Vol.14, No.6, 327-338 http://medscipublisher.com/index.php/ijccr 330 reducing postprandial blood glucose levels. Although specific studies on these enzymes were not detailed in the provided data, the general antidiabetic properties of E. ulmoides suggest its potential in this mechanism. The inhibition of glucose transport in Caco-2 cells by Eucommia ulmoides could further contribute to its antidiabetic effects. This mechanism involves reducing the absorption of glucose in the intestines, thereby lowering blood glucose levels. While direct evidence from the provided data is lacking, the overall antidiabetic potential of E. ulmoides supports this mechanism. 3.3 Antioxidant activity Eucommia ulmoides has been shown to enhance endogenous antioxidant activity in type 2 diabetic mice. The upregulation of Nrf2, a key regulator of antioxidant response, indicates that E. ulmoides can boost the body's natural antioxidant defenses, thereby mitigating oxidative stress associated with diabetes (Do et al., 2018). The reduction of oxidative stress through the activation of Glo1 and Nrf2 pathways is a significant antidiabetic mechanism of Eucommia ulmoides. By increasing the activity of Glo1, which detoxifies harmful AGE precursors, and upregulating Nrf2, E. ulmoides effectively reduces oxidative damage in diabetic conditions (Do et al., 2018). This dual action not only protects renal function but also contributes to the overall antioxidant capacity of the organism. 4 In Vitro Studies on Antidiabetic Potential 4.1 Cell-based assays for glucose uptake Cell-based assays are crucial for evaluating the antidiabetic potential of phytochemicals by measuring their effects on glucose uptake in various cell lines. For instance, ethanolic extracts of Psidium guajava leaves significantly increased glucose uptake in murine C2C12 skeletal muscle cells, demonstrating a 161.4% increase compared to the control, which was comparable to the effects of metformin and insulin (Beidokhti et al., 2020). This suggests that phytochemicals fromEucommia ulmoides could similarly enhance glucose uptake in muscle cells, potentially improving glucose homeostasis in diabetic conditions. 4.2 Enzyme inhibition studies Enzyme inhibition studies are pivotal in understanding how phytochemicals can modulate carbohydrate metabolism. Several studies have demonstrated the inhibitory effects of natural compounds on key enzymes like α-glucosidase and α-amylase. For example, phenolic compounds have shown effective inhibition of α-amylase and α-glucosidase with IC50 values ranging from 175.01 to 626.58 nM and 120.53 to 892.36 nM, respectively (Gulcin et al., 2018). Similarly, novel 1,3,5-trisubstituted-2-thioxoimidazolidin-4-ones exhibited significant inhibitory activity against these enzymes, with compound 5a showing IC50 values of 5.08 µg/mL for α-glucosidase and 0.21 µg/mL for α-amylase (Khirallah et al., 2022). These findings indicate that phytochemicals fromEucommia ulmoides could potentially inhibit these enzymes, thereby reducing postprandial hyperglycemia. In the study by Khirallah et al. (2022), the inhibitory effects of newly synthesized 1,3,5-trisubstituted-2-thioxoimidazolidin-4-one analogs (compounds 4a–b, 5a–b, 7a–b) on α-amylase were analyzed at different concentrations and compared with the standard drug acarbose. The results showed that these compounds exhibited strong inhibitory activity, with compound 4b demonstrating particularly high inhibition at lower concentrations, and its IC50 value was significantly lower than that of acarbose. This suggests that these compounds could be potential candidates for diabetes treatment, warranting further research and development (Figure 2). 4.3 Antioxidant activity assays Antioxidant activity assays are essential for evaluating the potential of phytochemicals to mitigate oxidative stress, which is a significant factor in diabetes complications. For instance, Annona muricata leaf extracts demonstrated strong antioxidant properties, with ORAC values of 3964 ± 53 µmol trolox eq/g and DPPH IC50 values of 4.3 ± 0.7 µg/mL (Justino et al., 2018). Similarly, Smallanthus sonchifolius leaf extract exhibited notable antioxidant
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