## 4 Plant-Derived Flavonoids That Induce AMPK Activation  
Flavonoids, a diverse group of over 6000 phenolic compounds, are abundantly found in various plant-based foods and beverages, including fruits, vegetables, tea, and red wine. Structurally, flavonoids consist of two aromatic rings connected by a three-carbon chain, forming an oxygenated heterocyclic ring. These compounds are categorized into several classes, such as flavan-3-ols, flavanones, flavonoids, anthocyanin, flavones, and isoflav, based on their structural variations [51; 52]. Numerous studies, including epidemiological research and meta-analyses, suggest that diets rich in flavonoids are associated with a reduced risk of cardiovascular disease and diabetes [53; 54]. Moreover, in vitro and animal studies have demonstrated that flavonoids positively influence glucose metabolism by affecting processes such as carbohydrate digestion, insulin secretion, and glucose uptake in insulin-sensitive tissues [55]. One notable flavonoid, dihydromyricetin, has been shown to enhance insulin sensitivity in skeletal muscle by promoting autophagy through the AMPK signaling pathway. Treatment with dihydromyricetin (50 mg/kg/day for 3 months) significantly improved insulin sensitivity while increasing the levels of p-AMPK, PGC-1\(\alpha\), and SIRT3 in skeletal muscle. SIRT3, a critical member of the sirtuin family, plays a key role in regulating insulin resistance in skeletal muscle, where its expression is notably diminished in diabetic mice. Additionally, PGC-1\(\alpha\) has been identified as an endogenous regulator of SIRT3, further linking the AMPK-PGC-1\(\alpha\) pathway to improved insulin sensitivity. These findings underscore the potential of dihydromyricetin as a therapeutic agent for managing T2 DM [56]. [PERSON] and her team explored the effects of bavachin, a flavonoid derived from _Powalena corylifolia_, on glucose uptake in 3T3-L1 adipocytes [57]. Their research revealed that bavachin significantly enhances insulin-stimulated glucose uptake by activating both the Akt and AMPK pathways. This effect is achieved through increased GLUT4 translocation and elevated GLUT4 mRNA and protein expression. Notably, bavachin was shown to boost AMPK phosphorylation up to fourfold in insulin-stimulated adipocytes at a concentration of 10 \(\mu\)M, indicating its strong potential as a therapeutic agent for T2 DM through the enhancement of insulin sensitivity. [PERSON] and colleagues investigated the effects of 7-O-methylaromadendrin (7-O-MA), a flavonoid, on glucose uptake and insulin resistance in vitro [58]. Their study demonstrated that 7-O-MA enhances glucose uptake in HepG2 cells and 3T3-L1 adipocytes by activating the AMPK and PI3K pathways, suggesting its potential as a therapeutic agent for T2 DM. [PERSON] and her team focused on the activation of AMPK by baicalin in LKB1-deficient cell lines such as HeLa and A549 cells [59]. Their study demonstrated that baicalin activates AMPK via a CaMKK\(\beta\)-dependent pathway, leading to the phosphorylation of AMPK and its downstream targets. This suggests that CaMKK\(\beta\) acts as an upstream kinase for AMPK activation in response to baicalin. Similarly, [PERSON] and colleagues investigated the differential effects of baicalin on glucose disposal, focusing on its interactions with the AMPK and Akt pathways in adipocytes [60]. Their study revealed that baicalin selectively activates AMPK, leading to increased phosphorylation of AS160 and enhanced glucose uptake, while scutellarin primarily activates Akt. These findings suggest that baicalin's beneficial effects on glucose metabolism are largely mediated through AMPK activation. [PERSON] and colleagues explored the effects of baicalin on high-fat-diet-induced metabolic syndrome in mice [61]. Their study found that baicalin significantly improved conditions such as obesity, dyslipidemia, fatty liver, diabetes, and insulin resistance.