## 5 Docking Analysis of AMPK with Flavonoids
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{2}{*}{**Flavonoids**} & \multirow{2}{*}{**Treatment**} & \multirow{2}{*}{**Model** **(Cell or Animal)**} & \multicolumn{2}{c}{**Change in**} & \multirow{2}{*}{**Results**} & \multirow{2}{*}{**Ref.**} \\  & & & & ADP/AMP & & \\  & & & & **Ratio** & & \\ \hline \multirow{4}{*}{Bialelin} & \multirow{4}{*}{Up to 5 \(\mu\)M} & HeLa cells, A549 cells, HepG2 cells & No & Activated AMPK via a & \multirow{4}{*}{[59]} \\  & & & cells, HepG2 cells & No & CaMKII\(\beta\)-dependent pathway, & \\  & & & cells, HepG2 cells & Increased intracellular calcium, and & & \\  & & & & reduced lipid accumulation. & & \\ \hline \multirow{4}{*}{Bialenia} & \multirow{4}{*}{400 mg/kg/day} & High-fat-diet-induced mice, primary hepatocytes & & \multirow{4}{*}{N.T} & Improved metabolic syndrome via the & \multirow{4}{*}{[61]} \\  & & & & & activation of AMPK\(\alpha\)2, inhibited & \\  & & & induced mice, & inflammation and insulin resistance, & & \\  & & & primary hepatocytes & & and promoted lipid oxidation through & \\  & & & & various pathways. & & \\ \hline \multirow{4}{*}{Quercetin} & \multirow{4}{*}{Up to 100 \(\mu\)M} & L6 myotubes & Yes (Increase) & Enhanced glucose uptake via the AMPK & \multirow{4}{*}{[62]} \\  & & (skeletal muscle cells) & Yes (Increase) & pathway and p38 MAPK, independent & \\  & & & [49] & of insulin signaling; involved changes in & \\  & & & [49] & mitochondrial potential and & \\  & & & & intracellular calcium. & \\ \hline \multirow{4}{*}{Genistein} & \multirow{2}{*}{20–200 \(\mu\)M} & 3T3-L1 adipocytes & Yes (Increase) [53] & Inhibited adipocyte differentiation and & \multirow{4}{*}{[63]} \\  & & & (cells) & (Increase) [53] & induced apoptosis in mature adipocytes & \\  & & & & via the rapid activation of AMPK. & \\ \hline \multirow{4}{*}{Derrone} & \multirow{4}{*}{Up to 25 \(\mu\)M} & \multirow{4}{*}{L6 myotubes (cells)} & \multirow{4}{*}{N.T} & Enhanced glucose uptake, activated & \multirow{4}{*}{[64]} \\  & & & & AMPK, increased GLUT4 and GLUT1 & \\  & & & & expression, and inhibited PTP1B activity & \\  & & & & without muscle cell toxicity. & \\ \hline \multirow{4}{*}{Alpinumisoflavone} & \multirow{4}{*}{Up to 25 \(\mu\)M} & \multirow{4}{*}{L6 myotubes (cells)} & \multirow{4}{*}{N.T} & Enhanced glucose uptake, activated & \multirow{4}{*}{[64]} \\  & & & & AMPK, upregulated GLUT4 and GLUT1 & \\  & & & expression, and inhibited PTP1B & \\  & & & & activity. & \\ \hline \multirow{4}{*}{Aspalathin} & \multirow{4}{*}{0.1\% (in diet)} & ob/ob mice, & \multirow{4}{*}{Yes (Increase)} & Increased glucose uptake, promoted & \multirow{4}{*}{[65]} \\  & & & & AMPK phosphorylation, enhanced & \\  & & L6 myotubes & & CLUT4 translocation, decreased fasting & \\  & & & blood glucose levels, and improved & \\  & & & glucose intolerance. & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: _Cont._tion without AMP. The \(\beta\) subunit, particularly the carbohydrate-binding module (CBM), plays a critical role in AMPK's stability and activation. Direct activators like A-769662 bind to the CBM, inducing structural changes that facilitate necessary phosphorylation events for AMPK activation. This allosteric activation mechanism allows AMPK to be activated even in the absence of AMP, highlighting the diverse pathways through which AMPK can be modulated for therapeutic benefits. In this review, 10 flavonoids known to activate AMPK were investigated. Among them, quercetin, genistein, and aspalathin have been shown to indirectly activate AMPK by modulating the cellular ADP/AMP ratio, which, in turn, adjusts energy homeostasis [62; 75; 76]. These compounds do not directly bind to AMPK but instead initiate its activation through changes in cellular energy status. Baicalin, however, activates AMPK via a different pathway. It induces AMPK activation through a CaMK\(\beta\)-dependent mechanism without altering the ADP/AMP ratio [46]. This indicates that AMPK activation can occur via calcium/CaMK\(\beta\), independent of direct energy shifts.