## 3 Discussion  
PTPs such as PTPN11, PTPN2, PTP1B, DUSP9, PTPRS, and PTPN9 are known to be associated with T2 DM, and the use of PTP inhibitors is considered an effective strategy for T2 DM treatment [19]. In previous research, we demonstrated that several natural products have antidiabetic effects by inhibiting PTPs linked to insulin resistance [8]. Specifically, we showed that ginkgolic acid, acting as a dual-targeting inhibitor of PTPN9 and DUSP9, enhances glucose uptake in 3T3-L1 adipocytes and C2C12 muscle cells by activating the AMPK signaling pathway, which suggests that ginkgolic acid has potential as a therapeutic candidate for T2 DM [19]. In our current study, we isolated ginkgolic acid derivatives and evaluated their inhibitory activity against specific PTPs, including PTP1B, PTPN2, PTPN9, PTPN11, DUSP9, and PTPRS, all associated with insulin resistance. When comparing the inhibition rates of these compounds, structural isomers 1 and 2, both featuring a hydroxy group, displayed similar inhibitory rates, which were lower than that of compound **4**, having the same length of the aliphatic chain. From these results, we can infer that the length of the aliphatic chain and the presence of a hydroxy group in the chain are important factors influencing the PTP inhibitory activity of ginkgolic acid derivatives. It is anticipated that ginkgolic acids with longer aliphatic chains and the absence of a hydroxy group in the chain will demonstrate more potent inhibitory activity against PTPs. The findings support the idea that both compound **5**, possessing a hydroxy group and a longer chain length than 1, and compound **3**, with no hydroxy group and a shorter chain length than 1, exhibited potent inhibitory activity. These results underscore the importance of chain length concerning PTP inhibitory activity [19] and suggest that functional group substitutions within the chain can significantly impact this activity. To reiterate, our study showcases that these six compounds (**1-6**) effectively inhibit the catalytic activity of specific PTPs associated with insulin resistance, highlighting their potential as PTP inhibitors. Exploring whether these six compounds can enhance glucose uptake by inhibiting PTPs would be an intriguing direction for future research. Natural product discovery for the treatment of diabetes is an area of growing interest in the field of medical research. The search for effective treatments for diabetes has led researchers to explore the vast reservoir of natural products found in plants, microorganism \begin{table}
\begin{tabular}{c c c c c c c} \hline  & **PTPN11** & **PTPN2** & **PTP1B** & **DUSP9** & **PTPRS** & **PTPN9** \\ \hline
**1** & 98.18 a & 92.83 & 79.8 & 82.21 & 62.58 & 65.39 \\
**2** & 98.11 & 92.29 & 81.66 & 81.07 & 41.55 & 59.39 \\
**3** & 98.84 & 94.4 & 98.97 & 90.98 & 99.31 & 96.06 \\
**4** & 98.9 & 96.2 & 99.27 & 94.8 & 99.33 & 96.85 \\
**5** & 98.81 & 97.76 & 99.22 & 95.66 & 99.54 & 98.77 \\
**6** & 97.83 & 72.5 & 71.86 & 6.25 & 56.55 & 42.48 \\ \hline \end{tabular} a  
\end{table} 
Table 1: Inhibition of PTPs by compounds **1–6** (50 \(\mu\)M). Figure 3: IC\({}_{50}\) values of compound **3** for PTP1B (**a**), PTPN9 (**b**), and PTPN11 (**c**) were estimated using a sigmoid curve against percent inhibition (%) for compound **3**. isms, and other natural sources. This approach capitalizes on the diverse array of bioactive compounds present in nature, offering a rich pool of potential therapeutic agents. One noteworthy aspect of natural product discovery is its incorporation of traditional medicine systems. Ancient practices like ayurveda and traditional Chinese medicine have long utilized natural products for various ailments, including diabetes. These traditions provide valuable insights and starting points for modern scientific investigation. Natural products with antidiabetic properties often act through multiple mechanisms. These may include enhancing insulin sensitivity, reducing blood glucose levels, protecting pancreatic beta cells, and mitigating oxidative stress.