Flavonoid compound from Agrimonia pilosa Ledeb improves adipose insulin resistance by alleviating oxidative stress and inflammation

by Selleckchem | Nov 09 2023

Background: Researches and practice of traditional Chinese medicine indicated that Agrimonia pilosa Ledeb could improve insulin resistance (IR) and treat type 2 diabetes (T2DM). To reveal its underling mechanisms, we isolated Flavonoid component (FC) from Agrimonia pilosa Ledeb and elucidated its effects on glucose metabolism to improve IR by suppressing oxidative stress and inflammation.

Methods: Adipocytes or mice IR model was established with overdosed glucose and insulin or high-fat diet. The uptake of 2-NBDG and glucose consumption were measured to verify insulin sensitivity in vitro and vivo. Reactive oxidative species (ROS) were detected by flow cytometry, and superoxide dismutase (SOD) activity as well as the malondialdehyde (MDA) content were also measured. Meanwhile, factors associated with insulin signal pathway including PPARγ, insulin receptor substrate-1 (IRS-1), GLUT4, and oxidative stress including NF-E2-related factor 2 (Nrf2), as well as the related inflammatory cytokines such as NF-κB, IL-1β, IL-6 and TNF-α were tested. Furthermore, the JNK/PI3K/Akt signal pathway was also explored.

Results: FC extracted from Agrimonia pilosa Ledeb ameliorated the impaired glucose metabolism significantly. Further study indicated that FC could regulate the insulin signal pathway to improve insulin resistance. Moreover, it could upregulate PPARγ with the similar efficacy as pioglitazone (Piog) straightway. FC also decreased the endogenous ROS and MDA content, increased SOD activity and Nrf2 expression to facilitate oxidative homeostasis. It attenuated expression and secretion of inflammatory cytokines obviously. At last, our results indicated JNK/PI3K/Akt pathway was regulated by FC in adipocytes and adipose tissue.

Conclusion: FC could ameliorate glucose metabolism and improve IR. It exerted these effects by suppressing oxidative stress and inflammation. FC from Agrimonia pilosa Ledeb has a good prospect to be drugs or functional foods for IR and T2DM.

Comments:

The study you described investigates the potential of a flavonoid component (FC) isolated from Agrimonia pilosa Ledeb, a traditional Chinese medicinal plant, in improving insulin resistance (IR) and treating type 2 diabetes (T2DM). The researchers aimed to elucidate the underlying mechanisms behind these effects, particularly focusing on glucose metabolism, oxidative stress, inflammation, and insulin signaling pathways. Here's a breakdown of the key findings:

1. **Experimental Models**: The study involved both in vitro and in vivo experiments. Adipocytes and mice were used to create IR models by exposing them to excessive glucose and insulin or a high-fat diet.

2. **Improved Insulin Sensitivity**: FC extracted from Agrimonia pilosa Ledeb was found to significantly improve impaired glucose metabolism. This improvement indicated that FC had a positive impact on insulin sensitivity.

3. **Regulation of Insulin Signaling Pathway**: FC was shown to regulate the insulin signaling pathway. It likely enhanced insulin sensitivity by influencing factors associated with insulin signaling, including PPARγ, insulin receptor substrate-1 (IRS-1), and GLUT4.

4. **Oxidative Stress**: FC reduced the levels of reactive oxidative species (ROS) and malondialdehyde (MDA) content, while increasing superoxide dismutase (SOD) activity. These changes suggest that FC helped maintain oxidative homeostasis.

5. **Inflammation**: FC decreased the expression and secretion of inflammatory cytokines such as NF-κB, IL-1β, IL-6, and TNF-α. This anti-inflammatory effect is beneficial in managing IR and T2DM, as inflammation is often associated with these conditions.

6. **Nrf2 Pathway**: FC upregulated NF-E2-related factor 2 (Nrf2), which plays a key role in cellular defense against oxidative stress. This could contribute to the reduction in oxidative stress observed in the study.

7. **JNK/PI3K/Akt Pathway**: The study also explored the JNK/PI3K/Akt signal pathway. FC was found to regulate this pathway in both adipocytes and adipose tissue, which may be linked to its effects on insulin sensitivity.

In summary, the study suggests that the flavonoid component extracted from Agrimonia pilosa Ledeb has the potential to ameliorate glucose metabolism and improve insulin resistance. It achieves these effects by reducing oxidative stress and inflammation, as well as regulating key signaling pathways associated with insulin sensitivity. This research indicates that FC could be considered as a potential candidate for the development of drugs or functional foods for managing insulin resistance and type 2 diabetes. However, further research, including clinical trials, would be needed to confirm these findings and assess the safety and efficacy of FC as a treatment option.