Luteolin: A Promising Natural Flavonoid for Ulcerative Colitis Treatment Through Mitochondrial and Notch Pathway Modulation
A recent study published in the Journal of Functional Foods by researchers from Hebei University of Chinese Medicine and Hebei Province Hospital of Chinese Medicine sheds light on the therapeutic potential of luteolin (Lut), a natural flavonoid, in addressing ulcerative colitis (UC). The research offers significant insights into how Lut influences mitochondrial dynamics and the Notch signalling pathway, presenting a promising avenue for the medical application of flavonoid compounds in inflammatory diseases.
Histopathological architecture of colon and histopathologic scores of the colon in mice following different treatment regimens. Credits: Liu, Moxixuan, et al. Journal of Functional Foods 124 (2025): 106644.
Protective Effect on UC-Induced Colonic Damage
The study demonstrated that Lut treatment alleviates dextran sulphate sodium (DSS)-induced intestinal mucosal injury in UC mice. This protective effect is closely associated with the regulation of the Notch signalling pathway, evidenced by the reduced expression of critical components such as Notch1, Notch2, RBPJ, MAML1, Hes1, Jagged1, and DLL4 in colonic tissues following Lut administration.
Role of miR-195-5p in Notch Signalling Regulation
The research highlights miR-195-5p as a critical mediator in the negative feedback regulation of the Notch signalling pathway. In vitro experiments using Caco-2 cells further substantiated the inhibitory role of miR-195-5p in the pathway.
Enhancement of Mitochondrial Dynamics
Lut demonstrated a restorative impact on mitochondrial dynamics by:
- Increasing the expression of mitochondrial fusion factors MFN1 and MFN2.
- Reducing the expression of mitochondrial fission factors Fis1 and Crmp1.
- Improving mitochondrial morphology, membrane potential, and energy metabolism.
These findings highlight Lut’s potential to counteract the mitochondrial dysfunction commonly associated with UC.
Effective Dosage
In animal models, a dosage of 100 mg/kg/day of Lut exhibited superior therapeutic benefits compared to 50 mg/kg/day, reinforcing its efficacy in mitigating UC-associated damage.
Implications for LPS-Induced Injury
The study also explored the effects of Lut on LPS-induced injury in Caco-2 cells. Lut effectively restored mitochondrial viability, improved fusion dynamics, and attenuated the activation of the Notch signalling pathway, showcasing its broader applicability.
This research highlights the growing interest in natural compounds like flavonoids for treating inflammatory diseases such as UC. By elucidating the mechanisms of Lut’s action, including its interplay with mitochondrial dynamics and Notch signalling, the study provides a robust foundation for the medical application of these compounds. Further clinical investigations could pave the way for incorporating Lut into therapeutic strategies for UC and related conditions.
