Emerging evidence suggests that hypothalamic inflammation plays a critical role in the disruption of whole-body glucose homeostasis. We found that butein, a rare chalcone found in the toxic plant Toxicodendron vernicifluum, modulates glucose metabolism by inhibiting the pro-inflammatory IKKβ/NF-κB signaling pathway in the brain (1).
We investigated whether the non-toxic plant Dahlia pinnata could serve as a natural and safe source of butein for therapeutic use in type 2 diabetes (T2D). In mice fed a high-fat diet (HFD) to induce glucose intolerance, oral administration of D. pinnata petal extract significantly improved glucose tolerance at doses of 3.3 and 10 mg/kg body weight. Interestingly, the beneficial effect was not due to butein alone, but to a synergistic interaction between butein and the structurally related flavonoids—sulfuretin and/or isoliquiritigenin.
Mechanistically, the extract enhanced systemic insulin sensitivity. Central insulin signalling was shown to be essential: pharmacological inhibition of brain phosphatidylinositol 3-kinase abolished the extract’s glucoregulatory effects. The extract restored hypothalamic insulin signalling and reversed HFD-induced astrogliosis, indicating a central anti-inflammatory mode of action.
To translate these findings to humans, we conducted a randomized, controlled cross-over clinical trial in individuals with prediabetes or T2D. The extract demonstrated efficacy in improving glucose regulation without any recorded side effects.
These discoveries have led to the development of a patented and fully commercialized D. pinnata extract, now available globally. Ongoing research currently focusses on additional health applications of the dahlia extract.
In summary, we have identified a safe, plant-derived extract that targets hypothalamic inflammation and central insulin signalling, offering a novel and mechanistically grounded option for supporting glucose metabolism.