Alkaloids of Calanthe davidii ameliorate STZ-induced diabetes by suppressing oxidative stress and inflammation.

BACKGROUND

Diabetes mellitus has become an epidemic worldwide. Although several oral antidiabetic drugs are currently available in clinical practice, most of these drugs are often inadequate in restoring β-cell function or effectively preventing the onset of diabetic complications. In our previous study, we found that the Tujia ethnic medicine, Calanthe davidii showed potential antidiabetic and hepatoprotective properties. However, its active constituents and the mechanisms are still unclear.

PURPOSE: To assess the anti-diabetic efficacy of alkaloids of C. davidii (CdA) in vivo, and further identify the active constituents and uncover their underlying mechanisms.

METHODS

DPPH• and OH• scavenging assays, ferric-reducing power test, anti-lipid peroxidation test, and LPS-stimulated macrophage model were employed to verify the antioxidant and anti-inflammatory properties of CdA in vitro. The antidiabetic activity and preliminary mechanisms of CdA were elucidated in mice with STZ-induced diabetes. Various chromatographic and spectroscopic techniques were used to purify and characterize chemical constituents. ELISA, RT-qPCR, RNA-seq, immunofluorescence, and western blotting were explored to elucidate the mechanism of the active ingredients.

RESULTS

CdA significantly inhibited hyperglycemia, ameliorated pancreatic β-cell damage, mitigated redox imbalance and inflammatory response in diabetic mice, and notably attenuated liver injury in diabetic mice. The phytochemical study resulted in the acquisition of nine alkaloids. Among them, glucoindican was identified as the primary active constituent, which potently inhibited the NF-κB, MAPK, and PI3K/AKT cascades, consequently blocking the synthesis of pro-inflammatory cytokines to treat diabetes.

CONCLUSION

CdA possesses notable antidiabetic functions in vivo. The indole alkaloids are the main components of CdA, and the underlying mechanism mainly includes antioxidation and anti-inflammation. These findings provide evidence for the potential translation of C. davidii into a therapeutic agent for the treatment of diabetes.