Molecular and Biochemical Pathways of Catalpol in Alleviating Diabetes Mellitus and Its Complications

Catalpol isolated from Rehmannia glutinosa is a potent antioxidant and investigated against many disorders. This review appraises the key molecular pathways of catalpol against diabetes mellitus and its complications. Multiple search engines including Google Scholar, PubMed, and Science Direct were used to retrieve publications containing the keywords Catalpol, Type 1 diabetes mellitus, Type 2 diabetes mellitus, and diabetic complications. Catalpol promotes IRS-1 /PI3K/AKT/GLUT2 activity and suppresses Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase) expression in the liver. Catalpol induces myogenesis by increasing MyoD/MyoG/MHC expression and improves mitochondria function through the AMPK/PGC-1 alpha/PPAR-gamma and TFAM signaling in skeletal muscles. Catalpol downregulates the pro-inflammatory markers and upregulates the anti-inflammatory markers in adipose tissues. Catalpol exerts antioxidant properties through increasing superoxide dismutase (sod), catalase (cat), and glutathione peroxidase (gsh-px) activity in the pancreas and liver. Catalpol has been shown to have antioxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis properties that in turn bring beneficial effects in diabetic complications. Its nephroprotective effect is related to the modulation of the AGE/RAGE/NF-kappa B and TGF-beta /smad2/ 3 pathways. Catalpol produces a neuroprotective effect by increasing the expression of protein Kinase-C (PKC) and Cav-1. Furthermore, catalpol exhibits a cardioprotective effect through the apelin/APJ and ROS/NF-kappa B/Neat1 pathway. Catalpol stimulates proliferation and differentiation of osteoblast cells in high glucose condition. Lastly, catalpol shows its potential in preventing neurodegeneration in the retina with NF-kappa B downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications.

Automated summary

Catalpol isolated from Rehmannia glutinosa shows potent antioxidant properties and has been investigated for its effects on diabetes mellitus and its complications. The molecular pathways involved include promoting IRS-1/PI3K/AKT/GLUT2 activity, suppressing PEPCK and G6Pase expression in the liver, inducing myogenesis in skeletal muscles, and exerting antioxidant effects in the pancreas and liver. Catalpol also demonstrates neuroprotective, cardioprotective, and osteoblast stimulating effects, as well as potential in preventing neurodegeneration in the retina.