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

Abstract

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-1α/PPAR-γ 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 anti-oxidative, 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-κB and TGF-β/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-κB/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-κB downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications.

Regulation of Apelin-13 on Bcl-2 and Caspase-3 and Its Effects on Adipocyte Apoptosis

“…e precursor peptide source of apelin is composed of 77 amino acid residues, and the C-terminal of its carboxyl group is a synthetic peptide sequence that can be decomposed by peptidase into a variety of mature apelin active peptides, including apelin- 10, 11, 12, 13, 15, 17, 19, 28, 36, etc., of which apelin-13 has the strongest biological activity [8]. Studies have shown that apelin-13 can improve heart failure, pulmonary hypertension, pancreatic injury, etc., and can also protect neurovascular injury and relieve pain [9][10][11]. Studies have also shown that apelin-13 is closely related to obesity, but its specific mechanism is not yet clear.…”

Placental and plasma early predictive biomarkers for gestational diabetes mellitus

“…Several studies have reported that the TGF‐β signaling pathway plays an important role in the development of insulin resistance and obesity [37 ‐ 39]. CD109, an upstream factor of TGF‐β/Smad2/3, is important for attenuating diabetic renal fibrosis through inactivation of the TGF‐β/Smad2/3 pathway, and could be a new therapeutic approach for diabetic nephropathy [40]. In the present study, we found for the first time that the expression of CD109 protein was significantly lower in the placental tissue and early pregnancy plasma of patients with GDM, and may therefore be a potential predictive biomarker for GDM.…”

Effects of high-dose folic acid on protein metabolism in breast muscle and performance of broilers

“…The process of skeletal muscle myogenesis is closely regulated by myogenic regulatory factors (MRFs), which means that muscle protein synthesis is inseparable from that ( Kevin et al, 2012 ; Zammit, 2017 ; Hwang et al, 2019 ). MyoD is a myogenic regulatory factor that can activate the myogenic differentiation program along with the downstream myogenin ( MyoG ) ( Zammit, 2017 ; Bhattamisra et al, 2021 ). Previous studies indicated that folic acid increased the mRNA expression of MRFs and induced the myogenic differentiation in C2C12 cell ( Hwang et al, 2018 ).…”