Vindoline is a key component of Catharanthus roseus leaf juice extract prepared through an Ayurveda-based method for ameliorating insulin-resistant type 2 diabetes

Catharanthus roseus leaves have been traditionally described to possess potent antidiabetic activity and some leaf-specific alkaloids, including vindoline, have been studied for their antidiabetic potential. The aim of the present study was to validate the antidiabetic property of the plant with special reference to vindoline. An Ayurveda-based method was used to prepare the Swaras [leaf juice extract (LJE)] of three familial C. roseus genotypes differing in their vindoline content [CIM-Sushil (CS) > Dhawal (D) > Nirmal (N)]. In vivo experiments using LJE were performed in Charles Foster rats, whereby metformin (M100, 100 mg/kg BW) and vindoline (V20, 20 mg/kg BW) were used for comparison. OGTT-based screening for LJE doses (N100, N300, N500, D100, D200, D300, CS100, CS200, CS300 mg/kg BW) was carried out. Further analysis of the effective doses (D100, D200, D300, CS100, CS200, CS300) in streptozotocin-induced diabetic rats indicated highest blood glucose depletion in D300 (52.51%) and CS200 (64.55%) together with V20 (56.96%) on the 14th day. CS-LJE was found to be safe up to 2000 mg/kg BW. The role of LJE/vindoline in maintaining glucose homeostasis in liver was found to be mediated through the expression of insulin pathway genes (IRS-1, PI3K, AKT, GLUT2). TNF-α-induced insulin resistance in L6 skeletal muscle cells was used to analyze the effect of LJE/vindoline through glucose uptake assay and expression analysis of insulin pathway genes (IRS-1, PI3K, AKT, GLUT4). The results indicated that the antidiabetic effect of LJE/vindoline is mediated through activation of IRS/PI3K/AKT/GLUT signaling pathway.