Metabolite profiling and biochemical investigation of the antidiabetic potential of Loranthus pulverulentus Wall n-butanol fraction in diabetic animal models

Abstract

Ethnopharmacological relevanceGlobally, 537 million individuals are estimated to have diabetes. The traditional use of herbs for ameliorating diabetes symptoms is a common practice in Pakistan and use of Loranthus pulverulentus Wall (L. pulverulentus) by local people in Azad Jammu and Kashmir has been reported. Aim of the studyIn the present study, the antidiabetic potential of standardized n-butanol fraction of leaves of L. pulverulentus Wall, which is a parasite of Dalbergia sisso Roxb was assessed in both alloxan (ALX) and streptozotocin (STZ) diabetic animal models. Materials and methodsChemical characterization of BF was performed using HPLC, GCMS and UHPLC-MS. The effect of the fraction (250 mg/kg) on insulin, plasma free fatty acids, L-lactate, pyruvate, MDA, HbA1c and glycogen levels in ALX and STZ animal models was determined. Liver and renal profiles were analyzed in the STZ model. Toxicological studies were performed by hemolytic, Ames mutagenicity, DNA protection, and thrombolytic assays. Histopathological analysis of the pancreas, liver, and kidney was performed. ResultsBF demonstrated highly significant (p < 0.001) antidiabetic potential in both diabetic models. BF significantly (p < 0.05) improved OGTT results in alloxanized diabetic mice and blocked the absorption of glucose from the gut. A significant (p < 0.001) increase in insulin levels and glycogen content in liver tissue and a decrease in plasma FFA, MDA, HbA1c, L-lactate, and pyruvate levels in STZ-diabetic mice were recorded. GC-MS and chromatographic analysis showed the presence of catechin, eugenol, longifolene, caryophyllene, Ar-tumerone and Geranyl-alpha-terpinene. Various metabolites with antidiabetic potential, including 4-hydroxycinnamyl alcohol 4-D-glucoside, zingerone glucoside, trans-trismethoxy resveratrol-d4, epigallocatechin 3-O-cinnamate, and β-glucogallin, were identified using UHPLC-MS. Animals treated with BF showed marked improvements in cellular structures of the pancreas, liver and kidneys. This fraction is non-mutagenic and protects the DNA. ConclusionThe experimental fraction contained potential antidiabetic bioactive compounds responsible for alleviating diabetes-associated biochemical dysregulation. The fraction increased insulin levels and enhanced glycogen storage in muscles and the liver. It blocked glucose absorption from the intestine and substantially decreased HbA1c, lactate, pyruvate, free fatty acids, lipid, liver and kidney damage. Therefore, the use of BF for the treatment of type-2 diabetes may be beneficial.