<i>Glycyrrhiza glabra</i> alcoholic root extract ameliorates hyperglycemia, hyperlipidemia, and glycation‐induced free iron‐mediated oxidative reactions

Hyperglycemia-associated oxidative stress leads to various pathophysiological complications in diabetes mellitus. Here, the effects of Glycyrrhiza glabra (G. glabra) root extract of streptozotocin (STZ)-induced diabetic changes and the associated free iron-mediated oxidative reactions were investigated. The animals were divided into five group, Group 1: Control (NC received buffer); Group 2: STZ-induced (DC); Group 3: Control treated with G. glabra root extract (NT, 60 mg/Kg b.w daily for 1 month); Group 4: Diabetic treated with the extract (60 mg/Kg b.w daily for 1 month); Group 5: Diabetic treated with glibenclamide (DTG, 8.6 mg/Kg b.w for 1 month). STZ (i) induced hyperglycemia, abnormal intraperitoneal glucose tolerance test (IPGTT), increased HbA1c and decreased plasma insulin levels (ii) hyperlipidemia (iii) lowered antioxidant enzyme activities (iv) diminished RBC membrane fluidity (v) enhanced hemoglobin glycation-induced iron release and associated free radical reactions. Treatment with the extract resulted in significant reversal of hyperglycemia (DC: 205.0 ± 7.0 mg/dl vs. DT: 87.5 ± 4.5 mg/dl, p < .05); HbA1c (DC: 11.5 ± 2.0 vs. DT: 7.5 ± 0.8 vs. DT: 7.5 ± 0.8, p < .05); insulin (DC: 0.3 ± 0.06 vs. DT: 1.25 ± 0.15 μgm/L, p < .05); free iron (DC: 150.4 ± 7.07 vs. DT: 98.8 ± 7.7 μgm/gm of Hb, p < .05); TBARS (DC + H2 O2 : 24.62 ± 11.30 vs. DC + H2 O2 : 9.82 ± 2.56 mmoles/h, p < .05); carbonyl (DC: 40.40 ± 1.57 vs. DT: 25.50 ± 1.12 mmoles/g of Hb, p < .05) levels and β-cell count/pancreatic islet (DC: 85 ± 15 vs. DT: 125 ± 20, p < .05). Thus, G. glabra extract is quite effective against hyperglycemia and the associated free iron-mediated oxidative stress. PRACTICAL APPLICATIONS: Chronic use of oral hypoglycemic synthetic drugs may produce side effects and drug resistance. Recently, various plant extracts are being researched to explore their antihyperglycemic potential. Here, the effects of this alcoholic powdered root extract on STZ-induced diabetic changes and associated oxidative stress, including hemoglobin-induced free iron-mediated oxidative reactions were examined. The STZ-induced diabetic changes and hemoglobin-glycation-induced free iron-mediated oxidative reactions were alleviated in the Wistar rats after 1-month of treatment with the extract. We have also reported previously that glycyrrhizin, a bioactive constituent of Glycyrrhiza glabra root inhibits peroxidase, esterase activities of hemoglobin and hemoglobin-mediated oxidative damage without affecting oxygen-binding capacity of the protein. This preclinical work further substantiates the potential therapeutic use of the G. glabra whole root extract in the treatment of diabetes mellitus.