RESUMO
OBJECTIVES: The use of medicinal plants for diabetes treatment is increasing owing to their effectiveness and safety compared to synthetic drugs. Thus, the ameliorative effects of Azanza garckeana (F. Hoffm.) fractions in diabetes-induced dyslipidemia, hepatopathy, and nephropathy in rats were evaluated in this study. METHODS: Rats with alloxan (120 mg/kg body weight (BW))-induced diabetes were randomized into different groups (n=5) and treated with the crude methanolic extract, and fractions (n-hexane, ethyl acetate, and aqueous fractions) of A. garckeana each at 100, 200, and 400 mg/kg BW. Glibenclamide (5 mg/kg BW) was used as a reference drug, and all treatments were administered orally daily for 6 weeks. RESULTS: Our data revealed that treatment with the crude extract caused a dose-dependent hypoglycemic effect of 61.32±3.45%, 76.05±3.05%, and 78.59±5.90% at 100, 200, and 400 mg/kg BW, respectively and improved the BW of the animals. The extract also ameliorated the elevated cholesterol, triglyceride, low-density lipoprotein cholesterol, and increased serum levels of high-density lipoprotein cholesterol compared with untreated control animals. The extract also reversed serum biochemical alterations in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, total and direct bilirubin, urea, and uric acid that were observed in untreated diabetic rats. Interestingly, the A. garckeana fraction also exhibited significant protection against diabetes-induced dyslipidemia, hepatopathy, and nephropathy in rats, with the ethyl acetate fraction exhibiting a remarkable protective effect. The LC-MS characterisation of the active fraction identified the presence of various phenolic and flavonoid compounds that could be responsible for the bioactivity of the fraction. CONCLUSION: Collectively, this study suggests the potential application of A. garckeana for effective treatment of diabetic nephropathy, with the ethyl acetate fraction of this plant representing a reserve of potential candidates for developing new drugs.
RESUMO
The present study evaluated the polyphenolic contents and hypoglycemic, antioxidant, and anti-inflammatory effects of the diethyl ether fraction of Thespesia garckeana using various in vitro and in vivo models. Total phenol and flavonoid contents of the extract were 613.65 ± 2.38 and 152.83 ± 1.56 mg/100 g dry weight, respectively. The extract exhibited in vitro antioxidant activities against DPPH, FRAP, LPO, and ABTS with respective half-maximal inhibitory concentration (IC50) values of 30.91 ± 0.23, 16.81 ± 0.51, 41.29 ± 1.82, and 42.39 ± 2.24 µg/mL. In vitro anti-inflammatory studies using membrane stabilization, protein denaturation, and proteinase activities revealed the effectiveness of the extract with respective IC50 values of 54.45 ± 2.89, 93.62 ± 3.04, and 56.60 ± 2.34 µg/mL, while in vitro hypoglycemic analysis of the extract revealed inhibition of α-amylase (IC5064.59 ± 3.29 µg/mL) and enhancement of glucose uptake by yeast cells. Interestingly, the extract demonstrated in vivo hypoglycemic and anti-inflammatory effects in streptozotocin- (STZ-) induced diabetic and xylene-induced ear swelling models, respectively. In addition, the extract improved insulin secretion, attenuated pancreatic tissue distortion and oxidative stress, and increased the activities of superoxide dismutase (SOD), catalase, and reduced glutathione (GSH), while reducing the concentration of LPO in the diabetic rats. A high-performance liquid chromatography (HPLC) analysis identified the presence of catechin (6.81e - 1 ppm), rutin (8.46 e - 1 ppm), myricetin, apigenin (4.019 e - 1 ppm), and luteolin (15.09 ppm) with respective retention times (RTs) of 13.64, 24.269, 27.781, 29.58, and 32.23 min, and these were subjected to a pharmacoinformatics analysis, which revealed their drug-likeness and good pharmacokinetic properties. A docking analysis hinted at the potential of luteolin, the most abundant compound in the extract, for targeting glucose-metabolizing enzymes. Thus, the present study provides preclinical insights into the bioactive constituents of T. garckeana, its antioxidant and anti-inflammatory effects, and its potential for the treatment of diabetes.
