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  • The inhibitory preference of B eurycoma

    2018-10-22

    The inhibitory preference of B. eurycoma and D. microcarpum extracts for α-glucosidase over α-amylase observed in this study is of interest as it may give the extracts pharmacological advantage over acarbose, a widely used synthetic oral hypoglycemic drug. Acarbose inhibits both α-amylase and α-glucosidase, but has some clinical side effects such as diarrhea, flatulence and abdominal discomfort which have been attributed to its excessive inhibition of pancreatic α-amylase [20]. Hence, the stronger inhibitory effect of the extracts on α-glucosidase than α-amylase may suggest lesser clinical side effects than acarbose. This finding is consonant with an earlier report that unlike acarbose, α-amylase and α-glucosidase inhibitors of plant origin have a stronger inhibitory effect on α-glucosidase activity than α-amylase activity [20]. The inhibition of AR activity by plant extracts has been reported as a possible therapeutic approach to ameliorating diabetic complications [7]. AR belongs to the aldo–keto reductase super family that reduces excess D-glucose into D-sorbitol with concomitant conversion of NADPH into NADP+[35], in the polyol pathway where it serves as the first and rate-limiting enzyme. This AR-catalyzed reaction that is favored in hyperglycemic condition has been implicated in the complications of DM, as previous studies provided evidence for the involvement of AR in diabetic neuropathy, retinopathy, nephropathy and cataract [36]. Abnormal activation of the polyol pathway during diabetes leads to accumulation of osmotically active sorbitol, which results in osmotic and oxidative stress that culminate in tissue injury [37]. In this study, both B. eurycoma and D. microcarpum seeds flour extracts inhibited AR in a dose-dependent manner, suggesting that they have the potential to mitigate the complications of T2D. However, the lower IC50 value of B. eurycoma relative to that of D. microcarpum indicates that B. eurycoma could be more potent than D. microcarpum. The result further showed that both extracts inhibited Fe2+-induced lipid peroxidation in rat dna pk homogenate in a dose-dependent pattern. Lipid peroxidation is an oxidative deterioration of polyunsaturated lipids, involving reactive oxygen species and transition metal ions, which yield diverse cytotoxic products, most of which are aldehydes [38]. These products, such as malondialdehyde (MDA), can impair membrane function; inactivate membrane-bound receptors and enzymes, and increase tissue permeability [39]. If not controlled, lipid peroxidation will in turn result in increased production of free radicals that can cause oxidative damage to the body cells, including the β-cells of the pancreas [40]. Hence, lipid peroxide-mediated tissue damages have been observed in type 1 and type 2 DM [41]. The ability of B. eurycoma and D. microcarpum extracts to inhibit Fe2+-induced lipid peroxidation in rat pancreas, therefore suggests that both seeds might be helpful in alleviating the vulnerability of the beta-cells of the pancreas to oxidative damage in T2D. However, as with the carbohydrate-metabolizing enzymes inhibition results B. eurycoma had a stronger inhibitory effect on lipid peroxidation than D. microcarpum. Increase in the free radicals and reactive oxygen species burden of the body without a corresponding robust antioxidant defense system leads to oxidative stress, which plays an important role in the pathogenesis of degenerative diseases such as diabetes [42]. Consequently, the ability of the extracts to scavenge DPPH and ABTS+ was tested (Table 2). The results revealed that both extracts scavenged both DPPH and ABTS+ to various extents. DPPH is a stable free radical with characteristic deep purple color in solution; antioxidants react with converting it to α,α-diphenyl-β-picryl hydrazine. DPPH solution loses its characteristic deep purple color, on accepting proton from antioxidants, leading to absorption decrease (λmax 515–517nm). Thus, the degree of discoloration is an indication of the scavenging ability of the antioxidant extract. Evidently, B. eurycoma exhibited a stronger DPPH scavenging ability than D. microcarpum, due to its lower IC50 value. The ABTS+ scavenging result of the extracts followed the same trend as the DPPH result, with B. eurycoma being significantly (P<0.05) higher than D. microcarpum. Unlike DPPH, ABTS+ is a moderately stable nitrogen-centered species, and the assay involves electron transfer process [43]. The reaction of ABTS+ with antioxidants results in its discoloration, and the level of discoloration reflects the amount of ABTS+ that is scavenged within a given time period in relation to that of Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). Both extracts were able to reduce Fe3+ to Fe2+, although B. eurycoma had a significantly (P<0.05) higher reducing power than D. microcarpum.