Molecular modeling of Ruellia tuberosa L compounds as a-amylase inhibitor: an in silico comparation between human and rat enzyme model

Abstract

Inhibition of α-amylase is an important strategy to control post-prandial hyperglycemia. The present study on Ruellia tuberosa, known as traditional anti-diabetic agent, is being provided in silico study to identify compounds inhibiting α-amylase in rat and human. Compounds were explored from PubChem database. Molecular docking was studied using the autodock4. The interactions were further visualized and analyzed using the Accelrys Discovery Studio version 3.5. Binding energy of compounds to α-amylase was varying between -1.92 to -6.66 kcal/mol in rat pancreatic alpha amylase and -3.06 to -8.42kcal/mol in human pancreatic alpha amylase, and inhibition konstanta (ki) was varying between 13.12- 39460µM in rat and 0.67-5600µM in human. The docking results verify that betulin is the most potential inhibitor of all towards rat model alpha amylase and human alpha amylase. Further analysis reveals that betulin could be a potential inhibitor with non-competitive pattern like betulinic acid. In comparison, betulin has smaller Ki (0.67µM) than acarbose (2.6 µM), which suggesting that betulin is more potential as inhibitor than acarbose, but this assumption must be verified in vitro.

A Multidirectional Perspective for Novel Functional Products: In vitro Pharmacological Activities and In silico Studies on Ononis natrix subsp. hispanica

“…Evidence from the literature supports the inhibitory action of apigenin on AChE and BChE (Katalinić et al, 2010 ; Xie et al, 2014 ). Apigenin was also reported to induce moderate inhibitory effect on α-amylase (Li et al, 2014 ; Wulan et al, 2014 ) and on α-glucosidase. On the other hand, we have found that the water extract possesses good inhibition activity toward tyrosinase.…”

Antidiabetic Activity ofRuellia tuberosaL., Role ofα-Amylase Inhibitor:In Silico,In Vitro, andIn VivoApproaches

“…Thus, the molecular docking predictions were used to find the probable inhibition mechanism. Ratna Wulan et al [ 8 ] have also reported in silico study that Betulin, steroid compound of R. tuberosa L., is an α -amylase inhibitor. Bisdemethoxycurcumin, Curcumin, Betulinic acid, and Betulin have a small E bingding , and a small inhibition Constanta ( k i ).…”

“…Betulin, an α -amylase inhibitor in R. tuberose , as a ligand [ 8 ], and maltose as a substrate were docked into Rattus α -amylase model. The Rattus α -amylase model is created according to Ratna Wulan et al [ 8 ]. The study about inhibition mechanism (competitive, uncompetitive, or noncompetitive) of Betulin has not been published yet.…”

“…In silico investigation of R. tuberosa L. compounds showed that the most potential inhibitor towards rat model α -amylase and human α -amylase is Betulin. Furthermore, the approximation based on the inhibition constant k i suggests that Betulin is more potential as an inhibitor α -amylase rather than Acarbose [ 8 ], but inhibition mechanism of Betulin has not been studied yet. Understanding the mechanism of action and inhibition mechanism of the target enzyme is critical in the early discovery and development of drug candidates.…”

Analysis on evolutionary relationship of amylases from archaea, bacteria and eukaryota

“…On the one hand, α-amylase plays a role in degradation of dietary components by digestive tract microbiotic flora (Tzuc et al 2014 ). On the other hand, inhibition of α-amylase is equally important for the control of post-prandial hyperglycemia (Wulan et al 2014 ), so the inhibition of human salivary α-amylase could be potentially useful in the prevention and treatment of obesity and type 2 diabetes as well (Bharathi et al 2014 ; Gupta et al 2014 ; Podsędek et al 2014 ; Tiwari 2014 ). In addition, applications of α-amylase are widely used in fruit juice industry (Dey and Banerjee 2014 ), for example, bioconversion of wastes into hydrogen and methane (Kumar et al 2014 ), bioethanol production (Pervez et al 2014 ), textile industry (Deng et al 2014 ), chicken feed enzyme (Jianhua et al 2014 ), paper recycling (Raul et al 2014 ), and detergent industry (Zaferanloo et al 2014 ).…”