Inhibitor discovery from pomegranate rind for targeting human salivary α-amylase
This study explored the effects of the main active compounds of the pomegranate (Punica granatum L.) rind extract on the activity of the human salivary α-amylase and their molecular inhibitory mechanisms. Four compounds exhibited remarkable inhibitory activities against α-amylase, including (1) rutin, (2) luteolin, (3) quercetin, and (4) kaempferol. The IC50 values were found to be 265.65, 59.67, 99.56, and 139.72 μM for rutin, luteolin, quercetin, and kaempferol, respectively. The kinetic study using the Lineweaver–Burk revealed the four compounds showed a non-competitive inhibition against α-amylase. However, the exact localization of the binding site and the potentiation mechanism at the molecular level are presently unknown. We have performed the “blind docking” of four compounds on the human salivary α-amylase. The molecular modeling demonstrated a high affinity and tight binding capacity of these compounds at the binding site of α-amylase, where the Glu 233 was supposed to play a key role in exerting the inhibition activity of these compounds. The results may provide an important insight for the applications of computational methods in the drug design with treating disorders of carbohydrate metabolism.
KeywordsPomegranate rind Human salivary α-amylase Inhibition activity Molecular docking Molecular dynamics simulation
This work was supported by grants from the National Natural Science Foundation of China (NO. 81173487, 81373904 and 81673535), Science and Technology Program of China (NO. 2014FY111100) and Special Scientific Research of Chinese Medicine Industry (NO. 201307008).
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Conflict of interest
The authors declare that they have no conflict of interest.
- Azhari SJ, Mlahi MR, Mostafa MM (2015) Comparative studies between 4-allyl-, 4-phenyl-and 4-ethyl-1-(2-hydroxybenzoyl) thiosemicarbazides and the synthesis, characterization and DFT calculations of binary and ternary complexes derived from 4-ethyl (L 1) and 2, 2’-dipyridyl. Spectrochim Acta Part A 150:949–958CrossRefGoogle Scholar
- Chakrabarti R, Rajagopalan R (2002) Diabetes and insulin resistance associated disorders: disease and the therapy. Curr Sci 83:1533–1538Google Scholar
- Doig AJ, Williams DH, Oelrichs PB, Baczynskyj L (1990) Isolation and structure elucidation of punicalagin, a toxic hydrolysable tannin, from Terminalia oblongata. J Chem Soc 8:2317–2321Google Scholar
- Greenberger NJ, Toskes PP (1991) Harrison’s principles of internal medicine. McGraw-Hill, New York, NYGoogle Scholar
- Hengesh EJ (1995) Principles of medical chemistry. Williams & Wilkins, BaltimoreGoogle Scholar
- Nauntofte B, Tenevuo JO, Lagerlöf F, Fejerskov O, Kidd E (2003) Dental caries: the disease and its clinical management. Blackwell Munksgard, OxfordGoogle Scholar
- Ramasubbu N, Ragunath C, Sundar K, Mishra PJ, Gyémánt G, Kandra L (2005) Structure-function relationships in human salivary α-amylase: role of aromatic residues. Biologia 60:47–56Google Scholar
- Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D (2005) In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem 16:360–367CrossRefPubMedGoogle Scholar
- Strelow J, Dewe W, Iversen PW, Brooks HB, Radding JA, McGee J, Weidner J (2012) Mechanism of action assays for enzymes. Assay Guidance ManualGoogle Scholar