HPLC-DAD profiles and pharmacological insights of Onobrychis argyrea subsp isaurica extracts

Onobrychis argyrea Boiss. subsp. Isaurica (Fabaceae), endemic to the eastern Mediterranean region, is a poorly studied medicinal plant. This study sets out to investigate into antioxidant and inhibitory activities of O. argyrea extracts (ethyl acetate, methanol, and water) against key enzymes linked to diabetes (α-amylase, α-glucosidase), Alzheimer's disease (acetylcholinesterase, butyrylcholinesterase), and skin hyperpigmentation (tyrosinase). Phytochemical composition was determined by HPLC-DAD and in silico approach used to provide additional insight of the possible interaction of the identified phenolic compounds with the studied enzymes. The methanol extract showed potent inhibitory action against acetylcholinesterase (1.55 mg GALAE/g extract), tyrosinase (61.61 mg KAE/g extract), and glucosidase (20.17 mmol ACAE/g extract). The methanol extract of O. argyrea exhibited potent radical scavenging potential (126.51 mg TE/g extract for DPPH scavenging assay) and reducing capacities (311.36 and 200.70 mg TE/g extract, for CUPRAC and FRAP assays, respectively). Quercetin, apigenin, and benzoic acid were identified in significant amounts in the methanol extract of O. argyrea. Quercetin interacted with the catalytic pocket of glucosidase by establishing hydrogen bonds with Ser157, Ser241, Asp307, and π-π interactions with His280 and Tyr158. The observed inhibitory effects of O. argyrea extracts on the studied enzyme suggest that this plant could be a promising source of naturally occurring chemical compounds for the management of diabetes, Alzheimer's disease, skin hyperpigmentation disorders, as well as, oxidative stress-related complications.

[1]  Huilin Zhang,et al.  Synthesis and biological evaluation of novel hydroxybenzaldehyde-based kojic acid analogues as inhibitors of mushroom tyrosinase. , 2017, Bioorganic & medicinal chemistry letters.

[2]  A. Justino,et al.  Antioxidant and anti-glycation capacities of some medicinal plants and their potential inhibitory against digestive enzymes related to type 2 diabetes mellitus. , 2018, Journal of ethnopharmacology.

[3]  A. Mollica,et al.  Functional constituents of wild and cultivated Goji (L. barbarum L.) leaves: phytochemical characterization, biological profile, and computational studies , 2017, Journal of enzyme inhibition and medicinal chemistry.

[4]  B. Dijkstra,et al.  Crystal structure of Agaricus bisporus mushroom tyrosinase: identity of the tetramer subunits and interaction with tropolone. , 2011, Biochemistry.

[5]  Ryan G. Coleman,et al.  ZINC: A Free Tool to Discover Chemistry for Biology , 2012, J. Chem. Inf. Model..

[6]  G. D’Onofrio,et al.  Apigenin as neuroprotective agent: Of mice and men , 2018, Pharmacological research.

[7]  S. Brimijoin,et al.  Cholinesterases and the fine line between poison and remedy , 2018, Biochemical pharmacology.

[8]  A. Yıldırım,et al.  Antibacterial and antitumour activities of some plants grown in Turkey , 2014, Biotechnology, biotechnological equipment.

[9]  Ximing Xu,et al.  Quercetin as a tyrosinase inhibitor: Inhibitory activity, conformational change and mechanism. , 2017, Food research international.

[10]  Xiaoxiong Zeng,et al.  Inhibitory activities of caffeoylquinic acid derivatives from Ilex kudingcha C.J. Tseng on α-glucosidase from Saccharomyces cerevisiae. , 2015, Journal of agricultural and food chemistry.

[11]  G. D. Liyanaarachchi,et al.  Tyrosinase, elastase, hyaluronidase, inhibitory and antioxidant activity of Sri Lankan medicinal plants for novel cosmeceuticals , 2018 .

[12]  A. Mollica,et al.  Multidirectional investigations on different parts of Allium scorodoprasum L. subsp. rotundum (L.) Stearn: Phenolic components, in vitro biological, and in silico propensities. , 2018, Food research international.

[13]  R. Cifelli,et al.  Recent Advances in the Separation and Determination of Impurities in Pharmaceutical Products , 2015 .

[14]  G. Zengin,et al.  In vitro tyrosinase inhibitory and antioxidant potential of Consolida orientalis, Onosma isauricum and Spartium junceum from Turkey , 2018, South African Journal of Botany.

[15]  Wei-Ming Chai,et al.  Rifampicin as a novel tyrosinase inhibitor: Inhibitory activity and mechanism. , 2017, International journal of biological macromolecules.

[16]  Josip Madunić,et al.  Apigenin: A dietary flavonoid with diverse anticancer properties. , 2018, Cancer letters.

[17]  K. Mochida,et al.  In vitro antioxidative effects and tyrosinase inhibitory activities of seven hydroxycinnamoyl derivatives in green coffee beans. , 2004, Journal of agricultural and food chemistry.

[18]  M. Ganzera,et al.  Recent advances on HPLC/MS in medicinal plant analysis. , 2011, Journal of pharmaceutical and biomedical analysis.

[19]  M. Ashraf,et al.  Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors. , 2017, European journal of medicinal chemistry.

[20]  P. Xiao,et al.  Deep in shadows: Epigenetic and epigenomic regulations of medicinal plants , 2018, Chinese Herbal Medicines.

[21]  G. Zengin,et al.  Ajuga chamaecistus subsp. scoparia (Boiss.) Rech.f.: A new source of phytochemicals for antidiabetic, skin-care, and neuroprotective uses , 2016 .

[22]  A. Mollica,et al.  Chemical and biological insights on Cotoneaster integerrimus: A new (-)- epicatechin source for food and medicinal applications. , 2016, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[23]  A. Mollica,et al.  Biological and chemical insights of Morina persica L.: A source of bioactive compounds with multifunctional properties , 2016 .

[24]  Matthew P. Repasky,et al.  Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. , 2006, Journal of medicinal chemistry.

[25]  André R. Gonçalves,et al.  Modeling Alzheimer's disease cognitive scores using multi-task sparse group lasso , 2017, Comput. Medical Imaging Graph..

[26]  Keizo Yamamoto,et al.  Steric hindrance by 2 amino acid residues determines the substrate specificity of isomaltase from Saccharomyces cerevisiae. , 2011, Journal of bioscience and bioengineering.

[27]  A. Mahdavi,et al.  Evaluation of thiazolidinone derivatives as a new class of mushroom tyrosinase inhibitors. , 2018, International journal of biological macromolecules.

[28]  Takayoshi Suzuki,et al.  Establishment of pancreatic microenvironment model of ER stress: Quercetin attenuates β-cell apoptosis by invoking nitric oxide-cGMP signaling in endothelial cells. , 2018, The Journal of nutritional biochemistry.

[29]  N. Mimica-Dukić,et al.  Antioxidant and anti-inflammatory activities of quercetin and its derivatives , 2018 .

[30]  Gokhan Zengin,et al.  In vitro and in silico evaluation of Centaurea saligna (K.Koch) Wagenitz - An endemic folk medicinal plant , 2018, Comput. Biol. Chem..

[31]  Qiaoli Zhao,et al.  Harmful and Protective Effects of Phenolic Compounds from African Medicinal Plants , 2014 .

[32]  S. Avcı,et al.  Analysis of Onobrychis genetic diversity using SSR markers from related legume species. , 2014 .

[33]  S. Sturm,et al.  Recent advances on HPLC/MS in medicinal plant analysis—An update covering 2011–2016 , 2018, Journal of pharmaceutical and biomedical analysis.

[34]  E. Giacobini Selective Inhibitors of Butyrylcholinesterase , 2001 .

[35]  V. L. Singleton,et al.  Total Phenol Analysis: Automation and Comparison with Manual Methods , 1977, American Journal of Enology and Viticulture.

[36]  Te-Sheng Chang,et al.  An Updated Review of Tyrosinase Inhibitors , 2009, International journal of molecular sciences.

[37]  N. Sato,et al.  Bidirectional interactions between diabetes and Alzheimer's disease , 2017, Neurochemistry International.

[38]  G. Zengin,et al.  In vitro enzyme inhibitory properties, antioxidant activities, and phytochemical profile of Potentilla thuringiaca , 2017 .

[39]  F. Shakeel,et al.  Utilizing spray drying technique to improve oral bioavailability of apigenin , 2018, Advanced Powder Technology.

[40]  S. Ha,et al.  Effects of friedelin on the intestinal permeability and bioavailability of apigenin. , 2017, Pharmacological reports : PR.

[41]  Manzoor Ahmad,et al.  Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors. , 2018, Bioorganic chemistry.

[42]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[43]  Jeremy R. Greenwood,et al.  Epik: a software program for pKa prediction and protonation state generation for drug-like molecules , 2007, J. Comput. Aided Mol. Des..

[44]  X. Chen,et al.  A systematic review on biological activities of prenylated flavonoids , 2014, Pharmaceutical biology.