Original Research Paper
Green synthesis of zinc oxide nanoparticles using Amygdalus scoparia Spach stem bark extract and their applications as an alternative antimicrobial, anticancer, and anti-diabetic agent

https://doi.org/10.1016/j.apt.2021.04.014Get rights and content

Highlights

  • ZnO NPs were green synthesized using Amygdalus scoparia extract.

  • ZnO NPs displayed remarkable inhibition activity against microbial pathogens.

  • ZnO NPs were active against cancer cell lines, while being nontoxic to normal cells.

  • ZnO NPs-treated rats showed high levels of IR, GluT2, and GCK expression.

Abstract

For the first time in this study, Zinc oxide nanoparticles were biosynthesized by the eco-friendly and cost-effective procedure using Amygdalus scoparia stem bark extract then used as antibacterial, antifungal, anticancer, and anti-diabetic agents. The characterization techniques confirmed the biosynthesis, crystalline nature, structure, size, elemental composition of ZnO NPs and bioactive compounds that exist in A. scoparia extract accounting for Zn2+ ion reduction, capping and stabilization of ZnO NPs. The ZnO NPs displayed remarkable inhibitory activity against E. coli, E. aerigenes, S. aureus, P. oryzae, F. thapsinum, and F. semitectum compared to antibiotic standards. The ZnO NPs showed significant inhibitory effects on cancer cell lines, while it had no toxic effect on Vero normal cell line. The ZnO NPs (30 mg/kg)-treated diabetic rats showed significantly higher levels of insulin and lower AST, ALT and blood glucose compared with the STZ induced diabetic group and other treated groups (P < 0.05). The ZnO NPs- and extract-treated rats showed significantly higher levels of IR, GluT2, and GCK expression and lower TNFα expression compared with the STZ induced diabetic rats. Our findings showed that ZnO NPs represented an outstanding performance for biological applications.

Introduction

Cancer, diabetes and bacterial infections are serious diseases with remarkable impacts on health worldwide. According to Centers for Disease Control and Prevention (CDC), cancer and diabetes are the second and seventh causes of death in the world, respectively. As stated by World Health Organization (WHO), the incidence rate of cancer is 14 million new cases every year and 9.6 million deaths. On the other hand, decreased physical activity, over nutrition, and changes in lifestyle lead to the increasing cases of chronic metabolic diseases such as diabetes. It should be noted that some epidemiologic studies suggest that people with diabetes are at significantly higher risk for many types of cancers. Due to the almost unknown relations between cancer and diabetes along with expensive, complicated and low effect treatment methods of the patients, it is important to develop and design new drugs and therapies with higher effectiveness and lower costs against these diseases [1], [2].

Bacterial infections are major cause of chronic infections and mortality. Several studies have demonstrated that the emergence of multidrug-resistant bacterial strains is a result of widespread use of antibiotics. Super-bacteria, which are resistant to nearly all antibiotics, have recently developed due to the irregular consumption of antibiotics [3]. Most of the antibiotic resistance mechanisms are irrelevant for nanoparticles (NPs) because the mode of action of NPs is direct contact with the bacterial cell wall, without the need to penetrate the cell.

Nanoparticles are tiny materials ranging from 1 to 100 nm. NPs have wide applications in medical, biological, agricultural, chemical, physical, and material sciences [4].

Due to the versatile characteristics, metallic oxide nanoparticles, specifically ZnO NPs, have gained great consideration in various fields. The effects of metallic oxide nanoparticles on cancer and diabetes have been widely investigated. Moreover, the antifungal antibacterial, and anti-inflammatory effects of these nanoparticles have also been questioned in several studies. It should be noted that metallic oxide nanoparticles have other applications such as waste water treatment, wound healing and bio imaging [5], [6]. Different methods are utilized for synthesis ZnO NPs, each of which plays a key role in establishing the physicochemical properties of the nanoparticles. Green synthesis of nanoparticles can be achieved by plants, bacteria, fungi, and algae, which can be used as an alternative method instead of chemical and physical methods [7], [8], [9], [10]. Plant-interceded synthesis of green nanoparticles is very cheap, stable, non-toxic, eco-friendly, and can provide large scale production [11]. It is demonstrated that medicinal plants possess numerous phenolic compounds, vitamins, and terpenoids. These compounds are probably responsible for antibacterial, antifungal, anticancer, anti-diabetic, and antimalarial effects [1]. In previous researches, extracts of M. mozaffarianii, C. pictus, and A. ampeloprasum were applied for the synthesis of ZnO NPs [5], [12], [13].

Amygdalus scoparia Spach is a deciduous large shrub belonging to the rose family, Rosaceae. It is a potentially multi-purpose wild almond species native to Iran, especially throughout the Zagros range. In Iranian folk medicine, the species has been traditionally used to treat cardiovascular and respiratory diseases, diabetes, hair loss, rheumatism, headaches, cancer, diarrhea, stomachache etc. [14], [15], [16].

The importance of the present work is viewed with respect to ascertaining the potential of the unexploited A. scoparia as medicine. This study highlights the antidiabetic, and anticancer activities of biosynthesized ZnO NPs mediated by A. scoparia stem bark extract against selected cancerous cell lines. In addition, the antibacterial and antifungal activities of the ZnO NPs against some pathogenic bacteria and fungi strains were tested under laboratory conditions. To the best of our knowledge, this is the first antidiabetic, anticancer and antimicrobial study of A. scoparia mediated biosynthesized ZnO NPs.

Section snippets

Preparation of A. scoparia bark extract

A. scoparia was collected from Zagros Mountains around Khorramabad, Lorestan Province, Iran. 5 g of dried barks powder were mixed in 100 ml of distilled water and incubated on a magnetic stirrer for 60 min at 80 °C. The extract was centrifuged at 5000 rpm for 25 min and filtered using Whatman No1 filter paper [17].

Preliminary phytochemical screening

Phytochemical compounds such as phenolic, flavonoids, and flavonols of A. scoparia stem bark extract were analyzed following Ranjbar et al. (2020) [18].

Synthesis of zinc oxide nanoparticles

12 ml of the stem extract was

Preliminary phytochemical assay

The results of our study demonstrated the presence of phenolic, flavonols, and flavonoid content in A. scoparia extract. Results showed that A. scoparia stem extract is rich in total phenolic content (119.56 mg of GAE /g of extract), total flavonoids (62.5 mg of QE /g of extract), and total flavonols (20.31 mg of QE /g of extract). Our results are consistent with the results reported by Abdollahi et al. (2018) describing the presence of Carotenoids- and total phenolic content in the methanolic

Conclusion

Our results proved that A. scoparia stem bark extract plays a fundamental role in the formation of ZnO NPs. The antimicrobial, anticancer, and anti-diabetic activities of ZnO NPs might be to some part due to the high surface-to-volume ratio of the nanoparticles. On the other hand, the secondary metabolites of extract may act as capping and stabilizing agents during ZnO NPs synthesis. The ZnO NPs showed remarkable antimicrobial activity against E. coli, E. aerigenes, S. aureus, P. oryzae, F.

CRediT authorship contribution statement

Mojtaba Ranjbar and Akbar Hajizadeh Moghaddam conceived and designed the expriment. Fatemeh Norouzi Jobie conducted the experiment and collected the data. Mojtaba Ranjbar performed the analysis. Mahmoud Kiani critically revised the manuscript.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (56)

  • C. Zhao et al.

    Biosynthesis of polyphenols functionalizedZnO NPs: Characterization and their effect on human pancreatic cancer cell line

    J. Photochem. Photobiol. B

    (2018)
  • N. Korkmaz et al.

    Biogenic nano silver: Synthesis, characterization, antibacterial, antibiofilms, and enzymatic activity

    Adv. Powder Technol.

    (2020)
  • K. Rajendran et al.

    Evaluation of cytotoxicity of hematite nanoparticles in bacteria and human cell lines

    Colloids Surf. B: Biointerfaces

    (2017)
  • K. Venugopal et al.

    Synthesis of silver nanoparticles (Ag NPs) for anticancer activities (MCF 7 breast and A549 lung cell lines) of the crude extract of Syzygium aromaticum

    Photochem. Photobiol. B

    (2017)
  • A. Kumar et al.

    An essential oil and its major constituent isointermedeol induce apoptosis by increased expression of mitochondrial cytochrome c and apical death receptors in human leukaemia HL-60 cells

    Chem. Biol. Interact.

    (2008)
  • Z. Wang et al.

    Antioxidant and anti-inflammatory activities of an anti-diabetic polysaccharide extracted from Gynostemma pentaphyllum herb

    Int. J. Biol. Macromol.

    (2020)
  • L.M.A. Ali et al.

    Effect of superparamagnetic iron oxide nanoparticles on glucose homeostasis on type 2 diabetes experimental model

    Life Sci.

    (2020)
  • Y. Guo et al.

    Green synthesis of gold nanoparticles from Fritillaria cirrhosa and its anti-diabetic activity on Streptozotocin induced rats

    Arab. J. Chem.

    (2020)
  • G. Wu et al.

    Antidiabetic effects of polysaccharide from azuki bean (Vigna angularis) in type 2 diabetic rats via insulin/PI3K/AKT signaling pathway

    Food Hydrocoll.

    (2020)
  • S.M. Sternisha et al.

    Molecular and cellular regulation of human glucokinase

    Arch. Biochem. Biophys.

    (2019)
  • K.P. Wang et al.

    Dendrobiurn officinale polysaccharide attenuates type 2 diabetes mellitus via the regulation of PI3K/Akt-mediated glycogen synthesis and glucose metabolism

    J. Funct. Foods

    (2018)
  • J. Jansen et al.

    Zinc and diabetes clinical links and molecular mechanisms

    J. Nutr. Biochem.

    (2009)
  • N.H. Nguyen et al.

    Potential antidiabetic activity of extracts and isolated compound from Adenosma bracteosum (Bonati)

    Biomolecules

    (2020)
  • M. Gupta et al.

    Effective antimicrobial activity of green ZnO nano particles of catharanthus roseus

    Front. Microbiol.

    (2018)
  • J. Suresh, G. Pradheesh, V. Alexramani, M. Sundrarajan, S.I. Hong, Green synthesis and characterization of zinc oxide...
  • O.M. El-Borady et al.

    Green synthesis of gold nanoparticles using Parsley leaves extract and their applications as an alternative catalytic, antioxidant, anticancer, and antibacterial agents

    Adv. Powder. Technol.

    (2020)
  • Sh. uzzaman, A. Ali, M. Asif, A. Mashrai, H. Khanam, Green synthesis ofZnO NPs using Bacillus subtilis and their...
  • A.B. Moghaddam, M. Moniri, S. Azizi, R. Abdul Rahim, A.B. Ariff, W. Zuhainis Saad, F. Namvar, M. Navaderi, R. Mohamad,...
  • Cited by (29)

    View all citing articles on Scopus
    View full text