Cancer preventive and neuroprotective potentials of red hulls, kernels and oleo-gum resins from Pistachio

This research was performed to assess cancer prevention and neuroprotective capacities of different parts of Pistachio (Pistachio vera L.). Red hulls, kernels and oleo-gum resins of Pistachio were extracted with methanol-MeOH and distilled water-dH2O, and subjected to in vitro biological assays varying from 100 to 1000 μg mL−1 concentrations. Their anticancer activities were evaluated against A549, MCF-7, and HeLa human cancer cells. Neuroprotective activities of the extracts were tested through enzyme inhibition on AChE, BChE, and TYR, which are closely related to pathogenesis of neurobiological disorders, particularly Alzheimer's and Parkinson’s diseases. Due to cancer and neurodegenerative diseases are associated with oxidative damage, the extracts were analyzed for their antioxidant activities. With respect to free radical scavenging activities of the extracts, red hull extracts were found as the most potent ones both DPPH (67.95±1.13 to 80.55±0.12%) and ABTS (86.92±0.10 to 92.04±1.06%) radicals. The highest anticancer activity were determined in MeOH and dH2O extracts obtained from oleo-gum resin against HeLa cells (IC50 = 18.50±0.85 and 28.97±0.08 µg mL-1, p< 0.01, respectively), whilst dH2O-kernel extract was found to have the weakest anticancer activity towards A549 cells (IC50 = 268.66±1.02 µg mL-1, p< 0.01). Neuroprotective potentials on AChE and BChE enzymes were resulted in the superiority of dH2O-red hull extract was exerted the highest inhibition on AChE and BChE enzymes with 81.50±0.08 and 62.96±1.01% inhibition, respectively. However, dH2O extract from oleo-gum resin showed the highest inhibitory effect on TYR enzyme (58.16±0.18% inhibition). P. vera is of valuable nutritional source for human diet. Other than kernel parts used as food, waste parts like red hulls and oleo-gum resins have been proven as a potential pharmacological source. Consequently, this study reveals that non-food parts of Pistachio could be valuable source for pharmaceutical industry.  

___

  • Almehdar, H., Abdallah, H.M., Osman, A.M., Abdel-Sattar, E.A. (2012). In vitro cytotoxic screening of selected Saudi medicinal plants. Journal of Natural Medicines, 66(2), 406-412. https://doi.org/10.1007/s11418-011-0589-8.
  • Belkhodja, H., Meddah, B., Gezici S. (2017). Anti-Inflammatory Effects of Essential Oils from Rosmarinus officinalis and Populus alba on Experimental Models of Acute and Chronic Inflammation in Rats. Indian Journal of Pharmaceutical Education and Research, 51(3), 180-184. https://doi.org/10.5530/ijper.51.3s.8.
  • Benamar, H., Rached, W., Derdour, A., Marouf, A. (2010). Screening of Algerian medicinal plants for acetylcholinesterase inhibitory activity. Journal of Biological Sciences, 10(1), 1- https://doi.org/10.3923/jbs.2010.1.9.
  • Bozorgi, M., Memariani, Z., Mobli, M., Salehi Surmaghi, M. H., Shams-Ardekani, M. R., Rahimi, R. (2013). Five Pistacia species (P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus): a review of their traditional uses, phytochemistry, and pharmacology. The Scientific World Journal, 2013. http://dx.doi.org/10.1155/2013/219815.
  • Das, K. and Gezici, S. (2018). Secondary plant metabolites, their separation and identification, and role in human disease prevention. Annals of Phytomedicine, 7(2), 13-24. https://doi.org/10.21276/ap.2018.7.2.3.
  • Das, K., Khan, M.S., Namratha, N., Swetha, R., Gezici, S. (2019). Comparative phytochemical screening, elemental content and chromatographic evaluation for detection and quantification of polyphenolic compounds for strong antioxidant activity of various extracts of Abutilon indicum (Link) Sweet leaves. Annals of Phytomedicine, 8(1), 36-44. https://doi.org/10.21276/ap.2019.8.1.4.
  • Dimas, K., Hatziantoniou, S., Wyche, J.H., Pantazis, P. (2009). A mastic gum extract induces suppression of growth of human colorectal tumor xenografts in immunodeficient mice. In Vivo, 23(1), 63-68.
  • Ellman, G.L., Courtney, K.D., Andres Jr, V., Featherstone, R.M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7, 88-95. https://doi.org/10.1016/0006-2952(61)90145-9.
  • Farzaei, M. H., Shahpiri, Z., Mehri, M. R., Bahramsoltani, R., Rezaei, M., Raeesdana, A., Rahimi, R. (2018). Medicinal plants in neurodegenerative diseases: perspective of traditional Persian medicine. Current drug metabolism, 19(5), 429-442.
  • Fathalizadeh, J., Bagheri, V., Khorramdelazad, H., Kazemi Arababadi, M., Jafarzadeh, A., Mirzaei, M.R., Hajizadeh, M.R. (2015). Induction of apoptosis by pistachio (Pistacia vera L.) hull extract and its molecular mechanisms of action in human hepatoma cell line HepG2. Cellular and Molecular Biology, 61(7), 128-134. https://doi.org/10.14715/cmb/2015.61.7.20.
  • Gezici, S., Sekeroglu, N., Kijjoa, A. (2017). In vitro Anticancer Activity and Antioxidant Properties of Essential Oils from Populus alba L. and Rosmarinus officinalis L. from South Eastern Anatolia of Turkey. Indian Journal of Pharmaceutical Education and Research, 51(3), 498-503. https://doi.org/10.5530/ijper.51.3s.74.
  • Gezici S. (2018). Promising anticancer activity of lavender (Lavandula angustifolia Mill.) essential oil through induction of both apoptosis and necrosis. Annals of Phytomedicine, 7(2), 38-45. https://doi.org/10.21276/ap.2018.7.2.55.
  • Gezici, S. and Sekeroglu, N. (2019a). Current perspectives in the application of medicinal plants against cancer: novel therapeutic agents. Anticancer Agents in Medicinal Chemistry, 19(1), 101-111. https://doi.org/10.2174/1871520619666181224121004.
  • Gezici, S. and Sekeroglu, N. (2019b). Neuroprotective potential and phytochemical composition of acorn kernels. Industrial Crops and Products, 128, 13-17. https://doi.org/10.1016/j.indcrop.2018.10.082.
  • Gezici, S. (2019a). Comparative anticancer activity analysis of saffron extracts and a principle component, crocetin for prevention and treatment of human malignancies. Journal of Food Science and Technology, 1-9. https://doi.org/10.1007/s13197-019-04014-y.
  • Gezici S. (2019b). Anticancer, antiproliferative, lysosomal and lactate dehydrogenase inhibitory effects of fruit extracts from sumac (Rhus coriaria L.) on human lung cancer cells. Acta Oncologica Turcica, 52(1), 160-168. https://doi.org/10.5505/aot.2019.093266.
  • Guizani, N., Waly, M.I., Rahman, M.S., Al-Attabi, Z. (2018). Natural products and their benefits in cancer prevention. Bioactive components, diet and medical treatment in cancer prevention. Springer, Cham, 51-61. https://doi.org/10.1007/978-3-319-75693-6_3.
  • Gundogdu, M., Tuncturk, M., Berk, S., Sekeroglu, N., Gezici, S. (2018). Antioxidant Capacity and Bioactive Contents of Mulberry Species from Eastern Anatolia Region of Turkey. Indian Journal of Pharmaceutical Education and Research, 52(4), 96-101. https://doi.org/10.5530/ijper.52.4s.82.
  • Hosseinzadeh, H., Tabassi, S. A. S., Moghadam, N. M., Rashedinia, M., Mehri, S. (2012). Antioxidant activity of Pistacia vera kernels, leaves and gum extracts. Iranian journal of pharmaceutical research, 11(3), 879-887. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813125/pdf/ijpr-11-879.pdf.
  • Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65(1-2), 55-63. https://doi.org/10.1016/0022-1759(83)90303-4.
  • Newman, D.J. and Cragg, G.M. (2016). Natural products as sources of new drugs from 1981 to 2014. Journal of Natural Products, 79(3), 629-661. https://doi.org/10.1021/acs.jnatprod.5b01055.
  • Orhan, I.E., Senol, F.S., Gulpinar, A.R., Sekeroglu, N., Kartal, M., Sener, B. (2012). Neuroprotective potential of some terebinth coffee brands and the unprocessed kernels of Pistacia terebinthus L. and their fatty and essential oil analyses. Food Chemistry, 130(4), 882-888. https://doi.org/10.1016/j.foodchem.2011.07.119.
  • Rajaei, A., Barzegar, M., Mobarez, A.M., Sahari, M. A., Esfahani, Z.H. (2010). Antioxidant, anti-microbial and antimutagenicity activities of pistachio (Pistachia vera) green hull extract. Food and Chemical Toxicology, 48(1), 107-112. https://doi.org/10.1016/j.fct.2009.09.023.
  • Reddy, L., Odhav, B., Bhoola, K.D. (2003). Natural products for cancer prevention: a global perspective. Pharmacology & therapeutics, 99(1), 1-13. https://doi.org/10.1016/S0163-7258(03)00042-1.
  • Rezaei, P.F, Fouladdel, S, Hassani S, Yousefbeyk F, Ghaffari SM, Amin G, et al. (2012). Induction of apoptosis and cell cycle arrest by pericarp polyphenol-rich extract of Baneh in human colon carcinoma HT29 cells. Food and Chemical Toxicology, 50(3-4), 1054-1059. https://doi.org/10.1016/j.fct.2011.11.012.
  • Roy, A., Jauhari, N., Bharadvaja, N. (2018). Medicinal Plants as a Potential Source of Chemopreventive Agents. Anticancer Plants: Natural Products and Biotechnological Implements. Springer, Singapore, 109-139.
  • Schieber, M. and Chandel, N.S. (2014). ROS function in redox signaling and oxidative stress. Current biology, 24(10), 453-462. https://doi.org/10.1016/j.cub.2014.03.034.
  • Seifaddinipour, M., Farghadani, R., Namvar, F., Mohamad, J., Abdul Kadir, H. (2018). Cytotoxic effects and anti-angiogenesis potential of pistachio (Pistacia vera L.) hulls against MCF-7 human breast cancer cells. Molecules, 23(1), 110. https://doi.org/10.3390/molecules23010110.
  • Sekeroglu, N. and Gezici, S. (2019). Astragalus neurocarpus Bioss. as a potential source of natural enzyme inhibitor associated with Alzheimer’s and Parkinson diseases along with its rich polyphenolic content and antioxidant activities. Annals of Phytomedicine, 8(1), 82-87. https://doi.org/10.21276/ap.2019.8.1.9.
  • Sekeroglu, N., Gezici, S., Tanriover, C.S., Yayla, F. (2019). Anticancer, Antiproliferative and Lactate Dehydrogenase Enzyme Activities of Astragalus elongatus subsp. nucleiferus on Human Cancer Cells. KSU Journal of Agriculture and Nature, 23(1). https://doi.org/10.18016/ksutarimdoga.vi.544872.
  • Sekeroglu, N., Senol, F.S., Orhan, I.E., Gulpinar, A.R., Kartal, M., Sener, B. (2012). In vitro prospective effects of various traditional herbal coffees consumed in Anatolia linked to neurodegeneration. Food Research International, 45, 197-203. https://doi.org/10.1016/j.foodres.2011.10.0088.
  • Sekeroglu, N., Urlu, E., Kulak, M., Gezici, S., Dang, R. (2017). Variation in Total Polyphenolic Contents, DNA Protective Potential and Antioxidant Capacity from Aqueous and Ethanol Extracts in Different Plant Parts of Hypericum perforatum L. Indian Journal of Pharmaceutical Education and Research, 51, 1-7. https://doi.org/10.5530/ijper.51.2s.43.
  • Senol, F.S., Sekeroglu, N., Gezici, S., Kilic, E., Orhan, İ.E. (2018). Neuroprotective potential of the fruit (acorn) from Quercus coccifera L. Turkish Journal of Agriculture and Forestry, 42, 82-87. https://doi.org/10.3906/tar-1711-18.
  • Shida, W., Tateishi, H., Fujita, M., Koga R., Radwan, M.O., Ciftci, H.I., Otsuka, M., Husham Al-Saadi, D., Watanabe, M., Gezici, S., Wada, M., Sekeroglu, N., Watanabe, T. (2019). Anticancer activity of extract from twigs of Caucasian beech in Turkey. The Fifth International Symposium on Pharmaceutical and Biomedical Sciences (ISPBS-5), Cappadocia-Turkey, p: 29 (Oral presentation) www.ispbs.org.
  • Tabatabaei-Malazy, O., Larijani, B., Abdollahi, M. (2013). A novel management of diabetes by means of strong antioxidants’ combination. Journal of Medical Hypotheses and Ideas, 7(1), 25-30. https://doi.org/10.1016/j.jmhi.2012.12.002.
  • World Health Statistics Overview 2019. World Health Organization, 2019. https://www.who.int/gho/publications/world_health_statistics/2019/en/.