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Nanoliposomal formulation of pistachio hull extract: preparation, characterization and anti-cancer evaluation through Bax/Bcl2 modulation

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Abstract

Background

Pistachio is one of the main crops in Iran. Pistachio green hull, as a by-product of this fruit, is obtained in large quantities after the processing of pistachios. This novel work was designed to examine the possible anti-cancer impact of the pistachio hull extract in the liposomal form (PHEL) on HepG2 cells.

Methods and results

The thin-film hydration approach was used for preparing liposomes and the physicochemical features of the liposomes were subsequently characterized. Afterward, apoptosis and the expression of genes related to apoptosis were assessed using flow cytometry assay and quantitative real-time polymerase chain reaction (qPCR), respectively. According to the results, the size range of PHEL was between 198 and 201 nm with a negative surface charge of − 39.2 to − 42.9 mV. As revealed by the flow cytometry results, this liposomal extract exhibits good potential for the induction of apoptosis. Moreover, the qPCR results demonstrated the up-regulation of p53 and Bax expressions and the down-regulation of Bcl-2 expression with an associated Bax/Bcl-2 ratio up-regulation.

Conclusion

The flow cytometry and real-time PCR results indicated the potential of this liposomal extract as an anti-cancer drug candidate for the treatment of liver cancer in the future, and the mitochondrial pathway involving the up-regulation of the Bax/Bcl-2 ratio can mediate its impact.

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Data availability

Data available on request from the authors.

References

  1. Patel S, Rauf A (2017) Adaptogenic herb ginseng (Panax) as medical food: status quo and future prospects. Biomed Pharmacother 85:120–127

    CAS  PubMed  Google Scholar 

  2. Oloumi MM, Vosough D, Derakhshanfar A, Nematollahi MH (2011) The healing potential of Plantago lanceolata ointment on collagenase-induced tendinitis in burros (Equus asinus). J Equine Vet 31(8):470–474

    Google Scholar 

  3. Sargazi ML, Juybari KB, Tarzi ME, Amirkhosravi A, Nematollahi MH, Mirzamohammdi S et al (2021) Naringenin attenuates cell viability and migration of C6 glioblastoma cell line: a possible role of hedgehog signaling pathway. Mol Biol Rep 48(9):6413–6421

    CAS  PubMed  Google Scholar 

  4. Roy A, Jauhari N, Bharadvaja N (2018) Medicinal plants as a potential source of chemopreventive agents. In: Anticancer plants: natural products and biotechnological implements, vol 2. Springer, Singapore, p 109

  5. Barreca D, Laganà G, Leuzzi U, Smeriglio A, Trombetta D, Bellocco E (2016) Evaluation of the nutraceutical, antioxidant and cytoprotective properties of ripe pistachio (Pistacia vera L., variety Bronte) hulls. Food Chem 196:493–502

    CAS  PubMed  Google Scholar 

  6. Grace MH, Esposito D, Timmers MA, Xiong J, Yousef G, Komarnytsky S et al (2016) Chemical composition, antioxidant and anti-inflammatory properties of pistachio hull extracts. Food Chem 210:85–95

    CAS  PubMed  Google Scholar 

  7. Al-Juhaimi F, Adiamo OQ, Alsawmahi ON, Gahfoor K, Islam Sarker MZ, Mohamed Ahmed IA et al (2017) Effect of pistachio seed hull extracts on quality attributes of chicken burger. CyTA J Food 15(1):9–14

    Google Scholar 

  8. Agrawal MM, Jawade S, Khan S (2012) A review on liposome. Int J Adv Res Pharm Bio Sci 2(1):453–465

    Google Scholar 

  9. Bozorgi M, Memariani Z, Mobli M, Salehi Surmaghi MH, Shams-Ardekani MR, 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. Sci World J. https://doi.org/10.1155/2013/219815

    Article  Google Scholar 

  10. Botterweck AA, Verhagen H, Goldbohm RA, Kleinjans J, Van den Brandt PA (2000) Intake of butylated hydroxyanisole and butylated hydroxytoluene and stomach cancer risk: results from analyses in the Netherlands cohort study. Food Chem Toxicol 38(7):599–605

    CAS  PubMed  Google Scholar 

  11. Lourenço SC, Moldão-Martins M, Alves VD (2019) Antioxidants of natural plant origins: from sources to food industry applications. Molecules 24(22):4132

    PubMed Central  Google Scholar 

  12. Rafiee Z, Barzegar M, Sahari MA, Maherani B (2018) Nanoliposomes containing pistachio green hull’s phenolic compounds as natural bio-preservatives for mayonnaise. Eur J Lipid Sci Technol 120(9):1800086

    Google Scholar 

  13. Arjeh E, Akhavan H-R, Barzegar M, Carbonell-Barrachina ÁA (2020) Bio-active compounds and functional properties of pistachio hull: a review. Trends Food Sci Technol 97:55–64

    CAS  Google Scholar 

  14. Raeiszadeh M, Pardakhty A, Sharififar F, Mehrabani M (2018) Phytoniosome: a novel drug delivery for myrtle extract. Iran J Pharm Res 17(3):804

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Barani MSE, Angarano M, Rajizadeh MA, Mehrabani M, Piazza S, Gangadharappa HV, Pardakhty A, Mehrbani M, Dell’Agli M, Nematollahi MH (2021) Phytosomes as innovative delivery systems for phytochemicals: a comprehensive review of literature. Int J Nanomed 16:6983–7022

    Google Scholar 

  16. Asadikaram G, Poustforoosh A, Pardakhty A, Torkzadeh-Mahani M, Nematollahi MH (2021) Niosomal virosome derived by vesicular stomatitis virus glycoprotein as a new gene carrier. Biochem Biophys Res Commun 534:980–987

    CAS  PubMed  Google Scholar 

  17. Shade CW (2016) Liposomes as advanced delivery systems for nutraceuticals. Integr Med 15(1):33

    Google Scholar 

  18. Kaye S, Richardson V (1979) Potential of liposomes as drug-carriers in cancer chemotherapy: a review. Cancer Chemother Pharmacol 3(2):81–85

    CAS  PubMed  Google Scholar 

  19. Khosravi-Darani K, Mozafari M (2010) Nanoliposome potentials in nanotherapy: a concise overview. Int J Nanosci Nanotechnol 6(1):3–13

    Google Scholar 

  20. Edwards BK, Noone AM, Mariotto AB, Simard EP, Boscoe FP, Henley SJ et al (2014) Annual report to the nation on the status of cancer, 1975–2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 120(9):1290–1314

    PubMed  Google Scholar 

  21. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74(11):2913–2921

    CAS  PubMed  Google Scholar 

  22. Mohammadpour-Gharehbagh A, Eskandari M, Sadegh MH, Nematollahi MH, Rezaei M, Rasouli A et al (2019) Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia. Apoptosis 24(3–4):301–311

    CAS  PubMed  Google Scholar 

  23. Noguera-Artiaga L, Pérez-López D, Burgos-Hernández A, Wojdyło A, Carbonell-Barrachina ÁA (2018) Phenolic and triterpenoid composition and inhibition of α-amylase of pistachio kernels (Pistacia vera L.) as affected by rootstock and irrigation treatment. Food Chem 261:240–5

    CAS  PubMed  Google Scholar 

  24. Harandi H, Majd A, Falahati-pour SK, Mahmoodi M (2018) Anti-cancer effects of hydro-alcoholic extract of pericarp of pistachio fruits. Asian Pac J Trop Biomed 8(12):598

    Google Scholar 

  25. Samareh Fekri M, Mandegary A, Sharififar F, Poursalehi HR, Nematollahi MH, Izadi A et al (2018) Protective effect of standardized extract of Myrtus communis L. (myrtle) on experimentally bleomycin-induced pulmonary fibrosis: biochemical and histopathological study. Drug Chem Toxicol 41(4):408–14

    CAS  PubMed  Google Scholar 

  26. Konttinen YT, Fuellen G, Bing Y, Porola P, Stegaev V, Trokovic N et al (2012) Sex steroids in Sjögren’s syndrome. J Autoimmun 39(1–2):49–56

    CAS  PubMed  Google Scholar 

  27. Raeiszadeh M, Esmaeili-Tarzi M, Bahrampour-Juybari K, Nematollahi-mahani S, Pardakhty A, Nematollahi M et al (2018) Evaluation the effect of Myrtus communis L. extract on several underlying mechanisms involved in wound healing: an in vitro study. S Afr J Bot 118:144–50

    Google Scholar 

  28. Nematollahi MH, Torkzadeh-Mahanai M, Pardakhty A, Ebrahimi Meimand HA, Asadikaram G (2018) Ternary complex of plasmid DNA with NLS-Mu-Mu protein and cationic niosome for biocompatible and efficient gene delivery: a comparative study with protamine and lipofectamine. Artif Cells Nanomed Biotechnol 46(8):1781–1791

    CAS  PubMed  Google Scholar 

  29. Harandi H, Majd A, Khanamani Falahati-Pour S, Mahmoodi M (2020) Toxicity effect of hydro-alcoholic extract of pistachio hull and its liposomal form on liver cancer cells (HepG2). J Rafsanjan Univ Med Sci 18(10):1035–1048

    Google Scholar 

  30. Mehrabani M, Nematollahi MH, Tarzi ME, Juybari KB, Abolhassani M, Sharifi AM et al (2020) Protective effect of hydralazine on a cellular model of Parkinson’s disease: a possible role of hypoxia-inducible factor (HIF)-1α. Biochem Cell Biol 98(3):405–414

    CAS  PubMed  Google Scholar 

  31. Roostaee M, Barzegar M, Sahari MA, Rafiee Z (2017) The enhancement of pistachio green hull extract functionality via nanoliposomal formulation: studying in soybean oil. J Food Sci Technol 54(11):3620–3629

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Goli AH, Barzegar M, Sahari MA (2005) Antioxidant activity and total phenolic compounds of pistachio (Pistachia vera) hull extracts. Food Chem 92(3):521–525

    CAS  Google Scholar 

  33. Heitefuss R (2010) Functions and biotechnology of plant secondary metabolites, 2nd edn, annual plant reviews, vol 39. J Phytopathol 159:72

    Google Scholar 

  34. Maherani B, Arab-Tehrany E, Kheirolomoom A, Geny D, Linder M (2013) Calcein release behavior from liposomal bilayer; influence of physicochemical/mechanical/structural properties of lipids. Biochimie 95(11):2018–2033

    CAS  PubMed  Google Scholar 

  35. Hasan M, Belhaj N, Benachour H, Barberi-Heyob M, Kahn C, Jabbari E et al (2014) Liposome encapsulation of curcumin: physico-chemical characterizations and effects on MCF7 cancer cell proliferation. Int J Pharm 461(1–2):519–528

    CAS  PubMed  Google Scholar 

  36. Lu Q, Lu P-M, Piao J-H, Xu X-L, Chen J, Zhu L et al (2014) Preparation and physicochemical characteristics of an allicin nanoliposome and its release behavior. LWT Food Sci Technol 57(2):686–695

    Google Scholar 

  37. Rafiee Z, Barzegar M, Sahari MA, Maherani B (2017) Nanoliposomal carriers for improvement the bioavailability of high–valued phenolic compounds of pistachio green hull extract. Food Chem 220:115–122

    CAS  PubMed  Google Scholar 

  38. Gibis M, Vogt E, Weiss J (2012) Encapsulation of polyphenolic grape seed extract in polymer-coated liposomes. Food Funct 3(3):246–254

    CAS  PubMed  Google Scholar 

  39. Adler K, Schiemann J (1985) Characterization of liposomes by scanning electron microscopy and the freeze-fracture technique. Micron Microsc Acta 16(2):109–113

    Google Scholar 

  40. Isailović BD, Kostić IT, Zvonar A, Đorđević VB, Gašperlin M, Nedović VA et al (2013) Resveratrol loaded liposomes produced by different techniques. Innov Food Sci Emerg Technol 19:181–189

    Google Scholar 

  41. Magkouta S, Stathopoulos GT, Psallidas I, Papapetropoulos A, Kolisis FN, Roussos C et al (2009) Protective effects of mastic oil from Pistacia lentiscus variation chia against experimental growth of lewis lung carcinoma. Nutr Cancer 61(5):640–648

    PubMed  Google Scholar 

  42. Mahassni SH, Al-Reemi RM (2013) Apoptosis and necrosis of human breast cancer cells by an aqueous extract of garden cress (Lepidium sativum) seeds. Saudi J Biol Sci 20(2):131–139

    PubMed  PubMed Central  Google Scholar 

  43. Hosseini FS, Falahati-pour SK, Hajizadeh MR, Khoshdel A, Mirzaei MR, Ahmadirad H et al (2017) Persian shallot, Allium hirtifolium Boiss, induced apoptosis in human hepatocellular carcinoma cells. Cytotechnology 69(4):551–563

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2(9):647

    CAS  PubMed  Google Scholar 

  45. Raisova M, Hossini AM, Eberle J, Riebeling C, Orfanos CE, Geilen CC et al (2001) The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J Invest Dermatol 117(2):333–340

    CAS  PubMed  Google Scholar 

  46. Chresta CM, Masters JR, Hickman JA (1996) Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high Bax: Bcl-2 ratio. Cancer Res 56(8):1834–1841

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran

    Hamidreza Harandi

  2. Pistachio Safety Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Soudeh Khanamani Falahati-pour

  3. Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Mehdi Mahmoodi, Hamidreza Shiri & Saba Fooladi

  4. Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran

    Sanaz Faramarz

  5. Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Science, Rafsanjan, Iran

    Haniyeh Maleki

  6. Department of Physics, Rafsanjan Branch, Islamic Azad University, Rafsanjan, Iran

    Fatemeh Bagheri Nasab

  7. Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran

    Mohammad Hadi Nematollahi

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  1. Hamidreza Harandi
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  8. Saba Fooladi
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  9. Mohammad Hadi Nematollahi
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Contributions

MM and MHN designed the study and supervision. HH, SF, SF carried out the experiment. MHN, HM, FBN, and SKF wrote the manuscript and analysis data. HSH & MHN Revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohammad Hadi Nematollahi.

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The present study was approved by the ethics committee of North Tehran branch, Islamic Azad University, Tehran, Iran.

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Harandi, H., Falahati-pour, S.K., Mahmoodi, M. et al. Nanoliposomal formulation of pistachio hull extract: preparation, characterization and anti-cancer evaluation through Bax/Bcl2 modulation. Mol Biol Rep 49, 2735–2743 (2022). https://doi.org/10.1007/s11033-021-07083-5

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