Omayma Abidi^1,2,* Houcine Selmi3 and Ouajdi Souilem^2,4

¹Faculty of Sciences of Tunis, University Tunis El Manar, Tunisia
²Laboratory of Physiology and Pharmacology, National School of Veterinary Medicine, University of Manouba, Tunisia
³Laboratoire de Ressources Sylvo-Pastorales, Institut Sylvo-Pastoral de Tabarka, Université de Jendouba, Tunisie
⁴BiotechPole, Ariana, Tunisia

*Corresponding Author: Omayma Abidi, Faculty of Sciences of Tunis, University Tunis El Manar, Tunisia.

Received: June 19, 2025; Published: July 02, 2025

Abstract

Oxidative stress is a central driver of neurodegeneration, yet safe, food derived antioxidants capable of penetrating the brain remain scarce. Pistacia lentiscus L., a Mediterranean shrub long celebrated in folk medicine, is unusually rich in redox active phenolics. We investigated whether a simple water decoction of P. lentiscus leaves confers neuroprotection in murine models of oxidative injury and characterized its bioactive metabolite profile.

Secondary metabolites were quantified (polyphenols, tannins, flavonoids, soluble sugars) by Folin–Ciocalteu, vanillin–HCl, AlCl₃ and phenol–sulfuric assays, respectively. Total in vitro antioxidant capacity was assessed by ABTS. Adult male Swiss mice (n = 10 per group) received tamoxifen (30 mg kg⁻¹), tamoxifen + decoction (1 g kg⁻¹), decoction alone, or vehicle for 28 days. Cerebral and cerebellar oxidative status were gauged by malondialdehyde (MDA), reduced thiols ( SH) and hydroperoxides (HéOé), while endogenous defenses were probed via superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities.

The decoction delivered 192 ± 5 mg gallic acid eq g⁻¹ DW of total polyphenols, 33 ± 2 mg catechin eq g⁻¹ DW of flavonoids, 11 ± 1 mg quercetin eq g⁻¹ DW of condensed tannins and 20 ± 0.1 % soluble sugars. ABTS•⁺ assays revealed potent antioxidant (30,0 mg E.A.G / g MS). In vivo, tamoxifen elevated cerebral MDA (+82 %) and hydroperoxides (+67 %), depleted SH (–40 %), and suppressed SOD/GPx activities (–34 %/–29 %). Co administration of the decoction normalized lipid peroxidation (MDA –44 %; H2O2 –38 %), restored thiol groups (+37 %), and up regulated SOD (+42 %) and GPx (+46 %) versus tamoxifen alone (p < 0.01). Decoction monotherapy produced comparable antioxidant reinforcement without signs of toxicity.

Aqueous metanolic leaf decoction of Pistacia lentiscus is a phenolic dense, low sugar preparation that potently scavenges radicals in vitro and fortifies endogenous antioxidant networks in vivo, thereby shielding brain and cerebellum from tamoxifen induced oxidative stress. These findings position lentisk decoction as a promising neuroprotective nutraceutical adjuvant against redox driven neural damage.

Keywords: Adjuvant Therapy; Antioxidant; Neuroprotective Effect; Phenolic Compounds; Oxidative Stress

References

1. Feng XH., et al. “The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation”. Genes and Development 14 (1998): 2153-2163.
2. Valko M., et al. “Free radicals, metals and antioxidants in oxidative stress-induced cancer”. Chemico-Biological Interactions 1 (2006): 1-40.
3. Tiku AR. “Antimicrobial compounds (phytoanticipins and phytoalexins) and their role in plant defense”. Co-Evolution of Secondary Metabolites (2020): 845-868.
4. Panikar S., et al. “Essential oils as an effective alternative for the treatment of COVID-19: Molecular interaction analysis of protease (Mpro) with pharmacokinetics and toxicological properties”. Journal of Infection and Public Health 5 (2021): 601-610.
5. Sun Y and J Qian. “Botanical drug clinical trial: Common issues and future options”. Acta Pharmaceutica Sinica B 1 (2021): 300-303.
6. Sain S., et al. “Beta caryophyllene and caryophyllene oxide, isolated from Aegle marmelos, as the potent anti-inflammatory agents against lymphoma and neuroblastoma cells”. Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistryrrent Medicinal Chemistry-Anti-Inflammatory and Anti-Allergy Agents)1 (2014): 45-55.
7. Bagheri S., et al. “Effects of Pistacia atlantica on oxidative stress markers and antioxidant enzymes expression in diabetic rats”. Journal of the American College of Nutrition3 (2019): 267-274.
8. Kim KE., et al. “Artemisia annua leaf extract attenuates hepatic steatosis and inflammation in high-fat diet-fed mice”. Journal of Medicinal Food3 (2016): 290-299.
9. Yisak H., et al. “Total phenolics and antioxidant capacity of the white and brown teff [Eragrostic tef (Zuccagni) Trotter] varieties cultivated in different parts of Ethiopia”. Bulletin of the Chemical Society of Ethiopia 4 (2022): 749-766.
10. Hagos M., et al. “Determination of total phenolic, total flavonoid, ascorbic acid contents and antioxidant activity of pumpkin flesh, peel and seeds”. Bulletin of the Chemical Society of Ethiopia 5 (2023): 1093-1108.
11. Auerbach L. “Endokrine antihormonelle Therapie in der Prämenopause”. Journal für Gynäkologische Endokrinologie/Österreich4 (2017): 147-152.
12. Du J., et al. “Dual-targeting topotecan liposomes modified with tamoxifen and wheat germ agglutinin significantly improve drug transport across the blood− brain barrier and survival of brain tumor-bearing animals”. Molecular pharmaceutics3 (2009): 905-917.
13. Ferguson MW and S O'Kane. “Scar–free healing: from embryonic mechanisms to adult therapeutic intervention”. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences1445 (2004): 839-850.
14. Fatiha B., et al. “Phenolic composition, in vitro antioxidant effects and tyrosinase inhibitory activity of three Algerian Mentha species: M. spicata (L.), M. pulegium (L.) and M. rotundifolia (L.) Huds (Lamiaceae)”. Industrial Crops and Products  74 (2015): 722-730.
15. Brahmi F HD., et al. “Phenolic composition, in vitro antioxidant effects and tyrosinase inhibitory activity of three Algerian Mentha species: spicata (L.), M. pulegium (L.) and M. rotundifolia (L.) Huds (Lamiaceae)”. Industrial Crops and Products 74 (2015): 722-730.
16. Julkunen-Tiitto R. “Phenolic constituents in the leaves of northern willows: methods for the analysis of certain phenolics”. Journal of Agricultural and Food Chemistry 2 (1985): 213-217.
17. Draper HH and M Hadley. “Malondialdehyde determination as index of lipid Peroxidation”. Methods Enzymol 186 (1990): 421-431.
18. Ellman GL. “Tissue sulfhydryl groups”. Archives of Biochemistry and Biophysics 1 (1959): 70-77.
19. Kakkar P., et al. “A modified spectrophotometric assay of superoxide dismutase”. IJBB (1984).
20. Beghlal D., et al. “Phytochemical, organoleptic and ferric reducing properties of essential oil and ethanolic extract from Pistacia lentiscus (L.)”. Asian Pacific Journal of Tropical Disease 4 (2016): 305-310.
21. Lagadec C., et al. “Tamoxifen and TRAIL synergistically induce apoptosis in breast cancer cells”. Oncogene10 (2008): 1472-1477.
22. Tomková V., et al. “Mitochondrial fragmentation, elevated mitochondrial superoxide and respiratory supercomplexes disassembly is connected with the tamoxifen-resistant phenotype of breast cancer cells”. Free Radical Biology and Medicine 143 (2019): 510-521.
23. Abidi O., et al. “Pistacia lentiscus revealed in vitro anti-proliferative activity on MCF-7 breast cancer cells and in vivo anti-mammary cancer effect on C57BL/6 mice through necrosis, anti-inflammatory and antioxidant enhancements”. Plos One 19.4 (2024): e0301524.
24. Abidi O., et al. “Phytochemical analysis and biological activities of two oil-bearing extracts from fresh Pistacia lentiscus”. Bulletin of the Chemical Society of Ethiopia 6 (2023): 1487-1501.
25. Catalani S., et al. “Oxidative stress and apoptosis induction in human thyroid carcinoma cells exposed to the essential oil from Pistacia lentiscus aerial parts”. PloS One 2 (2017): e0172138.

Citation

Citation: Omayma Abidi., et al. “From Leaves to Neurons: Neuroprotective Effects of a Pistacia lentiscus Decoction in Oxidative Stress Models".Acta Scientific Nutritional Health 9.8 (2025): 03-13.

Copyright

Copyright: © 2025 Omayma Abidi., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.