Pomegranate
Pomegranate (Punica granatum) is a fruit-bearing deciduous shrub native to the Mediterranean area. Extracts of the peel and seed have been explored extensively for their antioxidant properties. The bioactive component punicic acid, an “omega-5” polyunsaturated fatty acid with antioxidant properties, has garnered particular interest for its role in preventing and managing chronic metabolic1 and neurodegenerative2 diseases.
In an animal model of MS, an extract of pomegranate peel (dose 100 mg/kg) yielding phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins, was administered to mice with EAE. Treatment not only effectively relieved EAE and inhibited CNS inflammatory factor infiltration and myelin loss, it also reshaped gut microbiota, with fecal transplantation from a treated donor significantly delaying disease development. This suggests prebiotic value of pomegranate peel for the treatment of autoimmune diseases3.
In a similar animal model, a nano-preparation of pomegranate seed oil produced a reduction in disease burden, a beneficial effect that improved with low concentrations of the oil. Close evaluation revealed that the treatment dramatically reduced demyelination and oxidation of lipids in the brains of EAE animals4.
A pilot clinical study in MS patients of all types suggested that a 125 mg of a nano-preparation of pomegranate seed oil standardized to yield 80-90% punicic acid may improve/stabilize cognitive disability in the disease. Treated participants demonstrated improvement in mental tests that are known to be sensitive in detection of dysfunction in MS5.
Pregnant mice fed 220 mg/day (approximately 11 mg/kg/day) of pomegranate peel powder (yielding 30% polyphenols) were found to be at lower risk of pregnancy loss/embryo death6, while in pregnant rats 150 mg/kg/day was associated with improved heart health in both diabetic mothers and their offspring7. Pomegranate juice (8 fluid ounces or 240 ml) daily provided to pregnant women has been observed to protect the fetal/infant brain during impaired body growth8 and to provide antioxidative support to placental tissue and thus the fetus/offspring9. Lactating rabbits fed 6.75 g/day of pomegranate peel pomace (2.9 g/kg, likely yielding at least 27% polyphenols) demonstrated increased milk production due to increased reproductive hormone levels10.
The dose of punicic acid found to be valuable in MS is equivalent to approximately half of a 4-inch (10-cm) pomegranate fruit.
References
1.Shabbir MA, Khan MR, Saeed M, Pasha I, Khalil AA, Siraj N. Punicic acid: A striking health substance to combat metabolic syndromes in humans. Lipids Health Dis. May 30 2017;16(1):99. doi:10.1186/s12944-017-0489-3
2.Mizrahi M, Friedman-Levi Y, Larush L, et al. Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD. Nanomedicine. Aug 2014;10(6):1353-63. doi:10.1016/j.nano.2014.03.015
3.Lu L, Qi S, Chen Y, et al. Targeted immunomodulation of inflammatory monocytes across the blood-brain barrier by curcumin-loaded nanoparticles delays the progression of experimental autoimmune encephalomyelitis. Biomaterials. Jul 2020;245:119987. doi:10.1016/j.biomaterials.2020.119987
4.Binyamin O, Larush L, Frid K, et al. Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant. Int J Nanomedicine. 2015;10:7165-74. doi:10.2147/IJN.S92704
5.Petrou P, Ginzberg A, Binyamin O, Karussis D. Beneficial effects of a nano formulation of pomegranate seed oil, GranaGard, on the cognitive function of multiple sclerosis patients. Mult Scler Relat Disord. Sep 2021;54:103103. doi:10.1016/j.msard.2021.103103
6.Al-Gubory KH, Garrel C. Diet Supplementation with Pomegranate Peel Improves Embryonic Survival in a Mouse Model of Early Pregnancy Loss. J Diet Suppl. 2022;19(2):243-258. doi:10.1080/19390211.2020.1865499
7.El-Mansi AA, Al-Kahtani MA. Calcitriol and Punica Granatum Extract Concomitantly Attenuate Cardiomyopathy of Diabetic Mother Rats and Their Neonates via Activation of Raf/MEK/ERK Signalling and Mitigation of Apoptotic Pathways. Folia Biol (Praha). 2019;65(2):70-87.
8.Ross MM, Cherkerzian S, Mikulis ND, et al. A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR. Sci Rep. Feb 11 2021;11(1):3569. doi:10.1038/s41598-021-82144-0
9.Chen B, Tuuli MG, Longtine MS, et al. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts. Am J Physiol Endocrinol Metab. May 15 2012;302(9):E1142-52. doi:10.1152/ajpendo.00003.2012
10.Bakeer M, Abdelrahman H, Khalil K. Effects of pomegranate peel and olive pomace supplementation on reproduction and oxidative status of rabbit doe. J Anim Physiol Anim Nutr (Berl). May 2022;106(3):655-663. doi:10.1111/jpn.13617