Pomegranate (Punica granatum L.) Extract Effects on Inflammaging
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Pomegranate and Central Nervous System
3.1.1. Pomegranate in Alzheimer’s Disease
3.1.2. Pomegranate in Parkinson’s Disease
3.2. Pomegranate and Skin
3.2.1. Skin-Inflammaging Mechanism
3.2.2. Anti-Inflammaging Skin Effects of Pomegranate Extract
3.3. Pomegranate in Other Diseases
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Author | Study Model | Aims | Outcome |
---|---|---|---|
Choi et al. [48] | In vitro (PC12 cells) and in vivo (mice) | To study the antioxidant and neuroprotective effects of pomegranate against oxidative stress-induced cytotoxicity. | Pomegranate ethanolic extracts protected PC12 cells from H2O2-induced oxidative stress. Furthermore, in mouse models, pomegranate inhibited neuronal cell death caused by Aβ-induced oxidative stress and Aβ-induced learning and memory deficits. |
Velagapudi et al. [49] | In vitro (SK-N-SH cells) | To evaluate the effects of freeze-dried pomegranate on PGE2 production in IL-1β-stimulated SK-N-SH cells. | There was a dose-dependent reduction in COX-2-dependent PGE2 production and an inhibitory effect on NF-κB transactivation and BACE-1 expression. |
Essa et al. [50] | In vivo (APPsw/Tg2576 mice) | To investigate the beneficial effects of dietary supplements such as pomegranate, figs, or dates on suppressing inflammatory cytokines. | Supplementation significantly reduced levels of inflammatory cytokines (IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, and TNF-α) and the activity of eotaxin, while also delaying the formation of senile plaques. |
Kumar et al. [51] | In vivo (scopolamine treated mice) | To evaluate the effect of ethanolic extract of pomegranate seeds on the cognitive performance of aged and scopolamine-treated young mice. | Chronic administration of Pomegranate and vitamin C significantly reversed age- or scopolamine-induced retention deficits, reduced the level of lipid peroxidation, and increased the level of antioxidant glutathione in brain tissues. |
Subash et al. [52] | In vivo (APPsw/Tg2576 mice) | To evaluate the antioxidant effects of polyphenols on animal models | Supplementation with 4% pomegranate attenuated oxidative damage by reducing LPO and protein carbonyl levels and by restoring the activity of antioxidant enzymes. |
Ahmed et al. [53] | In vivo (R1.40 transgenic mice) | To demonstrate the anti-AD effects of pomegranate extract | The extract did not demonstrated benefits on cognitive performance but demonstrated an anti-amyloidogenic effect. This benefit may be related to effects on the γ-secretase enzyme. |
Braidy et al. [54] | In vivo (APPsw/Tg2576 mice) | To study the effects of dietary supplementation of 4% pomegranate extract on neuroinflammation and synaptic plasticity | Supplementation for 15 months reduced the loss of synaptic structure proteins (PSD-95, Munc18-1, SNAP25, and synaptophysin), the phosphorylation of p-CaMKIIα/CaMKIIα and pCREB/CREB, and neuroinflammatory activity. Furthermore, enhanced autophagy and activation of the mammalian target of rapamycin signaling pathway were observed. |
Morzelle et al. [55] | In vivo (C57Bl/6 mice) | To demonstrate the effects of pomegranate peel extract on spatial memory, neuroplasticity biomarkers, oxidative stress, and inflammation | Consumption of pomegranate reduced amyloid plaque density, increased the expression of the neurotrophin BDNF, and reduced the activity of the enzyme acetylcholinesterase without side effects. |
Almuhayawi et al. [56] | In vivo (AlCl 3-induced AD rat model) | To evaluate the therapeutic and protective effects of pomegranate extract in standard formulation and in nanoparticles | Pomegranate extract has proven effective in preventing oxidative damage and reducing histopathological signs of AD. Extract-loaded nanoparticles demonstrated greater efficacy. |
Khokar et al. [57] | In vitro | To determine the phenolic content of Omani pomegranate peel extracts and study their antioxidant and anticholinesterase activities. | Butanol extract is rich in phenolic compounds and has excellent antioxidant activity, demonstrating anti-AD effects. |
Karagecili et al. [58] | In vitro | To evaluate the antioxidant effects of polyphenols. | The ethanolic extract of pomegranate was found to be rich in phenolic content, exhibiting antioxidant effects and reducing power and the ability to inhibit AChE, α-glycosidase, α-amylase, and hCA II. |
Ali et al. [59] | In vitro (Aβ42-induced N2a/APP cells) | To evaluate the anti-AD effects of pomegranate extracts and which of these is the most active | Among the various compounds, gallagic acid and castalagin markedly reduced the secretion of Aβ peptides, the production of ROS, and the expression levels of BACE1 and APPsβ. |
Rojanathammanee et al. [60] | In vitro (Primary microglia culture) + in vivo (APP/PS1 transgenic mice) | Evaluation of the effects of pomegranate extract supplementation (6.25 mL/L) over three months in attenuating microgliosis. | The treatment improved the mice’s mnemonic functions, reducing the concentration of TNF-α and the transcriptional activity of NFAT. In vitro studies demonstrated that punicalagin and ellagic acid attenuated NFAT activity and decreased TNF-α secretion. |
Kim et al. [62] | In vitro (astrocytes and microglial BV-2 cells) | To investigate the effects of punicalagin on memory deficiency induced by LPS | Punicalagin demonstrated neuroprotective effects by inhibiting LPS-induced expression of iNOS and Cox-2 and the production of ROS, NO, TNF-α, and IL-1β. It also inhibited LPS-induced NF-κB activation and Aβ1–42 generation. |
Clementi et al. [64] | In vitro (human neuroblastoma IMR-32 cells) | To evaluate the effects of resveratrol and punicalagin on the enzymatic activity of methionine sulfoxide reductase A (MsrA) | Pretreatment with resveratrol and punicalagin increased the expression and enzymatic activity of MsrA, resulting in a lowering of the oxidative potential of the cells and a protective effect on the CNS. |
Chen et al. [63] | In vivo (D-gal-induced brain aging mouse model) | To evaluate the neuroprotective effects of punicalagin in animal models | Punicalagin improved learning and memory deficits by reducing neuroinflammation by inhibiting microglial activity. In mouse models, a reduction in MDA and ROS and an inhibition of the NLRP3 inflammasome were observed. |
Yuan et al. [71] | In vitro + in vivo (Caenorhabditis elegans). | To demonstrate which of the main compounds has the characteristics to pass the blood–brain barrier and determine its anti-AD properties | Among the 21 components studied, only urolithins have been shown to have the full characteristics to pass the blood–brain barrier. Urolithins prevented β-amyloid fibrillation in vitro, and methyl-urolithin B demonstrated a protective effect in animal models. |
DaSilva et al. [73] | In vitro (murine BV-2 microglia, human SH-SY5Y neurons) | To evaluate the effects of urolithins on neuroinflammation and search for biomarkers | Urolithins reduce nitric oxide, IL-6, PGE2, and TNF-α levels in microglia. Urolithins also reduce apoptosis and the release of caspase 3/7 and 9 caused by H2O2-induced oxidative stress. |
Author | Study Model | Aims | Outcome |
---|---|---|---|
Braidy et al. [80] | In vitro (human primary neuronal cells) | To evaluate the neuroprotective effects of pomegranate juice extracts against MPTP-induced neurotoxicity. | Pomegranate juice can reverse the effects of MPTP on antioxidant enzyme activities and attenuate neurotoxicity in a dose-dependent manner. The Helow and Malasi varieties have proven superior to the Qusum and Hamadh. |
Tapias et al. [81] | In vivo (rotenone-induced parkinsonism mouse models) | To evaluate the protective effects against PD of pomegranate juice. | Pomegranate juice did not mitigate the disease, but increased nigrostriatal terminal depletion, loss of dopaminergic neurons, inflammatory response, and caspase activation, thus increasing neurodegeneration. |
Małgorzata Kujawska et al. [82] | In vivo (rotenone-induced parkinsonism mouse models) | To evaluate the protective effects against PD of pomegranate juice | Pomegranate juice improved postural stability and neuronal survival and protected against oxidative damage. Furthermore, supplementation reduced α-synuclein aggregation and increased mitochondrial aldehyde dehydrogenase activity, maintaining the antiapoptotic protein Bcl-xL at the control level. |
Małgorzata Kujawska et al. [83] | In vivo (rotenone-induced parkinsonism mouse models) | To study the ability of pomegranate juice to protect against olfactory, motor, and neurochemical alterations in PD. | Pomegranate juice treatment protected against rotenone-induced depletion of dopaminergic neurons in the midbrain, resulting in improved olfactory function and vertical activity. |
Fathy et al. [84] | In vivo (Paraquat-induced parkinsonism mouse models) | To evaluate the protective effects of pomegranate seed extract and juice against PD. | The treatment led to an increased level of tyrosine hydroxylase, dopamine, and its metabolite in the striatum, also improving oxidative stress and significantly inhibiting the expression of the striatal NF-κB gene. A reduction in apoptosis and a decrease in pro-inflammatory cytokines were observed, with a significant increase in IL-10 levels. |
Sarkaki et al. [85] | In vivo (6-OHDA lesioned mice) | To study the effects of ellagic acid on motor disorders, local pallidal EEG, and its frequency band power, and brain antioxidant content. | Ellagic acid improves motor deficits and electrophysiological performance by increasing brain antioxidant content. |
Baluchnejadmojarad et al. [86] | In vivo (6-OHDA lesioned mice) | To study the effects of ellagic acid. | Ellagic acid attenuated rotational distortion, reduced onset latency and total time in the narrow beam task, decreased striatal MDA levels, ROS, and DNA fragmentation, and enhanced antioxidant expression. |
Liu et al. [87] | In vitro (PC12 cells) + In vivo (6-OHDA lesioned mice) | To understand the mechanisms underlying the role of urolithin A in 6-OHDA-induced neurotoxicity. | Urolithin A was effective in inducing protection against 6-OHDA-induced cytotoxicity and apoptosis in cellular models. Furthermore, administration to mouse models improved both motor deficits and nigral-striatal dopaminergic neurotoxicity, while attenuating mitochondrial dysfunction. |
Authors | Sample | Hazardous Factor | Pomegranate Formulation | Outcome | Activity |
---|---|---|---|---|---|
Huang et al. [127] | In vivo (Human keratinocytes) | Stimulation with TNF-α and IFN-γ | Punicalagin isolated from the peel | Suppression of the NF-κB pathway; stimulation of the Nrf2/HO-1 signaling pathway; reduction in IL-8, MCP-1, CCL5, CCL17, and CCL20; downregulation of COX-2 and iNOS activity. | Anti-inflammatory |
Rapa et al. [128] | In vivo (Human keratinocytes) | Stimulation with 5-FU | Juice extract | Reduction in NF-κB pathway activation and the release of TNF-α, IL-6, and IL-1β; stimulation of Nrf2-related enzymes; reduced apoptosis; reduced ROS generation; improved wound repair. | Anti-inflammatory; Antioxidative stress; Pro-healing |
Afaq et al. [129] | In vivo (Human keratinocytes) | UVB | Whole fruit extract | Reduction in NF-κB and MAPK inflammatory pathway activation and the production of IL-1, IL-6, and IL-8. | Anti-inflammatory; photo-aging protection |
Houston et al. [130] | Ex vivo (Full thickness porcine skin) | None | Rind extract (topical) | Downregulation of COX-2. | Anti-inflammatory |
Hamouda et al. [131] | In vivo (Mice) | Phenobarbital and formaldeyde | Seed oil extract (topical) | Downregulation of COX-2. | Anti-inflammatory |
Khan et al. [132] | In vivo (Mice) | UVB | Whole fruit extract (oral) | Downregulation of COX-2, iNOS, and MMP-2, -3, and -9. | Anti-inflammatory; photo-aging protection |
BenSaad et al. [133] | In vivo (Murine macrophages) | LPS | Ellagic acid, gallic acid, and punicalagin | Reduction in NO, PGE-2, and IL-6 production. | Anti-inflammatory |
Bae et al. [134] | In vivo (Human fibroblasts and keratinocytes) + In vivo (mice) | UVB | Ellagic acid (topical in mice) | Reduction in IL-1b and IL-6 and macrophages infiltration in mouse skin sample; reduction in MMP-1 mRNA expression in human fibroblasts and ICAM-1 expression in human keratinocytes. | Anti-inflammatory |
Liu et al. [135] | In vivo (Human keratinocytes) | H2O2 | Fruit extract, punicalagin, ellagic acid, and urolithin A | Reduction in ROS production and H2O2-stimulated caspase-3 activity. | Antioxidative stress |
Seok et al. [136] | In vivo (Human keratinocytes) | PM10 | Punicalagin and (-)-epigallocatechin-3-gallate | Reduction in ROS production and the expression of NOX-1, NOX-2, TNF-α, IL-1β, IL-6, IL-8, and MMP-1. | Antioxidative stress; anti-inflammatory |
Quiles et al. [137] | In vivo (Human fibroblast) | H2O2 | Pomegranate, Centella asiatica, Citrus aurantium var. sinensis, and Herba Cistanche fruits extract | Reduction of ROS production | Antioxidative stress |
Ghimeray et al. [138] | In vivo (21 female patients) + in vivo (spectrophotometric evaluation) | H2O2; O2−; 1,1-diphenyl-2-picrylhydrazyl (in vivo) | Pomegranate, Ginkgo biloba, Ficus carica, and Morus alba fruit extract (2% topical cream in vivo) | High scavenging activities and dose-dependent inhibition of collagenase (in vivo); reduced wrinkle depth (in vivo). | Antioxidative stress; anti-aging |
Chan et al. [139] | In vivo (80 female patients) + in vivo (spectrophotometric evaluation) | 1,1-diphenyl-2-picrylhydrazyl; NO· | Gallic acid-rich fermented extract (oral) | High scavenging activities (in vivo); improvement in moisture, brightness, elasticity, and collagen density (in vivo). | Antioxidative stress; anti-aging |
Abdellatif et al. [140] | In vivo (12 patients) | None | Anthocyanin from fresh arils extract (topical) | Improvements in skin shape, hydration, wrinkle reduction, and firmness | Anti-aging |
Mariné-Casadó et al. [141] | In vivo (Human fibroblast) | UVB | Natural extract | Reduction in ROS levels; increase in pro-collagen type I, total collagen, and hyaluronic acid levels, along with a decrease in MMP-1 levels | Photo-aging protection |
Park et al. [142] | In vivo (Human fibroblast) | UVB | Whole fruit extract | Reduction in MMP-1 expression and increased pro-collagen type I levels | Photo-aging protection |
Abd-Elghany et al. [143] | In vivo (Human fibroblast) | UVA | Ellagic acid | Increased expression of the Co1A1 gene; downregulation of MMP-3. | Photo-aging protection |
Pacheco-Palencia et al. [144] | In vivo (Human fibroblast) | UVA; UVB | Punicalagins-rich extract | Reduced transcription of NF-κB and ROS production; downregulation of caspase-3. | Anti-inflammatory; antioxidative stress; Photo-aging protection |
Zaid et al. [145] | In vivo (Human keratinocytes) | UVB | Polyphenol-rich fruit extract | Reduced upregulation of MMP-1, -2, -7, and -9, and phosphorylation of MAPKs and c-jun | Anti-inflammatory; Photo-aging protection |
Baccarin et al. [146] | In vivo (Human keratinocytes) | UVB | Seed oil nanoemulsion | Reduced cell DNA damage in a dose-dependent manner | Photo-aging protection |
Kang et al. [147] | In vivo + in vivo + ex vivo (mice) | UVB | Juice concentrated powder (oral) | Reduction in skin wrinkles, improvement of skin water contents, collagen type I, and hyaluronan contents (in vivo); reduced IL-1β levels and MPO activity; increased IL-10 levels; reduced skin MMP-1, -9, and -13, and Nox2 mRNA expression (in vivo); dose-dependent decreases in dermis sclerosis and inflammation (ex vivo). | Anti-inflammatory; Photo-aging protection; Anti-aging |
Henning et al. [148] | In vivo (74 female patiens) | UVB | Whole fruit extract and juice extract | No significant changes in the skin microbiota composition; increased of minimum erythema dose | Photo-aging protection |
Murthy et al. [149] | In vivo + ex vivo (mice) | Wound | Peel extract (topical) | Reduction of wound healing (in vivo); increased hydroxyproline content (ex vivo). | Pro-healing |
Hayouni et al. [150] | In vivo (pigs) | Wound | Peel extract (topical) | Increased wound contraction and decreased period of epithelialization, collagen, DNA, and proteins synthesis. | Pro-healing |
Nayak et al. [151] | In vivo + ex vivo (mice) | Wound | Peel extract (topical) | Increased wound contraction, decreased period of epithelialization (in vivo); increased hydroxyproline content (ex vivo). | Pro-healing |
Zekavat et al. [152] | In vivo (mice) | Wound | Peel extract (topical) | Reduced wound healing time. | Pro-healing |
Nasiri et al. [153] | In vivo (mice) | Wound | Flower extract (topical) | Increased wound contraction. | Pro-healing |
Elzayat et al. [154] | In vivo (mice) | Wound | Pomegranate, henna, and myrrh extract (topical) | Increased wound contraction and decreased period of epithelialization. | Pro-healing |
Lukiswanto et al. [155] | Ex vivo (mice) | Wound | Ellagic acid rich-whole fruit extract | Decreased period of epithelialization; increased density of collagen and angiogenesis; reduced number of inflammatory cells (PMNs) | Pro-healing; anti-inflammatory |
Yuniarti et al. [156] | Ex vivo (mice) | Wound | Ellagic acid rich-whole fruit extract | Increased density of collagen and angiogenesis; reduced number of inflammatory cells (PMNs). | Pro-healing; anti-inflammatory |
Aslam et al. [157] | In vivo (Human keratinocytes and fibroblasts) | None | Peel, juice, and seed extract | Stimulation of keratinocytes proliferation (seed oil); increased type I procollagen synthesis and inhibition of MMP-1 production (peel extract). | Pro-healing; anti-inflammatory |
Zhang et al. [158] | In vivo + ex vivo (pigs) | Wound | Peel extract | Reduction in epithelialization and fur growing time (in vivo); early VEGF-A and TGF-β1 mRNA expression. | Pro-healing |
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Cordiano, R.; Gammeri, L.; Di Salvo, E.; Gangemi, S.; Minciullo, P.L. Pomegranate (Punica granatum L.) Extract Effects on Inflammaging. Molecules 2024, 29, 4174. https://doi.org/10.3390/molecules29174174
Cordiano R, Gammeri L, Di Salvo E, Gangemi S, Minciullo PL. Pomegranate (Punica granatum L.) Extract Effects on Inflammaging. Molecules. 2024; 29(17):4174. https://doi.org/10.3390/molecules29174174
Chicago/Turabian StyleCordiano, Raffaele, Luca Gammeri, Eleonora Di Salvo, Sebastiano Gangemi, and Paola Lucia Minciullo. 2024. "Pomegranate (Punica granatum L.) Extract Effects on Inflammaging" Molecules 29, no. 17: 4174. https://doi.org/10.3390/molecules29174174