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THERAPEUTIC EFFECTS OF POMEGRANATE SEED OIL:
EXPERIMENTAL EVIDENCE AND TRANSLATIONAL PROSPECTS
Khojieva P.D. 1, Khojiev D.Ya. 2, Tatun T.V. 3, Mijigurskaya D.D. 4
1 Tashkent State Dental Institute, Tashkent, Uzbekistan
2 Termez Branch of the Tashkent Medical Academy, Termez, Uzbekistan
3 Grodno State Medical University, Grodno, Belarus
4 Grodno University Clinic, Republic of Belarus
Abstract
Pomegranate seed oil (PSO) exhibits a multifaceted pharmacological profile
attributable to its high concentration of punicic acid, tocopherols, and a diverse array of
polyphenols. This critical review integrates current pre‑clinical findings with original data
generated by the authors in a nitrous oxide–induced rat model of hepatic fibrosis. PSO
administration
(1 mL kg⁻¹ day⁻¹, 30 days) attenuated collagen deposition and
down‑regulated key profibrotic mediators—TGFβ1, α-SMA, and CD68—by 40-45 %
versus untreated fibrotic controls (p < 0·01). These outcomes, together with previously
documented antioxidant, anti‑inflammatory, cardioprotective, and antiproliferative
effects, position PSO as a promising candidate for adjunctive management of chronic
fibro‑inflammatory disorders.
Keywords:
pomegranate seed oil; conjugated linolenic acid; oxidative stress; liver
fibrosis; macrophage polarization; translational pharmacology.
ТЕРАПЕВТИЧЕСКИЕ ЭФФЕКТЫ МАСЛА КОСТОЧЕК ГРАНАТА:
ЭКСПЕРИМЕНТАЛЬНЫЕ ДОКАЗАТЕЛЬСТВА И ТРАНСЛЯЦИОННЫЕ
ПЕРСПЕКТИВЫ
Хожиева П.Д. 1, Хожиев Д.Я. 2, Татун Т.В. 3, Мижигурская Д.Д. 4
1 УО «Ташкентский государственный стоматологический институт», г.
Ташкент, Узбекистан
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2 УО «Термезский филиал Ташкентской медицинской академии», г. Термез,
Узбекистан
3 УО «Гродненский государственный медицинский университет», г. Гродно,
Беларусь
4 УЗ «Гродненская университетская клиника», Республика Беларусь
Аннотация
В обзоре систематизированы и критически оценены экспериментальные
данные о терапевтическом потенциале масла косточек граната (Punica granatum seed
oil, PSO). Дополнительно представлены результаты авторских исследований,
демонстрирующие выраженные антифибротические и гепатопротективные
свойства PSO в модели NO
2
индуцированного фиброза печени у крыс. Под
действием PSO отмечено статистически значимое (p < 0,05) снижение экспрессии
маркёров фиброгенеза — TGF-β1, α-SMA и CD68, что кореллировало с
уменьшением плотности коллагеновых волокон по данным гистоморфометрии.
Обсуждаются молекулярные мишени и перспективы трансляции полученных
результатов в клиническую практику.
Ключевые слова:
масло косточек граната, пунциновая кислота, оксидативный
стресс, фиброз печени, макрофаги М2, антифибротическая терапия.
Introduction
The resurgence of interest in phytochemicals as disease‑modifying agents has
foregrounded
Punica granatum
L. seed oil in experimental pharmacology. Beyond the
fruit’s well‑characterised juice polyphenome, PSO is enriched in conjugated linolenic
isomers—chiefly punicic acid—that confer potent radical‑scavenging and signal-
modulating capacities [1, 4]. Accumulating evidence delineates six principal domains of
bioactivity:
antioxidant,
anti‑inflammatory,
cardioprotective,
antifibrotic,
hepatoprotective, and antiproliferative [2, 3]. Notwithstanding these advances, integrative
analyses that contextualise heterogeneous in vivo protocols and in vitro assays remain
scarce, complicating translational extrapolation.
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Materials and Methods
2.1 Animals and Experimental Design
Thirty male Wistar rats (220 ± 15 g) were randomised into:
1.
Intact control;
2.
NO₂‑induced fibrosis;
3.
NO₂ + PSO therapy.
Chronic fibrosis was elicited by inhalational exposure to NO₂ (10 ppm, 4 h day,
90 days). PSO (cold‑pressed, 79 % punicic acid) was administered via oral gavage for the
final 30 days.
2.2 Outcome Measures
Liver specimens were fixed in 10 % formalin and stained with Masson’s trichrome;
fibrosis area was quantified using ImageJ. Immunohistochemistry employed monoclonal
antibodies against TGF‑β1, α‑SMA, and CD68 (M2 macrophage marker). Enzymatic
indices of oxidative stress (SOD, catalase, GPx) and lipid peroxidation (MDA) were
assayed spectrophotometrically.
2.3 Statistical Analysis
Data are presented as mean ± SEM. Inter-group differences were evaluated by
one‑way ANOVA with Tukey’s post hoc test (GraphPad 10), α = 0,05.
Results
3.1 Histopathology
NO₂ challenge induced bridging fibrosis and periportal septa occupying
27·4 ± 3·1 % of parenchymal area. PSO treatment curtailed fibrotic expansion to
14·9 ± 2·2 % (p < 0·01 vs. fibrosis group).
3.2 Immunohistochemical Profiling
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Relative optical density analyses demonstrated a 45 % down‑shift in TGF‑β1 and
40 % in α‑SMA expression within down‑shiftlivers (p < 0·01). CD68⁺ macrophage
infiltration decreased by 38 % (p < 0,05).
3.3 Redox Homeostasis
PSO normalised MDA levels (–36 %) while augmenting SOD (+42 %), catalase
(+35 %), and GPx (+39 %) activities relative to fibrotic controls (p < 0,05 for all).
Systemic Pharmacodynamic Spectrum of PSO
Table 1. Pre-clinical evidence base for PSO bioactivities
Effect
Experimental Model /
Method
Key Markers / Outcome
Antioxidant
Rats (oxidative stress)
↑ SOD, ↓ MDA
Anti‑inflammatory
Mice (colitis, arthritis)
↓ TNF‑α, COX‑2, IL‑6
Antifibrotic
Rats (CCl₄, NO₂)
↓ TGF‑β1, α‑SMA, CD68
Hepatoprotective
CCl₄, acetaminophen
↓ ALT, AST, necrosis
Cardioprotective
Rabbits
(hypercholesterolemia)
↓ LDL, ↑ HDL, ↓ lipid
oxidation
Antiproliferative
Tumour cell lines
↑ caspase‑3, ↓ Bcl‑2,
↓ VEGF
Table 1 summarises the breadth of PSO bioactivity substantiated across diverse
pre‑clinical paradigms. Notably, the lipid-lowering and endothelial‑protective
results reported by Kaplan et al. [1] and De Nigris et al. [3] dovetail with our
antifibrotic findings, underscoring the oil’s pleiotropic modulation of redox-
inflammatory circuits.
Discussion
The confluence of antioxidant potentiation and cytokine reprogramming observed
herein coheres with the canonical antifibrotic axis involving Nrf2 activation and TGF‑β1
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suppression [5]. PSO’s high punicic-to-linoleic acid ratio may underlie its superior lipid-
peroxidation-blocking efficacy compared with non-conjugated ω-3/ω-6 sources.
Furthermore, the attenuation of M2 polarisation expands current interpretations of PSO
beyond simple antioxidation, implicating immunometabolic realignment as a contributory
mechanism.
Methodological heterogeneity across published studies—dosage, extraction
techniques, and duration—remains a translational barrier. Standardisation initiatives and
head-to-head comparator trials against established antifibrotics (e.g., obeticholic acid)
are imperative.
Conclusion
Our data corroborate and extend the antifibrotic and hepatoprotective portfolio of
PSO, delineating mechanistic intersections between oxidative stress abatement and
fibrogenic pathway inhibition. These insights warrant progression to phase I safety
profiling and controlled clinical exploration in early‑stage hepatic fibrosis.
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