Punicalagin, a natural product isolated and purified from the peel of Punica granatum L., is a potential alternative or supplemental agent for prevention of Salmonella infection, has a greater antifungal activity against T[3]. Punicalagin (100 mg/ml) induces apoptosis in HT-29, HCT116 colon cells[4]. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration[5]. Punicalagin slightly inhibits the PLpro activity with an IC50 of over 50 μM. Punicalagin inhibits the plaque formation of SARS-CoV-2 in a dose-dependent manner, with EC50 values of 7.20 μM[6]. Punicalagin (10 mg/kg) inhibits the edema rate of 58.15% in rats[7].
Punicalagin/安石榴甙 细胞实验
Cell Line
Concentration
Treated Time
Description
References
THP-1 cells
50 µM
12 hours
PUN upregulated AhR expression in THP-1 cells.
Cell Commun Signal. 2024 Oct 3;22(1):473.
Mouse peritoneal macrophages
50 µM
12 hours
PUN alone or in combination with LPS upregulated AhR expression, with the combination being more potent.
Cell Commun Signal. 2024 Oct 3;22(1):473.
Bovine endometrial epithelial cells (bEECs)
5, 10, 20 µg/ml
2 hours pretreatment followed by LPS stimulation for 12 hours
To evaluate the inhibitory effect of punicalagin on LPS-induced pro-inflammatory cytokine expression. Results showed that punicalagin significantly reduced mRNA expression of IL-1β, IL-6, IL-8, and TNF-α.
J Zhejiang Univ Sci B. 2017 Jun;18(6):481-491.
ARPE-19 cells
10 µM
24 hours
To evaluate the protective effect of PUN against UV-A radiation-induced oxidative damage. PUN pre-treatment significantly increased cell viability, reduced ROS levels, and activated the Nrf2/HO-1 signaling pathway.
Antioxidants (Basel). 2020 Jun 2;9(6):473.
Lactic Acid Bacteria (LAB)
30 μg/mL
24 hours
To assess the ability of LAB to transform punicalagin into bioactive molecules such as ellagic acid. Results showed all tested LAB strains could convert punicalagin into ellagic acid, but no biosynthesis of urolithins was observed.
J Agric Food Chem. 2022 Dec 28;70(51):16273-16285.
RAW264.7 macrophages
12.5, 25, 50 µM
24 hours
To evaluate the anti-inflammatory effects of punicalagin on LPS-induced RAW264.7 macrophages. Results showed that punicalagin significantly inhibited LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration, and inhibited NF-κB and MAPK signaling pathways.
Nutrients. 2019 Nov 15;11(11):2794.
Mouse chondrocytes
50 μg/mL
24 hours
To evaluate the effect of Punicalagin on chondrocyte viability, results showed that Punicalagin at 50 μg/mL had no significant cytotoxicity within 24 hours and reversed TBHP-induced decrease in cell viability
Drug Des Devel Ther. 2020 Dec 15;14:5521-5533.
Human U87MG glioma cells
1-30 µg/mL
24 or 48 hours
Punicalagin dose-dependently inhibited cell viability, associated with increased cyclin E levels and decreased cyclin B and A levels.
Acta Pharmacol Sin. 2013 Nov;34(11):1411-9.
CCD 841 (normal colon epithelial cells)
0–100 µg/mL
24, 48, 72 hours
To assess the toxicity of PU on normal cells. Results showed PU did not induce significant cytotoxicity on CCD 841 cells.
Nutrients. 2020 Aug 13;12(8):2430.
VeroE6 cells
0, 50, 100 µM
30 minutes
Evaluate the inhibitory ability of Punicalagin on the binding of SARS-CoV-2 Spike protein to ACE2. Results showed Punicalagin exhibited the highest activity in inhibiting Spike-ACE2 interaction.
Elife. 2023 Aug 29;12:e84899.
NCI-H460 cells
0, 50, 100 µM
30 minutes
Evaluate the inhibitory ability of Punicalagin on the binding of SARS-CoV-2 Spike protein to ACE2. Results showed Punicalagin exhibited the highest activity in inhibiting Spike-ACE2 interaction.
Elife. 2023 Aug 29;12:e84899.
293T-ACE2 cells
0, 50, 100 µM
30 minutes
Evaluate the inhibitory ability of Punicalagin on the binding of SARS-CoV-2 Spike protein to ACE2. Results showed Punicalagin exhibited the highest activity in inhibiting Spike-ACE2 interaction.
Elife. 2023 Aug 29;12:e84899.
Human podocyte cell line
1.5 µM
30 minutes
Inhibited PAR2-mediated activation of ERK1/2 and NF-κB signaling pathways, reduced ICAM-1 and VCAM-1 expression
Int J Mol Sci. 2020 Jul 14;21(14):4975.
Punicalagin/安石榴甙 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NZB/W F1 mice
Lupus nephritis model
Intraperitoneal injection
0.3, 1, 3 mg/kg
3 times per week for 7 weeks
PCG significantly improved kidney injury and splenomegaly, reduced proteinuria and renal ICAM-1 and VCAM-1 expression
Int J Mol Sci. 2020 Jul 14;21(14):4975.
Kunming mice
Hyperuricemia mice model
Oral gavage
100, 200, 300 mg/kg
Once daily for two weeks
To evaluate the effect of PU on hyperuricemia and its mechanisms. PU significantly decreased serum uric acid levels in hyperuricemia mice and effectively alleviated kidney and intestinal damage caused by hyperuricemia.
J Adv Res. 2025 Mar;69:449-461
C57BL/6 mice
LPS-induced inflammation model
Intraperitoneal injection
12.5 mg/kg
Single dose, lasting 12 hours
PUN increased the percentage of AhR-positive peritoneal macrophages in LPS-induced mice.
Cell Commun Signal. 2024 Oct 3;22(1):473.
Wistar albino rats
DENA-induced hepatocarcinogenesis model
Oral
18.5 mg/kg
Daily administration for 11 weeks
To investigate the chemoprevention effects of Punicalagin against DENA-induced hepatocarcinogenesis. Results showed that Punicalagin induced some modulation in DENA-treated rats but did not show potent chemoprevention activity and induced some side effects.
Cancer Cell Int. 2022 Nov 2;22(1):333
C57BL/6 mice
Destabilization of the medial meniscus (DMM) model
Oral gavage
20 mg/kg
Once daily for 8 weeks
To evaluate the therapeutic effect of Punicalagin on osteoarthritis in DMM model mice, results showed that Punicalagin treatment significantly alleviated cartilage degeneration and synovitis
Drug Des Devel Ther. 2020 Dec 15;14:5521-5533.
C57BL/6J mice
High-fat diet/streptozotocin-induced diabetic mice model
Intragastric administration
20 mg/kg
Once a day for 8 weeks
Punicalagin ameliorates diabetic nephropathy by inhibiting pyroptosis via the TXNIP/NLRP3 pathway. Results showed that punicalagin significantly decreased blood urea nitrogen, serum creatinine, and urine albumin to creatinine ratio in diabetic mice, and alleviated symptoms of glomerular interstitial hyperplasia and glomerular hypertrophy.
Nutrients. 2020 May 22;12(5):1516
Swiss albino mice
Methotrexate-induced hepatotoxicity model
Oral
25 and 50 mg/kg
Once daily for 10 days
Punicalagin protects against the development of methotrexate-induced hepatotoxicity in mice via activating Nrf2 signaling and decreasing oxidative stress, inflammation, and cell death.
Int J Mol Sci. 2022 Oct 15;23(20):12334
Sprague-Dawley rats
Parkinson's disease model (induced by MnCl2) and social isolation model
Oral
30 mg/kg
Once daily for 5 weeks
To evaluate the neuroprotective effects of Punicalagin against Parkinson's disease and social isolation. Punicalagin significantly improved behavioral, biochemical, and histopathological changes by modulating multiple pathways (e.g., HMGB1/RAGE/TLR4/NF-κB/NLRP3/Caspase-1, JAK-2/STAT-3, PI3K/AKT/GSK-3β/CREB, AMPK/SIRT-1, Nrf2/HO-1, and PERK/CHOP/Bcl-2) to mitigate oxidative stress, neuroinflammation, and neuronal apoptosis.
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