Pharmacological Activities of Punicalagin: A Review
Traditional medicine was becoming more popular as a component of complementary and alternative medicine around the world. The ability to provide information on the pharmacological effects of plants requires a thorough understanding of the chemical components found in plants. One of the chemical compounds reported having pharmacological activity was punicalagin. Punicalagin was a polyphenol compound found in Punica granatum, Lafoensia pacari, and genus Terminalia. This review provides information on the pharmacological activities of punicalagin. The bibliographic databases used as the sources of information were PubMed, Google Scholar, and ScienceDirect. The pharmacological activities of punicalagin have been reported as anticancer, antioxidant, hepatoprotective, antimicrobial, antivirus, neuroprotective, antiinflammation, gastroprotective, pre-eclampsia, antidiabetic, and anti hyperlipidemia.
Keywords: Punicalagin, Antioxidant, Anticancer, Antivirus.
2. Potì F, Santi D, Spaggiari G, Zimetti F, Zanotti I. Polyphenol health effects on cardiovascular and neurodegenerative disorders: A review and meta-analysis. Int J Mol Sci. 2019; 20(2):1-26. https://doi.org/10.3390/ijms20020351
3. Atrahimovich D, Samson AO, Khattib A, Vaya J, Khatib S. Punicalagin decreases serum glucose levels and increases PON1 activity and HDL anti-inflammatory values in Balb/c Mice Fed a high-fat diet. Oxid Med Cell Longev. 2018; 2018. https://doi.org/10.1155/2018/2673076
4. Jain V, Murugananthan G, Deepak M, Viswanatha GL, Manohar D. Isolation and standardization of various phytochemical constituents from methanolic extracts of fruit rinds of Punica granatum. Chin J Nat Med. 2011; 9(6):414-20. http://dx.doi.org/10.3274/SP.J.1009.2011.00414
5. Feng L, Yin Y, Yang X, Tang H, Jiao Q. Dynamic variations in punicalagin and related metabolic substances in pomegranate fruit and leaves during development periods. Hortic J. 2019; 88(4):444-54. https://doi.org/10.2503/hortj.UTD-088
6. Giamogante F, Marrocco I, Cervoni L, Eufemi M, Chichiarelli S, Altieri F. Punicalagin, an active pomegranate component, is a new inhibitor of PDIA3 reductase activity. Biochimie. 2018; 147:122-9. https://doi.org/10.1016/j.biochi.2018.01.008
7. Carneiro CC, da Costa Santos S, de Souza Lino R, Bara MTF, Chaibub BA, de Melo Reis PR, Chaves DA, da Silva AJR, Silva LS, de Melo E Silva D, Chen LC. Chemopreventive effect and angiogenic activity of punicalagin isolated from leaves of Lafoensia pacari A. St. Hil. Toxicol Appl Pharmacol. 2016; 310:1-8. https://doi.org/10.1016/j.taap.2016.08.015
8. PubChem. [cited 2021 Nov 29]. https://pubchem.ncbi.nlm.nih.gov/compound/44584733#section=2D-Structure
9. Pan L, Duan Y, Ma F, Lou L. Punicalagin inhibits the viability, migration, invasion, and EMT by regulating GOLPH3 in breast cancer cells. J Recept Signal Transduct. 2020; 40(2):173-80. https://doi.org/10.1080/10799893.2020.1719152
10. Benchagra L, Berrougui H, Islam MO, Ramchoun M. Antioxidant effect of Moroccan pomegranate (Punica granatum L). Foods. 2021; 10:2219. https://doi.org/10.3390/foods10092219
11. Guan S, Wang Z, Huang Y, Huang G, Guan Y, Jiang W, Lu J. Punicalagin exhibits negative regulatory effects on LPS-induced acute lung injury. Eur Food Res Technol. 2014; 239(5):837-45. https://doi.org/10.1007/s00217-014-2280-2
12. Huang M, Wu K, Zeng S, Liu W, Cui T, Chen Z, Lin L, Chen D, Ouyang H. Punicalagin inhibited inflammation and migration of fibroblast-like synoviocytes through Nf-κB pathway in the experimental study of rheumatoid arthritis. J Inflamm Res. 2021; 14:1901-13. https://doi.org/10.2147/JIR.S302929
13. Aloqbi A, Omar U, Yousr M, Grace M, Lila MA, Howell N. Antioxidant Activity of Pomegranate Juice and Punicalagin. Nat Sci. 2016; 08(06):235-46. https://doi.org/10.4236/ns.2016.86028
14. Chaibub BA, Martins JLR, de Paula JR, da C. Santos S, Costa EA, Bara MTF. Gastroprotective activity of punicalagin and Lafoensia pacari in mice. Rev Bras Farmacogn. 2020; 30(3):423-6. https://doi.org/10.1007/s43450-020-00007-7
15. Zhang XR, Kaunda JS, Zhu HT, Wang D, Yang CR, Zhang YJ. The genus Terminalia (Combretaceae): An ethnopharmacological, phytochemical and pharmacological review. Nat Products Bioprospect. 2019; 9(6):357-92. https://doi.org/10.1007/s13659-019-00222-3
16. Cheng X, Yao X, Xu S, Pan J, Yu H, Bao J, Guan H, Lu R, Zhang L. Punicalagin induces senescent growth arrest in human papillary thyroid carcinoma BCPAP cells via NF-κB signaling pathway. Biomed Pharmacother. 2018; 103(January):490-8. https://doi.org/10.1016/j.biopha.2018.04.074
17. Li Y, Ye T, Yang F, Hu M, Liang L, He H, Li Z, Zeng A, Li Y, Yao Y, Xie Y, An Z, Li S. Punica granatum (pomegranate) peel extract exerts potent antitumor and anti-metastasis activity in thyroid cancer. RSC Adv. 2016; 6(87):84523-35. https://doi.org/10.1039/C6RA13167K
18. Subkorn P, Norkaew C, Deesrisak K, Tanyong D. Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia. PeerJ. 2021; 9:e12303. https://doi.org/10.7717/peerj.12303
19. Wang Y, Chen B, Longtine MS, Nelson DM. Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis. Reproduction. 2016; 151(2):97-104. https://doi.org/10.1530/REP-15-0287
20. Wang SG, Huang MH, Li JH, Lai FI, Lee HM, Hsu YN. Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma cells. Acta Pharmacol Sin. 2013; 34(11):1411-9. https://doi.org/10.1038/aps.2013.98
21. Khalil AA, Khan MR, Shabbir MA, Rahman KU. In vitro antioxidant activity and punicalagin content quantification of pomegranate peel obtained as agro-waste after juice extraction. Pakistan J Agric Sci. 2018; 55(1):197-201. https://doi.org/10.21162/PAKJAS/18.5663
22. Oudane B, Boudemagh D, Bounekhel M, Sobhi W, Vidal M, Broussy S. Isolation, characterization, antioxidant activity, and protein-precipitating capacity of the hydrolyzable tannin punicalagin from pomegranate yellow peel (Punica granatum). J Mol Struct. 2018; 1156:390-6. https://doi.org/10.1016/j.molstruc.2017.11.129
23. Fouad AA, Qutub HO, Al-Melhim WN. Punicalagin alleviates hepatotoxicity in rats challenged with cyclophosphamide. Environ Toxicol Pharmacol. 2016; 45:158-62. https://doi.org/10.1016/j.etap.2016.05.031
24. Yan C, Sun W, Wang X, Long J, Liu X, Feng Z, Liu J. Punicalagin attenuates palmitate-induced lipotoxicity in HepG2 cells by activating the Keap1-Nrf2 antioxidant defense system. Mol Nutr Food Res. 2016; 60(5):1139-49. https://doi.org/10.1002/mnfr.201500490
25. Xu Y, Shi C, Wu Q, Zheng Z, Liu P, Li G, Peng X, Xia X. Antimicrobial Activity of Punicalagin Against Staphylococcus aureus and Its Effect on Biofilm Formation. Foodborne Pathog Dis. 2017; 14(5):282-7. https://doi.org/10.1089/fpd.2016.2226
26. Gosset-Erard C, Zhao M, Lordel-Madeleine S, Ennahar S. Identification of punicalagin as the bioactive compound behind the antimicrobial activity of pomegranate (Punica granatum L.) peels. Food Chem. 2021; 352(October 2020):129396. https://doi.org/10.1016/j.foodchem.2021.129396
27. Yang Y, Xiu J, Zhang L, Qin C, Liu J. Antiviral activity of punicalagin toward human enterovirus 71 in vitro and in vivo. Phytomedicine. 2012; 20(1):67-70. https://doi.org/10.1016/j.phymed.2012.08.012
28. Saadh MJ, Almaaytah AM, Alaraj M, Dababneh MF, Sa'Adeh I, Aldalaen SM, Khashid AM, Alboghdadly A, Hailt M, Khaleel A, Al-Hamaideh KD. Punicalagin and zinc (II) ions inhibit the activity of SARS-CoV-2 3CL-protease in vitro. Eur Rev Med Pharmacol Sci. 2021; 25(10):3908-13. http://dx.doi.org/10.26355/eurrev_202105_25953
29. Li H, Xu F, Liu C, Cai A, Dain JA, Li D, Seeram NP, Cho BP, Ma H. Inhibitory effects and surface plasmon resonance-based binding affinities of dietary hydrolyzable tannins and their gut microbial metabolites on SARS-CoV-2 main protease. J Agric Food Chem. 2021; 69(41):12197-208. https://doi.org/10.1021/acs.jafc.1c03521
30. Olajide OA, Kumar A, Velagapudi R, Okorji UP, Fiebich BL, Uchechukwu P. Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia. Mol Nutr Food Res. 2014; 58(9):1843-51. https://doi.org/10.1002/mnfr.201400163
31. Peng J, Wei D, Fu Z, Li D, Tan Y, Xu T, Zhou J, Zhang T. Punicalagin ameliorates lipopolysaccharide-induced acute respiratory distress syndrome in mice. Inflammation. 2015; 38(2):493-9. https://doi.org/10.1007/s10753-014-9955-5
32. Yaidikar L, Byna B, Thakur SR. Neuroprotective effect of punicalagin against cerebral ischemia reperfusion-induced oxidative brain injury in rats. J Stroke Cerebrovasc Dis . 2014; 23(10):2869-78. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.07.020
33. Wang Y, Huang M, Yang X, Yang Z, Li L, Mei J. Supplementing punicalagin reduces oxidative stress markers and restores angiogenic balance in a rat model of pregnancy-induced hypertension. Korean J Physiol Pharmacol. 2018; 22(4):409-17. https://doi.org/10.4196/kjpp.2018.22.4.409
34. Koren-gluzer M, Aviram M, Meilin E, Hayek T. The antioxidant HDL-associated paraoxonase-1 ( PON1 ) attenuates diabetes development and stimulates β-cell insulin release. Atherosclerosis. 2011; 219(2):510-8. https://doi.org/10.1016/j.atherosclerosis.2011.07.119
35. Zou X, Yan C, Shi Y, Cao K, Xu J, Wang X, Chen C, Luo C, Li Y, Gao J, Pang W, Zhao K, Zhao F, Li H, Zheng A, Sun W, Long J, Szeto IMY, Zhao Y, Dong Z, Zhan Pl Wang J, Lu W, Zhang Y, Liu J, Feng Z. Mitochondrial dysfunction in obesity-associated nonalcoholic fatty liver disease: The protective effects of pomegranate with its active component punicalagin. Antioxidants Redox Signal. 2014; 21(11):1557-70. https://doi.org/10.1089/ars.2013.5538
36. Zhong J, Reece EA, Yang P. Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects. Biochem Biophys Res Commun. 2015; 467(2):179-84. Available from: https://doi.org/10.1016/j.bbrc.2015.10.024
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).