Waste valorization utilizing green nanotechnology: a sustainable approach for pomegranate peel agro wastes in skincare formulations

Abstract

Pomegranate peels, a valuable waste byproduct, aligned with the Sustainable Development Goals by United Nations offering a possibility for use as a raw material in herbal formulations. The review aims to highlight the pharmaceutical importance of pomegranate peel bioactive compounds and their applications in the skincare industry. A systematic search of studies identified through scientific databases resulted in the PRISMA chart. Additionally, an exhaustive search using keywords such as pomegranate peel, skincare, ADME, nanoparticles, therapeutics, and bioactive compounds led to a bibliometric analysis. The peels support the waste-to-wealth concept with a rich repertoire of flavonoids, including quercetin, kaempferol, and catechin, as well as polyphenolic compounds and other tannin compounds, such as punicalagin and ellagic acid. These compounds serve as natural reducing agents for synthesizing various nanoparticles and unveiling therapeutic activities, including antibacterial, anti-inflammatory, anticancer, and antioxidant properties. Furthermore, an attempt to bridge the gap by examining the pharmacokinetic studies on key bioactive compounds identified through ADME analysis, supported the transdermal and topical applications of these compounds. The profiling suggests that tannin compounds, such as punicalagin, have low skin permeability, indicating potential roles in topical applications. In contrast, ellagic acid exhibits high skin permeability, suggesting possible applications in products such as sunscreens. The combinatorial formulation, consisting of pomegranate peel-derived nanoparticles, has potential additional benefits by facilitating skincare products with photoprotection, enhanced hydration, and topical applications. The study also calls for future research focused on clinical validation and scalable commercial applications.

Graphical Abstract

Keywords

Sustainability / Waste valorization / Pomegranate peels / Circular economy / Green nanotechnology / Bioactive components / Skincare formulations

References

[1] Abbas R, Aamir M, Saeed F, Shankar A, Kaur J, Nadeem R, Chauhan A, Imran A, Afzaal M, Kinki A. Development and nutritional evaluation of pomegranate Peel enriched bars. PLoS ONE, 2025, 20: e0315830

[2] Abdelmigid HM, Hussien NA, Alyamani AA, et al. . Green synthesis of zinc oxide nanoparticles using pomegranate fruit Peel and solid coffee grounds vs. Chemical method of synthesis, with their biocompatibility and antibacterial properties investigation. Molecules, 2022, 27: 1236

[3] Abu-Dalo M, Jaradat A, Albiss BA, Al-Rawashdeh NAF (2019) Green synthesis of TiO₂ NPs/pristine pomegranate peel extract nanocomposite and its antimicrobial activity for water disinfection. J Environ Chem Eng 7. https://doi.org/10.1016/j.jece.2019.103370

[4] Abu-Niaaj LF, Al-Daghistani HI, Katampe I, et al. . Pomegranate peel: bioactivities as antimicrobial and cytotoxic agents. Food Sci Nutr, 2024, 12: 2818-2832.

[5] Afzaal M, Saeed F, Ahmad A, Saeed M, Usman I, Nouman M (2022) Microbial processing for valorization of waste and application. Environ Microbiology: Adv Res Multidisciplinary Appl 187–210. https://doi.org/10.2174/9781681089584122010012

[6] Ahmed HM, Sobhy NA, Elkhateeb MA, et al. . Preparation and characterization of iron nanoparticles by green synthesis method and its application in water treatment. SSP, 2023, 342: 11-25.

[7] Ahmed RM, Esmaeil DAM, El-Nagdy SY, El-Sisi NA. Antitumoral properties of the pomegranate Peel and blueberry extracts against tongue carcinoma ( study). Saudi Dent J, 2023, 35: 985-995.

[8] Ain HBU, Tufail T, Bashir S, et al. . Nutritional importance and industrial uses of pomegranate peel: A critical review. Food Sci Nutr, 2023, 11: 2589-2598.

[9] Alam M, Ahmed S, Elasbali AM, Adnan M, Alam S, Hassan M I, Pasupuleti V R (2022) Therapeutic implications of caffeic acid in cancer and neurological diseases. Front Oncol 12. https://doi.org/10.3389/fonc.2022.860508

[10] Ammar NM, Hassan HA, Elkady MA, et al. . Promising anticancer activity of pomegranate peels extract (PPE) against bacterial pathogens-induced colon cancer in mice model. Egypt J Chem, 2023, 66: 1259-1277.

[11] Aneja D, Debnath M, Darbari P, et al. . The emerging superfruit: ’s role in revolutionizing the nutraceutical and food industries. Curr Nutr Rep, 2025, 14: 73.

[12] Ansari MO, Ahmad MF, Parveen N, et al. . Iron oxide Nanoparticles-Synthesis, surface Modification, applications and toxicity: A review. Mater Focus, 2017, 6: 269-279.

[13] Arunkumar J, Rajarajan S. Study on antiviral activities, drug-likeness and molecular Docking of bioactive compounds of L. to herpes simplex virus – 2 (HSV-2). Microb Pathog, 2018, 118: 301-309.

[14] Aswathi VP, Meera S, Maria CGA, Nidhin M. Green synthesis of nanoparticles from biodegradable waste extracts and their applications: a critical review. Nanotechnol Environ Eng, 2023, 8: 377-397.

[15] Baccarin T, Lemos-Senna E. Potential application of nanoemulsions for skin delivery of pomegranate Peel polyphenols. AAPS PharmSciTech, 2017, 18: 3307-3314.

[16] Ballistreri G, Amenta M, Fabroni S, et al. . Sustainable extraction protocols for the recovery of bioactive compounds from By-Products of pomegranate fruit processing. Foods, 2024, 13: 1793

[17] Baniasadi H, Fathi Z, Lizundia E, Cruz CD, Abidnejad R, Fazeli M, Tammela P, Kontturi E, Lipponen J, Niskanen (2025) Development and characterization of pomegranate peel extract-infused carboxymethyl cellulose composite films for functional, sustainable food packaging. Food Hydrocoll 158:110525. https://doi.org/10.1016/j.foodhyd.2024.110525

[18] Bandara UY, Soysa P, Witharana C. Induction of apoptosis and antiproliferative activity of MCF-7 human breast cancer cells with sonicated aqueous Peel extract of L. (Nimali sp). Asian Pac J Cancer Prev, 2024, 25: 3967

[19] Bandeira M, Giovanela M, Roesch-Ely M, Devine D M, da Silva Crespo (2020) Green synthesis of zinc oxide nanoparticles: a review of the synthesis methodology and mechanism of formation. Sustain Chem Pharm 15. https://doi.org/10.1016/j.scp.2020.100223

[20] Baranwal J, Barse B, Fais A, et al. . Biopolymer: A sustainable material for food and medical applications. Polymers, 2022, 14: 983

[21] Barghchi H, Milkarizi N, Belyani S, et al. . Pomegranate ( L.) Peel extract ameliorates metabolic syndrome risk factors in patients with non-alcoholic fatty liver disease: a randomized double-blind clinical trial. Nutr J, 2023, 22: 1-17.

[22] Bialonska D, Kasimsetty SG, Khan SI, Daneel F. Urolithins, intestinal microbial metabolites of pomegranate ~ ellagitannins, exhibit potent antioxidant activity in a cell-based assay. J Agric Food Chem, 2009, 57: 10181-10186.

[23] Bibi I, Nazar N, Ata S, et al. . Green synthesis of iron oxide nanoparticles using pomegranate seeds extract and photocatalytic activity evaluation for the degradation of textile dye. J Mater Res Technol, 2019, 8: 6115-6124.

[24] Chen J, Liao C, Ouyang X, et al. . Antimicrobial activity of pomegranate Peel and its applications on food preservation. J Food Qual, 2020, 2020: 8850339

[25] Cheng J, Li J, Xiong RG, et al. . Bioactive compounds and health benefits of pomegranate: an updated narrative review. Food Biosci, 2023, 53: 102629

[26] Čižmárová B, Hubková B, Tomečková V, Birková A. Flavonoids as promising natural compounds in the prevention and treatment of selected skin diseases. Int J Mol Sci, 2023, 24: 6324.

[27] Čolić M, Mihajlović D, Bekić M, Marković M, Dragišić B, Tomić S, Miljuš N, Šavikin K, Škrbić R (2022) Immunomodulatory activity of punicalagin, punicalin, and ellagic acid differs from the effect of pomegranate peel extract. Molecules 27. https://doi.org/10.3390/molecules27227871

[28] Cui H, Surendhiran D, Li C, Lin L (2020) Biodegradable zein active film containing chitosan nanoparticle encapsulated with pomegranate peel extract for food packaging. Food Packag Shelf Life 24. https://doi.org/10.1016/j.fpsl.2020.100511

[29] Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep, 2017, 7: 1-13.

[30] Danjolli-Hashani D, Isbilir SS, Yılmaz AŞ. L. Peel: anticancer activity on Hep3B, Drug-likeness, ADMET Prediction, and molecular Docking with EGFR-TK. ChemistrySelect, 2025, 10: e202403976

[31] Daré RG, Nakamura CV, Ximenes VF, Lautenschlager SOS. Tannic acid, a promising anti-photoaging agent: evidences of its antioxidant and anti-wrinkle potentials, and its ability to prevent photodamage and MMP-1 expression in L929 fibroblasts exposed to UVB. Free Radic Biol Med, 2020, 160: 342-355.

[32] de Souza Mesquita LM, Contieri LS, Vaz BMC, et al. . Valorization of pomegranate waste through green solvent extraction and Biochar production: a zero-waste biorefinery approach. Green Chem, 2024, 26: 11695-11712.

[33] Deng Y, Li Y, Yang F, et al. . The extract from (pomegranate) Peel induces apoptosis and impairs metastasis in prostate cancer cells. Biomed Pharmacother, 2017, 93: 976-984.

[34] Dhand C, Dwivedi N, Loh XJ, et al. . Methods and strategies for the synthesis of diverse nanoparticles and their applications: A comprehensive overview. RSC Adv, 2015, 5: 105003-105037.

[35] Du L, Li J, Zhang X , Wang L, Zhang W, Yang M, Hou C (2019) Pomegranate peel polyphenols inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4/NF-κB pathway activation. Food Nutr Res 63. https://doi.org/10.29219/fnr.v63.3392

[36] Du J, Wang H, Zhong L, Wei S, Min X, Deng H, Zhang X, Zhong M, Huang Y (2025) Bioactivity and biomedical applications of pomegranate peel extract: a comprehensive review. Front Pharmacol 16. https://doi.org/10.3389/fphar.2025.1569141

[37] Duan H, Wang D, Li Y. Green chemistry for nanoparticle synthesis. Chem Soc Rev, 2015, 44: 5778-5792.

[38] Eghbali S, Askari SF, Avan R, Sahebkar A (2021) Therapeutic Effects of Punica granatum (Pomegranate): an updated review of clinical trials. J Nutr Metab 2021. https://doi.org/10.1155/2021/5297162

[39] El Nady GH, El. Zaater MM, Ahmed AT, Abdel Razik AB, El-Dougdoug KA, Ibrahim MI (2024) Assessment of wound healing potential of Punica granatum peel extract in rheumatoid arthritis mice: in silico and in vivo study. Egypt Acad J Biol Sci C Physiol Mol Biol 16:329–350. https://doi.org/10.21608/eajbsc.2024.393106

[40] Esther Lydia D, Khusro A, Immanuel P, Esmail GA, Al-Dhabi NA, Arasu MV. (2020) Photo-activated synthesis and characterization of gold nanoparticles from Punica granatum L. seed oil: an assessment on antioxidant and anticancer properties for functional yoghurt nutraceuticals. J Photochem Photobiol B 206. https://doi.org/10.1016/j.jphotobiol.2020.111868

[41] Fares MM, Radaydeh SK, AlAmeen HM. Green tannins /Avocado oil composites; suncare and skincare materials. Arab J Chem, 2023, 16: 104764

[42] Farouk SM, Abu-Hussien SH, Abd-Elhalim BT , Mohamed RM, Arabe NM, Hussain AA, Mostafa ME, Hemdan B, El-Sayed SM, Bakry A, Ebeed NM (2023) Biosynthesis and characterization of silver nanoparticles from Punica granatum (pomegranate) peel waste and its application to inhibit foodborne pathogens. Sci Rep 13. https://doi.org/10.1038/s41598-023-46355-x

[43] Feng Y, Lin J, He G, Liang L, Liu Q, Yan J, Yao Q (2022) Compositions and biological activities of pomegranate peel polyphenols extracted by different solvents. Molecules 27. https://doi.org/10.3390/molecules27154796

[44] Ferreira DF, da Silva TM, de Melo RCG, et al. . Development of a gel formulation with pomegranate Peel extract ( L.) for antimicrobial and wound healing action. S Afr J Bot, 2024, 173: 284-294.

[45] Flament F, Bazin R, Laquieze S, et al. . Effect of the sun on visible clinical signs of aging in Caucasian skin. Clin Cosmet Investig Dermatol, 2013, 6: 221-232.

[46] Gosset-Erard C, Zhao M, Lordel-Madeleine S, Ennahar S (2021) Identification of punicalagin as the bioactive compound behind the antimicrobial activity of pomegranate (Punica granatum L.) peels. Food Chem 352 https://doi.org/10.1016/j.foodchem.2021.129396

[47] Goula AM, Lazarides HN. Integrated processes can turn industrial food waste into valuable food by-products and/or ingredients: the cases of Olive mill and pomegranate wastes. J Food Eng, 2015, 167: 45-50.

[48] Gour A, Jain NK. Advances in green synthesis of nanoparticles. Artif Cells Nanomed Biotechnol, 2019, 47: 844-851.

[49] Guan LL, Lim HW, Mohammad TF. Sunscreens and photoaging: A review of current literature. Am J Clin Dermatol, 2021, 22: 819-828.

[50] Gull H, Ikram A, Khalil AA, et al. . Assessing the multitargeted antidiabetic potential of three pomegranate peel-specific metabolites: an and pharmacokinetics study. Food Sci Nutr, 2023, 11: 7188-7205.

[51] Hashem AH, El-Sayyad GS. Antimicrobial and anticancer activities of biosynthesized bimetallic silver-zinc oxide nanoparticles (Ag-ZnO NPs) using pomegranate Peel extract. Biomass Convers Biorefin, 2023

[52] Hashemi Poor MH, Hosseinzadeh S, Aminlari M. Wound healing potential of pomegranate Peel extract in human dermal fibroblasts through regulating the expression of FN1 gene. S Afr J Bot, 2022, 146: 222-229.

[53] Huang Z, Foo SC, Choo WS (2025) A review on the extraction of polyphenols from pomegranate peel for punicalagin purification: techniques, applications, and future prospects. SFT https://doi.org/10.1039/D4FB00304G

[54] Ibadi EA, Al-Hetty HRAK, Alwardi MAW, et al. . Anticorrosion, antimicrobial and antioxidant study of ZnO nanoparticles synthesized from (Pomegranate) extract. Int J Corros Scale Inhib, 2022, 11: 1569-1582.

[55] Ifeanyichukwu UL, Fayemi OE, Ateba CN. Green synthesis of zinc oxide nanoparticles from pomegranate (Punica granatum) extracts and characterization of their antibacterial activity. Molecules 25, 2020

[56] Imran M, Salehi B, Sharifi-Rad J, Aslam Gondal T, Saeed F, Imran A, Shahbaz M, Tsouh Fokou PV, Umair Arshad M, Khan H, Guerreiro SG(2019) Kaempferol: a key emphasis to its anticancer potential. Molecules 24: 2277. https://doi.org/10.3390/molecules24122277

[57] Jadoun S, Arif R, Jangid NK, Meena RK (2021) Green synthesis of nanoparticles using plant extracts: a review. Environ Chem Lett 19:355–374 https://doi.org/10.1007/s10311-020-01074-x

[58] Jalal H,Pal MA, Hamdani H, Rovida M, Khan NN. (2018) Antioxidant activity of pomegranate peel and seed powder extracts. J Pharmacogn Phytochem 7:992-997

[59] Jamkhande PG, Ghule NW, Bamer AH, Kalaskar MG (2019) Metal nanoparticles synthesis: an overview on methods of preparation, advantages and disadvantages, and applications. J Drug Deliv Sci Technol 53

[60] Jawad M, Schoop R, Suter A, Peter Klein P, Eccles R (2013) Perfil de eficacia y Seguridad de Echinacea purpurea En La prevención de episodios de Resfriado común: estudio clínico aleatorizado, doble Ciego y Controlado Con placebo. Revista De Fitoterapia 13:125–135. https://doi.org/10.1002/jsfa

[61] Jing T, Liao J, Shen K, et al. . Protective effect of urolithin a on cisplatin-induced nephrotoxicity in mice via modulation of inflammation and oxidative stress. Food Chem Toxicol, 2019, 129: 108-114.

[62] Kaderides K, Kyriakoudi A, Mourtzinos I, Goula AM. Potential of pomegranate Peel extract as a natural additive in foods. Trends Food Sci Technol, 2021, 115: 380-390.

[63] Kalouta K, Eleni P, Boukouvalas C, et al. . Dynamic mechanical analysis of novel cosmeceutical facial creams containing nano-encapsulated natural plant and fruit extracts. J Cosmet Dermatol, 2020, 19: 1146-1154.

[64] Kandylis P, Kokkinomagoulos E (2020) Food applications and potential health benefits of pomegranate and its derivatives. Foods 9:122 https://doi.org/10.3390/foods9020122

[65] Kang I, Buckner T, Shay NF, Gu L, Chung S (2016) Improvements in metabolic health with consumption of ellagic acid and subsequent conversion into urolithins: evidence and mechanisms. Adv Nutr 7:961-972. https://doi.org/10.3945/an.116.012575

[66] Khajuria A. Nexus of circular economy and industry 4.0 to achieve the UN sustainable development goals. IJES, 2021, 10: 30-34.

[67] Khan AA, Alanazi AM, Alsaif N, et al. . Pomegranate Peel induced biogenic synthesis of silver nanoparticles and their multifaceted potential against intracellular pathogen and cancer. Saudi J Biol Sci, 2021, 28: 4191-4200.

[68] Kokabi M, Ebrahimi SN. Polyphenol enriched extract of pomegranate peel; A novel precursor for the biosynthesis of zinc oxide nanoparticles and application in sunscreens. Pharm Sci, 2021, 27: 102-110.

[69] Kumar N, Pratibha N, et al. . Effects of drying methods and solvent extraction on quantification of major bioactive compounds in pomegranate Peel waste using HPLC. Sci Rep, 2022, 12: 1-9.

[70] Lee CJ, Chen LG, Liang WL, Wang CC (2017) Multiple activities of Punica granatum Linne against Acne vulgaris. Int J Mol Sci 18. https://doi.org/10.3390/ijms18010141

[71] Li Y, Ye T, Yang F, et al. . Punica granatum (pomegranate) Peel extract exerts potent antitumor and anti-metastasis activity in thyroid cancer. RSC Adv, 2016, 6: 84523-84535.

[72] Li HM, Kouye O, Yang DS, Zhang YQ, Ruan JY, Han LF, Zhang Y, Wang T (2022) Polyphenols from the peels of Punica granatum L. and their bioactivity of suppressing lipopolysaccharide-stimulated inflammatory cytokines and mediators in RAW 264.7 cells via activating p38 MAPK and NF-κB signaling pathways. Molecules 27. https://doi.org/10.3390/molecules27144622

[73] Liu H, Li J, Yan C, et al. . Punicalagin ameliorates DSS-induced colitis in mice through strengthening gut barrier, decreasing oxidative stress and downregulating inflammation via AMPK–NF–κB-STAT3 pathway. Food Biosci, 2024, 60: 104384

[74] Lu X, Ye Z, Jiang L, Wen L, Liu J, Cui Q (2024) UPLC-Q-TOF-MS/MS analysis of pomegranate peel polyphenols and preliminary study on the biosynthesis of ellagic acid and flavonoids. Beverage Plant Res 4. https://doi.org/10.48130/bpr-0024-0031

[75] Lyu W, Qian M, Yang F. Nanoparticles in sunscreen: exploration of the effect and harm of titanium oxide and zinc oxide. High Sci Eng Technol, 2022, 13: 155-162.

[76] Maggiore I, Setti L. New biorefinery approach for the valorization of fruit processing waste at a local scale: pomegranate pomace as case study. Waste Biomass Valorization, 2025, 16: 2749-2766.

[77] Mahmoud MH, Azab DESH. Upcycling Mango and pomegranate Peel as pectin source: characterization, fat substitute and retarded lipid oxidation in caramel candy. Discover Food, 2025, 5: 1-17.

[78] Mahmoud NMR, Mohamed HI, Ahmed SB, Akhtar S. Efficient biosynthesis of CuO nanoparticles with potential cytotoxic activity. Chem Pap, 2020, 74: 2825-2835.

[79] Malviya S, Arvind, Jha A, Hettiarachchy N. Antioxidant and antibacterial potential of pomegranate Peel extracts. J Food Sci Technol, 2014, 51: 4132-4137.

[80] Manna K, Mishra S, Saha M, et al. . Amelioration of diabetic nephropathy using pomegranate Peel extract-stabilized gold nanoparticles: assessment of NF-ΚB and Nrf2 signaling system. Int J Nanomed, 2019, 14: 1753-1777.

[81] Mastrogiovanni F, Bernini R, Basiricò L, et al. . Antioxidant and anti-inflammatory effects of pomegranate Peel extracts on bovine mammary epithelial cells BME-UV1. Nat Prod Res, 2020, 34: 1465-1469.

[82] Min DH, Yu YB, Kim TH, et al. . Pharmacological effects of pentacyclic triterpenoids isolated from centella Asiatica. Hortic Environ Biotechnol, 2024, 65: 189-197.

[83] Mo Y, Ma J, Gao W, Zhang L, Li J, Li J, Zang J (2022) Pomegranate Peel as a source of bioactive compounds: a mini review on their physiological functions. Front Nutr 9 https://doi.org/10.3389/fnut.2022.887113

[84] Mohamad Sukri SNA, Shameli K, Mei-Theng Wong M, et al. . Cytotoxicity and antibacterial activities of plant-mediated synthesized zinc oxide (ZnO) nanoparticles using (pomegranate) fruit peels extract. J Mol Struct, 2019, 1189: 57-65.

[85] Monika P, Chandraprabha MN, Hari Krishna R, et al. . Recent advances in pomegranate Peel extract mediated nanoparticles for clinical and biomedical applications. Biotechnol Genet Eng Rev, 2022

[86] Morzelle MC, Salgado JM, Telles M , Mourelle D, Bachiega P, Buck HS, Viel TA.(2016) Neuroprotective effects of pomegranate peel extract after chronic infusion with amyloid-β peptide in mice. PLoS ONE 1 https://doi.org/10.1371/journal.pone.0166123

[87] Muhammad A, Dayisoylu KS, Pei J, Khan MR, Salman M, Ahmad R, Ullah H, Noor GR (2023) Compositional analysis of natural pomegranate peel powder dried by different methods and nutritional and sensory evaluation of cookies fortified with pomegranate peel powder. Front Nutr 10. https://doi.org/10.3389/fnut.2023.1118156

[88] Nafisi S, Maibach HI (2017) Nanotechnology in cosmetics. Cosmetic science and technology: theoretical principles and applications. Elsevier Inc., pp 337–361

[89] Naseema A, Kovooru L, Behera AK, Kumar KP, Srivastava P (2021) A critical review of synthesis procedures, applications and future potential of nanoemulsions. Adv Colloid Interface Sci 287:102318 https://doi.org/10.1016/j.cis.2020.102318

[90] Nazeam JA, AL-Shareef WA, Helmy MW, El-Haddad AE (2020) Bioassay-guided isolation of potential bioactive constituents from pomegranate agrifood by-product. Food Chem 326. https://doi.org/10.1016/j.foodchem.2020.126993

[91] Nile A, Nile SH, Shin J, Park G, Oh JW(2021) Quercetin-3-glucoside extracted from apple pomace induces cell cycle arrest and apoptosis by increasing intracellular ROS levels. Int J Mol Sci 22 :10749 https://doi.org/10.3390/ijms221910749

[92] Noreen S, Hashmi B, Aja PM, Atoki AV. Phytochemicals and Pharmacology of pomegranate (Punica granatum L.): nutraceutical benefits and industrial applications: a review. Front Nutr, 2025, 12: 1528897.

[93] Ong WTJ, Nyam KL (2022) Evaluation of silver nanoparticles in cosmeceutical and potential biosafety complications. Saudi J Biol Sci 29:2085–2094 https://doi.org/10.1016/j.sjbs.2022.01.035

[94] Parisio C, Lucarini E, Micheli L, et al. . Pomegranate mesocarp against colitis-induced visceral pain in rats: effects of a Decoction and its fractions. Int J Mol Sci, 2020, 21: 1-16.

[95] Patel M, Siddiqi NJ, Sharma P, Alhomida AS, Khan HA (2019) Reproductive toxicity of pomegranate peel extract synthesized gold nanoparticles: a multigeneration study in C. elegans. J Nanomater 2019 : 8767943 https://doi.org/10.1155/2019/8767943

[96] Pereira DTV, Zabot GL, Martínez J (2025) Economic evaluation of a promising strategy for the extraction and concentration of bioactive compounds from passion fruit rinds. Food Bioprod Process 153:536–545. https://doi.org/10.1016/J.FBP.2025.08.007

[97] Pirzadeh M, Caporaso N, Rauf A, et al. . Pomegranate as a source of bioactive constituents: a review on their characterization, properties and applications. Crit Rev Food Sci Nutr, 2021, 61: 982-999.

[98] Priya N, Kaur K, Sidhu AK (2021) Green synthesis: an eco-friendly route for the synthesis of iron oxide nanoparticles. Front Nanotechnol 3:655062 https://doi.org/10.3389/fnano.2021.655062

[99] Rafique M, Sadaf I, Rafique MS, Tahir MB (2017) A review on green synthesis of silver nanoparticles and their applications. Artif Cells Nanomed Biotechnol 45:1272–1291 https://doi.org/10.1080/21691401.2016.1241792

[100] Rak-Pasikowska A, Hałucha K, Kamińska M, et al. . The effect of pomegranate Peel extract on the oxidative and inflammatory status in the spleens of rats with metabolic syndrome. Int J Mol Sci, 2024, 25: 12253

[101] Rakshit M, Muduli S, Srivastav PP, Mishra S. Pomegranate Peel polyphenols prophylaxis against SARS-CoV-2 main protease by in-silico Docking and molecular dynamics study. J Biomol Struct Dyn, 2022, 40: 12917-12931.

[102] Rana J, Diwakar G, Saito L, Scholten JD, Mulder T (2013) Inhibition of melanin content by punicalagins in the super fruit pomegranate (Punica granatum). J Cosmet Sci 64:445-453

[103] Jahromi SB, Pourshafie MR, Mirabzadeh E, Tavasoli A, Katiraee F, Mostafavi E, Abbasian S. (2015) Punica granatum peel extract toxicity in mice. Jundishapur J Nat Pharm Prod 10:23770 https://doi.org/10.17795/jjnpp-23770

[104] Riaz S, Rasul A, Ahmad M, et al. . Pomegranate Peel extract as 6-Phosphogluconate dehydrogenase (6PGD) inhibitor for treatment of breast cancer. Cell Biochem Biophys, 2024, 83: 537-553.

[105] Riseh RS, Vazvani MG, Hassanisaadi M, Thakur VK. Agricultural wastes: A practical and potential source for the isolation and Preparation of cellulose and application in agriculture and different industries. Ind Crops Prod, 2024

[106] Romes NB, Abdul Wahab R, Abdul Hamid M (2021) The role of bioactive phytoconstituents-loaded nanoemulsions for skin improvement: a review. Biotechnol Biotechnol Equip 35:711–729 https://doi.org/10.1080/13102818.2021.1915869

[107] Rosenblat M, Hayek T, Aviram M. Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages. Atherosclerosis, 2006, 187: 363-371.

[108] Ruan JH, Li J, Adili G, et al. . Phenolic compounds and bioactivities from pomegranate (Punica granatum L.) peels. J Agric Food Chem, 2022, 70: 3678-3686.

[109] Salama AA, Ismael NM, Bedewy M. The Anti-inflammatory and antiatherogenic in vivo effects of pomegranate Peel powder: from waste to medicinal food. J Med Food, 2021, 24: 145-150.

[110] Salvioni L, Morelli L, Ochoa E, Labra M, Fiandra L, Palugan L, Prosperi D, Colombo M (2021) The emerging role of nanotechnology in skincare. Adv Colloid Interface Sci 293102437. https://doi.org/10.1016/j.cis.2021.102437

[111] Sani A, Cao C, Cui D (2021) Toxicity of gold nanoparticles (AuNPs): a review. Biochem Biophys Rep 26:100991. https://doi.org/10.1016/j.bbrep.2021.100991

[112] Saparbekova AA, Kantureyeva GO, Kudasova DE, Konarbayeva ZK, Latif AS et al (2023) Potential of phenolic compounds from pomegranate (Punica granatum L.) by-product with significant antioxidant and therapeutic effects: a narrative review. Saudi J Biol Sci 30: 103553. https://doi.org/10.1016/j.sjbs.2022.103553

[113] Sarkar A, Haque MA, Alam M. Unlocking the potential of pomegranate peels as a valuable source of bioactive compounds through effective drying strategies. Food Chem Adv, 2024, 4: 100622.

[114] Sayed S, Alotaibi SS, El-Shehawi AM, et al. . The Anti-Inflammatory, Anti-Apoptotic, and antioxidant effects of a Pomegranate-Peel extract against Acrylamide-Induced hepatotoxicity in rats. Life, 2022, 12: 224

[115] Scappaticci RAF, Berretta AA, Torres EC, Buszinski AF, Fernandes GL, Dos Reis TF, de Souza-Neto FN, Gorup LF, de Camargo ER, Barbosa DB (2021) Green and chemical silver nanoparticles and pomegranate formulations to heal infected wounds in diabetic rats. Antibiotics 10:1343. https://doi.org/10.3390/antibiotics10111343

[116] Seeram NP, Adams LS, Henning SM, et al. . In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem, 2005, 16: 360-367.

[117] Shaban AS, Owda ME, Basuoni MM, et al. . Punica granatum Peel extract mediated green synthesis of zinc oxide nanoparticles: structure and evaluation of their biological applications. Biomass Convers Biorefin, 2022

[118] Sharma D, Bisht D (2017) M. tuberculosis hypothetical proteins and proteins of unknown function: hope for exploring novel resistance mechanisms as well as future target of drug resistance. Front Microbiol 8. https://doi.org/10.3389/fmicb.2017.00465

[119] Siddiqui SA, Singh S, Nayik GA. Bioactive compounds from pomegranate peels - Biological properties, structure–function relationships, health benefits and food applications – A comprehensive review. J Funct Foods, 2024, 116: 106132

[120] Singh B, Mal G, Sharma D, Gautam SK, Kumar M, Solimene U, Metalla M, Marotta F. (2018) Plant polyphenols: the futuristic bioactive therapeutics for skin care. Polyphenols: prevention and treatment of human disease. Elsevier, pp 385–394

[121] Singh H, Desimone MF, Pandya S, Jasani S, George N, Adnan M, Aldarhami A, Bazaid AS, Alderhami SA (2023a) Revisiting the green synthesis of nanoparticles: uncovering influences of plant extracts as reducing agents for enhanced synthesis efficiency and its biomedical applications. Int J Nanomed 18:4727–4750. https://doi.org/10.2147/IJN.S419369

[122] Singh J, Kaur HP, Verma A, et al. . Pomegranate Peel Phytochemistry, Pharmacological Properties, methods of Extraction, and its application: A comprehensive review. ACS Omega, 2023, 8: 35452-35469.

[123] Sivamani RK, Chakkalakal M, Pan A, et al. . Prospective Randomized, Double-Blind, Placebo-Controlled study of a standardized oral pomegranate extract on the gut Microbiome and Short-Chain fatty acids. Foods, 2024, 13: 15

[124] Song W, Wang L, Jin M, Guo X, Wang X, Guan J, Zhao Y (2022) Punicalagin, an inhibitor of sortase A, is a promising therapeutic drug to combat methicillin-resistant Staphylococcus aureus infections. Antimicrob Agents Chemother 66. https://doi.org/10.1128/aac.00224-22

[125] Sonia SS, Linda Jeeva Kumari LJKH, Ruckmani RK, Sivakumar SM. Antimicrobial and antioxidant potentials of biosynthesized colloidal zinc oxide nanoparticles for a fortified cold cream formulation: A potent nanocosmeceutical application. Mater Sci Eng C, 2017, 79: 581-589.

[126] Su L, Wu S, Fu G, Zhu W, Zhang X, Liang B (2024) Creep characterisation and microstructural analysis of municipal solid waste incineration fly ash geopolymer backfill. Sci Rep 14:1–16. https://doi.org/10.1038/S41598-024-81426-7

[127] Sun S, Huang S, Shi Y, Shao Y, Qiu J, Sedjoah RC, Yan Z, Ding L, Zou D, Xin Z (2021) Extraction, isolation, characterization and antimicrobial activities of non-extractable polyphenols from pomegranate peel. Food Chem 351:129232 . https://doi.org/10.1016/j.foodchem.2021.129232

[128] Suručić R, Travar M, Petković M, et al. . Pomegranate Peel extract polyphenols attenuate the SARS-CoV-2 S-glycoprotein binding ability to ACE2 receptor: in Silico and in vitro studies. Bioorg Chem, 2021, 114: 105145.

[129] Swilam N, Nematallah KA (2020) Polyphenols profile of pomegranate leaves and their role in green synthesis of silver nanoparticles. Sci Rep 10. https://doi.org/10.1038/s41598-020-71847-5

[130] Tavan M, Hanachi P, Mirjalili MH, Dashtbani-Roozbehani A. Comparative assessment of the biological activity of the green synthesized silver nanoparticles and aqueous leaf extract of Perilla frutescens (L). Sci Rep, 2023, 13: 6391

[131] Teniente SL, Flores-Gallegos AC, Esparza-González SC, Campos-Múzquiz LG, Nery-Flores SD, Rodríguez-Herrera R (2023) Anticancer effect of pomegranate peel polyphenols against cervical cancer. Antioxidants 12:127. https://doi.org/10.3390/antiox12010127

[132] Tumbarski Y, Ivanov I, Vrancheva R, Mazova N, Nikolova K (2025) Pomegranate Peels: a promising source of biologically active compounds with potential application in cosmetic products. Cosmetics 12:169. https://doi.org/10.3390/COSMETICS12040169

[133] Venusova E, Kolesarova A, Horky P, Slama P (2021) Physiological and immune functions of punicalagin. Nutrients 13:2150. https://doi.org/10.3390/nu13072150

[134] Vijayakumar M, Janani B, Kannappan P, et al. . In Silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies. Saudi J Biol Sci, 2022, 29: 18-29.

[135] Villa-Ruano N, Rosas-Bautista A, Rico-Arzate E, et al. . Study of nutritional quality of pomegranate (Punica granatum L.) juice using 1H NMR-based metabolomic approach: A comparison between conventionally and organically grown fruits. LWT, 2020, 134: 110222

[136] Vučić V, Grabež M, Trchounian A, Arsić A. Composition and potential health benefits of pomegranate: A review. Curr Pharm Des, 2019, 25: 1817-1827.

[137] Wu Y, Zhu C, ping, Zhang Y, et al. . Immunomodulatory and antioxidant effects of pomegranate Peel polysaccharides on immunosuppressed mice. Int J Biol Macromol, 2019, 137: 504-511.

[138] Xie X, Hu L, Liu L, Wang J, Liu Y, Ma L, Sun G, Li C, Aisa HA, Meng S (2022) Punicalagin promotes autophagic degradation of human papillomavirus E6 and E7 proteins in cervical cancer through the ROS-JNK-BCL2 pathway. Transl Oncol 19. https://doi.org/10.1016/j.tranon.2022.101388

[139] Xu P, Xu L, Huang S, et al. . Analysis of the molecular mechanism of Punicalagin in the treatment of alzheimer’s disease by Computer-Aided drug research technology. ACS Omega, 2022, 7: 6121-6132.

[140] Yadwade R, Gharpure S, Ankamwar B (2021) Nanotechnology in cosmetics pros and cons. Nano Express 2 https://doi.org/10.1088/2632-959X/abf46b

[141] Yamada M, Mohammed Y, Prow TW (2020) Advances and controversies in studying sunscreen delivery and toxicity. Adv Drug Deliv Rev 153:72–86 https://doi.org/10.1016/j.addr.2020.02.001

[142] Yazdi MR, Mrowietz U. Fumaric acid esters. Clin Dermatol, 2008, 26: 522-526.

[143] Yu ZY, Xu K, Wang X, Wen YT, Wang LJ, Huang DQ, Chen XX, Chai WM (2022) Punicalagin as a novel tyrosinase and melanin inhibitor: inhibitory activity and mechanism. LWT 161. https://doi.org/10.1016/j.lwt.2022.113318

[144] Zam T, D’Auria JC, Jaisi A. (2025) Advancements in biotechnological approaches for the production of high-value metabolites in Punica granatum. ACS FST 5:2086-2097. https://doi.org/10.1021/acsfoodscitech.5c00190

Funding

Manipal University Jaipur

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