{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:30:45Z","timestamp":1784259045381,"version":"3.55.0"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Ulcerative colitis (UC) is a chronic inflammatory condition associated with the colon and rectum, often predisposing individuals to inflammatory bowel disease-related colorectal cancer (IBD-CRC). Current therapeutic options for UC, including corticosteroids and immunosuppressive drugs, pose significant side effects. Punica granatum peel powder (PPPG), a traditional herbal remedy in Ayurveda medicine for colitis, exhibits promising therapeutic effects with a favorable safety profile. Objectives: This study aims to explore the therapeutic potential and mechanism of action of a modified PPPG formulation in UC treatment. Methods: Using NCM460 cells and an acetic acid-induced UC murine model, the efficacy of modified PPPG was evaluated. Results: Therapy with modified PPPG significantly improved UC-associated symptoms, such as improvements in body weight, colon length, and disease activity index, as validated by histological examination. Transcriptomic sequencing identified downregulation of the IL-6\/STAT3 signaling pathway and reduced inflammatory markers like p-NF-\u03baB, IL-1\u03b2, and NLRP3 on PPPG therapy. Conclusions: These findings suggest that modified PPPG holds promise as a novel therapeutic strategy for UC intervention, targeting key inflammatory pathways implicated in UC pathogenesis and potentially mitigating the risk of IBD-CRC.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070843","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T06:46:12Z","timestamp":1751438772000},"page":"843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic Evaluation Punica granatum Peel Powder for the Ailment of Inflammatory Bowel Disorder in NCM460 Cell Line and in Albino Rats"],"prefix":"10.3390","volume":"17","author":[{"given":"Parikshit","family":"Roychowdhury","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty 643001, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyanendra Kumar","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, KLE College of Pharmacy, KLE Academy of Higher Education and Research, Belagavi 590010, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupesh","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, St. John\u2019s Pharmacy College, Vijayanagar, Bengaluru 560104, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasanna","family":"Gurunath","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, SBD Institute of Pharmacy, Bengaluru 560019, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"C","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, East West College of Pharmacy, Bengaluru 560091, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowthamarajan","family":"Kuppuswamy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty 643001, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0838-9474","authenticated-orcid":false,"given":"Anindita","family":"De","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, JSS University, Noida 201301, Uttar Pradesh, India"},{"name":"Department of Pharmaceutics, College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Loddo, I., and Romano, C. (2015). Inflammatory bowel disease: Genetics, epigenetics, and pathogenesis. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00551"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/PAP.0000000000000325","article-title":"Histologic diagnosis of inflammatory bowel diseases","volume":"29","author":"Friedman","year":"2022","journal-title":"Adv. Anat. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sanderson, J., and Escudier, M.P. (2021). Diseases of the Gastrointestinal Tract. Burket\u2019s Oral Medicine, John Wiley & Sons, Inc.","DOI":"10.1002\/9781119597797.ch15"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mathias, C.B., McAleer, J.P., and Szollosi, D.E. (2020). Inflammatory Diseases of the Gastrointestinal Tract and Pharmacological Treatments. Pharmacology of Immunotherapeutic Drugs, Springer.","DOI":"10.1007\/978-3-030-19922-7_6"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1038\/ajg.2009.264","article-title":"Cost-effectiveness of ulcerative colitis surveillance in the setting of 5-aminosalicylates","volume":"104","author":"Rubenstein","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1017\/S0950268814003185","article-title":"An assessment of the human health impact of seven leading foodborne pathogens in the United States using disability adjusted life years","volume":"143","author":"Scallan","year":"2015","journal-title":"Epidemiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rafeeq, M., Murad, H.A.S., Abdallah, H.M., and El-Halawany, A.M. (2021). Protective effect of 6-paradol in acetic acid-induced ulcerative colitis in rats. BMC Complement. Med. Ther., 21.","DOI":"10.1186\/s12906-021-03203-7"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1053\/j.gastro.2016.10.012","article-title":"Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches","volume":"152","author":"Sartor","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/00054725-200005000-00007","article-title":"Probiotics and inflammatory bowel disease: Is there a scientific rationale?","volume":"6","author":"Shanahan","year":"2000","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41575-018-0022-9","article-title":"The role of diet in the aetiopathogenesis of inflammatory bowel disease","volume":"15","author":"Khalili","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"70","DOI":"10.12688\/f1000research.17430.2","article-title":"Anti-infective potential of hydroalcoholic extract of Punica granatum peel against gram-negative bacterial pathogens","volume":"8","author":"Joshi","year":"2019","journal-title":"F1000Research"},{"key":"ref_12","first-page":"23","article-title":"Therapeutic Effects of Pomegranate (Punica granatum)","volume":"2","author":"Suthar","year":"2022","journal-title":"J. Pharm. Res. Innov. (JPRI)"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4103\/2231-0738.99469","article-title":"Pomegranate (Punica granatum L.). Ancient seeds for modern cure? Review of potential therapeutic applications","volume":"2","author":"Bhandari","year":"2012","journal-title":"Int. J. Nutr. Pharmacol. Neurol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s43088-020-00049-9","article-title":"Potential of peel extracts of Punica granatum and Citrus aurantifolia on alloxan-induced diabetic rats","volume":"9","author":"Ramya","year":"2020","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yassin, M.T., Mostafa, A.A.-F., and Al Askar, A.A. (2021). In vitro evaluation of biological activities and phytochemical analysis of different solvent extracts of Punica granatum L. (Pomegranate) peels. Plants, 10.","DOI":"10.3390\/plants10122742"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0031-9422(00)00235-1","article-title":"Advances in flavonoid research since 1992","volume":"55","author":"Harborne","year":"2000","journal-title":"Phytochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/S0031-9422(00)82884-8","article-title":"Comparative biochemistry of the flavonoids-IV.: Correlations between chemistry, pollen morphology and systematics in the family plumbaginaceae","volume":"6","author":"Harborne","year":"1967","journal-title":"Phytochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1021\/jf0115589","article-title":"Thermal processing enhances the nutritional value of tomatoes by increasing total antioxidant activity","volume":"50","author":"Dewanto","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1134\/S1068162022070214","article-title":"Method for Determining the Total Content of Phenolic Compounds in Plant Extracts with Folin\u2013Denis Reagent and Folin\u2013Ciocalteu Reagent: Modification and Comparison","volume":"48","author":"Nikolaeva","year":"2022","journal-title":"Russ. J. Bioorganic Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.37022\/WJCMPR.2020.2214","article-title":"In Vitro Evaluation of Anti Inflammatory Activity of Methanolic And Ethanolic Leaf Extract of Psidium guajava","volume":"2","author":"Hotta","year":"2020","journal-title":"World J. Curr. Med. Pharm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Huangfu, S., Dou, R., Zhong, S., Guo, M., Gu, C., Jurczyszyn, A., Yang, Y., and Jiang, B. (2020). Modified Pulsatillae decoction inhibits DSS-induced ulcerative colitis in vitro and in vivo via IL-6\/STAT3 pathway. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-02974-9"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/17425247.2023.2162876","article-title":"Why mRNA-ionizable LNPs formulations are so short-lived: Causes and way-out","volume":"20","author":"De","year":"2023","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"De, A., Kang, J.H., Lee, O.H., and Ko, Y.T. (2024). Optimizing long-term stability of siRNA using thermoassemble ionizable reverse pluronic-Bcl2 micelleplexes. Int. J. Biol. Macromol., 264.","DOI":"10.1016\/j.ijbiomac.2024.130783"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10448","DOI":"10.1039\/D0FO02081H","article-title":"Flavonoid-rich extracts from okra flowers exert antitumor activity in colorectal cancer through induction of mitochondrial dysfunction-associated apoptosis, senescence and autophagy","volume":"11","author":"Deng","year":"2020","journal-title":"Food Funct."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"De, A., Roychowdhury, P., Bhuyan, N.R., Ko, Y.T., Singh, S.K., Dua, K., and Kuppusamy, G. (2023). Folic Acid Functionalized Diallyl Trisulfide\u2013Solid Lipid Nanoparticles for Targeting Triple Negative Breast Cancer. Molecules, 28.","DOI":"10.3390\/molecules28031393"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115056","DOI":"10.1016\/j.jep.2022.115056","article-title":"Ethanolic extract from Lepidium virginicum L. ameliorates DNBS-induced colitis in rats","volume":"289","author":"Alba","year":"2022","journal-title":"J. Ethnopharmacol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/843\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:03Z","timestamp":1760032803000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":26,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["pharmaceutics17070843"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17070843","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]}}}