{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T22:38:31Z","timestamp":1773527911152,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>S. indicus<\/jats:italic> has demonstrated promising therapeutic potential due to its bioactive compounds. This study investigated the cytotoxic and pro-apoptotic effects of <jats:italic>Sphaeranthus indicus<\/jats:italic> extract, its active fraction, and biosynthesized silver nanoparticles (AgNPs) on human gastric cancer (HGT-1) cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The plant was collected and subjected to Soxhlet extraction using ethanol, followed by sequential solvent partitioning and silica gel column chromatography to isolate bioactive fractions. Green synthesis of AgNPs was conducted using <jats:italic>S. indicus<\/jats:italic> extract. Structural characterization was conducted via UV- spectroscopy, FTIR, XRD, and FESEM. Cytotoxicity was assessed using MTT and CCK-8 assays, while apoptosis induction was evaluated through qPCR and Western blot analysis of key apoptotic markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The ethanolic extract exhibited moderate cytotoxicity against HGT-1 cells, whereas biosynthesized AgNPs demonstrated enhanced anticancer activity with reduced toxicity to normal hepatocytes. The active fraction, identified as cryptomeridiol, showed the highest selectivity and potency against cancer cells. qPCR revealed significant upregulation of p21 and downregulation of CDK2, suggesting cell cycle arrest. Western blot analysis confirmed increased expression of caspase-3 and caspase-9 and a reduction in XIAP, indicating apoptosis activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study underscores the potential of <jats:italic>S. indicus<\/jats:italic> bioactive compounds and AgNPs as therapeutic agents, particularly against gastric cancer. The findings provide a basis for further exploration into their mechanism of action and broader pharmacological applications. Keywords: <jats:italic>S. indicus<\/jats:italic>, Bioactive compounds, Silver nanoparticles (AgNPs), Gastric cancer-HGT-1, Apoptosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1565308","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T06:58:10Z","timestamp":1743663490000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Synergistic anticancer potential of biogenic nanoparticles and cryptomeridiol from Sphaeranthus indicus: targeting gastric cancer through apoptosis and cell cycle arrest"],"prefix":"10.3389","volume":"16","author":[{"given":"Pan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jigang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nrc2657","article-title":"p21 in cancer: intricate networks and multiple activities","volume":"9","author":"Abbas","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/j.gendis.2022.02.007","article-title":"Cancer chemotherapy and beyond: current status, drug candidates, associated risks and progress in targeted therapeutics","volume":"10","author":"Anand","year":"2022","journal-title":"Genes Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"15593258221088709","DOI":"10.1177\/15593258221088709","article-title":"Green synthesis of silver nanoparticles (AgNPs), structural characterization, and their antibacterial potential","volume":"20","author":"Asif","year":"2022","journal-title":"Dose Response"},{"key":"B4","doi-asserted-by":"publisher","first-page":"855136","DOI":"10.3389\/fbioe.2022.855136","article-title":"Investigation of antimicrobial and cytotoxic properties and specification of silver nanoparticles (AgNPs) derived from cicer arietinum L. Green leaf extract","volume":"10","author":"Baran","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.3390\/biom11081176","article-title":"Role of phytonutrients in nutrigenetics and nutrigenomics perspective in curing breast cancer","volume":"11","author":"Bhattacharya","year":"2021","journal-title":"Biomolecules"},{"key":"B6","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-0716-1162-3_1","article-title":"Determination of caspase activation by western blot","volume":"2255","author":"Chehade","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"19427","DOI":"10.18632\/oncotarget.24827","article-title":"Distinct molecular subtypes of gastric cancer: from Laur\u00e9n to molecular pathology","volume":"9","author":"Cis\u0142o","year":"2018","journal-title":"Oncotarget"},{"key":"B9","doi-asserted-by":"publisher","first-page":"247","DOI":"10.4103\/0974-7788.76790","article-title":"Sphaeranthus indicus Linn.: a phytopharmacological review","volume":"1","author":"Galani","year":"2010","journal-title":"Int. J. Ayurveda Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e61146","DOI":"10.7759\/cureus.61146","article-title":"Optimization of extraction conditions of bioactive compounds from kurdistan species Urtica dioica","volume":"16","author":"Haido","year":"2024","journal-title":"Cureus"},{"key":"B11","doi-asserted-by":"publisher","first-page":"892468","DOI":"10.3389\/fpubh.2022.892468","article-title":"Risk factors for gastric cancer: a comprehensive analysis of observational studies","volume":"10","author":"Hui","year":"2023","journal-title":"Front. Public Health"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.3748\/wjg.v28.i12.1187","article-title":"Epidemiology of stomach cancer","volume":"28","author":"Ilic","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.3390\/pharmaceutics14102185","article-title":"Comparative estimation of the cytotoxic activity of different parts of Cynara scolymus L.: crude extracts versus green synthesized silver nanoparticles with apoptotic investigation","volume":"14","author":"Khedr","year":"2022","journal-title":"Pharmaceutics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"8013","DOI":"10.2147\/IJN.S189295","article-title":"Selective cytotoxicity of green synthesized silver nanoparticles against the MCF-7 tumor cell line and their enhanced antioxidant and antimicrobial properties","volume":"13","author":"Khorrami","year":"2018","journal-title":"Int. J. Nanomedicine"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2854217","DOI":"10.1155\/2021\/2854217","article-title":"Molecular spectroscopic (FTIR and UV-vis) and hyphenated chromatographic (UHPLC-qTOF-MS) analysis and in vitro bioactivities of the Momordica balsamina leaf extract","volume":"2021","author":"Mabasa","year":"2021","journal-title":"Biochem. Res. Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"100220","DOI":"10.1016\/j.onano.2024.100220","article-title":"Biosynthesis, characterization, and in-vitro anticancer effect of plant-mediated silver nanoparticles using Acalypha indica Linn: in-silico approach","volume":"21","author":"Madaniyah","year":"2025","journal-title":"OpenNano"},{"key":"B17","doi-asserted-by":"publisher","first-page":"100845","DOI":"10.1016\/j.ctarc.2024.100845","article-title":"Gastric cancer-Epidemiology, modifiable and non-modifiable risk factors, challenges and opportunities: an updated review","volume":"41","author":"Mamun","year":"2024","journal-title":"Cancer Treat. Res. Commun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.3390\/cancers15051628","article-title":"A comprehensive review of prognostic factors in patients with gastric adenocarcinoma","volume":"15","author":"Mantziari","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"849","DOI":"10.3390\/molecules25040849","article-title":"Pharmacological evaluation of the anticancer activity of extracts and fractions of Lannea barteri oliv. (Anacardiaceae) on adherent human cancer cell lines","volume":"25","author":"Mbaoji","year":"2020","journal-title":"Molecules"},{"key":"B20","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1136\/jcp.55.10.770","article-title":"Features of gastritis predisposing to gastric adenoma and early gastric cancer","volume":"55","author":"Meining","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s43046-024-00252-0","article-title":"Eco-biofabrication of silver nanoparticles from Azadirachta indica, Gymnema sylvestre, and Moringa oleifera for lung cancer treatment","volume":"37","author":"Muthu","year":"2025","journal-title":"J. Egypt."},{"key":"B22","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1177\/1534735412451997","article-title":"Sphaeranthus indicus induces apoptosis through mitochondrial-dependent pathway in HL-60 cells and exerts cytotoxic potential on several human cancer cell lines","volume":"12","author":"Nahata","year":"2013","journal-title":"Integr. Cancer Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"469","DOI":"10.3390\/antibiotics11040469","article-title":"Phytocompounds as an alternative antimicrobial approach in aquaculture","volume":"11","author":"Nik Mohamad Nek Rahimi","year":"2022","journal-title":"Antibiot. (Basel)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s12668-025-01842-5","article-title":"A review on biosynthesis of nanoparticles via microalgal technology and their biomedical applications","volume":"15","author":"Ojha","year":"2025","journal-title":"BioNanoSci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12906-024-04381-w","article-title":"Green-synthesized silver nanoparticles from Zingiber officinale extract: antioxidant potential, biocompatibility, anti-LOX properties, and in silico analysis","volume":"24","author":"Ongtanasup","year":"2024","journal-title":"BMC Complement. Med. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1093\/carcin\/bgy176","article-title":"7-hydroxyfrullanolide, isolated from Sphaeranthus indicus, inhibits colorectal cancer cell growth by p53-dependent and -independent mechanism","volume":"40","author":"Pandey","year":"2019","journal-title":"Carcinogenesis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.3390\/pathogens12101247","article-title":"The green synthesis of silver nanoparticles from Avena fatua extract: antifungal activity against Fusarium oxysporum f.sp. lycopersici","volume":"12","author":"Qureshi","year":"2023","journal-title":"Pathogens"},{"key":"B28","doi-asserted-by":"publisher","first-page":"11315","DOI":"10.3390\/ijms222111315","article-title":"Bcl-2 modulation in p53 signaling pathway by flavonoids: a potential strategy towards the treatment of cancer","volume":"22","author":"Rahman","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1399937","DOI":"10.3389\/fmicb.2024.1399937","article-title":"Phytofabrication, characterization of silver nanoparticles using Hippophae rhamnoides berries extract and their biological activities","volume":"15","author":"Rana","year":"2024","journal-title":"Front. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"855","DOI":"10.3390\/cancers12040855","article-title":"Green chemistry synthesis of silver nanoparticles and their potential anticancer effects","volume":"12","author":"Ratan","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.3390\/antiox13091037","article-title":"Bioactivity profiling and phytochemical analysis of carissa carandas extracts: antioxidant, anti-inflammatory, and anti-urinary tract infection properties","volume":"13","author":"Saeed","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4314\/ajtcam.v8i1.60483","article-title":"Extraction, isolation and characterization of bioactive compounds from plants\u2019 extracts","volume":"8","author":"Sasidharan","year":"2010","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"598","DOI":"10.4103\/ijmr.ijmr_1821_22","article-title":"Cancer incidence estimates for 2022 and projection for 2025: result from national cancer registry programme, India","volume":"156","author":"Sathishkumar","year":"2022","journal-title":"Indian J. Med. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"5330","DOI":"10.3390\/app13095330","article-title":"Colorectal cancer cell spheroids Co-cultured with molecularly imprinted fluorescent particles targeting sialic acid show preserved cell viability","volume":"13","author":"Sj\u00f6berg","year":"2023","journal-title":"Appl. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"10053","DOI":"10.3748\/wjg.v22.i45.10053","article-title":"Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression","volume":"22","author":"Su","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B37","doi-asserted-by":"publisher","first-page":"965","DOI":"10.3390\/plants13070965","article-title":"Separation methods of phenolic compounds from plant extract as antioxidant agents candidate","volume":"13","author":"Susanti","year":"2024","journal-title":"Plants"},{"key":"B38","doi-asserted-by":"publisher","first-page":"747956","DOI":"10.3389\/fnut.2021.747956","article-title":"Curcumin extraction, isolation, quantification and its application in functional foods: a review with a focus on immune enhancement activities and COVID-19","volume":"8","author":"Tripathy","year":"2021","journal-title":"Front. Nutr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1215395","DOI":"10.1155\/2020\/1215395","article-title":"Green-synthesized silver nanoparticles induced apoptotic cell death in MCF-7 breast cancer cells by generating reactive oxygen species and activating caspase 3 and 9 enzyme activities","volume":"2020","author":"Ullah","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"8996","DOI":"10.7150\/thno.45413","article-title":"Silver nanoparticles: synthesis, medical applications and biosafety","volume":"10","author":"Xu","year":"2020","journal-title":"Theranostics"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3769","DOI":"10.1038\/s41598-019-40568-9","article-title":"Preparation of peroxidase and phenolics using discarded sweet potato old stems","volume":"9","author":"Yang","year":"2019","journal-title":"Sci. Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.3748\/wjg.v29.i16.2452","article-title":"Updates on global epidemiology, risk and prognostic factors of gastric cancer","volume":"29","author":"Yang","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e36957","DOI":"10.1097\/MD.0000000000036957","article-title":"Exploring the landscape of drug resistance in gastrointestinal cancer immunotherapy: a review","volume":"103","author":"Yao","year":"2024","journal-title":"Med. Baltim."},{"key":"B44","doi-asserted-by":"publisher","first-page":"591","DOI":"10.22034\/APJCP.2018.19.3.591","article-title":"Risk factors for gastric cancer: a systematic review","volume":"19","author":"Yusefi","year":"2018","journal-title":"Asian Pac J. Cancer Prev."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1565308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T06:58:12Z","timestamp":1743663492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1565308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":44,"alternative-id":["10.3389\/fphar.2025.1565308"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1565308","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]},"article-number":"1565308"}}