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In rodents, oral dosing faces extensive first-pass metabolism, while in vitro PB triggers intrinsic mitochondrial apoptosis by altering Bcl-2/Bax balance, releasing cytochrome c, and activating caspases-9/3; it also suppresses PI3K/AKT and STAT3 signaling, halts cell-cycle progression, and reduces metastatic markers. Corresponding in vivo xenograft/orthotopic studies show tumor growth inhibition and increased cleaved caspase-3. Nanocarriers improve pharmacokinetics and systemic exposure, while toxicology and early clinical data support tolerability. Remaining priorities include target validation, long-term safety, and prodrug development.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/pinocembrin-as-a-novel-anti-cancer-agent-exploring-preclinical-evidence-along-with-therapeutic-potential/435120/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/pinocembrin-as-a-novel-anti-cancer-agent-exploring-preclinical-evidence-along-with-therapeutic-potential/435120.png","ImageObject",300,407,{"name":92,"@type":93},"Aldword","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What anticancer mechanisms does pinocembrin (PB) show in preclinical studies?","Question",{"text":112,"@type":113},"PB induces intrinsic mitochondrial apoptosis, downregulating Bcl-2, upregulating Bax, promoting cytochrome C release, and activating caspases-9/3. It also inhibits PI3K/AKT and STAT3 signaling, arrests cell-cycle progression, and suppresses metastatic markers such as MMP-9 and VEGF.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is PB oral bioavailability limited, and how can it be improved?",{"text":117,"@type":113},"Oral PB in rodents undergoes rapid absorption followed by extensive first-pass glucuronidation and sulfation, producing mainly conjugates and limiting bioavailability (\u003C10%) with a short half-life. Nanocarriers such as MPEG-PDLLA micelles and D-α-tocopheryl polyethylene glycol 1000 succinate liposomes enhance oral bioavailability and extend half-life in rodents.",{"name":119,"@type":110,"acceptedAnswer":120},"What safety and translational evidence supports PB development?",{"text":121,"@type":113},"Toxicology reports a no-observed-adverse-effect level (NOAEL) of ≥500 mg/kg in rats without mutagenicity. Phase I trials (0.5–10 mg/kg) indicate human tolerability, though gaps remain for long-term toxicity, target validation, and prodrug development.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},435120,1790989955,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},2336478940917,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","| W | J | E | M | World Journal of\u003Cbr>Experimental Medicine |\n| --- | --- | --- | --- | --- |\n\nSubmit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Exp Med 2025 December 20; 15(4): 110482  \nDOI: 10.5493/wjem.v15.i4.110482 ISSN 2220-315x (online)  \nREVIEW  \nPinocembrin as a novel anti-cancer agent: Exploring preclinical evidence along with therapeutic potential  \nNeelam Singla, Piyush Mittal, M Arockia Babu, Soumya V Menon, Subhashree Ray, Haider Ali, Manish Purohit, Kavita Goyal, Rakhi Mishra, Md Sadique Hussain, Arcot Rekha, Gaurav Gupta  \nSpecialty type: Medicine, research and experimental  \nProvenance and peer review:  \nInvited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s classification Scientific Quality: Grade A, Grade B, Grade B  \nNovelty: Grade A, Grade A, Grade A  \nCreativity or Innovation: Grade B, Grade B, Grade B  \nScientific Significance: Grade A, Grade A, Grade A  \nP-Reviewer: Almalki WH, Deputy Director, Saudi Arabia; Kazmi I, Additional Professor, Saudi Arabia  \nReceived: June 10, 2025  \nRevised: July 2, 2025  \nAccepted: October 9, 2025  \nPublished online: December 20, 2025  \nProcessing time: 195 Days and 14.9 Hours  \nNeelam Singla, Manish Purohit, School of Pharmacy, Suresh Gyan Vihar University, Jaipur 302017, Rajasthan, India  \nPiyush Mittal, School of Pharmacy, Sharda University, Greater Noida 201306, India  \nM Arockia Babu, Institute of Pharmaceutical Research, GLA University, Mathura 281406, Uttar Pradesh, India  \nSoumya V Menon, Department of Chemistry and Biochemistry, Jain (Deemed to be University), Bengaluru 560041, Karnataka, India  \nSubhashree Ray, Department of Nephrology IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhuban 751003, Odisha, India  \nHaider Ali, Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 602105, Tamil Nadu, India  \nManish Purohit, Department of Pharmacy, Govt Polytechnic Malab, Nuh 122107, Haryana, India  \nKavita Goyal, Department of Biotechnology, Graphic Era (Deemed to be University), Dehra Dun 248002, Uttarakhand, India  \nRakhi Mishra, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida 201306, India  \nMd Sadique Hussain, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehra Dun 248007, Uttarakhand, India  \nArcot Rekha, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune 411018, Maharashtra, India  \nGaurav Gupta, Centre for Research Impact and Outcome-Chitkara College of Pharmacy, Chitkara University, Rajpura 433221, Punjab, India  \nGaurav Gupta, Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates  \nCorresponding author: Gaurav Gupta, PhD, Professor, Research Dean, Centre for Research Impact and Outcome-Chitkara College of Pharmacy, Chitkara University, Chitkara, Rajpura  \n WJEM  [https://www.wjgnet.com](https://www.wjgnet.com) 1 December 20, 2025  Volume 15  Issue 4   \nSingla N et al. Preclinical insights into pinocembrin’s anti-cancer potential  \n433221, Punjab, [India.](India. gauravpharma25@gmail.com)[ gauravpharma25@gmail.com](India. gauravpharma25@gmail.com)  \nAbstract  \nPinocembrin (PB) (5,7-dihydroxy flavanone) is a naturally occurring flavonoid sourced from propolis and Pinus spp., with the formula C15H12O4 and moderate lipophilicity (log P approximately 2.1-2.5), which underlies both its bioactivity and formulation challenges. In rodents, oral administration yields rapid absorption but extensive firstpass glucuronidation and sulfation, resulting in conjugates that dominate plasma, limit bioavailability (\u003C 10%) and confer a short half-life. In vitro, PB induces intrinsic mitochondrial apoptosis, downregulating Bcl-2, upregulating Bax, promoting cytochrome C release, and activating caspases-9/caspases-3 while inhibiting phosphoinositol-3 kinas","cbCaieleMxTXihM4","https://ap.wps.com/l/cbCaieleMxTXihM4","pdf",4289659,21,"English","# Abstract\n## Core Tip","[{\"question\":\"What anticancer mechanisms does pinocembrin (PB) show in preclinical studies?\",\"answer\":\"PB induces intrinsic mitochondrial apoptosis, downregulating Bcl-2, upregulating Bax, promoting cytochrome C release, and activating caspases-9/3. It also inhibits PI3K/AKT and STAT3 signaling, arrests cell-cycle progression, and suppresses metastatic markers such as MMP-9 and VEGF.\"},{\"question\":\"Why is PB oral bioavailability limited, and how can it be improved?\",\"answer\":\"Oral PB in rodents undergoes rapid absorption followed by extensive first-pass glucuronidation and sulfation, producing mainly conjugates and limiting bioavailability (\\u003c10%) with a short half-life. Nanocarriers such as MPEG-PDLLA micelles and D-α-tocopheryl polyethylene glycol 1000 succinate liposomes enhance oral bioavailability and extend half-life in rodents.\"},{\"question\":\"What safety and translational evidence supports PB development?\",\"answer\":\"Toxicology reports a no-observed-adverse-effect level (NOAEL) of ≥500 mg/kg in rats without mutagenicity. Phase I trials (0.5–10 mg/kg) indicate human tolerability, though gaps remain for long-term toxicity, target validation, and prodrug development.\"}]","Pinocembrin as a novel anti-cancer agent: Exploring preclinical evidence along with therapeutic potential | PDF",1790672029,53]