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Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Ethnopharmacological Relevance<\/jats:title>\n                    <jats:p>\n                      The medicinal relevance of\n                      <jats:italic>Inonotus hispidus<\/jats:italic>\n                      has been highlighted in various studies, particularly with respect to its antineoplastic, antioxidant, inflammation-modulating, and immunoregulatory capabilities. Nevertheless, its therapeutic value in renal cell carcinoma (RCC), especially the clear cell form (ccRCC), is yet to be defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      A systematic assessment of the antitumor potential and the underlying molecular mechanisms of\n                      <jats:italic>I<\/jats:italic>\n                      .\n                      <jats:italic>hispidus<\/jats:italic>\n                      against RCC by use of network pharmacology, docking simulations, and biological experiments was undertaken as the primary objective of this research.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      UHPLC-Q-Exactive HRMS and literature mining were used to identify bioactive constituents of\n                      <jats:italic>I<\/jats:italic>\n                      .\n                      <jats:italic>hispidus<\/jats:italic>\n                      . SwissTargetPrediction was used to predict potential molecular targets, which were then intersected with RCC-associated genes obtained in GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, DrugBank and PHARMGKB databases. To determine core targets, we built compound\u2013target and protein\u2013protein interaction (PPI) networks. GO and KEGG enrichment tools were applied for outlining the relevant pathways and biological functions to investigate the underlying biological mechanisms. Molecular docking was then implemented determine the binding potentials of active constituents with key protein targets. Antitumor activity of ethanol extract of\n                      <jats:italic>I. hispidus<\/jats:italic>\n                      (EEIH) was confirmed by\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments\u2014CCK-8, colony formation, apoptosis, wound-healing, and Western blot\u2014using 769-P and ACHN cell lines and\n                      <jats:italic>in vivo<\/jats:italic>\n                      xenograft models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      49 bioactive compounds and 169 overlapping targets of RCC were found. Based on target interactions, cerevisterol, withanolide, inonoterpene A and polyporusterone D were found to be major constituents. Network analysis and docking studies identified AKT1, EGFR, CTNNB1, STAT3, and BCL2 as core targets, exhibiting strong binding affinities with key compounds. The PI3K\/Akt\/mTOR and other cancer-related pathways were identified to be engaged in functional enrichment. EEIH treatment considerably inhibited RCC cell proliferation, colony formation, and migration, triggering apoptosis and downregulating phosphorylated Akt and mTOR. The\n                      <jats:italic>in vivo<\/jats:italic>\n                      antitumor efficacy of EEIH was evident in xenograft-bearing mice, where significant tumor suppression occurred in the absence of systemic toxic responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The antitumor mechanism of\n                      <jats:italic>I. hispidus<\/jats:italic>\n                      in ccRCC involves a network of interacting molecules and pathways, particularly those regulating PI3K\/Akt\/mTOR signaling. The current data support further investigation into\n                      <jats:italic>I. hispidus<\/jats:italic>\n                      as a promising natural compound for the management of ccRCC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1773406","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:44:24Z","timestamp":1778564664000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of Inonotus hispidus in suppressing renal cell carcinoma proliferation via regulation of the PI3K\/AKT\/mTOR pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Yujie","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Urology, Affiliated Hospital of Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Prescription and TCM, School of Traditional Chinese Medicine, Chengde Medical University","place":["Chengde, China"]},{"name":"Hebei Universities Characteristic Sericulture Application Technology Research and Development Center, Sericultural Research Institude, Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Prescription and TCM, School of Traditional Chinese Medicine, Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Prescription and TCM, School of Traditional Chinese Medicine, Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Affiliated Hospital of Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology, Affiliated Hospital of Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxue","family":"Song","sequence":"additional","affiliation":[{"name":"Mulberry Silkworm Research Institute, Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruining","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Prescription and TCM, School of Traditional Chinese Medicine, Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Affiliated Hospital of Chengde Medical University","place":["Chengde, China"]},{"name":"Hebei Key Laboratory of Panvascular Diseases, Affiliated Hospital of Chengde Medical University","place":["Chengde, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1674789","DOI":"10.3389\/fonc.2025.1674789","article-title":"Microfluidics and molecular diagnostics in renal cell carcinoma: advances, challenges, and future directions","volume":"15","author":"Abu-Dawas","year":"2025","journal-title":"Front. 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