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Pharm. Res."],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Tinospora crispa<\/jats:italic>\n                    \u00a0(Menispermaceae) has been traditionally consumed as a functional food and herbal remedy in Southeast Asia, notably in Thailand and India.\n                    <jats:italic>cis<\/jats:italic>\n                    -Clerodane-type diterpenoids represent the characteristic and predominant metabolites of the genus\n                    <jats:italic>Tinospora<\/jats:italic>\n                    . Chemical investigation of a MeOH extract of\n                    <jats:italic>T. crispa<\/jats:italic>\n                    leaves, guided by LC\/MS analysis coupled with an in-house UV spectral library, led to the isolation of five compounds (\n                    <jats:bold>1<\/jats:bold>\n                    \u2013\n                    <jats:bold>5<\/jats:bold>\n                    ), including four new\n                    <jats:italic>cis<\/jats:italic>\n                    -clerodane-type diterpenoids (\n                    <jats:bold>1<\/jats:bold>\n                    \u2013\n                    <jats:bold>4<\/jats:bold>\n                    ). Their structures were elucidated by 1D and 2D NMR spectroscopy, high-resolution mass spectrometry (HR-ESIMS), interproton distance analysis using NOE peak amplitude normalization for improved cross-relaxation (PANIC), Snatzke\u2019s method, and computational ECD and DP4\u207a probability calculations. The isolated compounds (\n                    <jats:bold>1<\/jats:bold>\n                    \u2013\n                    <jats:bold>5<\/jats:bold>\n                    ) were evaluated for their anticancer potential in both liver (Hepa1c1c7, Hepa1-6) and lung (LLC1, A549) cancer cell lines. All compounds\n                    <jats:bold>1<\/jats:bold>\n                    \u2013\n                    <jats:bold>5<\/jats:bold>\n                    reduced A549 cell viability by approximately 70%, at 200\u00a0\u03bcM and showing comparable activity in LLC1. Molecular analyses showed that compound\u00a0\n                    <jats:bold>3<\/jats:bold>\n                    \u00a0affected downstream Hippo signaling components (YAP, TAZ, pan-TEAD) in liver cancer cells and inhibited pro-survival pathways\u2014including phosphorylated AKT\u2014in lung cancer cells, where it also elevated apoptotic markers Bax and cleaved caspase-3 while reducing anti-apoptotic BCL-2. Overall, compound\u00a0\n                    <jats:bold>3<\/jats:bold>\n                    \u00a0exhibited the most consistent and potent cell-line specific anticancer effects across both models, highlighting its potential as a promising lead candidate for further anticancer drug development. Collectively, these results suggest concentration-dependent anticancer activity of\n                    <jats:italic>T. crispa<\/jats:italic>\n                    diterpenoids in liver and lung cancer models and further support compound\n                    <jats:bold>3<\/jats:bold>\n                    as promising leading candidate targeting key survival signaling pathways in cancer.\n                  <\/jats:p>","DOI":"10.1007\/s12272-026-01596-y","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T16:10:58Z","timestamp":1768925458000},"page":"158-173","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["cis-Clerodane-type diterpenoids from Tinospora crispa and their anticancer potential"],"prefix":"10.1007","volume":"49","author":[{"given":"Se Yun","family":"Jeong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Won","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norhayati","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurul Hazlina","family":"Zaini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Joo","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan Jung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonhwa","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5285-9138","authenticated-orcid":false,"given":"Ki Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"1596_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00059","volume":"7","author":"W Ahmad","year":"2016","unstructured":"Ahmad W, Jantan I, Bukhari SN (2016) Tinospora crispa (L.) 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