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<p><i>Tinospora crispa</i>&#xa0;(Menispermaceae) has been traditionally consumed as a functional food and herbal remedy in Southeast Asia, notably in Thailand and India. <i>cis</i>-Clerodane-type diterpenoids represent the characteristic and predominant metabolites of the genus <i>Tinospora</i>. Chemical investigation of a MeOH extract of <i>T. crispa</i> leaves, guided by LC/MS analysis coupled with an in-house UV spectral library, led to the isolation of five compounds (<b>1</b>–<b>5</b>), including four new <i>cis</i>-clerodane-type diterpenoids (<b>1</b>–<b>4</b>). 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’s method, and computational ECD and DP4⁺ probability calculations. The isolated compounds (<b>1</b>–<b>5</b>) were evaluated for their anticancer potential in both liver (Hepa1c1c7, Hepa1-6) and lung (LLC1, A549) cancer cell lines. All compounds <b>1</b>–<b>5</b> reduced A549 cell viability by approximately 70%, at 200&#xa0;μM and showing comparable activity in LLC1. Molecular analyses showed that compound&#xa0;<b>3</b>&#xa0;affected downstream Hippo signaling components (YAP, TAZ, pan-TEAD) in liver cancer cells and inhibited pro-survival pathways—including phosphorylated AKT—in lung cancer cells, where it also elevated apoptotic markers Bax and cleaved caspase-3 while reducing anti-apoptotic BCL-2. Overall, compound&#xa0;<b>3</b>&#xa0;exhibited 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 <i>T. crispa</i> diterpenoids in liver and lung cancer models and further support compound <b>3</b> as promising leading candidate targeting key survival signaling pathways in cancer.</p>

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cis-Clerodane-type diterpenoids from Tinospora crispa and their anticancer potential

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月20日

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  • Se Yun Jeong,
  • Jisun Kim,
  • Ji Won Ha,
  • Norhayati Ahmad,
  • Nurul Hazlina Zaini,
  • Yoon-Joo Ko,
  • Alan Jung Park,
  • Wonhwa Lee,
  • Ki Hyun Kim

摘要

Tinospora crispa (Menispermaceae) has been traditionally consumed as a functional food and herbal remedy in Southeast Asia, notably in Thailand and India. cis-Clerodane-type diterpenoids represent the characteristic and predominant metabolites of the genus Tinospora. Chemical investigation of a MeOH extract of T. crispa leaves, guided by LC/MS analysis coupled with an in-house UV spectral library, led to the isolation of five compounds (1–5), including four new cis-clerodane-type diterpenoids (1–4). 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’s method, and computational ECD and DP4⁺ probability calculations. The isolated compounds (1–5) were evaluated for their anticancer potential in both liver (Hepa1c1c7, Hepa1-6) and lung (LLC1, A549) cancer cell lines. All compounds 1–5 reduced A549 cell viability by approximately 70%, at 200 μM and showing comparable activity in LLC1. Molecular analyses showed that compound 3 affected downstream Hippo signaling components (YAP, TAZ, pan-TEAD) in liver cancer cells and inhibited pro-survival pathways—including phosphorylated AKT—in lung cancer cells, where it also elevated apoptotic markers Bax and cleaved caspase-3 while reducing anti-apoptotic BCL-2. Overall, compound 3 exhibited 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 T. crispa diterpenoids in liver and lung cancer models and further support compound 3 as promising leading candidate targeting key survival signaling pathways in cancer.