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

## TL;DR

This study identifies new diterpenoids from Tinospora crispa that show strong anticancer effects, especially in liver and lung cancer cells.

## Contribution

The discovery of four new cis-clerodane-type diterpenoids and their anticancer mechanisms in liver and lung cancer cells.

## Key findings

- Compounds 1–5 reduced A549 cell viability by ~70% at 200 μM.
- Compound 3 inhibited pro-survival pathways and induced apoptosis in lung cancer cells.
- Compound 3 affected Hippo signaling components in liver cancer cells.

## Abstract

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.

The online version contains supplementary material available at 10.1007/s12272-026-01596-y.