Rotundine (levo-tetrahydropalmatine)

L-THP reduced the FSP1 stability to trigger the ferroptosis of GC cells. In conclusion, this study shows that L-THP synergizes cytotoxic CD8+ T cell-mediated GC antitumor response and ferroptosis through FSP1, providing potent evidence for GC immunoregulation.

Moreover, these ligands significantly suppressed the hTERT mRNA expression (1.00 for control, 0.43 ± 0.02 for l-THP, 0.19 ± 0.01 for M1, 0.33 ± 0.03 for M2) and showed the potent antitumor activity in A549 cells and lung cancer xenograft model. Collectively, these findings establish l-THP and its derivatives as the promising lead compounds for the development of chemotherapeutics against non-small cell lung cancer as well as provide the plausible mechanism insights into potent antitumor activity.

Further analysis pinpointed key compound-target pairs, including Berberine targeting CYP1A1, and Honokiol, Tangeretin, α-Cyperone, 1-O-Acetylbritannilactone, Rotundine B, Cyperolone targeting HMOX1...Our findings offered a comprehensive insight into GERD treatment and herbal intervention, enhancing our understanding of accurate network pharmacology. It suggested that concentrating on a single pathway, specifically the ROS signaling pathway, could serve as a new therapeutic strategy for herbal medicine in GERD treatment.

Rotundine inhibits the development and progression of colorectal cancer by regulating the expression of these prognosis-related genes. Our findings could further provide new directions for the treatment of colorectal cancer.

When cells were co-treated with THP and chloroquine(CQ, an autophagy inhibitor), THP further increased mtROS and apoptosis. Meanwhile, THP significantly reduced the proliferation index and mitochondrial membrane potential of HCC cells accompanied by the increased apoptosis. This study demonstrates that the up-regulation of mtROS by THP significantly promotes HCC cell autophagy(protective autophagy) and impairs mitochondrial respiration through reprogramming energy metabolism, ultimately inducing the mitochondria-mediated apoptosis of SMMC-7721 and BEL-7402 cells.

Importantly, this is realized without causing systemic toxicity to other organs. Collectively, our work shows that the combinatorial therapy of autophagy activator THP and NOX4 inhibitor DPI may be considered as a therapeutic avenue against HCC.

More importantly, l-THP potently reduces the growth of xenograft HepG2 tumor in nude mice without affecting other organs. From this perspective, our findings support the conclusion that metabolic change is an alternative approach to influence the development of HCC.