Bioactive solanidane steroidal alkaloids from Solanum lyratum

Area of Science:

• Natural Products Chemistry
• Pharmacology
• Molecular Biology

Background:

• Solanum lyratum is a plant source of bioactive compounds.
• Steroidal alkaloids possess diverse pharmacological activities.
• Cancer metastasis involves complex cellular signaling pathways.

Purpose of the Study:

• To isolate and characterize novel steroidal alkaloids from Solanum lyratum.
• To evaluate the anti-cancer potential of isolated compounds, particularly against lung cancer.
• To elucidate the molecular mechanisms underlying the anti-metastatic effects of active compounds.

Main Methods:

• Isolation and structural elucidation of alkaloids using NMR, HRESIMS, UV, IR, and ECD.
• Cytotoxicity assays on A549 lung cancer cells.
• Assessment of cell migration, invasion, and adhesion.
• Analysis of JAK2/STAT3 signaling pathway and epithelial-mesenchymal transition (EMT) markers.

Main Results:

• Six new solanidane steroidal alkaloids (lyrasolanosides A-F) were identified.
• Lyrasolanoside B demonstrated significant inhibition of A549 cell migration, invasion, and adhesion.
• Lyrasolanoside B suppressed the JAK2/STAT3 pathway and downregulated phosphorylated JAK2/STAT3 in an exosome-dependent manner.
• Lyrasolanoside B upregulated E-cadherin and downregulated N-cadherin and vimentin, indicating suppression of EMT.

Conclusions:

• Lyrasolanoside B effectively inhibits lung cancer cell metastasis.
• The anti-metastatic mechanism involves the suppression of exosome-mediated epithelial-mesenchymal transition (EMT) via the JAK2/STAT3 pathway.
• Lyrasolanoside B represents a potential therapeutic agent for lung cancer treatment by targeting metastasis.