The extracts of Corydalis heterocarpa, a salt-tolerant plant, exhibit diverse physiological properties, including anti-inflammatory, anticancer, and antiadipogenic effects. However, the anti-aging effects of C. heterocarpa extract (CHE) on human skin cells have not yet been investigated. In the present study, we determined that CHE inhibited senescence-associated β-galactosidase (SA-β-gal)-stained senescent human dermal fibroblasts (HDFs). Furthermore, CHE markedly suppressed the expression of major regulatory proteins involved in senescence, including p53, p21, and caveolin-1. Interestingly, CHE promoted autophagic flux, as confirmed by the formation of microtubule-associated protein 1 light chain 3B (LC3B) puncta and lysosomal activity. Notably, using RNA sequencing (RNA-seq), we showed that CHE selectively regulated the gene expression of leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1), an important regulator of autophagy. The adenosine-monophosphate activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway, which is essential for autophagy regulation, was also modulated by CHE. LRSAM1 depletion not only inhibited LC3B expression but also decreased the autophagy flux induced by CHE. Moreover, the knockdown of LRSAM1 suppressed the reversal of CHE-induced senescence in old HDFs. Collectively, our study has revealed the rejuvenating effects and molecular mechanisms of CHE, suggesting that CHE may be a promising anti-aging agent.

Lung cancer, particularly non-small-cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality, with cisplatin-based chemotherapy being a standard treatment. However, the development of chemoresistance significantly limits its efficacy, necessitating alternative therapeutic approaches. Here, we demonstrate the anticancer effects of the extracts of Allium pseudojaponicum Makino (APE), a salt-tolerant plant, in cisplatin-resistant NSCLC. Metabolite profiling using UPLC-Q-TOF-MS^E identified 13 major compounds, predominantly alkaloids (71.65%) and flavonoids (8.81%), with key bioactive constituents such as lycorine (29.81%), tazettine (17.22%), and tricetin (8.19%). APE significantly inhibited cell viability in A549 and H460 cells, reducing viability to 38.6% (A549-Ctr), 37.2% (A549-CR), 28.4% (H460-Ctr), and 30.4% (H460-CR) at 40 µg/mL after 48 h. APE also suppressed colony formation by over 90% in both 2D and soft agar assays, while showing no cytotoxicity in normal human keratinocytes up to 80 µg/mL. Flow cytometry analysis revealed APE-induced G1 phase arrest, with the G1 population increasing from 50.4% to 56.6% (A549-Ctr) and 47.5% to 58.4% (A549-CR), accompanied by reduced S phase populations. This effect was associated with the downregulation of G1/S transition regulators, including cyclin D1, CDK4, cyclin E, and CDK2. Furthermore, proteomic analysis identified STAT3 signaling as a major target of APE; APE decreased phosphorylated STAT3 and c-Myc expression, and STAT3 knockdown phenocopied the effects of APE. These findings highlight the potential of APE as a natural product-based therapeutic strategy for overcoming cisplatin resistance in NSCLC.