NFKB1 and clear cell renal carcinoma: Synthesizing these findings, this study makes three key contributions: it provides a scalable, high-efficiency ISL extraction process using A. niger fermentation, addressing licorice resource underutilization; it validates ISL-b as a safe, potent antitumor derivative targeting the NF-κB pathway, laying a foundation for clear cell renal cell carcinoma treatment; and it uncovers ISL-b’s dual antitumor mechanism (direct pathway inhibition + indirect flora regulation), expanding insights into natural product pharmacology.