Fig 2: Schematic diagram of gallic acid treating dry eye through its anti-inflammatory and antioxidant effects. LPS, lipopolysaccharide; CD-14, clusterdifferentiation-14; MD-2, myeloid differentiation protein-2; TLR4, toll like receptor 4; IκB, inhibitor of NF-κB; P, phosphorylated; NF-κB P65, nuclear factor kappa-B P65; IL-6, interleukin 6; TNF-α, tumor necrosis factor alpha; NO, nitric oxide; ROS, reactive oxygen species; Keap1, Kelch-like ECH-associated protein 1; Nrf2, nuclear factor E2-relate factor-2; ARE, antioxidant response elements; HO-1, heme oxygenase-1; NQO-1, NADPH quinineoxidoreductase-1

Fig 3: Antioxidant effect of gallic acid (GA) on lipopolysaccharide (LPS)-activated oxidative stress. a Western blot analysis of p-Nrf2, HO-1, and NADPH quinone oxidoreductase-1 (NQO-1) proteins in RAW264.7 macrophages. b Confocal microscopy images of RAW264.7 macrophages. Cell nuclei are shown in blue (DAPI) and nuclear factor E2-related factor 2 (Nrf2) is shown in green. RAW264.7 macrophages were pre-treated with GA (100 µM) for 16 h followed by the stimulation of LPS (1 µg/mL) for another 8 h. Data are presented as mean ± SD (n = 3). *P < 0.05, **P < 0.01, ****P < 0.001 compared to the LPS group

Fig 4: Effects of SJZD combined with CDDP on autophagy and Keap1/Nrf2 signaling in cisplatin-resistant NSCLC xenografts. Effects of SJZD + CDDP on a total iron and b iron metabolism–related protein levels in xenografts were assessed via the colorimetric method and WB, respectively (n = 3/group). c TEM was used to observe whether the SJZD combination induced ferroptosis, and the results were quantified by calculating the percentage of mitochondria exhibiting ferroptotic morphology (white arrows indicate mitochondrial vacuolation and autophagy; black arrows indicate shrunken mitochondria). The effect of the SJZD combination treatment on apoptosis in xenografts was visualized and quantified by d TUNEL staining and e WB (n = 3/group). Effects of SJZD + CDDP on f GSH and g MDA levels in xenografts were determined via a colorimetric method (n = 3/group). h Effects of SJZD + CDDP on autophagy and Keap1/Nrf2 signaling were detected by WB (n = 3/group). i Effects of SJZD + CDDP on the expression of xCT, nuclear localization of Nrf2, and Keap1 in cisplatin-resistant NSCLC xenografts were visualized by IF (n = 3/group). The data represent mean ± SD

Fig 5: Schematic diagram depicting the mechanism of SJZD in cisplatin-resistant NSCLC. Although pharmacological targeting of glutamine metabolism represents a promising anticancer strategy, its efficacy is frequently limited by adaptive response in cisplatin-resistant NSCLC, as previously established (upper left panel). SJZD, a canonical TCM formulation, effectively counteracts this adaptation through (i) induction of oxidative stress; (ii) attenuation of TCA cycle flux; (iii) intracellular ferrous iron accumulation; and (iv) subsequent lipid peroxidation, collectively triggering p62/Keap1/Nrf2 axis-suppressed ferroptosis. The figure is generated by FigDraw