The guishe is a by-product of the fiber extraction from Agave lechuguilla. This material has no commercial value, although it contains metabolites that could be used as a resource for producing high-value products. This study optimized the DPPH^• (2,2-diphenyl-1-picrylhydrazyl) antioxidant activity through microwave-assisted extraction (MAE) of polyphenolic compounds from Agave lechuguilla residues. The MAE process was optimized using a Box-Behnken design, with extraction time (5–15 min), temperature (40–50 °C), and solvent: sample ratio (1:20–1:30 m/v) as independent variables. In contrast, the dependent variable was DPPH^• free radical scavenging activity. As a result, the highest antioxidant activity was at 8 min of irradiation, extraction temperature of 45 °C, and solvent: sample ratio 1:30 w/v, obtaining a total flavonoid content of 19.25 ± 0.60 mg QE/g DW, a total polyphenol content of 6.59 ± 0.31 mg GAE/g DW, a DPPH^• free radical scavenging activity of 73.35 ± 1.90%, and an ABTS^+• ([2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonate)]) free radical scavenging activity of 91.93 ± 0.68%.

Flourensia cernua, commonly known as hojasén, is an endemic species from northern Mexico used in herbal medicine as a remedy for various stomach and respiratory ailments. In addition to its medicinal applications, this plant has notable antioxidant potential, making it a promising area of study. A crucial aspect in plant studies is the extraction method used, as conventional approaches can diminish the bioactivities present and affect the environment. This study aims to compare two sustainable extraction techniques, ultrasound and microwave-assisted (UAE/MAE), to maximize the yield of polyphenolic compounds from F. cernua. The Taguchi L18 orthogonal array was employed to evaluate total polyphenols and to examine independent variables, such as solvent concentration, temperature, and time. Additionally, the total flavonoid content and antioxidant activity were evaluated using the radicals ABTS^●+ and DPPH^●, and the compounds were identified using RP-HPLC-ESI-MS. The results indicated that ultrasound showed better performance in recovering total bioactive compounds, correlating with antioxidant activity. Moreover, the in vitro, hemolytic, and antihemolytic assays demonstrated that F. cernua extracts are biocompatible and exhibit significant protective activity against oxidative damage in erythrocytes, supporting their potential cytoprotective and antioxidant properties. This suggests that ultrasound-assisted extraction (UAE) is an effective method for extracting phenolic compounds from F. cernua, with potential for optimizing conditions and facilitating biotechnological and therapeutic applications.