Mónica Aideé Díaz-Román

Persistent inflammatory and metabolic stress contribute to impaired tissue repair, particularly under diabetic conditions. Agave potatorum is traditionally used in Mexico to treat inflammation and wounds; however, its safety profile and potential to modulate stress-associated biological responses remain poorly investigated. This study evaluated the safety, anti-inflammatory, and wound-healing activities of the hydroalcoholic extract of A. potatorum and its fractions. Safety was assessed using human keratinocytes and fibroblasts, as well as an acute oral toxicity assay (OECD Guideline 420) in female CD-1 mice. Anti-inflammatory activity was evaluated using a TPA-induced ear edema model, while wound-healing activity was assessed in normoglycemic and alloxan-induced diabetic male CD-1 mice. The hydroalcoholic extract exhibited a favorable safety profile, showing low cytotoxicity at therapeutically relevant concentrations and no signs of systemic toxicity at 2000 mg/kg. The hydroalcoholic extract and its EtOAc and n-BuOH fractions significantly reduced TPA-induced ear edema. The n-BuOH fraction also accelerated wound contraction in diabetic mice from day 6 onward, whereas only limited effects were observed in normoglycemic animals. A. potatorum exhibits a favorable preclinical safety profile and modulates biological responses associated with inflammatory stress, supporting its therapeutic potential for chronic diabetic wound healing.

Various Croton species have been traditionally used to treat diabetes; however, the antidiabetic potential and safety of many of these species remain poorly understood. This study evaluated the chemical composition, antihyperglycemic activity, insulin-sensitizing effect, and acute oral toxicity of C. ehrenbergii. Dichloromethane, ethyl acetate, n-butanol, and aqueous residue fractions were obtained via liquid–liquid extraction from the hydroalcoholic extract obtained via maceration of the aerial parts. The primary compounds isolated from the fractions using column chromatography and identified by 1D nuclear magnetic resonance spectroscopy were 7,4′-di-O-methylnaringenin, β-sitosterol, tiliroside, rutin, nicotiflorin, isoquercetin, and l-quebrachitol. The in vivo antihyperglycemic activity of these compounds was assessed using oral sucrose and glucose tolerance tests, and the most active fractions were evaluated ex vivo to explore the mechanisms of action. The extract, fractions, and compounds were tested in vitro for their ability to inhibit α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) as well as for their agonistic activity on PPAR-γ. Tiliroside and nicotiflorin moderately inhibited PTP1B and α-glucosidase; whereas, l-quebrachitol acted as a PPAR-γ agonist. Acute oral toxicity studies indicated that the extract was safe at the tested dose. These results provide the first scientific evidence of the antihyperglycemic properties and preliminary safety of C. ehrenbergii.

The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products’ nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1–7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.

Agave applanata is a Mexican agave whose fresh leaves are employed to prepare an ethanol tonic used to relieve diabetes. It is also applied to skin to relieve varicose and diabetic foot ulcers, including wounds, inflammation, and infections. In this study, the chemical composition of this ethanol tonic is established and its association with antihyperglycemic, anti-inflammatory, antimicrobial, and wound healing activities is discussed. The fresh leaves of A. applanata were extracted with ethanol : H2O (85 : 15). A fraction of this extract was lyophilized, and the remainder was partitioned into CH2Cl2, n-BuOH, and water. CH2Cl2 and n-BuOH fractions were subjected to a successive open column chromatography process. The structure of the isolated compounds was established using nuclear magnetic resonance and mass spectrometry spectra. The antihyperglycemic activity was evaluated through in vivo sucrose and glucose tolerance experiments, as well as ex vivo intestinal absorption and hepatic production of glucose. Wound healing and edema inhibition were assayed in mice. The minimum inhibitory concentrations (MICs) of the hydroalcoholic extract, its fractions, and pure compounds were determined through agar microdilution against the most isolated pathogens from diabetic foot ulcers. Fatty acids, β-sitosterol, stigmasterol, hecogenin (1), N-oleyl-D-glucosamine, β-daucosterol, sucrose, myo-inositol, and hecogenin-3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)-β-D-glucopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (2) were characterized. This research provides evidence for the pharmacological importance of A. applanata in maintaining normoglycemia, showing anti-inflammatory activity and antimicrobial effects against the microorganisms frequently found in diabetic foot ulcers. This plant plays an important role in wound healing and accelerated tissue reparation.