Shengmai Yin Attenuates Hypobaric Hypoxia-Induced Erythrocyte Echinocytosis by Restoring Redox Homeostasis and Normalizing Band 3–Syk/SHP2 Interactions

Acute exposure to high-altitude hypobaric hypoxia (HH) disrupts redox homeostasis and impairs erythrocyte morphology and oxygen transport. Shengmai Yin (SMY) is a botanical formulation with reported antioxidant activity, but its effects on HH-induced erythrocyte injury remain unclear. Male C57BL/6J mice received SMY in drinking water for 3 days before 24 h of simulated HH equivalent to 6000 m. Complementary in vivo and in vitro experiments assessed redox indices, lipid peroxidation, hemoglobin redox status, erythrocyte morphology, arterial oxygenation, and Band 3-associated protein interactions. HH increased serum DHE-derived fluorescence, nitric oxide, and malondialdehyde, reduced antioxidant capacity, induced echinocytosis, decreased oxyhemoglobin, and increased methemoglobin. Among the tested redox challenges, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) most closely reproduced the combined morphological and hemoglobin abnormalities. SMY scavenged DPPH, hydroxyl-radical, and superoxide-related signals in cell-free assays; reduced PTIO- and hypoxia-induced erythrocyte damage; and reversed established echinocytosis within 30 min in vitro. In mice, SMY reduced echinocytosis and improved arterial oxygenation without detectable short-term hepatic, renal, or histological toxicity. SMY also normalized HH- and PTIO-induced changes in Band 3 interactions with Syk and SHP2. These findings support SMY as a redox-modulating intervention that preserves erythrocyte structure and function during acute HH.