Polysaccharide from Angelica sinensis protects H9c2 cells against oxidative injury and endoplasmic reticulum stress by activating the ATF6 pathway

OBJECTIVES: Angelica sinensis exerts various pharmacological effects, such as antioxidant and anti-apoptotic activity. This study aimed to investigate the active ingredients in A. sinensis with antioxidant properties and whether A. sinensis polysaccharide (ASP) protects H9c2 cells against oxidative and endoplasmic reticulum (ER) stress. METHODS: The ingredients of A. sinensis and their targets and related pathways were determined using web-based databases. Markers of oxidative stress, cell viability, apoptosis, and ER stress-related signalling pathways were measured in H9c2 cells treated with hydrogen peroxide (H(2)O(2)) and ASP. RESULTS: The ingredient–pathway–disease network showed that A. sinensis exerted protective effects against oxidative injury through its various active ingredients on regulation of multiple pathways. Subsequent experiments showed that ASP pretreatment significantly decreased H(2)O(2)-induced cytotoxicity and apoptosis in H9c2 cells. ASP pretreatment inhibited H(2)O(2)-induced reactive oxygen species generation, lactic dehydrogenase release, and malondialdehyde production. ASP exerted beneficial effects by inducing activating transcription factor 6 (ATF6) and increasing ATF6 target protein levels, which in turn attenuated ER stress and increased antioxidant activity. CONCLUSIONS: Our findings indicate that ASP, a major water-soluble component of A. sinensis, exerts protective effects against H(2)O(2)-induced injury in H9c2 cells by activating the ATF6 pathway, thus ameliorating ER and oxidative stress.