Hydroxysafflor yellow a

Methanol and formic acid were purchased from Fisher Scientific (Fair Lawn, NJ, USA). Dimethyl sulfoxide (DMSO) was acquired from Meridian Medical Technologies (MREDA, New York, NY, USA). Water for UHPLC/Q-Orbitrap-MS analysis was purified by the Milli-Q water purification system (Millipore, Billerica, MA, USA). QZC samples were provided by Shaanxi Buchang Pharmaceutical Co., Ltd. (Shaanxi, China). Reference compounds were obtained from Shanghai Yuanye Bio-Technology Co., Ltd. (Shanghai, China), including gallic acid, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, loganic acid, corilagin, loganin, isochlorogenic acids A−C, angelol A, columbianetin acetate, osthole, columbianadin, akebia saponin D, 5-hydroxymethyl furfural, 4-hydroxybenzoic acid, caffeic acid, hydroxysafflor yellow A, syringin, ferulic acid, secoxyloganin, ellagic acid, columbianetin, angelol G, and isoimperatorin. Benzoylmesaconine, benzoylaconine, and benzoylhypaconine were obtained from Shanghai Acmec Biochemical Co., Ltd. (Shanghai, China). Kaempferol-3-O-rutinoside was obtained from Chengdu Pufei De Biotech Co., Ltd. (Chengdu, China). The purities of these reference compounds were all determined to be above 98% by UPLC analysis.

We purchased the standard reference materials of amygdalin, hydroxysafflor yellow A, calycosin, and digoxin from Yuanye Bio-Technology Co., Ltd. (Shanghai, China). digoxin is not the endogenous compound of BYHWD and plasma, and it does not obviously interfere with the retention times of all three analytes. Qualitative analysis was carried out using an LC-MS system (Shimadzu 8050, Kyoto, Japan) in negative ion mode. The plasma samples were added with digoxin, vortex mixed for 10 s, and then vortex mixed for 1 min and centrifuged for 15 min (13,000 rpm, 4°C) after being added 800 μL acetonitrile. The obtained supernatants were dried in a nitrogen dryer, diluted with 10% acetonitrile–water, repeated the extraction above, and injected into the LC-MS for analysis (Supplementary Figure S1).

Xuebijing injection (catalog number: z20040033, batch number: 1905061) was manufactured by Tianjin Chase Sun Pharmaceutical Co., Ltd (Tianjin, China). Paeoniflorin (CAS #:23180-57-6), Hydroxysafflor yellow A (CAS #: 78281-02-4), Ferulic acid (CAS # 537- 98-4), and protocatechuic aldehyde (CAS #: 139-85-5) were purchased from Shanghai Yuanye Biotechnology Co., Ltd. (Shanghai, China). Mouse NT-proBNP ELISA (Cat#: ZC-37812-96T) kit, DCFH-DA (Cat#:CA1410-100T), RIPA tissue/cell lysate (Cat#: R0020), SDS-PAGE gel kit, and Rainbow 245 Spectrum Marker (Cat#:PR 1920), Mouse IL-6 ELISA kit (Cat#:ZC-37988-96T), Mouse IL-1β ELISA kit (Cat#:ZC-37974-96T), and EasySee Western Blot Kit (Lot#:O30807) were purchased from Solarbio (Beijing, China). The primary antibody of rabbit anti-CXCL2 (bs-1162R) was purchased from Bioss Inc., (Beijing, China) and GAPDH, 1:4,000 (14C10) was from Cell Signaling Technology (Beverly, MA, United States). The secondary antibody Goat anti-Rabbit IgG (1:4,000) (ZB-2301) was purchased from ZS bio (Beijing, China). 2, 2, 2-Tribromoalcohol (Cat#:T48402) and Bacterial lipopolysaccharide (Cat#: L2880-10 MG) were purchased from Sigma Aldrich (St. Louis, MO, United States). Rhod2-AM (Cat#: zy0129) and Anti-GRP78 (BiP) antibody (ab21685) were purchased from Abcam (Cambridge, MA, United States).