Nobiletin

Whey protein isolate (WPI, Hilmar? 9020) (protein content of 89.5%) was purchased from Hilmar Company (Hilmar Cheese, CA, USA). Soybean oil was supplied by Yihai Kerry Arawana Oils and Grains Industries Ltd. (Shanghai, China). Nobiletin (HPLC purity 98%) was obtained from Sichuan Weikeqi Biological Technology, Co., (Chengdu, China). Pancreatin from porcine pancreas and pepsin from porcine gastric mucosa were purchased from Sigma-Aldrich (St. Louis, MO, USA).

Methanol and acetonitrile (chromatographic purity) was purchased from Fisher company (USA), formic acid (MS grade) was purchased from ACS company (USA), and distilled water was purchased from Guangzhou Watsonsfood and beverage company (Guangzhou, China). Reference standards of sophocarpine, matrine, febrifugine, berberine, palmatine, Tangeratin, nobiletin, liensinine, neferine, scopoletin, isoliquiritigenin, liquiritigenin, naringenin, naringin, hesperidin and glycyrrhizic acid, jatrorrhizine were purchased from Sichuan Weikeqi Biotechnology Co., Ltd. or Shanghai Yuanye Biotechnology Co., Ltd. XSNC were supplied by Shanxi Momentum Pharmaceutical Co., Ltd (Shanxi, China).

Twelve reference standards (purity>98%) were pur-chased from Weikeqi (Sichuan, China). These standardswere  isoscopoletin,  scopoletin,  7-methoxycoumarin,7-hydroxycoumarin,  isomeranzin,  bergapten,  tan-geretin, nobiletin, hesperidin, limonin, ferulic acidand  bergamottin.  Chromatographic-grade  methanoland dichloromethane were purchased from WeikeqiBio-Technology (Sichuan, China). Formic acid and ACN(purity>99.9%) of HPLC-grade were provided by MerckKGaA (Darmstadt, Germany) and Thermo Fisher Scien-tific Inc. (NYSE:TMO), respectively. CO2(purity>99.9%)was provided by Messer Gas (Guangzhou, China).

The reference standards of stachydrine, scopoletin, hesperidin, 5,7-dimethoxycoumarin, limonin, nomilin, nobiletin, and tangeretin were obtained from Weikeqi (Sichuan, China). The compounds had purities higher than 98%. High-performance liquid chromatography (HPLC)-grade formic acid was purchased from Thermo Fisher Scientific (USA). HPLC-grade acetonitrile and n-hexane were obtained from Merck (Germany). Deionized water was prepared by a Milli-Q system (Millipore, USA).

QZWTT was provided by Liaoning Huarun Benxi Sanyao Co. Ltd(Benxi, China, lot no. 20200101). We used 26 chemical referencestandards in this study (Chengdu Pufeide BioTechnology Co. Ltd,Cheng du, China or Weikeqi Biological Technology Co. Ltd, Chengdu,China; Table S1). The acetonitrile, methanol (Merck, Germany) andformic acid (Fisher, USA) were of LC–MS grade, whereas the remain-ing chemicals were of analytically grade.

rhoifolin and poncirin were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Shanghai, China). Other standards, including dydimin, merazin, isomerazin, sinensetin, nobiletin, tangeritin, 5-O-demethylnobiletin and auraptene, were obtained from Sichuan Weikeqi Biological Technology Co., Ltd. (Chengdu, China). All the standards were confirmed by NMR analysis.

All 22 standard compounds used in this study (synephrine, gallic acid, chlorogenic acid, geniposide, peimine, peiminine, albiflorin, paeoniflorin, rutin, narirutin, crocin, naringin, hesperidin, neohesperidin, didymin, quercetin, benzoylpaeoniflorin, paeonol, sinensetin, nobiletin, hepta-3, and alisol B 23-acetate) were supplied by Weikeqi Biotechnology Co., Ltd (Chengdu, China), and the purity were all greater than 98%. UDCA administrated as positive control was supplied by Shanghai Aladdin Biochemical Co., Ltd. (Shanghai, China). ANIT and medical-grade soybean oil were purchased from Shanghai Aladdin Biochemical Co., Ltd. (Shanghai, China).