The other reagents were of analytical grade and purity and commercially available. The reference standards (gallic acid, synephrine, hesperidin, nobiletin, tangeretin, ferulic acid, narirutin, and limonin) were obtained from Must Biotechnology. The other reference standards (3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), isoscopoletin, scopoletin, scoparone, stachydrine) were purchased from Weikeqi Biological Technology Co., Ltd. and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF) was obtained from Spring & Autumn Biological Engineering Co., Ltd. The purity of these reference standards was above 98%.

The reference standards nobiletin (purity: 99.46%) and tangeretin (purity: 99.77%) were purchased from Must (Chengdu, China). The other two reference standards 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF, purity>98%) and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF, purity>98%) were purchased from Weikeqi (Sichuan, China) and Spring & Autumn (Nanjing, China), respectively. Formic acid (HPLC grade) was purchased from Thermo Fisher Scientific (Shanghai, China). Acetonitrile was purchased from Honeywell (Wicklow, USA).

HFD (normal chow supplemented with 1.25% cholesterol, 20% fat, and 0.5% cholic acid, w/w) for 6 weeks. For HMF experiments, mice were once daily oral gavage with vehicle, 25 or 50 mg/kg HMF (Weikeqi, China), or 30 mg/kg lovastatin (LOV, Aladdin, China) for 42 days.

Guangzhou Medical University. Eight compounds were used as reference standards with purity greater than 98%. Among them, 3,5,6,7,8,3′,4′-heptamethoxyflavone and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone were purchased from Sichuan Weikeqi Biotechnology Co., Ltd and Nanjing Chunqiu Biological Engineering Co. Ltd, respectively.

The reference standards (gallic acid, synephrine, limonin, hesperidin, nobiletin and tangeretin) were obtained from Must (Chengdu, China). The other two reference standards (3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF)) were purchased from Weikeqi (Sichuan, China) and Spring & Autumn (Nanjing, China), respectively.

Reference standards, namely limonin, hesperidin, neohesperidin, nobiletin, tangeretin, naringin, and synephrine, were purchased from Chengdu Mansite Biotechnology. 3,5,6,7,8,3′,4′-Heptamethoxyflavone was obtained from Sichuan Weikeqi Biotechnology, and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone was acquired from Nanjing Chunqiu Biological Engineering.

Hesperidin (Chengdu Must Bio-Technology, Chengdu, China), nobiletin (Chengdu Must Bio-Technology, Chengdu, China), 3,5,6,7,8,3′,4′-heptamethoxyflavone (Weikeqi, Sichuan, China), tangeretin (Chengdu Must Bio-Technology, Chengdu, China), and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (Spring & Autumn, Nanjing, China) were all of reference standard grade, with the high purity above 98%. All other reagents were of analytical grade and pure.

Besides, the reference standards of gallic acid, synephrine (C1), hesperidin (C2), ferulic acid (C3), limonin (C4), nobiletin (C5), and tangeretin (C7) were obtained from Must Bio-technology Co., Ltd. (Chengdu, Sichuan, China), whereas 3,5,6,7,8,3’,4’-hepatamethoxyflavone (C6) and 5-hydroxy-6,7,8,3’,4’-pentamethoxyflavone (C8) were obtained from Weikeqi Biological Technology Co., Ltd. (Chengdu, Sichuan, China) and Spring &Autumn Biological Engineering Co., Ltd (Nanjing, JInagsu, China), respectively.