Chow Junwei, Yang Xiaolei, Hu Jiarong, Yu Qiuxia, Zhong Yu, Hu Xinyi, Liang Jingru, Zhu Chenyang, Yan Shiwei, Li Longzhou, Liu Haiyang, Wang Tiandian, Wang Zihan, Gao Long, Ma Guo
School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P.R. China.
Sci Rep. 2025 Jan 3;15(1):658. doi: 10.1038/s41598-024-81823-y.
Hawthorn leave flavonoids (HLF) are widely used as an herb or dietary supplements for cardio-cerebrovascular diseases. However, its gastrointestinal absorption behavior and mechanism have not been disclosed. In this study, gastrointestinal absorption and its regulation of 4''-O-glucosylvitexin (GLV), 2''-O-rhamnosylvitexin (RHV), vitexin (VIT), rutin (RUT) and hyperoside (HP) in HLF were investigated using in vitro, in situ and in vivo models. Apparent permeability coefficient (P) of five flavonoids were (2.18 ± 0.15) ×10~(3.83 ± 0.22) ×10 cm·sec across the Caco-2 cells. GLV, RHV, VIT and RUT demonstrated similar and poor absorption in rat stomach (absorption percentage per hour (A), (1.78 ± 0.14 ~ 5.69 ± 0.51)%·h) and small intestine (absorption rate ([Formula: see text], (0.012 ± 0.006 ~ 0.055 ± 0.003) h), extent (A, (1.28 ± 0.14 ~ 2.82 ± 0.19)% ·h) and potential (P, (0.31 ± 0.05 ~ 1.41 ± 0.08)×10 cm·sec)), while HP showed relatively better absorption (P, (2.55 ± 0.15 ~ 4.27 ± 0.36)×10 cm·sec) in rat small intestine. Absorption of five flavonoids exhibited dose-dependence, pH-dependence and region-selectivity. Meanwhile, these flavonoids were excreted via intestine, secreted via bile and metabolized by intestinal microflora. Their absorption was significantly increased by absorption enhancers (cow bile salt and sodium dodecyl sulphate), transporter regulators (verapamil hydrochloride, digoxin and rifampicin). GLV and RHV exhibited enterohepatic circulation after oral administration of HLF. In conclusion, flavonoids in HLF were absorbed via passive diffusion accompanied with active transport, intestinal microflora metabolism, bile secretion and intestinal efflux. They belong to BCS class III ("like" drugs with high solubility and low permeability) and displayed poor oral bioavailability.
山楂叶黄酮（HLF）被广泛用作治疗心脑血管疾病的草药或膳食补充剂。然而，其胃肠道吸收行为和机制尚未明确。本研究采用体外、原位和体内模型，研究了HLF中4''-O-葡萄糖基牡荆素（GLV）、2''-O-鼠李糖基牡荆素（RHV）、牡荆素（VIT）、芦丁（RUT）和金丝桃苷（HP）的胃肠道吸收及其调控。五种黄酮类化合物在Caco-2细胞上的表观渗透系数（P）为（2.18±0.15）×10（3.83±0.22）×10 cm·sec。GLV、RHV、VIT和RUT在大鼠胃（每小时吸收百分比（A），（1.78±0.145.69±0.51）%·h）和小肠（吸收速率（[公式：见原文]，（0.012±0.0060.055±0.003）h）、吸收程度（A，（1.28±0.142.82±0.19）%·h）和吸收潜能（P，（0.31±0.051.41±0.08）×10 cm·sec））中的吸收表现相似且较差，而HP在大鼠小肠中的吸收相对较好（P，（2.55±0.154.27±0.36）×10 cm·sec）。五种黄酮类化合物的吸收呈现剂量依赖性、pH依赖性和区域选择性。同时，这些黄酮类化合物通过肠道排泄，经胆汁分泌，并由肠道微生物群代谢。吸收增强剂（牛胆盐和十二烷基硫酸钠）、转运体调节剂（盐酸维拉帕米、地高辛和利福平）可显著增加它们的吸收。口服HLF后，GLV和RHV表现出肠肝循环。总之，HLF中的黄酮类化合物通过被动扩散伴随主动转运、肠道微生物群代谢、胆汁分泌和肠道外排进行吸收。它们属于BCSⅢ类（高溶解性、低渗透性的“类”药物），口服生物利用度较差。
