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Bushen Huoxue Prescription（补肾活血方，BHP），a traditional Chinese medicine formula，is used for the treatment of diabetic retinopathy（DR）. It is composed of four herbal ingredients. However，the absorbed prototypes and metabolites of BHP have not been extensively studied.
The plasma，liver，heart，spleen，lung，kidney，intestine，stomach，eye，urine and feces of SD rats at different time points were collected after intragastric administration of BHP. The absorbed prototypes and metabolites of BHPin rats were characterized using the UHPLC-Q-Exactive-MS/MSstrategy. The metabolic networks in rats after oral administration of BHP were constructed by molecular network.
Seventy-five absorbed prototypes and 123 metabolites were identified in rats belonging to different groups in BHP，including iridoids，phenylethanol glycosides，tanshinones，ginsenosides，isoflavonoids and other types of compounds. Phenylethanoid glycosides were derived from Dihuang（Rehmanniae Radix），which had low bioavailability and were easy to be biotransformed into metabolites such as methylation and glucuronidation，and were more distributed in the kidney. The prototype components of tanshinones and isoflavones were derived from Danshen（Salviae Miltiorrhizae Radix et Rhizoma）and Gegen（Puerariae Lobatae Radix）respectively，which were easily detected in rat plasma and tissues. The metabolic pathways were mainly hydroxylation，methylation and glucuronidation，and the products were easily distributed in plasma and liver and kidney tissues. Ginsenosides were easily hydrolyzed into protopanaxadiol and protopanaxatriol in the gastrointestinal tract of rats. After phase I metabolism such as dehydrogenation and deoxidation，the products were more distributed in the spleen.
These findings could reveal the mechanism of action of BHPin DR treatment and provide a method for the discovery of metabolites and metabolic pathways.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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