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Outline
Stroke is characterized by high incidence, high disability, high mortality, and high recurrence rates. Current clinical management relies primarily on injectable thrombolytic therapy. While a variety of oral adjuvant medications are available, their therapeutic efficacy and underlying mechanisms have not been systematically evaluated. Traditional Chinese medicine (TCM), as a multi-component and multi-target therapeutic option, has demonstrated considerable potential in the prevention and treatment of stroke. Emerging evidence indicates that TCM exerts modulatory effects on stroke-related pathological processes by regulating the gut microbiota, maintaining gastrointestinal homeostasis, and acting through the gut-brain axis. The conventional pharmacological paradigm holds that drugs must enter the systemic circulation and traverse the blood-brain barrier (BBB) to exert central effects. Despite their low oral bioavailability and limited systemic exposure, certain pharmacologically active constituents nonetheless exert significant neuroprotective effects, suggesting that their in vivo activities may be mediated by indirect gut-derived regulatory mechanisms rather than direct systemic actions. Based on these observations, we propose the concept of "intestinal retention components" (IRC), referring to a class of orally administered bioactive constituents that are poorly absorbed across the intestinal epithelium and predominantly retained within the intestinal lumen due to their physicochemical properties. Although these compounds exhibit minimal systemic exposure, they are capable of modulating the intestinal microenvironment, thereby influencing brain function and improving stroke outcomes. This review aims to systematically elucidate the potential mechanisms by which IRC indirectly exerts anti-stroke effects via the gut-brain axis, encompassing microbiota-mediated biotransformation, attenuation of gut microbial dysbiosis and its associated metabolic perturbations, restoration of intestinal barrier integrity, and regulation of the intestinal mucosal immune microenvironment. Given that numerous central nervous system disorders are also accompanied by intestinal microenvironmental dysregulation, the IRC-centered research framework targeting the gut microenvironment may provide a valuable reference for mechanistic elucidation and the identification of candidate drugs among orally active constituents in the context of broader neurological diseases.
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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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