Exploring the Biological Connotation of "Invisible Phlegm" from the Perspective of Brain Fluid Exchange and Extracellular Microenvironment Regulation
10.13288/j.11-2166/r.2026.15.002
- VernacularTitle:从脑内液体交换与细胞外微环境调控探讨“无形之痰”的生物学内涵
- Author:
Yiming REN
1
;
Yueyang LU
1
;
Guoyuan ZHANG
2
;
Weiyi CAO
2
;
Zongliang YU
1
;
Haoling ZHANG
2
;
Rui GAO
2
Author Information
1. Beijing University of Chinese Medicine，Beijing，100029
2. Xiyuan Hospital，China Academy of Chinese Medical Sciences
- Publication Type:Journal Article
- Keywords:
brain extracellular space;
glymphatic system;
extracellular matrix;
metabolic waste clearance;
turbid phlegm obstructing the orifices;
invisible phlegm
- From:
Journal of Traditional Chinese Medicine
2026;67(15):1592-1598
- CountryChina
- Language:Chinese
-
Abstract:
Based on the traditional Chinese medicine （TCM） theories of body fluid metabolism and turbid phlegm obstructing the orifices， and drawing on recent advances in cerebrospinal fluid-interstitial fluid （CSF-ISF） exchange， glymphatic clearance， and extracellular matrix （ECM） regulation， this article discusses the possible scientific connotation of "invisible phlegm" from the perspectives of pathogenesis， clinical manifestations， and therapeutic implications. Impaired brain fluid exchange may lead to reduced clearance， the retention of metabolic wastes and pathological proteins. Abnormal ECM remodeling may further disrupt molecular diffusion and local microenvironmental homeostasis， resulting in a pathological process characterized by slowed fluid movement， reduced clearance， and abnormal retention. This process bears a certain functional resemblance to the TCM pathogenesis of impaired distribution of body fluids， endogenous formation of turbid phlegm and obstruction of the brain orifices， and may also be associated with manifestations such as a clouded sensation in the head， cognitive abnormalities， and emotional disturbances. On this basis， the potential effects of certain phlegm-dissolving Chinese medicines in improving brain clearance function and extracellular microenvironmental homeostasis warrant further investigation. We therefore propose that， the "invisible phlegm" of TCM in brain tissue may manifest as a pathological retention state characterized by restricted fluid exchange， impaired clearance function， and extracellular microenvironmental imbalance. This perspective may provide a new avenue for investigating TCM treatment of neurological and psychiatric disorders from the perspective of phlegm.
