Traditional Chinese Medicine (TCM) has gained global attention, particularly after Professor Youyou Tu was awarded the Nobel Prize for her discovery of artemisinin as a treatment for malaria. However, the theory behind TCM is often perceived as a "black-box" with complex components and an unclear structure and mechanism of action. This had hindered the development of TCM within the framework of modern medicine. The molecular compatibility theory proposed by Professor Tian Xie's team integrates TCM with Western medicine in clinical practice, and provide a feasible direction for TCM modernization. It is necessary to summarize and popularize this theory. This review aims to systematically introduce this theory to provide some new insight for development of TCM. According to the molecular compatibility theory, the desired effects can be achieved by organically combining multiple active molecules from TCM. These TCM molecular compounds have specific ingredients, precise mechanisms, and controllable quality that meet the standards of modern medicine. The molecular compatibility theory has guided the development of antitumor new drug elemene emulsions, and has also revealed extensive compatibility between TCM-derived active molecules and other TCM, Western medicine, or biomaterials. This discovery opens up potential TCM-based treatment options. In conclusion, the molecular compatibility theory holds promise as a strategy for modernizing TCM.

Background: As sentinel cells of innate immunity, macrophages exhibit microenvironment-driven functional plasticity critical for immune regulation and tissue homeostasis, yet maladaptive metabolic reprogramming-induced polarization dysregulation exacerbates disease progression by manifesting immune dysfunction. Summary: This review systematically deciphers the metabolic signatures governing macrophage polarization – spanning amino acid metabolism, glycolytic flux, lipid dynamics, and iron homeostasis – while dissecting how pathological microenvironments (encompassing tumor niches, atherosclerotic plaques, and obese adipose tissue) co-opt these pathways to drive pathogenesis. Crucially, this analysis demonstrates that cellular metabolism dictates macrophage phenotypic/functional states across disease contexts, with comprehensive decoding of their metabolic networks emerging as imperative for developing next-generation immunotherapies. Key Messages: Therapeutically, pathogenic polarization may be reversed through strategic interventions targeting metabolite-sensing receptors, pharmacologically blocking metabolic checkpoints, and reprogramming core metabolic modalities to restore immunoregulatory competence.

Alzheimer’s disease (AD) currently lacks curative treatments, and the gut–brain axis plays an important role in regulating neuroinflammation during AD progression. Multiple bioactive components from traditional Chinese medicine (TCM), including polysaccharides, alkaloids, flavonoids and saponins, protect neurons through regulating gut microbiota composition, maintaining intestinal barrier function and modulating short-chain fatty acid (SCFA) metabolism. Different from previous reviews that mainly elaborate correlational relationships, the present paper systematically sorts out a multi-level action network of TCM components along the gut-brain axis. We address an interesting discrepancy in current findings on SCFAs: acetate can inhibit inflammation in microglia under mechanical stretch, yet fails to produce the same effect under LPS exposure. Nevertheless, increased SCFA levels in vivo are able to alleviate microglial dysfunction linked to aging. Such findings indicate that SCFA activities are influenced by stimulus types, compound categories and applied doses, reminding researchers to treat existing conclusions with caution. We also outline six widely existing methodological issues in relevant researches, and propose feasible solutions, including the documentation of absolute SCFA concentrations, experimental verification of causal relationships, and the use of AD pathological stimuli like Aβ and tau. This review may facilitate the shift from correlational analysis to mechanistic exploration, and provide useful references for the development of AD therapies targeting the gut–brain axis with TCM components.