Jia Zhou

The gut microbiota is considered a central regulator of immune homeostasis, and microbial metabolites serve as key mediators that translate microbial activity into host immune responses. Traditional Chinese medicine (TCM) can modulate the composition of the gut microbiota; however, changes in microbial communities alone cannot fully explain its immunomodulatory effects. Therefore, this review summarizes the mechanisms by which TCM reshapes the gut microbial metabolome and, in turn, modulates host immune responses. TCM interventions effectively promote the production of beneficial microbial metabolites, suppress potentially harmful metabolites, and enhance microbial-mediated biotransformation of phytochemicals, thereby reshaping the gut immune microenvironment. Immune signaling pathways activated by microbial metabolites include G protein-coupled receptors, aryl hydrocarbon receptors, farnesoid X receptor, Takeda G protein-coupled receptor 5, and epigenetic regulatory mechanisms; these pathways synergistically regulate mucosal immunity, immune cell differentiation, inflammatory responses, and immune homeostasis. Furthermore, this study explored the therapeutic role of the “traditional Chinese medicine–gut microbiota–microbial metabolites” axis in inflammatory bowel disease, cancer, metabolic inflammation, autoimmune diseases, and other immune-mediated conditions. This research provides a new theoretical foundation for how TCM modulates host immunity by reshaping microbial metabolites, and offers new insights for the development of interventions targeting the gut microbiota.

Background/Objectives: Chronic insomnia commonly induces progressive memory decline, severely compromising human daily life and work capability. At present, there are no safe long-term available agents that can concurrently relieve insomnia symptoms and rescue accompanying memory dysfunction. This study aimed to optimize the preparation of deer brain peptides (DBPP) and zinc-chelated DBPP (Zn-DBPP), and explore their protective effects and molecular mechanism against insomnia-caused memory impairment, hoping to develop novel functional candidates for related neurological disorders. Methods: Single-factor experiments combined with response surface methodology were used to optimize the synthesis process of DBPP and Zn-DBPP. A para-chlorophenylalanine-induced insomnia mouse model was established. The structural characteristics, amino acid composition, and antioxidant activity of the products were verified via multiple spectroscopic and biochemical assays. Pentobarbital sodium sleep test and Morris water maze test assessed behavioral changes. Hippocampal neuronal morphology and BDNF-TrkB pathway expression were detected by histological staining, immunofluorescence and Western blotting. Results: The optimized DBPP achieved a hydrolysis rate of 43.89%, and Zn-DBPP possessed a zinc content of 143.37 mg/g. Successful zinc chelation, rich amino acid components, and strong antioxidant capacity were confirmed in Zn-DBPP. In vivo results showed that Zn-DBPP elevated brain zinc levels, improved learning and memory deficits, and restored hippocampal neuronal damage in insomniac mice. Mechanically, Zn-DBPP alleviated memory impairment by upregulating the BDNF-TrkB signaling pathway. Conclusions: The optimized Zn-DBPP exhibits excellent neuroprotective effects against insomnia-induced memory dysfunction. This work provides a reliable theoretical basis for the application of Zn-DBPP as a promising functional food or drug candidate for intervening in insomnia and cognitive decline.

Food-derived zinc-chelating peptides (ZCPs) have emerged as promising nutritional carriers that enhance zinc bioavailability and exert diverse biological activities. Compared with conventional zinc supplements, peptide-mediated zinc delivery systems exhibit superior gastrointestinal stability, reduced mineral precipitation, and improved intestinal transport efficiency. The present study demonstrates that ZCPs regulate zinc homeostasis through multiple mechanisms, including coordination chemistry, transporter-mediated absorption, regulation of the epithelial barrier, and interactions with the intestinal microenvironment. Beyond facilitating zinc absorption, peptide–zinc complexes exhibit antioxidant, anti-inflammatory, immunomodulatory, metabolic regulatory, and gut-protective activities through the synergistic effects of coordinated zinc ions and peptide bioactivity. Advances in spectroscopic characterization, computational modeling, and systems nutrition approaches have further expanded current understanding of peptide–zinc coordination behavior and physiological functionality. Nevertheless, current studies remain limited by insufficient clinical validation and an incomplete understanding of intestinal transport kinetics and controlled zinc release mechanisms. Overall, food-derived ZCPs demonstrate considerable potential for precision nutrition interventions and the development of next-generation functional zinc delivery systems.

Sugarcane polyphenols (SP) are investigated for their antidepressant potential using a CUMS-induced mouse model and a corticosterone-induced neuronal injury cell model. Results demonstrate that SP alleviates depressive-like behaviors, inhibits hippocampal neuronal apoptosis, and reduces neuroinflammation. Mechanistically, SP activates the MAPK/ERK pathway, which in turn suppresses NLRP3 inflammasome-mediated pyroptosis; this effect is attenuated by the MAPK/ERK inhibitor PD98059. Furthermore, SP synergizes with the caspase-1 inhibitor VX-765 to inhibit pyroptosis.

Ginseng (Panax ginseng C. A. Mey.) is a classic traditional Chinese herbal medicine with a history of clinical use that spans millennia. Its utilisation has long been established in the regulation of physical and mental equilibrium, in addition to the amelioration of conditions pertaining to the heart, spleen, and brain. Recent studies have indicated that the core biological activity of the substance under investigation is mediated by key active components such as ginsenosides, polysaccharides, and polyphenols. These components are closely associated with the regulation of the gut-brain axis (GBA). However, extant reviews have predominantly concentrated on individual diseases or specific mechanisms, thereby lacking a thorough investigation into the comprehensive analysis of how ginseng components exert systemic effects via the GBA. This review systematically searched and analyzed published studies in major databases regarding the regulation of the GBA by ginseng bioactive components, summarizing the latest advances in its role as a multifactorial disease intervention regulator targeting the GBA. It has been demonstrated that ginseng components exert a multifaceted GBA regulatory effect through interconnected mechanisms, including modulation of the gut microbiota, protection of the intestinal barrier, anti-inflammatory actions, and regulation of neurotransmitters, showing promising preclinical therapeutic potential in neurodegenerative diseases, mood disorders, metabolic diseases, and gastrointestinal disorders. Contrary to previous reviews, which focused on the description of individual ginseng components or specific diseases, this study provides a comprehensive analysis of how various bioactive components of ginseng modulate the gut-brain axis in relation to multiple disease categories through a systematic review. However, the preponderance of extant evidence derives from preclinical studies and necessitates further validation through clinical trials. This review provides pivotal directions and theoretical underpinnings for the clinical translation of ginseng’s bioactive components and the development of disease intervention strategies targeting the gut-brain axis.

Background/Objectives: Alzheimer’s disease (AD) has an irreversible disease course, making early intervention a key measure to delay disease progression. However, existing therapies are limited by weak brain-targeted delivery efficiency due to the blood–brain barrier (BBB) and low bioavailability of drugs, making it difficult to address the complexity of AD’s pathological mechanisms. Methods: Addressing these limiting factors, this research aims to develop an early AD intervention formulation with “high targeting, high bioavailability, and high biosafety.” Based on the principle of drug synergistic effects, this study employed the reverse solvent method and optimized the combination ratio of Ginsenoside Rg3 and Naringenin (Nar) to design and prepare a self-assembling nano-delivery system (Rg3-Nar-NPs, GNN). The study utilized intranasal administration to bypass the BBB through the direct pathway between the nasal mucosa and central nervous system. Results: This approach enabled targeted accumulation of the drug in brain lesion areas, significantly reducing Aβ deposition, oxidative stress, and inflammatory factor surges caused by early AD, thereby improving cognitive dysfunction in mice. Moreover, GNN demonstrated superior biosafety and bioavailability compared to the individual components. Through transcriptomic analysis, the study elucidated for the first time that GNN can activate the OXT/ERK/Fos pathway to break the malignant cycle of ROS–neuroinflammation, inhibiting the amplification effect of early AD pathological damage. Conclusions: This research provides new molecular targets and drug options for multi-target synergistic intervention of early AD, showing potential as a candidate strategy for precise early AD intervention and laying theoretical and experimental foundations for subsequent clinical translation.