Although the eradication of Helicobacter pylori is critical for preventing gastric cancer, current therapies often overlook the restoration of the gastric microenvironment, leading to a prevalence of delayed tissue healing and dysbiosis. Consequently, many patients remain in a persistent pathological state despite successful H. pylori clearance, presenting a major bottleneck in clinical treatment. This review summarizes recent advancements in gastric-targeted drug delivery systems, illustrating the evolution from a singular antibacterial approach to an integrated sequential strategy encompassing clearance, repair, and homeostasis reconstruction. We examine smart gastro-retentive and nanodelivery systems designed to overcome physiological barriers, highlighting formulations that extend gastric residence time and maintain local drug concentrations above the Minimum Inhibitory Concentration for prolonged periods. Furthermore, we discuss spatiotemporally controllable biomaterials, such as Janus hydrogels and ROS-responsive carriers. These systems demonstrate distinct pH-dependent release kinetics and high stability in simulated gastric fluids, effectively preserving bioactive payloads to modulate the immune microenvironment. By facilitating the transition from pro-inflammatory to anti-inflammatory phenotypes, these biomaterials support epithelial regeneration. The review concludes with an analysis of postbiotics and the proposed holistic strategy, offering a promising therapeutic framework for mitigating the inflammation-to-cancer transition and promoting gastric health remodeling.

Background: Chronic cough significantly affects human health and quality of life. Studies have shown that Sanao Decoction（SAD）can clinically treat chronic cough. To investigate its mechanisms, we used the method of network pharmacology to conduct research at the molecular level.Methods: The active ingredients and their targets were screened by pharmacokinetics parameters from the traditional Chinese medicine system pharmacology analysis platform (TCMSP). The relevant targets of chronic cough were obtained from two databases: GeneCards and DrugBank. Take the intersection to get potential targets of SAD to treat chronic cough and establish the component-target regulatory network by CytoScape3.7.2 and protein-protein interaction (PPI) network by STRING 1.0. The function of the target gene and related pathways were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) in the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The significant pathways and their relevant targets were obtained and the target-pathway network was established by CytoScape3.7.2. Finally, molecular docking of the core active components and relevant targets was performed.Results: A total of 98 active components, 113 targets were identified. The component-target and target-pathway network of SAD and PPI network were established. Enrichment analysis of DAVID indicated that 2062 terms were in biological processes, 77 in cellular components, 142 in molecular functions and 20 significant pathways. In addition, the molecular docking showed that quercetin and luteolin had a good combination with the corresponding targets.Conclusions: It indicates that the active compounds of SAD, such as quercetin, luteolin, may act on AKT1, MAPK1, RELA, EGFR, BCL2 and regulate PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications and Fluid shear stress and atherosclerosis pathway to exert the effects of anti-inflammatory, anti-airway remodeling, anti-oxidant stress and repair airway damage to treat chronic cough.

Metabolic diseases are jointly driven by insulin resistance, chronic inflammation, lipotoxicity, and disrupted organelle homeostasis arising from sustained nutrient overload. These disorders substantially increase the risk of cardiovascular, renal, and other multi-organ complications and have become a major global public health burden. Mitochondria are central organelles that integrate energy metabolism with stress signaling. They participate in fatty acid β-oxidation, the tricarboxylic acid cycle, and oxidative phosphorylation, while also regulating reactive oxygen species generation, mitochondrial DNA-related inflammatory signaling, calcium homeostasis, and cell death. Under chronic metabolic stress, the mitochondrial quality control (MQC) system shifts from adaptive repair toward decompensation, characterized by impaired mitochondrial biogenesis, abnormal mitochondrial dynamics, defective mitophagy, disrupted proteostasis and mitochondrial unfolded protein response, increased oxidative stress, and impaired metabolic reprogramming. Natural small molecules possess structural diversity and multi-target, multi-pathway regulatory properties. They can modulate multiple MQC processes and improve mitochondrial function and metabolic phenotypes in preclinical models. Novel formulations, structural optimization, and mitochondria-targeted delivery can further improve their solubility, bioavailability, tissue exposure, and subcellular localization, thereby enhancing therapeutic efficacy and translational potential. This review systematically summarizes the mechanisms of MQC dysregulation in metabolic diseases, the evidence supporting natural small-molecule interventions, and strategies for formulation and delivery optimization. Future studies should strengthen causal validation of MQC, quantify intramitochondrial drug exposure, and incorporate clinically relevant endpoints to facilitate the translation of natural small-molecule MQC modulators.