In traditional Chinese medicine (TCM), Pinellia ternata is widely used to treat respiratory and digestive disorders due to its efficacy in resolving phlegm, alleviating cough, and stopping nausea. Guided by the traditional concept that "the spleen generates phlegm and the lung stores it," this study established a sulfur-smoke combined with cold-damp exposure model in Sprague-Dawley rats to investigate the therapeutic effects and molecular mechanisms of P. ternata aqueous extract. Rats were assigned to blank (CK), model (MD), positive-drug (Y1/Y2), and low-, medium-, or high-dose P. ternata extract groups (0.75/1.5/3.0 g/kg). Lung function was assessed using a non-invasive Buxco system across 12 respiratory parameters. Lung and spleen pathology and mucin (MUC5AC/MUC5B) expression were evaluated by H&E staining and immunohistochemistry. Plasma IL-6, TNF-α, TGF-β, PCT, and other inflammatory markers were measured by ELISA. Plasma metabolite profiles were analyzed using LC-MS/GC-MS platforms, and lung and spleen transcriptomes were examined to determine gene expression changes. In parallel, the chemical constituents of the P.ternata aqueous extract were characterized using widely targeted metabolomics and high-performance liquid chromatography, and molecular docking was employed to elucidate the interactions between individual constituents and potential therapeutic targets. After 28 days of modeling, airway obstruction was most severe in the MD and low-dose extract groups, whereas the medium- and high-dose groups showed no significant difference from CK or the positive-drug groups, indicating effective symptom relief at adequate doses. The extract, especially at high dose, markedly improved lung and tracheal inflammation and restored spleen tissue architecture. It dose-dependently suppress MUC5AC overexpression in lung and tracheal tissues, while showing variable effects on MUC5B. The extract also reduced plasma pro-inflammatory cytokines and TGF-β and PCT levels, improving systemic immune imbalance. Metabolomics revealed that high-dose P.ternata downregulated amino acids related to mucin synthesis (e.g., proline) and inflammatory lysophosphatidylcholines, while increasing immune-regulatory lipids such as ω-3 PUFA and S1P. These metabolic shifts were accompanied by upregulation of key genes in the Notch pathway in the spleen and suppression of cytokine-storm-related signaling in the lung, including NF-κB(nuclear factor kappa-B), JAK-STAT(Janus kinase/signal transducer and activator of transcription), and PI3K-Akt(phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)) signaling pathways, collectively reducing inflammation and correcting metabolic dysregulation. Combined targeted metabolomics and high-performance liquid chromatography identified that the major constituent categories in Pinellia ternata aqueous extract are organic acids, alkaloids, and nucleosides. Analysis of constituent-target interactions revealed that nucleoside compounds exhibited the strongest binding affinity to the predicted targets. This study, through integrated pathological, metabolomic, and transcriptomic analyses, elucidates both the core pathological features of phlegm-dampness lung obstruction and the modern biological basis for the traditional role of P. ternata in "strengthening the spleen and resolving phlegm." Importantly, nucleoside compounds were identified as key active constituents contributing to its therapeutic effects. Collectively, these findings offer experimental support for the classical TCM concept that spleen dysfunction leads to phlegm accumulation in the lung.

Baihe Dihuang Decoction (BDD) is a traditional Chinese medicinal formula with well-documented antidepressant effects. However, the role of its polysaccharide fraction (BDDP) remains poorly understood. This study aimed to investigate the structural characteristics and antidepressant mechanisms of BDDP through chemical analysis and in vivo validation. BDDP was obtained by ethanol precipitation and analyzed by high-performance anion-exchange chromatography (HPAEC), revealing a heteropolysaccharide composed of rhamnose, arabinose, galactose, glucose, mannose, and fructose, with an average molecular weight of 20.7 kDa and a β-configured glycosidic backbone. In a chronic unpredictable mild stress (CUMS) rat model, BDDP administration significantly alleviated depression-like behaviors and restored monoamine neurotransmitter levels. Integrated proteomic and metabolomic analyses of hippocampal and serum samples indicated that BDDP exerts antidepressant effects primarily through metabolic reprogramming. Key mechanisms include modulation of nitrogen metabolism via CA1/CA3 (which helps rebalance glutamate/GABA and sustain pH homeostasis), enhancement of energy metabolism via branched-chain amino acid catabolism and NAD+ biosynthesis, suppression of neuroinflammation via ω-3/ω-6 fatty acid regulation, and activation of glutathione-mediated antioxidant defense. These findings show that BDDP acts as a multi-target macromolecular therapeutic candidate for depression and links its structural features to systemic metabolic regulation.

N-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) are essential for physiological requirements and disease prevention throughout life but are not adequately consumed worldwide. Dietary supplementation with plant-derived α-linolenic acid (ALA) has the potential to rebalance the fatty acid profile and enhance health benefits but faces challenges such as high β-oxidation consumption, low hepatic conversion efficiency, and high oxidative susceptibility under stress. This review focuses on the metabolic fate and potential regulatory targets of ALA-containing lipids in vivo, specifically the pathway from the gastrointestinal tract to the lymph, blood circulation, and liver. We propose a hypothesis that positively regulates the conversion of ALA into n-3 LCPUFAs based on the model of "fast" or "slow" absorption, transport, and hepatic metabolic fate. Furthermore, the potential effects of dietary nutrients on the metabolic conversion of ALA into n-3 LCPUFAs are discussed. The conversion of ALA is differentially regulated by structured lipids, phospholipids, other lipids, carbohydrates, specific proteins, amino acids, polyphenols, vitamins, and minerals. Future research should focus on designing a steady-state and precise delivery system for ALA, coupled with specific nutrients or phytochemicals, to effectively improve its metabolic conversion and ultimately achieve synergistic regulation of nutrition and health effects. The regulatory targets of ALA for conversion into n-3 LCPUFAs were elucidated.A hypothesis for positively regulating the conversion into n-3 LCPUFAs was proposed.Dietary regulation is an effective strategy for improving ALA conversion.Constructing a precise ALA delivery system is a key direction for future research.Emerging pathways and resources for n-3 PUFA uptake are a matter of concern.

Alzheimer’s disease (AD) is the most common form of dementia, and its incidence is projected to triple worldwide over the next 25 years. The most prevalent form, late-onset Alzheimer’s disease (LOAD), develops in genetically predisposed individuals exposed to environmental risk factors. Hallmarks of AD include accumulation of amyloid-β (Aβ), neurofibrillary tangles (NFTs), neuroinflammation, and mitochondrial dysfunction, resulting in oxidative stress, impaired glucose metabolism, and cognitive decline. Such metabolic disruptions result in early cerebral glucose hypometabolism and other metabolic disruptions, including altered lipid and branched-chain amino acid profiles. Recent evidence suggests that gut microbiota alterations, although individually variable, are a consistent and influential factor in AD progression via inflammatory and metabolic pathways. This narrative review explores therapeutic interventions targeting the gut-brain axis, including fecal microbiota transplantation (FMT), probiotic and antibiotic treatments, and dietary strategies such as the ketogenic and Mediterranean diets, as well as nutritional compounds such as omega-3 fatty acids. The aim is to evaluate the latest findings in both preclinical and clinical studies to identify multi-targeted, microbiota-based approaches for the prevention and management of AD. [Image: see text]

Sarcopenia is a syndrome characterized by the progressive and generalized loss of skeletal muscle mass and strength. This condition is associated with physical disability, decreased quality of life, and increased mortality. Therefore, reducing the prevalence of sarcopenia could significantly lower healthcare costs. Sarcopenia can be classified into primary and secondary sarcopenia. The former is related to aging and begins after the fourth decade of life; after that, there is a muscle loss of around 8% per decade until age 70 years, which subsequently increases to 15% per decade. On the other hand, secondary sarcopenia can affect all individuals and may result from various factors including physical inactivity, malnutrition, endocrine disorders, neurodegenerative diseases, inflammation, and cachexia. Understanding the multiple mechanisms involved in the onset and progression of sarcopenia allows for us to develop strategies that can prevent, treat, or at least mitigate muscle loss caused by increased protein breakdown. One potential treatment of sarcopenia is based on nutritional interventions, including adequate caloric and protein intake and specific nutrients that support muscle health. Such nutrients include natural food rich in whey protein and omega-3 fatty acids as well as nutritional supplements like branched-chain amino acids, β-hydroxy-β-methylbutyrate, and vitamin D along with food for special medical purposes. It is important to emphasize that physical exercises, especially resistance training, not only promote muscle protein synthesis on their own but also work synergistically with nutritional strategies to enhance their effectiveness.