1.QingNangTCM: a parameter-efficient fine-tuning large language model for traditional Chinese medicine
Xuming TONG ; Liyan LIU ; Yanhong YUAN ; Xiaozheng DING ; Huiru JIA ; Xu YANG ; Sio Kei IM ; Mini Han WANG ; Zhang XIONH ; Yapeng WANG
Digital Chinese Medicine 2026;9(1):1-12
Objective:
To develop QingNangTCM, a specialized large language model (LLM) tailored for expert-level traditional Chinese medicine (TCM) question-answering and clinical reasoning, addressing the scarcity of domain-specific corpora and specialized alignment.
Methods:
We constructed QnTCM_Dataset, a corpus of 100 000 entries, by integrating data from ShenNong_TCM_Dataset and SymMap v2.0, and synthesizing additional samples via retrieval-augmented generation (RAG) and persona-driven generation. The dataset comprehensively covers diagnostic inquiries, prescriptions, and herbal knowledge. Utilizing P-Tuning v2, we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM. A multi-dimensional evaluation framework, assessing accuracy, coverage, consistency, safety, professionalism, and fluency, was established using metrics such as bilingual evaluation understudy (BLEU), recall-oriented understudy for gisting evaluation (ROUGE), metric for evaluation of translation with explicit ordering (METEOR), and LLM-as-a-Judge with expert review. Qualitative analysis was conducted across four simulated clinical scenarios: symptom analysis, disease treatment, herb inquiry, and failure cases. Baseline models included GLM-4-9B-Chat, DeepSeek-V2, HuatuoGPT-II (7B), and GLM-4-9B-Chat (freeze-tuning).
Results:
QingNangTCM achieved the highest scores in BLEU-1/2/3/4 (0.425/0.298/0.137/0.064), ROUGE-1/2 (0.368/0.157), and METEOR (0.218), demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy, coverage, and consistency. Although its ROUGE-L score (0.299) was lower than that of HuatuoGPT-II (7B) (0.351), it significantly outperformed domain-specific models in expert-validated win rates for professionalism (86%) and safety (73%). Qualitative analysis confirmed that the model strictly adheres to the “symptom-syndrome-pathogenesis-treatment” reasoning chain, though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes.
Conclusion
Combining domain-specific corpus construction with parameter-efficient prompt tuning enhances the reasoning behavior and domain adaptation of LLMs for TCM-related tasks. This work provides a technical framework for the digital organization and intelligent utilization of TCM knowledge, with potential value for supporting diagnostic reasoning and medical education.
2.Association between meat consumption and anxiety symptoms in first year junior high school students in Yunnan Province
DING Shaocai, SHI Zelin, YANG Yongfu, YANG Yijun, LU Qiuan, XUE Yanfeng, WANG Yuan,〖JZ〗 XUE Wei, HUANG Xiaoli, XU Honglü ;
Chinese Journal of School Health 2026;47(3):384-387
Objective:
To explore the association between meat consumption and anxiety symptoms in first year junior high school students in Yunnan Province, and to provide theoretical support for preventing and relieving anxiety symptoms in junior high school students.
Methods:
From October to December 2022, a random cluster sampling method was used to select 8 500 first year junior high school students from 11 counties in Yunnan Province as the survey subjects for a questionnaire survey. The study used Food Frequency Questionnaire and the Chinese version of the Depression Anxiety Stress Scale-21 (DASS-21) to assess the meat consumption and anxiety symptoms of junior high school students.The distribution differences in anxiety symptoms among first year junior high school students with different demographic characteristics were analyzed statistically by using the Chi-square test,and the association between meat consumption and anxiety symptoms in students was analyzed by using a generalized linear model.
Results:
The detection rate of anxiety symptoms was 48.47%. After controlling for demographic variables and confounding factors, the consumption of livestock meat, poultry meat, processed meat, cured meat, barbecued meat and raw skin meat was statistically significant with anxiety symptoms ( β =-0.05, 0.04, 0.04, 0.08, 0.14, 0.17, all P <0.05). Stratified by ethnicity, The consumption of livestock meat, cured meat and barbecue was statistically correlated with anxiety symptoms in Han adolescents ( β =-0.07, 0.14, 0.22 ); the consumption of processed meat and raw skin meat was statistically correlated with anxiety symptoms in ethnic minority adolescents ( β =0.08, 0.18) (all P <0.05).
Conclusions
There is a statistical association between meat comsumption and the risk of anxiety symptoms in first year junior high school students in Yunnan Province. Guidance on meat consumption should be strengthened to prevent the occurrence of anxiety symptoms.
3.Polygonati Rhizoma Polysaccharides Improve Cognitive and Emotional Functions of Ovariectomy-AD Model Rats Through Modulating ERα/PI3K/Akt Pathway
Gengchao ZHANG ; Li YANG ; Yuan ZHANG ; Tao ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):154-162
ObjectiveThis study aims to investigate the effectiveness and mechanisms of Polygonati Rhizoma polysaccharides (PRP) on improving cognitive and emotional functions in the ovariectomy (OVX)-Alzheimer's disease (AD) model rats. MethodsAfter being randomly divided into blank group, model group, estradiol group (0.18 mg·kg-1·d-1), low-PRP group (200 mg·kg-1), medium-PRP group (400 mg·kg-1), and high-PRP group (800 mg·kg-1), 60 SPF female Sprague-Dawley (SD) rats were subjected to OVX. One week later, vaginal smear examination as well as D-galactose intraperitoneal injection (150 mg·kg-1·d-1, once daily, for eight weeks) were adopted to establish the OVX-AD model, and drug intervention was initiated nine weeks after surgery. Upon completion of the treatment course, cognitive and emotional functions, as well as hippocampal CA3 region damage were assessed in all rats by open-field test, new object recognition test, Morris water maze test, and transmission electron microscopy. Indicators of inflammation [interleukin-6 (IL-6), tumor-necrosis-factor-α (TNF-α), interleukin-1β (IL-1β)), oxidative-stress (superoxide-dismutase (SOD), glutathione-peroxidase (GSH-Px)] were measured by enzyme-linked immunosorbent assay (ELISA) and biochemical methods. The mRNA and protein expression levels of estrogen-receptor α (ERα)/phosphoinositide 3kinase (PI3K)/protein-kinase-B (Akt) signaling pathway, apoptosis [Bcl-2 associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2)] and the indicators of pathological sedimentary proteins [amyloid β-protein1-42 (Aβ1-42), microtubule-associated protein Tau, phosphorylated site 404 of microtubule-associated protein Tau [p-Tau (Ser404)] were detected by using real-time polymerase chain reaction (Real-time PCR) and western blot analysis. ResultsCompared with those in blank group, the rats in model group exhibited marked ultra-structural damage to hippocampal CA3 neurons, along with the reduction of activity time and shuttle frequency in central area, the index and exploration frequency of new object recognition, and the platform crossings and time spent in target quadrant, as well as the prolonged latency (P<0.05, P<0.01). Furthermore, the contents and expression levels of IL-6, TNF-α, IL-1β, Bax, Aβ1-42, Tau, and p-Tau (Ser404) were significantly increased, and the activity and expression of SOD, GSH-Px, ERα, PI3K, Akt, and Bcl-2 were significantly decreased (P<0.05, P<0.01). Compared to those in model group, the rats in estradiol group and groups with different doses of PRP noticeably presented with amelioration of neuronal damage, along with increased activity time and shuttle frequency in the central zone, elevated new object recognition index and exploration frequency, shortened latency, prolonged activity time, and increased platform crossings in the target quadrant (P<0.05, P<0.01). What is more, the contents and expression levels of IL-6, TNF-α, IL-1β, Bax, Aβ1-42, Tau, and p-Tau (Ser404) were significantly reduced, whereas the activity and expression levels of SOD, GSH-Px, ERα, PI3K, Akt, and Bcl-2 were markedly elevated (P<0.05, P<0.01). ConclusionPRP can improve the cognitive and emotional functions of AD model rats, and its mechanisms are probably related to modulating the ERα/PI3K/Akt pathway as well as inhibiting Aβ, Tau, neuro-inflammation, oxidative stress, and apoptosis, resulting in alleviation of neuronal damage.
4.Clinical and Mechanistic Research Progress on Classical Traditional Chinese Medicine Formulas in Treatment of Chronic Heart Failure
Guo YANG ; Yan ZHANG ; Ziyang YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):256-265
Chronic heart failure (CHF) is a clinical syndrome characterized by impaired ventricular ejection function due to cardiac abnormalities, representing the terminal stage of most cardiovascular diseases. With its rising prevalence and significant impact on patients' quality of life, CHF has emerged as a major global public health concern. Current Western medicine treatments mainly involve the oral administration of the "new quadruple therapy" drugs and diuretics. Despite substantial progress in pathological research and clinical treatment, challenges persist, including considerable side effects, drug resistance, and marked interindividual variability in therapeutic response. Therefore, exploring and leveraging the advantages of traditional Chinese medicine (TCM) in treating CHF has become an urgent research priority. TCM has a millennia-long history in the prevention and treatment of heart failure, accumulating extensive clinical experience. Characterized by its multi-component and multi-target properties, TCM enables holistic regulation of multiple systemic functions and intervention in the progression of heart failure, demonstrating significant clinical relevance in its management. By employing therapeutic strategies such as warming Yang, promoting diuresis, replenishing Qi, nourishing Yin, and activating blood circulation, TCM effectively improves myocardial fibrosis, inhibits oxidative stress responses, enhances myocardial contractility, and ameliorates ventricular remodeling. Modern proprietary Chinese medicines derived from classic formulas, based on the theoretical foundation of traditional prescriptions, not only exhibit favorable clinical efficacy but also offer notable advantages in convenience, stability, and safety. This review systematically examined the significant therapeutic effects and underlying mechanisms of classical TCM formulas in the treatment of CHF, and provided an overview of the clinical application of modern proprietary Chinese medicines. It aims to provide new strategies for the clinical diagnosis and treatment of CHF.
5.Protective effect and mechanism of chikusetsu saponin Ⅳa on the kidney in diabetic nephropathy rats
Yongli WANG ; Hai CHEN ; Xiaofang TIAN ; Xuechun WANG ; Liying YUAN ; Dan LIU ; Zhongfa LI ; Yanfang MENG ; Xiuyong YANG
China Pharmacy 2026;37(7):908-913
OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a (chsⅣ) on renal function in diabetic nephropathy (DN) model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group (i.g. administration of normal saline, high-fat diet), chsⅣ low-dose and high-dose groups (i.g. administration of 90, 180 mg/kg chsⅣ, high-fat diet), with 12 rats in each group. Additionally, 10 normal rats were set as the control group (i.g. administration of normal saline, regular diet). From the 5th to the 12th week after streptozotocin injection, they were given intragastric administration of relevant drug or normal saline, once a day. After the last medication, the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine and urine protein as well as the levels of reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissues were measured. Additionally, the insulin resistance index was calculated. Hematoxylin-eosin, periodic acid-Schiff, and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group, the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved, with significant decreases in renal histological scores, mesangial expansion index, and glomerulosclerosis scores ( P <0.05); the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine, urine protein and homeostasis model assessment for insulin resistance, as well as MDA content, the expression levels of Notch1, Notch intracellular domain, hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased ( P <0.05). The levels of GSH and SOD in renal tissue were significantly elevated ( P <0.05). Moreover, the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group ( P <0.05). CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity, attenuation of renal oxidative stress, and suppression of aberrant Notch signaling pathway activation.
6.Expert consensus on the clinical application of parenteral direct thrombin inhibitors in special populations
Xin YAO ; Yuan BIAN ; Lizhu HAN ; Qinan YIN ; Yang LEI ; Zimeng WAN ; Luyao HUANG ; Danjie ZHAO ; Yu YAN ; Qin LI ; Baorong HU
China Pharmacy 2026;37(8):965-975
OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors (DTIs) in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital(the Affiliated Hospital of UESTC), a multidisciplinary working group was formed comprising experts from multiple fields, including clinical pharmacy, cardiac surgery, obstetrics, pediatrics and evidence-based medicine. Through literature review and the Delphi method, clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” (PICO) framework;systematic searches were conducted in CJFD, PubMed, Embase and other databases. Relevant evidence from randomized controlled trials,cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment,Development and Evaluation (GRADE) approach, and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected (with a consensus rate exceeding 90%), resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations, including children, pregnant women, patients with hepatic or renal impairment, patients with mesenteric venous thrombosis, and individuals with thrombophilia. These recommendations clarify the preferred agents, dosing ranges, monitoring parameters, and safety management strategies for parenteral DTIs in these special populations. This expert consensus, which is formulated based on the best available evidence, provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.
7.Network meta-analysis of the efficacy and safety of dual amoxicillin-based regimens for Helicobacter pylori eradication
Ziwen SONG ; Xinmiao YUAN ; Liyuan LUO ; Yufang HE ; Lingshu YANG ; Yixu HUANG ; Jianpeng SHE ; Peihan WEI ; Sihan GUO ; Fei DUAN
China Pharmacy 2026;37(8):1074-1079
OBJECTIVE To evaluate the efficacy and safety of amoxicillin combined with proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) for Helicobacter pylori (Hp) eradication. METHODS Randomized controlled trial (RCTs) on amoxicillin combined with PPI or P-CAB for Hp eradication were retrieved from PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, and VIP data. The search time frame was from database inception to September 5, 2025. After literature screening, data extraction, and quality assessment, a network meta-analysis was performed using Stata 17.0 software. RESULTS A total of 12 RCTs involving 5 515 patients were included, encompassing 8 therapeutic regimens: PPI combined with high-dose amoxicillin for 14 days (TR1), PPI combined with low-dose amoxicillin for 14 days (TR2), P-CAB combined with high-dose amoxicillin for 7 days (TR3), P-CAB combined with high-dose amoxicillin for 14 days (TR4), P-CAB combined with high-dose amoxicillin for 10 days (TR5), P-CAB combined with low-dose amoxicillin for 7 days (TR6), P-CAB combined with low-dose amoxicillin for 14 days (TR7), and P-CAB combined with low-dose amoxicillin for 10 days (TR8). The network meta-analysis results showed that, in terms of intention-to-treat Hp eradication rates, the eradication rates of TR5 and TR4 were significantly higher than those of TR3, TR8, TR6 and TR1 ( P <0.05). The surface under the cumulative ranking curve (SUCRA) values from highest to lowest were: TR4 (89.7%)>TR5 (82.3%)>TR7 (71.5%)> TR2 (48.6%)>TR1 (43.9%)>TR8 (28.7%)>TR3 (22.7%)>TR6 (12.6%). Regarding safety, the incidence of adverse reactions in TR3 and TR5 was significantly lower than that in TR1 ( P <0.05). The SUCRA values from highest to lowest were: TR1 (91.3%)>TR4 (79.8%)>TR5 (55.0%)>TR7 (50.9%)>TR8 (41.3%)>TR2 (36.4%)>TR3 (27.6%) >TR6 (17.7%). CONCLUSIONS Although the regimen of P-CAB combined with high-dose amoxicillin for 14 days demonstrates the best efficacy, the combination of P-CAB with high-dose amoxicillin for 10 days exhibits a better balanced profile in terms of both efficacy and safety.
8.Species of sandflies and prevalence of Leishmania infections in sandflies in selected areas of northern and northwestern China
Yaqi HE ; Lei CUI ; Yi ZHANG ; Yuanyuan LI ; Limin YANG ; Yuan FANG ; Zhongqiu LI ; Zhengbin ZHOU
Chinese Journal of Schistosomiasis Control 2026;38(1):20-28
Objective To investigate the species of sandflies and the prevalence of Leishmania infections in sandflies from selected areas of northern and northwestern China, so as to provide insights into identification of leishmaniasis vectors and assessment of epidemiological trends of leishmaniasis in China. Methods Sandfly samples were collected from Mentougou District of Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County of Karamay District of Karamay City, Gaochang District of Turpan City in Xinjiang Uygur Autonomous Region from July 2023 to July 2024. Approximately 100 intact female sandfly samples were randomly selected from each site and the species of sandflies was identified according to morphological characteristics and molecular assays. Female sandflies originating from the same habitat were grouped into pools of 10 individuals. Leishmania infection was detected using polymerase chain reaction (PCR) assay targeting the internal transcribed spacer 1 (ITS-1) gene, and the prevalence of Leishmania infection was calculated in sandflies from different sampling sites using the minimum infection rate (MIR) method. In addition, positive amplicons were sequenced and subjected to phylogenetic analysis. Results A total of 6 155 sandflies were collected from different environments at sampling sites across the six aforementioned regions from July 2023 to July 2024. Phlebotomus chinensis (96.00%) was the dominant sandfly species in Mentougou District, Beijing Municipality, with a small proportion of Ph. sergenti (4.00%), and only Ph. chinensis was found in Xiangning County, Linfen City, Shanxi Province. Ph. wui was the only sandfly species detected in Ejin Banner, Alxa League, Inner Mongolia Autonomous Region, and Payzawat County, Kashgar City, Xinjiang Uygur Autonomous Region, and Ph. caucasicus (97.70%) was the dominant sandfly species in Karamay District, Karamay City, Xinjiang Uygur Autonomous Region, with a small proportion of Ph. wui (2.30%), while Ph. alexandri was the only species in Gaochang District, Turpan City, Xinjiang Uygur Autonomous Region. A total of 40, 60, 34, 18, 18, and 22 pools of sandfly samples were tested from Mentougou District in Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, Payzawat County in Kashgar City, Karamay District in Karamay City, and Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region, respectively. L. infantum was detected in Ph. chinensis samples from Mentougou District in Beijing Municipality, and Xiangning County of Linfen City in Shanxi Province, with MIR of 0.25% to 1.00%, and L. donovani was detected in Ph. wui from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region, with MIR of 0.56% to 0.88%; however, no Leishmania infection was detected in Ph. caucasicus from Karamay District in Karamay City or Ph. alexandri from Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region. Phylogenetic analysis showed that the Leishmania ITS-1 gene sequences obtained from Mentougou District in Beijing Municipality and Xiangning County in Linfen City of Shanxi Province were clustered into the same clade with the reference sequences of L. infantum ITS-1 gene, while the Leishmania ITS-1 gene sequences obtained from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region were clustered into the same clade with the reference sequences of L. donovani ITS-1 gene. Conclusions There are variations in sandfly species in selected areas of northern and northwestern China, and variations in the species of Leishmania infecting sandflies. Improved surveillance of sandfly vectors and targeted control strategies with adaptations to geographical features and leishmaniasis vectors are recommended.
9.Mechanistic Interpretation of Zheng’s San Qi San Powder in Treating Skeletal Muscle Injury via Bioinformatics Prediction, Chemical Analysis and Experimental Verification
Ding-Rui WANG ; Yun-Xin LIU ; Jun-Jie XU ; Liu YANG ; Jia-Hao LÜ ; Cheng-Yuan XING ; Lei LÜ ; Bei-Bei QIE
Progress in Biochemistry and Biophysics 2026;53(4):1028-1047
ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.
10.Olfactory Receptors Expressed in The Intestine and Their Functions
Pei-Wen YANG ; Meng-Meng YUAN ; Ying ZHOU ; Peng LI ; Gui-Hong QI ; Ying YANG ; Zhong-Yi MAO ; Meng-Sha ZHOU ; Xiao-Shuang MAO ; Jian-Ping XIE ; Yi-Nan YANG ; Shi-Hao SUN
Progress in Biochemistry and Biophysics 2026;53(3):534-549
Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.


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