Background Qihuang Biwen Formula (QHBWF), derived from the classic Yupingfeng Powder, is traditionally used for immune regulation. While clinically applied, its mechanism of action in ulcerative colitis (UC) remains unclear. Purpose The effectiveness and underlying principles of QHBWF for UC treatment were investigated using both Drosophila and mice models, and its bioactive components were identified. Methods In the dextran sulfate sodium (DSS)-induced adult fly, the survival rate, locomotion, excretion, smurf, digestive capacity, intestinal length, death of intestinal epithelial cells (IECs), and proliferation of intestinal stem cells (ISCs) were measured. Meanwhile, the body weight, intestinal length, disease activity index, histopathology, serum cytokine levels, and ROS levels were detected in the UC mouse. Additionally, the mechanism of QHBWF was investigated by bioinformatics analysis, transcriptomic analysis, qRT-PCR, immunohistochemistry and western blotting (WB). Finally, UCPL-MS/MS technology and phenotype assays in UC flies were used to screen the key bioactive components of QHBWF. Results QHBWF significantly improved survival rate, locomotor activity, and intestinal function. It restored intestinal morphology, suppressed aberrant intestinal stem cell (ISC) proliferation, and reduced intestinal epithelial cell (IEC) apoptosis in DSS treated flies. In mice, QHBWF alleviated weight loss, colon shortening, and DAI scores, improved histopathology, and reduced IL-6, IL-1β, and intestinal ROS. These results indicated that QHBWF could alleviate the intestinal injury in both UC models. Mechanistically, QHBWF down-regulated mRNA levels of Toll signaling and the Imd signaling, and up-regulated the gene expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes in the intestines of UC flies. Consistently, QHBWF decreased the protein levels of TLR4, MyD88 and NF-κB p65, and promoted the protein expresses of NDUFB8, SDHB and ATP5A in the guts of UC mice. These indicated that QHBWF inhibited the TLR4/NF-κB signaling pathway and activated the OXPHOS function. Furthermore, kaempferol, emodin, quercetin, isochlorogenic acid, and chlorogenic acid could extend the survival rate, increased the intestinal length, and facilitated intestinal barrier repair in UC flies. Conclusion QHBWF exerted anti-colitis effects by regulating immunity and metabolism, targeting the TLR4/NF-κB signaling pathway and mitochondrial oxidative phosphorylation. Kaempferol, emodin, quercetin, isochlorogenic acid, and chlorogenic acid were the bioactive compounds of QHBWF against UC. This study provides the potential of QHBWF as a multi-target treatment for UC.

Intestinal mucositis is one of the most debilitating side effects of chemotherapeutic agents. Angelica sinensis polysaccharide (ASP), the crucial active ingredient of Angelica sinensis, has been reported to possess anti-colitis activity. However, the efficacy of ASP against chemotherapy-induced intestinal mucositis (CIM) remain to be clarified. The aim of this study using Drosophila melanogaster and mouse models was to investigate the potential effect of ASP on intestinal mucositis and its underlying mechanism. ASP significantly alleviated overall physiological and intestinal damage caused by CPT-11 in adult flies, including increased survival rate and intestinal length, improved digestive capacity, restored intestinal acid-base balance and reduced death of intestinal epithelial cells. NIR imaging indicated that ASP was absorbed through the intestine and metabolized via the hepatic and renal systems in mice. Furthermore, ASP reduced intestinal damage and restored the intestinal barrier function in CPT-11 treated mice, including increased intestinal length, elevated levels of ZO-1 and an increased number of goblet cells. Mechanistically, ASP markedly down-regulated the over-activated innate immunity by inhibiting the Toll-IMD and TLR4/NF-κB/MyD88 signaling pathways in CPT-11 induced flies and mice. Besides, ASP also exerted a protective effect against structural damage to the spleen induced by CPT-11. Moreover, ASP ameliorated gut microbiota imbalances and increased the levels of short-chain fatty acids (SCFAs), particularly propionate and butyrate. Fecal microbiota transplantation (FMT) further confirmed that ASP could modulate gut microbiota and protect against intestinal mucositis in mice. Collectively, these results demonstrate that ASP effectively ameliorates CIM and has the potential to serve as a novel adjunctive therapy to CPT-11.

Dunhuang Gancao Fuling Xingren decoction (GFXD) is a traditional formulation derived from the Dunhuang Ancient Medical Prescriptions, has been historically utilized for its immunomodulatory and anti-inflammatory properties. However, the protective effect against irinotecan (CPT-11)-induced intestinal mucositis (CIM) remains poorly elucidated. To investigate the therapeutic efficacy of GFXD in alleviating CIM and elucidate its underlying mechanism and components using Drosophila melanogaster and C57BL/6 J mouse models. The therapeutic efficacy of GFXD was assessed in both Drosophila and mouse models by phenotype assay, hematoxylin and eosin (H E) staining, and Alcian blue-periodic acid schiff (AB-PAS) staining. Transcriptomic profiling combined with 16S rRNA sequencing were employed to identify potential mechanisms of GFXD regulating CPT-11-induced mucositis. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including Toll-Imd and JAK-STAT pathways were analyzed via qRT-PCR, immunofluorescence, fecal microbiota transplantation (FMT) experiment, and antibiotic treatment. Furthermore, functional components of GFXD were characterized via liquid chromatography-mass spectrometry (LC–MS), and their efficacy was validated in CPT-11-treated Drosophila. GFXD significantly mitigated CPT-11-induced systemic and intestinal damage in Drosophila, evidenced by improved survival rate, restored digestive function, elongated intestinal length, reduced acid–base imbalance, and enhanced epithelial and stem cell proliferation. In mice, GFXD alleviated mucositis symptoms, attenuated histopathological damage, and normalized inflammatory cytokine levels. Mechanistically, GFXD suppressed gut microbiota dysbiosis by enriching probiotics (Lactobacillus, Prevotella) and reducing pathogens (Bacteroides, Enterobacter, Enterococcus and Helicobacter). Transcriptomic and molecular analyses revealed that GFXD inhibited hyperactivation of Toll-Imd pathways and JAK-STAT signaling. Finally, three compounds of GFXD, formononetin, kaempferol, and ergosterol were found to alleviate CPT-11 induced intestinal injury. GFXD alleviates CPT-11-induced intestinal mucositis by modulating gut microbiota composition, suppressing JAK-STAT and Toll-Imd pathways. Thus, this study demonstrates GFXD and its bioactive constituents as novel therapeutic agents to mitigate CIM.

Ulcerative colitis(UC)is a complex chronic inflammatory disease.It is characterized by a prolonged and persistent clinical course,accompanied by a rising tendency in the risk of colorectal cancer.The incidence of UC continues to rise,with a complex etiology and a lack of effective therapeutic agents.TCM has unique advantages in the prevention and treatment of UC,due to its multi-target regulation properties,multi-pathway action,mild side effects,and diverse pharmacological activities.Angelicae Sinensis Radix(AS)contains various active components,including angelica polysaccharides,volatile oils,and organic acids.These components can alleviate UC by a multi-target regulation mechanism,including the inhibition of NF-κB,NLRP3 inflammasome activation,the reduction of the expression of inflammatory factors such as TNF-α and IL-1β,the enhancement of antioxidant enzyme activity,and the up-regulation of tight junction proteins such as ZO-1 and Occludin.Such multi-pathway synergistic effects fully highlight the preventive and therapeutic advantages of TCM,demonstrating the potential application value of AS in the treatment of intestinal diseases.This review systematically elucidated the multidimensional anti-UC mechanisms of the core active ingredients of AS and discussed the translational value of colon-targeted delivery systems,providing effective evidence for clinical precision medication.

Chemotherapy-induced intestinal mucositis (CIM) is a significant dose-limiting adverse effect of cancer treatment. Huangqi Baihe Granules (HQBHG) derived from Dunhuang’s ancient medical texts could alleviate radiation brain injury and hypobaric hypoxia-induced acute lung injury. Here, the protective effect and mechanism of HQBHG against irinotecan (CPT-11)-induced intestinal mucositis were detected by using Drosophila melanogaster and mouse models. Oral administration of HQBHG could significantly ameliorate body injury caused by CPT-11, including increased survival rate, rescued locomotion, altered metabolic capacity, restoration of ovarian morphology in flies, and also alleviated body weight loss and diarrhea in mice. Meanwhile, HQBHG supplementation resumed intestinal length and gastrointestinal acid-based homeostasis, reduced epithelial cell death in CPT-11 treated flies. In CPT-11 treated mice, HQBHG increased the gut length, recovered the architecture of the mucosa, and increased the expressions of tight junction proteins (ZO-1 and occludin ). Mechanism study showed that HQBHG remarkably down-regulated the expression levels of NF-κB signaling, the levels of cytokines IL-1β and TNF-α, and intestinal ROS accumulation; whereas it significantly up-regulated the levels of IL-10, and the expression of the Keap1/Nrf2 signaling in the guts. In addition, integrated analysis of 16S rDNA gene sequencing and untargeted metabolomics revealed that HQBHG reversed CPT-11-induced disordered amino acid metabolism of phenylalanine, tyrosine, tryptophan and glycine, which was closely related to the diversity and abundance of gut microbiota such as Escherichia-Shigella and Clostridium_sensu_stricto. Therefore, HQBHG has the potential to be an effective agent for the treatment of CIM by inhibiting the NF-κB pathway, activating the Nrf2/Keap1 pathway and regulating the amino acid metabolism balance in the gut.

Astragalus membranaceus is a widely utilized medicinal and edible herb, serving as immunostimulant, metabolic regulator, anticancer agent, and hepatoprotectant agent. However, its protective effect against chemotherapy-induced intestinal mucositis (CIM) remains poorly elucidated. The study aimed to investigate the therapeutic efficacy and mechanism of Astragalus membranaceus extract (AME) in alleviating CIM using Drosophila melanogaster and C57BL/6J mouse models. The mechanisms of AME were evaluated via multi-omics approaches, including transcriptomic profiling, 16 S rRNA sequencing, and targeted metabolomics. The expression levels of the TLR4/NF-κB pathway and glutathione metabolic pathway were analyzed by RT-qPCR and immunofluorescence. AME supplementation significantly mitigated CPT-11-induced systemic and intestinal damage in adult flies and mice. Mechanistically, AME markedly down-regulated the TLR4/NF-κB pathway and up-regulated glutathione metabolism. AME also modulated gut microbiota composition, increased relative abundance of Lactobacillus, unidentified_Lachnospiraceae, and Ruminococcus, and decreased abundance of Streptococcus, Bacteroides, and Alistipes. Meanwhile, AME decreased the levels of glutamine (Gln), lysine (Lys), phenylalanine (Phe), proline (Pro), and valine (Val), while increasing threonine (Thr). In conclusion, AME alleviates CIM via regulating gut microbiota-related innate immunity and amino acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE:Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe conditions associated with high mortality rates and limited treatment options. Short-chain fatty acids (SCFAs) serve as central immunomodulatory metabolites mediate the crosstalk between the gut and lung. Traditional Chinese medicine (TCM), with its holistic approach, shows promise in restoring gut-lung balance and alleviating respiratory inflammation by modulating gut microbiota and SCFA metabolism. AIM OF THE STUDY:To elucidate the protective role and mechanism of SCFAs in ALI and ARDS via the gut-lung axis. Meanwhile, to evaluate the therapeutic potential of TCM in treating ALI by modulating the gut microbiota and enhancing SCFA production. METHODS:A comprehensive literature search was conducted across PubMed, Ovid-Embase, Web of Science, and CNKI databases (2010-2025). Keywords included "short-chain fatty acid", "gut microbes", "acute lung injury", "traditional Chinese medicine", and related terms. The search focused on preclinical and mechanistic studies investigating SCFA signaling, gut microbiota remodeling, and the therapeutic effects of herbal compounds or their active constituents in ALI/ARDS models. RESULTS:This review identified acetate, propionate, and butyrate as key mediators that protect against ALI through distinct mechanisms, including anti-oxidation, anti-inflammation, immunomodulation, apoptosis reduction, airway tight-junction protection, and regulation of intestinal homeostasis. In addition, 9 bioactive components, 5 single-herb extracts, and 4 Chinese herb formulations were found to ameliorate ALI by enriching SCFA-producing bacteria, such as Akkermansia, Lactobacillus, and Lachnospiraceae, thereby elevating systemic and local levels of acetate, propionate, and butyrate. CONCLUSION:SCFAs represent critical molecular mediators of the gut-lung axis, and their modulation by natural products offers a promising microbiota-centered strategy for ALI treatment. This microbiota-centered strategy holds great promise for ALI precision medicine.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic and recurrent gastrointestinal inflammatory disorder. It is characterized by persistent mucosal inflammation, damage to the intestinal epithelium, and impaired tissue repair. The primary clinical symptoms of IBD include abdominal pain, diarrhea, and bloody stools, with the frequency and severity of episodes often exhibiting a distinct circadian rhythm pattern. Various studies have proven that circadian rhythm disorders (CRD) are implicated in the pathogenesis, exacerbation, and treatment outcomes of IBD. This connection arises from the crucial role that circadian and biological clock molecules play an important role in regulating the diversity and colonization of gut microbiota, modulating mucosal barrier function through the expression of tight junction proteins, and exerting immunoregulatory effects via regulating immune cell activation, proliferation, and migration. However, disruptions to these rhythms often stem from modern lifestyle factors such as shift work, sleep deprivation, or irregular eating patterns. This leads to dysbiosis of the gut microbiota, increased intestinal permeability, and abnormal activation of the immune system, thereby inducing the onset of IBD or exacerbating its progression. IBD symptoms exhibit significant circadian rhythmic fluctuations. For example, disease activity, gut microbiota composition, intestinal mucosal barrier function, and inflammatory cytokine expression levels often exhibit diurnal patterns. Furthermore, drug metabolism and efficacy are also regulated by circadian rhythms, influencing the pharmacokinetic characteristics and pharmacodynamic performance of common IBD treatment regimens, such as glucocorticoids and immunomodulators. For instance, administering certain medications at specific times can enhance bioavailability and reduce toxicity. It suggests the potential feasibility of chronotherapy strategies. Accordingly, this review explores the application prospects of chronotherapy in the management of IBD, including multiple potential pathways that restores circadian synchrony and improve the intestinal microenvironment. These include: timed medication administration that is based on chronopharmacology and disease activity fluctuations, time-restricted eating that means consuming meals within a prescribed window during active phases, and behavioral interventions like adequate light exposure and sleep. These approaches aim not only to enhance therapeutic efficacy, but also to mitigate drug side effects and improve the quality of life for patients, particularly IBD patients with sleep disturbances. In summary, integrating circadian biology into IBD research offers new insights into disease mechanisms and paves the way for personalized time-based therapeutic interventions. Future efforts should further advance clinical translational studies to identify optimal time windows and individualized treatment strategies for different IBD subtypes. This review synthesizes existing evidence to establish a foundational framework for future clinical research, emphasizing the critical importance of considering circadian rhythms in IBD management and treatment.

Ethnopharmacological relevance Danggui Buxue Decoction (DBD) as a traditional Chinese medicine compound was firstly found in “Nei Wai Shang Bian Huo Lun” for more than 700 years, which mainly composed of Astragalus and Angelica. In clinical practice, DBD is employed therapeutically for a range of respiratory conditions. However, investigations into the therapeutic mechanism of DBD against chronic obstructive pulmonary disease (COPD) remain scarce. Aim of the study Mitigating effect and mechanism of DBD and its bio-active compounds on COPD tracheal injury were studied using Drosophila melanogaster and SD rat models. Methods The protective effects of DBD against cigarette smoke(CS)-induced injury in Drosophila and rats were assessed. In Drosophila, protection was evaluated using metrics including survival rate, locomotion capacity, tracheal length and thickness, and the number of nuclei in tracheal epithelial cells. In rats, lung function, histological changes in the lungs, collagen fibers, and overall inflammation levels were measured. Subsequently, the molecular mechanism of DBD was detected by transcriptome sequencing, bioinformatics, immunofluorescence, ELISA and real-time PCR. Meanwhile, liquid chromatography-mass spectrometry (LC-MS), ADME online prediction, fly larval phenotyping experiments, molecular docking and molecular dynamics simulation were utilized to further identify core active components of DBD for ameliorating COPD tracheal injury. Results DBD significantly extended the survival rate, increased the motility, and also restored pupal area, larval tracheal length, tracheal wall thickness, and the number of tracheal epithelial cell nuclei in flies. In COPD rats, DBD improved lung function, reduced alveolar septal thickening and inhibited the expression of inflammatory factors. Meanwhile, DBD remarkably down-regulated the gene and protein expressions in JAK1-STAT3 pathway, inhibited the tracheal ROS accumulation, increased protein expressions of glutathione metabolic pathway and GSH content. Additionally, ferulic acid, rhein, curcumin and gallic acid were found to alleviate CS-induced injury in flies, in which curcumin and rhein as the core compounds of DBD can bind stably to STAT3 and GSTT1, respectively. Conclusion DBD could ameliorate COPD tracheal injury via inhibiting the JAK-STAT pathway and activating the glutathione metabolic pathway. Curcumin, and rhein are the core bioactive compounds in DBD that alleviate COPD tracheal injury.

Intestinal mucositis is a common and debilitating complication of the chemotherapeutic agent irinotecan (CPT-11), characterized by intestinal barrier disruption, oxidative stress, inflammation, and gut microbiota dysbiosis. Radix Hedysari polysaccharides (HPS) possess anti-inflammatory, antioxidant, and microbiota-regulating properties, but their protective effects against CPT-11-induced intestinal injury remain unclear. In this study, we investigated the protective effect and mechanism of HPS in CPT-11-induced intestinal mucositis using Drosophila melanogaster and BALB/c mouse models. HPS supplementation significantly improved survival and locomotor activity in CPT-11-induced flies, and ameliorated intestinal phenotypes including excessive feeding, increased excretion, crop enlargement, shortened gut length, impaired acid-base balance, and elevated intestinal cell death. HPS also suppressed reactive oxygen species (ROS) levels and modulated antioxidant-related genes (gstD1, cat, sod1, sod2) and the JAK pathway (STAT92E, UPD3, UPD3-1) in fly guts. In mice, administration of HPS reversed the CPT-11-induced gut microbial dysbiosis, restored microbial diversity, and suppressed serum pro-inflammatory cytokines (TNF-α and IL-6). Mechanistic studies revealed that HPS alleviated colonic injury by up-regulating the Keap1/Nrf2 antioxidant response and down-regulating the JAK1/STAT6 inflammatory signaling. These findings suggest that HPS has a protective role in CPT-11-induced intestinal mucositis via antioxidant, anti-inflammatory, and microbiota-modulatory activities, supporting its potential as a therapeutic agent for chemotherapy-induced intestinal injury.

Acute Lung Injury (ALI) and its severe form, Acute Respiratory Distress Syndrome (ARDS), involve the breakdown of the alveolar-capillary barrier. This breakdown drives an uncontrolled inflammatory cascade. The final outcome is often fatal respiratory failure. Currently, there are no specific clinical therapies. The emerging "gut-lung axis" concept offers a new perspective. An imbalance in gut microbiota can worsen lung inflammation through three main pathways,including the disrupted metabolites, the immune cell migration, and the activation of the TLR4/ MyD88/ NF-κB pathway. It provides a key target for treatment. Active components in natural products, such as flavonoids, saponins, and alkaloids, have multi-target and holistic effects. They show strong potential in regulating gut-lung communication, including modulating the gut microbiota and improving barrier function and maintain immune homeostasis. As a result, they help alleviate lung inflammation. However, their clinical translation still requires better drug efficacy utilization and clearer mechanistic understanding. Therefore, this review systematically summarizes the core mechanism of the gut-lung axis. It focuses on the synergy between "microbiota-barrier-immunity." It also explores how natural products such as forsythin and rhubarb may combat ALI by targeting this axis. Additionally, it examines the role of compound formulas like Qingyi Tang and Xuanfei Baidu Decoction. This work aims to provide a theoretical basis and research ideas for developing multi-target Natural products strategies for clinical use.

ETHNOPHARMACOLOGICAL RELEVANCE:Dabupi Decoction (DBPD) originates from the ancient Dunhuang medical literature "Fu Xing Jue Visceral to Drug law legend" for more than 1000 years, which has been extensively employed to treat various diseases related to the spleen and stomach. However, limited studies focus on the mechanism of DBPD against ulcerative colitis (UC). AIM OF THE STUDY:The beneficial effect and mechanism of DBPD against UC were detected by adopting both Drosophila melanogaster and C57BL/6J mouse models. METHODS:The protective effect of DBPD against DSS-induced intestinal damage in flies was investigated by utilizing survival rate, locomotion, excretion, smurf, intestinal length, intestinal acid-base homeostasis, and Tepan blue assay. In mice, HE staining and ELISA kit were employed to assess serum histopathological damage and inflammatory factor levels. Subsequently, the molecular mechanism of DBPD was subsequently detected via DHE staining, immunofluorescence, transmission electron microscopy (TEM), real-time PCR, and transcriptomic sequencing. Additionally, liquid chromatography-mass spectrometry (LC-MS) and phenotype experiments in UC flies were utilized to identify the bioactive components of DBPD against UC. RESULTS:Oral administration of DBPD remarkably alleviated DSS-induced body damage in flies by improving survival rate, locomotion, and excretion. It also remarkably rescued intestinal morphological damage, repaired acid-base homeostatic imbalance, inhibited intestinal epithelial cells (IECs) death and excessive proliferation of intestinal stem cells (ISCs), and improved ultrastructural damage of IECs in flies treated with DSS. Consistently, DBPD attenuated colitis symptoms, alleviated intestinal histopathological damage, and restored the expression of inflammatory factors in DSS-induced UC mice. As suggested by an integration of transcriptome data with molecular biology experiments, DBPD not only dramatically alleviated oxidative damage by activating the glutathione metabolic pathway, but also lowered inflammatory reaction by inhibiting the JAK-STAT pathway. Additionally, four compounds of DBPD, rhein acid, isoquercitrin, curcumin, and zeaxanthin were identified to alleviate the DSS-induced intestinal injury. CONCLUSION:DBPD demonstrate immense potential for intestinal injury predominantly by activating the glutathione metabolic pathway to alleviate oxidative damage, and inhibiting the JAK-STAT pathway to mitigate inflammatory response. Rhein acid, isoquercitrin, curcumin, and zeaxanthin were the bioactive compounds of DBPD against UC.

Astragalus polysaccharide (APS) is the crucial active ingredient of Astragalus membranaceus, which has antioxidant, immunomodulatory and anti-inflammatory properties. However, the therapeutic effects and biological mechanisms of APS on chemotherapeutic intestinal mucositis (CIM) have not been clarified yet. Here, the protective mechanism and functional components of APS against CIM was investigated in both Drosophila melanogaster (fruit fly) and mice models. Administration of APS could remarkably attenuate the overall physiological impairments caused by CPT-11 in flies, including increased the survival rate, improved motility, restored the size of ovary and reproduction. APS supplementation could significantly alleviate CPT-11-induced intestinal damage, which involved in restoration of intestinal length, reduction of crop size and excretion, improvement of intestinal homeostatic imbalance, and restoration of intestinal shortened villi. Furthermore, the integration of transcriptomics and microbiomics demonstrated that APS exerted its protective effect mainly by mitigating oxidative stress associated with FoxO signaling, over-activated innate immunity and dysbiosis of intestinal flora. Subsequently, three molecular weight components (APS-I, APS-II and APS-III) were extracted from APS. Among the studied substances, APS-III as the lowest molecular weight demonstrated the highest efficacy in reducing intestinal mucositis compared to both APS-I and APS-II. Collectively, these results support that APS is intended to be constructed as an effective medication for addressing intestinal diseases.

Background:Sleep is vital for maintaining the health of the organism. Chronic sleep deprivation (CSD) is a key contributor to significant health risks, including the induction of gastrointestinal disorders. However, the mechanism of CSD caused intestinal damage remains unclear. Methods:Drosophila melanogaster as an in vivo model was used to investigate the mechanism of CSD-induced intestinal injury, as well as the ameliorative effect of caffeic acid. Results:CSD resulted in reduced survival and severely affected intestinal homeostasis in flies, as evidenced by disruption of intestinal acid-base homeostasis, increased feeding, increased intestinal permeability and shortened intestinal length. Meanwhile, the expressions of the immune deficiency (IMD) pathway-related genes PGRP-SB1, Dpt, AttA, AttB and Mtk were significantly up-regulated in the intestine of CSD flies. On the other hand, Caffeic acid supplementation restored intestinal acid-base homeostasis and intake, while improving intestinal barrier permeability and intestinal length, and effectively reducing intestinal damage. In addition, administration of caffeic acid decreased the expressions of PGRP-SB1, Dpt, AttA and Mtk genes in the CSD flies gut. Discussion:These results suggested that CSD could disrupt gut homeostasis in adult flies by overactivating the IMD pathway, while Caffeic acid has an obvious protective role on the gut homeostasis.

Background: Sleep is vital for maintaining the health of the organism. Chronic sleep deprivation (CSD) is a key contributor to significant health risks, including the induction of gastrointestinal disorders. However, the mechanism of CSD caused intestinal damage remains unclear. Methods: Drosophila melanogaster as an in vivo model was used to investigate the mechanism of CSD-induced intestinal injury, as well as the ameliorative effect of caffeic acid. Results: CSD resulted in reduced survival and severely affected intestinal homeostasis in flies, as evidenced by disruption of intestinal acid-base homeostasis, increased feeding, increased intestinal permeability and shortened intestinal length. Meanwhile, the expressions of the immune deficiency (IMD) pathway-related genes PGRP-SB1, Dpt, AttA, AttB and Mtk were significantly up-regulated in the intestine of CSD flies. On the other hand, Caffeic acid supplementation restored intestinal acid-base homeostasis and intake, while improving intestinal barrier permeability and intestinal length, and effectively reducing intestinal damage. In addition, administration of caffeic acid decreased the expressions of PGRP-SB1, Dpt, AttA and Mtk genes in the CSD flies gut. Discussion: These results suggested that CSD could disrupt gut homeostasis in adult flies by overactivating the IMD pathway, while Caffeic acid has an obvious protective role on the gut homeostasis.

The atmospheric oxygen concentration is significantly reduced in highland regions compared to lowland areas. The first entering the plateau can induce sleep disorders in individuals, primarily attributed to insufficient oxygen supply. This study used Drosophila melanogaster as a model organism to better understand the molecular mechanism of acute hypoxia-induced sleep disorders. The Drosophila activity monitoring system (DAMS) was employed to observe the sleep-wake in adult (w1118, simaKG07607, and clockjrk) female flies. Quantifying the relative mRNA expression levels of sima and circadian clock genes in the head of flies was accomplished by utilizing qRT-PCR. Acute hypoxia caused sleep disorders in w1118 flies, such as shortened sleep duration and length, and prolonged sleep latency. PCR results showed that sima and clock genes were up-regulated in ZT6 and ZT12 and down-regulated in ZT0 and ZT18 in acute hypoxic w1118 flies compared to normoxic w1118 flies. Under normoxic conditions, sleep indexes in simaKG07607 flies were not substantially different from w1118 flies. However, clockjrk flies demonstrated a reduced sleep duration, decreased sleep bout length, and increased sleep latency and activities. Sleep and gene expression in simaKG07607 flies under acute hypoxic conditions were not significantly different from those under normoxic conditions. Surprisingly, sleep and gene expression in clockjrk flies showed opposite trends to w1118 flies. The present study indicates that acute hypoxia disrupt circadian rhythms through the activation of sima/HIF-1α, leading to the onset of sleep disorders, with Clock signaling potentially serving as a contributing factor.

Background Chemotherapy-induced intestinal mucositis (CIM) is one of the most common side effects of chemotherapy agents. Astragalus licorice prescription (ALP), a traditional Chinese formula, commonly used to treat gastrointestinal disorders, has an unclear mechanism and potential active components in alleviating CIM. Purpose This study aims to comprehensively explore the mechanism and bioactive components of ALP in alleviating CIM. Methods ALP’s efficacy on CIM was evaluated in Drosophila melanogaster (flies) and C57BL/6 mice using phenotype assays, hematoxylin-eosin (H&E) staining, and immunohistochemistry. ALP’s synergistic effect with 5-FU (5-fluorouracil) on tumors was assessed in 615 tumor-bearing mice by measuring tumor volume/weight and performing HE/immunohistochemical staining. Ki67 staining assessed tumor proliferation. Multi-omics integration (transcriptomics, lipidomics, microbiome analysis, network pharmacology) analyzed ALP’s mechanism against CIM. Functional pathways were validated via RT-qPCR, biochemical kits, and immunofluorescence, as well as transgenetic flies targeted with GFP. ALP’s functional components were characterized by liquid chromatography-mass spectrometry (LC-MS) and validated in CIM flies. Results ALP significantly mitigated chemotherapy-induced systemic and intestinal damage in flies, evidenced by improved survival rate, elongated intestinal length, reduced acid-base imbalance, and enhanced epithelial and stem cell proliferation. Similarly, ALP alleviated intestinal mucositis symptoms and pathological damage in 5-FU-treated mice, such as reducing diarrhea levels, increasing intestinal length and villus height. Mechanistically, ALP inhibited the expressions of the JAK/STAT pathway related genes (upd3, stat92E, hop, dome, and Dronc) and proteins (UPD3, STAT92E, cleaved caspase-3), and reduced intstinal cells apoptosis. Concurrently, ALP elevated lipid metabolism levels by activating the fatty acid β-oxidation (FAO) pathway related genes expressions (Wdh, Mtp-α, Mtp-β, and Scully) and decreased intestinal free fatty acids. Integrated microbiome, lipidomic, and transcriptomic analyses revealed that ALP corrected multiple gut microbial and lipid metabolic disorders associated with the JAK/STAT apoptotic pathway and FAO lipid metabolism pathway. Furthermore, ALP combined with 5-FU enhanced the anti-tumor effect of 5-FU, as shown by reduced tumor volume and weight, and decreased the proliferation of tumor cells. Finally, four bioactive compounds in ALP, including berberine, dihydrotanshinone I, licochalcone A, and resveratrol, were identified as alleviating CIM. Conclusion ALP mitigated CIM by inhibiting the JAK/STAT pathway to reduce cellular apoptosis and activating the FAO pathway to improve lipid metabolism, thereby positioning it as a promising novel therapeutic option. Meanwhile, four bioactive compounds of ALP demonstrated protective effects against CIM.

Background:Ulcerative colitis (UC) is a chronic intestinal inflammation that is prone to relapse and is difficult to fully recover; therefore, there is a need for safer alternative treatments. Caffeic acid (CA) is a natural polyphenolic compound that has antioxidant and anti-inflammatory properties. However, the beneficial effects and mechanisms of action of CA in UC remain unclear. Purpose:This study evaluated the protective effect of CA against dextran sulfate sodium (DSS)-induced intestinal injury in Drosophila melanogaster model. Results:Oral administration of CA significantly reduced body damage in UC flies, improved their survival rate, restored damaged digestion, and improved locomotion. CA supplementation significantly alleviated intestinal damage in UC flies by restoring excretion balance, repairing intestinal atrophy, improving acid-base balance imbalance, inhibiting intestinal structural destruction, inhibiting intestinal epithelial cell death and intestinal stem cell (ISC) excessive proliferation, and reducing the number of harmful bacteria. Mechanistic studies found that CA significantly reduced the expression of Toll and Imd pathway genes (including Myd88, Dif, PGRP-LC, Imd, Rel, and Dpt), reduced ROS levels and the expression of apoptosis-related genes (Debcl, Cyt-c-p, DrlCE, Dronc, and Dark), and increased ATP and MFN2 levels. Conclusion:CA alleviated intestinal damage mainly by inhibiting the Toll and Imd signaling pathways and inhibiting apoptosis mediated by mitochondrial damage. These findings suggest that CA holds promise as a potential therapeutic for UC treatment.