Stigmasterol glucoside (SG), a phytosterol glycoside derived from plants, is widely distributed in numerous natural sources—particularly medicinal and edible plants—and is recognized to possess potential anti-inflammatory properties, although its mechanisms of action remain incompletely understood. Experimental results demonstrated that SG significantly attenuated lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages. In a murine model of systemic inflammatory response syndrome (SIRS) established by LPS challenge, SG effectively mitigated systemic inflammation and ameliorated LPS-induced hepatic dysfunction. Integrated network pharmacological analysis and transcriptomic sequencing revealed that SG primarily exerts its anti-inflammatory activity through modulation of the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathways, thereby conferring protection against liver injury and systemic inflammation. These findings highlight SG as a promising therapeutic candidate for inflammation-related disorders.
BackgroundRuscogenin-1-O-[β-D-glucopyranosyl (1→2)][β-D-xylopyranosyl (1→3)] -β-D-fucopyranoside (Rus-GXF) is a ruscogenin glycoside of Liriope muscari (Decaisne) L. H. Bailey, yet its protective effects against acute lung injury—a condition characterized by exacerbated inflammation and barrier damage have not been fully elucidated.MethodsIn this study, the preventive and therapeutic effects of Rus-GXF on acute lung injury (ALI) were investigated using transcriptome RNA sequencing, network pharmacology, molecular docking, molecular dynamics simulation and other in vitro and in vivo experiments.ResultsRus-GXF suppressed inflammatory responses in two key cell types involved in lung injury. In immune cells (RAW264.7), it inhibited the production of pivotal pro-inflammatory mediators and their regulatory genes. Similarly, in pulmonary epithelial cells (BEAS-2B), it reduced the expression of inflammatory signals and concurrently enhanced markers of cellular tight junction proteins. In mice, Rus-GXF alleviated ALI severity, evidenced by decreased lung wet/dry ratio, bronchoalveolar lavage fluid protein content, pro-inflammatory cytokine levels, and histopathological scores. Integrated network pharmacology and transcriptomics indicated that Rus-GXF acts through multi-target mechanisms in ALI. Molecular docking and dynamics simulations revealed that Rus-GXF acts as an allosteric inhibitor of JAK1, thereby preventing its activation and subsequent STAT3 phosphorylation. The inhibitory effect of Rus-GXF on the JAK1/STAT3 signaling pathway was investigated by immunohistochemistry (IHC) and Western blot analysis (WB).ConclusionThese results demonstrate that Rus-GXF suppresses the macrophage-derived cytokine storm, alleviates inflammation, and improves barrier function. It functions as a JAK1 inhibitor to regulate ALI progression via the JAK1/STAT3 signaling pathway.
ETHNOPHARMACOLOGICAL RELEVANCE:Lonicera similis Hemsl leaves (LSHL), a widely distributed traditional Chinese herbal remedy, possesses anti-inflammatory properties. However, its regulatory role in mitigating heat stress-induced intestinal impairment in broilers remains inadequately elucidated. AIM OF THE STUDY:This study identified LSHL's active components, established a broiler heat stress model, and investigated its intestinal protective effects and mechanisms. MATERIALS AND METHODS:Liquid chromatography-mass spectrometry (LC-MS) analyzed LSHL's active components. Network pharmacology predicted mechanisms, and molecular docking verified key component-target interactions. In vivo experiments evaluated LSHL's effects via growth performance, immune organ indices, histopathology, antioxidant enzyme activities, inflammatory cytokine levels, and qPCR. RESULTS:LC-MS identified 42 active components (e.g., Alizarin, Caffeic Acid, Quinic Acid). Network pharmacology revealed 41 overlapping targets (core: ESR1, CASP3, MAPK10) and involvement of the MAPK signaling pathway. Molecular docking confirmed strong component-target binding. Dietary LSHL granules (1-3 g/kg) improved growth performance, alleviated intestinal villi damage, reduced oxidative stress (decreased MDA; increased GSH-Px, CAT), attenuated inflammation (decreased TNF-α, IL-6, IL-1β), upregulated immunoglobulins (IgG, IgM, IgA), and downregulated HSP70 and MAPK pathway-related proteins. CONCLUSIONS:LSHL exerts multi-component and multi-target protective effects on the intestinal tract of heat-stressed broilers. These findings provide a theoretical foundation for the application of LSHL as a natural anti-heat stress feed additive.
Autoimmune demyelinating diseases (ADDs) are chronic inflammatory disorders caused by immune system dysfunction. Antigen-specific immune tolerance therapy (AITT) offers a promising strategy to selectively reprogram immune responses against self-antigens. However, the hostile lymph node microenvironment suppresses tolerogenic dendritic cell (tDC) differentiation, posing a major obstacle to AITT efficacy. Here, we developed a reactive oxygen species (ROS)-scavenging nanovaccine (polymeric prodrug [PPR]/myelin oligodendrocyte glycoprotein [MOG]) that integrates MOG peptides with an ROS-responsive cinnamaldehyde PPR to restore antigen-specific tolerance by neutralizing oxidative stress in lymph nodes. In MOG-induced experimental autoimmune encephalomyelitis (EAE) model mice, PPR/MOG significantly reduced pathogenic immune infiltration into the central nervous system (CNS) and expanded regulatory T cells (Tregs) in the spleen, effectively halting disease progression. Single-cell RNA sequencing further revealed enhanced oligodendrocyte differentiation and myelin repair, linking immune tolerance induction to CNS protection. By targeting ROS-driven immune dysregulation, this study establishes a new paradigm for AITT and provides support for restoring AIT in autoimmune demyelination.
Polysaccharides are the main active ingredients in Dendrobium; however, the systematic comparison of monosaccharide compositions, anti-inflammatory, and antioxidant activities across diverse Dendrobium species remains insufficient. In this study, 21 wild Dendrobium species were collected from Yunnan and Sichuan provinces, and their polysaccharide yield, chemical composition, monosaccharide profile, and protective effects (anti-inflammatory and antioxidant activities) against LPS-induced injury in IPEC-J2 cells were investigated. The polysaccharides yield ranged from 0.29
Precise identification of vulnerable plaque (VAP) is essential for the prevention of acute cardiovascular diseases, yet current molecular probes are hampered by poor VAP lesion penetration and high background. Here, the innate tropism of circulating inflammatory monocytes for VAP, and their differentiation-driven expression of legumain (Lgmn) in response to the VAP microenvironment is exploited. A monocyte differentiation-activated fluorescent (MDAF) probe is conceived that hitchhikes monocytes to precisely migrate to VAP and is activated by Lgmn during monocyte differentiation. This activation triggers in situ self-assembly, resulting in spatiotemporally controlled aggregation-induced emission (AIE) fluorescence signals, and turning the monocyte itself into an on-site "scout" that reports plaque instability. In Apoe-/- mice bearing both vulnerable and stable plaques, the MDAF produces a striking OFF/ON fluorescence switch confined to vulnerable lesions, yielding a markedly improved signal-to-noise ratio (SNR). By integrating fluorescence emission computed tomography (FLECT), MDAF probe surpasses the depth limitations of conventional fluorescence imaging. Therefore, the AIE signal of the MDAF probe is more than just a "fluorescent read-out," and it also acts as a crucial safety switch that transforms the monocyte into a ratiometric immune scout for plaque instability. This innovative strategy offers a translatable approach for the precision diagnosis of VAP.
Poor drug penetration due to local skin thickening and microenvironmental redox imbalance remain a critical challenge in the treatment of epidermal diseases. Considering that oxidative stress due to the overproduction of Reactive Oxygen Species (ROS) in the skin microenvironment is one of the main mechanisms in the pathogenesis of psoriasis, we developed a ROS-sensitive transdermal drug delivery system to enhance topical treatment of psoriasis. Cross-linked cyclodextrin metal-organic framework (COF) containing curcumin (CUR) was dispersed in two types of dissolving polysaccharide microneedles (CPPAP-MNs-CUR@COF, CPPNP-MNs-CUR@COF) made from Codonopsis pilosula neutral polysaccharides (CPPNP) and acidic polysaccharides (CPPAP) for topical administration. COF contains peroxyoxalate bonds that scavenge H2O2, hydrolyse and eliminate ROS generated at the site of inflammation. Microneedles (MNs) that break through the skin's physical barrier improve drug penetration, while Codonopsis pilosula Polysaccharides (CPP) can synergise with CUR to significantly attenuate inflammation and oxidative stress and ameliorate imiquimod (IMQ)-induced symptoms of psoriasis in mice through inhibition of the IL-23/IL-17 inflammatory axis. It is a promising drug delivery system that is expected to provide new strategies for the topical treatment of psoriasis in the clinical setting.
Paeoniae Radix alba polysaccharide (PRP-AP), a pectic polysaccharide, has shown potential for treating intestinal damage in vitro. However, the role and mechanism of PRP-AP in vivo remained unclear. The 6-week-old C57BL/6 male mice and Dextran sulfate sodium salt (DSS) were selected to construct a colitis mouse model. Using DSS-induced colitis mice, we observed that 7-days' PRP-AP administration (i.g, 50, 100, 200 mg/kg) significantly (p < 0.001) alleviated colitis in a dose-dependent manner. This was achieved by restoring gut microbiota balance, particularly involving Akkermansia muciniphila, and modulating both microbial and peripheral metabolites. PRP-AP also improved colonic barrier function by increasing the expression of Zonula occludens-1 (p = 0.004) and the number of goblet cells (p < 0.001). In addition, PRP-AP promoted the Enteric Nervous System (ENS) function by regulating dopamine metabolism in enteric glial cells and enhancing acetylcholine and vasoactive intestinal peptide biosynthesis in neurons. Further analysis suggested a link between gut microbiota, fatty acid biosynthesis, and gene expression, particularly the upregulation of Phox2a by microbial activity. Collectively, our findings demonstrate the potential of PRP-AP to serve as a novel strategy for colitis by targeting the gut microbiota-metabolite-ENS axis, revealing that PRP-AP is a promising prebiotic agent for the maintenance of gut health.
Excessive fat deposition is considered as an important factor impairing reproductive performance in sows, and resveratrol (RES) has shown a hypolipidemic effect in previous studies. This study aimed to investigate the impact of fat deposition on reproductive performance of Shaziling sows, and further clarify the intervention by RES. Fifty-six lard-type Shaziling sows at 75 d of gestation (G75d) were divided into four groups (n = 14) based on backfat thickness (BT): backfat thickness between 20 to 24 mm (NBT) and backfat thickness between 26 to 30 mm (HBT). The NBT-CTL and HBT-CTL groups were fed a basal diet, while NBT-RES and HBT-RES were fed a diet containing 500 mg/kg RES until delivery. Results showed that HBT sows had lower total litter weight (P = 0.008), average weight of total births (P < 0.001), live litter weight (P < 0.001), average weight of live birth (P < 0.001), and placental efficiency (P = 0.013), but higher average process of farrowing (P < 0.001) and stillbirth (P = 0.005), while RES recovered these indicators significantly. In addition, HBT sows showed lower placental vascular density with decreased fluorescence intensity of platelet endothelial cell adhesion molecule-1 (CD31; P = 0.006) and fibroblast growth factor (FGF; P = 0.001), and expression of nutrient transport genes including sodium coupled neutral amino acid transporter 1 (SNAT1; P = 0.029), cluster of differentiation 36 (CD36; P = 0.004). RES increased nutrient transport genes including glucose transporter protein 3 (GLUT3; P < 0.001), GLUT4 (P = 0.014), cationic amino acid transporter 1 (CAT-1; P = 0.005), SNAT2 (P = 0.015), and plasma membrane fatty acid binding protein (FABPpm; P = 0.009), but increased placental vascular density by increasing the expression of placental angiogenesis (FGF; P = 0.013), placental growth factor (PlGF; P < 0.001) and vascular endothelial growth factor (VEGF-A; P = 0.013) in placenta. Additionally, RES recovered the phosphorylation of phosphoinositide 3-kinase (PI3K; P < 0.001), protein kinase B (AKT; P < 0.001), and mammalian target of rapamycin (mTOR; P < 0.001) in placenta of HBT sows. These findings suggest that excessive fat deposition can impair reproductive performance, which is rescued by RES by increasing the expression of placental nutrient transport and angiogenesis genes in lard-type Shaziling sows, and PI3K may play an important role.
Based on screening results, a series of nitrogen-containing five-membered heterocyclic compounds were designed and synthesized for anticancer evaluation. Among them, 7s, featuring a 1,2,3-triazole scaffold, exhibited the most potent antiproliferative activity against four human cancer cell lines (IC₅₀ < 10 μM). Mechanistic studies revealed that 7s downregulated phosphorylated AKT (p-AKT) protein at 5 μM. It also demonstrated moderate metabolic stability (T₁/₂ = 38.9 min, clearance = 23.4 mL/min/kg) and acceptable aqueous solubility (2.6 mg/100 mL). SwissADME predictions confirmed its good oral bioavailability and gastrointestinal absorption. Importantly, 7s showed low cytotoxicity toward normal HEK293 cells (IC₅₀ = 56.2 μM), suggesting a favorable safety. These results support 7s as a promising lead compound for further development in anticancer drug discovery.
Ethnopharmacological relevance: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. Aim of the study: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, antiinflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. Materials and methods: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-I in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. Results: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-I (35.34 kDa), and the structural characterization indicated that CVP-AP-I was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-I attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of proinflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. Conclusion: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.
Background Comprehending the patterns of alteration in boar semen quality and identifying effective nutritional interventions are crucial for enhancing the productivity of commercial pig systems. This study aimed to examine the alteration in semen quality in boars, and assess the impact of protocatechuic acid (PCA) on semen quality during the phase of declining semen quality. Methods In Exp. 1, a total of 38 Pig Improvement Company (PIC) boars were selected and their semen quality data were recorded from the age of 9 to 37 months. In Exp. 2, 18 PIC boars (28 months old) were randomly assigned into three groups (n = 6) and fed a basal diet, a basal diet containing 500 or 1,000 mg/kg PCA, respectively. The experiment lasted for 12 weeks. Results The semen volume, concentration, and total number of spermatozoa in boars exhibited an increase from 9 to 19 months old and showed a significant linear decreased trend in 28, 24, and 22 months old. Sperm motility displayed an upward trajectory, reaching its peak at 20 months of age, and showed a significant linear decreased trend at 20 months old. Dietary supplementation of PCA demonstrated an effect to mitigate the decrease in semen volume, concentration of spermatozoa, total number of spermatozoa (P > 0.05), and significantly increased the sperm motility (P < 0.05). Moreover, supplementation of 1,000 mg/kg PCA significantly increased the sperm viability (P < 0.05). Analysis on cellular signaling pathways revealed that PCA restored serum testosterone levels and alleviated oxidative damage by upregulating the expression of HO-1, SOD2, and NQO1 in testicular stromal cells. Notably, PCA can enhance phosphorylation by selectively binding to AMP-activated protein kinase (AMPK) protein, thereby improving sperm mitochondrial function and augmenting sperm motility via PGC-1/Nrf1. Conclusions These data elucidated the pattern of semen quality variation in boars within the age range of 9 to 37 months old, and PCA has the potential to be a natural antioxidant to enhance sperm quality through modulation of the AMPK/PGC-1/Nrf1 signaling pathway.
Background: Neoantigen nanovaccine has been recognized as a promising treatment modality for personalized cancer immunotherapy. However, most current nanovaccines are carrier -dependent and the manufacturing process is complicated, resulting in potential safety concerns and suboptimal codelivery of neoantigens and adjuvants to antigen -presenting cells (APCs). Methods: Here we report a facile and general methodology for nanoassembly of peptide and oligonucleotide by programming neoantigen peptide with a short cationic module at N -terminus to prepare nanovaccine. The programmed peptide can co -assemble with CpG oligonucleotide (TLR9 agonist) into monodispersed nanostructures without the introduction of artificial carrier. Results: We demonstrate that the engineered nanovaccine promoted the codelivery of neoantigen peptides and adjuvants to lymph node -residing APCs and instigated potent neoantigen-specific T -cell responses, eliciting neoantigen-specific antitumor immune responses with negligible systemic toxicity. Furthermore, the antitumor T -cell immunity is profoundly potentiated when combined with anti -PD -1 therapy, leading to significant inhibition or even complete regression of established melanoma and MC -38 colon tumors. Conclusions: Collectively, this work demonstrates the feasibility and effectiveness of personalized cancer nanovaccine preparation with high immunogenicity and good biosafety by programming neoantigen peptide for nanoassembly with oligonucleotides without the aid of artificial carrier.
Aging is a biological process that leads to the progressive deterioration and loss of physiological functions in the human body and results in an increase in morbidity and mortality, and aging-related disease is a major global problem that poses a serious threat to public health. Polysaccharides have been shown to delay aging by reducing oxidative damage, suppressing inflammatory responses, and modulating intestinal microbiota. Our previous studies have shown that polysaccharide CPP-1 extracted from the root of Codonopsis pilosula possesses noticeable anti-oxidant activity in vitro. Thus, in our study, we tested the anti-aging effect of CPP-1 in naturally aging mice (in vivo). Eighteen C57/BL mice (48-week-old, male) were divided into a control group, high-dose CPP-1 group (20 mg/mL), and low-dose CPP-1 group (10 mg/mL). We discovered that CPP-1 can exert a reparative effect on aging stress in the intestine and liver, including alleviating inflammation and oxidative damage. We revealed that CPP-1 supplementation improved the intestinal microbiota composition and repaired the intestinal barrier in the gut. Furthermore, CPP-1 was proved to modulate lipid metabolism and repair hepatocyte injury in the liver by influencing the enterohepatic axis associated with the intestinal microbiota. Therefore, we concluded that CPP-1 prevents and alleviates oxidative stress and inflammatory responses in the intestine and liver of aging mice by modulating the intestinal microbiota-related gut-liver axis to delay aging.
The roots of Angelica sinensis have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this herb (aboveground part) are commonly discarded during the process of root preparations. A polysaccharide (ASP-Ag-AP) in the aboveground parts of A. sinensis was isolated and preliminarily characterized as typical plant pectin. ASP-Ag-AP exhibited noticeable protective effects against dextran sodium sulfate (DSS)-induced colitis, including reduction of colonic inflammation, modulation of barrier function, and alteration of gut microbiota and serum metabolite profile. Anti-inflammatory effects of ASP-Ag-AP were observed by inhibiting TLR4/MyD88/NF-κB signaling pathway in vitro and in vivo. Additionally, the level of serum metabolite 5-methyl-dl-tryptophan (5-MT) was reduced by DSS and restored by ASP-Ag-AP, which also negatively correlated with Bacteroides, Alistipes, Staphylococcus and pro-inflammatory factors. The protection from inflammatory stress on intestinal porcine enterocytes cells (IPEC-J2) of 5-MT was observed through the inhibition of TLR4/MyD88/NF-κB pathway. Besides, 5-MT also exhibited robust anti-inflammatory effect in colitis mice with improving colitis symptoms, barrier function and gut microbiota, which was the same as presented by ASP-Ag-AP. Therefore, ASP-Ag-AP could be a promising agent for colitis prevention and 5-MT could be the signal metabolite of ASP-Ag-AP on defending against intestinal inflammatory stress.
Objective In order to study the quality consistency of Salvia miltiorrhiza from different districts and research the industrial layout of Salvia miltiorrhiza in Sichuan province, 22 batches of Salvia miltiorrhiza samples were collected from three districts(Bazhong, Deyang and Ziyang) in Sichuan province. Methods The contents of water, extract, tanshinone, salvianolic acid B and fingerprint were determined by legal methods respectively. Then the one-way ANOVA, the cluster analysis and the similarity evaluation system for chromatographic fingerprint of traditional chinese medicine(TCM) were used for statistical analysis.Results The results of one-way ANOVA show that 22 batches of Salvia miltiorrhiza samples from different districts are simliar. The result of cluster analysis show that the quality of Salvia miltiorrhiza samples from three districts has no essential differences. And the result of the similarity evaluation for chromatographic fingerprint of TCM indicates the quality of Salvia miltiorrhiza samples from Bazhong, Deyang and Ziyang districts have almost the same.Conclusion The Salvia miltiorrhiza samples from three districts in Sichuan province have high quality consistency, while Bazhong, Deyang and Ziyang are considered to be the suitable districts for Salvia miltiorrhiza cultivation.
Trace elements play a crucial role in the growth and bioactive substance content of medicinal plants, but their utilization efficiency in soil is often low. In this study, soil and Aconitum carmichaelii samples were collected and measured from 22 different locations, followed by an analysis of the relationship between trace elements and the yield and alkaloid content of the plants. The results indicated a significant positive correlation between zinc, trace elements in the soil, and the yield and alkaloid content of A. carmichaelii. Subsequent treatment of A. carmichaelii with both bulk zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO NPs) demonstrated that the use of ZnO NPs significantly enhanced plant growth and monoester-type alkaloid content. To elucidate the underlying mechanisms responsible for these effects, metabolomic analysis was performed, resulting in the identification of 38 differentially expressed metabolites in eight metabolic pathways between the two treatments. Additionally, significant differences were observed in the rhizosphere bacterial communities, with Bacteroidota and Actinobacteriota identified as valuable biomarkers for ZnO NP treatment. Covariation analysis further revealed significant correlations between specific microbial communities and metabolite expression levels. These findings provide compelling evidence that nanoscale zinc exhibits much higher utilization efficiency compared to traditional zinc fertilizer.
泽泻是常用大宗中药材,病虫害是影响其优质高产高效的重要因素.本文通过查阅总结已有研究,对泽泻白斑病、莲缢管蚜、斜纹夜蛾、银纹夜蛾和福寿螺等常见病虫害的病原/虫源、危害症状、发生规律以及防治技术等进行了综述,分析了存在的问题,并加以展望,以期为泽泻病虫害防治及进一步研究提供新的思路,促进泽泻产业绿色发展.
ASPS is a kind of plant polysaccharides extracted from the fruits, roots and stems of Acanthopanax senticosus. Its chemical components include galactose, glucose, arabinose, rhamnose, xylose, etc. It has physiological functions such as enhancing immunity, lowering blood glucose, anti-oxidation and regulating intestinal microecological balance. It has great potential as a new feed additive in livestock and poultry production. The paper reviews the biological functions of ASPS and its application in livestock and poultry production, in order to provide reference for further research and application of ASPS.