Background and Objectives: To explore the mechanism of action of the differential components of medicinal and edible lilies in treating depression by network pharmacology using UPLC-Q-TOF-MS technology. Methods: The chemical composition of medicinal and edible lilies was analyzed, screening for unique medicinal compounds. Searched for depression-related targets. Constructed PPI networks. Performed GO and KEGG analyses. Built a network of differential components, and conducted molecular docking. In addition, the contents of regaloside before and after lily processing were compared Results: Medicinal lilies and edible lilies have 17 main differences, including regaloside B and regaloside E. There are 179 targets for actives, 2690 for antidepressants, and 98 intersected. Core targets (7) led to 238 GO processes and 107 KEGG pathways. The molecular docking results showed that 17 components, including regaloside B, regaloside E, (25R)-3β,17α-Dihydroxy-5α- spirostan-6-one 3-O-α-L- rhamnopyranosyl-(1→2)-β- D-glucopyranoside (Named: Lilium lancifolium saponin), etc. could act on 7 potential targets such as EGFR, HSP90AA1, STAT3, TNF, etc. to exert antidepressant effects. Conclusion: This study employed a network pharmacology combined with a molecular docking approach to compare the active constituents of medicinal and edible lilies in antidepressants, and their pharmacological mechanisms, both theoretically and technically. The phytoconstituents were found to act mainly by inhibiting the inflammatory response in depression. Especially Lilium lancifolium saponin may have a close relationship with antidepressants. These results provide some justification for lilies in the treatment of depression.
Dendrobii Officinalis Flos (DOF) is the flower of Dendrobium officinale Kimura et Migo (Fam. Orchidaceae), distinguished by its uniquely shaped and elegantly pale blossoms. In recent years, this flower has attracted considerable attention in the food industry due to its pleasant flavor and rich nutritional profile. The present study investigated the effects of different drying methods-microwave drying (MD), vacuum drying (VD), hot-air drying (HAD), and vacuum freeze-drying (VFD)-on the appearance, volatile organic compounds (VOCs), and antioxidant capacity of DOF. Analysis via gas chromatography-ion mobility spectrometry (GC-IMS) identified a total of 52 VOCs across the five sample groups, including 16 alcohols, 18 aldehydes, 10 ketones, 4 esters, 1 carboxylic acid, 2 heterocyclic compounds, and 1 disulfide. The findings revealed that fresh flowers contained higher levels of VOCs such as 2-octanone and 3-methyl-1-butanol. VFD-treated flowers showed higher levels of key flavor markers (e.g., (E)-2-butenal, (E)-2-heptenal, (E)-2-pentenal), suggesting their potential as flavor enhancers. VD-treated samples retained more tea-like aromatics (e.g., (Z)-2-penten-1-ol), making them suitable for enhancing premium tea beverages. In contrast, MD and HAD resulted in noticeable color darkening and a significant loss of volatile constituents. The antioxidant activity was evaluated using two complementary assays: the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation scavenging assay and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Fresh samples showed the strongest bioactivity, followed by VFD-treated ones. VFD was optimal for preserving morphology, flavor, and antioxidant capacity. This study provides a basis for optimizing DOF processing, with drying methods selected for specific applications.
BACKGROUND/OBJECTIVES:As a traditional Chinese medicinal herb, Cnidii Fructus is widely used in clinical practice. Its volatile organic compounds (VOCs) are closely related to its antipruritic effect and insecticidal properties. Due to the susceptibility of this medicinal herb to mold contamination, adopting appropriate sterilization measures is of great significance for its storage. 60Co irradiation is widely used for this purpose due to its various advantages. METHODS:This study employed Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) combined with multivariate statistical analysis to systematically investigate the influence of different 60Co irradiation doses (0, 3, 6, 9 kGy) on the VOCs of Cnidii Fructus and associated metabolic regulatory mechanisms. RESULTS:A total of 115 VOCs were tentatively identified. Statistical analysis revealed dose-dependent effects: 3 kGy irradiation caused the least compositional perturbation, best preserving original chemical characteristics; 6 kGy induced more pronounced compositional changes; and 9 kGy triggered substantial chemical composition reconstruction. Differential metabolite enrichment analysis indicated that medium and high doses of irradiation primarily perturbed central carbon metabolic pathways, including pyruvate metabolism, glycolysis/gluconeogenesis, and glyoxylate and dicarboxylate metabolism. Key differential components were tentatively identified (e.g., α-Thujone, α-Pinene, β-Pinene) that possess pharmacological activities closely associated with the traditional efficacy of Cnidii Fructus. CONCLUSIONS:When the irradiation dose is 3 kGy, the VOCs profile of Cnidii Fructus is most similar to that of the non-irradiated control group, suggesting that its compositional profile may be closer to that of traditional high-quality medicinal materials. Meanwhile, the differential metabolites and core metabolic pathways identified in this study can provide a chemical reference for the quality control of irradiated Cnidii Fructus. The findings provide a theoretical basis and technical support for the rational application of 60Co irradiation sterilization in the processing of Chinese medicinal materials and their powders.
ETHNOPHARMACOLOGICAL RELEVANCE:Ulcerative colitis (UC) is a complex inflammatory bowel disorder characterized by immune dysregulation, intestinal barrier dysfunction, and intestinal microbiota imbalance. Current therapies remain limited, highlighting the need for alternative strategies. Fufang Tongye Shaoshang You (TYY), a traditional ethnomedicine historically used for diarrhea and ulcers, exhibits promising therapeutic potential against UC. AIM OF THE STUDY:This study aims to evaluate the therapeutic efficacy of TYY in UC mice and to systematically elucidate its underlying mechanisms and potential bioactive constituents. MATERIALS AND METHODS:A dextran sulfate sodium (DSS)-induced UC mouse model was established to evaluate the reparative effect of TYY by assessing disease activity, colon length, and histopathology. Systemic effects were examined through spleen index and serum markers of liver and kidney function. Key UC-associated targets were identified via analysis of GEO transcriptomic datasets. The anti-inflammatory and barrier-protective mechanisms of TYY were explored using a series of molecular and histological techniques. Intestinal microbiota changes were analyzed with 16S rRNA gene sequencing. Furthermore, serum pharmacochemistry (UPLC-Q-TOF-MS) identified and prioritized circulating components, which were validated in a lipopolysaccharide (LPS)-stimulated Caco-2 cell model for their regulatory effects in vitro. RESULTS:TYY exerted comprehensive therapeutic effects on UC by inhibiting IL-17 signaling pathway, rebalancing intestinal microbiota, and protecting intestinal mucosa, while also improving DSS-induced liver, kidney, and spleen dysfunction. Seven key bioactive components were identified as the primary pharmacodynamic substances responsible for TYY's efficacy. CONCLUSIONS:This work systematically elucidates the multi-target mechanism of TYY in treating UC, demonstrating that its therapeutic efficacy arises from a balanced strategy encompassing inflammation inhibition, microbiota regulation, and mucosa protection-showing demonstrable superiority over its vehicle alone and being friendly to extra-intestinal organs. The identification of seven bioactive components and their differential targeting of the IL-17 signaling network provides a mechanistic foundation for repurposing this topical ethnomedicine as a promising oral complementary therapy for UC.
The Hou-Yan-Qing oral liquid (HYQ) is a popular traditional Chinese medicine for the treatment of pharyngitis. However, due to its complex composition, little attention has been directed toward the analysis of its mechanism and active components. An ammonia-induced acute pharyngitis rat model was established, with HYQ's effects and mechanism assessed via histopathology, enzyme-linked immunosorbent assay, and Western blot. Furthermore, the active components of HYQ were analyzed using HPLC and ultra performance LC (UPLC)-QTOF-MS in conjunction with an in vitro lipopolysaccharide-induced RAW264.7 cell model. Treatment with HYQ significantly reduced the levels of cytokines such as pro-inflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor α [TNF-α]) and inflammatory mediators (Prostaglandin E2 [PGE2]), inhibited the expression of cyclooxygenase-2 (COX-2), 5-LOX, p-IKKβ, p-nuclear factor-kappaB (NF-κB) and p-inhibitor of kappaBα (p-IκBα) proteins, and promoted the expression of nuclear factor-E2-related factor 2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase 1 proteins. Chemical profiling of ten batch HYQ specimens via HPLC and UPLC-QTOF-MS established characteristic fingerprints and identified 24 shared components. Using spectrum-effect relationship modeling, which employed gray relational analysis to correlate chromatographic peaks with bioactivity indices, we found that components such as 25S-Inokosterone and β-ecdysterone may be the key active components of HYQ's anti-inflammatory effect. Subsequent validation confirmed that β-ecdysterone (1-100 μM) exhibited no cytotoxicity in RAW264.7 cells. Furthermore, treatment with β-ecdysterone significantly reduced levels of pro-inflammatory cytokines (IL-6, TNF-α) and inflammatory mediators (PGE2), and inhibited the expression of COX-2, 5-LOX, p-IKKβ, p-NF-κB, and p-IκBα proteins.
Tomato Fusarium wilt, caused by Fusarium oxysporum f. sp. lycopersici (FOL), is a devastating disease that leads to yield losses of up to 67% in severely affected regions. Current control strategies, such as chemical treatments and resistant cultivars, face challenges including environmental toxicity and pathogen resistance. In this study, we isolated an endophytic fungus, Penicillium sp. JL76001 (JL76001), from the medicinal plant Asarum forbesii, which exhibited strong antagonism against FOL. Plate confrontation assays revealed a 40.48% inhibition of FOL growth, attributed to the secondary metabolite sclerotiorin (SCL). The minimum inhibitory concentration (MIC) of SCL against FOL was determined to be 12.5 μg/mL. Microscopic observations revealed severe hyphal distortion and ultrastructural damage in the fungal cells. Proteomic analysis identified 354 differentially expressed proteins in FOL under SCL treatment, which disrupted cysteine metabolism, oxidative phosphorylation, and cell membrane integrity. In simulated field trials, the crude metabolite extract (CME) of JL76001 achieved a control efficacy of 55.17% against tomato Fusarium wilt. Furthermore, JL76001 demonstrated the capability to produce SCL using agricultural waste residues, suggesting a sustainable strategy for waste valorization. Our study presents JL76001 and SCL as promising biocontrol agents for the sustainable management of tomato Fusarium wilt.
TCM is a treasure of Chinese civilization and a potential key to solving modern medical challenges. Research on the pharmacodynamic material basis, action targets, and mechanisms based on the traditional efficacy of TCM has become a consensus. Clarifying the pharmacodynamic material basis of TCM is not only a fundamental issue in TCM research but also a critical step in deciphering the complex TCM systems. However, the complexity of TCM systems poses significant challenges to the research of their pharmacodynamic material basis, leaving the pharmacodynamic material basis of treating diseases in most TCM largely unclear, which greatly limits people's scientific understanding of TCM in treating diseases. Currently, the research on the pharmacodynamic material basis of TCM has formed an interdisciplinary methodological system. Various methods have shown unique advantages, but they all have the common problem of being unable to balance the holistic view of TCM and research precision. The knock-out/knock-in technique can precisely disassemble and controllably integrate the complex TCM system and is a key technique to solve the challenges in the research of TCM material basis. Based on this, this paper proposed a new paradigm for identifying the material basis based on the knock-out/knock-in technique. This paradigm integrates the intrinsic connection among traditional efficacy, material basis, and action targets, aiming to provide new ideas for the research on the material basis of TCM and methodological support for the TCM modernization.
Carpesium abrotanoides L. (CA), a dried whole herb from the Asteraceae family, features prominent heat-clearing and detoxifying properties. However, a rigorous criterion for evaluating the quality of CA has yet to be established. Therefore, the aim of this study was to conduct quality control research on CA by combining ultra-high-performance liquid chromatography (UPLC) Fingerprint, chemometrics and quantitative analysis of multi-components by a single-marker (QAMS) method. Through the fingerprint analysis of 17 batches of CA, a total of 19 common peaks were identified by UPLC-QTOF-MS, and 10 components were confirmed via reference standards, including 5 phenolic acids, 4 sesquiterpenoids, and 1 flavonoid component. 12 differential components were screened out through chemometric analysis by hierarchical clustering analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares method-discriminant analysis (OPLS-DA). Using isochlorogenic acid A as the internal standard, relative correction factors were established for chlorogenic acid, caffeic acid, cynaroside, 11(13)-dehydroivaxillin, isochlorogenic acid C, 2,3,4,5-tetracaffeoyl-d-glucaric acid, 2-deoxy-4-epi-gaillardin, carabrone, and telekin, allowing for the quantification of 10 components. The QAMS and the external standard method (ESM) showed no substantial difference in their determination results, demonstrating the accuracy and reliability of the QAMS established with isochlorogenic acid A as the internal standard. The strategy combining fingerprint analysis, chemometrics, and QAMS proposed herein can control the quality of CA quickly and efficiently. This study lays a theoretical foundation for the quality control and clinical application of CA.
Osteoporosis (OP) is a systemic bone disorder characterized by reduced bone mass and deterioration of bone microarchitecture. Despite the widespread use of classic medicines such as parathyroid hormone and bisphosphonate in clinical practice, their adverse effects continue to be a major concern. Consequently, the exploration of safe and effective therapeutic agents derived from botanical drugs has emerged as a key research focus. Traditional Chinese medicine (TCM) constitutes a valuable therapeutic modality for osteoporosis, attributed to its abundant botanical resources, multi-target modulatory effects, and favorable safety and effectiveness validated by long-term clinical practice. In recent years, natural products from TCM have gained increasing attention for their potential in the prevention and treatment of osteoporosis. This review provides a comprehensive summary of the diverse classes of metabolites currently investigated for OP management, along with their underlying mechanisms of action. By elucidating the pharmacological mechanisms of these bioactive metabolites, this study aims to provide a reference for evaluating their potential as alternative or adjunctive therapeutic strategies in osteoporosis management.
Bacterial wilt, caused by the soil-borne phytopathogen Ralstonia solanacearum (R. solanacearum), poses a serious threat to global agriculture. In this study, 26 actinomycete strains were isolated from the rhizosphere of traditional Chinese medicinal plants. Among them, Streptomyces sp. JL2001 exhibited strong inhibitory activity against R. solanacearum both in vitro and in planta. UPLC-QTOF-MS/MS analysis identified aerugine as the major active compound, alongside five structurally related 2-hydroxyphenylthiazoline derivatives. Chemically synthesized aerugine showed broad-spectrum antibacterial activity, significantly inhibiting planktonic growth and biofilm formation and alleviating bacterial wilt symptoms in tomato seedlings under hydroponic and soil-based conditions. Mechanistically, aerugine disrupts bacterial membranes, interferes with lipid metabolism, and downregulates key virulence systems, including flagellar assembly and the type III secretion system. These findings were supported by electron microscopy, proteomic profiling, and qPCR validation. Whole-genome sequencing of JL2001 revealed a 7.75 Mb chromosome containing 22 biosynthetic gene clusters (BGCs), including a thiazostatin-like NRPS-dependent BGC likely responsible for aerugine biosynthesis. Importantly, soilbased assays demonstrated that aerugine significantly and dose-dependently suppressed R. solanacearum in natural soil, while also inducing changes in microbial composition. Later-stage increases in bacterial abundance and diversity, particularly of morphologically distinct non-pathogenic colonies, suggest that aerugine not only eliminates pathogens but may also promote beneficial microbiota -a dual protection mechanism. This study highlights Streptomyces sp. JL2001 and aerugine as promising agents for the sustainable control of bacterial wilt and provides new insights into their molecular antibacterial mechanisms.
ETHNOPHARMACOLOGICAL RELEVANCE:Fufang tongye shaoshang You (TYY) is an ethnomedicine derived from the traditional folk formula of the Tujia people in Hunan Province, which consists of Paulownia leaf and sesame oil, has shown promising potential in promoting Diabetic ulcer (DU) healing. However, its pharmacological substance and mechanism of action requirers further elucidation. AIMS OF THE STUDY:This study was designed to assess the healing effect of TYY on DU wounds in mice, and to explore systematically its potential mechanisms and pharmacodynamic material basis. METHODS:The combination of high-fat and high-sugar diet and streptozotocin injection was used to induce C57BL/6J mouse diabetic model, and the ulcer was surgically introduced. After TYY treatment, the skin lesions of diabetic mice were observed by H&E, Masson staining and transmission electron microscopy over a period of time. The wound tissues were collected. Transcriptomics were used to predict the potential mechanism of TYY, and then immunohistochemistry, immunofluorescence, ELISA, Western blotting, and qRT-PCR were used to detect the expression levels of key proteins and mRNA in related signaling pathways. The effect of TYY on tight junction proteins was detected by Western blotting. The chemical components of 10 batches of TYY were analyzed by multivariate analysis, and the iconic components of TYY were screened by molecular docking and dynamics simulation. HMEC-1 cells were induced by lipopolysaccharide and high glucose to simulate DU microenvironment and construct endothelial cell injury model. Scratch test and RT-qPCR were used to evaluate the effects of TYY active ingredients on endothelial cell injury models, and finally determine the pharmacodynamic material basis of TYY. RESULTS:The study have shown that TYY can not only effectively repair the skin barrier, but also regulate the IL-17-mediated NF-κB/AP-1 signaling pathway, inhibit the exacerbation of inflammation, and accelerate wound healing in DU mice. In addition, we further discovered the key active ingredients of TYY: maslinic acid, corosolic acid, oleanolic acid, ursolic acid and sesamin. CONCLUSION:This study provides scientific evidence for TYY as a potential drug to repair DU, and also provides a theoretical basis for its further clinical application and drug development.
This study aims to explore the anti-pharyngitis mechanisms of Achyranthes longifolia (Makino) Makino. extract (ALE) and the anti-inflammatory mechanisms of its major bioactive component, chikusetsusaponin IVa (CIVa). To this end, the present study established an ammonia-induced acute pharyngitis rat model to assess the therapeutic efficacy of ALE and a lipopolysaccharide (LPS)-induced RAW264.7 cells model to evaluate the anti-inflammatory and antioxidant properties of CIVa. Pharyngeal severity was evaluated using appearance index and HE staining, while ELISA was employed to quantify inflammatory cytokines TNF-α, PGE2, and IL-6. Additionally, the levels of SOD, CAT, and MDA were measured to assess antioxidant status. Western blot was conducted to analyze the expression of proteins associated with the Nrf2/NF-κB pathways. The findings indicate that ALE provides protection in the ammonia-induced acute pharyngitis rat model, as evidenced by reduced pharyngeal redness, swelling, and improved histopathological changes. CIVa, the primary constituent of ALE, demonstrates anti-inflammatory effects in LPS-induced RAW 264.7 cells by inhibiting NO production and reducing the levels of inflammatory cytokines in a dose-dependent manner. The underlying mechanism appears to involve the inhibition of the NF-κB pathway, activation of the Nrf2 pathway, modulation of oxidative stress, and reduction of pro-inflammatory cytokine release. These results position ALE and CIVa as promising alternative therapeutic agents for the management of acute pharyngitis and potentially other inflammatory disorders.
Prokaryotes have evolved diverse defense strategies against viral infection, including foreign nucleic acid degradation by CRISPR-Cas systems and DNA and RNA synthesis inhibition through nucleotide pool depletion. Here, we report an antiviral mechanism of type III CRISPR-Cas-regulated adenosine triphosphate (ATP) depletion in which ATP is converted into inosine triphosphate (ITP) by CRISPR-Cas-associated adenosine deaminase (CAAD) upon activation by either cA(4) or cA(6), followed by hydrolysis into inosine monophosphate (IMP) by Nudix hydrolase, ultimately resulting in cell growth arrest. The cryo-electron microscopy structures of CAAD in its apo and activated forms, together with biochemical evidence, revealed how cA(4) or cA(6) binds to the CRISPR-associated Rossmann fold (CARF) domain and abrogates CAAD autoinhibition, inducing substantial conformational changes that reshape the structure of CAAD and induce its deaminase activity. Our results reveal the mechanism of a CRISPR-Cas-regulated ATP depletion antiviral strategy.
Pseudomonas syringae (P. syringae) can infect over 50 different crops worldwide, causing significant economic losses, and it is one of the major bacterial pathogens affecting global crops. Currently, there are no effective control strategies for bacterial leaf spot disease caused by P. syringae. In this study, a high-throughput screening of 1680 natural products was conducted to evaluate their antibacterial effects. Microbial-derived compounds such as Polymyxin B sulfate (1), Methacycline hydrochloride (2), Tetracycline hydrochloride (3), Chlortetracycline hydrochloride (4), Demeclocycline hydrochloride (5), and Doxycycline hyclate (6) exhibited strong antibacterial activity against Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), with inhibition rates exceeding 60
[This corrects the article DOI: 10.3389/fmicb.2024.1504243.].
Growing evidence indicates an interesting interplay between kidney and bone. The pathophysiological condition of the skeletal system is intricately associated with the normal functioning of the kidneys. This relationship is modulated by various factors, including calcium and phosphate, 1-α-hydroxylase, erythropoietin (EPO), klotho, fibroblast growth factor 23 (FGF23), bone morphogenetic protein-7 (BMP-7), and extracellular vesicles (EVs). These interactions are notably evident in conditions such as chronic kidney disease with bone mineral density (CKD-BMD), renal osteodystrophy (ROD), and osteoporosis (OP). Furthermore, innovative methodologies such as cell co-culture, organ-on-a-chip, single-cell sequencing, and spatial transcriptomics are highlighted as instrumental in advancing the study of inter-organ interactions. This review, grounded in the pathogenesis, diagnostic and therapeutic modalities, and pharmacological treatments of OP, synthesizes evidence from molecular biology to clinical perspectives. It aims to establish a foundation for the development of more complex and physiologically relevant in vitro models and to propose potential therapeutic strategies.
Medicinal plants as the core component of Traditional Chinese Medicine (TCM) play a pivotal role in promoting the development of China's TCM industry. The frequent occurrence of soil-borne diseases significantly impacts the high and stable production of these medicinal plants. Common soil-borne diseases, such as root rot, seedling blight, and gray mold, can occur in more than ten commonly used medicinal plants, leading to a substantial reduction in yield or even total crop failure. This paper provides a comprehensive review of the types and pathogenic mechanisms of common soil-borne diseases during the cultivation of medicinal plants. It discusses chemical, biological, physical, and other control strategies and their current development status for soil-borne diseases. The paper also offers insights into existing challenges in the prevention and control of soil-borne diseases in medicinal plants, aiming to inform green prevention and control practices.
Morinda citrifolia L. (noni) is a tropical plant containing over 200 phytochemicals, including terpenoids, anthraquinones, coumarins, flavonoids, lignans, and polysaccharides, with demonstrated biological activities such as antioxidant, anti-inflammatory, hypoglycaemic, hepatoprotective, and cardioprotective effects. Studies indicate that noni and its bioactive components, such as scopoletin, quercetin, rutin, ursolic acid, and polysaccharides, exert beneficial effects on systemic metabolic disorder (SMD). SMD is a complex syndrome involving multi-organ metabolic dysregulation, characterized by conditions such as insulin resistance, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, hypertension, atherogenic dyslipidaemia, inflammation, heart failure, and kidney disease, which collectively increase morbidity and mortality. Given this significant disease burden, noni ameliorates obesity by regulating the gut microbiota, inhibiting lipases, and enhancing lipid metabolism; improves insulin sensitivity and glucose homeostasis via pathways like Nrf2/ARE and gut microbiota modulation; mitigates liver dysfunction by reducing lipid accumulation, oxidative stress, and inflammation; lowers blood pressure through ACE inhibition and eNOS activation; improves dyslipidaemia by regulating lipoprotein metabolism; suppresses inflammation via NF-κB inhibition; and protects against heart and kidney damage by alleviating oxidative stress and apoptosis. This review provides an overview of the bioactive components in noni and analyzes the in vitro and in vivo evidence regarding its bioactive compounds and their mechanisms, thus underscoring its potential as a natural intervention targeting multiple pathophysiological mechanisms for the treatment of SMD.