Insight into the sorption and desorption pattern of pyrrolizidine alkaloids and their N-oxides in acidic tea (Camellia sinensis) plantation soils.

Pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) are phytotoxins produced by various plant species and have been emerged as environmental pollutants. The sorption/desorption behaviors of PAs/PANOs in soil are crucial due to the horizontal transfer of these natural products from PA-producing plants to soil and subsequently absorbed by plant roots. This study firstly investigated the sorption/desorption behaviors of PAs/PANOs in tea plantation soils with distinct characteristics. Sorption amounts for seneciphylline (Sp) and seneciphylline-N-oxide (SpNO) in three acidic soils ranged from 2.9 to 5.9 µg/g and 1.7 to 2.8 µg/g, respectively. Desorption percentages for Sp and SpNO were from 22.2% to 30.5% and 36.1% to 43.9%. In the mixed PAs/PANOs systems, stronger sorption of PAs over PANOs was occurred in tested soils. Additionally, the Freundlich models more precisely described the sorption/desorption isotherms. Cation exchange capacity, sand content and total nitrogen were identified as major influencing factors by linear regression models. Overall, the soils exhibiting higher sorption capacities for compounds with greater hydrophobicity. PANOs were more likely to migrate within soils and be absorbed by tea plants. It contributes to the understanding of environmental fate of PAs/PANOs in tea plantations and provides basic data and clues for the development of PAs/PANOs reduction technology.

The Quinine Odyssey: A Barometer of the State of Organic Synthesis Over Centuries.

The year 2024 marks the 80th anniversary of the landmark formal synthesis of (±)-quinine completed by Woodward and Doering. This article examines the evolution of approaches to access this storied Cinchona alkaloid natural product which represent a microcosm the progress that has been made in organic synthesis over the past ~170 years. Seminal contributions led by Pasteur, Rabe, Woodward, Uskokovic, Stork, Jacobsen, Hayashi, Maulide and others are discussed.

Bis-benzylisoquinoline alkaloids inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy.

Flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV), represent a substantial public health challenge as there are currently no approved treatments available. Here, we investigated the antiviral effects of bis-benzylisoquinoline alkaloids (BBAs) on flavivirus infections. We evaluated five specific BBAs-berbamine, tetrandrine, iso-tetrandrine, fangchinoline, and cepharanthine-and found that they effectively inhibited infections by ZIKV, DENV, or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle. Furthermore, we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes, causing lysosomal pH alkalization. Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels, leading to lysosomal dysfunction and reducing the expression of NCAM1, a key receptor for the entry of ZIKV into cells, thereby decreasing cells susceptibility to ZIKV infection. Additionally, BBAs inhibited the fusion of autophagosomes and lysosomes, significantly reducing viral RNA replication. Collectively, our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy, respectively, underscoring the potential of BBAs as therapeutic agents against flavivirus infections.

Murraya koenigii (L.) Spreng. as a Natural Intervention for Diabesity: A Review.

BACKGROUND: Murraya koenigii (L.) Spreng. (family: Rutaceae), commonly known as curry leaf or sweet neem, is a tropical plant native to India and Southeast Asia. It is highly valued in Ayurveda for its medicinal properties. Almost every part (fresh leaves, fruits, bark, and roots) of this plant is used to treat various ailments. Its fresh leaves are considered to have numerous medicinal properties for various diseases, including piles, inflammation, itching, fresh cuts, dysentery, and edema. A combination of curry leaf and buttermilk is used to treat diseases, such as amoebiasis, diabetes, and hepatitis. Its leaves are also believed to possess antioxidant, anti-inflammatory, and antimicrobial properties. The bark has been traditionally used for treating snakebites. Its roots are utilized in Ayurveda for the treatment of body aches. Being a storehouse of carbazole alkaloids, M. koenigii has been reported to show anti-obesity and anti-diabetic activity in in vitro and in vivo studies. The review aimed to appraise the role of M. koenigii leaf in the prevention of diabesity. METHODS: We performed a literature search with the keywords "diabesity", "obesity", "diabetes", "adipose tissue", and "carbazole alkaloids" on Google Scholar, PubMed, and ScienceDirect databases. Several in vitro and in vivo studies conducted on cell lines and animals for anti-diabetic/anti-hyperglycemic and antihyperlipidemic activities have been included and appraised in the article, providing supporting evidence for the ethnomedicinal claims. RESULTS AND CONCLUSION: This review has been an attempt to summarize comprehensively the overall research done on M. koenigii with regard to obesity and diabetes. The studies on anti-diabetic/anti-hyperglycemic and anti-hyperlipidemic activities of the plant have ranged from studies on crude extracts to isolated compounds. However, some of the studies require further in-depth analysis and validation of obtained results.

Alkaloids in Chelidonium majus L: a review of its phytochemistry, pharmacology and toxicology.

Chelidonium majus L. (C. majus), commonly known as "Bai Qu Cai" in China, belongs to the genus Chelidonium of the Papaveraceae family. It has rich medicinal value, such as alleviating coughs, asthma, spasms and pain. Recent studies have demonstrated that C. majus is abundant in various alkaloids, which are the primary components of C. majus and have a range of pharmacological effects, including anti-microbial, anti-inflammatory, anti-viral, and anti-tumor effects. So far, 94 alkaloids have been isolated from C. majus, including benzophenanthridine, protoberberine, aporphine, protopine and other types of alkaloids. This paper aims to review the research progress in phytochemistry, pharmacology and toxicology of C. majus alkaloids, in order to provide a theoretical basis for the application of C. majus in the field of medicinal chemistry and to afford reference for further research and development efforts.

An overview: total synthesis of arborisidine, and arbornamine.

Arborisidine and Arbornamine are two monoterpenoid indole alkaloids that were isolated from the Malayan Kopsia arborea plant. This review provides valuable information about the total and formal syntheses of these alkaloids. The synthesis strategies discussed in this review, such as Pictet-Spengler cyclization, chemo- and stereoselective oxidative cyclization, Michael/Mannich cascade process, and intramolecular N-alkylation, can be useful for developing new methods to synthesize these and other similar compounds.

Accelerating diabetic wound healing with Ramulus Mori (Sangzhi) alkaloids via NRF2/HO-1/eNOS pathway.

Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus. Ramulus Mori (Sangzhi) alkaloids (SZ-A), an approved oral medication for type 2 diabetes, have not been explored for their potential to enhance the processes involved in diabetic wound healing. This study aims to investigate SZ-A's role in diabetic wound healing mechanisms. The in vivo experimentation involves dividing the subjects into NC and SZ-A groups, with SZ-A dosed at 200 and 400 mg/kg, to assess the therapeutic efficacy of SZ-A. The results of the animal studies show that SZ-A intervention accelerates the processes of diabetic angiogenesis and wound healing in a manner dependent on its concentration. Additionally, a pathological model using advanced glycation end products (AGEs) in HUVECs demonstrates SZ-A's cytoprotective effect. In vitro, SZ-A intervention significantly increases cell proliferation, migration and tube formation, protecting HUVECs from oxidative stress injury induced by AGEs. Mechanistically, SZ-A exerts a protective effect on HUVECs from oxidative stress damage through the activation of the NRF2/HO-1/eNOS signaling pathway. The findings suggest that SZ-A exhibits considerable potential as a promising candidate for treating DFUs, which will aid in more effectively integrating plant-based therapies into clinical settings.

Penicipyrrolizidinones A-C, three pyrrolizidinone alkaloids with unprecedented skeletons from the mangrove-derived fungus Penicillium sp. DM27.

Three previously undescribed pyrrolizidinone alkaloids, penicipyrrolizidinones A and B (1 and 2), possessing an unprecedented 2-methyl-2-(oct-6-enoyl)pyrrolizidin-3-one skeleton, and penicipyrrolizidinone C (3), featuring a rare 1-alkenyl-2-methyl-pyrrolizidin-3,7-dione skeleton, together with four known pyrrolidine derivatives (4-7) were isolated from the mangrove-derived fungus Penicillium sp. DM27. Their structures were elucidated through comprehensive spectroscopic analysis, theoretical calculations of ECD spectra, and the modified Mosher's method. A plausible biosynthetic pathway for penicipyrrolizidinones A-C (1-3) was proposed. Compounds 4 and 5 exhibited moderate cytotoxicity against B16-F10 melanoma cells with IC50 values of 10.5 µM and 15.5 µM, respectively.

Exploring TßRI inhibitors from Arenaria kansuensis based on 3D-QSAR, molecular docking and molecular dynamics simulation methods and its anti-pulmonary fibrosis molecular mechanism validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF) is a kind of interstitial lung disease that seriously threatens human life and health. Up to now, there is no specifically therapeutic drug. Arenaria kansuensis, a typical Tibetan medicine, has been previously proved to have anti-PF pharmacological activity by our group. However, the specific target and molecular mechanism of pharmacological active ingredients from it are still unknown. AIM OF THE STUDY: This study aimed to explore the molecular mechanism and specific target of pharmacological active ingredients from A. kansuensis for treating PF. MATERIALS AND METHODS: Virtual screening including 3D-QSAR, molecular docking and molecular dynamics simulation were used to screen TßRI inhibitor. CETSA experiment was used to verify the interaction between GAK (a ß-carboline alkaloid isolated from A.kansuensis) and TßRI. Cell and molecular experiments including observation of cell morphology and western blot were applied to investigate the molecular mechanism of action of GAK for treating PF. Animal experiments including physiological index, immunohistochemistry and ELISA were used to comprehensively evaluate the anti-PF effect of GAK and explore the corresponding mechanism of action. RESULTS: Results of 3D-QSAR experiment indicated that GAK is a much stronger potential TßRI inhibitor, molecular mechanism study showed that 30µM GAK could significantly keep TßRI more stable which indicated that the direct binding interaction between GAK and TßRI, it targetedly inhibited TßRI through forming hydrogen bonds with LYS232, SER280 and ASP351 and the binding energies is -56.05kcal/mol. In vitro experiment showed GAK could suppress downstream signal pathways of TßRI including MAPK, PI3K/AKT and NF-κB pathways during EMT process. In vivo experiment showed that GAK could improve the survival rate and body weight of PF mice, alleviate the symptoms of histopathological severity, inflammatory cell infiltration and collagen deposition in lung tissue of PF mice through inhibiting EMT process of PF. CONCLUSIONS: This work not only provided evidence to support GAK as a novel TßRI inhibitor for treating PF through multiple pathways, but also reveal the specific target and molecular mechanism of ß-carboline alkaloids from A. kansuensis for treating PF.

Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature.

Consumption of ergot alkaloids during the second half of gestation has been shown to decrease umbilical artery vasoactivity resulting in decreased birth weights. Negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. Vasoactivity of serotonin (5-HT) receptors 5-HT2A and 5-HT1B/1D in umbilical artery and vein from ewes receiving endophyte-infected seed (E + 1.77 mg ergovaline/hd/d) or a control total mixed ration (CON; 0 mg ergovaline/hd/d) tall fescue seed at d-110 and d-133 of gestation was evaluated. Gravid reproduction tracts were collected from ewes. Two-mm sections of umbilical artery and vein were exposed to increasing concentrations of a 5-HT1B/1D agonist and 5-HT2A agonist. The 5-HT1B/1D agonist did not stimulate a contractile response in artery or vein or either gestation time point. 5-HT2A agonist caused large responses in artery with greatest occurring at d-110 and decreasing in magnitude as days of gestation increased (p < 0.05). On d-110 and 133 of gestation, arteries from CON ewes had greater contractile response than arteries collected from E+ ewes (p < 0.05). Veins responded to increasing concentrations of the 5-HT2A agonist. Maximal d-110 vein response was greater than d-133 when exposed to 5-HT2A agonist (p < 0.05). Unlike the artery, veins from E+ ewes had greater d-133 contractile response than CON (p < 0.05). Vascular contractions of umbilical artery and vein are induced by 5-HT2A receptor activity and not 5-HT1B/1D. Umbilical artery 5-HT2A receptor activity was more sensitive to seed treatment and could be responsible for ergot alkaloid-induced intra-uterine growth restriction.

Zanthoxylum zanthoxyloides (Lam.) B. Zepernick & Timler alkaloidal extract exerts hepatoprotective effects in rats with a CCl4/olive oil-induced hepatocellular carcinoma-like phenotype.

Objective: This study assessed the prophylactic anti-HCC effects of a combined stem and root alkaloidal extract of Zanthoxylum zanthoxyloides (Z. zanthoxyloides) (SRAEZZ) in rats with a CCl4/olive oil-induced HCC-like phenotype. Methods: SRAEZZ was prepared from dried stems and roots of Z. zanthoxyloides in a 1:1 proportion and chemically characterized. A total of 30 healthy male Wistar rats (weighing 210-280 g) were randomly assigned to six groups (control, model, capecitabine, and SRAEZZ [50, 100, or 200 mg/kg]). All groups except the control received CCl4/olive oil (3 mL/kg, po) in the morning, whereas in the afternoon of the same dosing day, the model group received normal saline (5 mL/kg, po), the capecitabine group received capecitabine (50 mg/kg, po), and the SRAEZZ groups received SRAEZZ (50, 100, or 200 mg/kg, po, respectively) once per week for 36 days. Survival rate, serum α-fetoprotein (AFP), and C-reactive protein (CRP) were monitored. Gross liver anatomy, liver histology, liver enzymes (ALP, AST, and ALT), bilirubin, creatinine, urea, albumin, globulins, and hematological parameters were assessed. Results: SRAEZZ yield was 0.58% from the initial stem and root sample (520 g). Quaternary phenanthridin alkaloids were detected in SRAEZZ. Control rats had a 100% survival rate compared with rats in the model group. SRAEZZ treatment improved the survival rate with respect to that in the model group. Serum AFP, CRP, and bilirubin levels were greater in the model group than the control group. SRAEZZ decreased serum AFP, CRP, and bilirubin below the levels observed in the model group. ALP, AST, and AST were higher in the model group, but lower in SRAEZZ-treated group, than the control group. Conclusion: SRAEZZ demonstrated prophylactic anti-HCC effects against CCl4/olive oil-induced HCC-like phenotypes in rats. These findings highlight the potential of crude alkaloids from Z. zanthoxyloides as natural templates for semi-synthesis of anti-HCC pharmacotherapeutics.

A review on phytochemicals as combating weapon for multidrug resistance in cancer.

One can recognize multidrug resistance (MDR) and residue as a biggest difficulty in cancer specialist. Chemotherapy-resistant cancer may be successfully treated by combining MDR-reversing phytochemicals with anticancer drugs. Though, clinical application of phytochemicals either alone or in conjunction with chemotherapy is still in its early stages or requires more research to determine their safety and efficacy. In this review we highlighted topics related to MDR in cancer, including an introduction to subject, mechanism of action of efflux pump, specific proteins involved in drug resistance, altered drug targets, increased drug metabolism, and potential role of phytochemicals in overcoming drug resistance.

Comparison of Nutritional Quality and Functional Active Substances in Different Parts of Eight Lotus Seed Cultivars.

In this study, "Honghu White Lotus", "Red Lotus (HH)", "Hunan Cunshan Lotus (CS)", "Wuyi Xuanlian", "Space Lotus 36", "Fujian Jianning White Lotus (JB)", "Jiangsu Yangzhou Lotus (JY)", and "Suzhou Dongshan Lotus" were selected as experimental subjects. The lotus seed flesh and lotus plumule of each cultivar were selected for nutritional quality and functional active substance analyses. Comparing different cultivars of lotus seeds, the protein and crude fat contents of JY flesh were the highest at 65.59 mg/g and 13%, respectively. The VC content of JB flesh and lotus plumule is the highest at 41.56 mg/g and 204.29 mg/g, respectively. JB flesh has the lowest soluble sugar content, at 17.87 mg/g, while HB's lotus plumule and flesh have the highest content, at 33.67 mg/g and 29.62 mg/g, respectively. There was no significant difference in the crude fat content of the flesh and lotus plumule among the eight cultivars. TK flesh and lotus plumule have the highest amylose content, at 23.67 mg/g and 76.81 mg/g, respectively. Among them, the total starch content of JB (476.17 mg/g) was relatively high, whereas its amylose content was only 26.09 mg/g. Lower amylose content makes it less prone to aging. The total phenolic and flavonoid contents of the JY lotus plumule were the highest, at 18.64 and 21.04 mg/g, respectively. The alkaloid content of CS, HH, and JY was relatively high at 20.01, 19.29, and 18.68 mg/g, respectively. These can provide a consultation for the estimation and processing of the nutritional quality of different lotus seeds.

Recent Advances in the Research on Luotonins A, B, and E.

This digest review summarises the most recent progress in the study on luotonins A, B and E. The literature covered in this overview spans from January 2012 to April 2024 and presents synthetic methodologies for the assembly of the quinolinopyrrolo-quinazoline scaffold, the structural motifs present in luotonins A, B, and E, and the evaluation of the biological activities of their derivatives and structural analogues.

The Mediterranean Species Calendula officinalis and Foeniculum vulgare as Valuable Source of Bioactive Compounds.

Research studies on plant secondary metabolites have increased over the last decades as a consequence of the growing consumer demand for natural products in pharmaceutics and therapeutics, as well as in perfumery and cosmetics. In this perspective, many Mediterranean plant species could be an appreciated source of bioactive compounds with pharmacological and health-promoting properties, including antioxidant, antimicrobial, antiviral, anti-inflammatory, and antitumor ones. Calendula officinalis and Foeniculum vulgare are commercially important plants of the Mediterranean flora, with great therapeutic use in the treatment of many disorders since ancient times, and are now listed in several world pharmacopoeias and drug agencies. The present review offers an overview of the main phytochemicals, phenols, terpenes, and alkaloids, biosynthesized in C. officinalis and F. vulgare, both species endemic to the Mediterranean region. Further, all current knowledge and scientific data on taxonomic classification, botanical description, traditional uses, pharmacological studies, and potential toxicity of both species were reported. The principal aim of this review is to point out the prospective use of C. officinalis and F. vulgare as valuable reservoirs of beneficial plant-derived products with interesting biological properties, also providing suggestions and future challenges for the full exploitation of these two Mediterranean species for human life improvement.

Cheminformatics-Guided Exploration of Synthetic Marine Natural Product-Inspired Brominated Indole-3-Glyoxylamides and Their Potentials for Drug Discovery.

Marine natural products (MNPs) continue to be tested primarily in cellular toxicity assays, both mammalian and microbial, despite most being inactive at concentrations relevant to drug discovery. These MNPs become missed opportunities and represent a wasteful use of precious bioresources. The use of cheminformatics aligned with published bioactivity data can provide insights to direct the choice of bioassays for the evaluation of new MNPs. Cheminformatics analysis of MNPs found in MarinLit (n = 39,730) up to the end of 2023 highlighted indol-3-yl-glyoxylamides (IGAs, n = 24) as a group of MNPs with no reported bioactivities. However, a recent review of synthetic IGAs highlighted these scaffolds as privileged structures with several compounds under clinical evaluation. Herein, we report the synthesis of a library of 32 MNP-inspired brominated IGAs (25-56) using a simple one-pot, multistep method affording access to these diverse chemical scaffolds. Directed by a meta-analysis of the biological activities reported for marine indole alkaloids (MIAs) and synthetic IGAs, the brominated IGAs 25-56 were examined for their potential bioactivities against the Parkinson's Disease amyloid protein alpha synuclein (α-syn), antiplasmodial activities against chloroquine-resistant (3D7) and sensitive (Dd2) parasite strains of Plasmodium falciparum, and inhibition of mammalian (chymotrypsin and elastase) and viral (SARS-CoV-2 3CLpro) proteases. All of the synthetic IGAs tested exhibited binding affinity to the amyloid protein α-syn, while some showed inhibitory activities against P. falciparum, and the proteases, SARS-CoV-2 3CLpro, and chymotrypsin. The cellular safety of the IGAs was examined against cancerous and non-cancerous human cell lines, with all of the compounds tested inactive, thereby validating cheminformatics and meta-analyses results. The findings presented herein expand our knowledge of marine IGA bioactive chemical space and advocate expanding the scope of biological assays routinely used to investigate NP bioactivities, specifically those more suitable for non-toxic compounds. By integrating cheminformatics tools and functional assays into NP biological testing workflows, we can aim to enhance the potential of NPs and their scaffolds for future drug discovery and development.

Natural Alkaloids in Cancer Therapy: Berberine, Sanguinarine and Chelerythrine against Colorectal and Gastric Cancer.

The rising incidence of colorectal cancer (CRC) and gastric cancer (GC) worldwide, coupled with the limited effectiveness of current chemotherapeutic agents, has prioritized the search for new therapeutic options. Natural substances, which often exhibit cytostatic properties, hold significant promise in this area. This review evaluates the anticancer properties of three natural alkaloids-berberine, sanguinarine, and chelerythrine-against CRC and GC. In vivo and in vitro studies have demonstrated that these substances can reduce tumor volume and inhibit the epithelial-mesenchymal transition (EMT) of tumors. At the molecular level, these alkaloids disrupt key signaling pathways in cancer cells, including mTOR, MAPK, EGFR, PI3K/AKT, and NF-κB. Additionally, they exhibit immunomodulatory effects, leading to the induction of programmed cell death through both apoptosis and autophagy. Notably, these substances have shown synergistic effects when combined with classical cytostatic agents such as cyclophosphamide, 5-fluorouracil, cetuximab, and erlotinib. Furthermore, berberine has demonstrated the ability to restore sensitivity in individuals originally resistant to cisplatin GC. Given these findings, natural compounds emerge as a promising option in the chemotherapy of malignant gastrointestinal tumors, particularly in cases with limited treatment options. However, more research is necessary to fully understand their therapeutic potential.

Synthesis, biological activities and mechanistic studies of C20-ketone pachysandra alkaloids as anti-hepatocellular carcinoma agents.

The pachysandra alkaloids found in Sarcococca ruscifolia demonstrate notable anti-hepatocellular carcinoma activity. Despite their efficacy, the structural diversity of these compounds remains limited, and their precise antitumor mechanism is still unclear. In pursuit of identifying novel lead compounds with high efficacy and low toxicity for combating hepatocellular carcinoma, twenty-three compounds of C20-ketone pachysandra alkaloid derivatives were designed and synthesized by using 3-dimethylamine pachysandra alkaloids as scaffolds. Subsequent in vitro anticancer activity experiments showed that synthetic pachysandra alkaloids had a stronger effect on HepG2 cells than did their natural counterparts, with low toxicity and high selectivity. The most potent derivative, 6k, had an IC50 value of 0.75 µM, demonstrating 25.7-fold greater anticancer activity than sarcovagine D against HepG2 cells. Through network pharmacology and molecular docking analysis, it was revealed that synthetic pachysandra alkaloids may exert their effects by inhibiting the JAK2/STAT3 pathway, thereby preventing the proliferation of liver cancer cells. Further research through scratch tests, immunofluorescence experiments, and Western blot analysis revealed that compound 6k effectively inhibited the migration of HepG2 cells and induced mitochondria-mediated intrinsic apoptosis of HepG2 cells by regulating the JAK2/STAT3 signaling pathway. The aforementioned results indicate that compound 6k could be developed as a potential candidate for the treatment of hepatocellular carcinoma.

The Chemical Ecology of Plant Natural Products.

Plants are excellent chemists with an impressive capability of biosynthesizing a large variety of natural products (also known as secondary or specialized metabolites) to resist various biotic and abiotic stresses. In this chapter, 989 plant natural products and their ecological functions in plant-herbivore, plant-microorganism, and plant-plant interactions are reviewed. These compounds include terpenoids, phenols, alkaloids, and other structural types. Terpenoids usually provide direct or indirect defense functions for plants, while phenolic compounds play important roles in regulating the interactions between plants and other organisms. Alkaloids are frequently toxic to herbivores and microorganisms, and can therefore also provide defense functions. The information presented should provide the basis for in-depth research of these plant natural products and their natural functions, and also for their further development and utilization.

Adaptation of Ustilago maydis to phenolic and alkaloid responsive metabolites in maize B73.

The adaptation of pathogenic fungi to plant-specialized metabolites is necessary for their survival and reproduction. The biotrophic fungus Ustilago maydis can cause maize smut and produce tumors in maize (Zea mays), resulting in reduced maize yield and significant economic losses. Qualitative analysis using UPLC-MS/MS revealed that the infection of maize variety B73 with U. maydis resulted in increased levels of phytohormones, phenolics, and alkaloids in maize seedling tissues. However, correlation analysis showed that nearly all compounds in the mechanical damage group were significantly negatively correlated with the shoot growth indexes of maize B73. The correlation coefficients of 2-hydroxy-7-methoxy-1,4-benzoxazin-3-one (HMBOA) and maize B73 shoot length and shoot weight were r = -0.56 (p < 0.01) and r = -0.75 (p < 0.001), respectively. In the inoculation group, these correlations weakened, with the correlation coefficients between HMBOA and maize B73 shoot length and shoot weight being r = 0.02 and r = -0.1, respectively. The correlation coefficients between 6-methoxy-2-benzoxazolinone (MBOA) and the shoot weight were r = -0.73 (p < 0.001) and r = -0.15 in the mechanical damage group and inoculation group, respectively. These findings suggest that increased concentrations of these compounds are more positively associated with mechanical damage than with U. maydis infection. At high concentrations, most of these compounds had an inhibitory effect on U. maydis. This study investigated the ability of U. maydis to regulate various compounds, including phytohormones, phenolic acids, and alkaloids in maize B73, providing evidence that U. maydis has adapted to the specialized metabolites produced by maize B73.