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ABSTRACT Two new alkaloids, named migenomycin I (1) and II (2), along with nine known compounds (3–11), were isolated from the fungus Rhizopus oryzae from Atractylodes macrocephala Koidz. The structures of compounds 1 and 2 were determined by spectroscopic methods (MS, NMR, and CD). All compounds were isolated from Rhizopus oryzae for the first time. In addition, the antitumor activities of compounds 1 and 2 and the hypoglycemic activities of most compounds were evaluated. [ABSTRACT FROM AUTHOR]

Quinine is a historically important natural product containing a methoxy group that has been assumed to be incorporated at a late pathway stage. Here we show that the methoxy group in quinine and related alkaloids is introduced onto the starting substrate tryptamine. Feeding studies definitively show that 5‐methoxytryptamine is utilized as a quinine biosynthetic intermediate in planta. We discover the biosynthetic genes that encode the responsible oxidase and methyltransferase, and we use these genes to reconstitute the early steps of the alkaloid biosynthetic pathway in Nicotiana benthamiana to produce a mixture of methoxylated and non‐methoxylated alkaloid intermediates. Importantly, we show that the co‐occurrence of both tryptamine and 5‐methoxytryptamine substrates, along with the substrate promiscuity of downstream pathway enzymes, enable parallel formation of both methoxylated and non‐methoxylated alkaloids. [ABSTRACT FROM AUTHOR]

ABSTRACT Understanding the molecular signaling pathways of colorectal cancer (CRC) can be accepted as the first step in treatment strategy. Permanent mTOR signaling activation stimulates the CRC process via various biological processes. It supplies the survival of CRC stem cells, tumorigenesis, morbidity, and decreased response to drugs in CRC pathogenesis. Therefore, inhibition of the mTOR signaling by numerous bioactive components may be effective against CRC. The study aims to discuss the therapeutic capacity of various polyphenols, terpenoids, and alkaloids on CRC via the PI3K/Akt/mTOR pathway. The potential molecular effects of bioactive compounds on the mTOR pathway's upstream and downstream targets are examined. Each bioactive component causes various physiological processes, such as triggering free radical production, disruption of mitochondrial membrane potential, cell cycle arrest, inhibition of CRC stem cell migration, and suppression of glycolysis through mTOR signaling inhibition. As a result, carcinogenesis is inhibited by inducing apoptosis and autophagy. However, it should be noted that studies are primarily in vitro dose‐dependent treatment researchers. This study raises awareness about the role of phenolic compounds in treating CRC, contributing to their future use as anticancer agents. These bioactive compounds have the potential to be developed into food supplementation to prevent and treat various cancer types including CRC. This review has the potential to lead to further development of clinical studies. In the future, mTOR inhibition by applying several bioactive agents using advanced drug delivery systems may contribute to CRC treatment with 3D cell culture and in vivo clinical studies. [ABSTRACT FROM AUTHOR]

A concise total synthesis of Cuscutamine was achieved involving a diastereoselective intramolecular acyl iminium ion mediated Pictet‐Spengler reaction. This synthetic strategy provided a direct route to (11S, 13R)‐Cuscutamine (2) in only 3 steps with an overall yield of 56 % and an enantiomeric ratio of 88 %. The diastereoselectivity of the reaction is consistent with previous studies that proceed via more highly puckered transition states and the present results thus reveal the importance of the steric contributions to the observed diastereoselectivity. [ABSTRACT FROM AUTHOR]

Mitragyna speciosa is a perennial plant native to Asia, well known for its psychoactive properties. Its major alkaloid mitragynine is known to have sedative and euphoric effects. Hence, the plant has been a subject of abuse, leading to addiction, necessitating efficient analytical methods to detect its psychoactive constituents. However, current chromatography‐based methods for detecting the alkaloids are time consuming and costly. Quantitative nuclear magnetic resonance (qNMR) spectroscopy emerges as a promising alternative due to its nondestructive nature, structural insights, and short analysis time. Hence, a rapid and precise qNMR method was developed to quantify selected major psychoactive alkaloids in various parts of M. speciosa. Mitragynine, specioliatine, and speciogynine were quantified in relation to the integral value of the ‐OCH3 groups of the alkaloids and the internal standard 1,4‐dinitrobenzene. The precision and reproducibility of the method gave a relative standard deviation (RSD) of 2%, demonstrating the reliability of the method. In addition, the method showed excellent specificity, sensitivity, high linearity range (R2 = 0.999), and limits of detection (LOD) and quantification (LOQ) values. The analysis revealed that the red‐veined M. speciosa leaves contained higher levels of mitragynine (32.34 mg/g), specioliatine (16.84 mg/g) and speciogynine (7.69 mg/g) compared to the green‐veined leaves, stem bark, or fruits. [ABSTRACT FROM AUTHOR]

Daphenylline, a structurally unique triterpenoid Daphniphyllum alkaloid, has attracted considerable attention from the synthetic community since its isolation. Herein, we delineate an enantioselective total synthesis of (−)‐daphenylline, which is based on a gold‐catalyzed dearomatization reaction of β‐methoxynaphthalene. Other features include installation of the initial chiral stereocenter via an enantioselective rhodium‐catalyzed hydrogenation of an alkylidene‐indane derivative; construction of the other vital stereocenter by organocatalytic asymmetric Mukaiyama–Michael reaction of a structurally complex benzofused cyclohexanone; and a tandem reductive amination/amidation double cyclization reaction to assemble the distinctive azapolycyclic cage‐like architecture. [ABSTRACT FROM AUTHOR]

The selective borylation of specific C−H bonds in organic synthesis remains a formidable challenge. In this study, we present a novel spirobipyridine ligand that features a binaphthyl backbone. This ligand facilitates the iridium‐catalyzed selective C−H borylation of benzene derivatives. The ligand is designed with "side‐arm‐wall" substituents that allow vicinal di‐ or multi‐substituted benzene derivatives to approach metal center and effectively block other reactive sites by non‐covalent interactions with substrates. The effectiveness of this strategy is demonstrated by the successful selective distal C−H activation of various alkaloids and its broad compatibility with functional groups. [ABSTRACT FROM AUTHOR]

Reported herein is the first total synthesis of the poly‐pseudoindoxyl natural product baphicacanthcusine A. The synthesis leverages the oxidative rearrangement of indoles to pseudoindoxyls to install vicinal pseudoindoxyl heterocycles in a diastereoselective manner. Key steps include an acid‐mediated cyclization/indole transposition, two diastereoselective oxidative ring contractions, and a site‐selective C−H oxygenation. The synthesis of the oxidation precursors was guided by recognition of an element of hidden symmetry. This work provides a foundation for the chemical synthesis of other poly‐pseudoindoxyl alkaloids. [ABSTRACT FROM AUTHOR]

An unprecedented dyotropic rearrangement of β‐lactams has been developed, which provides an enabling tool for the synthesis of structurally diverse γ‐butyrolactams. Unlike the well‐established dyotropic rearrangements of β‐lactones, the present reaction probably proceeds through a dual‐activation mode, and thus displays unusual reactivity and chemoselectivity. The combined computational and experimental results suggest that the dyotropic rearrangement of β‐lactams may proceed through different mechanisms depending on the nature of migrating groups (H, alkyl, or aryl). Hinging on a chemoselective H‐migration dyotropic rearrangement of β‐lactams, we have completed the divergent synthesis of tricyclic marine alkaloids (−)‐lepadiformine A, (+)‐cylindricine C, and (−)‐fasicularin within 11–12 longest linear steps. [ABSTRACT FROM AUTHOR]

Maize originated in southern Mexico and various hybrid varieties have been bred during domestication. All maize tissues are rich in specialized plant metabolites (SPMs), which allow the plants to resist the stresses of herbivores and pathogens or environmental factors. To date, a total of 95 terpenoids, 91 phenolics, 31 alkaloids, and 6 other types of compounds have been identified from maize. Certain volatile sesquiterpenes released by maize plants attract the natural enemies of maize herbivores and provide an indirect defensive function. Kauralexins and dolabralexins are the most abundant diterpenoids in maize and are known to regulate and stabilize the maize rhizosphere microbial community. Benzoxazinoids and benzoxazolinones are the main alkaloids in maize and are found in maize plants at the highest concentrations at the seedling stage. These two kinds of alkaloids directly resist herbivory and pathogenic infection. Phenolics enhance the cross‐links between maize cell walls. Meanwhile, SPMs also regulate plant–plant relationships. In conclusion, SPMs in maize show a large diversity of chemical structures and broad‐spectrum biological activities. We use these to provide ideas and information to enable the improvement of maize resistances through breeding and to promote the rapid development of the maize industry. [ABSTRACT FROM AUTHOR]

ABSTRACT Based on 4‐([2,2′:6′,2″‐terpyridin]‐4′‐yl) benzoic acid ligand (Htpba), a fluorescent lanthanide coordination polymer was successfully synthesized, namely, [Eu (tpba)3]n (1). The single‐crystal diffraction analysis shows that Eu3+ ions in complex 1 are alternately connected with tpba3− ligands to form a one‐dimensional chain structure, which further constitutes a three‐dimensional supramolecular architecture through the π···π interactions. Complex 1 demonstrated excellent stability of thermogravimetry; and displayed good fluorescence intensity in aqueous solution with a wide pH range. In this work, complex 1 was used as a fluorescence sensor for the detection of jatrorrhizine molecule (JAT). It was found that complex 1 had high sensitivity with the detection limit of 1.02 × 10−8 M, and simultaneously displayed specific selectivity and reutilization for the exploration of JAT molecule. The static quenching, the absorption competition, the electrostatic interactions, and the photo‐induced electron transfer process are responsible for the recognition mechanism of complex 1 with sensing JAT. It is worth mentioning that a fluorescent film based on complex 1 and a light‐emitting diode device coated with the powder of complex 1 were successfully fabricated, which could rapidly recognize JAT molecule with the naked eye further. [ABSTRACT FROM AUTHOR]

A concise and efficient synthesis of the γ‐lactam‐fused azaphenanthrene alkaloid eupolauramine has been achieved. The key feature of the synthesis involves Au(I)‐catalyzed cycloisomerization of N‐naphthyl aminobutynamide intermediate and subsequent intramolecular Ullmann‐type coupling reaction. This study clearly demonstrated the usefulness of coinage metal‐catalyzed cycloisomerization strategy in the construction of architecturally sophisticated pyridine‐fused heterocyclic scaffolds. [ABSTRACT FROM AUTHOR]

Background and Aims: Cytisine (also known as cytisinicline) is a low‐cost partial agonist of nicotinic acetylcholine receptors used to assist tobacco cessation. We aimed to review the effectiveness of cytisine for tobacco cessation and the effects of dose and co‐use of behavioural or other pharmacological interventions on cessation outcomes. Methods: We searched seven databases, Google Scholar, and reference lists of included publications for randomised controlled trials investigating use of cytisine as a tobacco cessation aid. Studies were eligible if participants were ≥15 years old and used tobacco upon study enrolment. We conducted four random effects meta‐analyses and sensitivity analyses with fixed effects models. We used the Cochrane risk‐of‐bias tool for randomised trials version 2 to assess risk of bias in included studies, with adjustments recommended by the Cochrane Tobacco Addiction Group. Results: Participants using cytisine were significantly more likely to quit tobacco than participants who received placebo/no intervention/usual care (risk ratio [RR] = 2.65, 95% confidence interval [CI] = 1.50–4.67, 6 trials, 5194 participants) or nicotine replacement therapy (RR = 1.36, 95% CI = 1.06–1.73, p = 0.0152, 2 trials, 1511 participants). The difference in cessation rates among participants receiving cytisine versus varenicline was not statistically significant (RR = 0.96, 95% CI 0.63–1.45, P = 0.8464, 3 trials, 2508 participants). Two trials examined longer versus shorter treatment duration, finding higher abstinence rates with longer treatment (RR = 1.29, 95% CI = 1.02–1.63, 2 trials, 1009 participants). The differences in the number of adverse events reported by participants who received cytisine versus placebo (RR = 1.19, 95% CI = 0.99–1.41, P = 0.0624; 6 trials; 4578 participants) or cytisine versus varenicline (RR = 1.37, 95% CI = 0.57–3.33, P = 0.4835; 2 trials; 1345 participants) were not statistically significant. Most adverse events were mild (e.g. abnormal dreams, nausea, headaches). Conclusions: Cytisine is an effective aid for tobacco cessation and appears to be more effective for tobacco cessation than placebo, no intervention, usual care and nicotine replacement therapy. [ABSTRACT FROM AUTHOR]

The bisbenzylisoquinoline alkaloids (bisBIAs) have attracted tremendous attention from the synthetic community due to their diverse and intriguing biological activities. Herein, we report the convergent and modular chemoenzymatic syntheses of eight bisBIAs bearing various substitutes and linkages in 5–7 steps. The gram‐scale synthesis of various well‐designed enantiopure benzylisoquinoline monomers was accomplished through an enzymatic stereoselective Pictet–Spengler reaction, followed by regioselective enzymatic methylation or chemical functionalization in a sequential one‐pot process. A modified intermolecular copper‐mediated Ullmann coupling enabled the concise and efficient total synthesis of five different linear bisBIAs with either head‐to‐tail or tail‐to‐tail linkage. A biomimetic oxidative phenol dimerization selectively formed the sterically hindered, electron‐rich diaryl ether bond, and subsequent intramolecular Suzuki–Miyaura domino reaction or Ullmann coupling facilitated the first enantioselective total synthesis of three macrocyclic bisBIAs, including ent‐isogranjine, tetrandrine and O‐methylrepandine. This study highlights the great potential of chemoenzymatic strategies in the total synthesis of diverse bisBIAs and paves the way to further explore the biological functions of these natural products. [ABSTRACT FROM AUTHOR]

Morphine and codeine are essential medicines isolated from the opium poppy, whose biosynthesis is limited by the plant's L‐DOPA decarboxylase activity. In the present study, we use molecular dynamics and hybrid quantum mechanics/ molecular mechanics calculations to clarify the L‐DOPA decarboxylase chemical mechanism of decarboxylation and quinonoid intermediate protonation. In addition, the contribution of residues in the periphery of the active site to the rate‐limiting decarboxylation barrier was determined to guide future experimental mutagenesis aimed at increasing the catalytic activity of the aromatic amino acid decarboxylase enzyme, a fundamental step for the opiumpoppy‐free production of BIAs. Our calculations indicate that the decarboxylation barrier is higher in conformations in which the interaction between Tyr350B and the carboxylate leaving group is formed. Furthermore, the barrier for the protonation of the quinonoid intermediate by Tyr350B is predicted to be lower than the decarboxylation and dependent on His205A protonation by the bulk solvent. Residues Glu171, Asp270, Asp313 and Arg482 were identified as possible candidates for rate‐enhancing mutations of P. somniferum aromatic amino acid decarboxylase. [ABSTRACT FROM AUTHOR]

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, Uskoković, Stork, Jacobsen, Hayashi, Maulide and others are discussed. [ABSTRACT FROM AUTHOR]

Synthesis of poison dart frog indolizidine alkaloids (−)‐209D, (−)‐209B and (−)‐223V were accomplished, with a common tricyclic lactone skeleton as the starting compound, in overall yields of 8.8 %, 5.5 %, and 5.2 %, respectively. The construction of the C7−C8 bond in the synthesis of 209D involves simple ring closure metathesis and hydrogenation reactions. However, in the synthesis of 209B and 223V, the C7−C8 bond and the stereochemistry of C8, is achieved through radical cyclization reactions controlled by allylic 1,3‐strain. Cleavage of the excess carbon on the C5 for all the related intermediates were done by Barton decarboxylation protocol. Reduction of the corresponding indolizidin‐3‐ones by LAH completed the total synthesis of these three target molecules. The quantum mechanics calculations were performed on α‐amidyl carbon radical intermediates to account for the observed diastereomeric ratio (~9 : 1) of the key Barton decarboxylation step. Ultimately, the synthesis of 3‐epi‐(−)‐223AB was accomplished in 51.6 % through the cuprate addition to the activated lactam of a late intermediate in the synthesis of (−)‐167B. [ABSTRACT FROM AUTHOR]

Aconiti Lateralis Radix praeparata (also known as Fuzi in Chinese) has been extensively used in clinic. However, the toxicity issues limit the therapeutic range of Fuzi. Thus, a rapid and sensitive HPLC‐MS/MS method was developed to simultaneously quantify and compare six active/toxic constituents in decocting extracts from four different processed Fuzi products and in rat plasma after oral administration of its decocting extracts. The selectivity, linearity, sensitivity, precisions, accuracy, matrix effects, extraction recoveries, and stability were validated. The comparative analysis of six alkaloids in decocting extracts between the four kinds of Fuzi products were conducted by the validated HPLC‐MS/MS. Principal component analysis (PCA) and orthogonal partial least‐squares discriminate analysis (OPLS‐DA) were adopted to compare the differences of decocting extracts from the different processed Fuzi products. Besides, selecting Heishunpian (HSP) as the representative of the processed Fuzi products, we investigated the pharmacokinetic behaviors of these major alkaloids after oral administration. The developed HPLC‐MS/MS method to simultaneously analyze these aconitine‐type alkaloids in decocting extracts, and its pharmacokinetic behavior after oral administration may pave a way for quality control of Fuzi and monitoring the safety and rationality of clinical prescriptions. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the kynurenine pathway, it is reported that the essential amino acid tryptophan forms nicotinic acid (NA, vitamin B3) in biological systems. This pathway is part of the de novo pathway to perform nicotinamide adenine dinucleotide (NAD+) biosynthesis. Additionally, biosynthesis of NAD+ via the Preiss–Handler pathway involves NA and its analogue nicotinamide, both designated as niacin. Previous attempts were successful in converting myosmine (MYO) by organic synthesis to NA, and the assumption was that the alkaloid MYO, which is taken in from food, can be converted into NA by biological oxidation. RESULT: Incubation of HepG2 cells with MYO yielded NA. Moreover, a significant increase of NAD+ compared with the control has been found. CONCLUSION: Hence, MYO could be assumed to be the hitherto unknown origin of an alternative NA biosynthesis additionally influencing NAD+ biosynthesis positively. This novel MYO pathway may open new perspectives to improve knowledge and relevance of NA and NAD+ biosynthesis and bioactivation in cells and, moreover, in food staples, food, and diet. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Typical approaches to heterocycle construction require significant changes in synthetic strategy even for a change as minor as increasing the ring size. The ability to access multiple heterocyclic scaffolds through a common synthetic approach, simply through trivial modification of one reaction component, would enable facile access to diverse libraries of structural analogues of core scaffolds. Here, we show that urea‐derived ligands effectively promote Pd‐mediated chainwalking processes to enable remote heteroannulation for the rapid construction of six‐ and seven‐membered azaheterocycles under essentially identical reaction conditions. This method demonstrates good functional group tolerance and effectively engages sterically hindered substrates. In addition, this reaction is applicable to target‐oriented synthesis, demonstrated through the formal synthesis of antimalarial alkaloid galipinine. [ABSTRACT FROM AUTHOR]

We describe the first total syntheses of tabernanthine and ibogaline. Entry to these iboga alkaloid natural products is enabled by a thermal coupling of indoles and aziridines to furnish the requisite nosyl tryptamine starting materials. This route features a Friedel‐Crafts type alkylation to form the key indole‐isoquinuclidine C−C bond. Finally, a regio‐ and diastereoselective hydroboration‐oxidation enables C−N bond formation to close the isoquinuclidine ring system and deliver tabernanthine and ibogaline in 10 and 14 % yield respectively. Both syntheses were completed in eight steps. [ABSTRACT FROM AUTHOR]

We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A. These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis. [ABSTRACT FROM AUTHOR]

A trade‐off between growth and defence against biotic stresses is common in plants. Fungal endophytes of the genus Epichloë may relieve this trade‐off in their host grasses since they can simultaneously induce plant growth and produce antiherbivore alkaloids that circumvent the need for host defence. The Epichloë ability to decouple the growth‐defence trade‐off was evaluated by subjecting ryegrass with and without Epichloë endophytes to an exogenous treatment with gibberellin (GA) followed by a challenge with Rhopalosiphum padi aphids. In agreement with the endophyte‐mediated trade‐off decoupling hypothesis, the GA‐derived promotion of plant growth increased the susceptibility to aphids in endophyte‐free plants but did not affect the insect resistance in endophyte‐symbiotic plants. In line with the unaltered insect resistance, the GA treatment did not reduce the concentration of Epichloë‐derived alkaloids. The Epichloë mycelial biomass was transiently increased by the GA treatment but at the expense of hyphal integrity. The response of the phyllosphere bacterial microbiota to both GA treatment and Epichloë was also evaluated. Only Epichloë, and not the GA treatment, altered the composition of the phyllosphere microbiota and the abundance of certain bacterial taxa. Our findings clearly demonstrate that Epichloë does indeed relieve the plant growth‐defence trade‐off. Summary statement: A debate has been raised if fungal endophytes can relieve the plant growth‐defence trade‐off. Epichloë endophytes decoupled the trade‐off: the growth‐mediated penalisation of plant defences was observed in E− but not in E+ plants. The Epichloë production of alkaloids was likely the decoupling mechanism. [ABSTRACT FROM AUTHOR]

Ergot is a fungal disease of many plants but is perhaps most commonly associated with domesticated grasses or cereals, such as rye, wheat, barley, oat, sorghum, millet, maize and rice. Ergot is of historical significance, having been reported for several millennia, but is also of concern in modern agricultural production systems. Caused by many different species within the genus Claviceps, the fungi cause the production of sclerotia, which are typically dark in colour, in place of healthy grain. The sclerotia contain toxins that can make the grain unsafe for consumption by humans or livestock. Ergot can be managed both preharvest as well as postharvest to minimize the presence of sclerotia and their associated toxins in food and feed systems. In this review, we provide a detailed update on our current knowledge of ergot on cereals, with a focus on recent advances in our understanding of fungal toxins and their regulation, pathogen biology and disease management. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH), for which there are currently no effective preventive or treatment methods, has a very high fatality rate. Statins, such as atorvastatin (ATV), are the first‐line drugs for regulating blood lipids and treating hyperlipidemia‐related cardiovascular diseases. However, ATV‐associated ICH has been reported, although its incidence is rare. In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV‐induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 μM) and demonstrated the effects of BBR (10, 50, and 100 μM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish. BBR was found to reduce brain inflammation and locomotion injury in ICH‐zebrafish. Mechanism research showed that ATV increased the levels of VE‐cadherin and occludin proteins but disturbed their localization at the cell membrane by abnormal phosphorylation, which decreased the number of intercellular junctions between vascular endothelial cells (VECs), disrupting the integrity of vascular walls. BBR reversed the effects of ATV by promoting autophagic degradation of phosphorylated VE‐cadherin and occludin in ATV‐induced VECs examined by co‐immunoprecipitation (co‐IP). These findings provide crucial insights into understanding the BBR mechanisms involved in the maintenance of vascular integrity and in mitigating adverse reactions to ATV. This study investigated the effect of berberine on atorvastatin‐induced cerebral hemorrhage in zebrafish. Our results indicate that BBR enhances the survival rate of zebrafish with brain hemorrhage, reduces hemorrhage and inflammation, and improves the locomotion function of ICH‐zebrafish by stabilizing vascular integrity. In vitro experiments using HUVEC cells show that BBR counteracts the adverse effects of ATV on endothelial cell connections by promoting the autophagic degradation of intracellularly phosphorylated connexins. These findings suggest the potential of BBR as a treatment for hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Background and Objective: Periodontitis is intimately associated with the development of various systemic diseases, among which type 2 diabetes mellitus (T2DM) has a bidirectional relationship with the pathogenesis of periodontitis. The objective of the present work was to investigate the role of berberine (BBR) in periodontitis with T2DM and related mechanisms. Methods: The mRNA expression of macrophage polarization‐related factors in the microenvironment of periodontal inflammation was detected using real‐time quantitative PCR (RT‐qPCR). The experimental periodontitis model was constructed in wild‐type (WT) and T2DM (db/db) mice, which were administered BBR after 7 days of modeling. Alveolar bone loss (ABL) in each group of mice was measured utilizing micro‐computed tomography images. RT‐qPCR was performed to analyze the levels of macrophage polarization‐related factors in mouse gingiva. Lastly, using western blotting and RT‐qPCR, the signaling pathway of BBR affecting macrophage polarization in the microenvironment of periodontitis was explored. Results: BBR inhibited M1 polarization and stimulated M2 polarization in the periodontitis microenvironment. BBR decreased ABL in the WT and T2DM periodontitis models. And BBR reduced the production of proinflammatory cytokines and increased anti‐inflammatory cytokine expression in the gingiva of WT and T2DM model mice. Ultimately, BBR mediates its anti‐inflammatory effects on periodontitis through inhibition of the NF‐κB pathway. Conclusions: BBR had a therapeutic effect on T2DM‐associated periodontitis via inhibiting the NF‐κB pathway to affect macrophage polarization, which may have implications for the new pharmacological treatment of T2DM‐associated periodontitis. [ABSTRACT FROM AUTHOR]

The Daphniphyllum alkaloids represent a particularly diverse class of complex diterpene alkaloids, which are characterized by their enormous structural diversity. The daphnicyclidins, a subgroup of these alkaloids, stand out due to their unique pentafulvene structural motif. This review article gives an overview of the compounds that have been isolated so far and can be assigned to this subgroup. Furthermore, all synthesis approaches and total syntheses published to date are presented. [ABSTRACT FROM AUTHOR]

Differential expression of genes is key to mediating developmental and stress‐related plant responses. Here, we addressed the regulation of plant metabolic responses to biotic stress and the developmental variation of defense‐related genes in four species of the genus Datura with variable patterns of metabolite accumulation and development. We combine transcriptome profiling with phylogenomic techniques to analyze gene expression and coexpression in plants subjected to damage by a specialist folivore insect. We found (1) common overall gene expression in species of similar chemical profiles, (2) species‐specific responses of proteins involved in specialized metabolism, characterized by constant levels of gene expression coupled with transcriptional rearrangement, and (3) induction of transcriptional rearrangement of major terpene and tropane alkaloid genes upon herbivory. Our results indicate differential modulation of terpene and tropane metabolism linked to jasmonate signaling and specific transcription factors to regulate developmental variation and stress programs, and suggest plastic adaptive responses to cope with herbivory. The transcriptional profiles of specialized metabolism shown here reveal complex genetic control of plant metabolism and contribute to understanding the molecular basis of adaptations and the physiological variation of significant ecological traits. [ABSTRACT FROM AUTHOR]

Inverse hydride shuttle catalysis provides a multicomponent platform for the highly efficient synthesis of alkaloid frameworks with exquisite diastereoselectivity. However, a number of limitations hinder this method, primarily the strict requirement for highly electron‐deficient acceptors. Herein, we present a general Lewis acid‐driven approach to address this constraint, and have developed two broad strategies enabling the modular synthesis of complex azabicycles that were entirely unattainable using the previous method. The enhanced synthetic flexibility facilitates a streamlined asymmetric cyclization, leading to a concise total synthesis of the alkaloid (−)‐tashiromine. [ABSTRACT FROM AUTHOR]

Summary: Daphniphyllum macropodum produces alkaloids that are structurally complex with polycyclic, stereochemically rich carbon skeletons. Understanding how these compounds are formed by the plant may enable exploration of their biological function and bioactivities.We employed multiple metabolomics techniques, including a workflow to annotate compounds in the absence of standards, to compare alkaloid content across plants and tissues.Different alkaloid structural types were found to have distinct distributions between genotypes, between tissues and within tissues. Alkaloid structural types also showed different isotope labelling enrichments that matched their biosynthetic relationships.The work suggests that mevalonate derived 30‐carbon alkaloids are formed in the phloem region before their conversion to 22‐carbon alkaloids which accumulate in the epidermis. This sets the stage for further investigation into the biosynthetic pathway. [ABSTRACT FROM AUTHOR]

Mitragyna speciosa, commonly known as kratom, is a narcotic plant that is used for its unique mood‐enhancing and pain‐relieving effects. It is marketed throughout the United States as a 'legal high' and has gained popularity as an alternative to opioids. However, kratom's increasing involvement in accidental overdoses, especially among polydrug users, has prompted warnings from the Drug Enforcement Agency (DEA) and the Food and Drug Administration (FDA). Despite these warnings, kratom remains legal federally, although it is banned in six states. This legal disparity complicates monitoring and enforcement efforts in states where kratom is illegal. Common forensic techniques using morphology or chemical analysis are beneficial in some instances but are not useful in source attribution because most seized kratom is powdered and the alkaloid content of samples can vary within products, making sourcing unreliable. This study focused on developing a DNA barcoding method to access sequence variation in commercial kratom products. It evaluated the utility of one nuclear barcode region (ITS) and three chloroplast barcode regions (matK, rbcL, and trnH‐psbA) in assessing sequence variation across commercially available kratom products. Novel polymorphisms were discovered, and the ITS region showed the greatest variation between samples. Among the 15 kratom products tested, only two haplotypes were identified across the four barcoding regions. The findings highlight the potential of DNA barcoding as a forensic tool in the traceability and enforcement against illegal kratom distribution. Nonetheless, the limited haplotypic diversity points to a need for further development and expansion of the M. speciosa DNA sequence database. [ABSTRACT FROM AUTHOR]

Introduction: Berberine (BBR) is an alkaloid found in plants. It has neuroprotective, anti‐inflammatory and lipid‐lowering activity. However, the efficacy of treatment with BBR and the mechanisms through which it acts need further study. Aims: This study investigated the therapeutic effects and the mechanism of action of BBR on obesity‐induced insulin resistance in peripheral tissues. Methods: High‐fat‐fed C57BL/6J mice and low‐fat‐fed C57BL/6J mice with miR‐27a overexpression were given BBR intervention (100 mg/kg, po), and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. Palmitic acid‐stimulated hypertrophic adipocyte models were treated with BBR (10 μM). Related indicators and protein expression levels were examined. Results: The AUCs of the OGTT and the ITT in the BBR intervention group were reduced significantly (p < 0.01) (p < 0.05), and the serum biochemical parameters, including FBG, TC, TG and LDL‐C were significantly reduced after BBR intervention. In the in vitro experiments, the triglyceride level and volume of lipid droplets decreased significantly after BBR intervention (p < 0.01) (p < 0.05). Likewise, BBR ameliorates skeletal muscle and pancreas insulin signalling pathways in vivo and in vitro. Discussion: The results showed that BBR significantly ameliorated insulin resistance, reduced body weight and percent body fat and improved serum biochemical parameters in mice. Likewise, BBR reduced triglyceride level and lipid droplet volume in hypertrophic adipocytes, BBR improved obesity effectively. Meanwhile, BBR ameliorated the histomorphology of the pancreas, and skeletal muscle and pancreas insulin related signalling pathways of islets in in vitro and in vivo experiments. The results further demonstrated that BBR inhibited miR‐27a levels in serum from obese mice and supernatant of hypertrophic adipocytes. miR‐27a overexpression in low‐fat fed mice indicated that miR‐27a caused insulin resistance, and BBR intervention significantly improved the miR‐27a induced insulin resistance status. Conclusion: This study demonstrates the important role of BBR in obesity‐induced peripheral insulin resistance and suggest that the mechanism of its effect may be inhibition of miR‐27a secretion. [ABSTRACT FROM AUTHOR]

The two‐step preconcentration technique consisting of large‐volume sample stacking (LVSS) and micelle to solvent stacking (MSS) in cyclodextrin‐modified electrokinetic chromatography (CDEKC) was developed for the analysis of five cationic alkaloids in complex Chinese herbal prescriptions. Relevant parameters affecting separation and stacking performance were optimized separately. Under the optimal LVSS–MSS–CDEKC conditions, less analysis time and organic solvent were required, and the enhancement factors of analytes ranged from 12 to 15 compared with the normal CDEKC separation mode. Further, all validation results demonstrated good applicability and multiple alkaloids (epiberberine, dehydrocorydaline, jatrorrhizine, coptisine and berberine) in Yangxinshi tablet (YXST) have been simultaneously determined. This approach presents powerful potential for the determination of multiple components in complex preparations of Chinese medicine. [ABSTRACT FROM AUTHOR]

BACKGROUND: Wood ants are promising biocontrol agents in fruit plantations because they prey on pest insects and inhibit plant diseases. However, these ants also attend plant‐feeding homopterans to harvest their honeydew secretions, thereby increasing their numbers. This problem can be solved by offering ants alternative sugar sources that are more attractive than honeydew. From natural interactions, it is known that some species manipulate mutualistic partners toward loyalty by adding alkaloids to the food they offer their mutualists. Inspired by this, the addition of alkaloids might be used to make ants loyal to artificial sugar feeders and thus used to reduce populations of ant‐farmed homopterans in ant‐mediated biological control. We aimed to explore whether wood ants (Formica polyctena) would develop a taste preference for morphine‐containing sugar solutions in two‐choice laboratory tests. RESULTS: After having fed on a morphine/sugar solution for 1 week, ants showed a significant preference for morphine solutions compared with equal concentration sugar solutions without morphine. Furthermore, ants lost this preference after 6–9 days on a morphine‐free diet. CONCLUSION: The results show that wood ants react to morphine in their food, enabling chemical manipulation of their behavior, most likely through a taste preference. Thus, ants are susceptible to manipulation by mutualistic partners in natural interactions and furthermore may be manipulated artificially in biocontrol programs to avoid ant‐mediated build‐up of homopteran populations. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

There are many indole alkaloids that contain diverse functional groups attached to the benzene ring on the indole core. Promising biological activities of these alkaloids have been reported. Herein, we report the indole C5‐selective bromination of indolo[2,3‐a]quinolizidine alkaloids by adding nearly equimolar amounts of Br3 ⋅ PyH and HCl in MeOH. The resulting reaction plausibly proceeds through an indoline intermediate by the nucleophilic addition of MeOH to the C3‐brominated indolenine intermediate. Data support the intermediacy of a C3‐, C5‐dibrominated indolenine intermediate as a brominating agent. These conditions demonstrate excellent selectivity for indole C5 bromination of natural products and their derivatives. Thus, these simple, mild, and metal‐free conditions allow for selective, late‐stage bromination followed by further chemical modifications. The utility of the brominated product prepared from naturally occurring yohimbine was demonstrated through various derivatizations, including a bioinspired heterodimerization reaction. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: An asymmetric synthesis of dihydrospirotryprostatin B was achieved in 15 steps (8 purifications) from L‐tryptophan. The main feature of our synthetic strategy is the efficient construction of spirocyclic oxindole intermediate containing a chiral quaternary carbon center, involving the silica gel‐mediated cyclization of tryptamine‐ynamide and oxidation under neat conditions. [ABSTRACT FROM AUTHOR]

Background: Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood. Methods: Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2H‐tetrazolium bromide (MTT), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase‐like 3 (METTL3), and insulin‐like growth factor‐2 mRNA‐binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)‐qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay. Results: BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR‐treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A‐IGF2BP3‐dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo. Conclusion: BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3‐mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment. [ABSTRACT FROM AUTHOR]

A recent study published in the Journal of Integrative Plant Biology has discovered the enzyme responsible for the biosynthesis of camptothecin, a commonly used anticancer drug. The researchers used chemoproteomics to identify the enzyme, OpCYP716E111, in the camptothecin-producing plant Ophiorrhiza pumila. They found that expressing OpCYP716E111 in Nicotiana benthamiana and yeast led to the production of strictosamide epoxide 2, a precursor to camptothecin. This discovery lays the foundation for synthetic biological synthesis of camptothecin and highlights the potential of chemoproteomics for discovering enzymes involved in natural product biosynthesis. [Extracted from the article]

SUMMARY: Aporphine alkaloids are a large group of natural compounds with extensive pharmaceutical application prospects. The biosynthesis of aporphine alkaloids has been paid attentions in the past decades. Here, we determined the contents of four 1‐benzylisoquinoline alkaloids and five aporphine alkaloids in root, stem, leaf, and flower of Aristolochia contorta Bunge, which belongs to magnoliids. Two CYP80 enzymes were identified and characterized from A. contorta. Both of them catalyze the unusual C‐C phenol coupling reactions and directly form the aporphine alkaloid skeleton. AcCYP80G7 catalyzed the formation of hexacyclic aporphine corytuberine. AcCYP80Q8 catalyzed the formation of pentacyclic proaporphine glaziovine. Kingdom‐wide phylogenetic analysis of the CYP80 family suggested that CYP80 first appeared in Nymphaeales. The functional divergence of hydroxylation and C‐C (or C‐O) phenol coupling preceded the divergence of magnoliids and eudicots. Probable crucial residues of AcCYP80Q8 were selected through sequence alignment and molecular docking. Site‐directed mutagenesis revealed two crucial residues E284 and Y106 for the catalytic reaction. Identification and characterization of two aporphine skeleton‐forming enzymes provide insights into the biosynthesis of aporphine alkaloids. [ABSTRACT FROM AUTHOR]

The morbidity and mortality associated with type 2 diabetes mellitus (T2DM) have grown exponentially over the last 30 years. Together with its associated complications, the mortality rates have increased. One important complication in those living with T2DM is the acceleration of age‐related cognitive decline. T2DM‐induced cognitive impairment seriously affects memory, executive function, and quality of life. However, there is a lack of effective treatment for both diabetes and cognitive decline. Thus, finding novel treatments which are cheap, effective in both diabetes and cognitive impairment, are easily accessible, are needed to reduce impact on patients with diabetes and health‐care systems. Carnosine, a histidine containing dipeptide, plays a protective role in cognitive diseases due to its antioxidant, anti‐inflammation, and anti‐glycation properties, all of which may slow the development of neurodegenerative diseases and ischemic injury. Furthermore, carnosine is also involved in regulating glucose and insulin in diabetes. Herein, we discuss the neuroprotective role of carnosine and its mechanisms in T2DM‐induced cognitive impairment, which may provide a theoretical basis and evidence base to evaluate whether carnosine has therapeutic effects in alleviating cognitive dysfunction in T2DM patients. [ABSTRACT FROM AUTHOR]

We present an Ugi multicomponent approach to explore the chemical space around Aspidosperma‐type monoterpene indole alkaloids. By variation of the isocyanide and carboxylic acid inputs we demonstrate the rapid generation of molecular diversity and the possibility to introduce handles for further modification. The key Ugi three‐component reaction showed full diastereoselectivity towards the cis‐fused ring system, which can be rationalized by DFT calculations that moreover indicate that the reaction proceeds via a Passerini‐type hydrogen bonding mechanism. Several post‐Ugi modifications were also performed, including Pictet‐Spengler cyclization to highly complex nonacyclic natural product hybrid scaffolds. [ABSTRACT FROM AUTHOR]

A Cp*Ir‐catalyzed C−H arylation of 1‐isoquinolinone and 2‐pyridones with N‐2‐pyridyl as a directing group to afford 6‐phenylpyridin‐2(1H)‐ones and 3‐phenylisoquinolin‐1(2H)‐ones by using arylsilanes is described in this paper. This method tolerates a series of functional groups, such as halide, trifluoromethyl, C=C double bond and offers a synthetic approach to the core structure of protoberberine alkaloids. Several experiments on mechanism studies were conducted to reveal the possible process of this Cp*Ir‐catalytic cycle. [ABSTRACT FROM AUTHOR]

β‐Carbolines represent a large class of bioactive natural products, whereby most of these alkaloids bear residues at C1, and occasionally at C3, and only limited examples of 1,4‐disubstituted β‐carbolines are known. In this project we worked out a novel approach to 1,4‐disubstituted β‐carbolines and performed a comprehensive analysis of the scope and limitations of this methodology. The 1,4‐disubstituted β‐carbolines were synthesized via 3‐substituted 2‐acylindoles, for which effective synthesis procedures were developed. Our studies revealed that a broad range of target compounds with electron‐withdrawing substituents at C4 are accessible. Limitations of this method arose from competing CH and NH acidities of precursors. Nevertheless, the work described herein provides a unique approach to highly substituted β‐carbolines. In addition, intermediates from this route opened a novel approach to 1‐substituted β‐carbolines utilizing a chemoselective Mo(CO)6‐catalyzed amide reduction with tetramethyldisiloxane. [ABSTRACT FROM AUTHOR]

We report the discovery and biosynthesis of new piperazine alkaloids‐arizonamides, and their derived compounds‐arizolidines, featuring heterobicyclic and spirocyclic isoquinolone skeletons, respectively. Their biosynthetic pathway involves two crucial non‐heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3‐alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG. [ABSTRACT FROM AUTHOR]

The first total synthesis of dragocins A−C, remarkable natural products containing an unusual C4' oxidized ribose architecture bridged by a polyhydroxylated pyrrolidine, is presented through a route featuring a number of uncommon maneuvers. Several generations towards the target molecules are presented, including the spectacular failure of a key C−H oxidation on a late‐stage intermediate. The final route features rapid, stereocontrolled access to a densely functionalized pyrrolidine and an unprecedented diastereoselective oxidative electrochemical cyclization to forge the hallmark 9‐membered ring. Preliminary studies suggest this electrochemical oxidation protocol is generally useful. [ABSTRACT FROM AUTHOR]

This contribution reports extensive studies on structure–property correlations of two isoelectronic betaine metamers (positional isomers). These zwitterions differ from each other with respect to bonding modes of pyridinium acceptors (Reichardt's mode: through N‐atom versus Brooker's mode: through C‐atom) with the p‐phenylene bridged phenolate donors. Various quantum chemical methodologies are used in this investigation, with time‐dependent (TD) and coupled perturbed (CPHF) theories for computations of many molecular response properties. Analysis of first hyperpolarizabilities (β) indicates that Reichardt's metamer (ωB97xD: β = 349.5 × 10−30 esu) is more efficient chromophore (~5‐fold enhanced) than Brooker's metamer (ωB97xD: β = 69.4 × 10−30 esu). The gyratory abilities of the bridge junctions resulted in a cohort of metastable conformations, in the rotational potential energy surfaces (PES) of the two metamers. Moreover, rotational PES establishes that intermediary torsions are suitable for optimal chromophore design strategies (Reichardt's metamer: β = 956.5 × 10−30 esu, and Brooker's metamer: β = 1104.7 × 10−30 esu), Thus suitable conformational manipulations, can be used to obtain more efficient zwitterionic molecular chromophores. Compared unbridged prototype molecules, p‐phenylene bridged zwitterions showed ~6–9 times enhanced values of β. In addition, important aspects of suitable chromophore design strategies are suggested. [ABSTRACT FROM AUTHOR]

Pressure ulcer (PU) is a worldwide problem that is difficult to address because of the related inflammatory response, local hypoxia, and repeated ischaemia/reperfusion, causing great suffering and financial burden to patients. Traditional Chinese medicine turtle plate powder can treat skin trauma, but its composition is complex and inconvenient to use. Here, we combined cholesterol myristate (S8) with berberine (BBR), with anti‐inflammatory and antibacterial effects, as a drug and used hydroxypropyl methylcellulose and polyvinylpyrrolidone K30 as carriers to construct a novel film‐forming polymeric solution (S8 + BBR FFPS), comprehensively study its reparative effect on PU and explore the potential mechanism in rat PU models. The results showed that S8 + BBR FFPS inhibits excessive inflammatory response, promotes re‐epithelialization, and promotes hair follicle growth during the healing process of PU, which may be related to the activation of the Wnt/β‐catenin signalling pathway by S8 + BBR FFPS to mediate hair follicle stem cell proliferation and maintain skin homeostasis. Therefore, S8 + BBR FFPS may be a potential candidate for the treatment of chronic skin injury, and its association with the Wnt/β‐catenin signalling pathway may provide new ideas to guide the design of biomaterial‐based wound dressings for chronic wound repair. [ABSTRACT FROM AUTHOR]

Hormone-sensitive lipase (HSL) is active throughout the brain and its genetic ablation impacts brain function. Its activity in the brain was proposed to regulate bioactive lipid availability, namely eicosanoids that are inflammatory mediators and regulate cerebral blood flow (CBF). We aimed at testing whether HSL deletion increases susceptibility to neuroinflammation and impaired brain perfusion upon diet-induced obesity. HSL−/−, HSL+/−, and HSL+/+ mice of either sex were fed high-fat diet (HFD) or control diet for 8 weeks, and then assessed in behavior tests (object recognition, open field, and elevated plus maze), metabolic tests (insulin and glucose tolerance tests and indirect calorimetry in metabolic cages), and CBF determination by arterial spin labeling (ASL) magnetic resonance imaging (MRI). Immunofluorescence microscopy was used to determine coverage of blood vessels, and morphology of astrocytes and microglia in brain slices. HSL deletion reduced CBF, most prominently in cortex and hippocampus, while HFD feeding only lowered CBF in the hippocampus of wild-type mice. CBF was positively correlated with lectin-stained vessel density. HSL deletion did not exacerbate HFD-induced microgliosis in the hippocampus and hypothalamus. HSL−/− mice showed preserved memory performance when compared to wild-type mice, and HSL deletion did not significantly aggravate HFD-induced memory impairment in object recognition tests. In contrast, HSL deletion conferred protection against HFD-induced obesity, glucose intolerance, and insulin resistance. Altogether, this study points to distinct roles of HSL in periphery and brain during diet-induced obesity. While HSL−/− mice were protected against metabolic syndrome development, HSL deletion reduced brain perfusion without leading to aggravated HFD-induced neuroinflammation and memory dysfunction. [ABSTRACT FROM AUTHOR]

Plants produce an array of defensive compounds with toxic or deterrent effects on insect herbivores. Pollen can contain relatively high concentrations of such defense compounds, but the causes and consequences of this enigmatic phenomenon remain mostly unknown. These compounds could potentially protect pollen against antagonists but could also reduce flower attractiveness to pollinators. We combined field observations of the pollen‐rewarding Lupinus argenteus with chemical analysis and laboratory assays to test three hypotheses for the presence of pollen defense compounds: (1) these compounds are the result of spillover from adjacent tissues, (2) they protect against pollen thieves, and (3) they act as antimicrobial compounds. We also tested whether pollen defense compounds affect pollinator behavior. We found a positive relationship between alkaloid concentrations in pollen and petals, supporting the idea that pollen defense compounds partly originate from spillover. However, pollen and petals exhibited quantitatively (but not qualitatively) distinct alkaloid profiles, suggesting that plants can adjust pollen alkaloid composition independently from that of adjacent tissues. We found no relationship between pollen alkaloid concentration and the abundance of pollen thieves in Lupinus flowers. However, pollen alkaloids were negatively associated with bacterial abundance. Finally, plants with more alkaloids in their pollen received more pollinator visits, but these visits were shorter, resulting in no change in the overall number of flowers visited. We propose that pollen defense compounds are partly the result of spillover from other tissues, while they also play an antimicrobial role. The absence of negative effects of these compounds on pollinator visitation likely allows their maintenance in pollen at relatively high concentrations. Taken together, our results suggest that pollen alkaloids affect and are mediated by the interplay of multiple interactions. [ABSTRACT FROM AUTHOR]

This study monitored the growth, biochemical, and developmental responses of Datura seedlings to the cold plasma. The effectiveness of different methods was explored to break seed dormancy. Germinating seeds were exposed to corona discharge plasma for different durations, including 0, 60, 120, 180, and 300 s. A procedure consisting of illumination with a red light (20 min), soaking in water (4°C for 48 h), and removing a part of Testa was the best method for breaking seed dormancy. The plasma treatments of 60, 120, and 180 s improved the plant growth performance, while this trait was declined in response to the plasma treatment of 300 s. The proline concentrations in both root and leaves displayed a linear significant upward trend in response to the plasma treatments. The plasma for 180 s was the most effective method to increase tropane alkaloids. With increasing the exposure time from 60 to 300 s, the leaf soluble phenols were linearly enhanced. The plasma application for 60, 120, and 180 s significantly augmented total protein concentration, while the exposure of seeds for 300 s significantly diminished it. The highest amounts of photosynthetic pigments (chlorophylls and carotenoids) were recorded in the seedlings treated with plasma for 120 and 180 s. The activities of enzymatic antioxidants (catalase and peroxidase) showed a similar upward trend to that of proline. The plasma priming also improved the phenylalanine ammonia‐lyase activity (a secondary metabolism index). Further investigations are needed to optimize plasma parameters and understand the involved mechanisms to maximize its benefits while minimizing potential risks. [ABSTRACT FROM AUTHOR]