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Avocado ripening entails intricate physicochemical transformations resulting in desirable characteristics for consumption; however, its impact on specific metabolites and its cultivar dependence remains largely unexplored. This study employed LC-MS to quantitatively monitor 30 avocado pulp metabolites, including phenolic compounds, amino acids, nucleosides, vitamins, phytohormones, and related compounds, from unripe to overripe stages, in three commercial varieties (Hass, Fuerte, and Bacon). Multivariate statistical analysis revealed significant metabolic variations between cultivars, leading to the identification of potential varietal markers. Most monitored metabolites exhibited dynamic quantitative changes. Although phenolic compounds generally increased during ripening, exceptions such as epicatechin and chlorogenic acid were noted. Amino acids and derivatives displayed a highly cultivar-dependent evolution, with Fuerte demonstrating the highest concentrations and most pronounced fluctuations. In contrast to penstemide, uridine and abscisic acid levels consistently increased during ripening. Several compounds characteristic of the Bacon variety were delineated but require further research for identification and role elucidation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ancient humans used dietary plants and herbs to treat disease and to pursue eternal life. Today, phytochemicals in dietary plants and herbs have been shown to be the active ingredients, some of which have antiaging and longevity-promoting effects. Here, we summarize 210 antiaging phytochemicals in dietary plants and herbs, systematically classify them into 8 groups. We found that all groups of phytochemicals can be categorized into six areas that regulate organism longevity: ROS levels, nutrient sensing network, mitochondria, autophagy, gut microbiota, and lipid metabolism. We review the role of these processes in aging and the molecular mechanism of the health benefits through phytochemical-mediated regulation. Among these, how phytochemicals promote longevity through the gut microbiota and lipid metabolism is rarely highlighted in the field. Our understanding of the mechanisms of phytochemicals based on the above six aspects may provide a theoretical basis for the further development of antiaging drugs and new insights into the promotion of human longevity.

The evolutionarily conserved extracellular signal-regulated kinase 2 (ERK2) is involved in regulating cellular signaling in both normal and pathological conditions. ERK2 expression is critical for human development, while hyperactivation is a major factor in tumor progression. Up to now, there have been no approved inhibitors that target ERK2, and as such, here we report on screening of a naturally occurring plant-based anticancerous compound-activity-target (NPACT) database for prospective ERK2 inhibitors. More than 1,500 phytochemicals were screened using in-silico molecular docking and molecular dynamics (MD) approaches. NPACT compounds with a docking score lower than a co-crystallized LHZ inhibitor (calc. -10.5 kcal/mol) were subjected to MD simulations. Binding energies (ΔG binding ) of inhibitor-ERK2 complexes over the MD course were estimated using an MM-GBSA approach. Based on MM-GBSA//100 ns MD simulations, the steroid zhankuic acid C (NPACT01034) demonstrated greater binding affinity against ERK2 protein than LHZ, with ΔG binding values of -50.0 and -47.7 kcal/mol, respectively. Structural and energetical analyses throughout the MD course demonstrated stabilization of zhankuic acid C complexed with ERK2 protein. The anticipated ADMET properties of zhankuic acid C indicated minimal toxicity. Moreover, in-silico evaluation of fourteen ERK2 inhibitors in clinical trials demonstrated the higher binding affinity of zhankuic acid C towards ERK2 protein., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Orthopterygium huaucui, commonly known as "Pate", is a medicinal shrub belonging to the Anacardiaceae family used locally to treat burns and stomach pains. Endemic to Peru, chemical studies on O. huaucui are limited. In this study, Ultra-High Performance Liquid Chromatography Quadrupole/Orbitrap Electrospray Ionization Tandem Mass Spectrometry (UHPLC Q/Orbitrap/ESI/MS/MS) was used to identify secondary metabolites in leaves, stems and fruits, and the antioxidant capacities of the different parts were compared. In addition, several compounds such as methyl gallate, gallic acid, kaempferol, quercetin, and quercetin 3-O-β-glucuronide were successfully isolated from the methanolic extract of the leaves of this species for the first time. Untargeted UHPLC Q/Orbitrap/ESI/MS/MS analysis tentatively identified seventy-six compounds in the different parts of the plant, showing that this species as an interesting source of flavonoids, procyanidins and tannins. The phenolic content in leaves and stems was 334.31±4.34 and 295.18±6.38 gallic acid equivalents/100 g dry plant, respectively, while that of fruits was lower (99.92±5.45 mg/100 g). Leaves had twice the flavonoid content than fruits (210.38±3.85 versus 87.42±3.85 quercetin equivalents/100 g). 2,2-Diphenyl-1-picrylhydrazyl (DPPH) results indicated high antioxidant activity in all parts, with stems and leaves showing IC 50 of 12.8 μg/mL, and fruits showing less activity (IC 50 =38.6 μg/mL). The Oxygen Radical Absorbance Capacity (ORAC) test showed higher antioxidant values in the stems (467.82±21.17 μmol Trolox equivalents/100 g). This study provides valuable information on the chemistry of O. huaucui and highlights its antioxidant potential, especially in leaves and stems., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: The utilization of nutrition management, has recently been developed as a means of improving the growth and production of phytochemical compounds in herbs. The present study aimed to improve the growth, physiological, and phytochemical characteristics of lemon balm (Melissa officinalis L.) using different NH 4 + (ammonium) to NO 3 ̄ (nitrate) ratios (0:100, 25:75, 50:50, 75:25 and 100:0) under floating culture system (FCS)., Results: The treatment containing 0:100 - NH 4 + :NO 3 ̄ ratio showed the most remarkable values for the growth and morpho-physiological characteristics of M. officinalis. The results demonstrated that maximum biomass (105.57 g) earned by using the ratio of 0:100 and minimum at 75:25 ratio of NH 4 + : NO 3 ̄. The plants treated with high nitrate ratio (0:100 - NH 4 + :NO 3 ̄) showed the greatest concentration of total phenolics (60.40 mg GAE/g DW), chlorophyll a (31.32 mg/100 g DW), flavonoids (12.97 mg QUE/g DW), and carotenoids (83.06 mg/100 g DW). Using the 75:25 - NH 4 + :NO 3 ̄ ratio caused the highest dry matter (DM), N and K macronutrients in the leaves. The highest antioxidant activity by both DPPH (37.39 µg AAE/mL) and FRAP (69.55 mM Fe ++ /g DW) methods was obtained in 75:25 - NH 4 + :NO 3 ̄ treatment. The p-coumaric acid as a main abundant phenolic composition, was detected by HPLC analysis as the highest content in samples grown under 0:100 - NH 4 + :NO 3 ̄ treatment. Also, the major compounds in M. officinalis essential oil were identified as geranial, neral, geranyl acetate and geraniol by GC analysis. With increasing NO 3 ̄ application, geraniol and geranyl acetate contents were decreased., Conclusions: The findings of present study suggest that the management of NH4 + to NO 3 ̄ ratios in nutrient solutions could contribute to improving growth, physiological and phytochemical properties of M. officinalis. The plants treated with high nitrate ratio (especially 0:100 - NH 4 + :NO 3 ̄) showed the greatest effects on improving the growth and production of morpho-physiological and phytochemical compounds. By comprehensively understanding the intricate dynamics among nitrogen sources, plants, and their surroundings, researchers and practitioners can devise inventive approaches to optimize nitrogen management practices and foster sustainable agricultural frameworks., (© 2024. The Author(s).)

The current study explores the effects of microwave treatment at varying wattage and durations on the phytoconstituents, antioxidant status, anti-nutritional factors (ANFs), and metabolite profiles of de-oiled rice bran. The total phenolics and flavonoids showed both increases and decreases depending on specific microwave parameters, while flavonol content consistently increased across all treated groups compared to the control. The DPPH and ABTS free radical scavenging activity, total antioxidant capacity, FRAP, CUPRAC, metal chelating activity, and ascorbic acid content were enhanced in most of the microwaved samples; however, longer microwave exposure at higher wattage led to their reduction. A treatment-specific decrease in ANFs, including condensed tannins, oxalates, and phytates, was observed. HRMS-based untargeted metabolomics identified a diverse range of primary and secondary metabolites, which clustered in a group-specific manner, indicating notable group-wise metabolite variations. Analysis of discriminating metabolites revealed no significant differences in the overall levels of phenolics, flavonoids, vitamins and cofactors, sugars, amino acids, terpenoids, fatty acids, and their derivatives among the treated groups compared to the control; however, several individual metabolites within these metabolite classes differed significantly. These findings suggest that optimized microwaving of de-oiled rice bran can enhance phytochemicals and antioxidants while improving the metabolite profile., (© 2024. The Author(s).)

Horticulture in controlled environments has been increasingly used to tackle limitations on crop production. As a crucial environmental factor, light regulate plant growth and metabolism. In the present study, basil plants were subjected to different light durations and intensities considering constant daily light integral (DLI). The lighting environment included 200, 300, and 400 µmol m - 2 s - 1 intensities for 18, 12, and 9 h, respectively. DLI amounted to 12.96 mol m - 2 d - 1 among all light treatments (LI200 for 18 h, LI300 for 12 h, and LI400 for 9 h). Half of the plants under each light treatment were exposed to 30 µmol m - 2 s - 1 of far-red light. The results indicated the general negative impact of LI400/9 on the growth of basils. Exposure to far-red light hurt the growth of the shoot, while it enhanced stem and petiole elongation. This effect was due to higher gibberellin accumulation, which resulted in shade avoidance responses. Exposure to far-red light also reduced anthocyanin and flavonoid contents, as two important nutritional components. Soluble carbohydrates increased, while storage carbohydrates decreased by increasing lighting duration/decreasing light intensity or by far-red light inclusion. The lowest antioxidant activity was detected in LI400/9. In the LI200/18, the highest level of auxin and the lowest level of cytokinin were detected, while the LI300/12 exhibited the highest level of gibberellin hormone. Low light intensity and long photoperiod enhanced plant biomass and phytochemical production and are recommended for basil production in controlled environments., (© 2024. The Author(s).)

Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin ( 1 ), tamirin ( 2 ), tanachin ( 3 ), reynosin ( 4 ), baynol C ( 5 ), desacetyl-β-cyclopyrethrosin ( 6 ), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide ( 7 ), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide ( 8 ), 1β-hydroxy-arbusculin A ( 9 ), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate ( 10 ) and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate ( 11 ); one lignan, pinoresinol ( 12 ); one norisoprenoid, loliolide ( 13 ); six flavonoids (four genins and two glycosides), hispidulin ( 14 ), nepetin ( 15 ), jaceosidin ( 16 ), eriodictyol ( 17 ), eriodictyol-3'-O-β-D-glucoside ( 18 ) and eriodictyol-7-O-β-D-glucuronide ( 19 ); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid ( 20 ), arbutin ( 21 ) and nebrodenside A ( 22 ). From the isolated compounds, only nepetin ( 15 ) has been reported previously from the Staehelina genus and, to the best of our knowledge, it is the first time that compound ( 18 ) has been identified in Asteraceae. A number of these substances were tested for (a) inhibition of lipoxygenase and acetylocholinesterase, (b) their antioxidant activity using the DPPH (1,1-Diphenyl-2-picrylhydrazyl) method or/and (c) inhibition of lipid peroxidation. The tested components exhibited low antioxidant activity with the exception of 5 and 22 , while the effectiveness of these compounds in the inhibition of acetylocholinesterase is limited. Furthermore, Molinspiration, an online computer tool, was used to determine the bioactivity ratings of the isolated secondary metabolites. The compounds' bioactivity ratings for potential therapeutic targets were very promising.

The secondary plant metabolites are of enormous importance because of their extensive medicinal, nutraceutical, and industrial applications. In plants, these secondary metabolites are often found in extremely small amounts, therefore, following the discovery of any prospective metabolite, the main constraining element is the ability to generate enough material for use in both industrial and therapeutic settings. In order to satisfy the rising demand for value-added metabolites, researchers prefer to use different molecular approaches for scalable and sustainable production of these phytocompounds. Here, we discuss the emerging regulatory trends in engineering these bioactive-phytocompounds and provide recommendation on successful employment of these state-of-the-art technologies for translation of these academic researches into novel process and products., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Indoor farming systems enable plant production in precisely controlled environments. However, implementing stable growth conditions and the absence of stress stimulants can weaken plants' defense responses and limit the accumulation of bioactive, health-beneficial phytochemicals. A potential solution is the controlled application of stressors, such as supplemental ultraviolet (UV) light. To this end, we analyzed the efficiency of short-term pre-harvest supplementation of the red-green-blue (RGB, LED) spectrum with ultraviolet B (UV-B) or C (UV-C) light to boost phytochemical synthesis. Additionally, given the biological harm of UV radiation due to high-energy photons, we monitored plants' photosynthetic activity during treatment and their morphology as well as sensory attributes after the treatment. Our analyses showed that UV-B radiation did not negatively impact photosynthetic activity while significantly increasing the overall antioxidant potential of lettuce through enhanced levels of secondary metabolites (total phenolics, flavonoids, anthocyanins), carotenoids, and ascorbic acid. On the contrary, UV-C radiation-induced anthocyanin accumulation in the green leaf cultivar significantly harmed the photosynthetic apparatus and limited plant growth. Taken together, we showed that short-term UV-B light supplementation is an efficient method for lettuce biofortification with healthy phytochemicals, while UV-C treatment is not recommended due to the negative impact on the quality (morphology, sensory properties) of the obtained leafy products. These results are crucial for understanding the potential of UV light supplementation for producing functional plants.

Nuclear receptor binding SET domain protein 2 (NSD2) significantly contributes to the development of cancer, making it a promising target for cancer drug discovery. This research explores natural compounds as potential selective inhibitors for NSD2 in cancer treatment. Employing a comprehensive in silico approach, the study utilized pharmacophore modeling, molecular docking, pharmacokinetic profiling, and molecular dynamics simulations. An e-pharmacophore model-based screening using the first selective and potent ligand bound to NSD2 identified 49,248 natural compounds from the SuperNatural 3.0 database (containing 449,008 molecules) with acceptable alignment with the developed pharmacophore hypotheses. Subsequently, molecular docking was executed to assess the standout compounds which led to the selection of ten candidates that surpassed the reference inhibitor in accordance w the binding affinity expressed as a G score. Ligand-residue interaction analyses of the top three hits (SN0450102, SN0410255, and SN0142336) revealed diverse crucial interactions with the NSD2 active site, including hydrogen bonds, pi-pi stacking, and hydrophobic contacts with key amino acid residues in the NSD2-PWWP1 domain. Pharmacokinetic profiling confirmed the drug-likability for the refined hits, indicating good cellular permeability and minimal blood-brain barrier penetration. Molecular dynamics simulations for 200 nanoseconds affirmed the stability of protein-ligand complexes, with minimal fluctuations in root mean square deviation and root mean square fluctuation analyses. Overall, this study identified promising natural compounds as potential pharmaceutical agents in the treatment of NSD2-associated cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2024 Mohamed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Endophytic fungi (EF) reside within plants without causing harm and provide benefits such as enhancing nutrients and producing bioactive compounds, which improve the medicinal properties of host plants. Selecting plants with established medicinal properties for studying EF is important, as it allows a deeper understanding of their influence. Therefore, the study aimed to investigate the impact of EF after inoculating the medicinal plant Perilla frutescens, specifically focusing on their role in enhancing medicinal properties., Results: In the current study, the impact of two EF i.e., Irpex lenis and Schizophyllum commune isolated from A. bracteosa was observed on plant Perilla frutescens leaves after inoculation. Plants were divided into four groups i.e., group A: the control group, group B: inoculated with I. lenis; group C: inoculated with S. commune and group D: inoculated with both the EF. Inoculation impact of I. lenis showed an increase in the concentration of chlorophyll a (5.32 mg/g), chlorophyll b (4.46 mg/g), total chlorophyll content (9.78 mg/g), protein (68.517 ± 0.77 mg/g), carbohydrates (137.886 ± 13.71 mg/g), and crude fiber (3.333 ± 0.37%). Furthermore, the plants inoculated with I. lenis showed the highest concentrations of P (14605 mg/kg), Mg (4964.320 mg/kg), Ca (27389.400 mg/kg), and Mn (86.883 mg/kg). The results of the phytochemical analysis also indicated an increased content of total flavonoids (2.347 mg/g), phenols (3.086 mg/g), tannins (3.902 mg/g), and alkaloids (1.037 mg/g) in the leaf extract of P. frutescens inoculated with I. lenis. Thus, overall the best results of inoculation were observed in Group B i.e. inoculated with I. lenis. GC-MS analysis of methanol leaf extract showed ten bioactive constituents, including 9-Octadecenoic acid (Z)-, methyl ester, and hexadecanoic acid, methyl ester as major constituents found in all the groups of P. frutescens leaves. The phenol (gallic acid) and flavonoids (rutin, kaempferol, and quercetin) were also observed to increase after inoculation by HPTLC analysis. The enhancement in the phytochemical content was co-related with improved anti-oxidant potential which was analyzed by DPPH (% Inhibition: 83.45 µg/ml) and FRAP (2.980 µM Fe (II) equivalent) assay as compared with the control group., Conclusion: Inoculation with I. lenis significantly enhances the uptake of nutritional constituents, phytochemicals, and antioxidant properties in P. frutescens, suggesting its potential to boost the therapeutic properties of host plants., (© 2024. The Author(s).)

Although Boraginaceae have been classified as good sources of nectar for many insects, little is still known about their nectar and nectaries. Thus, in the present contribution, we investigated the nectar production dynamics and chemistry in Borago officinalis L. (borage or starflower), together with its potential interaction capacity with pollinators. A peak of nectar secretion (∼5.1 µL per flower) was recorded at anthesis, to decrease linearly during the following 9 days. In addition, TEM and SEM analyses were performed to understand ultrastructure and morphological changes occurring in borage nectary before and after anthesis, but also after its secretory phase. Evidence suggested that nectar was transported by the apoplastic route (mainly from parenchyma to epidermis) and then released essentially by exocytotic processes, that is a granulocrine secretion. This theory was corroborated by monitoring the signal of complex polysaccharides and calcium, respectively, via Thiéry staining and ESI/EELS technique. After the secretory phase, nectary underwent degeneration, probably through autophagic events and/or senescence induction. Furthermore, nectar (Nec) and other flower structures (i.e., sepals, gynoecia with nectaries, and petals) from borage were characterized by spectrophotometry and HPLC-DAD, in terms of plant secondary metabolites, both at early (E-) and late (L-) phase from anthesis. The content of phytochemicals was quantified and discussed for all samples, highlighting potential biological roles of these compounds in the borage flower (e.g., antimicrobial, antioxidant, staining effects). Surprisingly, a high significant accumulation of flavonoids was registered in L-Nec, with respect to E-Nec, indicating that this phenomenon might be functional and able to hide molecular (e.g., defence against pathogens) and/or ecological (e.g., last call for pollinators) purposes. Indeed, it is known that these plant metabolites influence nectar palatability, encouraging the approach of specialist pollinators, deterring nectar robbers, and altering the behaviour of insects., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest about the present work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Brassica oleracea and Allium vegetables are known for their unique, family specific, water-soluble phytochemicals, glucosinolates, and S-alk(en)yl-l-cysteine sulfoxides, respectively. However, they are also important delivery systems of several other health-related compounds, such as carotenoids (lipid-soluble phytochemicals), vitamin C (water-soluble micronutrient), and vitamin K1 (lipid-soluble micronutrient). When all-year-round availability or transport over long distances is targeted for these often seasonal, locally grown vegetables, processing becomes indispensable. However, the vegetable processing chain, which consists of multiple steps (e.g., pretreatment, preservation, storage, preparation), can impact the nutritional quality of these vegetables corresponding to the nature of the health-related compounds and their susceptibility to (bio)chemical conversions. Since information about the impact of the vegetable processing chain is scattered per compound or processing step, this review targets an integration of the state of the art and discusses needs for future research. Starting with a discussion on substrate-enzyme location within the vegetable matrix, an overview is provided of the impact and potential of processing, encompassing a wide range of (nonenzymatic) conversions.

Codonopsis convolvulacea is a highly valued Chinese medicinal plant containing diverse bioactive compounds. While roots/tubers have been the main medicinal parts used in practice, leaves and stems may also harbor valuable phytochemicals. However, research comparing volatiles across tissues is lacking. This study performed metabolomic profiling of leaves, stems, and tubers of C. convolvulacea to elucidate tissue-specific accumulation patterns of volatile metabolites. Ultra-high performance liquid chromatography-tandem mass spectrometry identified 302 compounds, belonging to 14 classes. Multivariate analysis clearly differentiated the metabolic profiles of the three tissues. Numerous differentially accumulated metabolites (DAMs) were detected, especially terpenoids and esters. The leaves contained more terpenoids, ester, and alcohol. The stems accumulated higher levels of terpenoids, heterocyclics, and alkaloids with pharmaceutical potential. The tubers were enriched with carbohydrates like sugars and starch, befitting their storage role, but still retained reasonable amounts of valuable volatiles. The characterization of tissue-specific metabolic signatures provides a foundation for the selective utilization of C. convolvulacea parts. Key metabolites identified include niacinamide, p-cymene, tridecanal, benzeneacetic acid, benzene, and carveol. Leaves, stems, and tubers could be targeted for antioxidants, drug development, and tonics/nutraceuticals, respectively. The metabolomic insights can also guide breeding strategies to enhance the bioactive compound content in specific tissues. This study demonstrates the value of tissue-specific metabolite profiling for informing the phytochemical exploitation and genetic improvement of medicinal plants.

Aflatoxin B 1 (AFB 1 ), the most toxic and harmful mycotoxin, has a high likelihood of occurring in animal feed and human food, which seriously affects agriculture and food safety and endangers animal and human health. Recently, natural plant products have attracted widespread attention due to their low toxicity, high biocompatibility, and simple composition, indicating significant potential for resisting AFB 1 . The mechanisms by which these phytochemicals resist toxins mainly involve antioxidative, anti-inflammatory, and antiapoptotic pathways. Moreover, these substances also inhibit the genotoxicity of AFB 1 by directly influencing its metabolism in vivo , which contributes to its elimination. Here, we review various phytochemicals that resist AFB 1 and their anti-AFB 1 mechanisms in different animals, as well as the common characteristics of phytochemicals with anti-AFB 1 function. Additionally, the shortcomings of current research and future research directions will be discussed. Overall, this comprehensive summary contributes to the better application of phytochemicals in agriculture and food safety.

Angiotensin-converting enzyme 2 (ACE2) is a key enzyme in the renin-angiotensin system (RAS), also serving as an amino acid transporter and a receptor for certain coronaviruses. Its primary role is to protect the cardiovascular system via the ACE2/Ang (1-7)/MasR cascade. Given the critical roles of ACE2 in regulating numerous physiological functions, molecules that can upregulate or activate ACE2 show vast therapeutic value. There are only a few ACE2 activators that have been reported, a wide range of molecules, including food-derived compounds, have been reported as ACE2 up-regulators. Effective doses of bioactive peptides range from 10 to 50 mg/kg body weight (BW)/day when orally administered for 1 to 7 weeks. Protein hydrolysates require higher doses at 1000 mg/kg BW/day for 20 days. Phytochemicals and vitamins are effective at doses typically ranging from 10 to 200 mg/kg BW/day for 3 days to 6 months, while Traditional Chinese Medicine requires doses of 1.25 to 12.96 g/kg BW/day for 4 to 8 weeks. ACE2 activation is linked to its hinge-bending region, while upregulation involves various signaling pathways, transcription factors, and epigenetic modulators. Future studies are expected to explore novel roles of ACE2 activators or up-regulators in disease treatments and translate the discovery to bedside applications.

While the flowers of Matricaria recutita L., German chamomile, are widely used for medicinal and cosmetic purposes, little is known about its roots, which are used in complementary medicine for the preparation of aqueous fermented extracts for the treatment of cramps and anxiety. To broaden the understanding of the active principles involved, a model fermentation approach was developed and fermentates were compared to commercially manufactured tinctures. Coumarins and hydroxycinnamates were among the major secondary metabolites characterized using HPLC-MS n . After six months of fermentation and storage, low-molecular organic acids were detected by GC-MS. Fermentation contributed to the stabilization of antioxidant and radical scavenging activities, which were in a range of about 8-10 mg gallic acid equivalents/g dry weight and 20-24 mg trolox equivalents/g dry weight, determined by Folin-Ciocalteu and DPPH assays, respectively. In addition, antibacterial activities of the extracts against Gram-positive and -negative bacteria increased during the first week of fermentation. Fermentates were neither cytotoxic nor pro- or anti-inflammatory. Thus, fermentation of chamomile roots is a suitable method for the safe production of biofunctional aqueous chamomile root extracts that remain stable without the addition of synthetic preservatives., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The history of pharmacology is deeply intertwined with plant-derived compounds, which continue to be crucial in drug development. However, their complex structures and limited availability in plants challenge drug discovery, optimization, development, and industrial production via chemical synthesis or natural extraction. This review delves into the integration of metabolic and enzyme engineering to leverage micro-organisms as platforms for the sustainable and reliable production of therapeutic phytochemicals. We argue that engineered microbes can serve a triple role in this paradigm: facilitating pathway discovery, acting as cell factories for scalable manufacturing, and functioning as platforms for chemical derivatization. Analyzing recent progress and outlining future directions, the review highlights microbial biotechnology's transformative potential in expanding plant-derived human therapeutics' discovery and supply chains., Competing Interests: Declaration of Competing Interest MKJ has financial interests in Biomia ApS. MH and CGA-R declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Main Conclusion: A gene-to-metabolite approach afforded new insights regarding defence mechanisms in oat plants that can be incorporated into plant breeding programmes for the selection of markers and genes related to disease resistance. Monitoring metabolite levels and changes therein can complement and corroborate transcriptome (mRNA) data on plant-pathogen interactions, thus revealing mechanisms involved in pathogen attack and host defence. A multi-omics approach thus adds new layers of information such as identifying metabolites with antimicrobial properties, elucidating metabolomic profiles of infected and non-infected plants, and reveals pathogenic requirements for infection and colonisation. In this study, two oat cultivars (Dunnart and SWK001) were inoculated with Pseudomonas syringae pathovars, pathogenic and non-pathogenic on oat. Following inoculation, metabolites were extracted with methanol from leaf tissues at 2, 4 and 6 days post-infection and analysed by multiple reaction monitoring (MRM) on a triple quadrupole mass spectrometer system. Relatedly, mRNA was isolated at the same time points, and the cDNA analysed by quantitative PCR (RT-qPCR) for expression levels of selected gene transcripts associated with avenanthramide (Avn) biosynthesis. The targeted amino acids, hydroxycinnamic acids and Avns were successfully quantified. Distinct cultivar-specific differences in the metabolite responses were observed in response to pathogenic and non-pathogenic strains. Trends in aromatic amino acids and hydroxycinnamic acids seem to indicate stronger activation and flux through these pathways in Dunnart as compared to SWK001. A positive correlation between hydroxycinnamoyl-CoA:hydroxyanthranilate N-hydroxycinnamoyl transferase (HHT) gene expression and the abundance of Avn A in both cultivars was documented. However, transcript profiling of selected genes involved in Avn synthesis did not reveal a clear pattern to distinguish between the tolerant and susceptible cultivars., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Kidney problems are becoming more common globally and are considered a major health issue in the modern world with high mortality rate. Polyalthia longifolia (Sonn.) Thwaites is a tropical ethnomedicinal plant used to treat various diseases like diabetes, hypertension and urinary disorders and possess antioxidant and anti-inflammatory properties., Aim of the Study: This study aimed to investigate the phytochemical composition of 70% ethanolic leaf extract of Polyalthia longifolia (Sonn.) Thwaites (PL) and evaluates its nephroprotective effects against cisplatin-induced nephrotoxicity in Wistar rats., Materials and Methods: The leaves of PL were extracted with 70% ethanol and performed the phytochemical profiling using Liquid Chromatography-Mass Spectrometry (LC-MS). The nephroprotective effect of PL leaf extract was evaluated at three doses (150, 300 and 600 mg/kg, p.o.) for 14 days against cisplatin toxicity (16 mg/kg, i.p., once) in male Wistar rats. Body and kidney weight indices, kidney function markers and lipid profile markers in serum, and oxidative stress markers in kidney tissue were performed along with the histopathological analysis of kidney., Results: The LC-MS chromatograph confirmed the presence of various phytocompounds include N-Methylhernagine (aporphine alkaloid), 4-Acetamidobutanoic acid (gamma amino acid) and choline, etc. in the PL leaf extract. Exposure of cisplatin (16 mg/kg, i.p., once only) to the animals significantly elevated the levels of kidney functional markers (i.e. serum urea, uric acid, creatinine) and the lipid markers (triglyceride and total cholesterol) in blood circulation with depletion of serum albumin which were reversed by the therapy of PL leaf extract (150, 300 and 600 mg/kg) in dose-dependent manner. The altered level of body and kidney weight in cisplatin treated group was also restored by the therapy. PL leaf extract effectively improved the antioxidant defense system of kidney at all doses by restoring the levels of tissue glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase with the dose-dependent reduction of lipid peroxidation against cisplatin-induced renal oxidative stress. The histopathological observations also showed the significant recovery in cellular morphology after PL treatment when compared to the cisplatin toxicity group. The highest dose 600 mg/kg of PL leaf extract showed more pronounced renal recovery (p < 0.001) followed by other two doses, which was similar to the silymarin treatment group (a reference drug) against nephrotoxicity., Conclusion: The results of this study revealed the nephroprotective effects of PL leaves against cisplatin-induced nephrotoxicity by reversing the level of biochemical markers and mitigating oxidative stress as well as improving the architecture of renal tissues. This renal protection by PL might be due to the synergistic effect of its phytoconstituents and antioxidant efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Trillium govanianum is traditionally used to treat innumerable alignments like sexual disorders, cancer, inflammation etc. Mainly rhizomes of T. govanianum have been explored for phytochemical profiling but comprehensive metabolomics of other parts has not been yet deeply investigated. Thus, current study was aimed for organs-specific (roots, rhizomes, rhizomatous buds, stems, leaves, and fruits) phytochemical profiling of T. govanianum via metabolomics approach. Targeted (steroidal saponins and free sugars) and non-targeted metabolomics were performed by UPLC-PDA/ELSD & UHPLC-Q-TOF-IMS. Among steroidal compounds, 20-hydroxyecdysone, pennogenin-3-O-β-chacotrioside, dioscin were found predominantly in all samples while diosgenin was identified only in rhizomes. Further, four free sugars viz. 2-deoxyribose (116.24 ± 1.26 mg/g: leaves), fructose (454.76 ± 12.14 mg/g: rhizomes), glucose (243.21 ± 7.53 mg/g: fruits), and galactose (69.06 ± 2.14 mg/g: fruits) were found significant in respective parts of T. govanianum. Elemental analysis of targeted samples was determined by atomic absorption spectrophotometer. Heavy metals (Cd, Hg, Pd, As) were absent while micro- (Mn, Na, Zn, Cu) and macro- (Ca, Fe, Mg, K) elements were found in all samples. Furthermore, UHPLC-Q-TOF-IMS had identified 103 metabolites based on their mass fragmentation patterns and 839 were tentatively predicted using METLIN database. The multivariate statistical analysis showed organs specific clustering and variance of metabolites. Apart from this, extracts were evaluated for in vitro anticholinesterase activity, and found potentials inhibitors with IC 50 values 2.02 ± 0.15 to 27.65 ± 0.89 mg/mL and 3.58 ± 0.12 to 16.81 ± 2.48 mg/mL of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme, respectively. Thus, comprehensive metabolomics and anti-cholinesterase activity of different parts of T. govanianum would lay the foundation for improving medicinal importance and health benefits of T. govanianum., (© 2024. The Author(s).)

The current study investigated the impact of cold stress on the morphological, physiological, and phytochemical properties of Juglans regia L. ( J. regia ) using in vitro microclone cultures. The study revealed significant stress-induced changes in the production of secondary antioxidant metabolites. According to gas chromatography-mass spectrometry (GC-MS) analyses, the stress conditions profoundly altered the metabolism of J. regia microclones. Although the overall spectrum of metabolites was reduced, the production of key secondary antioxidant metabolites significantly increased. Notably, there was a sevenfold (7×) increase in juglone concentration. These findings are crucial for advancing walnut metabolomics and enhancing our understanding of plant responses to abiotic stress factors. Additionally, study results aid in identifying the role of individual metabolites in these processes, which is essential for developing strategies to improve plant resilience and tolerance to adverse conditions.

Floral biochemistry and stress physiology is an underexplored aspect of mangroves, which should be investigated as part of preservation and restoration efforts. A thriving true mangrove tree (Bruguiera gymnorrhiza (L.) Lamk.) and a threatened mangrove-associate species (Heritiera fomes Buch. Ham.) were studied in the Sundarban region of India for seasonal variations in floral odours, non-volatile phytochemicals, antioxidant enzyme activities, and surface water chemistry in surrounding habitat. Both species were found to exhibit significant differences in floral volatilomes, protein contents, antioxidant enzyme activities, total flavonoids, and total phenolic contents between spring and autumn blooms. The bird-pollinated flowers of B. gymnorrhiza also showed considerable seasonal differences in floral anthocyanin and proline contents, indicating vulnerability of the post-anthesis open flowers to environmental factors. Contrarily to previous findings, B. gymnorrhiza floral bouquet appeared to be enriched in various classes of volatiles - dominated by sulphurous compounds in bud stage and terpenoids in open stage. Floral anthocyanins, contributing to the striking colouration of the calyx, were found to comprise cyanidin and delphinidin derivatives. Other glycosides of cyanidin and delphinidin were detected in H. fomes flowers, contributing to visual guides to potential food rewards for pollinating insects. Floral tissue in H. fomes was found to be protected by densely overlapping layers of stellate trichomes containing sesquiterpenoids as phytoprotectants. Comparison of the two floral species suggested that H. fomes flowering is optimized to oligohaline (but not freshwater) vernal conditions; whereas B. gymnorrhiza blooms are adapted for biologically enriched (including abundant herbivores and microbial growth), mesohaline forest habitats., (© 2024. The Author(s) under exclusive licence to The Botanical Society of Japan.)

Nonalcoholic fatty liver disease (NAFLD) is described by too much hepatic fat deposition causing steatosis, which further develops into nonalcoholic steatohepatitis (NASH), defined by necroinflammation and fibrosis, progressing further to hepatic cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD is linked to different aspects of the metabolic syndrome like obesity, insulin resistance, hypertension, and dyslipidemia, and its pathogenesis involves several elements including diet, obesity, disruption of lipid homeostasis, and a high buildup of triglycerides and other lipids in liver cells. It is therefore linked to an increase in the susceptibility to developing diabetes mellitus and cardiovascular diseases. Several interventions exist regarding its management, but the availability of natural sources through diet will be a benefit in dealing with the disorder due to the immensely growing dependence of the population worldwide on natural sources owing to their ability to treat the root cause of the disease. Anthocyanins (ACNs) are naturally occurring polyphenolic pigments that exist in the form of glycosides, which are the glucosides of anthocyanidins and are produced from flavonoids via the phenyl propanoid pathway. To understand their mode of action in NAFLD and their therapeutic potential, the literature on in vitro, in vivo, and clinical trials on naturally occurring ACN-rich sources was exhaustively reviewed. It was concluded that ACNs show their potential in the treatment of NAFLD through their antioxidant properties and their efficacy to control lipid metabolism, glucose homeostasis, transcription factors, and inflammation. This led to the conclusion that ACNs possess efficacy in the amelioration of NAFLD and the various features associated with it. However, additional clinical trials are required to justify the potential of ACNs in NAFLD., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Although cholesterol plays a key role in many physiological processes, its dysregulation can lead to several metabolic diseases. Statins are a group of drugs widely used to lower cholesterol levels and cardiovascular risk but may lead to several side effects in some patients. Therefore, the development of a plant-based therapeutic adjuvant with cholesterol-lowering activity is desirable. The maintenance of cholesterol homeostasis encompasses multiple steps, including biosynthesis and metabolism, uptake and transport, and bile acid metabolism; issues arising in any of these processes could contribute to the etiology of cholesterol-related diseases. An increasing body of evidence strongly indicates the benefits of phytochemicals for cholesterol regulation; traditional Chinese medicines prove beneficial in some disease models, although more scientific investigations are needed to confirm their effectiveness. One of the main functions of cholesterol is bile acid biosynthesis, where most bile acids are recycled back to the liver. The composition of bile acid is partly modulated by gut microbes and could be harmful to the liver. In this regard, the reshaping effect of phytochemicals on gut microbiota has been widely reported in the literature for its significance. Therefore, we reviewed studies conducted over the past 5 years elucidating the regulatory effects of phytochemicals or herbal medicines on cholesterol metabolism. In addition, their effects on the recomposition of gut microbiota and bile acid metabolism due to modulation are discussed. This review aims to provide novel insights into the treatment of cholesterol dysregulation and the anticipated development of natural-based compounds in the near and far future.

" Candidatus Liberibacter asiaticus" (CLas), the causal agent of citrus Huanglongbing (HLB), is able to multiply to a high abundance in citrus fruit pith. However, little is known about the biological processes and phytochemical substances that are vital for CLas colonization and growth in fruit pith. In this study, CLas-infected fruit pith of three citrus cultivars ("Shatangju" mandarin, "Guanxi" pomelo, and "Shatian" pomelo) exhibiting different tolerance to CLas were collected and used for dual RNA-Seq and untargeted metabolome analysis. Comparative transcriptome analysis found that the activation of the CLas noncyclic TCA pathway and pathogenic-related effectors could contribute to the colonization and growth of CLas in fruit pith. The pre-established Type 2 prophage in the CLas genome and the induction of its CRISPR/ cas system could enhance the phage resistance of CLas and, in turn, facilitate CLas population growth in fruit pith. CLas infection caused the accumulation of amino acids that were correlated with tolerance to CLas. The accumulation of most sugars and organic acids in CLas-infected fruit pith, which could be due to the phloem blockage caused by CLas infection, was thought to be beneficial for CLas growth in localized phloem tissue. The higher levels of flavonoids and terpenoids in the fruit pith of CLas-tolerant cultivars, particularly those known for their antimicrobial properties, could hinder the growth of CLas. This study advances our understanding of CLas multiplication in fruit pith and offers novel insight into metabolites that could be responsible for tolerance to CLas or essential to CLas population growth.IMPORTANCECitrus Huanglongbing (HLB, also called citrus greening disease) is a highly destructive disease currently threatening citrus production worldwide. HLB is caused by an unculturable bacterial pathogen, " Candidatus Liberibacter asiaticus" (CLas). However, the mechanism of CLas colonization and growth in citrus hosts is poorly understood. In this study, we utilized the fruit pith tissue, which was able to maintain the CLas at a high abundance, as the materials for dual RNA-Seq and untargeted metabolome analysis, aiming to reveal the biological processes and phytochemical substances that are vital for CLas colonization and growth. We provided a genome-wide CLas transcriptome landscape in the fruit pith of three citrus cultivars with different tolerance and identified the important genes/pathways that contribute to CLas colonization and growth in the fruit pith. Metabolome profiling identified the key metabolites, which were mainly affected by CLas infection and influenced the population dynamic of CLas in fruit pith., Competing Interests: The authors declare no conflict of interest.

In this study, phytochemical and biological activity studies supported by docking were carried out on a species of the genus Glaucium, a repository of isoquinoline alkaloids. The GC-MS (Gas Chromatography-Mass Spectrometry) method is used to characterize the isoquinoline alkaloids of Glaucium flavum Crantz. (Papaveraceae). G. flavum was collected from seven different regions of Türkiye (Antalya, Urla-Izmir, Mordogan-Izmir, Mugla, Assos-Canakkale, Karabiga-Canakkale, Giresun) and totally 17 compounds were detected by GC-MS. Glaucine was found to be the major constituent in the sample collected from Mugla, whereas isocorydine was recorded to be the principal alkaloid in other samples. Further fractionation studies on G. flavum collected from Antalya province in Southwestern Türkiye, yielded five major alkaloids (isocorydine 1, dihydrosanguinarine 2, glaucine 3, dehydroglaucine 4, protopine 5) which were characterized by spectroscopic methods. Anticholinesterase activities of the extracts and isolated alkaloids were also tested by in vitro Ellman method. The isolated compounds were also analyzed by a molecular docking technique to determine the binding orientations in the gorge of the active site of acetylcholinesterase (AChE) and a homology model of butyrylcholinesterase (BuChE). This is the first comparative investigation of the phytochemical composition and biodiversity of Glaucium flavum species growing in Türkiye., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Ethnopharmacological Relevance: In Morocco carob fruits are used traditionally to treat hypercholesterolemia, diabetes and related diseases., Aims: This study was designed to evaluate the hypolipidemic activity of Ceratonia siliqua green pods extract and its fractions in Triton WR-1339 and high fat/cholesterol diet (HFCD) induced hyperlipidemia mice, as well as their ability to prevent lipoproteins oxidation in vitro., Materials and Methods: High performance liquid chromatography (HPLC) analysis was used to determine the phenolic composition of the immature carob pods extract (HWCE). Antioxidant activities were evaluated using the DPPH radical scavenging test as well as MDA measurement in oxidized lipoprotein rich plasma. Plasma lipids, glucose and biliary total cholesterol, as well as lipids level in liver and feces, were analyzed. The acute oral toxicity was performed in mice single dosed with the HWCE at 2000 and 5000 mg/kg body weight., Results: HPLC analysis shows that gallic acid is the main phenolic compound in the HWCE. The acute oral toxicity assessment revealed that the HWCE is not toxic (LD 50 is greater than 5000 mg/kg body weight). In the acute hypolipidemic study, mice treated with the HWCE and its fractions exhibited a significant (P < 0.001) reduction in plasma total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels. Importantly, immature carob aqueous extract was more effective in lowering mice hypercholesterolemia than its fractions. Indeed, mice fed the HFCD for 12 weeks showed a significant raise in plasma TC, TG and LDL-C, as well as in hepatic and fecal TC and TG levels. The HWCE at 100 and 200 mg/kg body weight significantly (P < 0.001) reversed the plasmatic levels of these lipid parameters, increased plasma HDL-C level, reduced hepatic lipids accumulation, but increased cholesterol level in the bile and fecal lipids excretion. The HWCE decreased also the atherogenic index, the LDL-C/HDL-C ratio and plasma glucose level after 12 weeks' experiment. On the other hand, the HWCE was more effective in preventing mice lipoprotein-rich plasma oxidation than its fractions, with a concentration-dependent manner., Conclusion: C. siliqua green fruits extract could be effective in preventing atherosclerosis and related cardiovascular complications through the inhibition of lipoprotein oxidation and cholesterol clearance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Dietary interventions are crucial in modulating inflammation in humans. Strawberries are enjoyed by people of different ages as a result of their attractive phenotype and taste. In addition, the active compounds in strawberries may contribute to the reduction of inflammation. When developing new strawberry cultivars to address agricultural and environmental threats, the bioactivity of strawberries must be improved to maintain their health benefits., Results: We determined the phytochemical contents of extracts from a new Korean strawberry cultivar, with the CN7 cultivar extract possessing the highest total polyphenol and flavonoid contents compared to the CN5 and Seolhyang cultivar extracts. The new Korean strawberry cultivars reduced the expression of inflammatory-related genes in lipopolysaccharide (LPS)-induced RAW264.7 cells via the nuclear factor-kappa B signaling pathway, indicating an anti-inflammatory effect. The CN7 cultivar showed greater bioactivity potential and the highest ellagic acid content; hence, we assessed the effect of the CN7 cultivar in an LPS-stimulated mouse model. The CN7 cultivar treatment demonstrated its effectiveness in reducing inflammation via the downregulation of inflammatory cytokines secretion and gene expression., Conclusion: The results obtained in the present study have revealed the observable differences of the newly developed strawberry cultivars with Seolhyang in mitigating inflammation induced by LPS. The enhanced phytochemical content of the CN7 cultivar extract may contribute to its improved anti-inflammatory effect. Therefore, it is crucial to maintain the nutritive benefits of strawberry during the development of new cultivation. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Phytonutrients (PTN) namely saponins (SP) and condensed tannins (CT) have been demonstrated to assess the effect of rumen fermentation and methane mitigation. Phytonutrient pellet containing mangosteen, rambutan, and banana flower (MARABAC) and lemongrass including PTN, hence these plant-phytonutrients supplementation could be an alternative plant with a positive effect on rumen fermentation. The aim of this experiment was to evaluate the effect of supplementation of MARABAC and lemongrass (Cymbopogon citratus) powder on in vitro fermentation modulation and the ability to mitigate methane production. The treatments were arranged according to a 3 × 3 Factorial arrangement in a completely randomized design. The two experimental factors consisted of MARABAC pellet levels (0%, 1%, and 2% of the total substrate) and lemongrass supplementation levels (0%, 1%, and 2% of the total substrate). The results of this study revealed that supplementation with MARABAC pellet and lemongrass powder significantly improved gas production kinetics (P < 0.01) and rumen fermentation end-products especially the propionate production (P < 0.01). While rumen methane production was subsequently reduced by both factors. Additionally, the in vitro dry matter degradability (IVDMD) and organic matter degradability (IVOMD) were greatly improved (P < 0.05) by the respective treatments. MARABAC pellet and lemongrass powder combination showed effective methane mitigation by enhancing rumen fermentation end-products especially the propionate concentration and both the IVDMD and IVOMD, while mitigated methane production. The combined level of both sources at 2% MARABAC pellet and 2% lemongrass powder of total substrates offered the best results. Therefore, MARABAC pellet and lemongrass powder supplementation could be used as an alternative source of phytonutrient in dietary ruminant., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Scope: Piper excelsum (kawakawa) has a history of therapeutic use by Māori in Aotearoa New Zealand. It is currently widely consumed as a beverage and included as an ingredient in "functional" food product. Leaves contain compounds that are also found in a wide range of other spices, foods, and medicinal plants. This study investigates the human metabolism and excretion of kawakawa leaf chemicals., Methods and Results: Six healthy male volunteers in one study (Bioavailability of Kawakawa Tea metabolites in human volunteers [BOKA-T]) and 30 volunteers (15 male and 15 female) in a second study (Impact of acute Kawakawa Tea ingestion on postprandial glucose metabolism in healthy human volunteers [TOAST]) consume a hot water infusion of dried kawakawa leaves (kawakawa tea [KT]). Untargeted Liquid Chromatography-Tandem Mass spectrometry (LC-MS/MS) analyses of urine samples from BOKA-T identified 26 urinary metabolites that are significantly associated with KT consumption, confirmed by the analysis of samples from the independent TOAST study. Seven of the 26 metabolites are also detected in plasma. Thirteen of the 26 urinary compounds are provisionally identified as metabolites of specific compounds in KT, eight metabolites are identified as being derived from specific compounds in KT but without resolution of chemical structure, and five are of unknown origin., Conclusions: Several kawakawa compounds that are also widely found in other plants are bioavailable and are modified by phase 1 and 2 metabolism., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Heavy metals are ubiquitous environmental toxicants that have been known to have a serious effect on human and animal health. Aluminum (Al) is a widely distributed metal in nature. Al exposure has a detrimental impact on human fertility. This review focused on Al-induced male reproductive toxicity and the potential therapeutic approaches with some phytochemicals. Data from the literature showed that Al exposure is accompanied by a drastic decline in blood levels of FSH, LH, and testosterone, reduced sperm count, and affected sperm quality. Al exposure at high levels can cause oxidative stress by increasing ROS and RNS production, mediated mainly by downregulating Nrf2 signaling. Moreover, several investigations demonstrated that Al exposure evoked inflammation, evidenced by increased TNF-α and IL-6 levels. Additionally, substantial evidence concluded the key role of apoptosis in Al-induced testicular toxicity mediated by upregulating caspase-3 and downregulating Bcl2 protein. The damaging effects of Al on mitochondrial bioenergetics are thought to be due to the excessive generation of free radicals. This review helps to clarify the main mechanism involved in Al-associated testicular intoxication and the treatment strategy to attenuate the notable harmful effects on the male reproductive system. It will encourage clinical efforts to target the pathway involved in Al-associated testicular intoxication., Competing Interests: Declaration of competing interest The author declares no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Salt stress is a recognized annihilating abiotic stress that has a significant impact on agricultural and horticulture crop productivity. Plant development faces three distinct dangers as a result of salt stress: oxidative stress, osmotic stress, and ionic toxicity. It has been shown that plants can forecast diurnal patterns using the circadian clock; moreover, they can manage their defensive mechanism for the detoxification of reactive oxygen species (ROS). Circadian rhythmicity in gene expression assembles transcription and translation feedback networks to govern plant shape, physiology, cellular and molecular activities. Both external and internal variables influence the systemic rhythm via input routes. The Malav Jyoti (MJ) and Delhi Green (DG) genotypes of spinach (Spinacia oleracea) were grown in the plant growth chamber. The chamber had an optimized temperature of 25 °C and humidity of 65% containing light emitting diode (LED) having Red: Blue: white (one side) and White fluorescent (other side) under salinity stress. The samples were collected on the basis of 4 h intervals of circadian hours (0 h, 4 h, 8 h and 12 h) during Day-10 and Day-20 of salt treatments. Under salt stress, the circadian and light-emitting diode-based strategy had a substantial influence on spinach's anti-oxidative responses, stomatal movement, CO 2 assimilation, PS-I and II efficiency, phytochrome pigment efficiency, and photosynthesis. Based on the findings of the free radical scavenging enzyme tests, the photoperiodic hours for the proteome analysis were set to 11 am and 3 pm on Day-20. When compared to white fluorescent, this study found that LED has the capacity to influence the entrainment cues of the circadian clock in the cultivation of salt-sensitive spinach genotypes. According to our findings, changing the cellular scavenging mechanism and chloroplast proteome has increased the survival rate of spinach genotypes under LED when compared to white fluorescent., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Kale (Brassica oleracea L. var. sabellica L.), kohlrabi (Brassica oleracea L. var. gongylodes L.) and wheat (Triticum aestivum L. cv. Bancal) microgreens were cultivated in presence of selenium 20 μmol L -1 as sodium selenite and sodium selenate mixture. The influence of this biofortification process was evaluated in terms of biomass production, total Se, macro- and micronutrients concentration, polyphenols, antioxidant activity, chlorophylls and carotenoids levels and total soluble proteins content. The results obtained have shown a significant concentration of total Se in the biofortified microgreens of kale (133 μg Se·g -1 DW) and kohlrabi (127 μg Se·g -1 DW) higher than that obtained for wheat (28 μg Se·g -1 DW). The Se uptake in all the species did not produce oxidative damage to the plants reflected in the bioactive compounds, antioxidant capacity or pigments concentration. These Se-enriched microgreens may contribute to the recommended intake of this nutrient in human diet as to overcome Se-deficiency., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ethnopharmacological Relevance: Origanum majorana L. is a member of the Lamiaceae family and is commonly used in Egyptian cuisine as a seasoning and flavor enhancer. It is also recognized as a well-known traditional medicine in Egypt and is widely used for treating abdominal colic due to its antispasmodic properties. However, the protective effects of Origanum majorana L. against ulcerative colitis and its underlying mechanisms remain unclear., Aim of the Study: This study aimed to identify the biologically active components present in methanol extracts of Origanum majorana L. using gas chromatography/mass spectrometry (GC/MS). Additionally, it aimed to investigate the therapeutic effects of these extracts on acetic acid-induced ulcerative colitis and elucidate the potential mechanisms involved., Materials and Methods: We conducted a GC-MS analysis of the methanolic extract obtained from Origanum majorana L. Thirty-two male rats were included in the study and divided into four experimental groups, with eight rats in each group: sham, UC, UC + O. majorana, and UC sulfasalazine. After euthanizing the rats, colon tissue samples were collected for gross and microscopic examinations, assessment of oxidative stress, and molecular evaluation. GC-MS analysis identified 15 components in the extracts. Pretreatment with O. majorana L. extract and sulfasalazine significantly improved the disease activity index (DAI) and resulted in notable improvements in macroscopic and microscopic colon findings. Additionally, both treatments demonstrated preventive effects against colonic oxidative damage by reducing the levels of malondialdehyde (MDA) and increasing the levels of the antioxidant systems superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), which operate through the Nrf2/HO-1 signaling pathway. Moreover, these treatments downregulated the colonic inflammatory cascade by inhibiting NFκB, TNFα, IL-1β, IL6, IL23, IL17, COX-2, and iNOS, subsequently leading to downregulation of the JAK2/STAT3 signaling pathway and a decrease in the Th17 cell response. Furthermore, a reduction in the number of apoptotic epithelial cells that expressed caspase-3 was observed., Conclusion: pretreatment with O. majorana L. extract significantly ameliorated acetic acid-induced ulcerative colitis. This effect could be attributed to the protective, antioxidant, anti-inflammatory, and anti-apoptotic properties of the extract., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Pseudo-cereals such as buckwheat ( Fagopyrum esculentum ) are valid candidates to promote diet biodiversity and nutrition security in an era of global climate change. Buckwheat hulls (BHs) are currently an unexplored source of dietary fibre and bioactive phytochemicals. This study assessed the effects of several bioprocessing treatments (using enzymes, yeast, and combinations of both) on BHs' nutrient and phytochemical content, their digestion and metabolism in vitro (using a gastrointestinal digestion model and mixed microbiota from human faeces). The metabolites were measured using targeted LC-MS/MS and GC analysis and 16S rRNA gene sequencing was used to detect the impact on microbiota composition. BHs are rich in insoluble fibre (31.09 ± 0.22% as non-starch polysaccharides), protocatechuic acid (390.71 ± 31.72 mg/kg), and syringaresinol (125.60 ± 6.76 mg/kg). The bioprocessing treatments significantly increased the extractability of gallic acid, vanillic acid, p-hydroxybenzoic acid, syringic acid, vanillin, syringaldehyde, p-coumaric acid, ferulic acid, caffeic acid, and syringaresinol in the alkaline-labile bound form, suggesting the bioaccessibility of these phytochemicals to the colon. Furthermore, one of the treatments, EC&#95;2 treatment, increased significantly the in vitro upper gastrointestinal release of bioactive phytochemicals, especially for protocatechuic acid ( p < 0.01). The BH fibre was fermentable, promoting the formation mainly of propionate and, to a lesser extent, butyrate formation. The EM&#95;1 and EC&#95;2 treatments effectively increased the content of insoluble fibre but had no effect on dietary fibre fermentation ( p > 0.05). These findings promote the use of buckwheat hulls as a source of dietary fibre and phytochemicals to help meet dietary recommendations and needs.

Although the induction of cytochrome P450 monooxygenases involved in insect detoxification has been well documented, the underlying regulatory mechanisms remain obscure. In Spodoptera litura , CYP321A subfamily members were effectively induced by exposure to flavone, xanthotoxin, curcumin, and λ-cyhalothrin, while knockdown of the CYP321A genes increased larval susceptibility to these xenobiotics. Homology modeling and molecular docking analyses showed that these four xenobiotics could stably bind to the CYP321A enzymes. Furthermore, two transcription factor genes, CncC and MafK, were significantly induced by the xenobiotics. Knockdown of CncC or MafK reduced the expression of four CYP321A genes and increased larval susceptibility to the xenobiotics. Dual-luciferase reporter assays showed that cotransfection of reporter plasmids carrying the CYP321A promoter with CncC and/or MafK-expressing constructs significantly magnified the promoter activity. These results indicate that the induction of CYP321A subfamily members conferring larval detoxification capability to xenobiotics is mediated by the activation of CncC and MafK.

During aging, several tissues and biological systems undergo a progressive decline in function, leading to age-associated diseases such as neurodegenerative, inflammatory, metabolic, and cardiovascular diseases and cancer. In this review, we focus on the molecular underpinning of senescence and neurodegeneration related to age-associated brain diseases, in particular, Alzheimer's and Parkinson's diseases, along with introducing nutrients or phytochemicals that modulate age-associated molecular dysfunctions, potentially offering preventive or therapeutic benefits. Based on current knowledge, the dysregulation of microglia genes and neuroinflammation, telomere attrition, neuronal stem cell degradation, vascular system dysfunction, reactive oxygen species, loss of chromosome X inactivation in females, and gut microbiome dysbiosis have been seen to play pivotal roles in neurodegeneration in an interactive manner. There are several phytochemicals (e.g., curcumin, EGCG, fucoidan, galangin, astin C, apigenin, resveratrol, phytic acid, acacetin, daucosterol, silibinin, sulforaphane, withaferin A, and betulinic acid) that modulate the dysfunction of one or several key genes (e.g., TREM2, C3, C3aR1, TNFA, NF-kb, TGFB1&2, SIRT1&6, HMGB1, and STING) affected in the aged brain. Although phytochemicals have shown promise in slowing down the progression of age-related brain diseases, more studies to identify their efficacy, alone or in combinations, in preclinical systems can help to design novel nutritional strategies for the management of neurodegenerative diseases in humans.

Acne vulgaris is a highly prevalent skin condition caused by androgen-induced elevated sebum secretion, abnormal keratinization, bacterial colonization, and inflammation. Current research indicates a link between acne vulgaris and the metabolic syndrome, a group of disorders that includes obesity, insulin resistance, hypertension, and dyslipidemia. This link is thought to be modulated by excessive concentrations of oxidative stress markers and chronic inflammation, which are included in the pathophysiological mechanisms shared by both conditions. Excessive generation of reactive oxygen species damages cellular components and initiates an inflammatory response, hence promoting the development of both disorders. The current narrative review focuses on the molecular implications of inflammatory, hormonal, and environmental factors in the acne-metabolic syndrome correlation. Furthermore, it outlines the current state of knowledge related to the phyto-therapeutic approach to these conditions as an adjuvant strategy to allopathic treatment, but future multicenter and larger-scale research studies are needed establish new algorithms to be included in the future management of patients with these conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Herbal medicinal products containing Vaccinium myrtillus L. (bilberry) fruits and fruit extracts are widely available in the market. Although bilberry leaves and stems are considered as bio-waste, they contain much higher levels of phenolic compounds than fruits. The study aimed to investigate the antimicrobial and anticancer potential of aerial part extracts from Vaccinium myrtillus L. ( V. myrtillus , VM) plants harvested at high altitudes in Armenian landscape and characterize the bioactive phytochemicals., Material and Methods: For evaluation of antioxidant properties, chemical-based tests (total phenolic and flavonoid content, and antiradical activity in 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) tests) and cellular antioxidant activity (CAA) assay were applied. Genotoxicity and anticancer properties of the extract alone and in combination with fluorouracil were explored in human cancer and normal cell lines. Antibacterial properties of V. myrtillus extract alone and in combination with antibiotics, as well as their effect on proton-flux rate through cell membrane were explored on bacterial strains. The characterization of active phytochemicals was done using Liquid Chromatography-Quadrupole-Orbitrap High-Resolution Mass Spectrometry (LC-Q-Orbitrap HRMS)., Results: The V. myrtillus aerial part extract demonstrated promising antioxidant properties in all tests. The selective cytotoxic activity was documented against various cancer cell lines (human colon adenocarcinoma (HT29), human breast cancer (MCF-7) and human cervical carcinoma (HeLa)), while it did not inhibit the growth of tested human normal primary renal mixed epithelial cells (HREC) even at 10-fold higher concentrations. The extract did not have genotoxic properties in comet assay making it a potential source for the development of anticancer preparations. The investigated extract did not directly inhibit the growth of Escherichia coli ( E. coli ) and Salmonella typhimurium ( S. typhimurium ) strains at up to 1 mg/mL concentration. However, V. myrtillus extract enhanced the kanamycin intake and increased its efficiency against E. coli strain. The phytochemical characterization of the extract showed the presence of different groups of phenolics., Conclusions: Based on obtained data, we suggest the aerial parts of the V. myrtillus plant as an alternative source of bioactive natural products for food supplements, nutraceuticals, functional foods and medicine., Competing Interests: The authors declare no conflict of interest. Anne Vejux is serving as one of the Editorial Board Members and Guest Editors of this journal. We declare that Anne Vejux had no involvement in the peer review of this article and has no access to information regarding its peer review., (© 2023 The Author(s). Published by Discovery Medicine.)

Annona muricate is a tropical plant that is well-known for its edible fruit of therapeutic interest. LCMS/MS analyses were applied to identify phytoconstituents of the ethanolic extract of the whole fruits and the aqueous extract of the edible fruit part, in addition to the investigation of their anticancer properties against Ehrlich ascites carcinoma (EAC) in male albino mice. LCMS/MS analyses resulted in the identification of 388 components, representing a wide array of classes of compounds, including acetogenins as the major constituents, alkaloids, flavonoids, and phenolics. Among them, four compounds were tentatively characterized as new compounds ( 1 - 4 ), including an acid derivative, protocatechuic-coumaroyl-quinic acid ( 1 ), and three flavonoid derivatives, dihydromyricetin galloyl hexoside ( 2 ), apigenin gallate ( 3 ), and dihydromyricetin hexouronic acid hexoside ( 4 ). Induction with EAC cells resulted in abnormalities in the gene expression of pro-apoptotic genes (Bax and caspase-3) and anti-apoptotic gene (Bcl-2) in the tumor mass. Moreover, microscopic, histopathological, and immune-histochemical examinations of the tumor mass and liver tissues exhibited extensive growth of malignant Ehrlich carcinoma cells and marked hydropic degeneration of hepatocytes and infiltration by tumor cells to liver tissue with marked inflammatory reaction. These abnormalities were markedly ameliorated aftertreatment of EAC mice with A. muricata extracts.

Aflatoxin B1 is a secondary metabolite with a potentially devastating effect in causing liver damage in broiler chickens, and this is mainly facilitated through the generation of oxidative stress and malonaldehyde build-up. In the past few years, significant progress has been made in controlling the invasion of aflatoxins. Phytochemicals are some of the commonly used molecules endowed with potential therapeutic effects to ameliorate aflatoxin, by inhibiting the production of reactive oxygen species and enhancing intracellular antioxidant enzymes. Experimental models involving cell cultures and broiler chickens exposed to aflatoxin or contaminated diet have been used to investigate the ameliorative effects of phytochemicals against aflatoxin toxicity. Electronic databases such as PubMed, Science Direct, and Google Scholar were used to identify relevant data sources. The retrieved information reported on the link between aflatoxin B1-included cytotoxicity and the ameliorative potential/role of phytochemicals in chickens. Importantly, retrieved data showed that phytochemicals may potentially protect against aflatoxin B1-induced cytotoxicity by ameliorating oxidative stress and enhancing intracellular antioxidants. Preclinical data indicate that activation of nuclear factor erythroid 2-related factor 2 (Nrf2), together with its downstream antioxidant genes, may be a potential therapeutic mechanism by which phytochemicals neutralize oxidative stress. This highlights the need for more research to determine whether phytochemicals can be considered a useful therapeutic intervention in controlling mycotoxins to improve broiler health and productivity.

Wood-decaying fungi are the major decomposers of plant litter. Heavy sequencing efforts on genomes of wood-decaying fungi have recently been made due to the interest in their lignocellulolytic enzymes; however, most parts of their proteomes remain uncharted. We hypothesized that wood-decaying fungi would possess promiscuous enzymes for detoxifying antifungal phytochemicals remaining in the dead plant bodies, which can be useful biocatalysts. We designed a computational mass spectrometry-based untargeted metabolomics pipeline for the phenotyping of biotransformation and applied it to 264 fungal cultures supplemented with antifungal plant phenolics. The analysis identified the occurrence of diverse reactivities by the tested fungal species. Among those, we focused on O -xylosylation of multiple phenolics by one of the species tested, Lentinus brumalis . By integrating the metabolic phenotyping results with publicly available genome sequences and transcriptome analysis, a UDP-glycosyltransferase designated UGT66A1 was identified and validated as an enzyme catalyzing O -xylosylation with broad substrate specificity. We anticipate that our analytical workflow will accelerate the further characterization of fungal enzymes as promising biocatalysts.

In this study, we investigated in vitro the potential of Trichoderma harzianum to produce bioactive secondary metabolites that can be used as alternatives to synthetic compounds. The study focused on analyzing two extracts of T. harzianum using ethyl acetate and n -butanol solvents with different polarities. The extracts were examined using phytochemical analysis to determine the content of polyphenols, flavonoids, tannins, and alkaloids. Thin-layer chromatography (TLC) and Gas chromatography-mass spectroscopy (GC-MS) analysis were used to profile volatile organic metabolites (VOCs) present in the extracts. Furthermore, the extracts were tested for their antifungal ability using the poison food technique. For measuring antioxidant activity, the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) test was used. Trichoderma harzianum was shown to have a significantly high content of tannins and alkaloids, with a noticeable difference between the two extracts. GC-MS analysis identified 33 potential compounds with numerous benefits that could be used in agriculture and the medicinal industry. Moreover, strong antifungal activity was identified against Sclerotinia sclerotiorum by 94.44%, Alternaria sp. by 77.04%, and Fusarium solani by 51.48; similarly, the IC 50 of antioxidant activity was estimated for ethyl acetate extract by 71.47% and n -butanol extract by 56.01%. This leads to the conclusion that Trichoderma harzianum VOCs play a significant role as an antifungal and antioxidant agent when taking into account the advantageous bioactive chemicals noted in the extracts. However, to our knowledge, this is the first study in Algeria presenting detailed phytochemical analysis and GC-MS profiling of Trichoderma harzianum for two extracts, ethyl acetate and n -butanol.

Trembling aspen (Populus tremuloides) is arguably the most important deciduous tree species in the Intermountain West of North America. There, as elsewhere in its range, aspen exhibits remarkable genetic variation in observable traits such as morphology and phenology. In contrast to Great Lakes populations, however, relatively little is known about phytochemical variation in western aspen. This survey of phytochemistry in western aspen was undertaken to assess how chemical expression varies among genotypes, cytotypes (diploid vs. triploid), and populations, and in response to development and mammalian browsing. We measured levels of foliar nitrogen, salicinoid phenolic glycosides (SPGs) and condensed tannins (CTs), as those constituents influence organismal interactions and ecosystem processes. Results revealed striking genotypic variation and considerable population variation, but minimal cytotype variation, in phytochemistry of western aspen. Levels of SPGs and nitrogen declined, whereas levels of CTs increased, with tree age. Browsed ramets had much higher levels of SPGs, and lower levels of CTs, than unbrowsed ramets of the same genotype. We then evaluated how composite chemical profiles of western aspen differ from those of Great Lakes aspen (assessed in earlier research). Interestingly, mature western aspen trees maintain much higher levels of SPGs, and lower levels of CTs, than Great Lakes aspen. Phenotypic variation in chemical composition of aspen - a foundation species - in the Intermountain West likely has important consequences for organismal interactions and forest ecosystem dynamics. Moreover, those consequences likely play out over spatial and temporal scales somewhat differently than have been documented for Great Lakes aspen., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lavandula species are one of the most useful aromatic and medicinal plants and have great economic potential. The phytopharmaceutical contribution of the secondary metabolites of the species is unquestionable. Most recent studies have been focusing on the elucidation of the genetic background of secondary metabolite production in lavender species. Therefore, knowledge of not only genetic but especially epigenetic mechanisms for the regulation of secondary metabolites is necessary for the modification of those biosynthesis processes and the understanding of genotypic differences in the content and compositional variability of these products. The review discusses the genetic diversity of Lavandula species in relation to the geographic area, occurrence, and morphogenetic factors. The role of microRNAs in secondary-metabolites biosynthesis is described.

Interaction of different pollutants can aggravate hazards to biotic components in agroecosystems. Microplastics (MPs) are especially needed to be focused on because of their increasing use in life around the globe. We investigated the interactive impacts of polystyrene microplastics (PS-MP) and lead (Pb) on mung bean (Vigna radiata L.). Toxicity of MPs and Pb directly impeded V. radiata attributes. In combination i.e., M2P2 (40 µM Pb + 4.0 mg L-1 MPs) predominantly reduced the shoot root fresh and dry weights. \ Pb and PS-MP impaired the Rubisco activity and chlorophyll contents. The dose dependent relationship (M2P2) discomposed indole 3-acetic acid by 59.02%. Individual treatments P2 (40 µM Pb) and M2 (4.0 mg L -1 MPs) respectively instigated a decline (44.07% and 27.12%) in IBA, while ABA was elevated. M2 significantly enhanced the contents of Alanine (Ala), Arginine (Arg), Proline (Pro), and glycine (Gly) by 64.11%, 63%, and 54% compared to control. Lysine (Lys) and Valine (Val) presented a converse relationship with other amino acids. Except for control, a gradual decline in yield parameters were observed in individual and combined applications of PS-MP. Proximate composition of carbohydrates, lipids and proteins also reflected a clear decrease in these compounds after combined application of Pb and MPs. Although, individual doses caused a decline in these compounds but effect of combined doses Pb and PS-MP was highly significant. Our results demonstrated the toxicity effect of Pb and MP in V. radiata attributes that is mainly linked with cumulative physiological and metabolic perturbations. These collective negative impacts of different doses of MPs and Pb on V. radiata would certainly pose serious implications for humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Phytochemicals are a class of potential pesticides for pest control. Our previous studies have demonstrated that the development of Spodoptera litura is suppressed by two phytochemicals, flavone and xanthotoxin. Generally, phytochemical is metabolized by insect detoxification enzyme systems. Nuclear receptor (NR) is the ligand-activated transcription factor that involved in the regulation of detoxification gene expressions. To explore how NR responds to phytochemical to mediate detoxification gene expression, in the present study, 19 NRs were firstly identified in S. litura genome. The transcriptional levels of most NRs were significantly induced in the midgut of S. litura larvae after exposure to flavone and xanthotoxin. RNAi-mediated knockdown of FTZF1, EcR, Dsf, and HR3 remarkably reduced the larval tolerance to flavone or xanthotoxin. In addition, many crucial detoxification genes were downregulated by dsNR administrations, which might be responsible for the high sensitivity of S. litura to phytochemicals. Molecular docking indicated that phytochemicals as the potential ligands had high affinity to bind to NRs. This study suggested that NR potentially regulated the transcriptional expression of detoxification genes in response to phytochemical stresses, which partially elucidated the mechanism of extensive host adaptation in S. litura and provided the theoretical evidences for the development of NR-targeted insecticides., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)