Steroidal Alkaloids Research Articles

Enhanced steroidal alkaloids accumulation under abiotic elicitation of in vitro cultures of Fritillaria roylei using response surface methodology

Enhanced steroidal alkaloids accumulation under abiotic elicitation of in vitro cultures of Fritillaria roylei using response surface methodology

A scaffold protein manages the biosynthesis of steroidal defense metabolites in plants.

Solanaceae plants produce two major classes of valuable sterol derived natural products-steroidal glycoalkaloids and steroidal saponins-from a common cholesterol precursor. Attempts to heterologously produce these molecules have consistently failed, although the genes responsible for each biosynthetic step have been identified. Here we identify a cellulose synthase like protein, an unexpected biosynthetic component that interacts with the early pathway enzymes, enabling steroidal scaffolds production in plants. Moreover, knockout of this gene in black nightshade, Solanum nigrum resulted in plants lacking both steroidal alkaloids and saponins. Unexpectedly, these knockout plants also revealed that steroidal saponins deter serious agricultural insect pests. This discovery provides the missing link to engineer these high value steroidal molecules, and also pinpoints the ecological role for the steroidal saponins.

Fritillaria steroidal alkaloids and their multi-target therapeutic mechanisms: insights from network pharmacology.

Medicinal Fritillaria herbs, known for their rich content of steroidal alkaloids, have emerged as promising candidates in the treatment of chronic diseases due to their diverse pharmacological properties. Leveraging advancements in network pharmacology and molecular docking, this study explores the multi-target mechanisms through which these alkaloids exert therapeutic effects. The integration of bioinformatics, systems biology, and pharmacology in drug discovery has provided insights into the molecular interactions and pathways influenced by Fritillaria steroidal alkaloids. This review synthesizes comprehensive literature from 1985 to 2024, revealing the potential of these compounds in addressing respiratory diseases, inflammation, and cancer. The integration of traditional Chinese medicine (TCM) with modern pharmacological techniques underscores the relevance of these compounds in next-generation drug discovery. While initial findings are promising, further empirical validation is necessary to fully harness the therapeutic potential of Fritillaria steroidal alkaloids.

Natural Products-Based Anticancer Agents: Synthesis and Anticancer Activities of Funtumine Amide/sulfonamide Derivatives.

Funtumine is a pregnene-type steroidal alkaloid exhibiting moderate anticancer activity. To discovernovel natural product-based anticancer drugs, a series of novel funtumine amide/sulfonamide derivatives were papered and identified using spectroscopic techniques. Additionally, the structures of compounds 2j, 3a, and 4kwere further confirmed through X-ray diffraction analysis. Biological activity experiments conducted against three cancer cell lines revealed that several of the synthesized compounds demonstrated inhibition activities comparable to or exceeding those of the commercial anticancer agent, 5-Fluorouracil. Especially compound 4idemonstrated a notably strong growth inhibitory effect on HePG2 (IC50= 14.89 μM) and HCT116 (IC50= 15.67 μM) cell lines, while exhibiting minimal cytotoxicity towards human normal BEAS-2B cells. Preliminary structure-activity relationships (SARs) analysis indicated that the conversion of the carbonyl group at the C-20 position of funtumine to a hydroxyl group could yield more potent compounds.

Plants’ Impact on the Human Brain—Exploring the Neuroprotective and Neurotoxic Potential of Plants

Background: Plants have long been recognized for their potential to influence neurological health, with both neuroprotective and neurotoxic properties. This review explores the dual nature of plant-derived compounds and their impact on the human brain. Discussion: Numerous studies have highlighted the neuroprotective effects of various phytoconstituents, such as those found in Ginkgo biloba, Centella asiatica, Panax ginseng, Withania somnifera, and Curcuma longa. The neuroprotective compounds have demonstrated antioxidant, anti-inflammatory, and cognitive-enhancing properties, making them promising candidates for combating neurodegenerative diseases and improving brain function. Polyphenolic compounds, triterpenic acids, and specific phytocompounds like the ones from EGb 761 extract have shown interactions with key enzymes and receptors in the brain, leading to neuroprotective outcomes. However, this review also acknowledges the neurotoxic potential of certain plants, such as the Veratrum species, which contains steroidal alkaloids that can cause DNA damage and disrupt neurological function, or Atropa belladonna, which interfere with the normal functioning of the cholinergic system in the body, leading to a range of symptoms associated with anticholinergic toxicity. Conslusions: This review also emphasizes the need for further research to elucidate the complex mechanisms underlying the neuroprotective and neurotoxic effects of plant-derived compounds, as well as to identify novel phytoconstituents with therapeutic potential. Understanding the complex relationship between plants and the human brain is crucial for harnessing the benefits of neuroprotective compounds while mitigating the risks associated with neurotoxic substances. This review provides a comprehensive overview of the knowledge on the neurological properties of plants and highlights the importance of continued research in this field for the development of novel therapeutic strategies targeting brain health and neurological disorders.

The fate of a Solanum steroidal alkaloid toxin in the cabbage looper (Trichoplusia ni)

Plants produce complex chemical defenses against herbivores, resulting in the emergence of detoxification strategies in phytophagous insects. While enzymatic detoxification and target site mutagenesis are well-documented, the quantitative contribution of excretion remains less studied. We focus on the cabbage looper (Trichoplusia ni), a generalist herbivore, to elucidate the detoxification of a steroidal alkaloid, solanidine, produced in potato (Solanum tuberosum). Through larval feeding experiments and chemical analysis of metabolites using high-resolution mass spectrometry, we identify solanidine 3-O-β-glucopyranoside and solanidine 3-phosphate as major metabolization products of solanidine. Glycosylation and phosphorylation reactions have not previously been observed in cabbage looper. Modified solanidine derivatives exhibit reduced lipophilicity, preventing passive transport as predicted by physicochemical analyses, and only solanidine was detected in body tissue. In addition, the metabolism of solanidine in a T. ni mutant strain with midgut cadherin protein knocked out was also investigated to examine the potential role of the cadherin, an important receptor for Bt toxins, in steroidal alkaloid detoxification. T. ni cadherin-knockout strain showed lower solanidine conversion (33.9% ± 2.2) and uptake (27.41 ± 0.49 nmol/g) compared to the wild-type strain (51.3% ± 4.1, 33.66 ± 2.48 nmol/g) but similar excretion kinetics. Although solanidine negatively impacted the feeding performance of both strains the cadherin-knockout does not affect the feeding performance. Our study expands the metabolization enzyme repertoire in cabbage loopers, emphasizing the complexity of detoxification mechanisms in generalist herbivores.

Biochemometric-guided isolation of new Isosteroidal alkaloids from Fritillaria cirrhosa D.Don (Liliaceae, syn. Fritillaria roylei Hook) as acetylcholinesterase inhibitors.

Globally, Alzheimer's disease is an urgent public health concern with the ageing population in developing nations. Recent studies have identified isosteroidal alkaloids as promising therapeutic agents for Alzheimer's treatment. Fritillaria species are well-known rich sources of steroidal and isosteroidal alkaloids. In this context, the current study focuses on the biochemometric-guided isolation of three previously undescribed and two known isosteroidal alkaloids as acetylcholinesterase (AChE) inhibitors from the bulbs of Fritillaria cirrhosa D.Don. The isolated molecules were characterized by NMR, HR-ESI-MS, FT-IR, and DP4+ analysis. Subsequently, all isolates were evaluated for AChE inhibitory activity using Ellman's method. Among the evaluated molecules, 1 (IC50: 33.0 ± 4.4 μM) and 5 (IC50: 24.7 ± 4.5 μM) showed promising AChE inhibition in vitro. Enzyme kinetic studies of isolated molecules revealed mixed inhibition kinetics with Ki varying from 1.3 to 24.4 μM. Moreover, the in silico studies showed excellent binding affinities of isolated molecules with the target protein and good drug-like ADMET properties. The present study identified new isosteroidal alkaloids as promising AChE inhibitors from F. cirrhosa bulbs via a biochemometric approach and advocated their further exploration for treating neurodegenerative disorders.

A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes

Numerous eukaryotic toxins that accumulate in geophytic plants are valuable in the clinic, yet their biosynthetic pathways have remained elusive. A notable example is the >150 Amaryllidaceae alkaloids (AmAs), including galantamine, an FDA-approved treatment for Alzheimer's disease. We show that while AmAs accumulate to high levels in many daffodil tissues, biosynthesis is localized to nascent, growing tissue at the leaf base. A similar trend is found in the production of steroidal alkaloids (e.g., cyclopamine) in corn lily. This model of active biosynthesis enabled the elucidation of a complete set of biosynthetic genes that can be used to produce AmAs. Taken together, our work sheds light on the developmental and enzymatic logic of diverse alkaloid biosynthesis in daffodils. More broadly, it suggests a paradigm for biosynthesis regulation in monocot geophytes, where plants are protected from herbivory through active charging of newly formed cells with eukaryotic toxins that persist as above-ground tissue develops.

Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis.

Steroidal glycoalkaloids (SGAs) are specialized metabolites produced by hundreds of Solanum species including food crops, such as tomato, potato and eggplant. Unlike true alkaloids, nitrogen is introduced at a late stage of SGA biosynthesis through an unknown transamination reaction. Here, we reveal the mechanism by which GLYCOALKALOID METABOLISM12 (GAME12) directs the biosynthesis of nitrogen-containing steroidal alkaloid aglycone in Solanum. We report that GAME12, a neofunctionalized γ-aminobutyric acid (GABA) transaminase, undergoes changes in both active site specificity and subcellular localization to switch from its renown and generic activity in core metabolism to function in a specialized metabolic pathway. Moreover, overexpression of GAME12 alone in engineered S. nigrum leaves is sufficient for de novo production of nitrogen-containing SGAs. Our results highlight how hijacking a core metabolism GABA shunt enzyme is crucial in numerous Solanum species for incorporating a nitrogen to a steroidal-specialized metabolite backbone and form defensive alkaloids.

Integration of induction, system optimization and genetic transformation in Veratrum californicum var. vitro cultures to enhance the production of cyclopamine and veratramine

Cyclopamine, a compound found in wild Veratrum has shown promising potential as a lead anti-cancer drug by effectively blocking cancer signaling pathways. However, its complex chemical structure poses challenges for artificial synthesis, thus limiting its supply and downstream drug production. This study comprehensively utilizes induction, system optimization, and transgenic technologies to establish an efficient suspension culture system for the high-yield production of cyclopamine and its precursor, veratramine. Experimental results demonstrate that methyl jasmonate (MeJA) effectively promotes the content of veratramine and cyclopamine in Veratrum californicum var. callus tissue, while yeast extract (YE) addition significantly increases cell biomass. The total content of veratramine and cyclopamine reached 0.0638 mg after synergistic treatment of suspension system with these two elicitors. And the content of the two substances was further increased to 0.0827 mg after the optimization by response surface methodology. Subsequently, a genetic transformation system for V. californicum callus was established and a crucial enzyme gene VnOSC1, involved in the steroidal alkaloid biosynthesis pathway, was screened and identified for genetic transformation. Combined suspension culture and synergistic induction system, the total content of the two substances in transgenic suspension system was further increased to 0.1228 mg, representing a 276.69% improvement compared to the initial culture system. This study proposes a complete and effective genetic transformation and cultivation scheme for V. californicum tissue cells, achieving milligram-level production of the anticancer agent cyclopamine and its direct precursor veratramine for the first time. It provides a theoretical basis for the industrial-scale production of these substances.

Tomatidine, a Steroidal Alkaloid, Synergizes with Cisplatin to Inhibit Cell Viability and Induce Cell Death Selectively on FLT3-ITD+ Acute Myeloid Leukemia Cells.

Acute Myeloid Leukemia (AML) is a hematological cancer that frequently presents with a range of side effects and drug resistance during anticancer drug treatment. The current study aims to achieve increased efficacy by combining lower doses of cisplatin with increasing concentrations of tomatidine in AML cells to increase efficacy. Anti-proliferative effects of single and combination of cisplatin and tomatidine were assessed via MTT cell viability assay. The Annexin V/Propidium Iodide Double Staining method was used to measure the apoptotic effects of combined tomatidine and cisplatin treatment. Then, Western Blot analysis was performed to measure Poly (ADP-ribose) polymerase (PARP) and Caspase-3 protein expression levels. Cisplatin treatment with lower concentrations displayed high cytotoxic effects on AML cells, compared with tomatidine. The combination of the Inhibitory Concentration (IC) 20 value of cisplatin and increasing doses of tomatidine exhibited a significant decrease in cell viability relative to single treatments. The combination index analysis revealed a mild synergistic effect of cisplatin IC20 and varying tomatidine doses. The apoptosis induced when cisplatin was combined with 500 µM tomatidine by almost 20%, while the percentage of apoptosis in combination with 1 mM tomatidine was measured by 50% for both cell lines. The upregulation of proapoptotic cleaved-PARP (3.2 and 1.08-fold for THP-1 and MOLM-13, respectively) and downregulation in Caspase-3 (0.23 and 0.13-fold for THP-1 and MOLM-13, respectively) was detected. Together, the study indicated that when tomatidine combined with cisplatin on AML cell lines, a combinatorial anti-proliferative and apoptotic effect is observed. The combination of cisplatin with tomatidine may be a promising approach.

Unveiling the hidden potential: Above-ground parts of Paris yunnanensis Franch. Is promise as an anti-acne therapeutic beyond traditional medicinal sites

The dried rhizomes of Paris yunnanensis Franch. have been extensively utilized in traditional Chinese medicine as hemostatic, antitumor, and antimicrobial agents. An examination of classical texts and renowned Chinese medical formulations showcased its efficacy in acne treatment. Presently, there is a significant scarcity of Paris resources. Consider directing attention towards the non-medicinal parts of Paris to mitigate the strain on medicinal resources within this realm. To address these resource limitations, this study investigated the bioactivity and pharmacodynamics of the above-ground parts of Paris (AGPP). A synergistic approach integrating network pharmacology, molecular docking (in silico validation), and animal experimentation (in vivo validation) was employed to elucidate the potential mechanisms underlying the efficacy of AGPP against acne vulgaris in this study. The active constituents in AGPP extracts were identified via UHPLC-Q-Orbitrap HRMS analysis, with their targets extracted for network pharmacological analysis. KEGG pathway analysis unveiled potential therapeutic mechanisms, validated through molecular docking and rat auricular acne model experiments. Comprehensive chemical characterization revealed fifty constituents, including steroidal saponins, flavonoids, amino acids, organic acids, phytohormones, phenolic acids, and alkaloids. Diosgenin, Quercetin, Kaempferol, Ecdysone, and α-linolenic acid were identified as main constituents with acne-treating potential. Core targets included SRC, MAPK3, and MAPK1, with key signaling pathways implicated. Histologically, AGPP mitigated acne-induced follicular dilatation and inflammation, inhibiting inflammatory cytokine production (IL-6, IL-1β, TNF-α). This study offers insight into AGPP's mechanism for acne treatment, laying groundwork for Paris development and drug discovery.

Botrytis cinerea combines four molecular strategies to tolerate membrane-permeating plant compounds and to increase virulence

Saponins are plant secondary metabolites comprising glycosylated triterpenoids, steroids or steroidal alkaloids with a broad spectrum of toxicity to microbial pathogens and pest organisms that contribute to basal plant defense to biotic attack. Secretion of glycosyl hydrolases that enzymatically convert saponins into less toxic products was thus far the only mechanism reported to enable fungal pathogens to colonize their saponin-containing host plant(s). We studied the mechanisms that the fungus Botrytis cinerea utilizes to be tolerant to well-characterized, structurally related saponins from tomato and Digitalis purpurea. By gene expression studies, comparative genomics, enzyme assays and testing a large panel of fungal (knockout and complemented) mutants, we unraveled four distinct cellular mechanisms that participate in the mitigation of the toxic activity of these saponins and in virulence on saponin-producing host plants. The enzymatic deglycosylation that we identified is novel and unique to this fungus-saponin combination. The other three tolerance mechanisms operate in the fungal membrane and are mediated by protein families that are widely distributed in the fungal kingdom. We present a spatial and temporal model on how these mechanisms jointly confer tolerance to saponins and discuss the repercussions of these findings for other plant pathogenic fungi, as well as human pathogens.

Investigating Changes in Pharmacokinetics of Steroidal Alkaloids from a Hydroethanolic Fritillariae thunbergii Bulbus Extract in 2,4-Dinitrobenzene Sulfonic Acid-Induced Colitis Rats.

Fritillariae thunbergii Bulbus (FTB), a member of the Liliaceae family, has a long history of use in many herbal formulations for traditional and modern clinical applications to treat various infections and inflammation. To understand FTB's diverse physiochemical properties, it is important to determine the pharmacokinetic properties of its active constituents, the steroidal alkaloids. The aim of the present study was to investigate the pharmacokinetic alterations of the alkaloids, the active components of FTB, in the presence of colitis. A single oral dose of FTB (1 g/kg) was treated to a 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis rat model to assess whether the colitis condition could influence the pharmacokinetics of the major alkaloids present in FTB. Among the four major alkaloids, peimisine exhibited a significantly increased systemic exposure, approximately five times higher, under the colitis condition compared with the normal state. Meanwhile, peimine, peiminine, and sipeimine exhibited shorter half-lives in the DNBS group without significant changes in systemic absorption. As herbal medicine may contain active substances with different or opposing efficacies, careful consideration of pharmacokinetic changes in individual components due to diseases is necessary. Further experiments on peimisine are required to ensure the effectiveness and safety of FTB's clinical application in the presence of colitis.

Verazine biosynthesis from simple sugars in engineered Saccharomyces cerevisiae

Steroidal alkaloids are FDA-approved drugs (e.g., Zytiga) and promising drug candidates/leads (e.g., cyclopamine); yet many of the ≥697 known steroidal alkaloid natural products remain underutilized as drugs because it can be challenging to scale their biosynthesis in their producing organisms. Cyclopamine is a steroidal alkaloid produced by corn lily (Veratrum spp.) plants, and it is an inhibitor of the Hedgehog (Hh) signaling pathway. Therefore, cyclopamine is an important drug candidate/lead to treat human diseases that are associated with dysregulated Hh signaling, such as basal cell carcinoma and acute myeloid leukemia. Cyclopamine and its semi-synthetic derivatives have been studied in (pre)clinical trials as Hh inhibitor-based drugs. However, challenges in scaling the production of cyclopamine have slowed efforts to improve its efficacy and safety profile through (bio)synthetic derivatization, often limiting drug development to synthetic analogs of cyclopamine such as the FDA-approved drugs Odomzo, Daurismo, and Erivedge. If a platform for the scalable and sustainable production of cyclopamine were established, then its (bio)synthetic derivatization, clinical development, and, ultimately, widespread distribution could be accelerated. Ongoing efforts to achieve this goal include the biosynthesis of cyclopamine in Veratrum plant cell culture and the semi-/total chemical synthesis of cyclopamine. Herein, this work advances efforts towards a promising future approach: the biosynthesis of cyclopamine in engineered microorganisms. We completed the heterologous microbial production of verazine (biosynthetic precursor to cyclopamine) from simple sugars (i.e., glucose and galactose) in engineered Saccharomyces cerevisiae (S. cerevisiae) through the inducible upregulation of the native yeast mevalonate and lanosterol biosynthetic pathways, diversion of biosynthetic flux from ergosterol (i.e., native sterol in S. cerevisiae) to cholesterol (i.e., biosynthetic precursor to verazine), and expression of a refactored five-step verazine biosynthetic pathway. The engineered S. cerevisiae strain that produced verazine contains eight heterologous enzymes sourced from seven different species. Importantly, S. cerevisiae-produced verazine was indistinguishable via liquid chromatography-mass spectrometry from both a commercial standard (Veratrum spp. plant-produced) and Nicotiana benthamiana-produced verazine. To the best of our knowledge, this is the first report describing the heterologous production of a steroidal alkaloid in an engineered yeast. Verazine production was ultimately increased through design-build-test-learn cycles to a final titer of 83 ± 3 μg/L (4.1 ± 0.1 μg/g DCW). Together, this research lays the groundwork for future microbial biosynthesis of cyclopamine, (bio)synthetic derivatives of cyclopamine, and other steroidal alkaloid natural products.

A strategy integrating improved mass defect filtering, diagnostic product ions, and molecular network for rapid screening and systematic characterization of steroidal alkaloids in Fritillaria ussuriensis

An ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) method was employed to efficiently and rapidly analyze the chemical composition of steroidal alkaloids in Fritillaria ussuriensis Maxim (FM). The integration of nitrogen rule and improved mass defect filtering eliminated 84.61% of interfering MS1 peaks and facilitated subtype classification. Subsequently, six diagnostic product ions (DPIs) for Fritillaria alkaloids were summarized, guiding structural identification. Additionally, the adoption of molecular networks to infer potential compounds forms a new four-step comprehensive strategy for systematic screening and identification of Fritillaria alkaloids. By screening with the MDF window constructed from the Fritillaria alkaloids MS database combined with the nitrogen rule, a significant number of interfering MS1 peaks were eliminated, and different subtypes were distinguished. In FM, the number of positive-mode MS1 peaks was reduced by 84.61% (from 8,728 to 1,343). By summarizing the fragmentation behaviors of 22 reference standards, the fragmentation pathways and DPIs of five types of steroidal alkaloids were confirmed, providing the first evidence for DPIs of cevanine-seven-membered type Fritillaria alkaloids. Structural confirmation of MS1 peaks was carried out using an in-house database and DPIs. Furthermore, a feature-based molecular network (FBMN) was employed to cluster similar compounds into network clusters for rapid classification and to infer potential steroidal alkaloids using known compounds. A total of 103 Fritillaria alkaloids (65 cevanine type, 7 cevanine-seven-membered type, 18 jervine type, 5 veratramine type, 5 secosolanidine type, and 3 solanidine type) were identified, including 4 potential new compounds and 20 compounds that have been identified for the first time. This innovative comprehensive strategy, which includes NRF, improved MDF, DPIs, and FBMN, can be applied to rapidly screen, classify components, and conduct comprehensive characterization of complex samples such as herbal medicines.

Ethnomedicinal Usage, Phytochemistry and Pharmacological Potential of Solanum surattense Burm. f.

Solanum surattense Burm. f. is a significant member of the Solanaceae family, and the Solanum genus is renowned for its traditional medicinal uses and bioactive potential. This systematic review adheres to PRISMA methodology, analyzing scientific publications between 1753 and 2023 from B-on, Google Scholar, PubMed, Science Direct, and Web of Science, aiming to provide comprehensive and updated information on the distribution, ethnomedicinal uses, chemical constituents, and pharmacological activities of S. surattense, highlighting its potential as a source of herbal drugs. Ethnomedicinally, this species is important to treat skin diseases, piles complications, and toothache. The fruit was found to be the most used part of this plant (25%), together with the whole plant (22%) used to treat different ailments, and its decoction was found to be the most preferable mode of herbal drug preparation. A total of 338 metabolites of various chemical classes were isolated from S. surattense, including 137 (40.53%) terpenoids, 56 (16.56%) phenol derivatives, and 52 (15.38%) lipids. Mixtures of different parts of this plant in water-ethanol have shown in vitro and/or in vivo antioxidant, anti-inflammatory, antimicrobial, anti-tumoral, hepatoprotective, and larvicidal activities. Among the metabolites, 51 were identified and biologically tested, presenting antioxidant, anti-inflammatory, and antitumoral as the most reported activities. Clinical trials in humans made with the whole plant extract showed its efficacy as an anti-asthmatic agent. Mostly steroidal alkaloids and triterpenoids, such as solamargine, solanidine, solasodine, solasonine, tomatidine, xanthosaponin A-B, dioscin, lupeol, and stigmasterol are biologically the most active metabolites with high potency that reflects the new and high potential of this species as a novel source of herbal medicines. More experimental studies and a deeper understanding of this plant must be conducted to ensure its use as a source of raw materials for pharmaceutical use.

Comparative metabolomics reveals how the severity of predation by the invasive insect Cydalima perspectalis modulates the metabolism re-orchestration of native Buxus sempervirens.

The recent biological invasion of box tree moth Cydalima perspectalis on Buxus trees has a major impact on European boxwood stands through severe defoliation. This can hinder further regrowth and threaten survival of populations. In a mesocosm approach and controlled larval density over a 2-month period, responses of B. sempervirens essential and specialized metabolites were characterized using metabolomics, combining 1H-NMR and LC-MS/MS approaches. This is the first metabolome depiction of major Buxus responses to boxwood moth invasion. Under severe predation, remaining green leaves accumulate free amino acids (with the noticeable exception of proline). The leaf trans-4-hydroxystachydrine and stachydrine reached 10-13% and 2-3% (DW), while root content was lower but also modulated by predation level. Larval predation promoted triterpenoid and (steroidal) alkaloid synthesis and diversification, while flavonoids did not seem to have a relevant role in Buxus resistance. Our results reveal the concomitant responses of central and specialized metabolism, in relation to severity of predation. They also confirm the potential of metabolic profiling using 1H-NMR and LC-MS to detect re-orchestration of metabolism of native boxwood after severe herbivorous predation by the invasive box-tree moth, and thus their relevance for plant-insect relationships and ecometabolomics.

Assessing Plasma Accumulation of Steroidal Alkaloids and Their Metabolites in Healthy Adults Following Long-Term Tomato-Based Vegetable Juice Consumption

Assessing Plasma Accumulation of Steroidal Alkaloids and Their Metabolites in Healthy Adults Following Long-Term Tomato-Based Vegetable Juice Consumption

ANTIOXIDANT ENZYMES INVOLVED IN SEEDS’ GERMINATION MODULATED BY ACTIVE PRINCIPLES FROM PLANT EXTRACTS AND HYDROLYZED PROTEINS

Transition to organic farming requires the development of new methods to protect seeds from adverse factors. The germinative process and the post-germinative phase are strictly controlled by the oxidative balance involving lipid peroxidation, reactive oxygen species and enzymes activity, directing the plant viability and its further development. We focus our studies mainly on the seeds protection and fortification through natural solutions based on marigold and fenugreek extracts, steroid alkaloids from tomatoes and hydrolyzed proteins derived from leather waste industry. The structural configuration of the plant protection products proves significant effects fighting on different mechanisms of seeds’ oxidative stress. As well as the experimental design highlighted a tandem correlative mechanism between germination, decrease of lipid peroxidase and activation of catalase and superoxide-dismutase. SEM-PROTECT II was the most active biopesticide involved in these processes. Our findings directed complex research oriented to technological and experimental optimizations for the development of an innovative, efficient and competitive plant protection product to meet modern agriculture requirement.