Kaurenoic Acid Research Articles

Isolation of Allelochemicals from Rhododendron capitatum and Their Allelopathy on Three Perennial Herbaceous Plants.

Rhododendron capitatum community expansion is a major threat to alpine meadow. Allelopathy is an important mediator in managing relationships between plants in natural ecosystems. However, allelopathy and specific allelochemicals of R. capitatum have not been studied yet. In this study, the allelopathy of the foliage litter of R. capitatum was explored on Elymus nutans, Poa pratensis and Medicago ruthenica, and the chemical composition and their allelopathy were studied. The results showed that the aqueous extract of the foliage litter of R. capitatum had an allelopathy of "low concentration promotion and high concentration inhibition" on the germination of E. nutans, P. pratensis, and M. ruthenica. Organic acids, fatty acids, terpenes, phenols, and phenolic acid compounds were identified, with Zanamivir (77.81%), alpha-linolenic acid (18%), Kaurenoic acid (23.50%), 4-hydroxyphenylglycolic acid (21.54%), and Quinic acid (28.24%) having the highest relative content, and all five compounds showed significantly inhibitory effects on seed germination and seedling growth of E. nutans, P. pratensis, and M. ruthenica, which further suggests that the five compounds are the critical allelochemicals for negative allelopathy of R. capitatum. These results highlight the crucial role of inhibitory allelopathy produced by R. capitatum in the establishment and expansion of its populations.

Inactivation Pathway of Diterpenoid Regulator in the Moss Physcomitrium patens

AbstractThe endogenous levels of plant hormones, including gibberellins (GAs), are strictly regulated and maintained during growth and development in seed plants. The regulation of endogenous levels of bioactive GAs is mediated by the mechanisms of their biosynthesis and inactivation. The moss Physcomitrium patens harbors a partial GA biosynthetic pathway from geranylgeranyl diphosphate to ent-kaurenoic acid (KA). Recently, we have identified ent-3β-hydroxy kaurenoic acid (3OH-KA) as a biologically active metabolite of KA to control the protonemal cell differentiation. In addition, ent-2α-hydroxy kaurenoic acid catalyzed by KA 2-oxidase (KA2ox) was also identified as inactive product. Although the activation and inactivation pathways from KA have been identified, the inactivation pathway of 3OH-KA remains to be elucidated. Considering the GA inactivation mechanism of flowering plants, in which GA2ox hydroxylates the C-2 position of GAs as part of the biosynthetic pathway, it was presumed that 3OH-KA was converted to 2,3-dihydroxy KA by PpKA2ox; however, this work shows that PpKA2ox undergoes hydroxylation at the C-16 position to synthesize a new compound ent-3β,16β-dihydroxy kaurenoic acid (3,16diOH-KA) from 3OH-KA. The protonemal cell differentiation activity of 3,16diOH-KA was low, and 3,16diOH-KA was detected in wild-type strains. These results indicate that 3,16diOH-KA was the major inactivating metabolite of 3OH-KA.

Targeting human inosine 5’ monophosphate dehydrogenase type 2 for anti-dengue lead identification – a computational approach

Dengue is a rapidly evolving arboviral disease that mainly affects tropical and subtropical regions of the world. The lack of therapeutic drugs and effective vaccines suggests that further resources need to be investigated. The effectiveness of the existing dengue vaccine is improbable as its efficacy depends on prior exposure to the dengue virus(DENV). Although the mechanism underlying the action of bioactive compounds to limit viral replication is less studied and still needs to be further explored, medicinal plants are excellent alternatives to combat DENV infection. In the current study, an in silico screening of phytochemicals from Annona reticulata Linn. against human Impdh2 was performed using Autodock Vina. Daucosterol (−9.0 kcal/mol) and Kaurenoic acid (−8.5 kcal/mol) were chosen as the top hits based on molecular interaction analysis. The hits were further exposed to pharmacokinetics and toxicity properties to determine their drug-like parameters. Molecular dynamics simulation studies of the Impdh2-top hits were carried out to investigate their kinetic behaviour and structural stabilities. The binding free energies of the Impdh2-hit complexes were determined using MM-PBSA analysis. According to the overall conclusions of the study, Daucosterol showed good binding affinity and high structural stability to the binding site residues of the target, therefore it is recommended as a lead compound against dengue. Communicated by Ramaswamy H. Sarma

Full-length transcriptome profiling of Acanthopanax gracilistylus provides new insight into the kaurenoic acid biosynthesis pathway.

The online version contains supplementary material available at 10.1007/s12298-024-01436-7.

In Silico Analysis of Selected Mikania Constituents As Human HMG-CoA Reductase, Human Inducible Nitric Oxide Synthase, and Human Squalene Synthase Inhibitory Agents.

Background Numerous pharmacological activities have been reportedin Mikania species. In the present investigation, we aimed to evaluate 26 selected constituents of Mikania as potent inhibitory agents of human HMG-CoA reductase (hHMGR), human inducible nitric oxide synthase (hiNOS), and human squalene synthase (hSQS) using the in silico method. Methodology Twenty-six selected constituents of Mikania were investigated based on the docking behavior of three target enzymes, namely hHMGR, hiNOS, and hSQS, using the Cdocker method (Discovery Studio® 3.1, Accelrys, Inc., San Diego, CA). Results Docking analysis showed that methyl-3,5-di-O-caffeoyl quinate (MCQ) has the maximum binding energy (BE) (-39.63, -50.65, and -58.56 kcal/mol) with hHMGR, hiNOS, and hSQS enzymes. On the other hand, six ligands (kaurenoic acid (KAA), stigmasterol (SS), grandifloric acid (GA), kaurenol (KA), spathlenol (SP), and taraxerol (TA)) of Mikania failed to dock with either of the targetenzymes (hHMGR, hiNOS, or hSQS). Conclusions The findings of the current study provide new insight regarding 26 selected ligands of Mikania as potent inhibitory agents of hHMGR, hiNOS, and hSQS.

Aromatase inhibition using Juniperus procera phytochemical constituents: molecular docking study

The key step in the biosynthesis of estrogen is the enzyme activity of aromatase. Several malignancies, including breast cancer, have been linked to the initiation and progression of estrogen overexpression. Exemestane, Arimidex and Femara are the most common aromatase inhibitors used to treat hormone-dependent breast cancers. Drug resistance and side effects are commonly associated with these treatments. The purpose of this in silico study was to list the chemical compounds of Juniperus procera that have been published in scientific papers. The second goal was to evaluate the inhibitory activity of 124 phytochemicals of Juniperus procera compared to known aromatase inhibitors such as Exemestane, Arimidex and Femara. The 3D structure of aromatase (PDB id: 3s7s) employed for docking studies using AutoDock Tools as well as normal mode analysis studies utilizing the NMSim web server. Juniperolide, Kaurenoic acid and Isocupressic acid were identified as competitive aromatase inhibitors compared to FDA approved anti-cancer drugs, specifically Exemestane, Arimidex and Femara. The stability of the ligand–protein interface was studied to support the docking findings. To our knowledge, this is the first study that investigates the possible inhibition roles of some compounds of Juniperus procera on the aromatase enzyme.

Sargassum pallidum reduces inflammation to exert antidepressant effect by regulating intestinal microbiome and ERK1/2/P38 signaling pathway.

Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.

Applicability of NMR in combination with chemometrics for the characterization and differentiation of oil-resin extracted from Copaifera langsdorffii and Copaifera spp.

Copaiba oil-resin is a natural product widely used in popular medicine and as raw material for pharmaceutical and cosmetic industry. Differences between species or extraction sites can cause changes in the product composition, which highlights the importance of its quality control regarding purity and identification of the Copaifera species from which the oil-resin was extracted. Thus, this work proposes to use the NMR technique associated with chemometric to differentiate and characterize samples of copaiba oil-resin obtained from different species and regions of Brazil. For this, 1H and 13C NMR spectra of 26 samples of copaiba oil-resin were acquired and submitted to chemometric analysis, which allows the recognition of patterns between the samples, as well as indicate the main variables responsible for the clustering. Based on these results, two-dimensional NMR experiments were carried out to identify the structure of the molecules that can be used as chemical markers to differentiate the oil-resin extracted from the Copaifera langsdorffii from other Copaifera species (Copaifera spp.). The structural elucidation of three terpenes (hardwickic acid, caryophyllene oxide, and kaurenoic acid) was successfully achieved, thus showing a decisive role in distinguishing the Copaifera langsdorffii samples.

Safety evaluation of the food additive steviol glycosides, predominantly Rebaudioside M, produced by fermentation using Yarrowia lipolyticaVRM.

The EFSA Panel on Food Additive and Flavourings (FAF Panel) provides a scientific opinion on the safety of a new process to produce steviol glycosides by fermentation of simple sugars using a genetically modified strain of Yarrowia lipolytica (named Y. lipolytica VRM). The manufacturing process may result in impurities different from those that may be present in the other steviol glycosides E 960a-d, therefore the Panel concluded that separate specifications are required for the food additive produced as described in the current application. Viable cells and DNA from the production strain are not present in the final product. The Panel considered that the demonstration of the absence of kaurenoic acid in the proposed food additive, using a method with a limit of detection (LOD) of 0.3 mg/kg, is adequate to dispel the concerns for potential genotoxicity. Given that all steviol glycosides follow the same metabolic pathways, the Panel considered that the current steviol glycosides would fall within the same group of substances. Therefore, the Panel considered that the already existing data on rebaudioside M and structurally related steviol glycosides are sufficient, and a similar metabolic fate and toxicity is expected for the food additive. The results from the bacterial reverse mutation assay and the invitro micronucleus assay were negative and indicated absence of genotoxicity from the food additive. The existing acceptable daily intake (ADI) of 4 mg/kg body weight (bw) per day, expressed as steviol equivalents, was considered to be applicable to the proposed food additive. The Panel concluded that there is no safety concern for steviol glycosides, predominantly Rebaudioside M, produced by fermentation using Y. lipolytica VRM, to be used as a food additive at the proposed uses and use levels.

Long-day photoperiodic requirements for steviol glycosides and gibberellins biosynthesis and bio-sweetener levels optimization in Stevia rebaudiana Bertoni

Stevia rebaudiana, as a short-day perennial, produces steviol glycoside (StGlys) metabolites recognized as healthy natural sweeteners, ca. 300 times sweeter than sucrose, being stevioside (ST) and rebaudioside A (Reb-A), the main StGlys for the natural sweetener demanding industries. Nevertheless, discussions persist regarding the ideal light regimen and respective StGlys biosynthesis regulation in S. rebaudiana aimed at enhancing and optimizing the StGlys large-scale production for industrial purposes. The present work reports on the biosynthesis and the contents of StGlys in leaves and stems in different developmental stages of S. rebaudiana plants submitted to different photoperiods. The final contents resulted from the response of genes in the shared StGlys and gibberellins (GAs) biosynthesis pathway, notably showing differential gene expression patterns in leaves and stems at the different developmental stages. Plants developing under 16/8 h (light/dark) photoperiod increased StGlys contents resulting from the upregulation of S. rebaudiana kaurenoic acid 13-hydroxylase (SrKAH) and uridine diphosphate glycosyltransferase (SrUGTs) genes in association with the downregulation of GAs biosynthesis-related genes in leaves. In contrast, the positive overall regulation of GAs biosynthesis genes in stems appeared as a requirement of GAs for stem elongation and plant growth. Conclusively, the research reports a deeper understanding of transcriptional responses, biosynthesis, and ST and Reb-A yield mechanisms in S. rebaudiana plants under different photoperiodic conditions. Altogether, leading to the potential optimization of commercial production, extraction, and purification while highlighting photoperiodic-responsive StGlys/GAs genes as potential molecular targets for metabolic engineering and future development of superior S. rebaudiana genotypes aiming further large-scale StGlys production and yield to attend the continuous increasing commercial and industrial demand.

Exploring the pharmacological mechanism of Qufeng Tongluo Formula in the treatment of rheumatoid arthritis using network pharmacology methods and in vitro experimental validation

BackgroundQufeng Tongluo Formula (QTF) is a clinical prescription for the treatment of rheumatoid arthritis. However, the mechanism and targets of action of QTF remain unclear. This study aims to uncover the pharmacological mechanism of QTF by employing a combination of network pharmacology and in vitro experimental validation. MethodsMultiple databases were searched to identify the targets of the ingredients present in Qufeng Tongluo Formula (QTF) and the targets associated with rheumatoid arthritis. The common targets between the component targets and disease targets were analyzed, and a visualization network representing the relationship between traditional Chinese medicine (TCM) components, diseases, and their targets was constructed. The STRING database was utilized to construct a protein-protein interaction (PPI) network of the common targets, and the CytoNCA plugin of Cytoscape software was utilized to identify the core targets. Metascape database was employed for GO and KEGG enrichment analysis of the common targets. The active ingredients of QTF and core targets were verified through molecular docking test. In vitro validation of the analysis results was performed using RA-FLS cells. ResultsAfter data summarization and de-duplication, a total of 70 active ingredients and 994 targets were identified for QTF, while 4242 targets were associated with rheumatoid arthritis. Among them, 463 targets were found to be common to both. The PPI network screening identified AKT1, TNF, TP53, JUN, and INS as the core targets. GO analysis yielded a total of 4041 entries, with 3411 related to biological processes, 449 to molecular functions, and 181 to cellular components. The KEGG enrichment analysis primarily revealed significant involvement in signaling pathways such as Chemokine, NF-kappa B, Calcium, cAMP, and JAK-STAT. Kaurenoic acid, the active ingredient of the QTF, showed good results in molecular docking with the core targets. In vitro cellular experiments, QTF exhibited inhibition of proliferation, migration, and invasion of RA-FLS, while also reducing the release of inflammatory factors by blocking the activation of the TNF-α-induced NF-κB signaling pathway. ConclusionsThis study conducted a comprehensive analysis of the targets and mechanisms that underlie the efficacy of QTF in the treatment of rheumatoid arthritis. Additionally, preliminary validation was achieved through in vitro experiments.

STITCH, Physicochemical, ADMET, and In Silico Analysis of Selected Mikania Constituents as Anti-Inflammatory Agents

The Mikania genus has been known to possess numerous pharmacological activities. In the present study, we aimed to evaluate the interaction of 26 selected constituents of Mikania species with (i) cyclooxygenase 2 (COX 2), (ii) human neutrophil elastase (HNE), (iii) lipoxygenase (LOX), matrix metalloproteinase ((iv) MMP 2 and (v) MMP 9), and (vi) microsomal prostaglandin E synthase 2 (mPGES 2) inhibitors using an in silico approach. The 26 selected constituents of Mikania species, namely mikamicranolide, kaurenoic acid, stigmasterol, grandifloric acid, kaurenol, spathulenol, caryophyllene oxide, syringaldehyde, dihydrocoumarin, o-coumaric acid, taraxerol, melilotoside, patuletin, methyl-3,5-di-O-caffeoyl quinate, 3,3′,5-trihydroxy-4′,6,7-trimethoxyflavone, psoralen, curcumene, herniarin, 2,6-dimethoxy quinone, bicyclogermacrene, α-bisabolol, γ-elemene, provincialin, dehydrocostus lactone, mikanin-3-O-sulfate, and nepetin, were assessed based on the docking action with COX 2, HNE, LOX, MMP 2, MMP 9, and mPGES 2 using Discovery Studio (in the case of LOX, the Autodock method was utilized). Moreover, STITCH (Search Tool for Interacting Chemicals), physicochemical, drug-likeness, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses were conducted utilizing the STITCH web server, the Mol-inspiration web server, and Discovery Studio, respectively. In the present study, STITCH analysis revealed only six ligands (dihydrocoumarin, patuletin, kaurenol, psoralen, curcumene, and nepetin) that showed interactions with human proteins. Physicochemical analysis showed that seventeen ligands complied well with Lipinski’s rule. ADMET analysis showed eleven ligands to possess hepatotoxic effects. Significantly, the binding free energy estimation displayed that the ligand methyl-3, 5-di-O-caffeoyl quinate revealed the highest binding energy for all the target enzymes, excluding LOX, suggesting that this may have efficacy as a non-steroidal anti-inflammatory drug (NSAID). The current study presents a better understanding of how Mikania is used as a traditional medicinal plant. Specifically, the 26 ligands of the Mikania plant are potential inhibitor against COX 2, HNE, LOX, MMP 2, MMP 9, and mPGES 2 for treatments for acute and/or chronic inflammatory diseases.

Key secondary metabolite markers for Wuchang Daohuaxiang rice discrimination in China

This study aimed to comprehensively elucidate the vital secondary metabolites of Wuchang Daohuaxiang (DHX) rice through widely targeted metabolomics analysis. Among the secondary metabolites detected, a total of 30 differential ones were screened out and categorized into 4 different classes, including 6 alkaloids (20%), 15 flavonoids (50%), 6 phenolic acids (20%), and 3 terpenoids (10%) between DHX and control groups. Of these, compounds as zarzissine, fagomine, arbutin, p-Hydroxypheny-β-D-allopyranoside, pimaric acid, kaurenoic acid, and isopimaric acid were more abundant in DHX than control group, with the possibility in serve as key secondary metabolites of DHX rice. Furthermore, arbutin, trigonelline and 6′-O-Feruloyl-D-sucrose were optimized as potential biomarkers for DHX rice discrimination. This study would supply data support for DHX rice authenticity and quality improvement.

Kaurenoic Acid Reduces Ongoing Chronic Constriction Injury-Induced Neuropathic Pain: Nitric Oxide Silencing of Dorsal Root Ganglia Neurons

Kaurenoic acid (KA) is a diterpene extracted from Sphagneticola trilobata (L.) Pruski. KA presents analgesic properties. However, the analgesic activity and mechanisms of action of KA in neuropathic pain have not been investigated so far; thus, we addressed these points in the present study. A mouse model of neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Acute (at the 7th-day post-CCI surgery) and prolonged (from 7-14th days post-CCI surgery) KA post-treatment inhibited CCI-induced mechanical hyperalgesia at all evaluated time points, as per the electronic version of von Frey filaments. The underlying mechanism of KA was dependent on activating the NO/cGMP/PKG/ATP-sensitive potassium channel signaling pathway since L-NAME, ODQ, KT5823, and glibenclamide abolished KA analgesia. KA reduced the activation of primary afferent sensory neurons, as observed by a reduction in CCI-triggered colocalization of pNF-κB and NeuN in DRG neurons. KA treatment also increased the expression of neuronal nitric oxide synthase (nNOS) at the protein level as well as the intracellular levels of NO in DRG neurons. Therefore, our results provide evidence that KA inhibits CCI neuropathic pain by activating a neuronal analgesic mechanism that depends on nNOS production of NO to silence the nociceptive signaling that generates analgesia.

Brown Macroalgae Sargassum cristaefolium Extract Inhibits Melanin Production and Cellular Oxygen Stress in B16F10 Melanoma Cells.

The brown macroalgae Sargassum has been reported for its anti-UV and photoprotective potential for industrial applications. This study evaluated the melanin inhibition activity of Sargassum cristaefolium (SCE) ethanol extract. Melanogenesis inhibition by SCE was assessed in vitro with B16-F10 melanoma cell models and in silico against melanin regulatory proteins Tyrosinase (TYR) and Melanocortin 1 Receptor (MC1R). The regulatory properties evaluated were the melanin content, intracellular tyrosinase activity and cellular antioxidant activities. In addition, the bioactive compounds detected in SCE were subjected to molecular docking against TYR and MC1R. Based on the results, 150 µg/mL SCE effectively inhibited the production of melanin content and intracellular tyrosinase activity. Cellular tyrosinase activity was reduced by SCE-treated cells in a concentration-dependent manner. The results were comparable to the standard tyrosinase inhibitor kojic acid. In addition, SCE effectively decreased the intracellular reactive oxygen species (ROS) levels in B16-F10 cells. The antioxidant properties may also contribute to the inhibition of melanogenesis. In addition, LCMS UHPLC-HR-ESI-MS profiling detected 33 major compounds. The results based on in silico study revealed that the bioactive compound putative kaurenoic acid showed a strong binding affinity against TYR (-6.5 kcal/mol) and MC1R (-8.6 kcal/mol). However, further molecular analyses are needed to confirm the mechanism of SCE on melanin inhibition. Nevertheless, SCE is proposed as an anti-melanogenic and antioxidant agent, which could be further developed into cosmetic skin care products.

Kaurenoic acid nanocarriers regulates cytokine production and inhibit breast cancer cell migration.

Breast cancer is the type of cancer with the highest incidence in women around the world. Noteworthy, the triple-negative subtype affects 20% of the patients while presenting the highest death rate among subtypes. This is due to its aggressive phenotype and the capability of invading other tissues. In general, tumor-associated macrophages (TAM) and other immune cells, are responsible for maintaining a favorable tumor microenvironment for inflammation and metastasis by secreting several mediators such as pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, chemokines like CCL2, and other proteins, as metalloproteinases of matrix (MMP). On the other hand, immunomodulatory agents can interfere in the immune response of TAM and change the disease prognosis. In this work, we prepared nanostructured lipid carriers containing kaurenoic acid (NLC-KA) to evaluate the effect on cytokine production in vitro of bone marrow-derived macrophages (BMDM) and the migratory process of 4T1 breast cancer cells. NLC-KA prepared from a blend of natural lipids was shown to have approximately 90nm in diameter with low polydispersity index. To test the effect on cytokine production in vitro in NLC-KA treated BMDM, ELISA assay was performed and pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified. The formulation reduced the secretion of IL-1β and TNF-α cytokines while presenting no hemolytic activity. Noteworthy, an anti-migratory effect in 4T1 breast cancer cells treated with NLC-KA was observed in scratch assays. Further, MMP9 and CCL2 gene expressions in both BMDM and 4T1 treated cells confirmed that the mechanism of inhibition of migration is related to the blockade of this pathway by KA. Finally, cell invasion assays confirmed that NLC-KA treatment resulted in less invasiveness of 4T1 cells than control, and it is independent of CCL2 stimulus or BMDM direct stimulus. Ultimately, NLC-KA was able to regulate the cytokine production in vitro and reduce the migration of 4T1 breast cancer cells by decreasing MMP9 gene expression.

In vitro efficacy of isoflavonoids and terpenes against Leishmania (Leishmania) infantum and L. amazonensis

The main form of control of leishmaniasis is the treatment, however various side effects and poor efficacy are associated with presently available drugs. The investigation of bioactive natural products for new antileishmanial drugs is a valid approach. The present study reports the in vitro efficacy of natural isoflavonoids and terpenes against Leishmania infantum and L. amazonensis and their cytotoxicity against HepG2 cells. L. infantum and L. amazonensis promastigotes were exposed to the terpenes kaurenoic acid, xylopic acid, and (−)-α-bisabolol and to the isoflavonoids (−)-duartin and (3R)-claussequinone for antileishmanial activity and to cytotoxicity to HepG2 cells. The most effective substance against both L. infantum and L. amazonensis species was (3R)-claussequinone (IC50 = 3.21 μg/mL and 2.47 μg/mL, respectively) that disclosed low cytotoxicity against HepG2 cells (CC50 = 387.79 μg/mL). The efficacy of (3R)-claussequinone against intracellular amastigotes of L. infantum and the externalization of phosphatidylserine in promastigotes of this isoflavanoid were investigated by infection of Raw 264.7 macrophages and marking with Annexin V-FITC and propidium Iodide for flow cytometry analysis. The results for amastigotes showed that (3R)-claussequinone was able to reduce the rate of infection with IC50 = 4.61 μg/mL and did not alter the externalization of phosphatidylserine. In conclusion it is presently reported, for the first time, the striking antileishmanial activity of (3R)-claussequinone against L. infantum and L. amazonensis associated to low cytotoxicity. Furthermore, these results suggest that (3R)-claussequinone is a new hit aiming to develop new therapeutic alternatives.

Paclobutrazol Ameliorates Low-Light-Induced Damage by Improving Photosynthesis, Antioxidant Defense System, and Regulating Hormone Levels in Tall Fescue.

Paclobutrazol (PBZ) is a plant-growth regulator (PGR) in the triazole family that enhances plant tolerance to environmental stresses. Low-light (LL) intensity is a critical factor adversely affecting the growth of tall fescue (Festuca arundinacea Schreb.). Therefore, in this study, tall fescue seedlings were treated with PBZ under control and LL conditions to investigate the effects of PBZ on enhancing LL stress resistance by regulating the growth, photosynthesis, oxidative defense, and hormone levels. Our results reveal that LL stress reduced the total biomass, chlorophyll (Chl) content, photosynthetic capacity, and photochemical efficiency of photosystem II (PSII) but increased the membrane lipid peroxidation level and reactive oxygen species (ROS) generation. However, the application of PBZ increased the photosynthetic pigment contents, net photosynthetic rate (Pn), maximum quantum yield of PSII photochemistry (Fv/Fm), ribulose-1,5-bisphosphate carboxylase (RuBisCO) activity, and starch content. In addition, PBZ treatment activated the antioxidant enzyme activities, antioxidants contents, ascorbate acid-glutathione (AsA-GSH) cycle, and related gene expression, lessening the ROS burst (H2O2 and O2∙−). However, the gibberellic acid (GA) anabolism was remarkably decreased by PBZ treatment under LL stress, downregulating the transcript levels of kaurene oxidase (KO), kaurenoic acid oxidase (KAO), and GA 20-oxidases (GA20ox). At the same time, PBZ treatment up-regulated 9-cis-epoxycarotenoid dioxygenase (NCED) gene expression, significantly increasing the endogenous abscisic acid (ABA) concentration under LL stress. Thus, our study revealed that PBZ improves the antioxidation and photosynthetic capacity, meanwhile increasing the ABA concentration and decreasing GA concentration, which ultimately enhances the LL stress tolerance in tall fescue.

Identification of the antibacterial action mechanism of diterpenoids through transcriptome profiling.

Effective antibacterial substances of Aralia continentalis have anti-biofilm and bactericidal activity to the oral pathogen Streptococcus mutans. In this study, three compounds extracted from A. continentalis were identified as acanthoic acid, continentalic acid, and kaurenoic acid by NMR and were further investigated how these diterpenoids affect the physiology of the S. mutans. When S. mutans was exposed to individual or mixed fraction of diterpenoids, severe growth defects and unique morphology were observed. The proportion of unsaturated fatty acids in the cell membrane was increased compared to that of saturated fatty acids in the presence of diterpenoids. Genome-wide gene expression profiles with RNA-seq were compared to reveal the mode of action of diterpenoids. Streptococcus mutans commonly enhanced the expression of 176 genes in the presence of the individual diterpenoids, whereas the expression of 232 genes was considerably reduced. The diterpenoid treatment modulated the expression of genes or operon(s) involved in cell membrane synthesis, cell division, and carbohydrate metabolism of S. mutans. Collectively, these findings provide novel insights into the antibacterial effect of diterpenoids to control S. mutans infection, which causes human dental caries.

Selective Oxidations in the Synthesis of Complex Natural ent-Kauranes and ent-Beyeranes.

Syntheses of two natural products derived from the ent-kaurene kaurenoic acid are described for the first time using regio- and diastereoselective oxidations. Palladium- and manganese-mediated oxidations were used to accomplish the syntheses of two ent-beyerane metabolites. The use of the White-Gormisky-Zhao catalyst Mn(CF3-PDP) enabled the first application of a nondirected metal-catalyzed oxidation in an unactivated C-H bond in a total synthesis.