Lavandula angustifolia mill. (Lamiaceae) ethanol extract and its main constituents as promising agents for the treatment of metabolic disorders: chemical profile, in vitro biological studies, and molecular docking.

Lavandula angustifolia Mill. (lavender) is one of the most used medicinal plants. Herein, we chemically characterised and investigated the antioxidant properties and the capability to inhibit key enzymes for the treatment of type 2 diabetes (TD2) and obesity such as pancreatic lipase, α-glucosidase, and α-amylase of the ethanolic extract of two lavender samples (La1 and La2) from southern Italy. Both extracts significantly inhibited α-glucosidase, while La1 inhibited α-amylase and lipase more effectively than La2. To investigate whether these properties could be due to a direct interaction of the main constituents of the extracts with the targeted enzymes, molecular docking studies have been performed. As a result, the selected compounds were able to interact with the key residues of the binding site of the three proteins, thus supporting biological data. Current findings indicate the new potential of lavender ethanolic extract for the development of novel agents for T2D and obesity.

Leonotis nepetifolia Transformed Root Extract Reduces Pro-Inflammatory Cytokines and Promotes Tissue Repair In Vitro.

Inflammation is closely related to asthma and its defining feature: airway remodeling. The aim of this study was to determine the effects of extracts of normal (NR) and transformed (TR) Leonotis nepetifolia roots on respiratory cells and against the gingival epithelium. Extracts from NR and TR roots were added to lung fibroblast, bronchial epithelial and gingival fibroblast cell lines, in the presence of HRV-16 infection, to determine their impact on inflammation. The expression of inflammatory cytokines (IL-6, IL-1ß, GM-CSF and MCAF) as well as total thiol contents were assessed. The TR extract inhibited rhinovirus-induced IL-6 and IL-1ß expression in all tested airway cells (p < 0.05). Additionally, the extract decreased GM-CSF expression in bronchial epithelial cells. The tested extracts had positive effects on total thiol content in all tested cell lines. The TR root extract demonstrated wound healing potential. While both tested extracts exhibited anti-inflammatory and antioxidative effects, they were stronger for the TR extract, possibly due to higher concentrations of beneficial metabolites such as phenols and flavonoids. Additionally, wound healing activity was demonstrated for the TR root extract. These results suggest that TR root extract may become a promising therapeutic agent in the future.

Uncovering a miltiradiene biosynthetic gene cluster in the Lamiaceae reveals a dynamic evolutionary trajectory.

The spatial organization of genes within plant genomes can drive evolution of specialized metabolic pathways. Terpenoids are important specialized metabolites in plants with diverse adaptive functions that enable environmental interactions. Here, we report the genome assemblies of Prunella vulgaris, Plectranthus barbatus, and Leonotis leonurus. We investigate the origin and subsequent evolution of a diterpenoid biosynthetic gene cluster (BGC) together with other seven species within the Lamiaceae (mint) family. Based on core genes found in the BGCs of all species examined across the Lamiaceae, we predict a simplified version of this cluster evolved in an early Lamiaceae ancestor. The current composition of the extant BGCs highlights the dynamic nature of its evolution. We elucidate the terpene backbones generated by the Callicarpa americana BGC enzymes, including miltiradiene and the terpene (+)-kaurene, and show oxidization activities of BGC cytochrome P450s. Our work reveals the fluid nature of BGC assembly and the importance of genome structure in contributing to the origin of metabolites.

Controlled Production of Carnosic Acid and Carnosol in Cell Suspensions of Lepechinia meyenii Treated with Different Elicitors and Biosynthetic Precursors.

Lepechinia meyenii is a medicinal plant specialized in the biosynthesis of different types of antioxidants including the diterpenes carnosic (CA) acid and carnosol (CS). Herein we present the results of plant tissue culture approaches performed in this medicinal plant with particular emphasis on the generation and evaluation of a cell suspension system for CA and CS production. The effect of sucrose concentration, temperature, pH, and UV-light exposure was explored. In addition, diverse concentrations of microbial elicitors (salicylic acid, pyocyanin, Glucanex, and chitin), simulators of abiotic elicitors (polyethylene glycol and NaCl), and biosynthetic precursors (mevalonolactone, geranylgeraniol, and miltiradiene/abietatriene) were evaluated on batch cultures for 20 days. Miltiradiene/abietatriene obtainment was achieved through a metabolic engineering approach using a recombinant strain of Saccharomyces cerevisiae. Our results suggested that the maximum accumulation (Accmax ) of CA and CS was mainly conferred to stimuli associated with oxidative stress such as UV-light exposure (Accmax , 6.2 mg L-1 ) polyethylene glycol (Accmax , 6.5 mg L-1 ) NaCl (Accmax , 5.9 mg L-1 ) which simulated drought and saline stress, respectively. Nevertheless the bacterial elicitor pyocyanin was also effective to increase the production of both diterpenes (Accmax , 6.4 mg L-1 ). Outstandingly, the incorporation of upstream biosynthetic precursors such as geranylgeraniol and miltiradiene/abietatriene, generated the best results with Accmax of 8.6 and 16.7 mg L-1 , respectively. Optimized batch cultures containing 100 mg L-1 geranylgeraniol, 50 mg L-1 miltiradiene/abietatriene (95 : 5 %) and 5 g L-1 polyethylene glycol treated with 6 min UV light pulse during 30 days resulted in Accmax of 26.7 mg L-1 for CA and 17.3 mg L-1 for CS on days 18-24. This strategy allowed to increase seven folds the amounts of CA and CS in comparison with batch cultures without elicitation (Accmax , 4.3 mg L-1 ).

Foliar enrichment of copper oxide nanoparticles promotes biomass, photosynthetic pigments, and commercially valuable secondary metabolites and essential oils in dragonhead (Dracocephalum moldavica L.) under semi-arid conditions.

High alkaline and low organic carbon hinder micronutrients, such as copper (Cu), bioavailability in (semi-) arid soils, affecting plant nutrient quality and productivity. This study aimed at investigating the potential beneficial effects of foliar Cu oxide nanoparticles (CuONPs) and conventional chelated-Cu applications (0-400 mg Cu/L) on the biomass, physiological biomarkers of plant productivity and oxidative stress, Cu bioaugmentation, and essential oils and secondary metabolites in dragonhead (Dracocephalum moldavica [L.]) grown in Cu-limited alkaline soil in semi-arid condition. Employing a randomized complete block design with three replicates, two different sources of Cu (CuONPs and chelated-Cu), and a wide range of Cu concentrations (0, 40, 80, 160, and 400 mg Cu/L), plants were foliarly treated at day-60 and day-74. At day-120, plants were harvested at the end of the flowering stage. Results showed shoot Cu bioaccumulation, flavonoids and anthocyanin increased in a dose-dependent manner for both Cu compounds, but the beneficial effects were significantly higher with CuONPs compared to chelated-Cu treatments. Further, shoot biomass (23 %), photosynthetic pigments (chlorophyll-a and chlorophyll-b; 77 and 123 %, respectively), and essential oil content and yield (70 and 104 %, respectively) increased significantly with foliar application of 80 mg/L CuONPs compared to equivalent concentration of chelated-Cu, suggesting an optimal threshold beyond which toxicity was observed. Likewise, commercially important secondary metabolites' yield (such as geranyl acetate, geranial, neral, and geraniol) was higher with 80 mg/L CuONPs compared to 160 mg/L chelated-Cu (2.3, 0.5, 2.5, and 7.1 %, respectively). TEM analyses of leaf ultrastructure revealed altered cellular organelles for both compounds at 400 mg/L, corroborating the results of oxidative stress response (malondialdehyde and H2O2). In conclusion, these findings indicate significantly higher efficacy of CuONPs, with an optimal threshold of 80 mg/L, in promoting essential oil and bioactive compound yield in dragonhead and may pave a path for the use of nano-Cu as a sustainable fertilizer promoting agricultural production in semi-arid soils that are micronutrient Cu deficient.

Eco-friendly synthesis of Ag-NPs using Endostemon viscosus (Lamiaceae): Antibacterial, antioxidant, larvicidal, photocatalytic dye degradation activity and toxicity in zebrafish embryos.

Nanotechnology is a multidisciplinary area of study that has grown significantly in serving many functions and impacting human society. New fields of science have been facilitated by the clean, non-toxic, and biocompatible nature of plant-derived nanoparticles. The present study deals with the first green synthesis of silver nanoparticles (Ag-NPs) using Endostemon viscosus, and their synthesized Ag NPs were characterized by different spectral methods (UV-vis Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction Spectroscopy (XRD), Transmission Electron Microscopy (TEM) and Energy dispersive X-ray Spectroscopy (EDAX). The change initially observed the production of Ag-NPs in color from green to ash and then confirmed by SPR band at 435 nm in UV-vis spectral analysis. The FTIR findings indicate that many functional groups belong to the pharmaceutically useful phytochemicals, which interact as reducing, capping, and stabilizing agents in synthesizing silver nanoparticles. The predominant peaks in the XRD pattern belong to the planes 210°, 111°, 200°, 241°, and 311° and thus demonstrated the Ag-NPs FCC crystal structure. TEM analysis exhibited spherical-shaped particles with an average size of 13 nm, and the EDAX band showed a distinctive metallic silver peak at 3.0 keV. The antibacterial activity of Ag-NPs tested to show a maximum zone of inhibition of 19 mm for Staphylococcus aureus and 15 mm for Escherichia coli at 100 µg/mL, respectively. Bio-fabricated Ag-NPs were assessed for antioxidant activity (DPPH with % inhibition 57.54% and FRAP with % inhibition 70.89%). The biosynthesized Ag-NPs demonstrated potential larvicidal efficacy against Aedes aegypti with more than 90% at 250 µg/mL. Histological profiles were altered while treating with Ag-NPs at 250 µg/mL. The photocatalytic activity of synthesized E. viscosus Ag-NPs was tested against methylene blue (MB) and crystal violet (CV), and the maximum degradation efficiency was found as 90 and 94%, respectively. Furthermore, the toxicity test on zebrafish embryos demonstrated that aberrations have only been induced at concentrations higher than 500 µg/mL. We conclude that the greenly produced Ag-NPs may find use in biomedical applications based on bacteria and cost-effective industrial wastewater treatment.

The effect of different ammonium to nitrate ratios on antioxidant activity, morpho-physiological and phytochemical traits of Moldavian balm (Dracocephalum moldavica).

Improving yield and secondary metabolites production of medicinal plants through nutrition management recently has been considered. The present study was done to determine the effects of different ammonium (NH4+) to nitrate (NO3-) ratios (100:0, 75:25, 50:50, 25:75, 0:100) on morphophysiological, nutrient contents (N, P, K, Ca, and Mg), phenolic compounds (Total phenolics (TPC) and flavonoid (TFC) contents and individual phenolics including chlorogenic acid, rosmarinic acid, gallic acid, cinnamic acid, caffeic acid, rutin, p-Coumaric acid, apigenin, and quercetin by HPLC-DAD), essential oil composition (by GC and GC-MS), and antioxidant capacity (by DPPH and FRAP assays) of Moldavian balm (Dracocephalum moldavica L.) in deep water culture (DWC) system. The highest biomass and morphological traits values of D. moldavica observed in 0:100 ratio of NH4+:NO3-. Also, the highest TPC and TFC was earned in plants that supplied with 0:100 ratio of NH4+:NO3-. Using the 25:75 ratio of NH4+:NO3- caused the highest nutrient contents (N, Ca and Mg) in the leaves. p-Coumaric acid was detected as the major abundant phenolic compound in extracts and the application of 75:25 ratio of NH4+:NO3 resulted in the highest amounts of p-Coumaric acid, gallic acid, rosmarinic acid, caffeic acid, quercetin, and rutin. The highest antioxidant capacity by both FRAP and DPPH assays was obtained in 75:25 ratio of NH4+:NO3-. Also, the highest geranial and geranyl acetate, geraniol, and neral were obtained in 75:25, 25:75, and 50:50 ratios of NH4+:NO3-, respectively. Plants supplied with the 0:100 ratio of NH4+:NO3-, had the highest total carotenoids, while the highest chlorophyll a and b content gained with 75:25 ratio of NH4+:NO3-. These results suggest that the management of N source in nutrient recipe could contribute to enhance of morphophysiological traits, antioxidant activity and phytochemical compounds in Moldavian balm.

Mining, expression, and phylogenetic analysis of volatile terpenoid biosynthesis-related genes in different tissues of ten Elsholtzia species based on transcriptomic analysis.

We sequenced the leaf and inflorescence transcriptomes of 10 Elsholtzia species to mine genes related to the volatile terpenoid metabolic pathway. A total of 184.68 GB data and 1,231,162,678 clean reads were obtained from 20 Elsholtzia samples, and 333,848 unigenes with an average length of at least 1440 bp were obtained by Trinity assembly. KEGG pathway analysis showed that there were three pathways related to volatile terpene metabolism: terpenoid backbone biosynthesis (No. ko00900), monoterpenoid biosynthesis (No. ko00902), and sesquiterpenoid and triterpenoid biosynthesis (No. ko00909), with 437, 125, and 121 related unigenes, respectively. The essential oil content and composition in 20 Elsholtzia samples were determined by gas chromatography-mass spectrometry. The results showed that there were obvious interspecific differences among the 10 Elsholtzia species, but there were no significant differences between the different tissues among species. The expression levels of seven candidate genes involved in volatile terpenoid biosynthesis in Elsholtzia were further analyzed by quantitative real-time PCR. The results showed that HMGS had the highest expression among all genes, followed by GGPS4. In addition, there was not a significant correlation between the seven genes and the components with high essential oil contents. Combined with the essential oil components detected in this study, the possible biosynthetic pathway of the characteristic components in Elsholtzia plants was speculated to be a metabolic pathway with geraniol as the starting point and elsholtzione as the end product. Phylogenetic analysis was conducted using the nucleotide sequences of the geranyl diphosphate synthase candidate genes, and the results showed that genes related to the volatile terpenoid biosynthetic pathway may be more suitable gene fragments for resolving the Elsholtzia phylogeny.

Antifibrotic pyridine-containing monoterpene alkaloids from Caryopteris glutinosa.

Three undescribed dimeric pyridine-containing alkaloids, caryopterisines C - E, and four unreported cyclopenta[c]pyridine-derived alkaloids, caryopterisines F - I, were identified from Caryopteris glutinosa Rehder (Lamiaceae), together with two known monoterpene alkaloids. Caryopterisine C, featuring with an unprecedented 6/5/6/6/5 pentacyclic rings scaffold, may biosynthetically stem from a Diels-Alder reaction of two cyclopenta[c]pyridine-containing monomers and a following aromatization rearrangement reaction. Caryopterisines D and E, possessing an unprecedented 6/6/6/6/5 fused rings framework, may originate from a same Diels-Alder reaction of two monomers and subsequent aromatization arrangement, Baeyer-Villiger oxidation, and a set of tailoring reactions. Caryopterisine C showed strong inhibition on collagen accumulation in NIH3T3 cells (IC50 = 14.26 ± 1.46 µM). Caryopterisines G and I reduce collagen accumulation with IC50 values 88.91 ± 0.95 µM and 33.09 ± 1.38 µM, respectively. The Western blotting of the transforming growth factor-ß-activated signaling pathways revealed that caryopterisine C inhibits collagen expression and accumulation via suppression of the phosphorylation of ERK1/2, P38, and SMAD2/3. The present works indicate caryopterisine C is a potential lead compound for the development of antifibrotic drugs.

Elsholtzia splendens promotes phenanthrene and polychlorinated biphenyl degradation under Cu stress through enrichment of microbial degraders.

Co-contamination of heavy metals and organic pollutants is widespread in the environment. Metal-tolerant/hyperaccumulating plants have the advantage of enhancing co-operation between plants and rhizospheric microbes under heavy metal stress, but the underlying mechanism remains unclear. In the present study, the effects of Elsholtzia splendens and Lolium perenne on the rhizospheric microbial community and degraders of phenanthrene (PHE) and polychlorinated biphenyls (PCBs) were investigated. The results showed E. splendens could tolerate high Cu concentrations, while L. perenne was sensitive to Cu toxicity. Although Cu played the most important role in microbial community construction, both E. splendens and L. perenne caused shifts in the rhizospheric microbial community. For PHE and PCB degradation, L. perenne was more efficient under low Cu concentrations, whereas E. splendens performed better under high Cu concentrations. This difference can be attributed to shifts in the degrader community and key degradation genes identified by stable isotope probing. Moreover, higher abundances of various genes for organic pollutant degradation were observed in the rhizosphere of E. splendens than L. perenne based on gene prediction under high Cu stress. Our study reveals underlying mechanism of the advantages of heavy metal-tolerant plants for organic pollutant removal in soils co-contaminated with heavy metals.

Variation in phenolic, antioxidant and vitamin amounts among some medicinal plants and investigation by PCA analysis: Lamiaceae family / Variación en las cantidades de fenoles, antioxidantes y vitaminas entre algunas plantas medicinales e investigación poranálisis PCA: familia Lamiaceae

Aromatic and medicinal plants are of great importance to determine the contents of the active compounds of plant origin and to evaluate them depending on variety and climate factors in order to determine the phenolic, antioxidant enzyme activity, vitamin contents in species belonging to the Lamiaceae family. Examination of the characteristics of different species, the highest peroxidase (POD) enzyme activity, ascorbate peroxidase (AxPOD), total antioxidant (TA), malondialdehyte (MDA), caffeic acids (CA), vitamin C contents,and chloric acid (ChA) were obtained in the M. longifoliaspecies. The highest vitamin E and catalase (CAT) were determined in the S. hortensisspecies but the highest total phenolic (TP), superoxide dismutase (SOD) enzyme, hydrogen peroxide (H2O2) and chlorogenic acid (ChgA) were determined in the S. spicigeraspecies. As a result of PCA analysis, it can be said that Mentha longifolia(L.) Hudson and Satureja spicigeraspecies have significant value in terms of biochemical and phenolic content.

Las plantas aromáticas y medicinales son de gran importancia para determinar el contenido de los compuestos activos de origen vegetal y evaluarlos en función de la variedad y factores climáticos con el fin de determinar la actividad enzimática fenólica, antioxidante, contenido vitamínico en especies pertenecientes a la familia Lamiaceae. El examen de las características de diferentes especies, la mayor actividad enzimática de peroxidasa (POD), ascorbato peroxidasa (AxPOD), antioxidante total (TA), malondialdehído (MDA), ácidos cafeicos (CA), contenido de vitamina C y ácido clorhídrico (ChA) se obtuvieron en la especie M. longifolia. La mayor cantidad de vitamina E y catalasa (CAT) se determinó en la especie S. hortensis, pero la mayor cantidad total de enzima fenólica (TP), superóxido dismutasa (SOD), peróxido de hidrógeno (H2O2) y ácido clorogénico (ChgA) se determinó en la especie S. spicigera. Como resultado del análisis de PCA, se puede decir que las especies Mentha longifolia(L.) Hudson y Satureja spicigeratienen un valor significativo en términos de contenido bioquímico y fenólico.

Mesona chinensis Benth Polysaccharides Alleviate DSS-Induced Ulcerative Colitis via Inhibiting of TLR4/MAPK/NF-κB Signaling Pathways and Modulating Intestinal Microbiota.

SCOPE: Ulcerative colitis (UC) is a severe disease of the intestinal tract. To investigate the role of TLR4/Mitogen-activated protein kinase (MAPK)/Nuclear factor kappa-B(NF-κB) pathways and intestinal flora in UC, and the protective mechanisms of Mesona chinensis Benth polysaccharides (MBP), potential therapeutic agents due to their diabetes-relieving, cancer-suppressing, and immunomodulatory properties. METHODS AND RESULTS: A dextran sulfate sodium (DSS)-induced mouse colitis model is used for experiments; the histopathology, immunohistochemistry, and Western blotting's results suggest that MBP can alleviate the colitis symptoms, inhibits the overproduction of TNF-α, IL-1ß, promote IL-10, reduces myeloperoxidase activity, and alleviates the inflammatory response probably by inhibiting the activation of TLR4/MAPK/NF-κB pathways. Furthermore, MBP improvs the ratio of Bcl-2/BAX, maintains the intestinal integrity by promoting the levels of zonulin occludin-1 (ZO-1), occluding and mucin mucin-2 (MUC-2), reduces the levels of endotoxin (ET), lipopolysaccharide binding protein (LBP) in serum, and oxidative stress in liver. Moreover, using 16S rRNA Gene Sequencing analysis, MBP regulates gut microbiota by decreasing the abundances of Helicobacter and Prevotella and increasing the abundances of Lactobacillus and Coprococcus, reverses microbiota dysbiosis caused by DSS. CONCLUSION: These findings confirm the anti-inflammatory effects of MBP, restoration of the intestinal barrier and intestinal flora, and have therapeutic potential to attenuate the development of UC.

Amelioration of aluminum-induced hepatic and nephrotoxicity by Premna odorata extract is mediated by lowering MMP9 and TGF-ß gene alterations in Wistar rat.

This study aims to investigate the effect of Premna odorata (P. odorata) (Lamiaceae) on the hepatic and nephrotoxicity induced by aluminum chloride (AlCl3) in rat. Wistar male rats were equally classified into four groups: control, P. odorata extract (500 mg/kg B.W.), AlCl3 (70 mg/kg B.W.), and P. odorata extract plus AlCl3 groups. All treatments were given orally for 4 weeks. Serum transaminases and some biochemical parameters, hepatic and renal antioxidant/oxidant biomarker; tumor necrosis factor-α (TNF-α); matrix metalloproteinase (MMP9) and transforming growth factor-ß (TGF-ß) mRNA expression; histopathological examination of the liver, and kidneys were investigated. The obtained results revealed that AlCl3 significantly increased the activities of serum aspartate transaminase, alanine transaminase, and alkaline phosphatase as well as produced a significant increase in total cholesterol, triglyceride, urea, and creatinine concentrations, while there were no changes observed in the total protein, albumin, and globulin concentrations. Also, aluminum administration significantly decreased the reduced glutathione content and increased the catalase activity, malondialdehyde, and TNF-α concentrations in the liver and kidney tissue. Moreover, AlCl3 results in congestion, degeneration, and inflammation of the liver and kidney tissue. Co-treatment of P. odorata extract with AlCl3 alleviated its harmful effects on the previous parameters and reduced the histopathological alterations induced by AlCl3. Therefore, Premna odorata may have a potent protective effect against oxidative stress induced by Al toxicity through downregulation of MMP9 and TGF-ß gene expression.

NMR, LC-MS Characterization of Rydingia michauxii Extracts, Identification of Natural Products Acting as Modulators of LDLR and PCSK9.

Rydingia michauxii (Briq.) Scheen and V.A.Albert (Lamiaceae) is used in Iranian traditional medicine to treat malaria, diabetes, hyperlipidemia, rheumatism and cardiovascular diseases. NMR and LC-DAD-MSn analyses were used to establish extract composition and phenylethanoid, flavonoid glycosides, lignans, labdane diterpenes and iridoids were identified and quantified. The main constituents were isolated, and structures were elucidated based on NMR, polarimetric and MS measurements. A new natural compound, ent-labda-8(17),13-dien-18-glucopyranosyl ester-15,16-olide is described here. The effects of ent-labda-8(17),13-dien-18-oic acid-15,16-olide (1), ent-labda-8(17),13-dien-18-glucopyranosyl es-ter-15,16-olide (2), antirrhinoside (3), echinacoside (4), verbascoside (5), and apigenin 6,8-di-C-glucoside (6), on the low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9), were studied in the human hepatocarcinoma cell line Huh7. Among the six constituents, (3) showed the strongest induction of the LDLR (3.7 ± 2.2 fold vs. control) and PCSK9 (3.2 ± 1.5 fold vs. control) at a concentration of 50 µM. The in vitro observations indicated a potential lipid lowering activity of (3) with a statin-like mechanism of action.

Toxicity of Selected Monoterpenes and Essential Oils Rich in These Compounds.

Monoterpenes make up the largest group of plant secondary metabolites. They can be found in numerous plants, among others, the Lamiaceae family. The compounds demonstrate antioxidative, antibacterial, sedative and anti-inflammatory activity, hence, they are often employed in medicine and pharmaceuticals. Additionally, their fragrant character is often made use of, notably in the food and cosmetic industries. Nevertheless, long-lasting studies have revealed their toxic properties. This fact has led to a detailed analysis of the compounds towards their side effects on the human organism. Although most are safe for human food and medical applications, there are monoterpene compounds that, in certain amounts or under particular circumstances (e.g., pregnancy), can cause serious disorders. The presented review characterises in vitro and in vivo, the toxic character of selected monoterpenes (α-terpinene, camphor, citral, limonene, pulegone, thujone), as well as that of their original plant sources and their essential oils. The selected monoterpenes reveal various toxic properties among which are embryotoxic, neurotoxic, allergenic and genotoxic. It is also known that the essential oils of popular plants can also reveal toxic characteristics that many people are unaware of.

Phylogeny-Aware Chemoinformatic Analysis of Chemical Diversity in Lamiaceae Enables Iridoid Pathway Assembly and Discovery of Aucubin Synthase.

Countless reports describe the isolation and structural characterization of natural products, yet this information remains disconnected and underutilized. Using a cheminformatics approach, we leverage the reported observations of iridoid glucosides with the known phylogeny of a large iridoid producing plant family (Lamiaceae) to generate a set of biosynthetic pathways that best explain the extant iridoid chemical diversity. We developed a pathway reconstruction algorithm that connects iridoid reports via reactions and prunes this solution space by considering phylogenetic relationships between genera. We formulate a model that emulates the evolution of iridoid glucosides to create a synthetic data set, used to select the parameters that would best reconstruct the pathways, and apply them to the iridoid data set to generate pathway hypotheses. These computationally generated pathways were then used as the basis by which to select and screen biosynthetic enzyme candidates. Our model was successfully applied to discover a cytochrome P450 enzyme from Callicarpa americana that catalyzes the oxidation of bartsioside to aucubin, predicted by our model despite neither molecule having been observed in the genus. We also demonstrate aucubin synthase activity in orthologues of Vitex agnus-castus, and the outgroup Paulownia tomentosa, further strengthening the hypothesis, enabled by our model, that the reaction was present in the ancestral biosynthetic pathway. This is the first systematic hypothesis on the epi-iridoid glucosides biosynthesis in 25 years and sets the stage for streamlined work on the iridoid pathway. This work highlights how curation and computational analysis of widely available structural data can facilitate hypothesis-based gene discovery.

Understanding biochemical defense and phytoremediation potential of Leucas aspera in crude oil polluted soil.

The phytoremediation potential and enzymatic defense of a medicinal herb Leucas aspera was studied in the crude oil contaminated soil. The productivity, antioxidants, and phytochemical and functional group profiles of the plant species in stress conditions were investigated. Besides, changes in enzymes, beneficial bacterial population, and physico-chemical and total oil and grease (TOG) profiles in the contaminated soil were also studied. The results showed improvement in physico-chemical conditions, increase in beneficial bacterial population (4.1-5.4 folds), and decrease in TOG (31.3%) level of the contaminated soil by end of the experimental trials. The L. aspera treated contaminated soil showed enhancement in dehydrogenase (32.3%), urease (102.8%), alkaline phosphatase (174.4%), catalase (68.5%), amylase (76.16%), and cellulase (23.6%) activities by end of the experimental trials. Furthermore, there were significant variations in leaf area index, chlorophyll, and biomass contents of the experimental plant as against the initial level and control. Besides, the significant reduction in IC50 values (24-27.4%) of L. aspera samples grown in contaminated soil confirms the strong antioxidant enzymatic defense of the plant species against the crude oil associated abiotic stress. The Fourier-transform infrared (FT-IR) analysis confirmed the uptake and metabolism of aliphatic hydrocarbons, aldehydes, alkyl halides, and nitro compounds by the experimental plant from the contaminated soil.

Alternate gene expression profiling of monoterpenes in Hymenocrater longiflorus as a novel pharmaceutical plant under water deficit.

Hymenocrater longiflorus (surahalala) is a wild plant species with potential pharmaceutical and ornamental interest. To date, the genomics of this plant is unknown and the gene expression profiling of the genes related to its metabolite has never been studied before. In order to study the responses of in vitro-grown surahalala plants to abiotic stresses and the differential expression of the genes related to its essential oils under exogenous proline application; three levels of PEG600 (0, 10, and 20%) and five levels of proline (0, 5, 10, 15, and 20 µm) were combined in the culture media. Thus, water deficit increased oxidants levels and decreased fresh weight of surahalala tissues, whereas addition of proline up to 15 µm was able to relatively compensate the negative effect of water deficit. Contrarily, high proline level (20 µm) had a negative effect on surahalala plants probably due to the stress simulation (nutrition) under high proline concentration. In addition, the best combination for achieving highest essential oils content was 10 µm proline plus 10% PEG. The expressional profiling of the genes TPS27, L3H, TPS2, TPS1, OMT and GDH3 were successfully carried out and their involvement in 1,8-cineole, carvone, α-pinene, thymol, estragole and ß-Citronellol biosynthesis, respectively, was verified. In addition, our results indicated that these genes could also be involved in the synthesis of other metabolites under water deficit condition.

Polyphenol Composition, Anticholinesterase and Antioxidant Potential of the Extracts of Clinopodium vulgare L.

Clinopidium vulgare L. (wild basil, Lamiaceae) is a well-known medicinal plant used in the traditional medicine in many countries. Medicinal plants present potential sources of bioactive compounds. Many of them are rich in polyphenol compounds that show biological potential in terms of protecting biological molecules from oxidation and in inhibition of cholinesterase enzymes, which may be significant in the treatment of diseases related to oxidative stress. In this work, we examined the chemical composition of Clinopodium vulgare L. hot water and methanol extract using spectroscopic and HPLC/DAD techniques. Using DPPH and FRAP methods the antioxidant activity was analyzed. The ability to protect proteins and lipids from oxidation was also determined as well as the ability of extracts to inhibit cholinesterase enzymes using Ellman's method. Analyzed extracts were rich in polyphenol compounds. Among 16 identified and quantified phenolic compounds dominant were: rosmarinic (26.63 and 34.21 mg/g) and ellagic acid (23.11 and 29.31 mg/g) of hot water and methanol extract, respectively. They show good antioxidant activity and good potential in protecting lipids from oxidation. The ability of extracts to inhibit enzyme acetylcholinesterase was weak, while inhibition of the butyrylcholinesterase was missing. Extracts show prooxidant activity in terms of protecting proteins from oxidation.

Tanshinones: Leading the way into Lamiaceae labdane-related diterpenoid biosynthesis.

Tanshinones are the bioactive diterpenoid constituents of the traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), and are examples of the phenolic abietanes widely found within the Lamiaceae plant family. Due to the significant interest in these labdane-related diterpenoid natural products, their biosynthesis has been intensively investigated. In addition to providing the basis for metabolic engineering efforts, this work further yielded pioneering insights into labdane-related diterpenoid biosynthesis in the Lamiaceae more broadly. This includes stereochemical foreshadowing of aromatization, with novel protein domain loss in the relevant diterpene synthase, as well as broader phylogenetic conservation of the relevant enzymes. Beyond such summary of more widespread metabolism, formation of the furan ring that characterizes the tanshinones also has been recently elucidated. Nevertheless, the biocatalysts for the pair of demethylations remain unknown, and the intriguing potential connection of these reactions to the further aromatization observed in the tanshinones are speculated upon here.