Accumulation of the labdane diterpene Marrubiin in glandular trichome cells along the ontogeny of Marrubium vulgare plants

Background: Improvement in extract quality in terms of concentration of secondary metabolites and pharmacological activity has always been the need of the hour. In the present research, the target was to extract the selected medicinal herb using the ultrasound waves and to optimize the extraction conditions for the improvement in the quality of extract with respect to furan labdane diterpene (marrubiin) concentration and antihypertensive potential. Methods: The whole plant of Marrubium vulgare Linn. was collected from the fields of Pulwama district of Jammu and Kashmir state in India and extracted by cold maceration (MVM) and ultrasound assisted extraction techniques (MVU). The response surface methodology coupled with the central composite design was employed to optimize the selected extraction parameters in UAE method. The marrubiin concentration in different extracts was determined by HPTLC. The extracts were also evaluated for the antihypertensive potential by non-invasive blood pressure monitoring (NIBPM) method. Results: The extract yield (14.2 ± 0.9%) and concentration of marrubiin (0.91 ± 0.04%) were significantly improved at the optimized UAE conditions (Ultrasound power 467 W, sonication time of 47 minutes and solvent concentration of 33 mL per g of drug) as compared to the conventional method. Furthermore, the MVU extract (200 mg/kg) along with ethanol significantly (p<0.01) prevented the rise in mean systolic blood pressure (MSBP) of animals and also the GSH was significantly (p<0.05) enhanced as compared to ethanol-treated animals. Conclusion: The elevation in MSBP and decrease in reduced glutathione concentration (GSH) by the chronic ethanol consumption were significantly altered by MVU extract as compared to MVM extract. The enhanced antihypertensive effect of selected herb may be attributed to the improved concentration of secondary metabolites (marrubiin) in MVU extract obtained at optimized conditions.

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Marrubium vulgare L.: A Phytochemical and Pharmacological Overview

Molecules ◽

10.3390/molecules25122898 ◽

2020 ◽

Vol 25 (12) ◽

pp. 2898

Author(s):

Milica Aćimović ◽

Katarina Jeremić ◽

Nebojša Salaj ◽

Neda Gavarić ◽

Biljana Kiprovski ◽

...

Keyword(s):

Trichomonas Vaginalis ◽

Scientific Evidence ◽

Bovine Mastitis ◽

Complex Mixture ◽

Raw Material ◽

Bacterial Strains ◽

Labdane Diterpene ◽

Marrubium Vulgare ◽

Bioactive Potential ◽

Simplex Virus

Marrubium vulgare is a plant with high bioactive potential. It contains marrubiin, a labdane diterpene that is characteristic for this genus, as well as a complex mixture of phenolic compounds. According to numerous studies, M. vulgare acts as a good antioxidant agent, and due to this, it could potentially be useful in treatments of cancer, diabetes mellitus, and liver diseases. In addition, its anti-inflammatory, wound-healing, antihypertensive, hypolipidemic, and sedative potential are discussed. Apart from that, its antimicrobial activity, especially against Gram+ bacteria, fungi, herpes simplex virus, and parasites such as Toxoplasma gondii, Trichomonas vaginalis, and Plasmodium berghei-berghei was recorded. Additionally, it could be used as a chicken lice repellent, herbicide, and natural insecticide against mosquito larvae and natural molluscicide. In veterinary medicine, M. vulgare can be used as an anthelmintic against the eggs and larvae of bovine strongyles parasites, and as an antibiotic against bovine mastitis caused by resistant bacterial strains. Due to the mentioned benefits, there is a tendency for the cultivation of M. vulgare in order to ensure high-quality raw material, but more firm scientific evidence and well-designed clinical trials are necessary for the well-established use of M. vulgare herb and its preparations.

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Biosynthesis of the labdane diterpene marrubiin in Marrubium vulgare via a non-mevalonate pathway

Biochemical Journal ◽

10.1042/bj3260449 ◽

1997 ◽

Vol 326 (2) ◽

pp. 449-454 ◽

Cited By ~ 57

Author(s):

Werner KNÖSS ◽

Bernd REUTER ◽

Josef ZAPP

Keyword(s):

Mevalonate Pathway ◽

Alternative Pathway ◽

Mevalonic Acid ◽

13C Nmr Spectroscopy ◽

Shoot Cultures ◽

Isopentenyl Diphosphate ◽

Glucose Incorporation ◽

Labdane Diterpene ◽

Marrubium Vulgare ◽

Putative Precursor

The biosynthesis of the furanic labdane diterpene marrubiin has been studied in plantlets and shoot cultures of Marrubium vulgare(Lamiaceae). The use of [2-14C]acetate, [2-14C]pyruvate, [2-14C]mevalonic acid and [U-14C]glucose incorporation experiments showed that the labelling of sterols in etiolated shoot cultures of M. vulgare was in accordance with their biosynthesis via the acetate–mevalonate pathway. In contrast, the incorporation rates of these precursors into the diterpene marrubiin could not be explained by biosynthesis of this compound via the acetate–mevalonate pathway. Cultivation of etiolated shoot cultures of M. vulgare on medium containing [1-13C]glucose and subsequent 13C-NMR spectroscopy of marrubiin led to the conclusion that the biosynthesis of marrubiin follows a non-mevalonate pathway. All isoprenic units of 13C-labelled marrubiin were enriched in those carbons that correspond to positions 1 and 5 of a putative precursor isopentenyl diphosphate. This labelling pattern from [1-13C]glucose is consistent with an alternative pathway via trioses, which has already been shown to occur in Eubacteria and Gymnospermae. The labdane skeleton is a precursor of many other skeletal types of diterpenes. Therefore it becomes obvious that in connection with the few known examples of a non-mevalonate pathway to isoprenoids the formation of some isoprenoids in plants via a non-mevalonate pathway might be quite common.

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Antioxidant and Anti-inflammatory Activities of Organic and Aqueous Extracts of Northeast Algerian Marrubium vulgare

Phytothérapie ◽

10.3166/phyto-2018-0106 ◽

2018 ◽

Vol 16 (S1) ◽

pp. S119-S129

Author(s):

I. Namoune ◽

B. Khettal ◽

A.M. Assaf ◽

S. Elhayek ◽

L. Arrar

Keyword(s):

Ethyl Acetate ◽

Methanolic Extract ◽

Ethyl Acetate Extract ◽

Interleukin 1 ◽

Total Phenolic ◽

Dependent Manner ◽

Aqueous Extracts ◽

Traditional Use ◽

Marrubium Vulgare ◽

Anti Inflammatory

Marrubium vulgare (Lamiaceae) is frequently used in traditional medicine to treat many illnesses from ancient times. Its beneficial effects include antibacterial, antioedematogenic, and analgesic activities. This study was designed to evaluate the antioxidant and anti-inflammatory activities of organic and aqueous extracts of the leaves, the flowers, the stems, and the roots of Marrubium vulgare. The total phenolic and flavonoid contents as well as the antioxidant and the anti-inflammatory effects of methanol, chloroform, ethyl acetate, and aqueous extracts have been investigated by using different in-vitro methods. It was found that the ethyl acetate extract from Marrubium vulgare stems had the highest total phenolic content, while the ethyl acetate extract from the leaves yielded a high concentration of flavonoids. The ethyl acetate extract from the stems exhibited the highest activity in scavenging of 2,2-diphenyl- 1-picrylhydrazyl (DPPH), as well as in protecting erythrocytes. The leaves aqueous extract exhibited the highest ferrous chelating activity and its methanolic extract was found to be the strongest inhibitor of lipid peroxidation in β-carotene bleaching assay. The leaves chloroform extracts as well as the flowers methanol, chloroform, and ethyl acetate extracts were found to decrease the pro-inflammatory tumor necrosis factor alpha (TNF-α) cytokine levels in a dose-dependent manner. On the other hand, the flowers methanolic extract and the leaves methanol, ethyl acetate, and aqueous extracts decreased the interleukin-1 beta (IL- 1β) release. It was also found that the methanol extract from the flowers and the chloroform extract from the stems of Marrubium vulgare inhibited interleukin-8 (IL-8) release. This study provides a scientific basis for the traditional use of Marrubium vulgare as an anti-inflammatory agent and for the plant to be considered as an important resource of natural antioxidants.

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Acylated Flavonoid Glucoside from Marrubium vulgare

Letters in Organic Chemistry ◽

10.2174/1570178613666160209230106 ◽

2016 ◽

Vol 13 (4) ◽

pp. 277-282 ◽

Cited By ~ 3

Author(s):

Nuha I. Sweidan ◽

Musa H. Abu Zarga

Keyword(s):

Marrubium Vulgare

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A novel non-trichome based whitefly resistance QTL in Solanum galapagense

Euphytica ◽

10.1007/s10681-021-02770-7 ◽

2021 ◽

Vol 217 (3) ◽

Author(s):

Joris Santegoets ◽

Marcella Bovio ◽

Wendy van’t Westende ◽

Roeland E. Voorrips ◽

Ben Vosman

Keyword(s):

Frankliniella Occidentalis ◽

Recombinant Inbred Lines ◽

Glandular Trichomes ◽

Glandular Trichome ◽

Trialeurodes Vaporariorum ◽

Inbred Lines ◽

Adult Survival ◽

Greenhouse Whitefly ◽

Major Threat ◽

Type Iv

AbstractThe greenhouse whitefly Trialeurodes vaporariorum is a major threat in tomato cultivation. In greenhouse grown tomatoes non-trichome based whitefly resistance may be better suited than glandular trichome based resistance as glandular trichomes may interfere with biocontrol, which is widely used. Analysis of a collection of recombinant inbred lines derived from a cross between Solanum lycopersicum and Solanum galapagense showed resistance to the whitefly T. vaporariorum on plants without glandular trichomes type IV. The resistance affected whitefly adult survival (AS), but not oviposition rate. This indicates that S. galapagense, in addition to trichome based resistance, also carries non-trichome based resistance components. The effectiveness of the non-trichome based resistance appeared to depend on the season in which the plants were grown. The resistance also had a small but significant effect on the whitefly Bemisia tabaci, but not on the thrips Frankliniella occidentalis. A segregating F2 population was created to map the non-trichome based resistance. Two Quantitative trait loci (QTLs) for reduced AS of T. vaporariorum were mapped on chromosomes 12 and 7 (explaining 13.9% and 6.0% of the variance respectively). The QTL on chromosome 12 was validated in F3 lines.

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Transcriptome Analysis of Light-Regulated Monoterpenes Biosynthesis in Leaves of Mentha canadensis L.

Plants ◽

10.3390/plants10050930 ◽

2021 ◽

Vol 10 (5) ◽

pp. 930

Author(s):

Xu Yu ◽

Xiwu Qi ◽

Shumin Li ◽

Hailing Fang ◽

Yang Bai ◽

...

Keyword(s):

Essential Oil ◽

Transcriptome Analysis ◽

Average Length ◽

Glandular Trichomes ◽

Signal Transduction Pathway ◽

Glandular Trichome ◽

Light Treatment ◽

Light Signal ◽

Environmental Aspect ◽

Underlying Mechanisms

Light is a key environmental aspect that regulates secondary metabolic synthesis. The essential oil produced in mint (Mentha canadensis L.) leaves is used widely in the aromatics industry and in medicine. Under low-light treatment, significant reductions in peltate glandular trichome densities were observed. GC-MS analysis showed dramatically reduced essential oil and menthol contents. Light affected the peltate glandular trichomes’ development and essential oil yield production. However, the underlying mechanisms of this regulation were elusive. To identify the critical genes during light-regulated changes in oil content, following a 24 h darkness treatment and a 24 h recovery light treatment, leaves were collected for transcriptome analysis. A total of 95,579 unigenes were obtained, with an average length of 754 bp. About 56.58% of the unigenes were annotated using four public protein databases: 10,977 differentially expressed genes (DEGs) were found to be involved in the light signaling pathway and monoterpene synthesis pathway. Most of the TPs showed a similar expression pattern: downregulation after darkness treatment and upregulation after the return of light. In addition, the genes involved in the light signal transduction pathway were analyzed. A series of responsive transcription factors (TFs) were identified and could be used in metabolic engineering as an effective strategy for increasing essential oil yields.

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Two Labdane Diterpene and Megastigmane Glycosides from Aquilegia hybrida

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.56.1009 ◽

2008 ◽

Vol 56 (7) ◽

pp. 1009-1012 ◽

Cited By ~ 6

Author(s):

Hitoshi Yoshimitsu ◽

Makiko Nishida ◽

Toshihiro Nohara

Keyword(s):

Labdane Diterpene ◽

Megastigmane Glycosides

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Single Wavelengths of LED Light Supplement Promote the Biosynthesis of Major Cyclic Monoterpenes in Japanese Mint

Plants ◽

10.3390/plants10071420 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1420

Author(s):

Takahiro Ueda ◽

Miki Murata ◽

Ken Yokawa

Keyword(s):

Blue Light ◽

Solid Phase ◽

Glandular Trichomes ◽

Red Light ◽

Glandular Trichome ◽

Pulse Amplitude ◽

Light Treatment ◽

Led Light ◽

Trichome Formation ◽

Japanese Mint

Environmental light conditions influence the biosynthesis of monoterpenes in the mint plant. Cyclic terpenes, such as menthol, menthone, pulegone, and menthofuran, are major odor components synthesized in mint leaves. However, it is unclear how light for cultivation affects the contents of these compounds. Artificial lighting using light-emitting diodes (LEDs) for plant cultivation has the advantage of preferential wavelength control. Here, we monitored monoterpene contents in hydroponically cultivated Japanese mint leaves under blue, red, or far-red wavelengths of LED light supplements. Volatile cyclic monoterpenes, pulegone, menthone, menthol, and menthofuran were quantified using the head-space solid phase microextraction method. As a result, all light wavelengths promoted the biosynthesis of the compounds. Remarkably, two weeks of blue-light supplement increased all compounds: pulegone (362% increase compared to the control), menthofuran (285%), menthone (223%), and menthol (389%). Red light slightly promoted pulegone (256%), menthofuran (178%), and menthol (197%). Interestingly, the accumulation of menthone (229%) or menthofuran (339%) was observed with far-red light treatment. The quantification of glandular trichomes density revealed that no increase under light supplement was confirmed. Blue light treatment even suppressed the glandular trichome formation. No promotion of photosynthesis was observed by pulse-amplitude-modulation (PAM) fluorometry. The present result indicates that light supplements directly promoted the biosynthetic pathways of cyclic monoterpenes.

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Multi-omics analysis of the bioactive constituents biosynthesis of glandular trichome in Perilla frutescens

BMC Plant Biology ◽

10.1186/s12870-021-03069-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Peina Zhou ◽

Mengjiao Yin ◽

Shilin Dai ◽

Ke Bao ◽

Chenglin Song ◽

...

Keyword(s):

Glandular Trichomes ◽

Glandular Trichome ◽

Perilla Frutescens ◽

Morphological Features ◽

Limited Information ◽

Bioactive Constituents ◽

Edible Plant ◽

Cell Factories ◽

Custom Made ◽

Trichome Types

Abstract Background Perilla frutescens (L.) Britt is a medicinal and edible plant widely cultivated in Asia. Terpenoids, flavonoids and phenolic acids are the primary source of medicinal ingredients. Glandular trichomes with multicellular structures are known as biochemical cell factories which synthesized specialized metabolites. However, there is currently limited information regarding the site and mechanism of biosynthesis of these constituents in P. frutescens. Herein, we studied morphological features of glandular trichomes, metabolic profiling and transcriptomes through different tissues. Results Observation of light microscopy and scanning electron microscopy indicated the presence of three distinct glandular trichome types based on their morphological features: peltate, capitate, and digitiform glandular trichomes. The oil of peltate glandular trichomes, collected by custom-made micropipettes and analyzed by LC–MS and GC–MS, contained perillaketone, isoegomaketone, and egomaketone as the major constituents which are consistent with the components of leaves. Metabolomics and transcriptomics were applied to explore the bioactive constituent biosynthesis in the leaves, stem, and root of P. frutescens. Transcriptome sequencing profiles revealed differential regulation of genes related to terpenoids, flavonoids, and phenylpropanoid biosynthesis, respectively with most genes expressed highly in leaves. The genes affecting the development of trichomes were preliminarily predicted and discussed. Conclusions The current study established the morphological and chemical characteristics of glandular trichome types of P. frutescens implying the bioactive constituents were mainly synthesized in peltate glandular trichomes. The genes related to bioactive constituents biosynthesis were explored via transcriptomes, which provided the basis for unraveling the biosynthesis of bioactive constituents in this popular medicinal plant.

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