Breeding support for Valeriana officinalis L. s.l. : root structure, localization of value-determining secondary compounds and mating behavior at open pollination

Valerian (Valeriana officinalis L. s.l.) is an important medicinal plant, which is used for insomnia and restlessness. Preparations for treating of such indications are produced from the dried rootstock (roots and rhizome). The raw material comes invariably from field cultivation. Due to the very fine, carpet-like root structure, a high proportion of soil is attached to the root system after the harvest, which requires an extensive post-harvest treatment. Losses of root-yield and important secondary compounds are the consequences. Therefore, a breeding project was set up to develop varieties with coarser root structure and acceptable secondary compound contents by selection- and cross-breeding. The aim of this thesis was to investigate two fundamental aspects in order to support valerian breeding: • Root structure analyses and the localization of secondary compounds within the root system • Mating behavior under conditions of open pollination in the field Knowledge about the relationship between root structure and secondary compounds contents is of central importance for the breeding project. For instance, a decrease of secondary compound contents with increasing root thickness would be disadvantageous for the primary breeding goal. Two techniques were developed and applied to localize secondary compounds in different parts of the root system of four cloned valerian genotypes. An analytical determination of the valerenic acids and the essential oil contents was performed by HPLC and water-distillation, respectively. The horizontal distribution of the essential oil droplets within root cross-sections was determined by a fluorescence-microscopic image-analysis. Based on the analytical investigations on the sesquiterpene acids (sum of valerenic acid and acetoxyvalerenic acid) and essential oil contents, the adventitious roots showed 25 to 30 % higher contents than the lateral roots, and these in turn had a 25 to 30 % higher contents compared to the rhizomes. Differences between four root diameter fractions were not detectable for any secondary compound. The image analysis showed that 43 % of the detected oil droplets were located in the root cortex (parenchyma) close to the root surface (epidermis). The remaining 57 % were detected in the subjacent root cortex (inner parenchyma). The central cylinder was free of essential oil droplets. Differences in oil droplet distribution and density between the genotypes, the root thickness and the harvesting depth are detectable. In summary, the results indicate that a coarser root structure did not lead to a decrease of important secondary compounds. The second aim of this thesis dealt with the determination of the outcrossing rate under conditions of open pollination. Cross-pollination is described as the naturally pollination system of valerian, however self-pollination cannot be excluded. Within the offspring from open pollinated and random mated (panmixia) valerian plants, the proportion of descendants, who were generated by cross-pollination, was determined by marker based analyses (AFLP). The cross-pollination was accepted, if the reference marker of the crossing partner was detected. The determined proportion of cross-pollination ranged from 76.5 to 97.7 %. Thus, the predominant tendency of the valerian breeding material to outbreeding was confirmed

Neurobehavioral evaluation and phytochemical characterization of a series of argentine valerian species

Folkloric or galenic preparations of valerian roots and rhizomes have been used as sedatives/anxiolytics and sleep inducers since ancient times. “Valerianas” are plants that naturally grow in our region. Although some of them are used in folk medicine, they lack scientific information. We performed a comparative study of the phytochemical composition and the potential in vivo effects of ethanolic extracts of argentine valerian species: Valeriana carnosa Sm., V. clarionifolia Phil. and V. macrorhiza Poepp. ex DC., from “Patagonia Argentina”; V. ferax (Griseb.) Höck and V. effusa Griseb., from the central part of our country, and V. officinalis (as the reference plant). All these plants were rich in phenolic compounds, evidenced the presence of ligands for the benzodiazepine binding site of the GABAA receptor and were able to induce sedation as assessed by loss-of-righting reflex assays (500 mg/kg, i.p.). Mice treated with V. macrorhiza, V. carnosa and V. ferax extracts showed reduced exploratory behaviors while V. clarionifolia produced anxiolytic-like activities (500 mg/kg, i.p.) in the Hole board test. Oral administrations (300 mg/kg and 600 mg/kg, p.o.) evidenced sedative effects for V. ferax and anxiolytic-like properties for V. macrorhiza, V. carnosa and V. clarionifolia extracts. Our native valerian species are active on the CNS, validating its folkloric use as anxiolytic/sedative and sleep enhancers.Instituto de Recursos BiológicosFil: Marcucci, Carolina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini; ArgentinaFil: Anselmi Relats, Juan Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini; ArgentinaFil: Bach, Hernán Gerónimo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Cátedra de Farmacobotánica; ArgentinaFil: Kamecki, Fabiola. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini; ArgentinaFil: Varela, Beatriz G. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Cátedra de Farmacobotánica; ArgentinaFil: Wagner, Marcelo L. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Cátedra de Farmacobotánica; ArgentinaFil: Pastore, Valentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini; ArgentinaFil: Pastore, Valentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Colettis, Natalia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini; ArgentinaFil: Ricco, Rafael A. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Cátedra de Farmacobotánica; ArgentinaFil: Marder, Mariel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini; Argentin

VALERIANA JATAMANSI: AN ETHNOBOTANICAL REVIEW

 Objective: The main objective of review is an effort to give detailed information on Valeriana jatamansi and its multiple medicinal properties. Methods: As per the literature, the plant V. jatamansi is a perennial herb and found at subtemperate Himalayan regions of the Kumaon and Garhwal. The plant most popularly known as Valerian.†The plant belongs to the family Valerianaceae. The roots and rhizomes of the plants are traditionally used to treat ulcers, jaundice, dry cough, seminal weakness, skin diseases, leprosy, and for sleep enhancement due to the presence of a variety of different chemical constituents such as sesquiterpenes, coumarins, iridoids, lignanoids, alkaloids, and flavonoids. From literature, the reported methods performed for different pharmacological activities have been thoroughly discussed and complied. Results: Most of the studies compiled from literature shown that V. jatamansi possess antimicrobial, antioxidant, anti-inflammatory, cytotoxic, anxiolytic, and neuroprotective activities. Conclusion: The review reveals that continuous research on this plant is needed to know the exact molecular mechanism and further elaborative studies can lead to develop safe therapeutic use in modern medicine

Isolation of essential oil from different plants and herbs by supercritical fluid extraction

This is the author’s version of a work that was accepted for publication in Journal of Chromatography A. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Chromatography A, 1250 (2012) DOI: 10.1016/j.chroma.2012.04.051Supercritical fluid extraction (SFE) is an innovative, clean and environmental friendly technology with particular interest for the extraction of essential oil from plants and herbs. Supercritical CO2 is selective, there is no associated waste treatment of a toxic solvent, and extraction times are moderate. Further, supercritical extracts were often recognized of superior quality when compared with those produced by hydro-distillation or liquid–solid extraction. This review provides a comprehensive and updated discussion of the developments and applications of SFE in the isolation of essential oils from plant matrices. SFE is normally performed with pure CO2 or using a cosolvent; fractionation of the extract is commonly accomplished in order to isolate the volatile oil compounds from other co-extracted substances. In this review the effect of pressure, temperature and cosolvent on the extraction and fractionation procedure is discussed. Additionally, a comparison of the extraction yield and composition of the essential oil of several plants and herbs from Lamiaceae family, namely oregano, sage, thyme, rosemary, basil, marjoram and marigold, which were produced in our supercritical pilot-plant device, is presented and discussed.This work has been supported by project AGL2010-21565 (subprogram ALI) and project INNSAMED IPT-300000-2010-34 (subprogram INNPACTO) from Ministerio de Ciencia e Innovación (Spain) and Comunidad Autónoma de Madrid (project ALIBIRDS2009/ AGR-1469)

Therapeutic Effects of Valerian (Valeriana officinalis L.)

Valerian is a plant that is endemic to mild parts of the America, Europe and Asia. It is used as an opiate, especially in the cure of restlessness, and almost all herbal sleep aids contain valerian. Valerian contains many compounds who act synergistically. Preparations containing valerenic acid may be regulated. This species is spreading in spontaneous flora, in humid and cloudy areas (woods, wet meadows), especially in hilly and mountainous areas. It was taken and broad in culture and in the present the raw material of valerian comes, mostly, from cultures. Valerian essential oil is known for its calmative and anxiolytic activity, whereas valepotriates are known to apply a regulative effect on the autonomous nervous system. This medicinal plant used to help various health problems including insomnia, anxiety, heart problems and more others; has been used pharmaceutically for at least of 2000 years in the cures of brain disorders and also as treatment of varied nervous disorders, antispasmodic, anthelmintic, diuretic, diaphoretic, emmenagogue and hysteria. The present review presents the biological evidence of this plant which is very helpful in combating sleep problems and has no negative effects on long term. Although, the valerian tea is known to not have negative impacts, overdosing may lead to intestinal issues

Sur1 Receptor Interaction With Hesperidin And Linarin Predicts Possible Mechanisms Of Action Of Valeriana Officinalis In Parkinson

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. A theoretical approach of our previous experiments reporting the cytoprotective effects of the Valeriana officinalis compounds extract for PD is suggested. In addiction to considering the PD as a result of mitochondrial metabolic imbalance and oxidative stress, such as in our previous in vitro model of rotenone, in the present manuscript we added a genomic approach to evaluate the possible underlying mechanisms of the effect of the plant extract. Microarray of substantia nigra (SN) genome obtained from Allen Brain Institute was analyzed using gene set enrichment analysis to build a network of hub genes implicated in PD. Proteins transcribed from hub genes and their ligands selected by search ensemble approach algorithm were subjected to molecular docking studies, as well as 20 ns Molecular Dynamics (MD) using a Molecular Mechanic Poison/Boltzman Surface Area (MMPBSA) protocol. Our results bring a new approach to Valeriana officinalis extract, and suggest that hesperidin, and probably linarin are able to relieve effects of oxidative stress during ATP depletion due to its ability to binding SUR1. In addition, the key role of valerenic acid and apigenin is possibly related to prevent cortical hyperexcitation by inducing neuronal cells from SN to release GABA on brain stem. Thus, under hyperexcitability, oxidative stress, asphyxia and/or ATP depletion, Valeriana officinalis may trigger different mechanisms to provide neuronal cell protection. © 2016 Santos, Giraldez-Alvarez, ávila-Rodriguez, Capani, Galembeck, Neto, Barreto and Andrade.8MA

Effect of valerian root extracts (Valeriana officinalis) on acetaminophen glucuronidation: in vitro and in vivo studies

Herbal products have been shown to cause serious interactions when combined with conventional medications. A majority of these interactions are pharmacokinetic in nature and involve alteration in the activity of drug metabolizing enzymes. Valerian is a popular herbal product often used to treat insomnia and anxiety. Valerian extracts contain essential oils with sesquiterpenes such as valerenic acid and its derivatives. However, the drug interaction potential of valerian preparations is largely unknown. In human liver microsomes, valerenic acid forms a glucuronide conjugate suggesting that valerian extracts could interact with drugs that undergo glucuronidation. As glucuronidation is catalyzed by UDP- glucuronosyltransferase enzymes (UGT), the goal of this dissertation was to investigate the effect of valerian extracts on UGT activity. Acetaminophen was used as a probe substrate to measure UGT activity in these studies. A bioassay-guided fractionation approach was adopted to identify the major compounds in valerian extracts that are responsible for inhibition of UGT activity. The alcoholic extract of valerian was fractionated by liquid-liquid extractions followed by chromatographic methods. The organic extracts showed significant inhibitory activity compared to the aqueous extracts. Using various chromatographic and spectroscopic techniques, the major compounds present in the active fraction were identified as valerenic acid, acetoxyvalerenic acid and valerenal. The clinical implications of the inhibition of UGT enzymes by valerian extracts were investigated in a study in healthy human volunteers. Valerian administration resulted in an increased acetaminophen maximum plasma concentration (Cmax) and a decrease in time to reach the maximum plasma concentration (tmax), but did not affect the area under the plasma concentration-time curve (AUC) or half life. As these results were unexpected, human hepatocyte cultures were used to determine if enzyme induction potential of some components may offset the inhibition of UGT enzymes. We hypothesized that the inhibition observed in the microsomal study could be masked by an increase in enzyme activity due to induction of enzymes by chronic exposure to the extracts. In human hepatocyte cultures, valerian extracts inhibited UGT activity on acute exposure while chronic exposure increased UGT activity and mRNA levels. Our study indicates that there is no clinically significant interaction between acetaminophen and valereian. In vitro studies in human hepatocytes may better predict in vivo herb-drug interactions than studies in microsomes

Valerian Root in Treating Sleep Problems and Associated Disorders—A Systematic Review and Meta-Analysis

Sleep problems are widely prevalent and associated with various comorbidities including anxiety. Valerian ( Valeriana officinalis L.) is a popular herbal medicine used as a sleep aid, however the outcomes of previous clinical studies are inconsistent. This study was conducted to update and re-evaluate the available data in order to understand the reason behind the inconsistent outcomes and to provide a broader view of the use of valerian for associated disorders. PubMed, ScienceDirect, and Cochrane Library were searched to retrieve publications relevant to the effectiveness of valerian as a treatment of sleep problems and associated disorders. A total of 60 studies (n=6,894) were included in this review, and meta-analyses were performed to evaluate the effectiveness to improve subjective sleep quality (10 studies, n=1,065) and to reduce anxiety (8 studies, n=535). Results suggested that inconsistent outcomes were possibly due to the variable quality of herbal extracts and that more reliable effects could be expected from the whole root/rhizome. In addition, therapeutic benefits could be optimized when it was combined with appropriate herbal partners. There were no severe adverse events associated with valerian intake in subjects aged between 7 and 80 years. In conclusion, valerian could be a safe and effective herb to promote sleep and prevent associated disorders. However, due to the presence of multiple active constituents and relatively unstable nature of some of the active constituents, it may be necessary to revise the quality control processes, including standardization methods and shelf life

Evaluation of the Antimicrobial and Cytotoxic Activity of Cultivated Valeriana officinalis:

Drug resistance refers to the reduction in the effectiveness of a drug in treating a disease or improving the stability of symptoms. It can occur in various types of pathogens, including bacteria, parasites, viruses, fungi, and cancer cells. This experimental study was conducted between 2018 and 2019 in an area with an annual mean rainfall of 130mm. The sowing date was September 10th, and 2-3 seeds were planted per cell. MTT assays (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) were used to determine the percentage of viability in adenocarcinomic human alveolar basal epithelial cells (A549) and Medical Research Council cell strain 5 (MRC5) cell lines incubated with methanolic extract and valerenic acid for 48 hr. The methanol extract was prepared by adding 1000 mg of rhizomes to 100 mL of methanol, followed by sonication for 30 minutes, stirring, and centrifugation at 4000 rpm for 10 minutes. Minimum inhibitory concentration (MIC) and agar gel diffusion were used to assess the antimicrobial activity of the methanol extract of valerian against two important pathogenic microorganisms, Staphylococcus aureus and Candida albicans. However, valerenic acid did not reveal antimicrobial activity at doses of 200, 100, 50, 25, 12.5, and 6.25 µg/mL. The methanolic extract of V. officinalis contains high quantities of sesquiterpenes, specifically valerenic acid, which did not show cytotoxic effects on A549 and MRC5 cell lines as assessed by the MTT assay. In vivo evaluation of the extract in mice and guinea pigs did not reveal any toxic effects based on histopathological and clinical symptom assessments. Our study confirms that Valeriana officinalis has dose-dependent potential to improve existing treatment approaches for Staphylococcus aureus and Candida albicans infections