Effects of Passiflora incarnata and Valeriana officinalis in the control of anxiety due to tooth extraction: a randomized controlled clinical trial.

OBJECTIVE: This study evaluated the efficacy of Valeriana officinalis L. and Passiflora incarnata L. to control anxiety, surgical discomfort, and changes in vital signs of patients undergoing extraction of two unilateral third molars. MATERIALS AND METHODS: This study is a randomized, triple-blinded clinical trial. Fifty-four patients were allocated into three groups (Valeriana officinalis L., Passiflora incarnata L., and placebo). Anxiety levels were assessed using the State-Trace Anxiety Inventory (STAI) index, surgical discomfort using the QCirDental, and through the measurement of vital signs. The surgical times evaluated were before (T0), during (T1), and after surgery (T2). RESULTS: There was evidence that both Valeriana officinalis L. and Passiflora incarnata L., reduced STAY-S scores between T0 and T2 (p < .05), unlike placebo (p = .129). There was no change in surgical discomfort in all groups over time, and vital signs presented variable results. CONCLUSION: Phytotherapy drugs showed a reduction in anxiety state compared to the placebo group during third molar extraction procedure.  CLINICAL TRIAL REGISTRATION: klRBR-6kcxvrc, March 10, 2022.

Corrigendum: Phytotherapy for attention deficit hyperactivity disorder (ADHD): a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphar.2022.827411.].

New Iridoids and Acyclic Monoterpenoids from the Roots and Rhizomes of Valeriana officinalis var. latifolia.

Five new iridoids, valeralides A-E (1-5), two new acyclic monoterpenoids, valeralides F (6) and G (7), together with two known iridoids (8 and 9), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated based on 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The absolute configuration of compounds 1-4 were elucidated based on electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their inhibition on nitric oxide production, cytotoxicity and anti-influenza A virus activity.

Iridoids and other constituents from the leaves and stems of Valeriana officinalis var. latifolia.

Fifty-nine compounds, including nineteen previously undescribed iridoids (valeriananols A-S) and an undescribed alkaloid (5'-isovaleryl uridine), were isolated from the leaves and stems of Valeriana officinalis var. latifolia. Their structures were elucidated based on Mass spectrometry and NMR spectroscopy. The absolute configuration of valeriananols A-C, E-N, P, Q and S was determined by experimental and calculated electronic circular dichroism. Structurally, valeriananols A and B were two 1,3-seco-iridoids with a 3,6-epoxy moiety, valeriananols K and L were a pair of C-4 epimers, while valeriananol S was a 4'-deoxy iridoid glycoside. In addition, valeriananol P, stenopterin A and patriscabioin C exhibited significant inhibition on nitric oxide production with IC50 values of 10.31, 3.93 and 8.69 µM, respectively. Furthermore, stenopterin A and patriscabioin C showed anti-proliferation activity on the MCF-7 cell line with IC50 values of 17.28 and 13.89 µM, respectively.

Transplacental passage of hyperforin, hypericin, and valerenic acid.

Safe medications for mild mental diseases in pregnancy are needed. Phytomedicines from St. John's wort and valerian are valid candidates, but safety data in pregnancy are lacking. The transplacental transport of hyperforin and hypericin (from St. John's wort), and valerenic acid (from valerian) was evaluated using the ex vivo cotyledon perfusion model (4 h perfusions, term placentae) and, in part, the in vitro Transwell assay with BeWo b30 cells. Antipyrine was used for comparison in both models. U(H)PLC-MS/MS bioanalytical methods were developed to quantify the compounds. Perfusion data obtained with term placentae showed that only minor amounts of hyperforin passed into the fetal circuit, while hypericin did not cross the placental barrier and valerenic acid equilibrated between the maternal and fetal compartments. None of the investigated compounds affected metabolic, functional, and histopathological parameters of the placenta during the perfusion experiments. Data from the Transwell model suggested that valerenic acid does not cross the placental cell layer. Taken together, our data suggest that throughout the pregnancy the potential fetal exposure to hypericin and hyperforin - but not to valerenic acid - is likely to be minimal.

Chitosan based encapsulation of Valeriana officinalis essential oil as edible coating for inhibition of fungi and aflatoxin B1 contamination, nutritional quality improvement, and shelf life extension of Citrus sinensis fruits.

In this study, a novel chitosan nanoemulsion coating embedded with Valeriana officinalis essential oil (Ne-VOEO) was synthesized in order to improve the postharvest quality of Citrus sinensis fruits against infesting fungi, and aflatoxin B1 (AFB1) mediated nutritional deterioration. The developed nanoemulsion was characterized through SEM, FTIR, XRD, and DLS analyses. The nanoemulsion showed controlled delivery of VOEO responsible for effective inhibition of Aspergillus flavus, A. niger, A. versicolor, Penicillium italicum, and Fusarium oxysporum growth at 6.5, 5.0, 4.0, 5.5, and 3.5 µL/mL, respectively and AFB1 production at 5.0 µL/mL. The biochemical and molecular mechanism of aflatoxigenic A. flavus inhibition, and AFB1 diminution was associated with impairment in ergosterol biosynthesis, methylglyoxal production, and stereo-spatial binding of valerianol in the cavity of Ver-1 protein. During in vivo investigation, Ne-VOEO coating potentially restrained the weight loss, and respiratory rate of C. sinensis fruits with delayed degradation of soluble solids, titrable acidity, pH, and phenolic contents along with maintenance of SOD, CAT, APX activities (p < 0.05) and sensory attributes under specific storage conditions. Based on overall findings, Ne-VOEO nanoemulsion could be recommended as green, and smart antifungal coating agent in prolonging the shelf-life of stored fruits with enhanced AFB1 mitigation.

Bioactive Compounds of Underground Valerian Extracts and Their Effect on Inhibiting Metabolic Syndrome-Related Enzymes Activities.

Extractions of the underground parts of valerian were prepared with water and ethanol (25-95%) at 25-75 °C. Extraction yields, bioactive compounds, and the 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability of lyophilized extracts were determined. The inhibitory effects of the extracts, valerenic acid derivatives and phenolic acids, on metabolic syndrome (MS)-related enzymes activities were further examined. Both roots and rhizomes extracted with 95% ethanol at 75 °C had the highest levels of bioactive compounds. The antioxidant capacity and inhibition of MS-related enzymes of the roots extract were better than those of the rhizomes. The roots extract more strongly inhibited pancreatic lipase (inhibition of 50% of enzyme activity (IC50), 17.59 mg/mL), angiotensin-converting enzyme (ACE, IC50, 3.75 mg/mL), α-amylase (IC50, 12.53 mg/mL), and α-glucosidase (IC50, 15.40 mg/mL). These four phenolic acids inhibited the activity of MS-related enzymes. Valerenic acid demonstrated more of an inhibitory ability for ACE (IC50, 0.225 mg/mL, except for caffeic acid) and α-glucosidase (IC50, 0.617 mg/mL) than phenolic acids. Valerian extract inhibited key enzyme activities that were associated with obesity (lipase), hypertension (ACE), and type 2 diabetes (α-amylase and α-glucosidase), suggesting that it is a potential candidate for the development of functional supplements.

Sesquiterpenoids and monoterpenoids from the water decoction of Valeriana officinalis L.

Nine previously undescribed compounds including three sesquiterpenoids, three iridoids, two monoterpenoids and a furan fatty acid, along with seventeen known ones, were isolated from the water decoction of roots and rhizomes of Valeriana officinalis L. Structure elucidation of the twenty-six compounds were accomplished by analysis of the extensive spectroscopic data, and the absolute configurations of the nine previously undescribed ones were established by NOESY experiment and the electronic circular dichroism (ECD) simulations. Among them, ß-patchoulene-8-O-ß-D-glucopyranoside, 11-methoxyl-viburtinal, and protocatechuic acid showed anti-neuroinflammatory potentials by significantly inhibiting the secretion of nitric oxide (NO) on BV-2 cells upon LPS stimulation (p < 0.001) without affecting the cell viability.

Iridoids and sesquiterpenoids from Valeriana officinalis and their bioactivities.

Twenty-six iridoids, including six undescribed ones (iridoidvols A-F) and an undescribed natural one, along with ten known sesquiterpenoids were isolated from the roots and rhizomes of Valeriana officinalis. Structurally, iridoidvol A is the first example of iridoid with sesquiterpenoid acid ester. In addition, all of the isolates were evaluated for anti-inflammatory and anti-influenza virus activities. Among them, isovaltrate isovaleroyloxyhydrin exhibited a significant inhibitory effect on NO production with an IC50 value of 19.00 µM.

Intraspecific Variability of Wild-Growing Common Valerian (Valeriana officinalis L.).

Common valerian (Valeriana officinalis L.) is an important medicinal plant revealing sedative, hypotensive, anti-spasmodic and anxiolytic activity. The purpose of the study was to determine the intraspecific variability of the common valerian growing wild in Poland and the 'Lubelski' landrace, as to their developmental traits, chemical composition and selected genetic parameters. Both wild-growing populations (19) and the landrace (1) were evaluated under ex situ conditions. Observations of the underground organs parameters, both developmental and chemical (according to the European Pharmacopoeia) were carried out in the first year of the plant's development, while the characteristics of the aboveground organs, followed by the sowing value of seeds (according to the International Seed Testing Association)-in the second year. The genetic analyses were performed using the NGS-DArT-seq method. Results indicate the presence of five different gene pools covering the regions of population's origin, with a gene flow within and between them. A high level of developmental and chemical variabilities among the wild-growing populations was noticed, however without a clear relation to the region of the origin. The mass of underground organs ranged from 107.4 to 403.6 g FW × plant-1 with the content of sesquiterpenic acids at the level of 0.004-0.094%. Population no 18 was distinguished by the highest content of sesquiterpenic acids and the relatively high mass of underground organs, followed by the admixture of the gene pool, typical for the 'Lubelski' landrace. Unlike the 'Lubelski' landrace, the wild-growing populations were characterized by a high amount of an essential oils (3.90 to 10.04 mL/kg), which may be promising from the perspective of their potential use. In turn, the sowing value of the seeds obtained from the populations, expressed as the germinability, was rather low (25.25-62.25%).

Advanced in Vitro Safety Assessment of Herbal Medicines for the Treatment of Non-Psychotic Mental Disorders in Pregnancy.

When confronted with non-psychotic mental disorders, pregnant women often refrain from using synthetic drugs and resort to herbal medicines such as St. John's wort, California poppy, valerian, lavender, and hops. Nevertheless, these herbal medicines have not yet been officially approved in pregnancy due to lack of safety data. Using a variety of in vitro methods (determination of cytotoxicity, apoptosis induction, genotoxicity, effects on metabolic properties, and inhibition/induction of differentiation) in a commonly used placental cell line (BeWo b30), we were previously able to show that extracts from these plants are likely to be safe at the usual clinical doses. In the present work, we wanted to extend our safety assessment of these herbal medicines by 1) looking for possible effects on gene expression and 2) using the same in vitro methods to characterize effects of selected phytochemicals that might conceivably lead to safety issues. Proteomics results were promising, as none of the five extracts significantly affected protein expression by up- or down-regulation. Protopine (contained in California poppy), valerenic acid (in valerian), and linalool (in lavender) were inconspicuous in all experiments and showed no adverse effects. Hyperforin and hypericin (two constituents of St. John's wort) and valtrate (typical for valerian) were the most obvious phytochemicals with respect to cytotoxic and apoptotic effects. A decrease in cell viability was evident with hypericin (≥1 µM) and valtrate (≥10 µM), whereas hyperforin (≥3 µM), hypericin (30 µM) and valtrate (≥10 µM) induced cell apoptosis. None of the tested phytochemicals resulted in genotoxic effects at concentrations of 0.1 and 1 µM and thus are not DNA damaging. No decrease in glucose consumption or lactate production was observed under the influence of the phytochemicals, except for valtrate (at all concentrations). No compound affected cell differentiation, except for hyperforin (≥1 µM), which had an inhibitory effect. This study suggests that extracts from St. John's wort, California poppy, valerian, lavender, and hops are likely to be safe during pregnancy. High plasma concentrations of some relevant compounds-hyperforin and hypericin from St. John's wort and valtrate from valerian-deserve special attention, however.

Phytotherapy for Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-analysis.

Attention deficit hyperactivity disorder (ADHD) is commonly a neurodevelopmental behavioural disorder in children and adolescents. Mainly characterized by symptoms like lack of attention, hyperactivity, and impulsiveness, it can impact the overall mental development of the one affected. Several factors, both genetic and non-genetic, can be responsible for this disorder. Although several traditional treatment methods involve medication and other counselling techniques, they also come with different side effects. Hence, the choice is now shifting to alternative treatment techniques. Herbal treatments are considered one of the most popular complementary and alternative medicine (CAM) administered. However, issues related to the safety and efficacy of herbal remedies for the treatment of ADHD need to be investigated further. This study aims to find out the recent advancement in evidence-based use of herbal remedies for ADHD by a comprehensive and systematic review that depicts the results of the published works on herbal therapy for the disorder. The electronic databases and the references retrieved from the included studies present related randomized controlled trials (RCTs) and open-label studies. Seven RCTs involving children and adolescents diagnosed with ADHD met the inclusion criteria. There is a fair indication of the efficacy and safety of Melissa officinalis L., Bacopa monnieri (L.) Wettst., Matricaria chamomilla L., and Valeriana officinalis L. from the studies evaluated in this systematic review for the treatment of various symptoms of ADHD. Limited evidence was found for Ginkgo biloba L. and pine bark extract. However, various other preparations from other plants did not show significant efficacy. There is inadequate proof to strongly support and recommend the administration of herbal medicines for ADHD, but more research is needed in the relevant field to popularize the alternative treatment approach.

In Vitro Cytotoxicity and Oxidative Stress Evaluation of Valerian (Valeriana officinalis) Methanolic Extract in Hepg2 and Caco2 Cells

Objectives: Traditional treatment methods are becoming popular and commonly used in many societies and have become the first treatment option for most people. While some of these methods are helpful, they can interact with medications the patient is taking for another disease and cause a variety of life-threatening risks. Valerian (catweed) plant is used in traditional medicine as a sleep aid due to its sedative effects. Valerian may also exert anticancer effect in vitro. Materials and Methods: In this study, the cytotoxicty and oxidative stress effects of valerian root extract were evaluated in human liver hepatocellular carcinoma (Hepg2) and human colorectal adenocarcinoma (Caco2) cell lines. The cytotoxicity was evaluated via the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Total reactive oxygen species analysis was performed via a 2',7'-dichlorodihydrofluorescein diacetate assay in flow cytometry. Results: Inhibition concentration 50 values were calculated as 936.6 and 1097.5 µg/mL in the Hepg2 and Caco2 cell lines, respectively. It was observed that valerian root extract did not induce oxidative stress in HepG2 and Caco2 cell lines. Conclusion: These results indicate that the use of valerian root extract as an alternative method in cancer treatment may not be effective and may cause a risk for public health. On the other hand, it may be safe at recommended tolerated concentrations since it does not cause oxidative stress.

Back to the Roots-An Overview of the Chemical Composition and Bioactivity of Selected Root-Essential Oils.

Since ancient times, plant roots have been widely used in traditional medicine for treating various ailments and diseases due to their beneficial effects. A large number of studies have demonstrated that-besides their aromatic properties-their biological activity can often be attributed to volatile constituents. This review provides a comprehensive overview of investigations into the chemical composition of essential oils and volatile components obtained from selected aromatic roots, including Angelica archangelica, Armoracia rusticana, Carlina sp., Chrysopogon zizanioides, Coleus forskohlii, Inula helenium, Sassafras albidum, Saussurea costus, and Valeriana officinalis. Additionally, their most important associated biological impacts are reported, such as anticarcinogenic, antimicrobial, antioxidant, pesticidal, and other miscellaneous properties. Various literature and electronic databases-including PubMed, ScienceDirect, Springer, Scopus, Google Scholar, and Wiley-were screened and data was obtained accordingly. The results indicate the promising properties of root-essential oils and their potential as a source for natural biologically active products for flavor, pharmaceutical, agricultural, and fragrance industries. However, more research is required to further establish the mechanism of action mediating these bioactivities as well as essential oil standardization because the chemical composition often strongly varies depending on external factors.

8-hydroxypinoresinol-4-O-ß-D-glucoside from Valeriana officinalis L. Is a Novel Kv1.5 Channel Blocker.

ETHNOPHARMACOLOGY RELEVANCE: In folkloric medicine of many cultures, one of the medical uses of Valeriana officinalis Linn is to treat heart-related disease. Recently, it was shown that the ethanol extracts from V. officinalis could effectively prevent auricular fibrillation, and 8-hydroxypinoresinol-4-O-ß-D-glucoside (HPG) from the extracts is one of the two active compounds showing antiarrhythmia activities. AIM OF THE STUDY: The human Kv1.5 channel (hKv1.5) has potential antiarrhythmia activities, and this study arms at investigating the current blocking effects of HPG on hKv1.5 channel. MATERIAL AND METHODS: HPG was obtained from V. officinalis extracts, and hKv1.5 channels were expressed in HEK 293 cells. HPG was perfused while recording the current through hKv1.5 channels. Patch-clamp recording techniques were used to study the effects of HPG at various concentrations (10 µM, 30 µM, and 50 µM) on hKv1.5 channels. RESULTS: The present study demonstrated that HPG inhibited hKv1.5 channel current in a concentration-dependent manner; the higher the concentration, the greater is the inhibition at each depolarization potential. During washout, the channels did not full recover indicating that the un-coupling between HPG and hKv1.5 channels is a slow process. CONCLUSION: HPG may be an effective and safe active ingredient for AF having translational potential.

Identification of key genes associated with secondary metabolites biosynthesis by system network analysis in Valeriana officinalis.

Valeriana officinalis is a medicinal plant, a source of bioactive chemical compounds and secondary metabolites which are applied in pharmaceutical industries. The advent of ethnomedicine has provided alternatives for disease treatment and has increased demands for natural products and bioactive compounds. A set of preliminary steps to answers for such demands can include integrative omics for systems metabolic engineering, as an approach that contributes to the understanding of cellular metabolic status. There is a growing trend of this approach for genetically engineering metabolic pathways in plant systems, by which natural and synthetic compounds can be produced. As in the case of most medicinal plants, there are no sufficient information about molecular mechanisms involved in the regulation of metabolic pathways in V. officinalis. In this research, systems biology was performed on the RNA-seq transcriptome and metabolome data to find key genes that contribute to the synthesis of major secondary metabolites in V. officinalis. The R Package Weighted Gene Co-Expression Network Analysis (WGCNA) was employed to analyze the data. Based on the results, some major modules and hub genes were identified to be associated with the valuable secondary metabolites. In addition, some TF-encoding genes, including AP2/ERF-ERF, WRKY and NAC TF families, as well as some regulatory factors including protein kinases and transporters were identified. The results showed that several novel hub genes, such as PCMP-H24, RPS24B, ANX1 and PXL1, may play crucial roles in metabolic pathways. The current findings provide an overall insight into the metabolic pathways of V. officinalis and can expand the potential for engineering genome-scale pathways and systems metabolic engineering to increase the production of bioactive compounds by plants.

A Review Focused on Molecular Mechanisms of Anxiolytic Effect of Valerina officinalis L. in Connection with Its Phytochemistry through in vitro/in vivo Studies.

Valeriana officinalis L. (Valerianaceae) is one of the most reputed ancient medicinal plants used in modern phytotherapy and traditional medicine. Its root extract is one of the most effective herbal sedatives and tranquilizers, where the plant is also used for the treatment of gastrointestinal spasms. V. officinalis has complex phytochemistry consisting of the esterified iridoid derivatives known as valepotriates (e.g., valtrate, didrovaltrate, isovalerenic acid), sesquiterpenes (e.g., valerenic acid), flavonoids (e.g., linarin, apigenin), lignans (e.g., pinoresinol, hydroxypinoresinol), alkaloids (e.g., actinidine, valerine), triterpenes (e.g., ursolic acid), monoterpenes (e.g., borneol, bornyl acetate). Among them, valerenic acid is a marker compound for standardization of the root extracts of the plant and has been reported in many in vitro/in vivo studies to be responsible for anxiolytic action of the plant. Although modulation of gamma-aminobutyric acid (GABA) receptors has been revealed to be the leading mechanism of the plant-based on the existence of valerenic acid, several studies described the interaction of valerenic acid with glutamergic receptors. In addition to valerenic acid, isovaleric acid, didrovaltrate, borneol, and some lignans have also been proposed to contribute to the anxiolytic effect of the plant. In the current review, the data selectively scrutinized from the in vitro/in vivo studies about identifying anxiolytic molecular mechanisms of V. officinalis is focused.

Optimization of SRAP-PCR System for Valeriana officinalis var. latifolia and Primer Screening / 中国实验方剂学杂志

Objective:To establish the sequence-related amplified polymorphism （SRAP）-polymerase chain reaction （PCR） system for <italic>Valeriana officinalis</italic> var. <italic>latifolia</italic>，so as to lay the theoretical and technical foundations for the breeding of<italic> V. officinalis </italic>var. <italic>latifolia</italic>. Method:Single factor test was applied to investigate the effects of <italic>Taq</italic> Mix dose，Mg²⁺concentration，template DNA concentration，and <italic>Taq </italic>DNA polymerase content on SRAP-PCR amplification of <italic>V. officinalis </italic>var. <italic>latifolia</italic>，based on which the orthogonal experiments were performed to optimize the SRAP-PCR system for <italic>V. officinalis </italic>var. <italic>latifolia</italic>. The effective primers that could be used for genetic diversity studies of <italic>V. officinalis</italic> var. <italic>latifolia </italic>were selected under the optimal reaction condition. Result:The results of the single factor test showed that <italic>Taq </italic>Mix dose within the range of 8-11 μL resulted in better amplification. The addition of a low concentration of Mg²⁺，the medium to low concentrations of template DNA，or the low concentration of <italic>Taq</italic> DNA polymerase enhanced the amplification efficiency or richness. As demonstrated by the orthogonal experiments，the influencing degrees of related factors on SRAP-PCR amplification of <italic>V. officinalis</italic> var. <italic>latifolia </italic>were sorted in a descending order as follows： <italic>Taq</italic> Mix dose><italic>Taq</italic> DNA polymerase content>Mg²⁺ concentration>template DNA concentration. The optimal reaction system for <italic>V. officinalis</italic> var. <italic>latifolia </italic>was determined to consist of 11 μL of <italic>Taq</italic> Mix，30 ng of template DNA，0.025 mmol·L^-1Mg²⁺，1.5 U<italic> </italic>of<italic> Taq </italic>DNA polymerase，5 μmol·L^-1 forward primer，and 5 μmol·L^-1 reverse primer，which was supplemented to 20 μL with ddH₂O. The optimal annealing temperature was 36.8 ℃. A total of 17 pairs of effective primers with high band resolution and polymorphism were selected from 88 primer pairs for SRAP-PCR of <italic>V. officinalis</italic> var. <italic>latifolia</italic>. Conclusion:The established SRAP-PCR system for <italic>V. officinalis</italic> var. <italic>latifolia</italic> is stable， which can be used for genetic diversity studies of <italic>V. officinalis</italic> var. <italic>latifolia</italic>.

Valerian treatment during the postpartum period alters breast milk composition and impairs long-term memory in female rat offspring

Maternal anxiety symptoms in the perinatal period might have long-term health effects on both the mother and the developing child. Valerian is a phytotherapeutic agent that is widely used for the treatment of anxiety. This study investigated the effects of valerian treatment in postpartum rats on maternal care, toxicity, and milk composition. Postnatal development, memory, and anxiety behavior in the offspring were also assessed. Postpartum Wistar rats received the valerian (500, 1000, or 2000 mg·kg-1·day-1) by oral gavage. Clinical and biochemical toxicity was evaluated with commercial kits. Maternal behavior was observed daily. Milk composition was analyzed by colorimetric methods. Physical and neuromotor tests were used to analyze postnatal development. Anxiolytic activity was assessed by the elevated plus maze, and memory was evaluated by the step-down inhibitory avoidance task. Maternal toxicity and care behavior were not altered by the treatment, while only the highest dose promoted a significant increase of lactose, and the doses 1000 and 2000 mg·kg-1·day-1 promoted a reduction of protein contents in milk. Postnatal development was similar in all offspring. Adult offspring did not display altered anxiety behavior, while long-term memory was impaired in the female adult offspring by maternal treatment with 1000 mg·kg-1·day-1. These results suggested that high doses of valerian had significant effects on important maternal milk components and can cause long-term alterations of offspring memory; thus, treatment with high doses of valerian is not safe for breastfeeding Wistar rat mothers.

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.