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.

Valtrate, an iridoid compound in Valeriana, elicits anti-glioblastoma activity through inhibition of the PDGFRA/MEK/ERK signaling pathway.

BACKGROUND: Valtrate, a natural compound isolated from the root of Valeriana, exhibits antitumor activity in many cancers through different mechanisms. However, its efficacy for the treatment of glioblastoma (GBM), a tumor type with a poor prognosis, has not yet been rigorously investigated. METHODS: GBM cell lines were treated with valtrate and CCK-8, colony formation and EdU assays, flow cytometry, and transwell, 3D tumor spheroid invasion and GBM-brain organoid co-culture invasion assays were performed to assess properties of proliferation, viability, apoptosis and invasion/migration. RNA sequencing analysis on valtrate-treated cells was performed to identify putative target genes underlying the antitumor activity of the drug in GBM cells. Western blot analysis, immunofluorescence and immunohistochemistry were performed to evaluate protein levels in valtrate-treated cell lines and in samples obtained from orthotopic xenografts. A specific activator of extracellular signal-regulated kinase (ERK) was used to identify the pathways mediating the effect. RESULTS: Valtrate significantly inhibited the proliferation of GBM cells in vitro by inducing mitochondrial apoptosis and suppressed invasion and migration of GBM cells by inhibiting levels of proteins associated with epithelial mesenchymal transition (EMT). RNA sequencing analysis of valtrate-treated GBM cells revealed platelet-derived growth factor receptor A (PDGFRA) as a potential target downregulated by the drug. Analysis of PDGFRA protein and downstream mediators demonstrated that valtrate inhibited PDGFRA/MEK/ERK signaling. Finally, treatment of tumor-bearing nude mice with valtrate led to decreased tumor volume (fivefold difference at day 28) and enhanced survival (day 27 vs day 36, control vs valtrate-treated) relative to controls. CONCLUSIONS: Taken together, our study demonstrated that the natural product valtrate elicits antitumor activity in GBM cells through targeting PDGFRA and thus provides a candidate therapeutic compound for the treatment of GBM.

Secondary metabolites from the underground parts of Valeriana sisymbriifolia Vahl. and their in vitro cytotoxic activities.

Cytotoxic activity-guided isolation studies on the underground parts of Valeriana sisymbriifolia Vahl. led to the isolation of 12 secondary metabolites including two undescribed iridoids, sisymbriifolivaltrate and sisymbriifolioside, and two unreported sesquiterpene lactones, sisymbriifolins A and B. Chemical structures of the isolates were established by extensive 1D and 2D NMR analyses as well as HR-ESI-MS. The in vitro cytotoxic activities of the extract, sub-fractions and isolates on lung (A549), breast (MCF7), gastric (HGC27) and prostate (PC3) cancer cell lines were evaluated by MTS assay. Sisymbriifolivaltrate, didrovaltrate, valtrate, 7-homovaltrate and 1-α-acevaltrate exhibited promising cytotoxic activity on MCF7 cell line with IC50 values ranging from 2.5 to 12.3 µM, while valtrate demonstrated the best cytotoxicity against A549 cells with the IC50 value of 7.5 µM. Valtrate and 7-homovaltrate were found to exert noteworthy cytotoxicity towards HGC27 cell line (IC50 values: 2.3 and 3.7 µM, respectively), whereas valtrate, 7-homovaltrate and 1-α-acevaltrate (IC50 values: 2.3-9.7 µM) were found to be potent cytotoxic against PC3 cells. Among the tested compounds, particularly valepotriate-type iridoids were found to be the main cytotoxic principles of V. sisymbriifolia.

Genetic and Chemical Diversity of Commercial Japanese Valerian.

In order to investigate the relationship between the chemical composition of essential oils and haplotypes of the psbA-trnH intergenic spacer region of chloroplast DNA (psbA-trnH) in Valerianae Fauriei Radix (Japanese Valerian; JV), we analyzed the DNA sequence and GC-MS metabolome of JV from Japanese markets and of herbal specimens from related species. DNA analysis revealed that JV products from Japan consisted of three haplotypes, namely AH-1, -2 and -5 reported in our previous study. The GC-MS metabolome revealed five chemotypes (J1, J2, C, K and O), of which J1, J2 and C were detected in the JV products from Japan. Chemotypes J1 and J2, with kessyl glycol diacetate (KGD) as the main volatile component, were found in the products of Japanese origin whereas chemotype C, with 1-O-acetyl-2,10-bisaboladiene-1,6-diol (ABD), was found in the products of Chinese and Korean origin. The haplotypes were correlated with the chemotypes: haplotype AH-1 for chemotype J1, AH-2 for chemotype J2 and AH-5 for chemotype C, suggesting that the chemical diversity of JV is not attributed to the environmental factors rather to the genetic factors. Since KGD and ABD were reported to have sedative effects and nerve growth factor (NGF)-potentiating effects, respectively, understanding the chemotypes and selecting an appropriate one would be important for the application of JV. The psbA-trnH haplotypes could be useful DNA markers for the quality control and standardization of JV.

Anti-Proliferative Effects of Iridoids from Valeriana fauriei on Cancer Stem Cells.

We isolated seven new iridoid glucosides (valerianairidoids I-VII; 1-3, 6, 7, 9, and 12) and six known compounds from the methanol extract of the dried rhizomes and roots of Valeriana fauriei. Chemical and spectroscopic data were used to elucidate the chemical structures of the seven new iridoid glucosides, and their absolute configurations were determined by comparing their electronic circular dichroism (ECD) spectra with those determined experimentally. Aglycones 1a, 6a, and 9a, which were obtained by enzymatic hydrolysis of the isolated iridoid glucosides, exhibited anti-proliferative activities against cancer stem cells (CSCs) established by a sphere-formation assay using human breast cancer (MDA-MB-231) and human astrocytoma (U-251MG) cells. Interestingly, these iridoids selectively showed anti-proliferative activities against CSCs from MDA-MB-231 cells. These results suggest that the iridoids obtained in this study may have potency as a breast cancer treatment and as preventive agent via exterminating CSCs.

Plantas com ação no sistema nervoso central que constam na relação nacional de plantas medicinais de interesse ao sus (RENISUS) / Plants acting on the central nervous system: review plantas com ação no sistema nervoso central que constam na relação nacional de plantas medicinais de interesse ao sus (RENISUS) / Plantas con acción sobre el sistema nervioso central incluidas en la lista nacional de plantas medicinales de interés para sus (RENISUS)

A depressão é uma doença grave que atinge a população em geral, estudos epidemiológicos estimam que a prevalência da depressão ao longo da vida no Brasil está em torno de 15,5%. Os fatores que desencadeiam o aparecimento da depressão incluem fatores sociais, psicológicos, biológicos e também fatores externos específicos como eventos estressantes, solidão, consumo de álcool e drogas, doenças crônicas e dar á luz (depressão pós-parto). O objetivo da presente pesquisa consistiu em realizar uma revisão bibliográfica sobre as principais plantas medicinais com ação antidepressiva. A ansiedade vem se tornando um dos principais problemas da atualidade, sendo intensificada pela pandemia causada pelo coronavírus, onde constatou-se que durante o pico da pandemia onde os casos confirmados de COVID-19 no Brasil ascenderam de 45.757 para 330.890, e as mortes, de 2.906 para 21.048, o sentimento de tristeza/depressão atingiu 40% dos adultos brasileiros. Os sintomas de depressão podem ser amenizados quando a disponibilidade sináptica de monoaminas são aumentadas, e esse aumento pode ocorrer através da diminuição da metabolização desses neurotransmissores. Neste sentido, busca-se através da farmacoterapia a utilização de antidepressivos que disponibilizem as monoaminas na fenda sináptica. A escolha do fármaco é feita com base nos sintomas da depressão e na boa resposta a uma determinada classe de antidepressivos. Em fevereiro de 2009 o Ministério da saúde lançou a Relação Nacional de Plantas Medicinais de Interesse ao SUS (RENISUS), contendo 71 espécies vegetais que são distribuídas de forma in natura nas unidades básicas de saúde (UBS). Destas, somente três espécies apresentam efeito antidepressivo e ansiolítico comprovados na literatura sendo Matricharia chamomilla, Erytrinum mulungu e a Passiflora incarnata que também fazem parte da RENISUS. Além destas, outras espécies como a Melissa officinalis, Lippia alba, Valeriana officinalis e Piper methysticum são utilizadas pela população para tratar ansiedade, insônia e depressão, sugerindo desta forma que estas espécies sejam incluídas na RENISUS.

Depression is a serious disease that affects the general population, epidemiological studies estimate that the prevalence of depression throughout life in Brazil is around 15.5%. The factors that trigger the onset of depression include social, psychological, biological and also specific external factors such as stressful events, loneliness, alcohol and drug consumption, chronic diseases and giving birth (postpartum depression). The objective of the present research was to carry out a literature review on the main medicinal plants with antidepressant action. Anxiety has become one of the main problems of today, being intensified by the pandemic caused by the coronavirus, where it was found that during the peak of the pandemic where confirmed cases of COVID-19 in Brazil rose from 45,757 to 330,890, and deaths, from 2,906 to 21,048, the feeling of sadness/depression reached 40% of Brazilian adults. Symptoms of depression can be alleviated when synaptic availability of monoamines is increased, and this increase can occur through decreased metabolization of these neurotransmitters. In this sense, the use of antidepressants that make monoamines available in the synaptic cleft is sought through pharmacotherapy. The choice of drug is based on symptoms of depression and good response to a particular class of antidepressants. In February 2009, the Ministry of Health launched the National List of Medicinal Plants of Interest to the SUS (RENISUS), containing 71 plant species that are distributed in natura form in basic health units (UBS). Of these, only three species have antidepressant and anxiolytic effects proven in the literature, being Matricharia chamomilla, Erytrinum mulungu and Passiflora incarnata, which are also part of RENISUS. In addition to these, other species such as Melissa officinalis, Lippia alba, Valeriana officinalis and Piper methysticum are used by the population to treat anxiety, insomnia and depression, thus suggesting that these species are included in RENISUS.

Los estudios epidemiológicos estiman que la prevalencia de la depresión a lo largo de la vida en Brasil es de alrededor del 15,5%. Los factores que desencadenan la aparición de la depresión son sociales, psicológicos, biológicos y también factores externos específicos, como los acontecimientos estresantes, la soledad, el consumo de alcohol y drogas, las enfermedades crónicas y el parto (depresión posparto). El objetivo de esta investigación fue realizar una revisión bibliográfica sobre las principales plantas medicinales con acción antidepresiva. La ansiedad se ha convertido en uno de los principales problemas de la actualidad, intensificándose por la pandemia causada por el coronavirus, donde se encontró que durante el pico de la pandemia donde los casos confirmados de COVID-19 en Brasil aumentaron de 45.757 a 330.890, y las muertes, de 2.906 a 21.048, el sentimiento de tristeza/depresión alcanzó el 40% de los adultos brasileños. Los síntomas de la depresión pueden aliviarse cuando se aumenta la disponibilidad sináptica de las monoaminas, y este aumento puede producirse mediante una disminución de la metabolización de estos neurotransmisores. En este sentido, se busca a través de la farmacoterapia el uso de antidepresivos que hagan disponibles las monoaminas en la hendidura sináptica. La elección del fármaco se hace en función de los síntomas de la depresión y de la buena respuesta a una clase concreta de antidepresivos. En febrero de 2009, el Ministerio de Salud lanzó la Lista Nacional de Plantas Medicinales de Interés para el SUS (RENISUS), que contiene 71 especies de plantas que se distribuyen in natura en unidades básicas de salud (UBS). De ellas, sólo tres especies tienen efectos antidepresivos y ansiolíticos probados en la literatura: Matricharia chamomilla, Erytrinum mulungu y Passiflora incarnata, que también forman parte del RENISUS. Además de éstas, otras especies como Melissa officinalis, Lippia alba, Valeriana officinalis y Piper methysticum son utilizadas por la población para tratar la ansiedad, el insomnio y la depresión, lo que sugiere que estas especies se incluyan en el RENISUS.

Activity-Guided Isolation of Cytotoxic Non-Glycosidic Ester Iridoids from Valeriana alliariifolia Adams and Unravelling Their Cell Death Mechanisms.

The aim of this study was to isolate the cytotoxic compounds from V. alliariifolia via activity-guided isolation and to determine the mechanism of actions of the most potent ones. The crude EtOH extract as well as CHCl3 and AcOEt subextracts demonstrated remarkable cytotoxic activities against A549, MCF7, HGC27 and PC3 cancer cells. Sequential chromatographic separations on active subextracts yielded 14 secondary metabolites, including 11 iridoids (1-11) most of which belong to non-glycosidic ester iridoids, two phenylpropanoids (12 and 13) and one lignan (14). The chemical structures of purified compounds were elucidated by NMR and MS analysis. Among the isolates, 7-deisovaleroylvaltrate (3) was isolated for the first time as a natural product. According to the cytotoxic assay compounds, 2, 4-6 and 8 were found to be the potent cytotoxic compounds (IC50 <10 µM) against at least one of the tested cancer cell lines. Thus, 2, 4-6 and 8 were investigated for their effects on apoptotic, necrotic and autophagic pathways as well as cell cycle progression. They exerted anticancer activities by inducing different cell death mechanisms depending on the cancer cells. The results demonstrated that 2, 4-6 and 8 could be potential anticancer drug leads that deserve further in vivo and clinical studies on the way to discover novel natural compounds with anticancer properties.

Jatavaleridoids A-H, eight new iridoids from the roots and rhizomes of Valeriana jatamansi Jones.

Eight new iridoids, jatavaleridoids A-H (1-8), were isolated from the roots and rhizomes of Valeriana jatamansi. Their structures and absolute configurations were elucidated based on NMR and HRESIMS spectroscopic data, as well as quantum chemical calculation. Structurally, compounds 1-5 and 8 were rare iridoids with long-chain fatty acid esters at C-10. In addition, compound 7 showed cytotoxicity, while compounds 1 and 2 exhibited inhibition on NO production.

Valeridoids G - Q, Eleven seco-Iridoids from Valeriana jatamansi and Their Bioactivites.

Eleven new seco-iridoids, valeridoids G-Q (1-6 and 8-12), along with four known products, 9-epi-valtral C (7), desacylbaldrinal (13), 11-methoxyviburtinal (14) and baldrinal (15), were obtained from Valeriana jatamansi. Among them, the new compounds were identified by their NMR, HR-ESI-MS spectroscopic data and ECD calculation. Moreover, valeridoid N and O were a pair of C3 epimers, whose ether bonds between C-1 and C-3 opened, and new ether bonds formed between C-3 and C-6. Valeridoid Q belonged to the C-1 degradation of seco-iridoids. As a result, 9-epi-valtral C displayed significant inhibition on Streptococcus agalactiae, Staphylococcus aureus, Staphylococcus argenteus, Shigella flexneri and Klebsiella pneumoniae, and valeridoid Q exhibited the most significant inhibition against Salmonella enteritidis. 9-Epi-valtral C and baldrinal selectively inhibited the growth of human glioma stem cells. Valeridoid Q exhibited significant anti-influenza activity, while valeridoid O inhibited nitric oxide production.

Prolonging effects of Valeriana fauriei root extract on pentobarbital-induced sleep in caffeine-induced insomnia model mice and the pharmacokinetics of its active ingredients under conditions of glycerol fatty acid ester as emulsifiers.

ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana plant roots have traditionally been used to treat central nervous system-related disorders in European countries. Among this genus, the Japanese Pharmacopoeia registers the dried roots of V. fauriei Briq. (VF). However, insufficient pharmacological data are available for this species. AIM OF THE STUDY: We investigated the sedative effects of VF extract in a murine caffeine-induced insomnia model as well as the active ingredients and their pharmacokinetics to determine its basic pharmacological action mechanisms under conditions glycerol fatty acid ester is used as emulsifiers. MATERIALS AND METHODS: A murine insomnia model was created by caffeine. Samples derived from the ethanol extract of VF were administered per oral (p.o.), and caffeine was injected intraperitoneally (i.p.). Pentobarbital was injected i.p. and the sleep latency and duration were measured. To confirm the mechanism of action of VF, flumazenil, a specific γ-aminobutyric acid receptor type A (GABAA receptor) antagonist, was administered (i.p.) immediately prior to the sample administration. We examined the pharmacokinetic profiles of the active ingredients in the plasma, brain, urine, and feces of mice after the administration (p.o and intravenous (i.v.)) of VF samples. RESULTS: VF extract (5 g as VF/kg, p.o.) significantly shorten sleep latency and prolonged pentobarbital-induced sleep in caffeine-induced insomnia mice, partially mediated via the GABAergic nervous system, although a higher dose (10 g as VF/kg, p.o.) was required to exhibit the significant effects in normal mice. Kessyl glycol diacetate (KGD), the main constitutive compound in VF, did not shorten sleep latency but exhibited the same sleep prolonged effect at a dose related to VF extract. The concentration of kessyl glycol 8-acetate (KG8) in the plasma was higher than that of KGD in mice treated (p.o.) with VF extract. The profiles of brain concentrations of KGD and KG8 were similar to those in the plasma, and approximately 20% of those in the plasma were distributed throughout the brain. The excretions of KGD and KG8 in urine and feces was slightly detected, and an unknown large peak related to KG8 was detected in the urine of mice administered with VF extract by HPLC-MS/MS analysis. CONCLUSIONS: VF exhibits more sedative effects under stressed conditions, such as insomnia, and the major active ingredients are KGD and its metabolite KG8, which are distributed from the blood circulation into the brain by simple diffusion. KG8 is further metabolized into other metabolites that are easily excreted in the urine.

Stability of valeriana-type iridoid glycosides from rhizomes of Nardostachys jatamansi and their protection against H2O2-induced oxidative stress in SH-SY5Y cells.

Nardostachys jatamansi is close to Valerian in consideration of their same psychoactive effects, such as sedation and neuroprotection. Valeriana-type iridoids are major active components of Valerian, but few valeriana-type iridoids have been isolated from N. jatamansi. Iridoid-targeting chemical investigation of the rhizomes of N. jatamansi resulted in the isolation of seven valeriana-type iridoid glycosides, four of which are previously undescribed. Their structures were determined through NMR spectroscopy, high-resolution mass spectrometry, and optical rotation experiments. In addition, the inaccurate configurations of patrinalloside and 6″-acetylpatrinalloside from previous reports were corrected. These compounds, unstable due to alcoholic solvents, were more stable in the mixtures than in purified forms, as monitored by the qNMR method, supporting the use of natural products as mixtures. Furthermore, the isolates, as well as crude and solvent partition extracts, were found to have a protective effect against hydrogen-peroxide-induced toxicity in human neuroblastoma cells, as confirmed by assays for cell viability and antioxidation. These findings suggest the potential therapeutic application of the valeriana-type iridoid glycosides isolated herein with improved biochemical stability.

Antidiarrheal activity of the extracts of Valeriana jatamansi Jones on castor oil-induced diarrhea mouse by regulating multiple signal pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana jatamansi Jones, a traditional medicine, is used for various medicinal purposes worldwide. This species is popular for its gastro-protective properties and has been verified to exert antidiarrheal effects. Qiuxieling mixture, an oral liquid preparation used to treat diarrhea in children in clinical practice, was extracted from V. jatamansi Jones. AIM OF THE STUDY: Although Qiuxieling mixture has a good preventive effect on diarrhea children, the disgusting smell makes it intolerable. Therefore, we extracted odorless products from V. jatamansi Jones and Qiuxieling mixture. The present study is aimed to investigate the protective effects of two ethanolic extracts of V. jatamansi Jones and Qiuxieling mixture against castor oil-induced diarrhea and their possible mechanisms in mice. MATERIALS AND METHODS: The two extracts of V. jatamansi Jones and Qiuxieling mixture were detected by HPLC. A castor oil-induced diarrheal model was used to evaluate the antidiarrheal effects. The expression of Occludin in the small intestine was measured by IHC. Western blotting and immunofluorescence were used to detect the expression of proteins related to the oxidative stress and GSDMD-mediated pyroptosis signaling pathways. ELISA was used to detect the expression of IL-6 and IL-1ß in the small intestine of mice with diarrhea. RESULTS: The two extracts of V. jatamansi Jones and Qiuxieling mixture dose-dependently reduced the diarrhea index and the diarrhea rate, delayed the onset of diarrhea, and decreased the weight of the intestinal content. Meanwhile, they reversed the decreased expression of Occludin and restored the activity of Na+-K+-ATPase in the intestines of diarrheal mice. In addition, they reversed the depletion of GSH, attenuated the activation of the ERK/JNK pathway, promoted the Nrf2/SOD1 signaling pathways, and decreased the release of ROS in the intestines of diarrheal mice. Moreover, they suppressed GSDMD-mediated pyroptosis by downregulating the NLRP3/caspase-1/GSDMD signaling pathway. CONCLUSIONS: The two extracts of V. jatamansi Jones and Qiuxieling mixture exerted protective effects on castor oil-induced diarrhea in mice through a variety of mechanisms, including antioxidant stress, restoration of tight junctions between intestinal mucosal cells and regulation of the GSDMD-mediated pyroptosis pathway.

Biosynthesis of valerenic acid by engineered Saccharomyces cerevisiae.

OBJECTIVE: To produce valerenic acid (VA) in Saccharomyces cerevisiae by engineering a heterologous synthetic pathway. RESULT: Valerena-4,7(11)-diene synthase (VDS) derived from Valeriana officinalis (valerian) was expressed in S. cerevisiae to generate valerena-4,7(11)-diene as the precursor of VA. By overexpressing the key genes of the mevalonate pathway ERG8, ERG12 and ERG19, and integrating 4 copies of MBP (maltose-binding protein)-VDS-ERG20 gene expression caskets into the genome, the production of valerena-4,7(11)-diene was improved to 75 mg/L. On this basis, the cytochrome P450 monooxygenase LsGAO2 derived from Lactuca sativa was expressed to oxidize valerena-4,7(11)-diene to produce VA, and the most effective VA production strain was used for fermentation. The yield of VA reached 2.8 mg/L in the flask and 6.8 mg/L in a 5-L bioreactor fed glucose. CONCLUSIONS: An S. cerevisiae strain was constructed and optimized to produce VA, but the valerena-4,7(11)-diene oxidation by LsGAO2 is still the rate-limiting step for VA synthesis that needs to be further optimized in future studies.

Protective effect of valerian extract capsule (VEC) on ethanol- and indomethacin-induced gastric mucosa injury and ameliorative effect of VEC on gastrointestinal motility disorder.

CONTEXT: Valerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases. OBJECTIVE: To investigate the detailed pharmacological activity for VEC clinical effects in GI diseases. MATERIALS AND METHODS: Sprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01-1 mg/mL) on ACh/BaCl2-induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248-992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice. RESULTS: Compared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, p < 0.01; PGI2 p < 0.05;), along with the alleviation of the levels of MPO (ethanol: 15.56 ± 0.82 vs. 12.15 ± 2.60, p < 0.01; indomethacin: 9.65 ± 3.06 vs. 6.36 ± 2.43, p < 0.05), MDA (ethanol: 1.66 ± 0.44 vs. 0.81 ± 0.58, p < 0.01; indomethacin: 1.71 ± 0.87 vs. 1.09 ± 0.43, p < 0.05), and inflammatory mediators. VEC decreased the high tone induced by ACh/BaCl2 and promoted intestinal transit in normal and neostigmine/adrenaline-induced mice. DISCUSSION AND CONCLUSIONS: VEC showed a potential gastroprotective effect, suggesting that VEC is a promising phytomedicine for the treatment of GI diseases.

Valerian and postoperative sleep: a retrospective cohort analysis of gynecological, urologic, and general surgical patients.

STUDY OBJECTIVES: Postoperative sleep disturbances appear to be a common complication after surgery being treated with sleep-promoting medication such as valerian, but robust data and evidence of medicinal approaches are lacking. METHODS: We performed a retrospective cohort analysis of all 21 168 urological, gynecological, and general surgical patients of the University Medical Center Freiburg, Germany, who underwent surgery between 2015 and 2020. Target parameters were the usage of sleep-promoting medication to estimate the occurrence of postoperative sleep disturbances as well as the kind of sleep medication with a special focus on herbal medication such as valerian. RESULTS: Drug-treated sleep disturbances occurred in 15% (n = 3083) of the patients. Valerian was the second most applied drug (n = 814, 26.4%) after classic benzodiazepines (n = 1 138, 36.9%). The majority of patients got valerian as monotherapy. Age, length of stay, and comorbidities were associated with demand for sleep medication in general (p < .001). Valerian monotherapy was more common in women (OR 1.53, 95% CI: 1.33-1.77, p < .001), elderly patients (OR 1.50, 95% CI: 1.29-1.75, p < .001), and patients with prolonged hospital stay (OR 2.23, 95% CI: 1.91-2.61, p < .001). CONCLUSIONS: Valerian plays an important role in the treatment of postoperative sleep disturbances clinically, and it appears to be a promising therapeutic approach especially in women, older and sicker patients, and those with prolonged hospital stay. Further research has to clarify the efficacy of valerian postoperatively. CLINICAL TRIAL REGISTRATION: DRKS00027903, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027903.

Chemical Diversity of Essential Oil of Valeriana jatamansi from Different Altitudes of Himalaya and Distillation Methods.

Valeriana jatamansi is an important temperate herb that is used in the pharmaceutical and essential oil industries. In India, this species is now on the verge of extinction due to the over-exploitation of its rhizomes from its natural habitat. It is hypothesized that the variations in bioactive compounds in its essential oil are very high among the wild populations as well as cultivated sources. Thus, this study was conducted to evaluate the chemical profiling of essential oil of four wild populations (Rupena, Kugti, Garola, and Khani) and two cultivated sources (CSIR-IHBT, Salooni), which were distilled at three consecutive days. The variation in oil concentration in roots/rhizomes was found significant (p ≤ 0.05), and the maximum value (0.35%) was registered with the population collected from Kugti and Khani. In essential oil, irrespective of population and distillation day, patchouli alcohol was the major compound, which ranged from 19 to 63.1%. The maximum value (63.1%) was recorded with the essential oil obtained from Garola's population and distilled on the first day. The percentage of seychellene was abruptly increased with subsequent days of extraction in all the populations. The multivariate analysis revealed that the essential oil profiles of Rupena, Kugti, Garola, and CSIR-IHBT populations were found to be similar during the first day of distillation. However, during the second day, Rupena, Kugti, Khani, and CSIR-IHBT came under the same ellipse of 0.95% coefficient. The results suggest that the population of Kugti is superior in terms of oil concentration (0.35%), with a higher proportion of patchouli alcohol (63% on the first day). Thus, repeated distillation is recommended for higher recovery of essential oil. Moreover, repeated distillation can be used to attain V. jatamansi essential oil with differential and perhaps targeted definite chemical profile.

Iridoids and sesquiterpenoids from Valeriana jatamansi and their anti-influenza virus activities.

Twenty-one new iridoids, jatamansidoids A-U (1-12, 21-26, 32, 35 and 36), two new natural ones, jatamansidoids V (37) and W (38), eighteen known ones (13-20, 27-31, 33 and 34), together with three patchoulol-type sesquiterpenoids (39-41), were isolated from the roots and rhizomes of Valeriana jatamansi. Structurally, compounds 1-7 were the first examples of iridoids from V. jatamansi with unique α, ß, γ, δ-unsaturated aldehyde fragment between C-11, C-4, C-5, C-9 and C-8; compound 8 was an unprecedented iridoid derivative with a methyl group (Me-10) at C-1, rather than C-8, and its plausible biogenetic pathway was proposed in this paper; compounds 22 and 23 were the first examples of Δ4(5)-iridoids simultaneously replaced by oxygen-containing groups at C-3, C-6 and C-7; compound 24 was the first iridoid with both 6,7- and 1,10-epoxy fragments. The structures and absolute configurations of new compounds were elucidated based on extensive spectroscopic techniques and quantum chemical calculation. Furthermore, compounds 13-15 and 39-41 exhibited potent anti-influenza virus activities with H1N1 and H3N2 strains, with IC50 values of 0.21-1.48 µM.

Antioxidant Activity of Valeriana fauriei Protects against Dexamethasone-Induced Muscle Atrophy.

Skeletal muscle atrophy is defined as wasting or loss of muscle. Although glucocorticoids (GCs) are well-known anti-inflammatory drugs, their long-term or high-dose use induces skeletal muscle atrophy. Valeriana fauriei (VF) is used to treat restlessness, anxiety, and sleep disorders; however, its effects on skeletal muscle health have not been investigated. This study investigated whether Valeriana fauriei could ameliorate muscle atrophy. We induced muscle atrophy in vitro and in vivo, by treatment with dexamethasone (DEX), a synthetic GC. In DEX-induced myotube atrophy, Valeriana fauriei treatment increased the fusion index and decreased the expression of muscle atrophic genes such as muscle atrophy F-box (MAFbx/Atrogin-1) and muscle RING-finger protein 1 (MuRF1). In DEX-treated mice with muscle atrophy, Valeriana fauriei supplementation increased the ability to exercise, muscle weight, and cross-sectional area, whereas it inhibited myosin heavy chain isoform transition and the expression of muscle atrophy biomarkers. Valeriana fauriei treatment led to via the downregulation of muscle atrophic genes via inhibition of GC receptor translocation. Valeriana fauriei was also found to act as a reactive oxygen species (ROS) scavenger. Didrovaltrate (DI), an iridoid compound from Valeriana fauriei, was found to downregulate atrophic genes and decrease ROS in the DEX-induced myotube atrophy. Consolidated, our results indicate that Valeriana fauriei prevents DEX-induced muscle atrophy by inhibiting GC receptor translocation. Further, Valeriana fauriei acts as a ROS scavenger, and its functional compound is didrovaltrate. We suggest that Valeriana fauriei and its functional compound didrovaltrate possess therapeutic potentials against muscle atrophy.

Redox Pioneer: Professor Valerian Kagan.

Professor Valerian Kagan (PhD, 1972, MV Lomonosov Moscow State University; DSci, 1981, USSR, Academy of Sciences, Moscow) is recognized as a Redox Pioneer because he has published 4 articles in the field of redox biology that have been cited >1000 times and 138 articles in this field have been cited between 100 and 924 times. The central and most important impact of Dr. Kagan's research is in the field of redox lipidomics-a term coined for the first time by Dr. Kagan in 2004-and consequently the definition of signaling pathways by oxidatively modified phospholipids; this acquires further significance considering that oxygenated phospholipids play multifunctional roles as essential signals coordinating metabolism and physiology. Some examples are the selective oxidation of cardiolipin (CL) by a cytochrome c peroxidase activity leading to the activation of the intrinsic apoptotic pathway; the hydroperoxy-arachidonoyl/adrenoyl phosphatidylethanolamine (PE) species, driven by 15-lipoxygenases (15-LOX), as death signals leading to ferroptotic cell death; the regulation of ferroptosis by iNOS/NO• in pro-inflammatory conditions by a novel mechanism (realized via interactions of 15-LOX reaction intermediates formed from arachidonoyl phosphatidylethanolamine [PE] species) and Ca2+-independent phospholipase A2 (iPLA2ß; via elimination of peroxidized PE); the involvement of oxygenated (phospho)lipids in immunosuppression by myeloid cells in the tumor microenvironment; hydrolysis of peroxidized CL by Ca2+-independent phospholipase A2 (iPLA2γ) leading to pro- and anti-inflammatory signals and lipid mediators. Kagan continues his investigations to decipher the roles of enzyme-linked oxygenated phospholipids. Antioxid. Redox Signal. 36, 813-823.

Secondary metabolites from Valeriana jatamansi with their anti-inflammatory activity.

Valeriana jatamansi is hired as multiple remedies for treatment of insomnia, blood and circulatory disorders, asthma, dry cough, jaundice, seminal weakness, cardiac debility, and skin diseases in Vietnam. Our research discovered the phytochemical investigation of constituents from this herbal medicine resulted in the isolation of two new compounds (jatamansides A (4) and B (7)) together with 16 known ones from the whole plant. Their structures were established by using spectroscopic techniques (multinuclear and multidimensional nuclear magnetic resonance, infrared, ultraviolet-visible), mass spectrometry, hydrolysis analysis, or comparing their NMR data to those reported in the literature. In addition, all the isolates were evaluated for their inhibitory effect against TNF-α production in LPS-stimulated on RAW264.7 cells with significant inhibition.