Valeriana Fauriei Research Articles

Safety evaluation of continuous administration of a high dose of Valeriana fauriei root extract in mice and in humans through an open‐label study

AbstractAimThis study aimed to clarify the safety of Valeriana fauriei root (VF) ethanol extract through in vivo and clinical trials.MethodsMice were divided into VF and control groups. They were given VF (4 g VF/kg/day) or the vehicle mixed in the powdered food for four weeks. Food consumption and body weight changes were evaluated, and blood biochemistry and organ weights were assessed on the last day. In addition, an open‐label study was conducted on healthy subjects who took VF capsules (10 g VF/body/day) for four weeks and were asked to report any changes in their physical condition. Physical, hematologic, blood biochemical examination and urinalysis were performed before, two weeks, and four weeks into the study.ResultsFood consumption and weight gain in mice did not differ between the VF and control groups, except for experimental error, and there were no particular differences in the weights of the brain, lung, heart, liver, spleen, and kidney. In mice, VF administration resulted in small but significant decreases in albumin in males and females, and total cholesterol and high‐density lipoprotein cholesterol in females only. These levels were unchanged, but daytime sleepiness was observed in humans.ConclusionSince there was little change in the experimental values at continuous high doses of VF at 10 g/day, it can be concluded that approximately one‐fifth of this dose (2 g VF/day) is less harmful. However, daytime sleepiness should be considered.

Evaluation of capsules containing Valeriana fauriei root extract for sleep improvement: A randomized, double‐blind, placebo‐controlled, cross‐over comparative trial

AbstractAimThis clinical trial aimed to clarify the sleep‐ameliorating effects of capsules containing Valeriana fauriei root (VF) extract and their adverse effects.MethodsThe trial was a randomized, double‐blind, placebo‐controlled, cross‐over comparative clinical trial involving participants with an Athens Insomnia Scale (AIS) of 6 or higher, selected by prescreening questionnaires. After randomization, the participants took VF (2 g as VF/day) or placebo capsules for two weeks and were asked to complete the Obstructive Sleep Apnea (OSA) sleep questionnaire daily to assess their sleep status and any changes in their physical condition. On the last day of each term, the participants reported their sleep improvement experience.ResultsNo significant differences were found between the VF and placebo groups on the OSA sleep questionnaire. Significantly, more participants in the VF‐treated group experienced improvements in sleep onset and quality than those in the placebo group. The sleep onset improved particularly in those with early awakening, whereas the sleep quality particularly improved in those with midnight awakening. Although a few participants experienced physical, gastrointestinal and psychological changes when taking VF capsules, there was no significant difference from the placebo group, and no serious adverse events occurred.ConclusionWe clinically determined that VF, a folk medicine, improves sleep onset and sleep quality in people with suspected insomnia without serious adverse events at the dosage of 2 g VF/day.

Chemical Structures and Anti-proliferative Effects of Valeriana fauriei Constituents on Cancer Stem Cells.

We isolated the new sesquiterpenes, valerianaterpenes IV and V, and the new lignans valerianalignans I-III from the methanol extracts of the rhizomes and roots of Valeriana fauriei and elucidated their structures based on chemical and spectroscopic findings. The absolute configuration of valerianaterpene IV and valerianalignans I-III were established by comparing experimental and predicted electronic circular dichroism (ECD) data. Among the isolated compounds, valerianalignans I and II exerted anti-proliferative activity against human astrocytoma cells (U-251 MG) and their cancer stem cells (U-251 MG CSCs). Interestingly, valerianalignans I and II notably exerted anti-proliferative activities at lower concentrations against CSCs than non-CSCs, and the absolute configurations of these compounds affected their activities.

Conference report: Third annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

AbstractFour young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan‐yaku) at the third annual young researcher forum entitled “Respecting and Breaking Traditions,” held 1 week before the 2022 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Dr. Yokogawa presented her research focusing on the mechanism of the Ayurveda drug‐eluting string, Kshara Sutra, in treating anal fistulas, reporting on its effects on the anal tissue in an anal fistula rat model and its antibacterial activity against Escherichia coli and Staphylococcus aureus, the causative organisms of anal fistulas. Mr. Nakamichi presented his research focusing on the relationship between the efficacy of Kampo medicines with anti‐obesity effects and intestinal microbiota composition. His results partially revealed that bofutsushosan and boiogito affect lipid metabolism in mice and correlate with the intestinal microbiota composition. Dr. Manse reported the anti‐inflammatory activity of diterpenoid components in Enmei‐so (Isodonis Herba), revealing its novel inhibitory activity on nitric oxide released from activated macrophages and on inflammatory cytokines, and identified active components contributing to the inhibition and the mechanism of action. Mr. Yoshikawa reported the anticancer activity of small molecular compounds isolated from the medicinal plants, Valeriana fauriei and Hypericum erectum. His results suggest that five compounds may increase the sensitivity of human cervical carcinoma cells to adriamycin via HSP105 expression suppression. The event was conducted online, and included 78 participants. We intend to hold and improve this forum in 2023 and the future.

Structure Determination of Heishuixiecaoline A from Valeriana fauriei and Its Content from Different Cultivated Regions by HPLC/PDA Analysis

A germacrane-type sesquiterpenoid was isolated and purified from a methanol extract of the roots of Valeriana fauriei (RVF) through open column chromatography using silica gel. This compound was verified to be heishuixiecaoline A by spectroscopic analysis. This compound was isolated for the first time from RVF. Quantitative analysis of heishuixiecaoline A from RVF cultivated from three different regions (Eumseong, Jinbu, and Jinan regions) was performed by combining high-performance liquid chromatography with a photodiode array detector. The extract of RVF cultivated in the Jinbu region showed the highest content (9.23 mg/g). In addition, a significant amount of the compound was detected in all RVF samples, which could be expected since it is a characteristic compound of RVF. The sesquiterpenoid group heishuixiecaoline A was isolated from RVF, a resource for various pharmacological substances, and quantitative analysis of RVF cultivated from three different regions was performed. As a result of these experiments, basic data on RVF that can be used in the development and application of pharmaceuticals and health functional foods in the future were obtained.

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.

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 relevanceValeriana 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 studyWe 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 methodsA 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. ResultsVF 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. ConclusionsVF 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.

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.

Acaricidal properties of 5-methylfurfural identified from Valeriana fauriei and its structural analogues against synanthropic mites and Asian longhorned tick with color alterations

Acaricidal activities and color alterations of 5-methylfurfural derived from Valeriana fauriei essential oil and its structural analogues against Dermatophagoides farinae, D. pteronyssinus, Haemaphysalis longicornis and Tyrophagus putrescentiae were evaluated in the present study. Based on the LD50 values of 5-methylfurfural and its analogues, 4,5-dimethylfurfural showed the highest acaricidal activity (LD50; 9.95, 9.91, and 7.12 μg/cm2), followed by 5-methylfurfural (11.87, 11.00, and 8.59 μg/cm2), furfural (12.94, 13.25, and 10.36 μg/cm2), and V. fauriei essential oil (15.15, 13.64, and 10.14 μg/cm2) against D. farinae, D. pteronyssinus and T. putrescentiae, respectively. However, all tested compounds did not show the acaricidal activities against H. longicornis. Interestingly, the color alterations of the mites and ticks were observed by furfural, 5-methylfurfural, and 4,5-dimethylfurfural from colorless to red brown during the acaricidal experiments. Furthermore, 4,5-dimethylfurfural which exhibited the highest acaricidal activity was formulated as nanoemulsion. The nanoemulsion of 4,5-dimethylfurfural showed higher acaricidal activity than it was emulsified in ethanol. The nanoemulsion was also found to show color changes of the mites and ticks from colorless to red brown. The results suggest that 5-methylfurfural and its analogues could be developed as an effective and easy-to-recognize acaricides to mites and ticks.

Lineage-Specific Variation in IR Boundary Shift Events, Inversions, and Substitution Rates among Caprifoliaceae s.l. (Dipsacales) Plastomes.

Caprifoliaceae s.l. plastid genomes (plastomes) show that one inversion and two inverted repeat boundary shifts occurred in the common ancestor of this family, after which the plastomes are generally conserved. This study reports plastome sequences of five additional species, Fedia cornucopiae, Valeriana fauriei, and Valerianella locusta from the subfamily Valerianoideae, as well as Dipsacus japonicus and Scabiosa comosa from the subfamily Dipsacoideae. Combined with the published plastomes, these plastomes provide new insights into the structural evolution of plastomes within the family. Moreover, the three plastomes from the subfamily Valerianoideae exhibited accelerated nucleotide substitution rates, particularly at synonymous sites, across the family. The patterns of accD sequence divergence in the family are dynamic with structural changes, including interruption of the conserved domain and increases in nonsynonymous substitution rates. In particular, the Valeriana accD gene harbors a large insertion of amino acid repeat (AAR) motifs, and intraspecific polymorphism with a variable number of AARs in the Valeriana accD gene was detected. We found a correlation between intron losses and increased ratios of nonsynonymous to synonymous substitution rates in the clpP gene with intensified positive selection. In addition, two Dipsacoideae plastomes revealed the loss of the plastid-encoded rps15, and a potential functional gene transfer to the nucleus was confirmed.

Cell death-inducing activities via Hsp inhibition of the sesquiterpenes isolated from Valeriana fauriei.

Three new sesquiterpenes, valerianaterpenes I-III, and eight known compounds have been isolated from the methanol extract of the rhizomes and roots of Valeriana fauriei. The chemical structures of the three new sesquiterpenes were elucidated based on chemical and spectroscopic evidence. The absolute stereochemistry of valerianaterpene I was determined using X-ray crystallography. The cell death-inducing activity of isolated compounds alone or combination with Adriamycin (ADR) was observed by time-lapse cell imaging. Although the isolated compounds did not affect the number of mitotic entry cells and dead cells alone, kessyl glycol, kessyl glycol diacetate, and iso-teucladiol significantly increased the number of dead cells on ADR treated human cervical cancer cells. One of the mechanisms of cell death-inducing activity for the kessyl glycol acetate was suggested to be the inhibition of heat-shock protein 105 (Hsp105) expression level. This paper first deals with the naturally occurring compounds as Hsp105 inhibitor.

Identification and pathogenicity of plant viruses infecting Valeriana fauriei in Japan

Samples from Valeriana fauriei Briq. plants were collected from six prefectures to survey viral pathogens. By next-generation sequencing and RT-PCR analysis, asparagus virus 2 (AV-2), broad bean wilt virus 2 (BBWV-2), cucumber mosaic virus (CMV), gaillardia latent virus (GaILV), ligustrum necrotic ringspot virus (LNRSV), and tomato spotted wilt orthotospovirus (TSWV) were detected. Many collected samples were coinfected with 2–4 viruses. V. officinalis was also back-inoculated with one or a mixture of isolated viruses to confirm pathogenicity of isolated viruses. This report is the first of GaILV and LNRSV in Japan and the first of AV-2 on V. fauriei.

Iridoids of Valeriana fauriei contribute to alleviating hepatic steatosis in obese mice by lipophagy

Nonalcoholic fatty liver disease (NAFLD) is a common risk factor for metabolic syndrome that increases the risk of future cardiovascular disease, stroke, and diabetes. Recently, autophagy has been proposed as a means to prevent NAFLD. We investigated whether substances with autophagy-inducing activity alleviate NAFLD. The Valeriana fauriei (V. fauriei) was selected as a potential autophagy inducer among various natural materials using a Cyto-ID autophagy detection kit. V. fauriei 70 % ethanol extract (VFE) increased LC3II levels in the presence of the lysosomal inhibitor and reduced the GFP/mCherry puncta ratio, suggesting that VFE enhanced autophagy. VFE reduced oleic acid (OA)-induced lipid accumulation and increased the number of autophagosome in hepatocytes. Autophagy induction by VFE is due to inhibition of mTORC1 activity. VFE supplementation reduced fatty liver by downregulating lipogenesis-related genes and increased the autophagy, as revealed by TEM and IHC analysis in the fatty liver. We identified iridoids as main compounds of VFE; didrovaltrate (DI), valeriotriate B (VAL B), valeriotetrate C (VAL C), valtrate (VAL), and valechlorine (VC) were shown to enhance autophagy. These compounds also reduced OA-induced lipid accumulation in an Atg5-dependent manner. Taken together, VFE and its iridoids might be effective in alleviating fatty liver by acting as autophagy enhancers to break down LDs.

北缬草挥发油镇静作用的研究

北缬草挥发油镇静作用的研究

Valeriana fauriei Exerts Antidepressant-Like Effects Through Anti-inflammatory and Antioxidant Activities by Inhibiting Brain-Derived Neurotrophic Factor Associated with Chronic Restraint Stress.

Although depression is the most common psychiatric disorder, its pharmacological properties are not well known yet. It has been reported that Valeriana fauriei (VF) extract is beneficial for several neurological diseases. However, little information is available regarding its antidepressant activity. Therefore, the objective of this study was to determine antidepressant activity of VF and the underlying mechanism involved in its effect on chronic restraint stress (CRS)-induced depression using a mouse model. Oral treatment of VF extract for 14 days significantly ameliorated depression-like behavior (immobility time) in forced swimming and tail suspension tests following CRS induction, in accordance with decreased levels of serum corticosterone. VF extract ameliorated c-Fos expression, microglial activation, phosphorylated p38 expression, and inflammatory response (protein expression levels of cyclooxygenase-2 and inducible nitric oxide) in the prefrontal cortex, hippocampus, and amygdala of mice after CRS induction. However, VF extract enhanced the stimulation of nuclear factor erythroid 2-related factor 2 pathways, in accordance with upregulation in protein expression of brain-derived neurotrophic factor (BDNF). Collectively, our findings demonstrate that VF extract has antidepressant-like activity against CRS-induced depression through its anti-inflammatory and antioxidant effects by inhibiting BDNF expression. Further studies are warranted to investigate VF extract's fraction and components to develop possible antidepressants.

Valeriana fauriei exerts antidepressant-like effects through anti-inflammatory and anti-oxidant activities by inhibiting brain-derived neurotrophic factor associated in chronic restrained stress

Valeriana fauriei exerts antidepressant-like effects through anti-inflammatory and anti-oxidant activities by inhibiting brain-derived neurotrophic factor associated in chronic restrained stress

Vasorelaxant effect of the ethanol extract from Valeriana fauriei briquet root and rhizome on rat thoracic aorta

Background: Valeriana fauriei has been used to treat anxiety and cardiovascular disease in many countries; however, the mechanisms of the vasorelaxant effect of V. fauriei roots and rhizomes have not been elucidated. Purpose of the Study: Considering the increased use of traditional medicines for treating hypertension, the aim of this study was to examine the vasorelaxant effect and investigate the mechanisms of V. fauriei root and rhizome. Materials and Methods: Using an isolated organ-chamber technique, the vasorelaxant effects of 70% ethanol extract of V. fauriei root and rhizome (VFE) were tested in rat aortic ring segments. Results: VFE concentration dependently relaxed both endothelium-intact and endothelium-denuded aortic rings that were precontracted by phenylephrine (PE) or potassium chloride (KCl). VFE relaxed the aortic rings precontracted by PE (1 μM) irrespective of K+ channel blocker pretreatment such as tetraethylammonium, glibenclamide, or 4-aminopyridine. VFE inhibited vasoconstriction caused by extracellular Ca2+ influx through receptor-operative Ca2+ channels (ROCCs) or voltage-dependent Ca2+ channels (VDCCs) activated by PE or KCl, respectively, in Ca2+-free Krebs–Henseleit buffer. Conclusion: These results suggested that the vasorelaxant effects of VFE were endothelium independent and not related to K+ channels, such as Ca2+-activated K+ channels, ATP-sensitive K+ channels, and Voltage-gated K+ channels. In addition, VFE relaxed the aortic rings by blocking the influx of extracellular Ca2+ through ROCCs and VDCCs. Abbreviations used: ACE: Angiotensin-converting enzyme; VFE: The 70% EtOH extract of Valeriana fauriei root and rhizome; KH: Krebs–Henseleit; PE: Phenylephrine; KCl: Potassium chloride; TEA: Tetraethylammonium; 4-AP: 4-Aminopyridine; CaCl2: Calcium chloride; EGTA: Ethylene glycol-bis (2-aminoethylether)-N, N, N′, N′-tetraacetic acid; DMSO: Dimethyl sulfoxide; ROCCs: Receptor-operative Ca2+ channels; VDCCs: Voltage-dependent Ca2+ channels; KIR: Inward-rectifier K+ channels; KATP: ATP-sensitive K+ channels; KV: Voltage-gated K+ channels; KCa: Ca2+-activated K+ channels.

Antinociceptive effect of Valeriana fauriei regulates BDNF signaling in an animal model of fibromyalgia.

The genus Valeriana has been widely used in popular medicine for centuries, to treat sleep disorders, anxiety, epilepsy and insomnia. Recent studies have focused on the novel pharmacological effects of Valerianafauriei Briq.(VF) species. Previous studies have attempted to determine the pharmacological functions of Valeriana in various human diseases, particularly with regards to its neuroprotective effects, and its ability to reduce pain and stress. The present study constructed an animal model of fibromyalgia (FM), which was induced by intermittent cold stress with slight modification. Subsequently, the study aimed to determine whether VF exerts antinociceptive effects on the FM‑like model following oral administration of VF extracts. The effects of VF extracts on the FM model were investigated by analyzing behavioral activity, including pain, and detecting protein expression. In the behavioral analysis, the results of a nociception assay indicated that the pain threshold was significantly decreased in the FM group. Subsequently, western blotting and immunohistochemical analyses of the hippocampus demonstrated that the protein expression levels of brain‑derived neurotrophic factor(BDNF) and phosphorylated‑cAMP response element‑binding protein were downregulated in the FM group. Conversely, VF restored these levels. These results suggested that the effects of VF extract on a model of FM may be associated with its modulatory effects on the BDNF signaling pathway in the hippocampus and medial prefrontal cortex. In conclusion, the mechanism underlying the protective effects of VF as a therapeutic agent against FM may involve the BDNF signaling pathway.

Antioxidative Activities and Inhibition Effects on Oxidative DNA Damage of Valeriana fauriei

Background: Valeriana fauriei (Valerianaceae) has been used to as a traditional medicine to treat a variety of symptoms, including headache, insomnia, hypertension, and menstrual irregularity. However, the present study investigates the species' antioxidant activity and its inhibition of oxidative DNA damage, which have yet to be studied. Methods and Results: The antioxidant activity was assessed using radical scavenging assays with 1,1-diphenyl-2-picryl hydrazyl (DPPH) and, 2, 2'-azino-bis (3-ethylbenzothiazoline-6 sulfonic acid) diammonium salt (ABTS) and a reducing power assay. The total phenol content was also analyzed, and phenolic compounds were detected using HPLC/UV, whereas the inhibitory effect of Valeriana fauriei on oxidative DNA damage was measured using φ-174 RF I plasmid DNA cleavage assay. The DPPH and ABTS radical scavenging activity were 75.17 ± 3.55% and 95.83 ± 0.63%, repectively, and the reducing power was 93.14 ± 1.74 at 200 ㎍/㎖. The total phenol content was 10.24 ± 0.04㎎/g, whereas chlorogenic acid, catechin, caffeic acid and epicatechin were identified using HPLC/UV, and the φ-174 RF I plasmid DNA cleavage assay indicated that V. fauriei provided protection against oxidative damage. Conclusions: The results of the present study suggest that V. fauriei has powerful antioxidant activity that can provide protective effects against the oxidative DNA damage caused by free radicals. The species, therefore, provides a valuable resource for the development of natural pharmaceutical to treat aging, cancer, and degenerative diseases.

Effect of Valeriana fauriei Extract on the Neurodevelopmental Proteins Expression and Behavioral Patterns in Maternal Immune Activation Animal Model

Background: Prenatal exposure to infectious and/or inflammatory insults can increase the risk of developing neuropsychiatric disorder such as bipolar disorder, autism, and schizophrenia later in life. We investigated whether Valeriana fauriei (VF) treatment alleviates prepulse inhibition (PPI) deficits and social interaction impairment induced by maternal immune activation (MIA). Methods and Results: Pregnant mice were exposed to polyriboinosinic-polyribocytidilic acid (5㎎/㎏, viral infection mimic) on gestational day 9. The adolescent offspring received daily oral treatment with VF (100㎎/㎏) and injections of clozapine (5㎎/㎏) for 30 days starting on the postnatal day 35. The effects of VF extract treatment on behavioral activity impairment and protein expression were investigated using the PPI analysis, forced swim test (FST), open field test (OFT), social interaction test (SIT), and immunohistochemistry. The MIA-induced offspring showed deficits in the PPI, FST, OFT, and SIT compared to their non MIAinduced counterparts. Treatment with the VF extract significantly recovered the sensorimotor gating deficits and partially recovered the aggressive behavior observed in the SIT. The VF extract also reversed the downregulation of protein expression induced by MIA in the medial prefrontal cortex. Conclusions: Our results provide initial evidence of the fact that the VF extract could reverse MIA-induced behavioral impairment and prevent neurodevelopmental disorders such as schizophrenia.