Unveiling the potential of native arbuscular mycorrhizal fungi for growth promotion and phytochemical enrichment in Valeriana jatamansi Jones.

Medicinal plants are rich sources of pharmaceutically important compounds and have been utilized for the treatment of various diseases since ancient times. Valeriana jatamansi Jones, also known as Indian valerian, holds a special place among temperate Himalayan medicinal plants and is renowned for its therapeutic properties in addressing a variety of ailments. The therapeutic potential of V. jatamansi is attributed to the presence of valuable compounds such as valepotriates, sesquiterpenoids, valeriananoids, jatamanins, lignans, cryptomeridiol, maaliol, xanthorrhizzol, and patchouli alcohol found in its rhizome and roots. This study employed various treatments, including the cultivation of V. jatamansi with the inoculation of Funneliformis mosseae, F. constrictus, and a consortium of arbuscular mycorrhizal fungi (AMF), to investigate their influence on biomass production, chlorophyll content, and the accumulation of bioactive compounds in V. jatamansi. The results revealed significant improvement in these parameters in the inoculated plants. The parameters of plants inoculated with F. mosseae were the highest, followed by those of plants inoculated with F. constrictus and a mixture of AMFs. This study not only underscores the potential of native AMF for promoting the growth of V. jatamansi but also elucidates their role in influencing the synthesis of bioactive compounds. The cultivation of V. jatamansi with native AMF has emerged as a sustainable and eco-friendly approach, providing the dual benefit of enhancing both the medicinal and economic value of this valuable plant. This research contributes valuable insights into the practical application of mycorrhizal associations for the cultivation of medicinal plants, bridging the realms of agriculture and pharmaceuticals.

Therapeutic potential of hypnotic herbal medicines: A comprehensive review.

Insomnia affects millions of people worldwide, prompting considerable interest in herbal remedies for its treatment. This review aims to assess the therapeutic potential of such remedies for insomnia by analyzing current scientific evidence. The analysis identified several herbs, including Rosmarinus officinalis, Crocus sativus, Rosa damascena, Curcuma longa, Valeriana officinalis, Lactuca sativa, Portulaca oleracea, Citrus aurantium, Lippia citriodora, and Melissa officinalis, which show promise in improving overall sleep time, reducing sleep latency, and enhancing sleep quality. These plants act on the central nervous system, particularly the serotonergic and gamma-aminobutyric acid (GABA)ergic systems, promoting sedation and relaxation. However, further research is necessary to fully understand their mechanisms of action, optimal dosages, and treatment protocols. Combining herbal medicines with conventional treatments may offer an effective natural alternative for those seeking medication. Nevertheless, individuals should consult their healthcare provider before using herbal remedies for insomnia. While this review provides evidence supporting their use, additional high-quality studies are needed to firmly establish their clinical efficacy.

Behavioral differences among domestic cats in the response to cat-attracting plants and their volatile compounds reveal a potential distinct mechanism of action for actinidine.

BACKGROUND: It has been known for centuries that cats respond euphorically to Nepeta cataria (catnip). Recently, we have shown that Lonicera tatarica (Tatarian honeysuckle), Actinidia polygama (silver vine), and Valeriana officinalis (valerian) can also elicit this "catnip response". The aim of this study was to learn if the behavior seen in response to these plants is similar to the response to catnip. Furthermore, we studied if these responses are fixed or if there are differences between cats. While nepetalactone was identified decades ago as the molecule responsible for the "catnip response", we know that this volatile is found almost exclusively in catnip. Therefore, we also aimed to identify other compounds in these alternative plants that can elicit the blissful behavior in cats. Bioassays with 6 cats were performed in a low-stress environment, where 5 plants and 13 single compounds were each tested for at least 100 and 17 h, respectively. All responses were video recorded and BORIS software was used to analyze the cats' behavior. RESULTS: Both response duration and behavior differed significantly between the cats. While individual cats had preferences for particular plants, the behavior of individual cats was consistent among all plants. About half a dozen lactones similar in structure to nepetalactone were able to elicit the "catnip response", as were the structurally more distinct molecules actinidine and dihydroactinidiolide. Most cats did not respond to actinidine, whereas those who did, responded longer to this volatile than any of the other secondary plant metabolites, and different behavior was observed. Interestingly, dihydroactinidiolide was also found in excretions and secretions of the red fox, making this the first report of a compound produced by a mammal that can elicit the "catnip response". A range of different cat-attracting compounds was detected by chemical analysis of plant materials but differences in cat behavior could not be directly related to differences in chemical composition of the plants. Together with results of, among others, habituation / dishabituation experiments, this indicates that additional cat-attracting compounds may be present in the plant materials that remain to be discovered. CONCLUSIONS: Collectively, these findings suggest that both the personality of the cat and genetic variation in the genes encoding olfactory receptors may play a role in how cats respond to cat-attracting plants. Furthermore, the data suggest a potential distinct mechanism of action for actinidine.

Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis.

BACKGROUND: The oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis. METHODS: A luciferase assay was applied to screen potential inhibitors of Otub1/c-Maf. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity of AVT. RESULTS: Acevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against the Otub1/c-Maf/luciferase system. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity. CONCLUSIONS: The natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment. Video Abstract.

Use of Plant-Derived Natural Products in Sleep Disturbances.

Sleep disorders have a high prevalence both in the general population and especially in specific populations such older adults and oncologic patients. Impacting on quality of life, they often translate in drug prescription, with consequent increased risk of drug-drug interactions and adverse drug reactions. In the last years several products derived from plants have been developed with the aim of treating insomnia with lower risk of side effects. Despite several studies have been performed with this aim, the available evidence is inconclusive, and reviews summarizing the most recent evidences on the effectiveness of plant-derived products in treating insomnia are lacking.This narrative review aims at summarizing the evidences of the mechanism of action, effectiveness and safety of the most commonly used plant-derived products for the treatment of sleep disorders (Valerian, Lemon balm, Passionflower, Chamomile, Hops, and Jujube).

Acute Liver Injury After Long-Term Herbal "Liver Cleansing" and "Sleep Aid" Supplement Use.

BACKGROUND: Acute liver injury is reported in association with toxins, pharmaceuticals, and viral infections. Increasingly prevalent are cases of herbal- and dietary supplement-related hepatotoxicity. Early recognition of this potentially life-threatening complication by emergency care providers leads to more appropriate management and disposition. CASE REPORT: A 53-year-old woman presented to the emergency department with a 3-day history of jaundice and increased abdominal girth after a month-long use of a combination herbal "liver-cleansing" compound and a nightly herbal "sleep aid." The "Liver Detoxifier and Regenerator" listed multiple constituents, including concentrated scute root and turmeric root; "Restful Sleep" listed multiple constituents, including valerian. Emergency department evaluation revealed marked hyperbilirubinemia with liver enzyme elevations indicative of cholestatic jaundice. Imaging studies, including ultrasound and abdominal magnetic resonance imaging, revealed hepatomegaly and steatosis without biliary dilatation; a biopsy specimen was obtained, and the results were consistent with drug-induced liver injury. The patient's liver function abnormalities gradually improved with discontinuation of the products as well as a tapered course of corticosteroid therapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A significant proportion of the U.S. adult population uses herbal and dietary supplements. Most patients do not discuss nonprescription medication use with their providers and many physicians will not specifically ask about herbal supplements. It is important for emergency physicians to be aware of the potential for herbal supplements to contribute to acute liver injury and be able to investigate the active agents reported in these formulations. The diagnostic criteria for cholestatic jaundice and drug-induced liver injury are discussed.

Addition of Valerian and Lemon Balm Extract to Quetiapine Reduces Agitation in Critically Ill Patients with Delirium: A Pilot Randomized Clinical Trial.

BACKGROUND: This study was pointed to evaluate the efficacy and safety of valerian and lemon balm additional to the quetiapine in critically ill patients with delirium and agitation. METHODS: We conducted a randomized, double-blind, placebo-controlled study. Fifty-three adult intensive care unit (ICU) patients (according to ICU Confusion Assessment Method scores) who were treated for delirium received quetiapine and Neurogol syrup (a combination of valerian and lemon balm) or placebo 5 mL every 12 hours for five consecutive days. Improvement in agitation according to the Richmond Sedation and Restlessness Scale was considered the main outcome. RESULTS: The trial was completed for 53 patients (27 in the treatment group and 26 in the placebo group). The baseline characteristics between the groups were similar. In the treatment group, the number of agitated patients was significantly reduced and the difference was statistically significant (p = 0.000). Compared with the placebo group, the length of ICU stay in the treatment group was significantly reduced (p = 0.001). The Glasgow Coma Scale improved significantly at the end of day 5 (p = 0.04). There was no statistical difference in the improvement of delirium between the study groups (p = 0.14). Neurogol syrup was well tolerated. CONCLUSION: The addition of Neurogol to quetiapine (a combination of valerian and lemon balm) can reduce agitation and shorten the length of stay in the ICU without adverse effects. Clearly, more research is still needed to investigate the role of herbal medicines in ICUs and their efficacy and safety. HOW TO CITE THIS ARTICLE: Alikiaie B, Shahmoradi E, Yekdaneh A, Mousavi S. Addition of Valerian and Lemon Balm Extract to Quetiapine Reduces Agitation in Critically Ill Patients with Delirium: A Pilot Randomized Clinical Trial. Indian J Crit Care Med 2021;25(7):785-790.

Valerian extract alters functional brain connectivity: A randomized double-blind placebo-controlled trial.

Valerian root is the most commonly used herbal supplement for sedation and anxiolysis, but it is unknown whether it may affect functional brain connectivity. Our goal was to use electroencephalography (EEG) to investigate whether valerian root extract (VRE) affects resting-state connectivity changes and whether such changes are associated with clinical symptoms. This 4-week, double-blinded, randomized, placebo-controlled clinical trial was conducted with 64 nonclinical volunteers suffering psychological stress. The participants received VRE (100 mg) or a placebo thrice daily. We examined VRE's therapeutic effects on anxiety and stress-related psychological constructs. Functional brain connectivity changes were measured as EEG coherence in the alpha and theta frequency bands. The VRE and placebo groups both exhibited significant postintervention improvements on all clinical scales, but no significant between-group differences in these changes were noted. Compared with the placebo group, the VRE group exhibited significantly greater increases in frontal brain region alpha coherence across four electrode pairs, and these changes were significantly correlated with anxiolysis. The VRE group also exhibited significantly greater decreases in theta coherence across another four electrodes pairs. Our findings indicate that VRE alters functional brain connectivity in relation to anxiety. Further EEG studies are needed to confirm VRE's neurophysiological effects.

[Efficiency of the differentiated use of physiobalneotherapy for borderline mental disorders in mothers of children with cerebral palsy]. / Éffektivnost' differentsirovannogo primeneniia fiziobal'neoterapii pri pogranichnykh psikhicheskikh rasstroistvakh u materei detei c tserebral'nym paralichom.

BACKGROUND: Child disability, especially as a result of nervous system diseases, affects all aspects of family life, causing extreme emotional and physical exhaustion in parents. However, today there is not enough scientific evidence on the features of development of nonpsychotic mental disorders in parents raising children with cerebral palsy and on the possibilities of using modern physiotherapy methods to correct these conditions and comorbidities. Considering that sanatorium-resort rehabilitation in children with cerebral palsy is accompanied by their parents, it is urgent to optimize clinical and functional approaches to treating mothers with borderline mental disorders with the simultaneous rehabilitation of children in sanatorium-resort conditions. AIM: To study the efficiency of sanatorium-resort treatment aimed at the psychological correction of mothers accompanying children with cerebral palsy to a sanatorium. MATERIAL AND METHODS: The study enrolled 151 mothers who had borderline mental disorders and raised children with cerebral palsy. A study group included 103 women aged 33.2±0.6 years; a comparison group consisted of 48 mothers aged 31.8±0.5 years. The examination was conducted before sanatorium-resort treatment and after a therapy cycle. The mothers underwent clinical and psychodiagnostic examinations via the standardized Minnesota Multiphasic Personality Inventory (a short form) MMPI-mini (adapted by L.N. Sobchik, 2000); emotional and motivational sphere study the WAM (well-being, activity, mood) questionnaire, the Spielberger-Khanin Inventory, and the Depression Rating Scale (adapted by T.I. Balashova). The patients of both groups received combination treatment: the comparison group (n=48) had a general sanatorium-resort therapeutic complex and group psychotherapy; the study group (n=103) additionally took valerian-bromine baths based on sodium chloride water with a mineralization of 20 g/dm3), and a transcranial magnetic therapy cycle. RESULTS: The general sanatorium-and-resort complex with psychotherapy predominantly affected the quality of night sleep (p<0.01) and reduced personality disorders according to the hypochondria scale (from 74.60±7.52 to 52.91±4.04 scores, p<0.01). The additional use of transcranial magnetic therapy and valerian-bromine baths based on sodium chloride water in the mothers had a psychocorrecting effect recorded according to basic (hysteria, psychopathy, psychasthenia) scales. Reduced depression was noted in 36.4% of the mothers (7% in the comparison group). CONCLUSION: Transcranial magnetic therapy used in combination with valerian-bromine baths based on sodium chloride water and with psychotherapy in mothers with borderline mental disorders, by taking into account psychological dysregulation, contributed to increases in the body's clinical and functional reserves within 6-8 months and to the preservation of psychological adaptation in 54.7% of cases. Incorporation of a maternal psychocorrective complex into the sanatorium-resort treatment of a child with cerebral palsy is a promising method for improving the quality of treatment outcomes in a sanatorium.

Effect of valerian on cognitive disorders and electroencephalography in hemodialysis patients: a randomized, cross over, double-blind clinical trial.

BACKGROUND: The prevalence of cognitive disorders in hemodialysis patients is twice as high as the general population, while these disorders often are undiagnosed. Timely prevention and treatment can improve their personal and social functions. Aim of study was determined the effect of Valerian on cognitive disorders and electroencephalography (EGG) in hemodialysis patients. METHODS: This crossover, double-blind clinical trial was conducted on 39 hemodialysis patients. The patients were randomly divided into two groups. Group A (n = 19) took Valerian capsules and Group B (n = 20) received placebo capsules 60 min before bedtime for one month. The type of treatment was replaced between the two groups after a one-month wash-out. The Mini Mental State Examination (MMSE) questionnaire was completed and EGG was performed before and after intervention in both periods. RESULTS: The cognitive scores of the Group valerian were increased significantly in the first (p = 0.003) and the second (p = 0.005) periods. In addition, the mean increase in the cognitive scores in the Group valerian was significant in the first (p = 0.028) and the second periods (p = 0.030). However, the changes in EGG showed no significant difference before and after intervention in two groups. CONCLUSION: The findings of this study indicated that valerian could be effective and significantly improve patients' cognitive status; however, no significant changes were observed in the electroencephalography of the hemodialysis patients. TRIAL REGISTRATION: IRCT201606076318N7 -2016-06-17.

The effect of Valerian on the severity and frequency of hot flashes: A triple-blind randomized clinical trial.

Valerian is one of the most widely used herbal supplements and a phytoestrogenic herb. The aim of this study was to determine the effect of Valerian on the severity and frequency of hot flashes. This triple-blind, randomized, controlled clinical trial was conducted during a three-month period in Hamadan, Iran, in 60 postmenopausal women aged 45-55 years. Participants were randomly assigned to one of two groups- either placebo or Valerian. An oral Valerian 530 mg capsule was given twice per day for two months. An oral placebo 530 mg capsule (starch) was similarly administered. The severity and frequency of hot flashes were determined by the Kupperman index, before the intervention, one month after, and two months after initiation of the intervention. The severity of hot flashes in the Valerian group was significantly lower than that in the placebo group at one (p = .048) and two months (p = .020) after initiation of the intervention. Compared with the placebo group, the mean frequency of hot flashes was significantly reduced two months after initiating the use of Valerian (p = .033). Health-care providers should consider Valerian to be effective for menopausal women with hot flashes.

The roles of valerenic acid on BDNF expression in the SH-SY5Y cell.

The roots of Valeriana officinalis L. (Valerianaceae) are used for treating sleep disorders and/or mild nerve tension. The effect of valerenic acid on brain-derived neurotrophic factor (BDNF) has not yet been studied, although it is known that gamma-amino butyric acid A (GABAA) receptor is regulated by BDNF, which modulates the depressive-like behavior and neurogenesis. The purpose of this study is to determine the effect of V. officinalis root extract (VO), its main constituents valerenic acid (VA) and acetoxy valerenic acid (AVA) as well as valerenic acid-free (VAF), acetoxy valerenic acid-free (AVAF) extracts and increasing amounts of valerenic acid containing extracts on the BDNF expression in SH-SY5Y cell lines. The effect of methanolic extracts of VO, VA, AVA, VAF, AVAF, and the extracts whose amount of VA were increased gradually, were tested using a Human BDNF ELISA kit with 17ß-estradiol as a positive control. The VO and VA extracts caused a significant (p < 0.001) increase in the BDNF expression in SH-SY5Y cells compared to control. This effect completely disappeared when cells were treated with VAF extract. AVA alone did not show any significant change in the BDNF levels. The extracts with increasing amount of VA led to a concentration- dependent effect on the cells. In conclusion, our findings suggest that the antidepressant-like effect of the VO extract is also related to BDNF expression, and that this is mainly due to the presence of VA in the extract. Removing VA from VO extract leads to a loss of activity. Moreover, the concentration of VA plays a role for BDNF expressions in SH-SY5Y cells, which demonstrates the importance of quality control on the commercially available products.

Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in Humans.

BACKGROUND: Valeriana officinalis extract (VE) is a popular herbal medicine used for the treatment of anxiety and sleep disorders. Although the anxiolytic and sedative effects are mainly attributed to the modulation of GABA-ergic transmission, the mechanism of action has not been fully investigated in humans. Noninvasive brain stimulation protocols can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. In this study, we investigated the effects of a single dose of VE on cortical excitability as assessed with transcranial magnetic stimulation (TMS). METHODS: Fifteen healthy volunteers participated in a double-blind, randomized, cross-over, placebo-controlled study. Subjects were required to take either 900 mg of VE (valerenic acid 0.8%) or placebo (an equal dose of vitamin E). Motor cortex excitability was studied by single and paired TMS before and at 1 h and 6 h after the oral administration. Cortical excitability was assessed using different TMS parameters: resting motor threshold, motor-evoked potential amplitude, cortical silent period, short-interval intracortical inhibition, and intracortical facilitation. Furthermore, we assessed sensorimotor integration by short-latency and long-latency afferent inhibition. RESULTS: We found a significant reduction in ICF, without any significant changes in other TMS measures of motor cortex excitability. The amount of ICF returned to baseline value 6 h after the intake of the VE. CONCLUSION: A single oral dose of VE modulates intracortical facilitatory circuits. Our results in healthy subjects could be predictive markers of treatment response in patients and further support the use of pharmaco-TMS to investigate the neuropsychiatric effects of herbal therapies in humans.

Effect of Valerian in Preventing Neuropsychiatric Adverse Effects of Efavirenz in HIV-Positive Patients: A Pilot Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Several neuropsychiatric adverse effects of efavirenz are known. Preventing these adverse effects may improve patients' adherence to antiretroviral therapy (ART). OBJECTIVES: To evaluate the efficacy and safety of valerian in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients. METHOD: In this pilot randomized, double-blinded, placebo-controlled, clinical trial, 51 HIV-positive patients who were receiving efavirenz were recruited into the valerian (n = 25) or placebo (n = 26) group. Patients received valerian (530 mg) or placebo nightly 1 hour before sleep for 4 weeks. The neuropsychiatric status (sleep, anxiety, depression, suicidal thought, and psychosis) of patients was assessed at baseline and week 4 using validated questionnaires. RESULTS: Sleep ( P ≤ 0.001) and anxiety ( P = 0.001) significantly improved in the valerian group compared with the placebo group. Dizziness was the most common complaint of patients in first days of the intervention. In the valerian and placebo groups, 92% and 84.6% of patients experienced dizziness, respectively ( P = 0.35). Nausea was the second common adverse effect that 84% and 76.9% of patients in the valerian and placebo groups experienced ( P = 0.39). CONCLUSION: In the first 4 weeks of ART including efavirenz, valerian significantly improved sleep and anxiety in HIV-positive patients. Valerian may be considered as a potential option in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients.

Effect of Valerian/Hop Mixture on Sleep-Related Behaviors in Drosophila melanogaster.

The aim of this study was to investigate the sleep-promoting effect of a Valerian/Hops mixture in fruit flies. The HPLC analysis showed that Valerenic acid (1260.53 µg/g of extract) and Xanthohumol (Cascade: 827.49 µg/g, Hallertau: 763.60 µg/g, Saaz: 186.93 µg/g) were contained in Valerian and Hop, respectively. The sleep patterns of fruit flies on the Valerian/Hops were examined in both baseline and caffeine-treated conditions. Total activities of flies significantly decreased in 20 mg/mL Valerian (74%), 10 mg/mL Cascade (25%), and 5 mg/mL Hallertau (11%) during nighttime or daytime compared with the control. Valerian/Cascade mixture showed longer sleeping time (ca. 20%) than control group. This mixture-mediated effect was partly observed in caffeine-treated flies. Valerian/Cascade mixture upregulated mRNA expressions of gamma-aminobutyric acid (GABA) receptors and serotonin receptor, and GABA receptors were more strongly regulated than serotonin receptor. In competitive GABA receptor binding assay, Valerian/Cascade mixture extract showed a higher binding ability on GABA receptor than Valerenic acid or/and Xanthohumol which are estimated to be active compounds in the extract. This study demonstrates that a Valerian/Cascade mixture extract improves sleep-related behaviors, including sleeping time, by modulating GABAergic/serotonergic signaling.

Evaluation of nutritional composition and antioxidant activity of Borage (Echium amoenum) and Valerian (Valerian officinalis).

The nutritional composition and antioxidant activity (in aqueose and solvent extracts) of two medicinal plants of Iranian origin Borage (Echium amoenum) and Valerian (Valerian officinalis) used as tea were determined. Samples were analyzed for antioxidant components viz. polyphenols, vitamin C, ß carotene, flavonoids, anthocyanins and tannins. Antioxidant assays such as free radical scavenging activity, reducing power and total antioxidant activity were carried out for ethanol, methanol, acetone, 80% methanol and 80% ethanolic extracts. In borage highest and least activity was observed in water and acetone extract respectively in all assays. In Valerian, 80% methanolic extract showed highest activity in reducing power and free radical scavenging activity assay. Total polyphenols in borage and valerian were 1,220 and 500 mg in ethanolic extracts and 25 and 130 mg in acetonic extracts respectively. Total carotenoids and vitamin C contents were 31.6 and 133.69 mg and 51.2 and 44.87 mg for borage and valerian respectively. Highest amount of tannins were extracted in 80% methanolic extract. It can be concluded that borage and valerian exhibited antioxidant activity in all extracts. The antioxidant activity could be attributed to their polyphenol and tannin and flavonoids contents. In all assays borage showed higher activity than valerian.

Catching ZZZs: A Summary of the Most Common Herbal Medications Taken for Insomnia.

Insomnia is caused by a myriad of factors and can be very disruptive to a person's quality of life and health. When people see a health care provider, often a thorough assessment occurs and people are given various treatment options that include lifestyle interventions, medications, and/or cognitive behavior therapy. There are also many people that may choose to take over the counter or herbal medications as a remedy for insomnia. While there are many supplements that claim to have sleep benefits, clinical data supporting such claims are not always present. This article will briefly discuss the three most common herbal supplements taken for insomnia: melatonin, valerian, and lavender.

Standardized Extract of Valeriana officinalis Improves Overall Sleep Quality in Human Subjects with Sleep Complaints: A Randomized, Double-Blind, Placebo-Controlled, Clinical Study.

INTRODUCTION: Sleep deficit or poor sleep leads to ill-health, whereas sleep deprivation for longer periods of time increases the risk of developing adverse conditions associated with poor quality of life, and high socioeconomic impact. The treatments for sleep disturbances include melatonin and over-the-counter medicines like diphenhydramine and doxylamine, all of which have negative side effects. Valerian (Valeriana officinalis L.) is a traditional herb and the most preferred alternate sleep solution to manage sleep complaints. METHODS: Eighty adult subjects with sleep complaints were randomized in 1:1 ratio to receive either V. officinalis extract (VE) or placebo for 8 weeks in a double-blind, placebo-controlled, parallel, clinical study. Primary efficacy endpoints included the Pittsburgh Sleep Quality Index (PSQI) and sleep latency using wrist actigraphy (WA), as well as a number of secondary endpoints, including sleep parameters such as actual sleep time and sleep efficiency using WA, the Epworth Sleepiness Scale (ESS), the Beck Anxiety Inventory (BAI), the Visual Analogue Scale (VAS) for the feeling of waking up refreshed, and a tertiary endpoint of sleep parameters using polysomnography (PSG) in a subset of 20 subjects per group. Safety parameters included physical examination, vital sign measurements, hematology, and clinical chemistry tests. Adverse events and serious adverse events were monitored throughout the study period. RESULTS: Seventy-two subjects (35 and 37 subjects in the placebo and VE groups, respectively) completed the study and were included in the efficacy assessments. On Days 14, 28, and 56, the PSQI Total Score in the VE group decreased significantly (p < 0.05) compared to the placebo group. Further, the VE group showed significant improvements (p < 0.05) in sleep latency and actual sleep time on Days 3, 14, 28, and 56, and sleep efficiency on Days 14, 28, and 56, as evaluated by WA. There was a decrease (p < 0.05) in anxiety (BAI) on Days 14, 28, and 56, daytime drowsiness (ESS) on Days 28 and 56, and an increased feeling of waking up refreshed (VAS) on Days 28 and 56 compared to placebo. PSG results carried out in subset of subjects revealed significant improvements (p < 0.05) in total sleep time, sleep latency, and sleep efficiency on Day 56 in the VE group compared to the placebo group. No safety concerns were observed throughout the study. CONCLUSION: VE supplementation significantly improved various subjective and objective parameters of sleep in young subjects with mild insomnia symptoms, such as overall sleep quality, sleep latency, sleep efficiency, and total sleep time. We also observed decreased anxiety and daytime sleepiness, and improved feeling of being refreshed after waking up with VE supplementation. VE was found to be safe and well tolerated throughout the study. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2022/05/042818.

Impact of a Novel Valerian Extract on Sleep Quality, Relaxation, and GABA/Serotonin Receptor Activity in a Murine Model.

Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice.

Is It Possible to Mitigate Fear of Fireworks in Dogs? A Study on the Behavioural and Physiological Effects of a Psychoactive Supplement.

Canine fear of fireworks is a common problem worldwide, with serious implications for the welfare of both dogs and their owners. Therapies for the problem are available, and herbal and nutraceutical agents are increasingly suggested by professionals; nonetheless, studies on their real efficacy in reducing firework fear are lacking. In a randomised, double-blinded, placebo-controlled study, 44 dogs (25 in the "supplement" group and 19 in the "placebo" group) completed a long-term continuous treatment with either a supplement made of tryptophan, valerian, and passiflora or a placebo, including two real exposures to fireworks (on 2020 Christmas and 2021 New Years' Eve, after 42 and 48 days of treatment, respectively). Owners of both groups received the same general environmental management and food/toy offering recommendations for trying with their dogs on those nights. Behavioural (measured by LSSS-Lincoln Sound Sensitivity Scale and PANAS-Positive and Negative Activation scale, as rated by the owners) and stress (measured via salivary cortisol measures) reactions were evaluated. Significantly greater fear decrease (LSSS) was recorded in the "supplement" dogs, as compared to the "placebo" group. Cortisol dosages on New Year's Eve ("noisy" night) were in line with behavioural results; "supplement" dogs showed a smaller increase in the stress response from 22:30 to 00:30 h on New Year's Eve and a greater decrease in their stress response from 02:30 h to 10:30 h on New Year's Day compared to "placebo" dogs. Smaller cortisol levels were also shown by "supplement" dogs than "placebo" dogs on a controlled "quiet night" (27th December). Owners' rates on PANAS remained stable during the whole period of therapy for both groups. The evaluated supplement, a combination of tryptophan, valerian, and passiflora, showed satisfactory results and rare side effects when treating dogs fearful of fireworks.