The Human Host Defense Peptide LL-37 Overexpressed in Lung Cell Lines by Methanolic Extract of Valeriana officinalis

Abstract The present study investigated the effects of valerian methanolic extract and valerenic acid on the expression of LL-37 gene and protein in A549 and MRC5 line cells. After preparing Valerian seeds, sowing them in March 2020, and harvesting the rhizome in October 2020, the extract was prepared from the valerian rhizome by maceration method. Valerian acid content was determined using high performance liquid chromatography (HPLC). Two cell lines (A549 and MRC-5) were used to study the effects of valerian extract, and the MTT test was used to evaluate cell viability. The expression of LL-37 mRNA and protein was assessed by Real-Time PCR and western blot, respectively. In vivo safety assessments and histopathological analysis were also conducted. Data was analyzed by Graphpad Prism 8 software. Valerian methanolic extract and valerenic acid upregulated the LL-37 mRNA and protein expression in both treated cell lines. Valerenic acid showed a greater effect on upregulating LL-37 expression than valerian methanolic extract. A549 cells were more sensitive to valerian methanolic extract compared to MRC5 cells, and its cell viability was reduced. Furthermore, liver and kidney-related safety assessments showed that valerian methanolic extract had no toxic effects. In general, it was concluded that the methanolic extract of valerian as well as the resulting valerenic acid as the most important component of the extract has the ability to upregulate LL-37expression. Therefore, methanolic extract of valerian and valerenic acid can be considered for improving the immune system.

Analysis of spontaneous adverse drug reactions to echinacea, valerian, black cohosh and ginkgo in Australia from 2000 to 2015.

OBJECTIVE: Assessing adverse drug reactions (ADRs) is a proven method to estimate the safety of medicines. The ADRs to herbal medicines in Australia (and by inference, the safety of herbal medicines in Australia) remain unknown. This study examines spontaneous ADR cases to four of the most popular herbs in Australia from 2000 to 2015: echinacea (Echinacea purpurea), valerian (Valeriana officinalis), black cohosh (Actaea racemosa) and ginkgo (Ginkgo biloba). METHODS: ADRs of echinacea, valerian, black cohosh and ginkgo reported to the Australian Therapeutic Goods Administration (TGA) between 2000 and 2015 were obtained from the TGA database. Data were collated and analysed according to age, sex, severity, type of ADR and body system affected. Statistics were calculated using GraphPad Prism software. RESULTS: Most ADRs were mild or moderate. However, every herbal medicine was associated with life-threatening ADRs. In each life-threatening case, the herbal medicine was taken concomitantly with prescription medications. Black cohosh was associated with a significant number of severe ADRs (30.3% of the total), with 39.4% of these ADRs being associated with abnormal hepatic function, hepatitis or hepatotoxicity. CONCLUSION: This study highlights the lack of public awareness with regard to herb-drug interactions, since most of the severe ADRs involved a herb-drug interaction.

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.

Analgesic effect of Hypericum perforatum, Valeriana officinalis and Piper methysticum for orofacial pain

To evaluate in vivo the association of hypericum Hypericum perforatum, valerian Valeriana officinalis and kava Piper methysticum with analgesia by assessing their effects in reducing orofacial pain as well as the possible hepatic, hematologic and biochemical alterations induced by regular administration of these extracts. METHODS: Orofacial pain was induced in mice with the administration of 2.5% formalin in the upper lip. After 60 min, the animals were treated with saline, carbamazepine and hydroalcoholic plant extracts. The nociceptive intensity was determined by the timing at which the animal remained rubbing the injected area. To assess the hepatotoxic effect, mice were chronically treated for 25 days with saline, carbamazepine and hydroalcoholic extract. The animals were euthanized and the liver weighed, followed by a differential count of leukocytes and measurement of alanine transaminase and alkaline phosphatase. RESULTS: The evaluation of analgesic activity in phase 1 reduced the time of rubbing compared to the control by 86% 0.05 mL/10 g and 76% 0.10 mL/10 g. In phase 2, the extracts reduced rubbing time by 94% and 85%, respectively. In the evaluation of alkaline phosphatase, the groups treated with extracts at doses of 0.05 mL/10 g and 0.1 mL/10 g increased by 16.1% and 9.5% compared to the control group and a reduction of 8.5% and 9.1% in the evaluation of alanine transaminase respectively. It was demonstrated that in the differential counts showed an increase in eosinophils in the treated group with 0.05 mL/10 g. CONCLUSIONS: The use of hydroalcoholic extract of the associated plants reduced the orofacial formalin-induced pain with better results than carbamazepine, at both the neural conductor level of pain phase 1 and in inflammatory or later pain phase 2 without presenting hepatotoxicity. The observed eosinophilia is suggestive of a phenomenon called hormesis...

Saffron, passionflower, valerian and sage for mental health.

Many cultures have developed folk herbal remedies to treat symptoms of mental illness. An evidence-based view is now being developed for some of these so-called alternative herbal treatments. This article discusses clinically relevant scientific information on medicinal extracts of 4 herbs: saffron, passionflower, valerian, and sage.

Herbal medicines in pediatric neuropsychiatry.

An increasing number of studies have evaluated the role of herbal supplements in pediatric disorders, but they have numerous limitations. This review provides an overview of herbal components, regulation of supplements, and importance of product quality assurance. Use of herbal supplements is discussed with reference to factors that influence use in the pediatric population. The remainder of the article discusses the use of St John's wort, melatonin, kava, valerian, eicosapentaenoic acid, and docosahexaenoic acid, focusing on indications, adverse effects, and drug interactions, and providing a limited efficacy review. Herbal supplements used for weight loss are also briefly discussed.

Perioperative risks and benefits of herbal supplements in aesthetic surgery.

Most medications, herbal preparations, and nutraceutical supplements have notable effects on biochemical pathways and may influence wound healing, coagulation, and cardiovascular function. They can also interact with other drugs. A large portion of the data available regarding the effects of naturopathic medicines is anecdotal. Marketing of certain products may be misleading and potentially harmful, and quality control standards are highly variable. In order to ensure quality control and standardization of products, it is prudent to work with preparations manufactured by companies that adhere to pharmaceutical (good manufacturing practice [GMP]) standards. However, many of these higher-quality products are not readily available to the public over the counter. A large percentage of patients undergoing plastic surgery use one or more herbal medications, but the disclosure of such medications to allopathic providers is often incomplete. In addition, patients may not understand the importance of discontinuing such medications before surgery. The authors review research on the possible benefits and risks of commonly used herbal medications such as arnica montana, St. John's wort, bromelain, echinacea, ginkgo biloba, ephedra, valerian, and others, focusing on their potentially positive or negative impact during the perioperative period of aesthetic surgery. Good communication with surgical patients, including the administration of a presurgical questionnaire to help identify any use of herbal medications, is emphasized.

[Liver failure a la Eastern Europe]. / Májelégtelenség kelet-európai módra.

The use of valeriana was underplayed at the beginning of the 20th century because of its addictive and side effects. The 38-year-old woman, mother of a 20-month-old child from Eastern Europe, was treated with liver insufficiency and vascular, parenchymal decompensated cirrhosis needing plasmapheresis for the first time in our hospital. In case history, abusus of aethyl-alcohol and valeriana was found to be as toxic agent which was treated as the etiologic factor of the liver disease and liver failure. After intensive and conservative treatment her status was stabilised, during the follow-up she had no signs and symptoms, the laboratory results tend to be in normal range. Half year after her hospitalization intensive care treatment was necessary abroad due to gastric bleeding. In the background the histology of gastric biopsy taken during gastroscopic examination showed gastric sigillocellular carcinoma in our hospital. Total gastrectomy, omentectomy, lymphadenectomy were performed, the tumor was removed and she received cytostatic treatment. The use of valeriana and aethyl-alcohol is supposed to have a potential effect on tumorgenesis and on the increase of toxicity.

Up-date sobre los últimos estudios de valeriana, pasiflora y espino blanco / Up-date on the latest studies of valerian, passionflower and hawthorn

Los trastornos por ansiedad y las alteraciones del sueño, representan un problema de salud de una alta incidencia y un importante efecto potencial en la calidad de vida de la población, especialmente en los países económicamente desarrollados. Ante este tipo de cuadros clínicos, es fundamental en todos los casos la valoración por parte de un especialista, para descartar la existencia de una patología orgánica y/o psiquiátrica de base.

Potentially adverse interactions between haloperidol and valerian.

This study was designed to determine whether the treatment with haloperidol (HP), valerian or both in association impairs the liver or kidney functions. Valerian alone did not affect oxidative stress parameters in the liver or kidney of rats. HP alone only increased glutathione (GSH) depletion in liver, but not in kidney. However, when HP was associated with valerian, an increase in lipid peroxidation levels and dichlorofluorescein (DCFH) reactive species production was observed in the hepatic tissue. Superoxide dismutase (SOD) and Catalase (CAT) activities were not affected by the HP plus valerian treatment in the liver and kidney of rats. HP and valerian when administered independently did not affect the activity of hepatic and renal delta-aminolevulinate dehydratase (delta-ALA-D), however, these drugs administered concomitantly provoked an inhibition of hepatic delta-ALA-D activity. The delta-ALA-D reactivation index was higher in rats treated with HP plus valerian than other treated groups. These results strengthen the view that delta-ALA-D can be considered a marker for oxidative stress. Serum aspartate aminotransferase (AST) activity was not altered by any treatment. However, serum alanine aminotransferase (ALT) activity was higher in the HP group and HP plus valerian group. Our findings suggest adverse interactions between haloperidol and valerian.

Use of herbal drugs during early pregnancy in relation to maternal characteristics and pregnancy outcome.

PURPOSE: To study characteristics of women using herbal drugs and the possible impact of use in early pregnancy on pregnancy outcome. METHODS: Data on the use of herbal drugs during pregnancy were obtained from the Swedish Medical Birth Register during the period 1st July 1995 to end of 2004. Women who reported use of herbal drugs were compared to all women giving birth during the period. Outcome variables were prematurity, birth weight, Apgar score, number of infants in delivery and congenital malformations. RESULTS: Among the 860 215 women in the register, 787 (0.9%) reported use of herbal drugs during early pregnancy. The most frequently used herbal drugs were Floradix (iron-rich herbs), ginseng and valerian. Use of such drugs was independently associated with high maternal age, normal weight and 14-15 years of education. Risk factors for valerian differed from those for other herbal drugs, for example with respect to maternal smoking and country of birth. Concomitant drug use was common and the most frequently used drugs were multivitamins, folic acid, cardiovascular drugs (mainly antihypertensive drugs), non-steroid anti-inflammatory drugs (NSAIDs), analgesics and psycholeptics. None of the infant characteristics studied were influenced significantly by the mother's use of the examined herbal drugs during early pregnancy. CONCLUSIONS: The most commonly reported herbal drugs used during pregnancy were Floradix (iron-rich herbs), ginseng and valerian. No signs of unfavourable effect on pregnancy outcome were seen. The number of exposures, however, was low and therefore effects on rare outcomes (e.g. specific malformations) cannot be excluded.

Insomnia associated with valerian and melatonin usage in the 2002 National Health Interview Survey.

STUDY OBJECTIVE: Many people use dietary supplements or herbal products to help them sleep. We analyzed the associations between melatonin use and insomnia and between valerian use and insomnia in a representative sample of the United States population. DESIGN AND PARTICIPANTS: The data reported upon here were collected in the 2002 Alternative Health/Complementary and Alternative Medicine (CAM) Supplement to the National Health Interview Survey. This was a survey of 31,044 personal interviews that constituted an age-representative and socioeconomically representative sample of the civilian noninstitutionalized population of the United States. RESULTS: Of the survey sample, 5.9% used valerian and 5.2% used melatonin. Of those using valerian, 29.9% endorsed insomnia as 1 reason for CAM use, and, of melatonin users, 27.5% endorsed insomnia as 1 reason for CAM use. Relatively greater use occurred in individuals under age 60 years. The decision to use such substances was made in consultation with a health care provider less than half of the time. CONCLUSIONS: Large segments of the United States population used valerian or melatonin for insomnia within the year preceding the survey, and usage typically fell outside the purview of the health care system.

A systematic review of valerian as a sleep aid: safe but not effective.

Valerian is an herb that is widely available in a variety of commercial preparations and is commonly used as a sleep aid. A recent systematic review and meta-analysis of valerian concluded that evidence in support of the effectiveness of the herb was inconclusive. Therefore, in an effort to more closely examine this issue, a systematic review was conducted to examine the evidence on the efficacy of valerian as a sleep aid with specific attention to the type of preparations tested and the characteristics of the subjects studied. A comprehensive search of studies investigating valerian was conducted through computerized databases and hand searches of reference lists. Standardized forms were used to summarize findings and standardized criteria were used to assess study quality. Out of 592 articles initially identified, a total of 36 articles describing 37 separate studies met criteria for review: 29 controlled trials evaluated for both efficacy and safety, and eight open-label trials evaluated for safety only. Most studies found no significant differences between valerian and placebo either in healthy individuals or in persons with general sleep disturbance or insomnia. None of the most recent studies, which were also the most methodologically rigorous, found significant effects of valerian on sleep. Overall, the evidence, while supporting that valerian is a safe herb associated with only rare adverse events, does not support the clinical efficacy of valerian as a sleep aid for insomnia.

Effect of valerian, valerian/hops extracts, and valerenic acid on glucuronidation in vitro.

Valerian preparations alone or in combination with hops are popular over-the-counter products used for sleep disturbances or anxiety. Therefore, it is important to characterize the effect of these products on the activity of human drug-metabolizing enzymes. The inhibitory effects of valerian and valerian/hops extracts as well as valerenic acid (a major constituent of valerian) on glucuronidation were evaluated in human liver microsomes and with expressed uridine 5'-diphosphate (UDP)-glucuronosyltransferases (UGT). Methanolic extracts of two herbal preparations caused significant reductions in the rate of formation of acetaminophen, oestradiol, morphine, and testosterone glucuronides. Oestradiol glucuronidation at the 3-hydroxy position was inhibited by nearly 87% in microsomal incubations. In addition, marked reductions in UGT1A1 and UGT2B7 activities were observed in the presence of the herbal extracts using oestradiol and morphine as probe substrates, respectively. Valerenic acid also demonstrated significant inhibitory effects on the glucuronidation of acetaminophen, oestradiol, and morphine with both microsomes and expressed UGTs. The relatively low IC50 values obtained for valerenic acid in microsomal incubations may indicate that this essential oil contributes to the effects observed with herbal extracts in inhibiting glucuronidation in vitro. Overall, these findings suggest that valerian-containing products may interfere with the glucuronidation of endo- and xenobiotics.

An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia.

The herbal extracts kava and valerian are the leading dietary supplements used in the self-management of anxiety and insomnia, respectively. There is limited evidence to support their effectiveness for these common symptoms. The Internet has been used to a limited extent for research, but it is not known whether randomized controlled trials can be conducted entirely using Internet technology. We performed a randomized, double-blind, placebo-controlled trial using a novel Internet-based design to determine if kava is effective for reducing anxiety and if valerian is effective for improving sleep quality. E-mail recruitment letters and banner advertisements on websites were used to recruit a large pool of interested participants (1551) from 45 states over an 8-week period. Participants were first asked to read study information, complete an online informed consent process, and undergo electronic identity verification. In order to be eligible for the study, participants were required to have 1) anxiety as documented by scores of at least 0.5 standard deviations above the mean on the State-Trait Anxiety Inventory State subtest (STAI-State) on 2 separate occasions, and 2) insomnia, defined as a "problem getting to sleep or staying asleep over the past 2 weeks." We randomly assigned 391 eligible participants to 1 of the following 3 groups, and mailed 28 days' supply: kava with valerian placebo (n = 121), valerian with kava placebo (n = 135), or double placebo (n = 135). The primary outcome measures were changes from baseline in anxiety (STAI-State questionnaire) and insomnia (Insomnia Severity Index [ISI]) compared with placebo. Participants receiving placebo had a 14.4 point decrease in anxiety symptoms on the STAI-State score and an 8.3 point decrease in insomnia symptoms on the ISI. Those receiving kava had similar reductions in STAI-State score (2.7 point greater reduction in placebo compared with kava; 95% confidence interval [CI], -0.8 to +6.2). Those receiving valerian and placebo had similar improvements in sleep (0.4 point greater reduction in the placebo than the valerian group; 95% CI, -1.3 to +2.1). Results were similar when limited to the 83% of participants who adhered to study compounds for all 4 weeks. Neither kava nor valerian relieved anxiety or insomnia more than placebo. This trial demonstrates the feasibility of conducting randomized, blinded trials entirely via the Internet.