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Common valerian is a medicinal plant. The underground organs of this species are used as a mild sedative and sleeping aid. Poland is one of the largest producers of this raw material in Europe, with local cultivar ‘Lubelski’ as a primary cultivated form. Although valerian is the subject of more or less deliberate selection carried out by farmers, it is still genetically unstable. The aim of this study was to determine the diversity of the ‘Lubelski’ cultivar originating from four regions of Poland (forms: L1–L4) in relation to wild-growing populations of the species. The plants were assessed in terms of the mass of underground organs and the content of valerenic acids and essential oils (EOs). The content of valerenic acids was determined using HPLC, whereas the content of EOs was determined using hydrodistillation. The composition of EOs was assessed using GC-MS GC-FID. The ploidy level of the analyzed objects was determined as well. Wild-growing populations (diploids) were characterized by lower masses of underground organs and lower contents of valerenic acid than cultivated forms (tetraploids). However, they produced higher contents of EOs. All the cultivated forms were strongly diversified with respect to the analyzed traits, including the mass of the roots (CV 49–75%), the content of valerenic acids (CV 18–55%), and the content of EOs (CV 28–57%). A total of 44 compounds were identified in the EOs. The dominant compound of both wild-growing populations and the ‘Lubelski’ forms were: α-fenchene, bornyl acetate, and valerenal. Among ‘Lubelski’ forms, the most interesting seems to be the L2 form, which was characterized by a relatively high yield and high content of valerenic acids and EOs. Thus, it appears to be a promising source of objects for further valerian cultivar improvement.

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.

Valerian root extracts are widely used as mild sedatives to promote sleep, with clinical studies confirming their efficacy. Their sleep-promoting effects are associated with the adenosine A1 receptor (A1AR), a key regulator of sleep through neural activity inhibition. Adenosine, a neuromodulator that accumulates during wakefulness, activates A1ARs to facilitate sleep transitions. Using advanced analytics, we detected adenosine at 0.05% in the valerian extract Ze 911, supporting direct A1AR activation in vitro. Additionally, we explored A1ARs’ allosteric sites for modulatory activity. Valerenic acid and pinoresinol, key constituents of Ze 911, were identified as positive allosteric modulators (PAMs) of A1ARs. Valerenic acid exhibited strong PAM activity, with high cooperativity (αβ = 4.79 for adenosine and αβ = 23.38 for CPA) and intrinsic efficacy (τB = 5.98 for adenosine and τB = 3.14 for CPA). Pinoresinol displayed weaker PAM activity, with moderate cooperativity (αβ = 3.42 for adenosine and αβ = 0.79 for CPA) and limited efficacy (τB = 0.93 for adenosine and τB = 1.66 for CPA). The allosteric modulation observed in valerian extract Ze 911 suggests a mechanism of action in which valerenic acid and pinoresinol enhance receptor activation through allosteric interactions, potentially amplifying the effects of endogenous adenosine. By targeting A1ARs’ allosteric sites, valerian extract Ze 911 offers increased therapeutic selectivity and reduced off-target effects, emphasizing its potential for managing sleep disorders.

The use of new agricultural technologies such as soilless and aeroponic cultivation systems is a valuable approach to medicinal plant production. The present study investigated the prospects of enhancing yield and secondary metabolite production in Valeriana jatamansi under aeroponic cultivation using elicitors, such as yeast extract and methyl jasmonate. Plants were evaluated by measuring growth parameters, photosynthetic rate, and secondary metabolites contents (on a dry weight basis). Maximum plant height (36.83 cm), leaf number (17.67), rootlet number (37.33), and rootlet length (6.90 cm) were observed at 0.5 mg/L yeast extract treatment; whereas treatment levels of 1.5 mg/L yeast extract and 150 µM methyl jasmonate resulted in maximum leaf length (6.95 cm) and leaf width (5.43 cm), respectively. Maximum photosynthetic rate (5.4053 µmol m-2s-1) and stomatal conductance (0.0656 mmol m-2s-1) were recorded at treatment levels of 0.5 mg/L and 1.5 mg/L yeast extract respectively, whereas at 150 µM methyl jasmonate treatment, transpiration rate was 0.9046 mmol m-2s-1. In aeroponic cultivation, the maximum content of valerenic acid and hydroxy valerenic acid was detected in leaf (2.47 and 8.37 mg/g) and root (1.78 and 7.89 mg/g) at treatment levels of 100 µM and 150 µM methyl jasmonate, respectively. Acetoxy valerenic acid was highest in leaf (1.02 mg/g) at 1.5 mg/L yeast extract, and in the root (2.38 mg/g) at 150 µM methyl jasmonate. Gas chromatography-mass spectrometry analysis identified twenty-eight volatile compounds in roots, of which three—isovaleric acid (6.72-50.81%), patchouli alcohol (13.48-25.31%) and baldrinal (0.74-25.26%)—were the major constituents. The results revealed that, besides roots, leaves could also be utilized as a prominent alternative source for targeted secondary metabolites. In conclusion, aeroponic cultivation offers year-round quality biomass production and ease to access subsequent roots harvest in V. jatamansi , to meet the demand of the pharmaceutical industries.

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

Glioblastoma multiform (GBM) continues to threaten people's lives due to the limited therapeutic strategies. As a new drug, Valerenic Acid suppresses the progression of GBM, however, the mechanism is largely unknown. Here, we found that Valerenic Acid can inhibit cell proliferation, migration and invasion of GBM cells by increasing innate immune signals such as enhancing ROS levels and activating the AMPK pathway. Inhibition of ROS by N-acetylcysteine (NAC) or attenuation of AMPK by Compound C could block Valerenic Acid-induced cell death. Additionally, the xenograft mouse model also confirmed that Valerenic Acid had anti-tumor effect. Together, our results provide compelling rational to develop Valerenic Acid as an anti-tumor agent against GBM patients.

The changes in total phenolics, flavonoids, tannins, valerenic acid, and antioxidant activity were assessed in 25 populations of Valeriana jatamansi sampled from 1200 to 2775 m asl and four habitat types of Uttarakhand, West Himalaya. Significant ( p  < 0.05) variations in total phenolics, flavonoids, valerenic acid, and antioxidant activity in aerial and root portions and across the populations were observed. Antioxidant activity measured by three in vitro antioxidant assays, i.e., 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic) (ABTS) radical scavenging, 2,2′-diphenyl-1-picryylhydrazyl (DPPH) free radical scavenging, and ferric-reducing antioxidant power (FRAP) assays, showed significant ( p  < 0.05) differences across the populations. However, no clear pattern was found in phytochemicals across the altitudinal range. Among habitat types, (pine, oak, mixed forest, and grassy land), variation in phytochemical content and antioxidant activity were observed. Equal class ranking, neighbor-joining cluster analysis, and principal component analysis (PCA) identified Talwari, Jaberkhet, Manjkhali, and Khirshu populations as promising sources with higher phytochemicals and antioxidant activity. The results recommended that the identified populations with higher value of phytochemicals and antioxidants can be utilized for mass multiplication and breeding program to meet the domestic as well as commercial demand.

ObjectiveTo produce valerenic acid (VA) in Saccharomyces cerevisiae by engineering a heterologous synthetic pathway.ResultValerena-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.ConclusionsAn 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.

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 17β-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.

Plant raw materials with a calming effect on the nervous system are increasingly used in modern phytotherapy. Lavender belongs to this group of plants, due to the content of essential oil with known therapeutic properties and other phytoconstituents that can be responsible for the sedative effect. Our studies confirmed the presence of sesquiterpenic acids characterized by sedative activity in lavender extracts. The contents of valerenic acid and acetoxyvalerenic acids in flowers and leafy stalks of two various Lavandula angustifolia cultivars—‘Blue River’ and ‘Ellagance Purple’—were determined. Analyses of methanolic extracts performed using the HPLC method showed that content of these sesquiterpenic acids varied with the cultivars and the morphological parts of the plant. The amount of acetoxyvalerenic acid was significantly higher than the amount of valerenic acid. In the ‘Blue River’ cultivar, higher levels of both compounds characterized by sedative properties were found. The content of valerenic acid in flowers ranged from 0.50 mg/100 g d.m. in the ‘Ellagance Purple’ cultivar to 1.75 mg/100 g d.m. in the ‘Blue River’ cultivar. In turn, leafy stalks contained 0.81 mg/100 g d.m. of valerenic acid in the ‘Ellagance Purple’ cultivar and 1.16 mg/100 g d.m. in the ‘Blue River’ cultivar. Interestingly, the ‘Blue River’ cultivar contained about 10 times more acetoxyvalerenic acid (65.80 mg/100 g d.m.) in flowers and four times more acetoxyvalerenic acid in leafy stalks (50.1 mg/100 g d.m.), in comparison with the ‘Ellagance Purple’ cultivar. The higher content of valerenic and acetoxyvalerenic acids in the flowers and leafy stalks of the ‘Blue River’ lavender cultivar can be important for its possible medical applications.