Endophyte-based fungal elicitors for enhanced production of valepotriates and sesquiterpenoids in leaf cell suspension cultures of Valeriana jatamansi Jones.

AIMS: The immense therapeutic value of Valeriana jatamansi is attributed to the presence of bioactive secondary metabolites (valepotriates and sesquiterpenoids). Its over-exploitation in wild habitats resulted in extensive depletion, necessitating alternative approaches to produce its therapeutic metabolites. This study sought to assess the ability of endophytes of V. jatamansi to boost the biosynthesis of secondary metabolites in the leaf-cell suspension (LCS) culture of V. jatamansi. METHODS AND RESULTS: A total of 11 fungal endophytes were isolated from the rhizomes of V. jatamansi. Isolated endophytes were found to belong to phylum Ascomycota, Basidiomycota, and Mucoromycota. Supplementation of extracts of endophyte Phaeosphaeriaceae sp. VRzFB, Mucor griseocyanus VRzFD, Penicillium raistrickii VRzFK, and Penicillium sajarovii VRzFL in the LCS culture of V. jatamansi increased the fresh cell biomass by 19.6%-39.1% and dry cell biomass by 23.4%-37.8%. Most of the endophytes' extract could increase the content of valepotriates (26.5%-76.5% valtrate and 40.5%-77.9% acevaltrate) and sesquiterpenoids (19.9%-61.1% hydroxyl valerenic acid) in LCS culture. However, only two endophytes, Irpex lacteus VRzFI and Fusarium oxysporum VRzFF, could increase the sesquiterpenoids acetoxy valerenic acid (36.9%-55.3%). In contrast, some endophytes' extracts caused negative or no significant effect on the cell biomass and targeted metabolites. Increased secondary metabolites were corroborated with increased expression of iridoid biosynthesis genes in LCS culture. Production of H2O2 and lipid peroxidation was also varied with different endophytes indicating the modulation of cellular oxidative stress due to endophyte elicitors. CONCLUSIONS: The results suggest the distinct effect of different fungal endophytes-extract on LCS culture, and endophytes can serve as biotic elicitors for increasing the secondary metabolite production in plant in vitro systems.

Safety evaluation of aqueous extract from Valeriana officinalis L. roots: Genotoxicity, acute, subchronic and teratology toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana officinalis L., commonly known as "valerian", is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear. AIM OF THE STUDY: This study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR). MATERIALS AND METHODS: The genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague-Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague-Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR. RESULTS: AEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight. CONCLUSION: In vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.

Fabrication and characterization of Karaya gum-based films reinforced with bacterial nanocellulose stabilized valerian root extract Pickering emulsion for lamb meat preservation.

A novel biodegradable film was fabricated by incorporating bacterial nanocellulose stabilized valerian root extract (VRE) Pickering emulsion into karaya gum with better antioxidant and antibacterial properties for lamb meat preservation. The valerian root extract Pickering emulsion (VPE) exhibited 98 ± 1.84 % encapsulating efficiency and excellent physical stability with an average particle size of 274.6 nm. The incorporation of VPE-5 into the film matrix increased its elongation at break (EAB), and improved water resistance and barrier properties against oxygen, water vapor, and UV light. Moreover, the antioxidant and anti-bacterial properties against S.aerous and E. coli were also improved based on VPE-5 concentration. The SEM images showed a uniform distribution of VPE-5 while FTIR and XRD revealed its compatibility with karaya gum, which improved its thermal stability. The active films showed a significant preservative effect by reducing the pH, total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS), and total viable count (TVC) value of lamb meat and maintained its texture and color during the storage period of 9 days at 4 °C. These results demonstrated the inclusion of VPE-5 into Karaya gum was a promising technique and offers a great potential application as a bioactive material in food packaging.

Evaluation of the Effects of Extracts Containing Valeriana officinalis and Piper methysticum on the Activities of Cytochrome P450 3A and P-Glycoprotein.

This work investigated interactions ascribed to the administration of phytomedicines containing Valeriana officinalis and Piper methysticum with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (Cmax) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC(0-∞)) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although Valeriana increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing V. officinalis or P. methysticum inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.

Research progress in the ethnopharmacology, phytochemistry, pharmacology, toxicology, and quality control of Valeriana jatamansi Jones.

ETHNOPHARMACOLOGIC RELEVANCE: Valeriana jatamansi Jones, belongs to the Valerianaceae family, is widely used in traditional Chinese medicine (TCM) and Ayurveda, traditional Indian medicine (TIM). This traditional herb has been officially listed in the pharmacopoeia of sixteen countries. Its usage was first described in Diannan Bencao, also known as "Zhizhuxiang", is a famous folk medicine herb with a long history of medicinal usage in China, and it was used to treat indigestion, flu, and mental disorders in the Han, Achang, Bai, Blang, Dai, Jingpo, Naxi, and Wa ethnic groups. In recent years, V. jatamansi has attracted worldwide attention as an important medicinal due to its pharmacological activity especially in nervous and digestive systems, and multiple uses. AIM OF THE STUDY: The current review aims to provide a comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity, and quality control of V. jatamansi. MATERIALS AND METHODS: The relevant information of V. jatamansi was obtained from several databases including Web of Science, PubMed, ACS Publications, Google Scholar, Baidu Scholar, CNKI, Ph.D. and MSc dissertations, using "Valeriana jatamansi Jones", "Valeriana jatamansi", and "" as keywords. After eliminating repetitive and low-quality reports, the remaining reports were analyzed and summarized to prepare this review. Plant information was retrieved by www.worldfloraonline.org and www.gbif.org using "Valeriana jatamansi Jones" as keyword. RESULTS: V. jatamansi has been historically utilized as a traditional medicine to treat various diseases, including infectious, inflammatory, neurological, and gastrointestinal disorders. More than 400 compounds have been identified in V. jatamansi including iridoids, volatile oils, lignans, flavonoids, phenolic acids, phenylpropanoids, sesquiterpenes, sesquiterpene hydrocarbons, triterpenes as well as other compounds. The plant extracts and compounds showed various pharmacological activities such as antitumor, cytotoxic, antivirus, etc. In addition, V. jatamansi has found various applications in the agricultural, food, and cosmetics industry. CONCLUSION: A review of literature shows V. jatamansi has pharmacological properties valuable in treating diseases, particularly for antianxiety and gastrointestinal disorders. Despite a wide spectrum of effects from specific compounds, research mainly focuses on in vitro and in vivo, with a lack of pharmacokinetics, clinical trials and underlying mechanisms. Consequently, it becomes important to embark on additional researchs to elucidate the pharmacokinetics, material basis and mechanisms of V. jatamansi, thereby realizing the aspiration of its comprehensive utilization and sustainable development.

Effects of Passiflora incarnata and Valeriana officinalis in the control of anxiety due to tooth extraction: a randomized controlled clinical trial.

OBJECTIVE: This study evaluated the efficacy of Valeriana officinalis L. and Passiflora incarnata L. to control anxiety, surgical discomfort, and changes in vital signs of patients undergoing extraction of two unilateral third molars. MATERIALS AND METHODS: This study is a randomized, triple-blinded clinical trial. Fifty-four patients were allocated into three groups (Valeriana officinalis L., Passiflora incarnata L., and placebo). Anxiety levels were assessed using the State-Trace Anxiety Inventory (STAI) index, surgical discomfort using the QCirDental, and through the measurement of vital signs. The surgical times evaluated were before (T0), during (T1), and after surgery (T2). RESULTS: There was evidence that both Valeriana officinalis L. and Passiflora incarnata L., reduced STAY-S scores between T0 and T2 (p < .05), unlike placebo (p = .129). There was no change in surgical discomfort in all groups over time, and vital signs presented variable results. CONCLUSION: Phytotherapy drugs showed a reduction in anxiety state compared to the placebo group during third molar extraction procedure.  CLINICAL TRIAL REGISTRATION: klRBR-6kcxvrc, March 10, 2022.

Serum albumin exposure enhances cell invasiveness and paclitaxel resistance in human neuroblastoma cells, with attenuation by valeriana-type iridoid glycosides.

Neuroblastoma, a prevalent extracranial solid tumor in children, arises from undifferentiated nerve cells. While tumor vasculature, often characterized by increased permeability, influences metastasis and recurrence, the direct impact of blood-borne molecules on tumor progression remains unclear. In the present study, we focused on the effect of exposure to albumin, one of the most abundant proteins in the serum, on human neuroblastoma cells. Albumin exposure elevated oxidative stress and led to mitochondria dysfunction via the activation of TGFß and PI3K pathways, accompanied by an increase in the metastatic and invasive properties of neuroblastoma cells. Proteins relevant to the induction of autophagy were upregulated in response to prolonged albumin exposure. Additionally, pre-exposure to albumin before treatment resulted in increased resistance to paclitaxel. Two valeriana-type iridoid glycosides, patrisophoroside and patrinalloside, recently isolated from Nardostachys jatamansi significantly mitigated the effect of albumin on oxidative stress, cell invasiveness, and chemoresistance. These findings illuminate the potential role of blood-borne molecules, such as albumin, in the progression and metastasis of neuroblastoma, as well as the possible therapeutic implications of valeriana-type iridoid glycosides in anti-cancer treatment.

Acevaltrate promotes apoptosis and inhibits proliferation by suppressing HIF-1α accumulation in cancer cells.

Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers.

Optimizing the extract yield of bioactive compounds in Valeriana officinalis root: a D-optimal design.

It is estimated that 80% of all synthetic drugs are derived from medicinal plants, and nowadays, many synthetic drugs are derived from medicinal plants. Valeriana officinalis can treat many diseases of the nervous system. A crucial aspect of valerian extract is that it inhibits the proliferation of breast cancer cells. To optimize the yield of bioactive compounds in the V. officinalis root extraction, a response surface methodology-based D-optimal design was used. To fulfill this aim, the effects of various factors such as solvent type and concentration, mixing temperature, ultrasound time, and drying method were examined. The optimal conditions for solvent percentages, mixing temperature, ultrasound time, solvent type, and drying methods were determined to be 94.88%, 25 °C, 48.95 min, methanol, and microwave, respectively, with a desirability of 0.921. The predicted valerenic acid, total phenols, total flavonoids, and antioxidant activity in V. officinalis extract were 1.19 (mg/g DW), 8.22 (mg/g DW), 5.27 (mg/g DW), and 92.64%, respectively. In optimal conditions, the extracted amounts of valerenic acid, total phenols, total flavonoids, and antioxidant activity were 2.07 mg/g DW, 7.96 mg/g DW, 5.52 mg/g DW, and 78.68%, respectively, which were consistent with the model predicted amounts (based on 95% prediction interval). This study could be useful as a model for demonstrating the efficacy of microwave drying to maximize the biochemical content of V. officinalis, as well as the antioxidant activity of the root extracts of V. officinalis on industrial scale.

Physiological and biochemical regulation of Valeriana jatamansi Jones under water stress.

Understanding the physiological and biochemical regulations in a medicinal plant under stress environments is essential. Here, the effect of water stress such as flooding and water deficit [80% (control), 60%, 40%, 20% field capacity (FC)] conditions on Valeriana jatamansi was studied. Both types of water stresses retarded the plant growth and biomass. Photosynthetic pigments were reduced with maximum reduction under flood stress. Chlorophyll fluorescence study revealed distinct attributes under applied stresses. Better performance index (PI) of flood-grown plants (than 20% and 40% FC) and higher relative fluorescence decrease ratio (Rfd) in 40% FC and flood-grown plants than that of control plants, indicated the adaptation ability of plants under water deficit (40% FC) and flood stress. Reduction in net photosynthetic rate was lesser in flood stress (40.92%) compared to drought stress (73.92% at 20% FC). Accumulation of starch was also decreased (61.1% at 20% FC) under drought stress, while it was increased (24.59%) in flood stress. The effect of water stress was also evident with modulation in H2O2 content and membrane damage. Differential modulation of biosynthesis of secondary metabolites (valtrate, acevaltrate and hydroxyl valerenic acid) and expression of iridoid biosynthetic genes under water stress was also revealed. The present study demonstrated the distinct effect of drought and flood stress on V. jatamansi plants, and drought [20% FC] caused severe loss and more damage than flood stress. Therefore, severe drought should be avoided during cultivation of V. jatamansi and regulated water stress-applications have potential for modulation of biosynthesis of specific secondary metabolites.

Does valerian work for insomnia? An umbrella review of the evidence.

Valerian is one of the most used herbal agents (phytotherapeutics) to manage sleep disturbances, in particular, sleep-onset difficulties in young adults. However, the evidence based on primary studies and systematic reviews that supports its use in this domain is weak or inconclusive. In the current study, an umbrella review was performed on the efficacy of valerian for sleep disturbances with a focus on insomnia. As such, only systematic reviews (with or without meta-analysis) were considered for this study. Systematic searches in PubMed, Web of Science, Scopus, Cochrane Database of Systematic Reviews, PROSPERO and CNKI databases retrieved 70 records. Only 8 articles were considered eligible for qualitative analysis. Overall, data suggested that valerian has a good safety profile, however, the results showed no evidence of efficacy for the treatment of insomnia. Moreover, valerian appears to be effective concerning subjective improvement of sleep quality, although its effectiveness has not been demonstrated with quantitative or objective measurements. Despite its widespread use and prescription by general practitioners, psychiatrists and other professionals, valerian does not have empirical support for insomnia. Further studies, in particular high quality randomized controlled trials, are highly recommended since there are scarce studies and the existing ones are quite heterogeneous and with low methodological quality. The implications of our findings for clinical practice are critically discussed.

Valeriana jatamansi: Bioactive Compounds and their Medicinal Uses.

Valeriana jatamansi is a reputed perennial medicinal herb distributed throughout the world, where it is used in cytotoxicity, neuronal problems, insomnia, leishmania and acetylcholinesterase inhibitor, antioxidant, antiviral and α-glucosidase inhibition activities. This review describes the current state of chemical characterization of isolated metabolites, which are well accepted for the treatment of various ailments in the indigenous system of medicine. This comprehensive review covers previously published research articles and reviews up to 2023 with an emphasis on the structural characterization of isolated bioactive compounds using different analytical techniques. Furthermore, the present review also focuses on the detailed medicinal and pharmacological properties of isolated compounds from this threatened herb.

New Iridoids and Acyclic Monoterpenoids from the Roots and Rhizomes of Valeriana officinalis var. latifolia.

Five new iridoids, valeralides A-E (1-5), two new acyclic monoterpenoids, valeralides F (6) and G (7), together with two known iridoids (8 and 9), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated based on 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The absolute configuration of compounds 1-4 were elucidated based on electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their inhibition on nitric oxide production, cytotoxicity and anti-influenza A virus activity.

Eighteen iridoids from the roots and rhizomes of Valeriana jatamansi and their protective effects against α-hemolysin.

Thirteen previously undescribed iridoids (1-13), together with five known iridoids (14-18) were isolated from the roots and rhizomes of Valeriana jatamansi Jones. Their structures with absolute configurations were elucidated by analysis of MS, NMR, optical rotation and their experimental and calculated electronic circular dichroism spectra. All of the isolated compounds were tested for their protective effects against α-hemolysin-induced cell death in A549 cells. Compounds 14, 16 and 17 showed moderate protective effects, and compounds 15 and 18 showed weak protective effects.

Exploring In-Silico, In-Vitro Antioxidant, and Cytotoxic Potential of Valerian wallichii by On Cervical Epithelial Carcinoma (HeLa) Cell Lines.

Traditional medicinal practices often utilize herbal remedies for treating various diseases. This study focuses on exploring the phytochemical constituents, in-silico, in-vitro antioxidant, and anticancer activities of Valerian wallichii root extracts on human cervical epithelial carcinoma (HeLa) cell lines. The molecular docking approach was employed to predict the ligand molecule's orientation within the receptor like Epidermal growth factor receptor tyrosine kinase domain (PDB ID: 1M17) using Schrodinger's GLIDE model. Among the selected phytocompounds, hesperidin exhibited promising inhibitory activity against EGFR (Epidermal Growth Factor Receptor) domain with -8.701 kcal/mol docking score and interactions with MET 769, ASP 831, ASP776, LEU694 and ASN818 residues as compared to standard doxorubicin with -7.6 kcal/mol docking score and interactions with ASP 831, ASN818 and ASP776 residues and further, various antioxidant activity was assessed and In-vitro anticancer activity against HeLa cell lines was evaluated by hydroalcoholic root extracts demonstrated antioxidant capacities, and selective cytotoxicity was observed, with IC50 : 45.759±0.42 µg/mL for the overall extract and IC50 : 30.245±0.58 µg/mL for the EAF fraction as compared to standard doxorubicin with IC50 : 25.9891±0.25 µg/mL, respectively. The present study concluded that Valerian wallichii L possesses potential human cervical epithelial carcinoma cell line inhibition properties based on the computer aided drug design models and in-vitro activity.

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.

Iridoids and other constituents from the leaves and stems of Valeriana officinalis var. latifolia.

Fifty-nine compounds, including nineteen previously undescribed iridoids (valeriananols A-S) and an undescribed alkaloid (5'-isovaleryl uridine), were isolated from the leaves and stems of Valeriana officinalis var. latifolia. Their structures were elucidated based on Mass spectrometry and NMR spectroscopy. The absolute configuration of valeriananols A-C, E-N, P, Q and S was determined by experimental and calculated electronic circular dichroism. Structurally, valeriananols A and B were two 1,3-seco-iridoids with a 3,6-epoxy moiety, valeriananols K and L were a pair of C-4 epimers, while valeriananol S was a 4'-deoxy iridoid glycoside. In addition, valeriananol P, stenopterin A and patriscabioin C exhibited significant inhibition on nitric oxide production with IC50 values of 10.31, 3.93 and 8.69 µM, respectively. Furthermore, stenopterin A and patriscabioin C showed anti-proliferation activity on the MCF-7 cell line with IC50 values of 17.28 and 13.89 µM, respectively.

Simultaneously characterization of multiple constituents in Valeriana jatamansi Jones using an online supercritical fluid extraction-high-performance liquid chromatography/supercritical fluid chromatography-mass spectrometry system.

Valeriana jatamansi Jones is a commonly used traditional Chinese medicine, boasting rich effective compositions with versatile chemical structures and wide polarity, including iridoids, chlorogenic acid, and flavonoids. Previous reports indicate that conventional high-performance liquid chromatography (HPLC) analytical methods have proven inefficient performance in comprehensively characterizing components in Valeriana jatamansi. In the present study, a hybrid online analytical platform combining supercritical fluid extraction with both conventional HPLC separation (reverse phase) and supercritical fluid chromatography (normal phase) has been established and validated. This system can provide online extraction with two different chromatographic separation modes to increase separation ability and has been connected to a mass spectrometer to acquire high-resolution mass spectrometry data. Then, the online platform was applied to screening components in Valeriana jatamansi. A total of 117 compounds were identified, including five lignans, 18 organic acids, six flavonoids, and 88 iridoids. Thirty-three compounds were reported from Valeriana jatamansi for the first time. These results enrich our understanding of the components of Valeriana jatamansi and prove that the developed online platform in this study is a robust approach for accelerating working efficiency in comprehensively analyzing complicated samples.

Mechanism of Valeriana Jatamansi Jones for the treatment of spinal cord injury based on network pharmacology and molecular docking.

Spinal cord injury (SCI) is characterized by high rates of disability and death. Valeriana jatamansi Jones (VJJ), a Chinese herbal medicine, has been identified to improve motor function recovery in rats with SCI. The study aimed to analyze the potential molecular mechanisms of action of VJJ in the treatment of SCI. The main ingredients of VJJ were obtained from the literature and the SwissADME platform was used to screen the active ingredients. The Swiss TargetPrediction platform was used to predict the targets of VJJ, and the targets of SCI were obtained from the GeneCards and OMIM databases. The intersecting genes were considered potential targets of VJJ in SCI. The protein-protein interaction network was constructed using the STRING database and the hub genes of VJJ for SCI treatment were screened according to their degree values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape database. Cytoscape software was used to construct the "herb-ingredient-target-pathway" network. Preliminary validation was performed using molecular docking via Auto Dock Vina software. A total of 56 active ingredients of VJJ, mainly iridoids, were identified. There were 1493 GO items (P < .01) and 173 signaling pathways (P < .01) obtained from GO and Kyoto Encyclopedia of Genes and Genomes enrichment, including the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, hypoxia-inducible factor 1 signaling pathway, and tumor necrosis factor signaling pathway. Molecular docking revealed that 12 hub genes enriched in the PI3K/Akt signaling pathway had a high binding affinity for the active ingredient of VJJ. VJJ may exert its therapeutic effects on SCI through the iridoid fraction, acting on signal transducer and activator of transcription 3, CASP3, AKT1, tumor necrosis factor, mammalian target of rapamycin, interleukin 6, and other hub genes, which may be related to the PI3K/Akt signaling pathway.