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Comparative and Functional Screening of Three Species Traditionally used as Antidepressants: Valeriana officinalis L., Valeriana jatamansi Jones ex Roxb. and Nardostachys jatamansi (D.Don) DC.

ABSTRACT: The essential oils (EOs) of three Caprifoliaceae species, the Eurasiatic Valeriana officinalis (Vo), the Himalayan Valeriana jatamansi (Vj) and Nardostachys jatamansi (Nj), are traditionally used to treat neurological disorders. Roots/rhizomes micromorphology, DNA barcoding and EOs phytochemical characterization were carried out, while biological effects on the nervous system were assessed by acetylcholinesterase (AChE) inhibitory activity and microelectrode arrays (MEA). Nj showed the highest inhibitory activity on AChE (IC50 67.15 ?g/mL) followed by Vo (IC50 127.30 ?g/mL) and Vj (IC50 246.84 ?g/mL). MEA analyses on rat cortical neurons, carried out by recording mean firing rate (MFR) and mean bursting rate (MBR), revealed stronger inhibition by Nj (IC50 18.8 and 11.1 ?g/mL) and Vo (16.5 and 22.5 ?g/mL), compared with Vj (68.5 and 89.3 ?g/mL). These results could be related to different EO compositions, since sesquiterpenes and monoterpenes significantly contribute to the observed effects, but the presence of oxygenated compounds such as aldehydes and ketones is a discriminating factor in determining the order of potency. Our multidisciplinary approach represents an important tool to avoid the adulteration of herbal drugs and permits the evaluation of the effectiveness of EOs that could be used for a wide range of therapeutic applications.

SUBMITTER: Cornara L

PROVIDER: S-EPMC7464919 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Comparative and Functional Screening of Three Species Traditionally used as Antidepressants: Valeriana officinalis L., Valeriana jatamansi Jones ex Roxb. and Nardostachys jatamansi (D.Don) DC.

Cornara Laura L Ambu Gabriele G Trombetta Domenico D Denaro Marcella M Alloisio Susanna S Frigerio Jessica J Labra Massimo M Ghimire Govinda G Valussi Marco M Smeriglio Antonella A

Plants (Basel, Switzerland) 20200805 8

The essential oils (EOs) of three Caprifoliaceae species, the Eurasiatic Valeriana officinalis (Vo), the Himalayan Valeriana jatamansi (Vj) and Nardostachys jatamansi (Nj), are traditionally used to treat neurological disorders. Roots/rhizomes micromorphology, DNA barcoding and EOs phytochemical characterization were carried out, while biological effects on the nervous system were assessed by acetylcholinesterase (AChE) inhibitory activity and microelectrode arrays (MEA). Nj ...[more]

PMID: 32764268

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Project description:Zhi zhu xiang (ZZX) is the root and rhizome of Valeriana jatamansi Jones ex Roxb. Recent studies have shown that ZZX can exert antianxiety, antidepressant, and sedative effects. Because post-traumatic stress disorder (PTSD) is similar to depression and anxiety in terms of its etiology, pathogenesis, and clinical manifestations, it is possible that ZZX may also be useful for the prevention and treatment of PTSD. In this study, a mouse model of PTSD was established and used to study the pharmacological action of a 95% ethanol extract of ZZX on PTSD via a series of classic behavioral tests. We found that a 95% ethanol extract of ZZX was indeed effective for relieving the symptoms of PTSD in mice. Moreover, network pharmacology analysis was used to predict the potential active ingredients, targets, and possible pathways of ZZX in the treatment of PTSD. The neurotransmitter system, the hypothalamic-pituitary-adrenal (HPA) axis, and the endocannabinoid (eCB) system were identified to be the most likely pathways for anti-PTSD action in ZZX. Due to the lack of a falsification mechanism in network pharmacology, in vivo tests were carried out in mice, and the expression levels of neurotransmitters, hormones, and genes of key targets were detected by enzyme-linked immunosorbent assay and real-time PCR to further verify this inference. Analysis showed that the levels of norepinephrine, 5-hydroxytryptamine, and glutamic acid were increased in the hippocampus, prefrontal cortex, and amygdala of PTSD mice, while the levels of dopamine and γ-aminobutyric acid were decreased in these brain regions; furthermore, ZZX could restore the expression of these factors, at least to a certain extent. The levels of adrenocorticotropic hormone, corticosterone, and corticotropin-releasing hormone were increased in these different brain regions and the serum of PTSD mice; these effects could be reversed by ZZX to a certain extent. The expression levels of cannabinoid receptor 1 and diacylglycerol lipase α mRNA were decreased in PTSD mice, while the levels of fatty acid amide hydrolase and monoacylglycerol lipase mRNA were increased; these effects were restored by ZZX to a certain extent. In conclusion, our findings suggest that ZZX may provide new therapeutic pathways for treating PTSD by the regulation of neurotransmitters, the HPA, and expression levels of eCB-related genes in the brain.

Project description:The roots and rhizomes of Valeriana jatamansi have long been used as folk medicine in Asia and usually named as "Zhizhuxiang" in Chinese for the treatment of abdominal distention and pain. However, its active ingredients and molecular targets for treatment of abdominal pain remain unrevealed. Inhibitors of Cav2.2 N-type voltage-gated calcium channels (VGCCs) are actively sought after for their potential in treating pain, especially chronic pain. As far as we know, the method used for seeking analgesic active ingredient from plant material has rarely been reported. The analgesic potentials of the EtOH extract (0.01 mg/ml) of the roots and rhizomes of V. jatamansi and its EtOAc, n-BuOH and H2O soluble parts (0.01 mg/ml, respectively) were tested herein on Cav2.2, using whole-oocyte recordings in vitro by tow-electrode voltage clamp. The results indicated that the EtOAc-soluble part exhibited the most potent inhibition of Cav2.2 peak current (20 mv). The EtOAc-soluble part was then subjected to silica gel column chromatography (CC) and giving 9 fractions. Phytochemical studies were carried out by repeated CC and extensive spectroscopic analyses after the fraction (0.01 mg/ml) was identified to be active and got seventeen compounds (1-17). All isolates were then sent for further bioactive verification (1 and 3 at concentration of 10 μM, others at 30 μM). In addition, the selectivity of the active compounds 1 and 3 were tested on various ion channels including Cav1.2, Cav2.1 and Cav3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. The results indicated that compound 1 and 3 (an abundant compound) inhibited Cav2.2 with an EC50 of 3.3 and 4.8 μM, respectively, and had weaker or no effect on Cav1.2, Cav2.1 and Cav3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. Compounds 1 and 3 appear to act as allosteric modulators rather than pore blockers of Cav2.2, which may play crucial role in attenuating nociception. The results of present research indicated that the ethnopharmacological utilization of V. jatamansi for relieving the abdominal distention and pain may mediate through Cav2.2 channel. Our work is the first demonstration of inhibition of Cav2.2 by iridoids, which may provide a fresh source for finding new analgesics.

Dataset Information

Comparative and Functional Screening of Three Species Traditionally used as Antidepressants: Valeriana officinalis L., Valeriana jatamansi Jones ex Roxb. and Nardostachys jatamansi (D.Don) DC.

Publications

Comparative and Functional Screening of Three Species Traditionally used as Antidepressants: <i>Valeriana officinalis</i> L., <i>Valeriana jatamansi</i> Jones ex Roxb. and <i>Nardostachys jatamansi</i> (D.Don) DC.

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