In silico investigation on the probable macromolecular drug targets involved in the anti-schizophrenia activity of Nardostachys jatamansi

Abstract Existing medications i.e. the antipsychotic drugs are known to be effective in treating only the positive symptoms of schizophrenia, while being ineffective on negative and cognitive symptoms of the disease. In addition, these medications cause extrapyramidal symptoms, forcing many patients towards natural medicine in the hope of minimizing the unwanted adverse effects. Nardostachys jatamansi is a medicinal plant that has been traditionally prescribed for various types of brain disorders. The active constituents of the plant have beneficial effects on the negative and cognitive symptoms of schizophrenia. This study was designed to identify the active constituents of Nardostachys jatamansi with the highest binding affinities for the key macromolecular drug targets involved in the pathophysiology of schizophrenia and thereby elucidate the possible mechanism of action. These targets are dopamine receptors, Gamma-aminobutyric acid receptors, N-methyl-D-aspartate receptors and Phosphodiesterase 10A. The results of molecular docking showed that, β-sitosterol, chlorogenic acid, oleanic acid and ursolic acid, displayed high binding affinity toward all the macromolecular drug targets. Ligands with steroid backbone and pentacyclic triterpene structure have been found to possess high binding affinity toward the dopamine receptor and phosphodiesterase 10A. While ligands with carbonyl group form stronger binding interactions with the N-methyl-D-aspartate receptor.

Effects of Nardostachys jatamansi on gut microbiota of rats with Parkinson's disease / 中国中药杂志

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1β, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.

Inhibitory Effects of Methanol Extract from Nardostachys chinensis on 27-hydroxycholesterol-induced Differentiation of Monocytic Cells

27-Hydroxycholesterol (27OHChol) has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined the effect of methanol extract of Nardostachys chinensis (Nard) on 27OHChol-induced differentiation using THP-1, a human monocytic cell line. Treatment of monocytic cells with methanol extract of Nard resulted in decreased transcription and surface expression of CD80, CD83, and CD88 elevated by 27OHChol in a dose-dependent manner. Surface levels of MHC class I and II molecules elevated by 27OHChol were also reduced to basal levels by treatment with the Nard extract. Decreased endocytosis activity caused by 27OHChol was recovered by treatment with the Nard extract. CD197 expression and cell attachment were attenuated by the Nard extract. In addition, levels of transcription and surface expression of CD molecules involved in atherosclerosis, such as CD105, CD137, and CD166 upregulated by 27OHChol were significantly decreased by treatment with methanol extract of Nard. These results indicate that methanol extract of Nard down-regulates 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules associated with atherosclerosis. The current study suggests that biological activity of oxygenated cholesterol derivatives can be inhibited by herbal medication.

A new caffeate compound from Nardostachys chinensis / 药学学报

A new caffeate compound, (E)-erythro-syringylglyceryl caffeate (1), was isolated from the roots and rhizomes of Nardostachys chinensis Batal., together with nine known phenolic compounds, including (+)-licarin A (2), naringenin 4', 7-dimethyl ether (3), pinoresinol-4-O-β-D-glucoside (4), caraphenol A (5), Z-miyabenol C (6), protocatechuic acid (7), caffeic acid (8), gallic acid (9) and vanillic acid (10). Their chemical structures were elucidated on the basis of spectroscopic data and physicochemical properties. Furthermore, this is the first report of compounds 2, 5 and 6 from Nardostachys genus.

Anti-neuro-inflammatory effects of Nardostachys chinensis in lipopolysaccharide-and lipoteichoic acid-stimulated microglial cells / 中国天然药物

Excessive microglial cell activation is related to the progression of chronic neuro-inflammatory disorders. Heme oxygenase-1 (HO-1) expression mediated by the NFE2-related factor (Nrf-2) pathway is a key regulator of neuro-inflammation. Nardostachys chinensis is used as an anti-malarial, anti-nociceptive, and neurotrophic treatment in traditional Asian medicines. In the present study, we examined the effects of an ethyl acetate extract of N. chinensis (EN) on the anti-neuro-inflammatory effects mediated by HO-1 up-regulation in Salmonella lipopolysaccharide (LPS)- or Staphylococcus aureus lipoteichoic acid (LTA)-stimulated BV2 microglial cells. Our results indicated that EN suppressed pro-inflammatory cytokine production and induced HO-1 transcription and translation through Nrf-2/antioxidant response element (ARE) signaling. EN markedly inhibited LPS- and LTA-induced activation of nuclear factor-kappa B (NF-κB) as well as phosphorylation of mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT). Furthermore, EN protected hippocampal HT22 cells from indirect neuronal toxicity mediated by LPS- and LTA-treated microglial cells. These results suggested that EN impairs LPS- and LTA-induced neuro-inflammatory responses in microglial cells and confers protection against indirect neuronal damage to HT22 cells. In conclusion, our findings indicate that EN could be used as a natural anti-neuro-inflammatory and neuroprotective agent.

Antioxidant effect and study of bioactive components of Valeriana sisymbriifolia and Nardostachys jatamansii m comparison to Valeriana officinalis

The roots of Nardostachys jatamansi have been used as a substitute for valerian in Iranian traditions. Moreover, six species from Valeriana genus such as V. sisymbriifolia grow in Iran which has not been studied yet. We aimed to study of antioxidant effect of Valeriana officinalis, Nardostachys jatamansi and Valeriana sisymbriifolia and comparing their content of valerenic acid and valepotriate. Antioxidant effect was evaluated using diphenylpicrylhydrazyl [DPPH] inhibition and beta carotene-bleaching assays. Identification of valepotriates was achieved using chemical and TLC method. Qualitative and quantitative analysis of valerenic acid was performed using TLC and spectrophotometry methods. Among the tested samples, V. Officinalis showed the highest DPPH inhibition effect with IC[50] value of 38mg/mL. All of the tested plants potentially inhibited beta-carotene oxidation. The calibration curve of authentic valerenic acid was linear in the range of 2-51 mg L[-1] The most and least amount of valepotraites was detectable in V. officinalis and V. sisymbriifolia respectively. Total valerenic acid in different plant species ranged from 0.02% in V. sisymbriifolia to 0.07% [w/w] in V. Officinalis. Our results indicated that all three tested plants contain different amount of valepotriates and valerenic acid. The highest percentage of valepotriates and valerenic acid was detectable in V. officinalis. Overall can conclude that N. jatamansii and V. sisymbriifolia would be a good candidate for substitutation of V. officinalis with noticeable antioxidant effect

Study on two preparation methods for beta-CD inclusion compound of four traditional Chinese medicine volatile oils / 中国中药杂志

<p><b>OBJECTIVE</b>To compare inclusion effects and process conditions of two preparation methods-colloid mill and saturated solution-for beta-CD inclusion compound of four traditional Chinese medicine volatile oils and study the relationship between each process condition and volatile oil physical properties and the regularity of selective inclusion of volatile oil components.</p><p><b>METHOD</b>Volatile oils from Nardostachyos Radix et Rhizoma, Amomi Fructus, Zingiberis Rhizoma and Angelicaesinensis Radix were prepared using two methods in the orthogonal test. These inclusion compounds by optimized processes were assessed and compared by such methods as TLC, IR and scanning electron microscope. Inclusion oils were extracted by steam distillation, and the components found before and after inclusion were analyzed by GC-MS.</p><p><b>RESULT</b>Analysis showed that new inclusion compounds, but inclusion compounds prepared by the two processes had differences to some extent. The colloid mill method showed a better inclusion effect than the saturated solution method, indicating that their process conditions had relations with volatile oil physical properties. There were differences in the inclusion selectivity of components between each other.</p><p><b>CONCLUSION</b>The colloid mill method for inclusion preparation is more suitable for industrial requirements. To prepare volatile oil inclusion compounds with heavy gravity and high refractive index, the colloid mill method needs longer time and more water, while the saturated solution method requires higher temperature and more beta-cyclodextrin. The inclusion complex prepared with the colloid mill method contains extended molecular weight chemical composition, but the kinds of components are reduced.</p>

Preparation of beta-CD inclusion of volatile oil from Nardostachyos Radix et Rhizoma / 中国中药杂志

<p><b>OBJECTIVE</b>To study optimal process conditions for the inclusion of volatile oil from Nardostachyos Radix et Rhizoma using saturated water solution method.</p><p><b>METHOD</b>The optimal technology of inclusion was identified respectively by the utilization ratio of volatile oils and the yield of inclusion compound in an orthogonal experiment design, and the inclusion efficiency was evaluated by TLC, UV, IR, SE and GC-MS.</p><p><b>RESULT</b>The optimum preparation conditions for inclusion were established as follows: volatile oil: beta-CD was 1: 6, the inclusion temperature was 40 degrees C, the stirring speed and time were in 300 r x min(-1) and for 1 h. The analysis results showed that a new substance was conformed. The change of the volatile oil component was found before and after inclusion.</p><p><b>CONCLUSION</b>The optimal process conditions are easy for operation, and high in utilization ratio of volatile oils and the yield of inclusion compound.</p>

Stress modulating antioxidant effect of Nardostachys jatamansi.

The rhizomes of Nardostachysjatamansi, the plant commonly known as Jatamansi have been described in Ayurveda for their soothing and sedative action on the central nervous system. In the present study, the anti-stress effect of hydroethanolic extract (70%) of N. jatamansi (NJE) was evaluated in reference to its antioxidant property. Wistar rats were divided into four groups: naive, stressed, and T-200 and T-500 stressed with oral pre-treatment of NJE 200 and 500 mg/kg, respectively. Restraint of rats in metallic chambers for 4 h at 4 degreesC was followed by sacrifice and assessment of stress-induced alterations in biochemical parameters, incidence and severity of ulcers. Lipid peroxidation (LPO) and NO levels in stomach and LPO, NO levels and catalase activity in brain, plasma corticosterone level and adrenal ascorbic acid were measured. In vitro antioxidant activity of NJE was studied by measuring the free radical scavenging activity. NJE showed potent antioxidant activity and significantly reversed the stress-induced elevation of LPO and NO levels and decrease in catalase activity in the brain. It inhibited the incidence of gastric ulcerations and reversed the alterations in biochemical parameters/markers of stress-induced gastric ulceration. NJE also significantly altered stress-induced increase in adrenal and spleen weights and decrease in level of ascorbic acid in adrenal gland. Elevation of plasma corticosterone level was negated dose- dependently. The findings suggest that the NJE possesses significant anti-stress activity, which may be due to its antioxidant activity.

Inhibition of MAO and GABA: probable mechanisms for antidepressant-like activity of Nardostachys jatamansi DC. in mice.

Ethanolic extract (100, 200 and 400 mg/kg, po) of N. jatamansi administered for 14 successive days to Swiss young albino mice (either sex) produced significant antidepressant-like effect in both tail suspension and forced swim tests. The efficacy of the extract was found to be comparable to imipramine (15 mg/kg, po) and sertraline (20 mg/kg, po). Ethanolic extract (200 mg/kg, po) did not show any significant change on locomotor activity of mice as compared to control; hence it did not produce any motor effects. Further, the extract decreased the whole brain MAO-A and MAO-B activities as compared tocontrol, thus increased the levels of monoamines. The antidepressant effect of the extract was also significantly reversed by pretreatment of animals with baclofen (GABAB agonist); when tested in tail suspension test. The results suggested that the antidepressant-like effect of the extract may also be due to interaction with GABAB receptors, resulting in decrease in the levels of GABA in mouse brain. Thus, the extract may have potential therapeutic value for the management of mental depression.

role of herbal drugs in psychiatry

The therapeutic uses of various herbal drugs for psychiatric disorders have a long tradition in India, China and other Asian cultures. The unwanted side effects of synthetic psychotropics have contributed to the increasing interest in phytotherapeutic agents. Improved understanding of appropriate and safe uses of naturally occurring substances as psychotropic agents will greatly contribute to global mental care. An important objective of this paper is to stress the scientific evidence, supporting the use of natural products in psychiatry. Traditional Ayurvedic drugs used in psychiatry is briefly discussed. Knowledge of the properties of these therapies supported by clinical evidence, efficacy and safety profile can improve the care of psychiatric patients

Clinical evaluation of Unani formulation in myocardial ischaemia

Coronary Artery Disease [CAD] plays a major role in mortality worldwide. Thus there is a great challenge before clinicians to find out safe and effective therapy. There are some Unani drugs like Badranjaboya, Balchar, Jadwar and Arjun whose efficacy is mentioned in Unani literature without any known side effect. A clinical trial of these drugs on 60 patients of ischaemia was carried out which were selected on the ground of clinical presentation, ECG findings and ventricular dyskinesia in 2D, M-mode echocardiography. Drugs were given in the powder form orally [10 gm powder in two divided doses], study duration was set for two months and efficacy of the formulation was evaluated following modern parameters