Nardostachys Jatamansi DC Research Articles

Jatamansinol from Nardostachys jatamansi (D.Don) DC. Protects Aβ42-Induced Neurotoxicity in Alzheimer's Disease Drosophila Model

Nardostachys jatamansi (D. Don) DC. is an essential plant used in Indian Ayurveda to treat neurological disorders, and it enhances memory. Its active phytochemical(s) responsible for neuroprotection is not yet studied. One of the neurological disorders, namely Alzheimer's disease (AD) causes dementia, is not having pharmacological strategies to effectively prevent the onset of AD, cure or reverse AD progression, and treat cognitive symptoms. Here is an attempt to analyze the neuroprotective effect of jatamansinol isolated from N. jatamansi against Aβ42 protein-induced neurotoxicity using the Aβ42 protein expressed Drosophila Alzheimer's disease (AD) model. Oregon-K (OK) and AD flies were reared on regular or jatamansinol supplemented food and analyzed for their lifespan, locomotor activity, learning and memory, eye degeneration, oxidative stress levels, antioxidant activities, cholinesterase activities, Aβ42 protein, and Aβ42 gene expression. Jatamansinol extends the lifespan, improves locomotor activity, enhances learning and memory, and reduces Aβ42 protein levels in AD flies. Jatamansinol boosts the antioxidant enzyme activities, prevents Aβ42 protein-induced oxidative stress, ameliorates eye degeneration, and inhibits cholinesterase activities in the AD model. This study evidences the protective effect of jatamansinol against the Aβ42 protein-induced neurotoxicity in the AD Drosophila model, suggesting its possible therapeutic potential against AD.

Physiological insights into the role of temperature and light conditions on in vitro growth, membrane thermostability and antioxidative activity of Nardostachys jatamansi, an IUCN Red-listed critically endangered therapeutic plant

Habitat modifications induced by rapid climate change and anthropogenic activities over the years have led to the extinction or confinement of many plant species in their geographic ranges. Temperature and light are the major determinants in controlling plant growth; each plant species having specific temperature and light requirements for their development and proper functioning of the photosynthetic activity. An efficient in vitro propagation protocol via callus-mediated organogenesis from rhizome segments has been developed for Nardostachys jatamansi (D. Don) DC. or ‘Jatamansi’, an IUCN Red-listed critically endangered plant species of immense medicinal importance. To understand the temperature and light sensitivity, and oxidative stress response of this plant, the micro-shoots were raised in vitro in the culture room (24 ± 2 °C, 50 µmol m−2 s−1 PPFD) and growth chamber (13 ± 2 °C, 850 µmol m−2 s−1 PPFD) mimicking the natural habitats. Maximum shoot regeneration (84.5%) and number of shoots (16.8 ± 0.2) per explant were observed in MS medium supplemented with 1.0 mg/l meta-Topolin and 0.5 mg/l indole acetic acid under low temperature and higher light intensity in the growth chamber. The genetic fidelity was assessed using flow cytometry and no major genetic abnormalities was observed among the regenerants. The activities of antioxidant enzymes like superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase under same culture conditions were also recorded to have increased which revealed their active involvement against oxidative stress. On the other hand, a significant decline in these enzyme activities was observed in cultures incubated in culture room indicating impaired detoxification which could be due to their inactivation at high temperature and low light intensity. It was also observed that prolonged culture of in vitro-grown shoots in the culture room led to increased cell membrane damage, lipid peroxidation and higher endogenous H2O2 accumulation with reduced level of photosynthetic pigment contents, exhibiting severe oxidative stress. The in vitro-grown shoots were better maintained under conditions mimicking the natural conditions of growth which substantiated the understanding of survival strategies of this critically endangered plant species.

Jatamansinol from Nardostachys jatamansi: a multi-targeted neuroprotective agent for Alzheimer’s disease

Alzheimer’s disease (AD) is a multifactorial progressive and irreversible neurodegenerative disorder characterized by severe memory impairment and cognitive disability in the middle and old-aged human population. There are no proven drugs for AD treatment and prevention. In Ayurveda, medhya plants are used to prepare Rasayana, and its consumption improves memory and cognition. Nardostachys jatamansi (D.Don) DC is a medhya plant used in traditional medicine to treat neurological disorders, and its unique pyranocoumarins can be a potential drug candidate for AD. Given its traditional claims, this study aims to find the multi-target potential efficacy of the ligands (drug molecules) against the AD from N. jatamansi pyranocoumarins using computational drug discovery techniques. Drug likeliness analysis confirms that pyranocoumarins of N. jatamansi, such as seselin, jatamansinol, jatamansine, jatamansinone, and dihydrojatamansin are probable drug candidates for AD. Molecular docking, molecular dynamic simulations, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis confirm that dihydrojatamansin inhibits acetylcholinesterase (AChE), and jatamansinol inhibits butyrylcholinesterase (BuChE), glycogen synthase kinase 3β (GSK3β), and kelch-like ECH-associating protein 1 (Keap1) AD therapeutic targets. Therefore, this study provides potential multi-target inhibitors that would further validate experimental studies, leading to new treatments for AD. Communicated by Ramaswamy H. Sarma

Narjatamolide, an Unusual Homoguaiane Sesquiterpene Lactone from Nardostachys jatamansi.

Narjatamolide (1), an unusual homoguaiane sesquiterpene lactone, was isolated from the roots and rhizomes of Nardostachys jatamansi DC. It represents the new carbon skeleton of a homoguaiane sesquiterpenoid possessing an additional acetate unit spiro-fused with C-4 and C-15 to form a cyclopropane ring. The structure of 1 was elucidated by extensive spectroscopic analyses, and the absolute configuration was confirmed by the electronic circular dichroism (ECD) calculations and X-ray single-crystal diffraction analysis. Compound 1 showed antiproliferative effects against BEL-7402 cell lines with an IC50 value of 5.67 ± 1.43 μM, and the mechanism study showed that 1 induces cell cycle of BEL-7402 cell lines arrest at G2/M phase.

Effect of Nardostachys jatamansi DC. on Apoptosis, Inflammation and Oxidative Stress Induced by Doxorubicin in Wistar Rats.

The study aimed to investigate the protective action of jatamansi (Nardostachys jatamansi DC.) against doxorubicin cardiotoxicity. Methanolic extract of jatamansi (MEJ) was prepared and standardized using HPTLC fingerprinting, GC-MS chemoprofiling, total phenolic content, and antioxidant activity in vitro. Further in vivo activity was evaluated using rodent model. Animals were divided into five groups (n = 6) namely control (CNT) (Normal saline), toxicant (TOX, without any treatment), MEJ at low dose (JAT1), MEJ at high dose (JAT2), and standard desferrioxamine (STD). All groups except control received doxorubicin 2.5 mg per Kg intra-peritoneally for 3 weeks in twice a week regimen. After 3 weeks, the blood samples and cardiac tissues were collected from all groups for biochemical and histopathological evaluation. Treatment with MEJ at both dose levels exhibited significant reduction (p < 0.001 vs. toxicant) of serum CK-MB (heart creatine kinase), LDH (Lactate dehydrogenase) & HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) levels, and tissue MDA (melondialdehyde) level; insignificant difference was observed (p > 0.05) in TNF-alpha (tumour necrosis factor), IL-6 (interleukine-6) levels and caspase activity as compared to TOX. Histopathological evaluation of cardiac tissues of different treatment groups further reinforced the findings of biochemical estimation. This study concludes that jatamansi can protect cardiac tissues from oxidative stress-induced cell injury and lipid peroxidation as well as against inflammatory and apoptotic effects on cardiac tissues.

Efficacy and Toxicity Study of Nardostachys Jatamansi DC and Valeriana Wallichii DC in Sleep Disorders

Background: Sleep disorders are common in general population and adversely affects the health related quality of life. Many people do not want to rely upon allopathic drug easily available over the counter because of their side effects. Cases of sleep disorders have exponentially increased during pandemic (Covid -19) and new term Covid-somnia have been coined for the same. Two Perennial herbs from Valerianeaceae family i.e Nardostachys jatamansi DC and Valeriana wallicii DC which are known as high value medicinal plants were selected for the study. Nardostachys jatamansi DC is used in the treatment of epilepsy, hysteria, convulsive ailments whereas rhizome of Valeriana wallicii DC have shown anxiolytic, stress releasing and antidepressant effects.Materials and Methods: The present study was undertaken to evaluate the efficacy and toxicity of the selected herbs for Sleep Disorders. A dose dependent Phenobarbitone - induced sleep time measurement study was performed. Further measure the effect of motor coordination, walking assay was performed.Results and Conclusions: Results of acute toxicity study and Irwin test indicated that selected extracts of Nardostachys jatamansi DC and Valeriana wallichii are safe. Further dose dependent Phenobarbitone - induced sleep time measurement study showed significant increase in selected three doses for this study (125, 250, 500 mg/kg body weight compared to control. The result of the study demonstrated that oral administration of extracts produced a dose-dependent decrease in sleep latency and increase in sleep duration in mice treated with extracts. These extracts exhibited a non- significant reduction in the number of foot slips in non-dose dependent manner relative to Phenobarbitone treated group.

Correlation analysis between genetic and chemical differences of Nardostachys jatamansi from different habitats in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China

In the traditional Tibetan medicinal system, the medicinal parts of Nardostachys jatamansi (D.Don) DC. include the dried roots and rhizomes, which is effective in treating various diseases. In this study, molecular evolutionary analysis based on three markers (i.e., ITS, matK and rbcL), and principal component analysis (PCA) combined with 1H NMR measurements were used to assess the genetic and chemical differences of the N. jatamansi from different habitats in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China. The results showed that the ITS marker was highly effective to identify the intraspecific variation of N. jatamansi. Furthermore, the results of the chemical analysis indicated that the nardosinone and sucrose, as the metabolite landmarks, can distinguish the different habitats of N. jatamansi in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China. Moreover, combining the chemical analysis with phylogenetic analysis, the results indicated that the metabolites differences may be affected not only by genetic structures but also by environmental factors. These findings provide valuable references for the effective protection and exploitation of N. jatamansi resources.

Determination of Inorganic Element Concentrations in Nardostachys jatamansi DC

Background:: Nardostachys jatamansi DC. is indigenous to the Himalayan regions of India and Tibetan plateau of China, and widely used as drugs for treating various neurological disorders, insomnia, hysteria and depressive illness. However, beyond the huge efforts to the organic components in N. jatamansi, the elemental contents have not been investigated, which are important for the quality control and biosafety evaluation of N. jatamansi. Objective:: In this study, we quantified the element concentrations in N. jatamansi. Methods:: Twenty-five N. jatamansi samples were collected in Sichuan, Tibet, Qinghai and Gansu provinces. The samples were digested and subjected to inductively coupled plasma optical emission spectrometer (ICP-OES) measurements. Results:: The results indicated that Al, B, Ba, Ca, Cd, Co, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, P, Pd, Si, Sr, Ti and Zn were detected in N. jatamansi samples. The chemometrics approaches indicated that N. jatamansi samples from Sichuan and Tibet shared similar elemental patterns. The altitude did not statistically influence the elemental patterns of N. jatamansi samples, while the K, P, Ba and Cd showed meaningful decreases. The high Ba contents in all samples suggested the potential toxicity of heavy metal to patients. Conclusion:: The inorganic element quantification of N. jatamansi is useful in the genuine regional drug identification, quality control and biosafety evaluations.

Efficacy of Nardostachys jatamansi (D.Don) DC in essential hypertension: A randomized controlled study

BackgroundNardostachys jatamansi (D.Don) DC, commonly known as muskroot and Indian spikenard, is a small, perennial, flowering, rhizomatous species of the Caprifoliaceae family. Nardostachys jatamansi (D.Don) DC (Sumbul-ut-teeb) has been used in Unani Medicine since antiquity. It is one of the important drugs mentioned by Ibn-e-Sina (Avicenna) in his treatise “Kitab al-Adwiya al- Qalbiya” for cardiac diseases. The drug has been shown to exhibit anxiolytic, sedative, antispasmodic, tranquillizing, and anti hypertensive activity. AimThe aim of the present study was to examine the efficacy of Nardostachys jatamansi in reducing blood pressure in hypertensive patients. MethodsThe single blind randomized, placebo controlled study was conducted with 40 patients aged between 35–70 years. The participants were randomly allocated to receive either a total of 3 g of N. Jatamansi (1capsule 3 times a day) or placebo for 4 weeks. Patients using ≤ 2 antihypertensive drugs with stage 1 hypertension were included in the study. Systolic and diastolic Blood pressure was recorded at baseline and at every week for four weeks. MINICHAL score (for Quality of Life) was recorded at baseline and at the end of the trial. ResultsAfter the four weeks of treatment, there was a statistically significant reduction in average systolic blood pressure 144.20 ± 11.35 mmHg (CI, 138.89–149.51) to 134.30 ± 10.08 mmHg (CI, 129.58–139.02), p < 0.001) and diastolic blood pressure (94.9. ± 3.4 mmHg (CI 93.30–96.49) to 83.10 ± 5.29 mmHg (CI 80.62–85.57), p < 0.001) in the N. Jatamansi group whereas there was no significant difference in systolic blood pressure (143.40 ± 8.39 mmHg (CI, 139.47–147.33) to 142. ± 11.68 mmHg (CI, 136.53–147.47) p = 0.148) and diastolic blood pressure 95.10 ± 3.70 mmHg (CI, 93.37–96.83) to 94.80 ± 3.69 mmHg, (CI93.07–96.52) p = 0.186) in placebo group. A comparison between baseline and post treatment, MINICHAL score in N. Jatamansi group showed significant reduction 10.85 ± 1.27 (CI, 10.25–11.44) to 6.20 ± 1.77, (CI, 5.37–7.02) p < 0.001) whereas there was no significant difference in placebo group 11.05 ± 1.50 (CI, 10.34–11.75) to 10.85 ± 1.26, 95 % (CI, 10.25–11.44) p = 0.103). ConclusionThe present findings suggest that N. Jatamansi is effective in reducing both systolic and diastolic blood pressure in essential hypertension. Moreover studies on efficacy of different doses and treatment duration of test drug are required to finetune these observations.

Central nervous system depressant activity of Jatamansi (Nardostachys jatamansi DC.) rhizome.

Background:Sleep disorders have a comparatively high prevalence worldwide and create a burden on the health system. Pharmacological agents used for insomnia are associated with considerable side effects. Therefore, searching for safe and effective agents from plant-based natural sources is a worthy effort. Jatamansi (Nardostachys jatamansi DC.) rhizome has been recommended for insomnia and mental conditions in the Indian system of medicine.Aim:This study aimed to determine central nervous system (CNS) depressant activity of Jatamansi (N. jatamansi) rhizome on experimental animals.Materials and methods:Gross behavior study and open field test (locomotor activity) were performed by using Charle’s foster albino rats whereas rota-rod test and pentobarbital-induced sleep test in Swiss albino mice. Animals were divided into 3 groups (per model) having six animals in each group. The control group was treated with water, the standard group with diazepam and the test drug with powder of N. Jatamansi rhizome. Results were calculated by one-way ANOVA and post hoc test with P < 0.05 as significant.Results:Data suggested that Jatamansi did not produce a significant effect on the behavior of animals. It reduced the horizontal activity significantly (P < 0.001) in the open field apparatus. The test drug did not show a significant decrease in latency of fall-off time in rota-rod performance in mice. Still, it exerted a significant effect by a reduction in latency of onset of sleep (P < 0.01) and also extended the total duration of sleep (P < 0.05) in albino mice in comparison to the control group.Conclusion:This study shows that Jatamansi rhizome powder possesses CNS depressant activity without affecting gross behavior and muscle coordination in rats.

Efficacy of a vaginal tablet as a Persian medicine product on vulvovaginal candidiasis: a double-blind, randomised, placebo-controlled trial

Context In Persian medicine, topical ingredients such as Rosa damascena Mill. (Rosaceae), are usually recommended for the treatment of uterine diseases. Scientific evaluation of these historical documents can be valuable for finding new potential use in conventional medicine. Objective This clinical trial was performed to determine whether the use of the ‘ward’ vaginal tablet, which contains Rosa damascena, Punica granatum L. (Punicaceae), Querqus infectoria Oliv. (Fagaceae), Myrtus communis L. (Myrtaceae) and Nardostachys jatamansi (D.Don) DC. (Caprifoliaceae) could alleviate the symptoms of vulvovaginal candidiasis. Materials and methods A parallel double-blinded placebo-controlled study was done. Eighteen to fifty-year-old women with vulvovaginal candidiasis were divided into the ‘ward’ and placebo groups, 46 individuals in each group. The ‘ward’ group received the ‘ward’ vaginal tablet containing 200 mg of dried extract. Placebo group received a placebo (composed of corn starch and lactose). One tablet was applied through the vagina for 7 consecutive nights. Results Two weeks after medication administration, the vaginal discharge sample of patients was re-cultured; 29 patients (63.045%) in the ‘ward’ group and 6 (13.04%) patients in the placebo group had negative culture (p < 0.001). All clinical symptoms including itching, irritation, and vaginal discharge were significantly reduced in the ‘ward’ group compared with the placebo group following the intervention and the follow up (p < 0.05). Discussion and conclusions The findings suggest the ‘ward’ vaginal tablet could ameliorate vulvovaginal candidiasis. Future larger studies are recommended due to compare the therapeutic effect of the ‘ward’ vaginal tablet with common treatments.

Evaluation of antidepressant activity of hydro-alcoholic extract of rhizomes of Nardostachys jatamansi DC per se and in combination with fluoxetine in wistar albino rats and swiss albino mice

Background: Depression is a common mental disorder results due to deficiency of neurotransmitter in the brain. Various medicinal properties of jatamansi are mentioned in Ayurveda. This study evaluated effect of hydro-alcoholic extract of rhizomes of Nordostachys jatamansi DC per se and in combination with fluoxetine in wistar albino rats and swiss albino mice.Methods: Animals of either sex were selected and randomly divided in test group. Jatamansi extract 10:1 and fluoxetine hydrochloride dissolved in distilled water were used. Animals were tested for forced swimming test, tail suspension test and locomotor after given test drug. Results were compared with control and analysed.Results: Nardostachys jatamansi DC, when given to rats showed dose dependent increase in number of rotation during forced swimming test in rats. During forced swimming test in glass jar statistically significant decrease in immobility was observed. Nardostachys jatamansi DC, when given to mice dose dependent statistically significant decrease in immobility time, swimming time and climbing observed. When given along with combination of fluoxetine it shows statistically significant difference in result, confirmed that it can have synergistic antidepressant activity. When used for locomotor activity in mice none of the test drugs significantly increase or decrease the locomotor activity.Conclusions: Jatamansi showed antidepressant like property in various tests conducted on rats and mice. It showed statistically significant result with increasing dose and had synergic effect when given along with fluoxetine.

Nardostachys jatamansi (D.Don) DC.-Challenges and opportunities of harnessing the untapped medicinal plant from the Himalayas.

Nardostachys jatamansi (D.Don) DC. (family Caprifoliaceae) is prized in the Chinese, Tibetan, Nepalese, Bhutanese, Indian and Japanese systems of medicine. Its medicinal properties are well documented in ancient literature such as the Ayurvedic classics, the Old Testament, Ben-Cao- Shi-Yi, and Homer's Iliad. The plant is critically endangered and found in the alpine and sub-alpine regions of the Himalayas. Our study aims to show the challenges and opportunities of harnessing the untapped pharmaceutical resources of N. jatamansi. Another aim is to explore the possibilities of translating ethnobotanical information into health benefit applications. The sources of information used in the study are government reports, dissertations, books, research articles and databases like Science-Direct, SciFinder, Web of Science, PubMed, Wiley Online Library, and ACS Publications on N. jatamansi. In the study, we have examined and discussed reports on phytochemicals present in the plant, their structure, biological activity, pharmacological properties of extracts derived from plant parts, isolated compounds, and commercially available products from the plant. We have identified and discussed ambiguities and confusions about the plant's nomenclature and geographical distribution, and highlighted various studies that failed to discuss this issue. We analyzed the links between various reports on ethnobotanical information as well as studies on phytochemistry and pharmacologyconfirming the therapeutic properties of N. jatamansi. However, in many of these findings which had used dried samples, there was an uncanny resemblance between the phytochemical profiles and biological activities of N. jatamansi and Valeriana jatamansi Jones ex Roxb. (another genus from family, Caprifoliaceae). Since both the species share identical vernacular names, a possible reason could be that the samples may not have been of two separate species. Other limitations of different studies were the use of out-dated techniques for phytochemical profiling, absence of toxicology studies using animal models and clinical trials using human subjects. Analysis of various studies revealed a confusion about the botanical nomenclature of the plants and their geographical distributions. Absence of proper markers for identification of correct samples and improperly conducted studies on N. jatamansi were found to be the major hurdles to the use of ethnobotanical information and research findings into applications for human health. Development of markers using molecular, chemical and pharmacognosy based approaches for plant authentication and, in vitro propagation of authenticated material for easy availability of genuine plant material are the possible solutions to the problems identified.

Two isonardosinane-type sesquiterpenoids from Nardostachys jatamansi DC.

Two unique isonardosinane-type sesquiterpenoids, isonardosinonetriols A and B, together with six known sesquiterpenoids teucladiol, bullatantriol, (−)-globulol, (+)-maaliol, nardoguaianone J, and (+)-orobanchyl acetate, were isolated from the roots and rhizomes of Nardostachys jatamansi DC. (Caprifoliaceae). Their structures were elucidated by analysis of extensive spectroscopic data and the relative configurations were established by NOESY and circular dichroism (CD) experiments. Further, the results of SERT activity evaluations indicated that isonardosinonetriols A and B, (+)-maaliol and nardoguaianone J significantly enhanced SERT activity.

Desoxo-narchinol A and Narchinol B Isolated from Nardostachys jatamansi Exert Anti-neuroinflammatory Effects by Up-regulating of Nuclear Transcription Factor Erythroid-2-Related Factor 2/Heme Oxygenase-1 Signaling.

We previously reported that desoxo-narchinol A and narchinol B from Nardostachys jatamansi DC (Valerianaceae) inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2), and the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 protein in lipopolysaccharide (LPS)-stimulated BV2 and primary microglial cells. In this study, we aimed to elucidate the molecular mechanism underlying the anti-neuroinflammatory effects of desoxo-narchinol A and narchinol B. These two compounds inhibited the nuclear factor (NF)-κB pathway, by repressing the phosphorylation and degradation of inhibitor kappa B (IκB)-α, nuclear translocation of the p65/p50 heterodimer, and DNA-binding activity of the p65 subunit. Furthermore, both compounds induced heme oxygenase-1 (HO-1) protein expression, which was mediated by the activation of nuclear transcription factor erythroid-2-related factor 2 (Nrf2). Activation of the Nrf2/HO-1 pathway by desoxo-narchinol A was shown to be regulated by increased phosphorylation of p38 and extracellular signal-regulated kinase (ERK), whereas only p38 was involved in narchinol B-induced activation of the Nrf2/HO-1 pathway. In addition, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling was also involved in the activation of HO-1 by desoxo-narchinol A and narchinol B. These compounds also increased the phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at serine-9 residue, following phosphorylation of Akt. The anti-neuroinflammatory effect of desoxo-narchinol A and narchinol B was partially blocked by a selective HO-1 inhibitor, suggesting that this effect is partly mediated by HO-1 induction. In addition, both compounds also induced HO-1 protein expression in rat-derived primary microglial cells, which was correlated with their anti-neuroinflammatory effects in LPS-stimulated primary microglial cells. In conclusion, desoxo-narchinol A and narchinol B are potential candidates for the development of preventive agents for the regulation of neuroinflammation in neurodegenerative diseases.

Six kanshone C-derived sesquiterpenoid hybrids nardochalaristolones A–D, nardoflavaristolone A and dinardokanshone F from Nardostachys jatamansi DC.

Four sesquiterpenoid-chalcone hybrids (nardochalaristolones A–D, 1–4), a pair of epimeric sesquiterpenoid-flavonone hybrids ((2′S)- and (2′R)-nardoflavaristolone A, 5 and 6), and a sesquiterpenoid dimer (dinardokanshone F, 7), all sharing a kanshone C-derived sesquiterpenoid unit, were isolated from the underground parts of Nardostachys jatamansi (D.Don) DC. Their structures were elucidated by analysis of the extensive spectroscopic data, and the absolute configurations were established by analysis of 2D NMR spectroscopic data including NOESY data, combined with comparisons of experimental and calculated electronic circular dichroism spectra. Further, the plausible biosynthetic pathways for these compounds were proposed. And the results of SERT activity assay revealed that nardochalaristolones C–D (3 and 4) and nardoflavaristolone A (5 and 6) significantly enhanced SERT activity, while other compounds didn't show any SERT regulatory activities.

Nardostachys jatamansi DC Extract Alleviates Insulin Resistance and Regulates Glucose Metabolism in C57BL/KsJ-db/db Mice Through the AMP-Activated Protein Kinase Signaling Pathway.

This study investigated whether Nardostachys jatamansi DC extract (NJE) improved insulin sensitivity and suppressed hepatic glucose production in an animal model of type 2 diabetes. C57BL/KsJ-db/db mice were divided into three dietary groups: regular diet (control), NJE, and rosiglitazone. After 6 weeks of feeding, blood glucose, glycosylated hemoglobin, and plasma insulin levels were significantly lower in NJE than in diabetic control group mice. The oral glucose tolerance test also revealed a positive effect of NJE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in NJE than in diabetic control group mice. NJE markedly lowered the plasma lipid concentration compared to diabetic control group mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and plasma membrane glucose transporter type 4 increased more in NJE compared to diabetic control group mice. NJE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. These findings demonstrate that NJE alleviates hyperglycemia by improving insulin sensitivity and inhibiting gluconeogenesis in the liver.

Dinardokanshones C–E, isonardoeudesmols A–D and nardoeudesmol D from Nardostachys jatamansi DC.

Dinardokanshones C–E, three sesquiterpenoid dimers comprising an unusual nornardosinane-type sesquiterpenoid core and an aristolane-type sesquiterpenoid unit conjugated by an extra pyran or furan ring, together with monomeric sesquiterpenoids isonardoeudesmols A–D and nardoeudesmol D, were isolated from the underground parts of Nardostachys jatamansi DC. Structures of the eight compounds were elucidated by analysis of the extensive spectroscopic data, and their absolute configurations were established by analysis of NOESY and X-ray diffraction data, combined with computational electronic circular dichroism (ECD) calculations. The results of SERT activity assay revealed that isonardoeudesmol D and nardoeudesmol D significantly inhibited SERT activity, while dinardokanshones D–E and isonardoeudesmols B–C significantly enhanced SERT activity, among which dinardokanshone D exhibited the strongest effect.

Nardostachys jatamansi Ethanol Extract Ameliorates Aβ42 Cytotoxicity.

The Nardostachys jatamansi DC (NJ) root has been used as a sedative or analgesic to treat neurological symptoms and pain in traditional Korean medicine. Here, we investigate the potential effects of NJ on Alzheimer's disease (AD) and reveal the molecular mechanism through which NJ exerts its effects. The neuroprotective effect of the NJ root ethanol extract against β amyloid (Aβ) toxicity was examined in vitro using a cell culture system and in vivo using a Drosophila AD model. The NJ extract and chlorogenic acid, a major component of NJ, inhibited Aβ-induced cell death in SH-SY5Y cells. Moreover, the NJ extract rescued the neurological phenotypes of the Aβ42-expressing flies (decreased survival and pupariation rate and a locomotor defect) and suppressed Aβ42-induced cell death in the brain. We also found that NJ extract intake reduced glial cell number, reactive oxygen species level, extracellular-signal-regulated kinase (ERK) phosphorylation, and nitric oxide level in Aβ42-expressing flies, without affecting Aβ accumulation. These data suggest that the neuroprotective activity of NJ might be associated with its antioxidant and anti-inflammatory properties, as well as its inhibitory action against ERK signaling; thus, NJ is a promising medicinal plant for the development of AD treatment.

Anti-neuroinflammatory effects of sesquiterpenoids isolated from Nardostachys jatamansi

Two new nardosinone-type sesquiterpenoids, namely kanshone J (1) and kanshone K (2) along with seven known terpenoids (3–9) were isolated from the rhizomes and roots of Nardostachys jatamansi DC (Valerianaceae). The structures of these compounds were determined mainly by analysis of 1D-, 2D-NMR and MS data. In addition, the absolute configuration of compound 1 was assigned by application of the modified Mosher’s method. In an initial assay to evaluate their anti-neuroinflammatory effects, compounds 1–5 and 9 exhibited dose-dependent inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 cells, with IC50 values ranging from 2.43 to 46.54 μM. Particularly, desoxo-narchinol A (3) and narchinol B (4) significantly inhibited LPS-induced NO overproduction in BV2 cells with IC50 values of 3.48 ± 0.47 and 2.43 ± 0.23 μM, respectively. Furthermore, compounds 3 and 4 exhibited anti-neuroinflammatory effects by inhibiting the production of pro-inflammatory mediators, including prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins, and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF)-α, in LPS-stimulated BV2 and primary microglial cells.