Cycloolivil Isolated from Nardostachys jatamansi Inhibits TNF-α/IFN-γ-Induced Chemokine Production by Blocking NF-κB and JAK/STAT Activation in HaCaT Keratinocytes.

Nardostachys jatamansi is widely used as a traditional medicine in Asian countries. Numerous recent studies have reported the biological activities of its secondary metabolites and extracts. In this study, a total of 14 components were isolated, including cycloolivil and 2-(3'-hydroxy-5'-ethoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5-carboxylic acid, which were first discovered in N. jatamansi. The isolated compounds were investigated for their anti-inflammatory effects on HaCaT keratinocytes and their potential to alleviate skin inflammation. The results of the screening revealed that cycloolivil and 4ß-hydroxy-8ß-methoxy-10-methylene-2,9-dioxatricyclo[4.3.1.03,7]decane reduced the production of inflammatory cytokines induced by TNF-α/IFN-γ, such as IL-6, IL-8, and RANTES, in keratinocytes. This study focused on exploring the biological effects of cycloolivil, and the results suggested that cycloolivil inhibits the expression of COX-2 proteins. Further mechanistic evaluations confirmed that the anti-inflammatory effects of cycloolivil were mediated by blockage of the NF-κB and JAK/STAT signaling pathways. These results suggest that cycloolivil isolated from N. jatamansi could be used to treat skin inflammatory diseases.

The effects of Nardosinone on levodopa intervention in the treatment of Parkinson's disease.

BACKGROUND: The roots and rhizomes of Nardostachys jatamansi DC. are reported to be useful for the treatment of Parkinson's disease (PD). Previous research has also shown that Nardosinone, the main active component isolated from Nardostachys jatamansi DC., exhibits the potential to treat PD. AIM OF THE STUDY: To investigate how the effects of Nardosinone could assist levodopa in the treatment of PD, how this process changes the intestinal flora, and to explore the effective forms of Nardosinone in the intestinal flora. MATERIAL AND METHODS: We used behavioral experiments, and hematoxylin-eosin staining and immunohistochemical staining, to investigate the effects of a combination of Nardosinone and levodopa on rotenone-induced PD rats. In addition, we used LC/MS-MS to determine the levels of levodopa, 5-hydroxytryptamine, dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid, and homovanillic acid, to investigate the effect of the intestinal flora on co-administration in the treatment of PD. LC/MS-MS was also used to detect the metabolites of Nardosinone on the gastrointestinal tract and intestinal flora. RESULTS: The behavioral disorders and neuronal damage associated with PD were significantly improved following the co-administration. Analysis also revealed that the co-administration increased the levels of five neurotransmitters in the striatum, plasma and feces. In vitro experiments further demonstrated that the levels of dopamine and levodopa were increased in the intestinal flora. In total, five metabolites of Nardosinone were identified. CONCLUSION: Our findings indicate that Nardosinone and its metabolites might act as a potential adjutant to enhance the efficacy of levodopa via the intestinal flora, thus expanding the therapeutic potential of the combination of Chinese and Western medicine as a treatment method for PD.

Network Pharmacology and Bioinformatics Analyses Identify the Core Genes and Pyroptosis-Related Mechanisms of Nardostachys Chinensis for Atrial Fibrillation.

BACKGROUND: Nardostachys chinensis is an herbal medicine widely used in the treatment of atrial fibrillation (AF), but the mechanism is unclear. OBJECTIVE: To explore the molecular mechanism of N. chinensis against AF. METHODS: The TCMSP was used to screen the active N. chinensis compounds and their targets. Differentially expressed genes (DEGs) for AF were identified using open-access databases. Using Venn diagrams, the cross-targets of N. chinensis, pyroptosis, and AF were obtained. The genes underwent molecular docking as well as gene set enrichment analysis (GSEA). A nomogram based on candidate genes was constructed and evaluated with the clinical impact curve. After that, the immune infiltration of the dataset was analyzed by single sample GSEA (ssGSEA). Finally, microRNAs (miRNAs) and transcription factors (TFs) were predicted based on candidate genes. RESULTS: Tumor necrosis factor (TNF) and caspase-8 (CASP8) were obtained as candidate genes by taking the intersection of DEGs, targets of N. chinensis, and pyroptosis-related genes. Tolllike receptor (TLR) and peroxisome proliferator-activated receptor (PPAR) signaling pathways were linked to candidate genes. Additionally, immune cell infiltration analysis revealed that CASP8 was associated with natural killer T cells, natural killer cells, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), macrophages, CD8 T cells, and CD4 T cells. Finally, miR-34a-5p and several TFs were found to regulate the expression of CASP8 and TNF. CONCLUSION: CASP8 and TNF are potential targets of N. chinensis intervention in pyroptosisrelated AF, and the TLR/NLRP3 signaling pathway may be associated with this process.

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.

Nardostachys jatamansi: Phytochemistry, ethnomedicinal uses, and pharmacological activities: A comprehensive review.

A member of the Valerianacae family, Nardostachys jatamansi is the smallest, most primitive, perennial, dwarf, hairy, rhizomatous, herbaceous species. It has an enlarged antiquity of usage as ayurvedic medicine, homeopathic medicine, ethnomedicine, and the Indian system of medicine, and is now used in the modern medicine industry. In the ayurvedic medical system, the rhizomes of the plant are used as a bitter tonic, stimulant, antispasmodic, epileptic treatment, and for hysteria. Pharmacological reports on Nardostachys jatamansi revealed its antifungal activity, hepatoprotective activity, central nervous system activity, anticonvulsant activity, neuroprotective activity, antiparkinson's activity, antioxidant activity, antidiabetic activity, tranquilizing activity, antiestrogenic activity furthermore, Jatamansone has also been linked to anti-hypertensive, anti-arrhythmic, anti-asthmatic, nematicidal, and antibacterial effects. This review article's objective is to go over traditional uses, Phytochemistry, Ethnomedicinal Importance, pharmacological activities, precise procedures for variety improvement, protection, and appropriate utilization, and recognize prospects for Nardostachys jatamansi.

Nardostachys jatamansi and levodopa combination alleviates Parkinson's disease symptoms in rats through activation of Nrf2 and inhibition of NLRP3 signaling pathways.

CONTEXT: Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD. OBJECTIVE: To explore the synergistic effect of NJ combined with levodopa against PD. MATERIALS AND METHODS: The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways. RESULTS: Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23, p < 0.01), enhanced the stay time on the rotating rod (84.86 ± 18.15 vs. 71.36 ± 17.53, p < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway. DISCUSSION AND CONCLUSIONS: NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.

Protective effect of Nardostachys jatamansi extract against lithium-pilocarpine-induced spontaneous recurrent seizures and associated cardiac irregularities in a rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Nardostachys jatamansi (D.Don) DC. is a perennial herbaceous medicinal plant widely used for the ethnomedical treatment of various ailments. The underground parts of the plants are used in traditional medicine to manage epilepsy and other cardiovascular conditions. AIM OF THE STUDY: The present study was undertaken to investigate the efficacy of a characterized hydroalcoholic extract (NJET) of Nardostachys jatamansi in the lithium-pilocarpine rat model of spontaneous recurrent seizures (SRS) and associated cardiac irregularities. MATERIALS AND METHODS: NJET was prepared by percolation using 80% ethanol. The dried NEJT was subjected to UHPLC-qTOF-MS/MS for chemical characterization. Molecular docking studies were performed using the characterized compounds to understand mTOR interactions. The animals showing SRS following lithium-pilocarpine administration were treated with NJET for 6 weeks. Afterward, seizure severity, cardiac parameters, serum biochemistry, and histopathological parameters were studied. The cardiac tissue was processed for specific protein and gene expression studies. RESULTS: The UHPLC-qTOF-MS/MS characterized 13 compounds in NJET. The identified compounds subjected to molecular docking showed promising binding affinities toward mTOR. There was a dose-dependent decrease in the severity of SRS following the extract administration. A reduction in mean arterial pressure and serum biochemical markers (lactate dehydrogenase and creatine kinase) was also observed following NJET treatment in epileptic animals. Histopathological investigations revealed reduced degenerative changes and decreased fibrosis following the extract treatment. The cardiac mRNA level of Mtor, Rps6, Hif1a, and Tgfb3 was reduced in the extract-treated groups. Further, a similar reduction in the protein expression of p-mTOR and HIF-1α was also observed following NJET treatment in the cardiac tissue. CONCLUSIONS: The results concluded that NJET treatment reduces lithium-pilocarpine-induced recurrent seizures and associated cardiac irregularities via downregulation of the mTOR signalling pathway.

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 3ß (GSK3ß), 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.

Potential Anti-Tumor Activity of Nardoguaianone L Isolated from Nardostachys jatamansi DC. in SW1990 Cells.

Natural products (NPs) were a rich source of diverse bioactive molecules. Most anti-tumor agents were built on natural scaffolds. Nardostachys jatamansi DC. was an important plant used to process the traditional Chinese herbal medicines "gansong". Pancreatic cancer was the fourth most common cause of cancer-related death in the world. Hence, there was an urgent need to develop novel agents for the treatment of pancreatic cancer. In this paper, nardoguaianone L (G-6) is isolated from N. jatamansi, which inhibited SW1990 cells colony formation and cell migration, and induced cell apoptosis. Furthermore, we analyzed the differential expression proteins after treatment with G-6 in SW1990 cells by using iTRAQ/TMT-based quantitative proteomics technology, and the results showed that G-6 regulated 143 proteins' differential expression by GO annotation, including biological process, cellular component, and molecular function. Meanwhile, KEGG enrichment found that with Human T-cell leukemia virus, one infection was the most highly enhanced pathway. Furthermore, the MET/PTEN/TGF-ß pathway was identified as a significant pathway that had important biological functions, including cell migration and motility by PPI network analysis in SW1990 cells. Taken together, our study found that G-6 is a potential anti-pancreatic cancer agent with regulation of MET/PTEN/TGF-ß pathway.

Nardoguaianone L Isolated from Nardostachys jatamansi Improved the Effect of Gemcitabine Chemotherapy via Regulating AGE Signaling Pathway in SW1990 Cells.

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as "the king of cancers". Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from Nardostachys jatamansi DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer.

Stability of valeriana-type iridoid glycosides from rhizomes of Nardostachys jatamansi and their protection against H2O2-induced oxidative stress in SH-SY5Y cells.

Nardostachys jatamansi is close to Valerian in consideration of their same psychoactive effects, such as sedation and neuroprotection. Valeriana-type iridoids are major active components of Valerian, but few valeriana-type iridoids have been isolated from N. jatamansi. Iridoid-targeting chemical investigation of the rhizomes of N. jatamansi resulted in the isolation of seven valeriana-type iridoid glycosides, four of which are previously undescribed. Their structures were determined through NMR spectroscopy, high-resolution mass spectrometry, and optical rotation experiments. In addition, the inaccurate configurations of patrinalloside and 6″-acetylpatrinalloside from previous reports were corrected. These compounds, unstable due to alcoholic solvents, were more stable in the mixtures than in purified forms, as monitored by the qNMR method, supporting the use of natural products as mixtures. Furthermore, the isolates, as well as crude and solvent partition extracts, were found to have a protective effect against hydrogen-peroxide-induced toxicity in human neuroblastoma cells, as confirmed by assays for cell viability and antioxidation. These findings suggest the potential therapeutic application of the valeriana-type iridoid glycosides isolated herein with improved biochemical stability.

Mutivariate optimization strategy for the sonication-based extraction of Nardostachys jatamansi roots and analysis for chemical composition, anti-oxidant and acetylcholinesterase inhibitory potential.

Extracts from medicinal plants are generally obtained by conventional methods like percolation and maceration. Owing to limitations of traditional methods and to meet the rising demand of extracts, the development of new green approaches is need of hour. In the present research, we have developed an ultrasound-assisted extraction (UAE) method for the Nardostachys jatamansi (NJ) D. Don, DC roots and optimized the extraction parameters for possible improved extract yield. A multivariate optimization strategy using the Centre Composite Design coupled with response surface methodology was applied. A numerical optimization approach accurately predicted the extraction conditions (sonication time âˆ¼ 20 min, ethanol âˆ¼ 70 % and a liquid/solid ratio of about 21:1). Scanning electron microscopy of the plant samples after UAE also indicated the cavitation effect due to sound waves. GC-MS analysis of the optimized ultrasound extract (OUNJ) confirmed improvement in the concentration of various secondary metabolites like jatamansone (91.8 % increase), spirojatamol (42.3 % increase), globulol (130.4 % increase), sitosterol (84.6 % increase) as compared to the soxhlet extract (SXNJ). Different anti-oxidant parameters (DPPH, Glutathione, Catalase SOD and NO) were also significantly altered (p < 0.05) in the optimized extracts. The IC50 to inhibit acetylcholinesterase activity (AChE) in vitro and its concentration in brain homogenates were significantly (p < 0.05) improved by OUNJ extract as compared to the SXNJ ones. To conclude, we can say that established optimized conditions for UAE of N. jatamansi roots not only reduce the extraction time but also improved the pharmacological potential of the extracts.

Jatavaleridoids A-H, eight new iridoids from the roots and rhizomes of Valeriana jatamansi Jones.

Eight new iridoids, jatavaleridoids A-H (1-8), were isolated from the roots and rhizomes of Valeriana jatamansi. Their structures and absolute configurations were elucidated based on NMR and HRESIMS spectroscopic data, as well as quantum chemical calculation. Structurally, compounds 1-5 and 8 were rare iridoids with long-chain fatty acid esters at C-10. In addition, compound 7 showed cytotoxicity, while compounds 1 and 2 exhibited inhibition on NO production.

Antidiarrheal activity of the extracts of Valeriana jatamansi Jones on castor oil-induced diarrhea mouse by regulating multiple signal pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana jatamansi Jones, a traditional medicine, is used for various medicinal purposes worldwide. This species is popular for its gastro-protective properties and has been verified to exert antidiarrheal effects. Qiuxieling mixture, an oral liquid preparation used to treat diarrhea in children in clinical practice, was extracted from V. jatamansi Jones. AIM OF THE STUDY: Although Qiuxieling mixture has a good preventive effect on diarrhea children, the disgusting smell makes it intolerable. Therefore, we extracted odorless products from V. jatamansi Jones and Qiuxieling mixture. The present study is aimed to investigate the protective effects of two ethanolic extracts of V. jatamansi Jones and Qiuxieling mixture against castor oil-induced diarrhea and their possible mechanisms in mice. MATERIALS AND METHODS: The two extracts of V. jatamansi Jones and Qiuxieling mixture were detected by HPLC. A castor oil-induced diarrheal model was used to evaluate the antidiarrheal effects. The expression of Occludin in the small intestine was measured by IHC. Western blotting and immunofluorescence were used to detect the expression of proteins related to the oxidative stress and GSDMD-mediated pyroptosis signaling pathways. ELISA was used to detect the expression of IL-6 and IL-1ß in the small intestine of mice with diarrhea. RESULTS: The two extracts of V. jatamansi Jones and Qiuxieling mixture dose-dependently reduced the diarrhea index and the diarrhea rate, delayed the onset of diarrhea, and decreased the weight of the intestinal content. Meanwhile, they reversed the decreased expression of Occludin and restored the activity of Na+-K+-ATPase in the intestines of diarrheal mice. In addition, they reversed the depletion of GSH, attenuated the activation of the ERK/JNK pathway, promoted the Nrf2/SOD1 signaling pathways, and decreased the release of ROS in the intestines of diarrheal mice. Moreover, they suppressed GSDMD-mediated pyroptosis by downregulating the NLRP3/caspase-1/GSDMD signaling pathway. CONCLUSIONS: The two extracts of V. jatamansi Jones and Qiuxieling mixture exerted protective effects on castor oil-induced diarrhea in mice through a variety of mechanisms, including antioxidant stress, restoration of tight junctions between intestinal mucosal cells and regulation of the GSDMD-mediated pyroptosis pathway.

Jatamansinol from Nardostachys jatamansi Ameliorates Tau-Induced Neurotoxicity in Drosophila Alzheimer's Disease Model.

Nardostachys jatamansi has long been used to prepare Medhya Rasayana in traditional Indian Ayurveda medicine to treat neurological disorders and enhance memory. Jatamansinol from the N. jatamansi against Alzheimer's disease (AD) showed that it could be a multitargeted drug against AD. Drosophila is an ideal model organism for studying a progressive age-related neurodegenerative disease such as AD since its neuronal organizations and functioning are highly similar to that of humans. The current study investigates the neuroprotective properties of jatamansinol against Tau-induced neurotoxicity in the AD Drosophila model. Results indicate jatamansinol is not an antifeedant for larva and adult Drosophila. Lifespan, locomotor activity, learning and memory, Tau protein expression level, eye degeneration, oxidative stress level, and cholinesterase activities were analyzed in 10, 20, and 30-day-old control (wild type), and tauopathy flies reared on jatamansinol supplemented food or regular food without jatamansinol supplementation. Jatamansinol treatment significantly extends the lifespan, improves locomotor activity, enhances learning and memory, and reduces Tau protein levels in tauopathy flies. It boosts the antioxidant enzyme activities, prevents Tau-induced oxidative stress, ameliorates eye degeneration, and inhibits cholinesterase activities in Tau-induced AD model. This study provides the first evidence that jatamansinol protects against Tau's neurotoxic effect in the AD Drosophila model, and it can be a potential therapeutic drug candidate for AD.

Aristolone in Nardostachys jatamansi DC. induces mesenteric vasodilation and ameliorates hypertension via activation of the KATP channel and PDK1-Akt-eNOS pathway.

BACKGROUND: Nardostachys jatamansi DC. is a common medicinal herb used to treat cardiovascular diseases, particularly hypertension. Previously, our lab characterized the chemical compounds of N. jatamansi. However, the bioactive compounds of N. jatamansi and their mechanisms of action on blood pressure and blood vessels are unknown. PURPOSE: The vasorelaxant effects of the methanolic extract (MeOH ext.) of the roots and rhizomes of N. jatamansi, its main compounds, and their underlying mode of action, were investigated. METHODS: The main compounds of N. jatamansi were isolated and identified using UHPLC-TOF MS. The antihypertensive effect of N. jatamansi extracts and (-)-aristolone were determined using spontaneously hypertensive rats. The extracts, fractions, and compounds were also evaluated for their vasorelaxant effects on U46619 contractile responses in isolated thoracic aortic and mesenteric arterial rings. The endothelial-dependent relaxation, as well as the regulatory pathways and targets of (-)-aristolone, were studied in-vitro and ex-vivo. Molecular docking and biophysical characterization (Surface plasmon resonance) studies were utilized to investigate the molecular interaction between (-)-aristolone and the target protein. RESULTS: MeOH ext. (200 mg/kg) reduces the systolic and diastolic blood pressure in spontaneously hypertensive rats. MeOH ext. and its ethyl acetate fraction (EtOAc Fr.), but not the H2O fraction, had a significant relaxing effect on the thoracic aorta. (-)-aristolone and kanshone H from EtOAc Fr. induced vasorelaxation of the thoracic aorta and mesenteric artery. In human umbilical vein endothelial cells, (-)-aristolone treatment upregulated phosphorylation of Akt (T308) and eNOS. Molecular docking and surface plasmon resonance experiments revealed an interaction between (-)-aristolone and phosphoinositide-dependent protein kinase 1 (PDK1), an upstream protein kinase that phosphorylates Akt at T308. Treatment with PDK1 inhibitor PHT-427 and eNOS inhibitor L-NAME consistently inhibited (-)-aristolone-induced vasorelaxation. In addition, KATP channel inhibitor glibenclamide dramatically inhibited the vasorelaxant effects of (-)-aristolone and kanshone H in the endothelium-denuded thoracic aorta. Finally, (-)-aristolone lowers hypertensive rats' systolic and diastolic blood pressure. CONCLUSIONS: The extracts of N. jatamansi promote vasorelaxation and alleviate hypertension. The essential chemicals responsible for producing vasorelaxation effects are (-)-aristolone and kanshone H, which activate the PDK1-Akt-eNOS-NO relaxing pathway and stimulate the opening of the KATP channel. These findings point to N. jatamansi and aristolone as possible antihypertensive agents.

Terpenoids from Nardostachys jatamansi and their cytotoxic activity against human pancreatic cancer cell lines.

Five previously unreported terpenoids, together with fifteen known analogs, were isolated from a methanol extract of the roots and rhizomes of Nardostachys jatamansi. Their structures, including absolute configurations, were elucidated by spectroscopic data and electronic circular dichroism (ECD) spectra analyses, as well as single-crystal X-ray diffraction for crystalline compounds. Structurally, (4R,5S,6S,7R)-1(10)-aristolane-8,9-diacid is a novel 8,9-dicarboxylic acid derivative of aristolane-type sesquiterpenoid. (4R,6S,7R,10S)-10-Hydroxyguaia-1(5)-6,7-epoxy-2-one is an undescribed analogue of nardoguaianone K, with a rare 6,7-epoxide group. (4R,5R,6R,8R)-1(10)-Isonardosinone-8-ol-9-one-7,11-lactone is an isonardosinane-type sesquiterpene bearing a γ-lactone ring. Dinardokanshone F is a rare example of a sesquiterpene dimer from N. jatamansi connected by an oxo bridge. The isolates were evaluated for their cytotoxic activity against four human pancreatic cancer cell lines (CFPAC-1, PANC-1, CAPAN-2 and SW1990). Compound epoxynardosinone exhibited significant cytotoxicity against CAPAN-2 cell lines with IC50 value of 2.60 ± 1.85 µM. 1-Hydroxylaristolone displayed comparable cytotoxicity on CFPAC-1 cell lines (IC50 1.12 ± 1.19 µM), compared to Taxol (IC50 0.32 ± 0.13 µM). 1-Hydroxylaristolone, 1(10)-aristolane-9ß-ol, 1(10)-aristolen-2-one, alpinenone, valtrate isovaleroyloxyhydrine and nardostachin displayed stronger cytotoxicity against PANC-1 cell lines with IC50 values ranging from 0.01 ± 0.01 to 6.50 ± 1.10 µM. 1(10)-Aristolane-9ß-ol, 10-hydroxyguaia-1(5)-6,7-epoxy-2-one, nardoguaianone K, nardonoxide, epoxynardosinone, 1(10)-isonardosinone-8-ol-9-one-7,11-lactone, valtrate isovaleroyloxyhydrine and nardostachin showed remarkable cytotoxicity against SW1990 cell lines with IC50 values ranging from 0.07 ± 0.05 to 4.82 ± 6.96 µM. Furthermore, the primary mechanistic study of nardostachin demonstrated that it induced cell apoptosis via the mitochondria-dependent pathway, and induced SW1900 cell arrest at G2/M phase.

Chemical Diversity of Essential Oil of Valeriana jatamansi from Different Altitudes of Himalaya and Distillation Methods.

Valeriana jatamansi is an important temperate herb that is used in the pharmaceutical and essential oil industries. In India, this species is now on the verge of extinction due to the over-exploitation of its rhizomes from its natural habitat. It is hypothesized that the variations in bioactive compounds in its essential oil are very high among the wild populations as well as cultivated sources. Thus, this study was conducted to evaluate the chemical profiling of essential oil of four wild populations (Rupena, Kugti, Garola, and Khani) and two cultivated sources (CSIR-IHBT, Salooni), which were distilled at three consecutive days. The variation in oil concentration in roots/rhizomes was found significant (p ≤ 0.05), and the maximum value (0.35%) was registered with the population collected from Kugti and Khani. In essential oil, irrespective of population and distillation day, patchouli alcohol was the major compound, which ranged from 19 to 63.1%. The maximum value (63.1%) was recorded with the essential oil obtained from Garola's population and distilled on the first day. The percentage of seychellene was abruptly increased with subsequent days of extraction in all the populations. The multivariate analysis revealed that the essential oil profiles of Rupena, Kugti, Garola, and CSIR-IHBT populations were found to be similar during the first day of distillation. However, during the second day, Rupena, Kugti, Khani, and CSIR-IHBT came under the same ellipse of 0.95% coefficient. The results suggest that the population of Kugti is superior in terms of oil concentration (0.35%), with a higher proportion of patchouli alcohol (63% on the first day). Thus, repeated distillation is recommended for higher recovery of essential oil. Moreover, repeated distillation can be used to attain V. jatamansi essential oil with differential and perhaps targeted definite chemical profile.

Iridoids and sesquiterpenoids from Valeriana jatamansi and their anti-influenza virus activities.

Twenty-one new iridoids, jatamansidoids A-U (1-12, 21-26, 32, 35 and 36), two new natural ones, jatamansidoids V (37) and W (38), eighteen known ones (13-20, 27-31, 33 and 34), together with three patchoulol-type sesquiterpenoids (39-41), were isolated from the roots and rhizomes of Valeriana jatamansi. Structurally, compounds 1-7 were the first examples of iridoids from V. jatamansi with unique α, ß, γ, δ-unsaturated aldehyde fragment between C-11, C-4, C-5, C-9 and C-8; compound 8 was an unprecedented iridoid derivative with a methyl group (Me-10) at C-1, rather than C-8, and its plausible biogenetic pathway was proposed in this paper; compounds 22 and 23 were the first examples of Δ4(5)-iridoids simultaneously replaced by oxygen-containing groups at C-3, C-6 and C-7; compound 24 was the first iridoid with both 6,7- and 1,10-epoxy fragments. The structures and absolute configurations of new compounds were elucidated based on extensive spectroscopic techniques and quantum chemical calculation. Furthermore, compounds 13-15 and 39-41 exhibited potent anti-influenza virus activities with H1N1 and H3N2 strains, with IC50 values of 0.21-1.48 µM.

Jatamansinol from Nardostachys jatamansi (D.Don) DC. Protects Aß42-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 Aß42 protein-induced neurotoxicity using the Aß42 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, Aß42 protein, and Aß42 gene expression. Jatamansinol extends the lifespan, improves locomotor activity, enhances learning and memory, and reduces Aß42 protein levels in AD flies. Jatamansinol boosts the antioxidant enzyme activities, prevents Aß42 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 Aß42 protein-induced neurotoxicity in the AD Drosophila model, suggesting its possible therapeutic potential against AD.