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1.
Molecules ; 27(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364317

RESUMO

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.


Assuntos
Nardostachys , Neoplasias , Humanos , Apoptose , Fator de Crescimento Transformador beta
2.
Molecules ; 27(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36296442

RESUMO

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.


Assuntos
Nardostachys , Neoplasias Pancreáticas , Espécies Reativas de Oxigênio/farmacologia , Proteômica , Linhagem Celular Tumoral , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Apoptose , Proliferação de Células
3.
Phytochemistry ; 203: 113375, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35973611

RESUMO

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.


Assuntos
Produtos Biológicos , Nardostachys , Neuroblastoma , Valeriana , Humanos , Hidrogênio/análise , Peróxido de Hidrogênio/análise , Glicosídeos Iridoides/farmacologia , Iridoides/química , Estresse Oxidativo , Extratos Vegetais/química , Raízes de Plantas/química , Rizoma , Solventes , Valeriana/química
4.
Fitoterapia ; 162: 105286, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36029942

RESUMO

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.


Assuntos
Nardostachys , Valeriana , Ácidos Graxos/análise , Iridoides/química , Iridoides/farmacologia , Estrutura Molecular , Raízes de Plantas/química , Rizoma , Valeriana/química
5.
Ultrason Sonochem ; 89: 106133, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36037596

RESUMO

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.


Assuntos
Nardostachys , Acetilcolinesterase , Antioxidantes/química , Antioxidantes/farmacologia , Catalase , Etanol/química , Glutationa , Nardostachys/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sitosteroides , Sonicação , Superóxido Dismutase
6.
J Ethnopharmacol ; 298: 115560, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35863616

RESUMO

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.


Assuntos
Nardostachys , Valeriana , Animais , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Óleo de Rícino , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Camundongos , Ocludina , Extratos Vegetais/efeitos adversos , Transdução de Sinais
7.
Mol Neurobiol ; 59(10): 6091-6106, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35864434

RESUMO

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.


Assuntos
Doença de Alzheimer , Nardostachys , Doenças Neurodegenerativas , Síndromes Neurotóxicas , Tauopatias , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Antioxidantes/uso terapêutico , Colinesterases/uso terapêutico , Modelos Animais de Doenças , Drosophila/metabolismo , Humanos , Nardostachys/metabolismo , Proteínas tau/metabolismo
8.
Phytomedicine ; 104: 154257, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35738117

RESUMO

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.


Assuntos
Hipertensão , Nardostachys , Trifosfato de Adenosina/metabolismo , Animais , Anti-Hipertensivos/uso terapêutico , Aorta Torácica , Ciclopropanos , Células Endoteliais/metabolismo , Endotélio Vascular , Humanos , Hipertensão/metabolismo , Simulação de Acoplamento Molecular , Nardostachys/química , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Endogâmicos SHR , Tetra-Hidronaftalenos , Vasodilatação , Vasodilatadores/química
9.
Phytochemistry ; 200: 113228, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35561851

RESUMO

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.


Assuntos
Antineoplásicos , Nardostachys , Neoplasias Pancreáticas , Sesquiterpenos , Linhagem Celular , Humanos , Lactonas , Estrutura Molecular , Nardostachys/química , Neoplasias Pancreáticas/tratamento farmacológico , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Terpenos/farmacologia
10.
Molecules ; 27(8)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35458582

RESUMO

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.


Assuntos
Nardostachys , Óleos Voláteis , Valeriana , Altitude , Destilação/métodos , Óleos Voláteis/química , Valeriana/química
11.
Bioorg Chem ; 121: 105692, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35248903

RESUMO

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.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Nardostachys , Sesquiterpenos , Valeriana , Vírus da Influenza A Subtipo H3N2 , Iridoides/química , Iridoides/farmacologia , Estrutura Molecular , Raízes de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Valeriana/química
12.
Neurotoxicology ; 90: 62-78, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247505

RESUMO

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.


Assuntos
Doença de Alzheimer , Nardostachys , Síndromes Neurotóxicas , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Antioxidantes/uso terapêutico , Colinesterases , Drosophila/metabolismo , Nardostachys/metabolismo , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/prevenção & controle , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/toxicidade
13.
Zhongguo Zhong Yao Za Zhi ; 47(2): 499-510, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35178995

RESUMO

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-1ß(IL-1ß), 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-1ß, 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.


Assuntos
Microbioma Gastrointestinal , Nardostachys , Doença de Parkinson , Animais , NF-kappa B/metabolismo , Nardostachys/genética , Nardostachys/metabolismo , Doença de Parkinson/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
14.
Nat Prod Res ; 36(7): 1700-1706, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32820643

RESUMO

Investigation into the chemical diversity of Nardostachys chinensis Batal led to the discovery of three new (1-3) and one known (4) iridoid glycosides. Their structures were established through spectroscopic methods including 1 D and 2 D NMR experiments and HRESIMS analysis. Inhibitory effects of 1-4 on nitric oxide production were investigated in lipopolysaccaride (LPS)-mediated RAW 264.7 cells, and they displayed IC50 values in the range 7.8-15.2 µM.


Assuntos
Nardostachys , Animais , Glicosídeos/farmacologia , Glicosídeos Iridoides/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Nardostachys/química , Óxido Nítrico , Células RAW 264.7
15.
Braz. J. Pharm. Sci. (Online) ; 58: e191134, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1394031

RESUMO

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.


Assuntos
Plantas Medicinais/efeitos adversos , Pesquisa/classificação , Preparações Farmacêuticas/análise , Valerianaceae/classificação , Nardostachys/efeitos adversos , Esquizofrenia , Antipsicóticos
16.
J Ethnopharmacol ; 280: 114446, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34339792

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The plants of the genus Nardostachys (Caprifoliaceae) have been used for a long history in different cultural systems of medicine, including Chinese, Ayurvedic, Korean folk medicine and Islamic, for treatments of disorders in nervous, digestive, cardiovascular and integumentary systems. AIM OF THE REVIEW: This review aims to provide comprehensive information on Nardostachys plants including botany update, traditional uses, data mining of uses in traditional Chinese medicine (TCM) and current Chinese medicinal patents, chemical constituents, pharmacological effects, toxicity and analytical method studies. MATERIALS AND METHODS: Studies of the genus Nardostachys were collected via Google Scholar and Baidu Scholar, ScienceDirect, SciFinder, Wiley Online Library, ACS Publications, NLM/NCBI, Web of Science, CNKI, WANFANG DATA, EMBASE, Huabeing database and Traditional Chinese Medicine Resource Network and libraries. Some local books, PhD or MS's dissertations were also included. The literatures cited in this review covered the period from 1962 to March 2021. The Plant List and Kew Herbarium Catalogue databases were used to authenticate the scientific name. RESULTS: Botany description of Nardostachys genus is updated. Analysis of the literatures indicates that Nardostachys species are valuable herbs with therapeutic potentials for various disorders. Data mining on ancient TCM prescriptions and current Chinese medicinal patents containing Nardostachys revealed its common compatibility with other herbs in China. Phytochemical studies identified terpenoids and phenolic compounds as the main constituents in the genus Nardostachys and sesquiterpenoids as the major bioactive components. Experimental studies demonstrated that crude extracts, major fractions and the main constituents from Nardostachys species mainly exhibited pharmacological activities on nervous, digestive, cardiovascular and skin systems. Further, in vivo and in vitro toxicological studies demonstrated that Nardostachys plants showed either no or low toxicities, except at high doses. Finally, methods of qualitative and quantitative analyses on chemical constituents of genus Nardostachys were summarized, including TLC/HPTLC, GC and HPLC/UPLC methods, combined with common detectors including PDA, DAD and MS. CONCLUSIONS: This review summarizes the progress on phytochemistry, pharmacology, toxicology and analytical methods of the genus Nardostachys. Studies demonstrate traditional uses of the genus Nardostachys, and reveal novel bioactive effects for clinical uses. These achievements expand our knowledge on the genus Nardostachys and its clinical value.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Nardostachys/química , Animais , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Etnofarmacologia , Humanos , Compostos Fitoquímicos/efeitos adversos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Fitoterapia/métodos
17.
Anticancer Res ; 41(4): 1883-1893, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813393

RESUMO

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is a highly prevalent disease and treatment is limited. Therefore, development of new therapeutic agents is urgent. The aim of this study was to investigate the in vitro and in vivo anti-cancer effects of Nardostachys jatamansi root extract (NJRE) against HCC and underlying mechanisms involved in such effects. MATERIALS AND METHODS: Effects of NJRE on viability of HCC cell lines were determined by MTT analysis and annexin/PI apoptosis assays. Expression levels of proteins in MAPK and STAT3 pathways and caspase-3 and PARP after treatment with NJRE in HCC cell lines were determined by western blotting. In a syngeneic model using mouse HCC cells Hepa1-6, inhibition of tumor formation after oral administration of NJRE was determined and expression levels of phospho-ERK and phospho-STAT3 in liver tissues were analyzed by immunohistochemical staining. RESULTS: NJRE reduced the activation of STAT3 by inhibiting the expression of ERK and finally attenuated the proliferation of HCC. CONCLUSION: NJRE has anti-cancer effects against HCC. It has potential to be used in the treatment of human HCC.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Nardostachys , Raízes de Plantas , Fator de Transcrição STAT3/metabolismo , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos C57BL , Nardostachys/química , Fosforilação , Raízes de Plantas/química , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos
18.
Phytochemistry ; 184: 112681, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33548771

RESUMO

Seven undescribed (valejatadoids A-G) and 26 known iridoids were obtained from the roots and rhizomes of Valeriana jatamansi. Their structures were determined based on extensive spectroscopic data, especially 1D and 2D NMR, along with HRESIMS. Valejatadoid B is a monoene-type iridoid with a unique double bond between C-4 and C-5. Valejatadoids D-G, jatamanin U, jatamanin O, jatamanvaltrate E, valeriotetrate C, IVHD-valtrate, 10-isovaleroxy-valtrathydrin, jatamanvaltrate Q, valeriandoid F, jatamanvaltrate K, jatamanvaltrate W and isovaltrate were more potent than the positive control when evaluated for inhibition of NO production. Among them, valeriandoid F and jatamanvaltrate K exhibited the most significant inhibitory effects with IC50 values of 0.88 and 0.62 µM, respectively. In addition, valeriandoid F selectively inhibited the proliferation of human glioma stem cell lines, GSC-3# and GSC-18#, with IC50 values of 7.16 and 5.75 µM, respectively.


Assuntos
Nardostachys , Valeriana , Anti-Inflamatórios , Iridoides/farmacologia , Estrutura Molecular , Raízes de Plantas
19.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33236160

RESUMO

Through searching for anti­neuroinflammatory metabolites from Nardostachys jatamansi extracts, nardostachin was revealed to exert anti­neuroinflammatory effects against lipopolysaccharide (LPS)­induced overproduction of nitric oxide and prostaglandin E2 in BV2 and rat primary microglial cells. Furthermore, nardostachin inhibited the production of inducible nitric oxide synthase and cyclooxygenase­2 as well as pro­inflammatory cytokines, including interleukin (IL)­1ß, IL­6, IL­12 and tumor necrosis factor­α in LPS­stimulated BV2 and rat primary microglial cells. In a mechanistic study, nardostachin exhibited inhibitory activity on the nuclear factor (NF)­κB signaling pathway in LPS­stimulated BV2 and rat primary microglial cells by repressing IκB­α phosphorylation and blocking NF­κB translocation. Furthermore, nardostachin exhibited inhibitory effects on LPS­induced phosphorylation of c­Jun N­terminal kinase (JNK) mitogen­activated protein kinase (MAPK). Additionally, nardostachin repressed protein expression of Toll­like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in LPS­induced BV2 and rat primary microglial cells. These results suggested that nardostachin exerts anti­neuroinflammatory effects on LPS­induced BV2 and rat primary microglial cells by suppressing the TLR4­MyD88­NF­κB and JNK MAPK pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microglia/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Nardostachys/química , Receptor 4 Toll-Like/metabolismo , Animais , Anti-Inflamatórios/química , Linhagem Celular , Diterpenos/química , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Microglia/patologia , Ratos , Ratos Sprague-Dawley
20.
J Org Chem ; 86(16): 11006-11010, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33326231

RESUMO

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.


Assuntos
Nardostachys , Sesquiterpenos , Lactonas/farmacologia , Estrutura Molecular , Rizoma , Sesquiterpenos/farmacologia
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