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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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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 IC 50 values in the range 7.8-15.2  μ M.

The side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in the cardiovascular system mainly result from its inhibitory effect on cyclooxygenase-2 (COX-2). Since NSAIDs are one of the most commonly used anti-inflammatory drugs in the clinic, it is necessary to identify new anti-inflammatory drugs that are safer than NSAIDs. Nardosinanone N (NAN), a compound isolated from the roots and rhizomes of Nardostachys chinensis, was evaluated for its anti-inflammatory effects using the lipopolysaccharide (LPS)-stimulated RAW264.7 cell line and rat peritoneal macrophage models. First, we found that NAN down regulated the levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS) and prostaglandin E 2 (PGE 2 ), but not cyclooxygenase-2 (COX-2). Additionally, NAN reduced the M1 macrophage phenotype and increased the M2 macrophage phenotype. Furthermore, mechanistic studies showed that NAN activated the nuclear factor-erythroid 2 -related factor 2 (Nrf2) signaling pathway, which, in turn, increased the expression of antioxidant protein heme oxygenase-1 (HO-1) to achieve its anti-inflammatory effect. Finally, Nrf2 siRNA and the HO-1 inhibitor significantly attenuated the anti-inflammatory effect of NAN. More interestingly, we found that NAN did not affect COX-2 expression and activity but reduced the PGE 2 concentration by selective inhibition of microsomal prostaglandin E synthase-1 (mPGES-1). In conclusion, NAN may be a new anti-inflammatory drug that has fewer side effects than NSAIDs and can be a new potential Nrf2 activator and mPGES-1 inhibitor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nardochinoid B (NAB) is a new compound isolated from Nardostachys chinensis . Although our previous study reported that the NAB suppressed the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW264.7 cells, the specific mechanisms of anti-inflammatory action of NAB remains unknown. Thus, we examined the effects of NAB against LPS-induced inflammation. In this study, we found that NAB suppressed the LPS-induced inflammatory responses by restraining the expression of inducible nitric oxide synthase (iNOS) proteins and mRNA instead of cyclooxygenase-2 (COX-2) protein and mRNA in RAW264.7 cells, implying that NAB may have lower side effects compared with nonsteroidal anti-inflammatory drugs (NSAIDs). Besides, NAB upregulated the protein and mRNA expressions of heme oxygenase (HO)-1 when it exerted its anti-inflammatory effects. Also, NAB restrained the production of NO by increasing HO-1 expression in LPS-stimulated RAW264.7 cells. Thus, it is considered that the anti-inflammatory effect of NAB is associated with an induction of antioxidant protein HO-1, and thus NAB may be a potential HO-1 inducer for treating inflammatory diseases. Moreover, our study found that the inhibitory effect of NAB on NO is similar to that of the positive drug dexamethasone, suggesting that NAB has great potential for developing new drugs in treating inflammatory diseases.

Background: The medicinal plants of Radix et Rhizoma Nardostachyos include Nardostachys jatamansi and N. chinensis . Traditionally, the two plants have been used to treat many diseases. Because of their special aroma, they are also commonly used in the food and cosmetics industry. Recently, N. jatamansi and N. chinensis have been overexploited due to their economic importance, resulting in a sharp decline in their wild resources. Predicting potential distributions of the genus Nardostachys under different climate scenarios and understanding its preferred habitat are of great significance for their conservation, artificial cultivation, and assessment of their value., Methods: The Maxent model was used to predict the potential geographical distributions of the genus Nardostachys under current and future climatic conditions based on two representative concentration pathways (RCP2.6 and RCP8.5) for the 2050s and 2070s. These data were used to study the effects of climate variables., Results: The results show that the potential distribution of the two species will increase, thus more suitable habitats will be present in China. The suitable habitat for N. chinensis presents a relatively stable growth compared to N. jatamansi . In addition, precipitation plays a crucial role in modeling the effects of climate change on the genus Nardostachys . This study provides theoretical guidance for the cultivation of N. chinensis ., Competing Interests: The authors declare that they have no competing interests.

Four hitherto unknown aristolane-type sesquiterpenes, including one novel 8,9-secoaristolane, namely secoaristolenedioic acid (1), two aristolone derivatives, namely 1α,2β-dihydroxyaristolone (2), 9-epidebilon (3), and one rare aristolane-chalcone hybrid, namely 3'-hydroxynardoaristolone A (4) were isolated from the ethanol extract of the roots and rhizomes of Nardostachys chinensis. Their structures were elucidated on the basis of extensive spectroscopic analysis. In addition, the structure of aristolanhydride, recently isolated from the same species, was corrected by reanalysis of the published NMR data.

The roots and rhizomes of Nardostachys chinensis have neuroprotection and cardiovascular protection effects. However, the specific mechanism of N. chinensis is not yet clear. Nardochinoid C (DC) is a new compound with new skeleton isolated from N. chinensis and this study for the first time explored the anti-inflammatory and anti-oxidant effect of DC. The results showed that DC significantly reduced the release of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) in lipopolysaccharide (LPS)-activated RAW264.7 cells. The expression of pro-inflammatory proteins including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also obviously inhibited by DC in LPS-activated RAW264.7 cells. Besides, the production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also remarkably inhibited by DC in LPS-activated RAW264.7 cells. DC also suppressed inflammation indicators including COX-2, PGE 2 , TNF-α, and IL-6 in LPS-stimulated THP-1 macrophages. Furthermore, DC inhibited the macrophage M1 phenotype and the production of reactive oxygen species (ROS) in LPS-activated RAW264.7 cells. Mechanism studies showed that DC mainly activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, increased the level of anti-oxidant protein heme oxygenase-1 (HO-1) and thus produced the anti-inflammatory and anti-oxidant effects, which were abolished by Nrf2 siRNA and HO-1 inhibitor. These findings suggested that DC could be a new Nrf2 activator for the treatment and prevention of diseases related to inflammation and oxidative stress.

Background: Cardiovascular disease (CVD) is the leading cause of premature death throughout the world. An estimated 17.5 million people died from CVD in 2012, representing 31% of all global deaths. Nardostachys chinensis (NC), a typical traditional Chinese medicine (TCM), plays a crucial role in the management of patients with CVD, especially for those with cardiac arrhythmia. The purpose of this study was to evaluate the cardioprotective and antiarrhythmic effects of NC in animal and cell experiments., Methods: To review the cardioprotective and antiarrhythmic effects of NC, studies of NC on cardiovascular diseases in animal and cell experiments were identified from five databases through April 2016. Two investigators independently conducted the literature search, study selection, and data extraction., Results: A total of 16 studies were identified, including five animal experiments and eleven cell experiments. Four studies showed significant effects of NC on myocardial protection by inhibiting myocardial apoptosis, inflammation and oxidative stress. Twelve studies indicated significant beneficial effects of NC in cardiac arrhythmia primarily through the modulation of ion channels (I k , I k1 , I Na , I Ca-L , I to )., Conclusion: The above findings showed the possible efficacy of NC via its cardioprotective and antiarrhythmic effects, but the results should be interpreted with caution due to the limitations and the deficiencies in the studies.

Excessive microglial cell activation is related to the progression of chronic neuro-inflammatory disorders. Heme oxygenase-1 (HO-1) expression mediated by the NFE2-related factor (Nrf-2) pathway is a key regulator of neuro-inflammation. Nardostachys chinensis is used as an anti-malarial, anti-nociceptive, and neurotrophic treatment in traditional Asian medicines. In the present study, we examined the effects of an ethyl acetate extract of N. chinensis (EN) on the anti-neuro-inflammatory effects mediated by HO-1 up-regulation in Salmonella lipopolysaccharide (LPS)- or Staphylococcus aureus lipoteichoic acid (LTA)-stimulated BV2 microglial cells. Our results indicated that EN suppressed pro-inflammatory cytokine production and induced HO-1 transcription and translation through Nrf-2/antioxidant response element (ARE) signaling. EN markedly inhibited LPS- and LTA-induced activation of nuclear factor-kappa B (NF-κB) as well as phosphorylation of mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT). Furthermore, EN protected hippocampal HT22 cells from indirect neuronal toxicity mediated by LPS- and LTA-treated microglial cells. These results suggested that EN impairs LPS- and LTA-induced neuro-inflammatory responses in microglial cells and confers protection against indirect neuronal damage to HT22 cells. In conclusion, our findings indicate that EN could be used as a natural anti-neuro-inflammatory and neuroprotective agent., (Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)