Kanshone C

Metabolome and transcriptome associated analysis of sesquiterpenoid metabolism in Nardostachys jatamansi.[Pubmed:36523614]

Front Plant Sci. 2022 Nov 29;13:1041321.

BACKGROUND: Nardostachys jatamansi, an extremely endangered valuable plant of the alpine Himalayas, can synthesize specific sesquiterpenoids with multiple effective therapies and is widely exploited for the preparation of drugs, cosmetics and even religious functions (e.g., well-known spikenard). However, how accumulation trend of the sesquiterpenoids in tissues and the molecular mechanisms underlying the production of the active ingredients are not well understood. METHODS: The single-molecule real-time (SMRT) and RNA-seq transcriptome sequencing were combined to analyse the roots, rhizomes, leaves, flowers and anthocaulus of N. jatamansi. The phytochemical analysis was performed by gas chromatography‒mass spectrometry (GC‒MS) and ultrahigh-performance liquid chromatography (UPLC). RESULTS: A high-quality full-length reference transcriptome with 26,503 unigenes was generated for the first time. For volatile components, a total of sixty-five compounds were successfully identified, including fifty sesquiterpenoids. Their accumulation levels in five tissues were significantly varied, and most of the sesquiterpenoids were mainly enriched in roots and rhizomes. In addition, five aromatic compounds were only detected in flowers, which may help the plant attract insects for pollination. For nonvolatile ingredients, nardosinone-type sesquiterpenoids (nardosinone, Kanshone C, and isonardosinone) were detected almost exclusively in roots and rhizomes. The candidate genes associated with sesquiterpenoid biosynthesis were identified by transcriptome analysis. Consistently, it was found that most biosynthesis genes were abundantly expressed in the roots and rhizomes according to the functional enrichment and expression patterns results. There was a positive correlation between the expression profile of genes related to the biosynthesis and the accumulation level of sesquiterpenoids in tissues. Gene family function analysis identified 28 NjTPSs and 43 NjCYPs that may be involved in the biosynthesis of the corresponding sesquiterpenoids. Furthermore, gene family functional analysis and gene coexpression network analysis revealed 28 NjTPSs and 43 NjCYPs associated with nardosinone-type sesquiterpenoid biosynthesis. CONCLUSION: Our research results reveal the framework of sesquiterpenoids accumulation and biosynthesis in plant tissues and provide valuable support for further studies to elucidate the molecular mechanisms of sesquiterpenoid regulation and accumulation in N. jatamansi and will also contribute to the comprehensive utilization of this alpine plant.

Six kanshone C-derived sesquiterpenoid hybrids nardochalaristolones A-D, nardoflavaristolone A and dinardokanshone F from Nardostachys jatamansi DC.[Pubmed:30092385]

Bioorg Chem. 2018 Dec;81:35-43.

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.

Novel serotonin transporter regulators: Natural aristolane- and nardosinane- types of sesquiterpenoids from Nardostachys chinensis Batal.[Pubmed:29118341]

Sci Rep. 2017 Nov 8;7(1):15114.

Serotonin transporter (SERT) is a classic target of drug discovery for neuropsychiatric and digestive disorders, and against those disorders, plants of Nardostachys genus have been valued for centuries in the systems of Traditional Chinese Medicine, Ayurvedic and Unani. Herein, chemical investigation on the roots and rhizomes of Nardostachys chinensis Batal. led to the isolation of forty sesquiterpenoids including six new aristolane-type sesquiterpenoids and six new nardosinane-type sesquiterprenoids. Their structures were elucidated by extensive spectroscopic methods, combined with analyses of circular dichroism and single-crystal X-ray diffraction data. To explore natural product scaffolds with SERT regulating activity, a high-content assay for measurement of SERT function in vitro was conducted to evaluate the SERT regulating properties of these isolates. In conclusion, eleven compounds could be potential natural product scaffolds for developing drug candidates targeting SERT. Among which, Kanshone C of aristolane-type sesquiterpenoid inhibited SERT most strongly, while desoxo-nachinol A of nardosinane-type sesquiterpenoid instead enhanced SERT potently.