Alkaloids of Delphinium grandiflorum and their implication to H2O2-induced cardiomyocytes injury.

Three new diterpenoid alkaloids (1-3), and eight known alkaloids (4-11) were isolated from the aerial parts of Delphinium grandiflorum. Grandifline A (1) represents an unprecedented diterpenoid alkaloid ring system featuring a C-7NC17 hemiaminal moiety and a lactone fragment through the linkage of C-17OC19 unit. And we named this newly-discovered class of rearranged C19-diterpenoid alkaloid scaffold as grandiflodines (B-12). Grandifline B (2) is the first naturally-occurring 7,17-secolycoctonine diterpenoid alkaloid with a C-7OC17 unit forming a hemiacetal. Their structures were elucidated via spectroscopic data and single-crystal X-ray diffraction analysis. The protective effects of compounds 1-11 on H2O2-induced cardiomyocytes injury were assayed. And compounds 6 and 10 showed significant protective effects, with IC50 values of 1.881 ± 0.680 µM and 1.904 ± 0.750 µM, respectively. Further, compound 6 could reduce oxidative damage by inhibiting cell death via the AMPK/AKT/mTOR signaling pathway in H2O2-induced H9C2 cells.

Grandiflolines A-F, new anti-inflammatory diterpenoid alkaloids isolated from Delphinium grandiflorum.

Delphinium grandiflorum L. (family Ranunculaceae), one of the most important and widely distributed Delphinium species, has received considerable interest due to its extremely high medicinal value. The discovery of novel metabolites from D. grandiflorum supported and broadened its application as an herbal medicine. In this study, the whole herb of D. grandiflorum was phytochemically investigated to obtain fourteen C19-lycaconitine-type diterpenoid alkaloids (1-14), including six undescribed alkaloids, grandiflolines A-F (1-6). The structural elucidation of them was accomplished by detailed spectroscopic analyses, mainly including HR-MS, 1D and 2D NMR (1H-1H COSY, NOESY, HMBC and HSQC), and IR spectra. New alkaloids 1-3 and 5 possess a characteristic △2,3 functional group in the A ring, while compounds 5 and 6 feature a rare OH-16 substituent. In addition, known compounds 7-12 were isolated from D. grandiflorum for the first time. Moreover, according to its medicinal use, new alkaloids 1-6 were estimated for their potential in vitro anti-inflammatory effects, and some of them exhibited inhibitory effects on NO production in LPS-activated RAW 264.7 macrophages. Our work enriched the chemical diversity of D. grandiflorum and the genus Delphinium and presented beneficial information for further investigations.

Diterpenoid alkaloids from the whole herb of Delphinium grandiflorum L.

Seven previously undescribed diterpenoid alkaloids, eight reaction products and thirteen known compounds were isolated from the whole plant of Delphinium grandiflorum L. (Ranunculaceae). Grandiflonines A and B have an unprecedented C20-diterpenoid alkaloid skeleton, which features inversion of the configuration of C-18. Their structures were determined by comprehensive analyses of spectroscopic data, X-ray diffraction and Mosher's method. The probable biosynthetic pathway of grandiflonine A was discussed. Additionally, the analgesic activity and anti-inflammatory activity by inhibition of NO production were evaluated. Among them, deoxylappaconitine (ED50 = 0.35 mg/kg, TI = 46.22) showed significant analgesic activity that was superior to the reference drug lappaconitine (ED50 = 3.5 mg/kg, TI = 3.34).

Analysis of codon usage patterns of the chloroplast genome in Delphinium grandiflorum L. reveals a preference for AT-ending codons as a result of major selection constraints.

BACKGROUND: Codon usage bias analysis is a suitable strategy for identifying the principal evolutionary driving forces in different organisms. Delphinium grandiflorum L. is a perennial herb with high economic value and typical biological characteristics. Evolutionary analysis of D. grandiflorum can provide a rich resource of genetic information for developing hybridization resources of the genus Delphinium. METHODS: Synonymous codon usage (SCU) and related indices of 51 coding sequences from the D. grandiflorum chloroplast (cp) genome were calculated using Codon W, Cups of EMBOSS, SPSS and Microsoft Excel. Multivariate statistical analysis combined by principal component analysis (PCA), correspondence analysis (COA), PR2-plot mapping analysis and ENC plot analysis was then conducted to explore the factors affecting the usage of synonymous codons. RESULTS: The SCU bias of D. grandiflorum was weak and codons preferred A/T ending. A SCU imbalance between A/T and G/C at the third base position was revealed by PR2-plot mapping analysis. A total of eight codons were identified as the optimal codons. The PCA and COA results indicated that base composition (GC content, GC3 content) and gene expression were important for SCU bias. A majority of genes were distributed below the expected curve from the ENC plot analysis and up the standard curve by neutrality plot analysis. Our results showed that with the exception of notable mutation pressure effects, the majority of genetic evolution in the D. grandiflorum cp genome might be driven by natural selection. DISCUSSIONS: Our results provide a theoretical foundation for elucidating the genetic architecture and mechanisms of D. grandiflorum, and contribute to enriching D. grandiflorum genetic resources.

Characterization of the complete chloroplast genome of Delphinium grandiflorum L.

Delphinium grandiflorum L. is a perennial herb, and has very high medicinal value. However, the evolutionary relationship analysis of D. grandiflorum is limited. Its cp genome was 157,339 bp in length, containing a pair of inverted repeated regions (52,304 bp), separated by a large single copy region of 88,098 bp, and a small single copy region of 16,937 bp. Moreover, a total of 117 functional genes were annotated, including 79 mRNA, 30 tRNA genes, and 8 rRNA genes. The phylogenetic relationships inferred that D. grandiflorum was closely related to Gymnaconitum gymnandrum. This study will provide a theoretical basis for species identification and biological research.