Kadsura coccinea is a medicinal plant from the Schisandraceae family that is native to China and has great pharmacological potential due to its lignans. However, there are significant knowledge gaps regarding the genetic and molecular mechanisms of lignans. We used transcriptome sequencing technology to analyze root, stem, and leaf samples, focusing on the identification and phylogenetic analysis of Cytochrome P450 (CYP) genes. High-quality data containing 158,385 transcripts and 68,978 unigenes were obtained. In addition, 36,293 unigenes in at least one database, and 23,335 across five databases (Nr, KEGG, KOG, TrEMBL, and SwissProt) were successfully annotated. The KEGG pathway classification and annotation of these unigenes identified 10,825 categorized into major metabolic pathways, notably phenylpropanoid biosynthesis, which is essential for lignan synthesis. A key focus was the identification and phylogenetic analysis of 233 Cytochrome P450 (CYP) genes, revealing their distribution across 38 families in eight clans, with roots showing specific CYP gene expression patterns indicative of their role in lignan biosynthesis. Sequence alignment identified 22 homologous single genes of these CYPs, with 6 homologous genes of CYP719As and 1 of CYP81Qs highly expressed in roots. Our study significantly advances the understanding of the biosynthesis of dibenzocyclooctadiene lignans, offering valuable insights for future pharmacological research and development.

Four new 14(13 → 12)-abeolanostane triterpenoids featuring extended π-conjugated systems, kadcoccitanes E-H (1-4), were obtained from the stems of Kadsura coccinea through using a HPLC - UV-guided approach. Their structural and configurational determination was accomplished through extensive spectroscopic analysis coupled with quantum chemical calculations. Kadcoccitanes E-H were tested for their cytotoxic activities against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, SW-480) but none of them exhibited activities at the concentration 40 μM.

BACKGROUND: The fruit of Kadsura coccinea (Lem.) A. C. Smith is an ethnomedicine used to treat abnormal menstruation, menopausal syndrome, and female infertility among the Dong Nationality in China.
OBJECTIVE: Our study aimed to identify the volatile oil profiles of the K. coccinea fruit and elucidate their estrogenic activity.
METHODS: The peel volatile oil (PeO), pulp volatile oil (PuO), and seed volatile oil (SeO) of K. coccinea were extracted using hydrodistillation and qualitatively analyzed using gas chromatography-mass spectrometry (GC-MS). Estrogenic activity was evaluated in vitro using cell assay and in vivo using immature female rats. Serum 17β-Estradiol (E2) and follicle-stimulating hormone (FSH) levels were detected using ELISA.
RESULTS: In total, 46 PeO, 27 PuO, and 42 SeO components representing 89.96%, 90.19%, and 97% of the total composition, respectively, were identified. The compounds with the highest content in PeO, PuO, and SeO were β-caryophyllene, γ-amorphene, and n-hexadecanoic acid, respectively. PeO induced proliferation of MCF-7 cells with an EC50 of 7.40 μg/mL. Subcutaneous administration of 10 mg/kg PeO significantly increased the weight of the uteri in immature female rats, with no effect on serum E2 and FSH levels. PeO acted as an agonist of ERα and ERβ. PuO and SeO showed no estrogenic activity.
CONCLUSIONS: The chemical compositions of PeO, PuO, and SeO of K. coccinea are different. PeO is the main effective fraction for estrogenic activities, providing a new source of phytoestrogen for the treatment of menopausal symptoms.

The changes of bioactive substances in peels and sarcocarps of three different varieties of Kadsura coccinea (Dahong, Fenhong, and Zihei) were evaluated by an in vitro simulation model. In this study, three varieties of K. coccinea fruits were digested in vitro to compare the changes and differences in antioxidant activity (DPPH, ABTS, FRAP) and bioaccessibility. The results showed that before digestion the highest content of total phenolics (TPC) (2.265 ± 0.127 mg GAE/g DW) and the highest content of flavonoids contents (TFC) (10.379 ± 0.093 mg GAE/g DW) were found in Fenhong fruit. The highest release of TPC and TFC after simulated gastric digestion was observed in the Dahong and Zihei sarcocarp, which increased by 98.7 and 20%, respectively. During oral and intestinal digestion, the content of bioactive compounds showed a decreasing trend. The radical scavenging ability of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), [2,2-azino-bis(3-ethylbenzothiazoline) (ABTS)] sulfonic acid free radical scavenging ability, and ferric ion reducing antioxidant power (FRAP) results showed that the antioxidant capacity of K. coccinea fruits increased most significantly (26.9∼181%) in gastric digestion stage and then decreased after intestinal digestion stage. The recoveries of TPC and TFC were all increased after whole simulated digestion, as well as their bioaccessibility in sarcocarps was higher than those in peels, especially for the bioaccessibility of TPC and TFC in Dahong reached 50.53 and 48.19%, respectively. These results indicated that the peel and sarcocarp of K. coccinea had good antioxidant activity, with high bioaccessibility of phenolics could be a promising antioxidant source for the food industry.

Heilaohu, the roots of Kadsura coccinea, has been used in Tujia ethnomedicine to treat rheumatic arthritis (RA). Heilaohuacid G (1), a new 3,4-seco-lanostane type triterpenoid isolated from the ethanol extract of Heilaohu, whose structure was determined using HR-ESI-MS data, NMR spectroscopic analyses, and ECD calculations. In this study, our purpose is to elucidate the mechanisms of Heilaohuacid G in the treatment of RA by inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells and inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. The biological activity screening experiments indicated that Heilaohuacid G significantly inhibited proliferation of RA-FLS cells with IC50 value of 8.16 ± 0.47 μM. CCK-8 assay, ELISA, flow cytometry assay, and Western blot were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Heilaohuacid G was found not only induced RA-FLS cell apoptosis, but also inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. Furthermore, Heilaohuacid G (p.o.) at doses of 3.0, 6.0, and 12.0 mg/kg and the ethanol extracts of Heilaohu (p.o.) at doses of 200, 400, and 800 mg/kg both were confirmed antiinflammatory effects on xylene-induced ear mice edema model.

Fruit color, as an important appearance attribute, is crucial for attracting consumers. However, the underlying mechanism regulating mature fruit color formation in Kadsura coccinea remains unclear. Here, a comprehensive metabolomics and transcriptomics analysis was performed to investigate the molecular mechanisms of anthocyanin accumulation between two K. coccinea cultivars with different mature fruit colors-\'Dahong No. 1\' (red) and \'Jinhu\' (yellow). Targeted metabolomic analysis revealed high anthocyanin levels, most of which were cyanidin and delphinidin derivatives, in \'Dahong No. 1\' mature fruit peel. The SNP analysis indicated that the two different cultivars had similar genetic background. Moreover, comparative transcriptomic analysis demonstrated that differentially expressed genes (DEGs) were related to flavonoid biosynthesis and metabolic process in the two K. coccinea cultivars. Gene expression profiling data showed that the structural and regulatory genes associated with anthocyanin biosynthesis were significantly upregulated in \'Dahong No. 1\' mature fruit peel, which was verified by quantitative real-time polymerase chain reaction (qRT-PCR). Notably, the key anthocyanin activator KcMYB1 was identified, which was significantly upregulated in \'Dahong No. 1\' compared with \'Jinhu\'. We further confirmed that KcMYB1 actively regulated the accumulation of anthocyanin by ectopic expression in vivo. Furthermore, allelic constitution of KcMYB1 in K. coccinea were investigated. The present study can provide insights for understanding the regulatory mechanisms of anthocyanin differential accumulation in the mature fruits of K. coccinea.

This study evaluated the phenolics profile and the antioxidative properties of K. coccinea fruits epicarp. A total of 13 phenolic compounds (six phenolic acids, four anthocyanins, two flavonols, and one flavone) were identified by ultra performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spetrometry(UPLC-QTOF-MS/MS). Two anthocyanins, cyanidin-3-xylosylrutinoside and cyanidin-3-rutinoside, comprise 30.89~74.76% and 13.90~46.17% of the total amount of anthocyanins in K. Coccinea. Cytoprotective effect results evidenced that pretreatment of Human umbilical vein endothelial cells(HUVECs) with Kadsura. coccinea fruits\' epicarp phenolic extracts at the concentrations of 50-200 µg/mL improved the cell viability after exposure to H2O2 significantly, and inhibited malonaldehyde(MDA) and reactive oxygen species(ROS) overproduction, as well as enhancing the content of superoxide dismutase (SOD) and glutathione Reductase (GR. This study proved that K. coccinea is a natural resource of phenolics rich with potential antioxidant ability, which may be valuable for developing nutraceuticals and dietary supplements.

One new 3,4-seco-17,13-friedo-lanostane triterpenoid heilaohuacid A (1), one new 3,4-seco-17,14-friedo-lanostane triterpenoid heilaohuacid B (2), five new 3,4-seco-lanostane triterpenoids heilaohuacids C-D (3-4) and heilaohumethylesters A-C (7-9), one new 3,4-seco-cycloartane triterpenoid heilaohuacid E (5), and one new intact-lanostane triterpenoid heilaohuacid F (6), together with twenty-two known analogues (10-31), were isolated from heilaohu. Their structures were determined using HR-ESI-MS data, 1D and 2D NMR spectra, 13C NMR calculations, and electronic circular dichroism (ECD) calculations. Heilaohuacids A and B (1 and 2) contain a 3,4-seco ring A and unprecedented migration of Me-18 from C-13 to C-17 or C-14 to C-18. This type of lanostane triterpenoid derivatives was rarely reported so far. More importantly, all compounds against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were evaluated, and compounds 4 and 31 significantly inhibited the release level of IL-6 with IC50 values of 8.15 and 9.86 μM, respectively. Meanwhile, compounds 17, 18, and 31 significantly inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells in vitro with IC50 values of 7.52, 8.85, and 7.97 μM, respectively.

The roots of Kadsura coccinea is commonly used in Tujia ethnomedicine, named \"heilaohu\", having the effect of treating rheumatic arthritis (RA). Chemical investigation on the ethanol extract of heilaohu led to the isolation of one undescribed cuparane sesquiterpenoid, heilaohusesquiterpenoid A, one undescribed carotane sesquiterpenoids, heilaohusesquiterpenoid B, and eighteen sesquiterpene derivatives. Their structures were subsequently determined based on their 1D and 2D-NMR, HR-ESI-MS, and ECD spectroscopic data. Gaultheriadiolide was the most cytotoxic compound against the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells with an IC50 value of 9.37 μM. In the same line, nine compounds exhibited significant inhibition effects against TNF-α and IL-6 release in the LPS-induced RAW264.7 cells with IC50 values ranging between 1.03 and 10.99 μM. The potential molecular mechanisms of the active compounds against RA were established through pharmacological network analysis based on the initial screening results. Experimental validation showed that gaultheriadiolide suppressed inflammation by inhibiting the NF-kB and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and anti-inflammatory studies.

暂无摘要。