[Chemical constituents from roots of Kadsura heteroclita].

The dichloromethane fraction of Kadsura heteroclita roots was separated and purified by chromatographic techniques(e.g., silica gel, Sephadex LH-20, ODS, MCI column chromatography) and semi-preparative HPLC. Twenty compounds were isolated from K. heteroclita, and their structures were identified by NMR, MS, UV, and X-ray single crystal diffraction techniques. Twenty compounds were isolated from K. heteroclita, which were identified as xuetongdilactone G(1), mallomacrostin C(2), 3,4-seco(24Z)-cychmrt-4(28),24-diene-3,26-dioic acid 3-methyl ester(3), nigranoic acid(4), methyl ester schizanlactone E(5), schisandronic acid(6), heteroclic acid(7), wogonin(8),(2R,3R)-4'-O-methyldihydroquercetin(9), 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid(10), stigmast-4-ene-6ß-ol-3-one(11), psoralen(12),(1R,2R,4R)-trihydroxy-p-menthane(13), homovanillyl alcohol(14), 2-(4-hydroxyphenyl)-ethanol(15), coniferaldehyde(16),(E)-7-(4-hydroxy-3-methoxyphenyl)-7-methylbut-8-en-9-one(17), acetovanillone(18), vanillic acid(19) and vanillin(20). Compound 1 is a new compound named xuetongdilactone G. Compounds 2-3 and 8-20 are isolated from K. heteroclita for the first time.

Neolignans with anti-inflammatory activity from Piper kadsura (Choisy) Ohwi.

Two novel neolignans, piperkadsurenin A (1) and kadsurenin N (2), along with six known neolignans (3-8) and two lignans (9-10) were isolated from the stems of Piper kadsura (Choisy) Ohwi. Extensive spectroscopic data interpretation and ECD calculations were used to identify the structures of the new compounds 1 and 2. Especially, compound 1 represents the first example of neolignan with cyclopenta[b]pyran framework. The anti-inflammatory efficacy of compounds 1-10 in vitro was systematically assessed through NO production inhibitory assay. Compounds 3 and 7 significantly inhibited LPS-induced NO generation in RAW 264.7 cells, with IC50 values of 34.29 ± 0.82 and 47.5 ± 5.81 µM, respectively.

Transcriptomic Insights and Cytochrome P450 Gene Analysis in Kadsura coccinea for Lignan Biosynthesis.

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.

[Research progress on chemical constituents from Kadsura genus and its pharmacological activities and clinical application].

The 29 plant species in the Kadsura genus of the Schisandraceae family are mainly distributed in eastern and southeas-tern Asia. Ten species of plants in this genus are distributed in China, some of which are folk medicinal plants with activating blood circulation, relieving pain, dispelling wind, and dehumidifying effects. Their main constituents are lignans and triterpenes. The current pharmacology and clinical studies have shown that their extracts and constituents have anti-rheumatoid arthritis, liver protection, antioxidation, anti-inflammatory, and other biological activities. The rheumatologic and liver diseases can also be treated with the plants in the clinic. The new chemical constituents reported in the last decade(2012 to date) from the plants of Kadsura genus in China, as well as their pharmacological effects and clinical applications in recent years were reviewed, so as to provide a theoretical basis for further research on the genus.

Galgravin Isolated from Piper kadsura Ameliorates Lipopolysaccharide (LPS)-Induced Endotoxemia in Mice.

Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura, can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-κB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-α, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-α and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-α, IL-6, and iNOS in the lungs and decreased TNF-α and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.

Potential natural product 3,4-seco-schitriterpenoids from Kadsura japonica L. as anti-neuroinflammatory agents.

In the present study, the undescribed schitriterpenoids, kadsujanonols A-I (1-9), and eleven reported compounds (10-20) were isolated from K. japonica L. vines. Their structures of 3,4-seco-schitriterpenoids were elucidated mainly by spectroscopic analyses including 1H-, 13C-, and 2D-NMR, IR, HRESIMS spectra. The spatial configurations were determined by the single-crystal X-ray diffraction analysis of kadsujapnonol A (1), 15, 17, and 18, CD data and computational analysis. Furthermore, all isolates were evaluated for the anti-neuroinflammatory activity on LPS-stimulated NO production in BV2 microglial cells and compounds 2, 4, 5, 7, 9, 11, 13-16, and 18 exposed better or comparable suppression abilities than PDTC. Among them, kadlongilactone B (14) showed the best significant inhibiting ability (IC50 = 0.87 µg/mL) and the effect is through the attenuation of the inflammatory transcription factor p65NF-κB. Preliminary structure-activity relationship revealed that δ-lactone at the side chain and 7-member lactone at C-3/C-4, and 3,4:9,10 ring opening are important.

New Dibenzocyclooctadiene Lignans and Phenolics from Kadsura heteroclite with Anti-Inflammatory Activity.

A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes (1 and 2) together with 14 known compounds (3-16) by using multiple chromatographic techniques. New compounds (1 and 2) were obtained and identified by spectroscopic methods (HR-ESI-MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC50 value of 6.16±0.14 µM. Whereas, compounds (1, 3, and 6) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54 µM), and compounds (2, 4, 9, 10, 13, 15, and 16) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64 µM) toward TNF-α production, respectively.

Comparative analysis of mitochondrial genomes of Schisandra repanda and Kadsura japonica.

The family Schisandraceae is a basal angiosperm plant group distributed in East and Southeast Asia and includes many medicinal plant species such as Schisandra chinensis. In this study, mitochondrial genomes (mitogenomes) of two species, Schisandra repanda and Kadsura japonica, in the family were characterized through de novo assembly using sequencing data obtained with Oxford Nanopore and Illumina sequencing technologies. The mitogenomes of S. repanda were assembled into one circular contig (571,107 bp) and four linear contigs (10,898-607,430 bp), with a total of 60 genes: 38 protein-coding genes (PCGs), 19 tRNA genes, and 3 rRNA genes. The mitogenomes of K. japonica were assembled into five circular contigs (211,474-973,503 bp) and three linear contigs (8,010-72,712 bp), with a total of 66 genes: 44 PCGs, 19 tRNA genes, and 3 rRNA genes. The mitogenomes of the two species had complex structural features with high repeat numbers and chloroplast-derived sequences, as observed in other plant mitogenomes. Phylogenetic analysis based on PCGs revealed the taxonomical relationships of S. repanda and K. japonica with other species from Schisandraceae. Finally, molecular markers were developed to distinguish between S. repanda, K. japonica, and S. chinensis on the basis of InDel polymorphisms present in the mitogenomes. The mitogenomes of S. repanda and K. japonica will be valuable resources for molecular and taxonomic studies of plant species that belong to the family Schisandraceae.

Four new lanostane triterpenoids featuring extended π-conjugated systems from the stems of Kadsura coccinea.

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.

Characterization of the volatile profile and its estrogenic activity in Kadsura coccinea fruit.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: Our study aimed to identify the volatile oil profiles of the K. coccinea fruit and elucidate their estrogenic activity. MATERIALS AND 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 17ß-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 ß-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 ERß. PuO and SeO showed no estrogenic activity. CONCLUSION: 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.

First Report of Leaf Spot Caused by Lasiodiplodia theobromae on Kadsura coccinea in China.

Kadsura coccinea (Lem.) A. C. Smith is an evergreen liana widely cultivated in China for its economic importance in traditional medicine. Many phytochemical studies on the stems and roots of K. coccinea have shown a variety of biological activities, such as anti-hepatitis, anti-HIV, and anti-tumor (Yang et al. 2020). In July 2021, symptoms of leaf spot were observed in a plantation of K. coccinea in Longan (23°03´N, 107°54´E), Guangxi province, China. The incidence of this disease was 36%, and severity varies from approximately 20 to 40% of leaf surface coverage. Symptoms began as small brown spots that expanded into irregular to nearly flower-shaped lesions. To isolate the pathogen, leaves with spots were collected, sterilized with 75% ethanol for 15 s followed by 2% sodium hypochlorite for 120 s, rinsed three times in sterilized distilled water, cut into 5 × 5 mm pieces, and placed onto potato dextrose agar (PDA) plates. The plates were kept in an incubator at 26°C in the dark for at least 2 days. A total of 27 fungal colonies of similar morphology out of 30 pieces of infected tissues were isolated. Four representative isolates (HBB1 to HBB4) were selected to study for further characterization. Fungal colonies were initially grayish-white and then turned greenish-gray on PDA. The black pycnidium and immature conidia appeared over PDA plates after 18 days. The immature conidia were colorless and transparent, elliptical, and had a single-cell structure. After 5 days, the immature conidia gradually become black and develop into mature conidia. The mature conidia were dark brown and two-celled with longitudinal striations, 20.41-29.93 × 12.42-17.19 µm (average 26.07×14.51 µm; n = 100). For DNA-based identification, the internal transcribed spacer (ITS) region, translation elongation factor 1 alpha (EF1-α), and ß-tubulin (TUB) genes of the isolates were amplified and sequenced using the primers ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999), and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. Sequences were submitted to GenBank (Accession nos. MW045412 to MW045415 for ITS, MW065559 to MW065562 for EF1-α, and MW065555 to MW065558 for TUB). A phylogenetic analysis was conducted using the Maximum Likelihood method on concatenated sequences of the three genes, which showed that the four Chinese isolates from K. coccinea were clustered with reference isolates of Lasiodiplodia theobromae including the ex-neotype CBS 164.96. Pathogenicity tests were performed on young, fully expanded leaves of 2-year seedlings. A 10 µL conidial suspension (1×106 conidia/mL) was inoculated on each wound on the left-half leaf and a 10 µL sterile water was inoculated on each wound on the right-half leaf (control). Each treatment was repeated three times. Inoculated leaves were wrapped in plastic bags for 5 days and plants were maintained in a growth chamber at 27°C, 85% relative humidity. Brown leaf spots appeared 5 to 6 days after inoculation, whereas the control leaves treated with sterile water showed no symptoms. All re-isolations from spots produced colonies with the same morphological characters as L. theobromae, completing Koch's postulates. To our knowledge, this is the first report of L. theobromae causing leaf spot on K. coccinea in China and worldwide. Severe leaf disease caused by L. theobromae threatens K. coccinea production. The disease threatens K. coccinea growth, and effective control measures should be identified to reduce losses.

Kadsindutalignans A-C: three new dibenzocyclooctadiene lignans from Kasura induta A.C.Sm. and their nitric oxide production inhibitory activities.

Phytochemical study on the methanol extract of the stems and leaves of Kadsura induta led to the isolation of six dibenzocyclooctadiene lignans, including three new compounds named kadsindutalignans A-C (1-3), and three known ones, heteroclitalignan B (4), kadsuphilin C (5) and kadsulignan E (6). Their structures were elucidated based on extensive spectroscopic analyses, including HRESIMS, 1D- (1H NMR and 13C NMR), 2D-NMR (HSQC, HMBC, 1H-1H COSY and NOESY), and experimental circular dichroism (CD) spectra. All the isolates inhibited NO production in LPS-activated RAW264.7 cells with IC50 values in the range from 5.67 ± 0.54 µM to 38.19 ± 2.03 µM, compared to that of the positive control of NG-monomethyl-L-arginine acetate (L-NMMA) with an IC50 value of 8.90 ± 0.48 µM. Interestingly, the new compound 2 showed potential inhibition of NO production with an IC50 value of 5.67 ± 0.54 µM, which was higher than that of the positive control.

Comparative transcriptomic analysis identifies KcMYB1 as a R2R3-MYB anthocyanin activator in Kadsura coccinea.

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.

Heilaohuacid G, a new triterpenoid from Kadsura coccinea inhibits proliferation, induces apoptosis, and ameliorates inflammation in RA-FLS and RAW 264.7 cells via suppressing NF-𝜠B pathway.

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.

Neolignans and amide alkaloids from the stems of Piper kadsura and their neuroprotective activity.

Four undescribed neolignans and three undescribed amide alkaloids, along with twelve known compounds, were isolated from the stems of Piper kadsura (Choisy) Ohwi. The structures of the new compounds were determined by spectroscopic analysis, quantum-chemical calculations, and Mo2(OAc)4-induced ECD analysis. The neuroprotective effects of these compounds against Aß25-35-induced cell damage in PC12 cells were investigated, and eight compounds exhibited significant neuroprotective effects against Aß25-35-induced PC12 cell damage, with the EC50 values of 3.06-29.3 µM. Three of these compounds were selected for further experiments, and they appear to reduce apoptosis and enhance autophagy against Aß25-35-induced PC12 cell damage.

Physicochemical Characterization and Antioxidant and Hypolipidaemic Activities of a Polysaccharide From the Fruit of Kadsura coccinea (Lem.) A. C. Smith.

Kadsura coccinea fruit, a novel fruit resource, has attracted wide interest, but the physicochemical characteristics and biological activities of its polysaccharides remain unclear. This study investigated the physicochemical properties of a polysaccharide extracted from K. coccinea fruit polysaccharide (KCFP) and evaluated its antioxidant and hypolipidaemic activities in vitro and in vivo. KCFP is an amorphous, thermally stable pectin heteropolysaccharide with an average molecular weight of 204.6 kDa that is mainly composed of mannose, rhamnose, glucose, galactose, xylose, arabinose, galacturonic acid (molar percentage >70%) and glucuronic acid. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays and an iron reducing antioxidant power assay showed that KCFP has strong antioxidant capacity, while the bile acid binding assay showed that KCFP has hypolipidaemic potential in vitro. The antioxidant and hypolipidaemic activities of KCFP were further evaluated in high-fat diet-induced hyperlipidaemic mice. KCFP significantly increased the activities of superoxide dismutase, glutathione peroxidase and catalase, decreased the malondialdehyde content, significantly reduced the total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels, and increased the amount of high-density lipoprotein cholesterol (HDL-C). These findings suggest that KCFP could be used as a functional food to remedy oxidative damage and hyperlipidaemia.

Schisandraceae triterpenoids: A review of phytochemistry, bioactivities and synthesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Schisandraceae family have a rich and medicinal history dating back to ancient times. Many of them are used as folk medicine in the treatment of chronic coughs, asthma, nocturnal emission, spontaneous sweating, night sweats, palpitation, insomnia and thirst. AIM OF THE REVIEW: The current review is carried out on triterpenoids from the Schisandraceae family, aiming to comprehensively summarize their phytochemistry, pharmacology and synthesis and provide new insights to the chemical and pharmacological study and rational utilization on medicinal plants of the Schisandarceae family. MATERIALS AND METHODS: The information was searched from the scientific literature published from June 2014 to November 2021 on the online databases (including PubMed, CNKI, Elsevier, SciFinder and Web of Science) and other bibliography (e.g. the Chinese Pharmacopoeia, 2020 edition, Chinese herbal books). The scientific literature related to phytochemistry, pharmacology, biological activites and synthesis of triterpenoids from the Schisandraceae family was gathered. RESULTS: From June 2014 to November 2021, there were approximately 211 novel triterpenoids isolated and identified from 18 species of the Schisandraceae family. These compounds exhibit tremendous diversity in their structures, and some of them possess promising pharmacological activities, including anti-viral, anti-tumor, anti-inflammatory, hepatoprotective, immunosuppressive activities and neuroprotective effects. In the attempt to synthesize active compounds, the total synthesis of 13 schinortriterpenoids belonging to five structural types was successfully completed. CONCLUSIONS: Studies of triterpenoids from the Schisandraceae family are well documented in this review (from June 2014 to November 2021), and it is also well acknowledged that they are valuable resources with medicinal efficacy. However, relevant pharmacological studies are limited to in vitro tests, and data from in vivo studies and toxicology are lacking or unavailable. Fortunately, there is growing interest in the synthesis of active compounds, which should serve as an approach for accessing active compounds to develop in vivo or toxicity studies, with a view of clarifying their in vitro and vivo mechanisms for more effective and safe natural drugs.

Anti-RAFLS Triterpenoids and Hepatoprotective Lignans From the Leaves of Tujia Ethnomedicine Kadsura heteroclita (Xuetong).

A pair of 3,4-seco-cycloartane triterpenoid isomers with a rare peroxy bridge, namely, xuetonins A and B (1 and 2), four new lignans xuetonlignans A-D (3-6), a new sesquiterpene xuetonpene (7), and a new natural product xuetonin C (8), along with 43 known compounds, were obtained from the leaves of Tujia ethnomedicine, Kadsura heteroclita. Their structures and configurations were determined with the help of a combination of 1D- and 2D-NMR, HRESIMS spectra, electronic circular dichroism (ECD), and X-ray diffraction data. Compounds 2, 10, 13-15, and 17-19 showed moderate-to-potent activity against rheumatoid arthritis fibroblast-like synoviocytes (RAFLS) with IC50 values of 19.81 ± 0.26, 12.73 ± 0.29, 5.70 ± 0.24, 9.25 ± 0.79, 5.66 ± 0.52, 11.91 ± 0.44, 13.22 ± 0.27, and 15.94 ± 0.36 µM, respectively. Furthermore, compounds 22, 25, and 31 exhibited significant hepatoprotective effects against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells at 10 µM, and the cell viability increased by 12.93, 25.23, and 13.91%, respectively, compared with that in the model group (cf. bicyclol, 12.60%).

RAD-Seq and Ecological Niche Reveal Genetic Diversity, Phylogeny, and Geographic Distribution of Kadsura interior and Its Closely Related Species.

Most plants of Kadsura have economic value and medicinal application. Among them, K. interior and its closely related species have been demonstrated to have definite efficacy. However, the taxonomy and phylogenetic relationship of Kadsura in terms of morphology and commonly used gene regions remain controversial, which adversely affects its rational application. In this study, a total of 107 individuals of K. interior, K. heteroclita, K. longipedunculata, K. oblongifolia, and K. coccinea were studied from the perspectives of genetic diversity, phylogeny, and ecology via single nucleotide polymorphisms (SNPs) developed through restriction site-associated DNA sequencing (RAD-seq). Based on these SNPs, the genetic diversity, phylogenetic reconstruction, and population genetic structure were analyzed. Subsequently, divergence time estimation and differentiation scenario simulation were performed. Meanwhile, according to the species distribution records and bioclimatic variables, the Last Glacial Maximum and current potential distributions of five species were constructed, and the main ecological factors affecting the distribution of different species were extracted. The F ST calculated showed that there was a moderate degree of differentiation among K. heteroclita, K. longipedunculata, and K. oblongifolia, and there was a high degree of genetic differentiation between K. interior and the above species. The phylogenetic tree indicated that each of the species was monophyletic. The results of population genetic structure and divergence scenario simulation and D-statistics showed that there were admixture and gene flow among K. heteroclita, K. longipedunculata, and K. oblongifolia. The results of ecological niche modeling indicated that the distribution areas and the bioclimatic variables affecting the distribution of K. interior and its related species were different. This study explored the differences in the genetic divergence and geographical distribution patterns of K. interior and its related species, clarifying the uniqueness of K. interior compared to its relatives and providing a reference for their rational application in the future.

Phenolics Profile and Protective Effect on Injuried HUVEC Cells of Epicarp Extracts from Kadsura 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.