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Objective Dianjixueteng is a geoherb in Yunnan Province, the source plant of which is Kadsura interior. However, the formation of this geoherb is not clear in genetic mechanism, in which genome size is the first step that should be known on the genomic level. In this study we aimed to estimate the genome sizes of source plants of K. interior and three related herbs K. heteroclita, K. longipedunculata, and K. coccinea by flow cytometry (FCM) and make a comparison. Methods The genome sizes of K. interior, K. heteroclita, K. longipedunculata and K. coccinea, i.e., the source plants of Dianjixueteng and its relative medicinal materials, were estimated by FCM. The nuclei of K. interior were isolated using modified LB01 buffer, for the rest species, by the Galbraith’s buffer. Results The genome sizes of K. interior, K. heteroclita, K. longipedunculata, and K. coccinea were 7.36, 7.12, 7.01, and 5.15 pg/1C, respectively. Genome size of K. interior had no significant variation with those of K. heteroclita and K. longipedunculata (P = 0.296), which was significantly larger than that of K. coccinea. Conclusion Genome size can not distinguish K. interior from K. heteroclita and K. longipedunculata, but could distinguish them from K. coccinea, which lays the foundation for future studies on genetic mechanism of the geoherb formation.

Kadsura belongs to the Schisandroideae subfamily of Magnoliaceae. Plants from genus Kadsura are widely distributed in the South and Southwest of China. The plants of the genus are widely used as folk medicine for a long time in history, with the functions of relieving pain, promoting ‘qi’ circulation, activating blood resolve stasis, and applications in the treatment of rheumatoid arthritis and gastroenteric disorders. Lignans are the primary characteristic constituents with various biological activities of plants from genus Kadsura. This paper summarized 81 lignans isolated from the plants of genus Kadsura over the past eight years (from 2014 to 2021), which belong to five types: dibenzocyclooctadienes, spirobenzofuranoid dibenzocyclooctadienes, aryltetralins, diarylbutanes and tetrahydrofurans. Each type of these lignans possess typical characteristics in proton magnetic resonance (1H NMR) and carbon-13 nuclear magnetic resonance (13C NMR) spectra, the NMR regularities of these types of lingans were summarized, which provided a useful reference for the structural analysis of lignans. The relationships between lignans and pharmacodynamics were also systematically analyzed, lignans were predicted to be the quality markers (Q-marker) of Kadsura genus.

Stems and roots of Kadsura plant species were the significant ingredients of traditional Chinese medicine. Kadsura heteroclita is one of the popular medicinal plants used in Tujia and Yao nationalities of China. Antioxidant compounds like lignan, sesquiterpenoid and triterpenoid are the major active components of K. hetroclita. Mass cultivation and bio-manufacturing strategies were being proposed to meet the increasing demand of Kadsura species plant parts. Therefore, it is important to reveal the molecular networks involved in biosynthesis of these highly efficient medicinal compounds. Here, transcriptomes of roots, stems and leaves in K. heteroclite seedling were sequenced by Hiseq2000 and unigenes involved in biosynthesis of lignan, sesquiterpenoid and triterpenoid biosynthesis were mined. As a result, 472 million clean reads were obtained which after aligning resulted in 160,248 transcripts and 98,005 genes. 191 and 279 unigenes were expected to be involved in biosynthesis of lignan, sesquiterpenoid and triterpenoid biosynthetic pathways respectively. Lignan, sesquiterpenoid and triterpenoid biosynthesis pathway genes were highly significant and differentially upregulated in roots and stems and downregulated in leaves. Also, genes encoding for MYB and bHLH transcription factors possibly involved in regulation of lignan, sesquiterpenoid and triterpenoid biosynthesis were discovered. These results provide the fundamental genomic resources for dissecting of biosynthetic pathways of the active components in K. hetroclita.

Oxidative stress plays a role in regulating a variety of physiological functions in living organisms and in the pathogenesis of articular cartilage diseases. Piper kadsura Ohwi is a traditional Chinese medicine that is used as a treatment for rheumatic pain, and the extracts have anti-inflammatory and antioxidant effects. However, there is still no study related to cell protection by P. kadsura. The P. kadsura extracts (PKE) were obtained by microwave-assisted extraction, liquid-liquid extraction, and column chromatography separation. The extracts could effectively scavenge free radicals in the antioxidant test, the EC50 of extracts is approximately the same as vitamin C. PKE decreased the apoptosis of SW1353 cells treated with H2O2 and could upregulate the gene expression of antioxidant enzymes (SOD-2, GPx, and CAT) and the Bcl-2/Bax ratio, as well as regulate PARP, thus conferring resistance to H2O2 attack. PKE protects cells against apoptosis caused by free radicals through the three pathways of JNK, MEK/ERK, and p38 by treatment with MAPK inhibitor. The identified components of PKE were bicyclo [2.2.1] heptan-2-ol-1,7,7-trimethyl-,(1S-endo)-, alpha-humulene, and hydroxychavicol by gas chromatography–mass spectrometry.

Phytochemical investigation on the roots of Kadsura coccinea led to the isolation five previously unknown dibenzocyclooctadiene lignans, named heilaohusuins A-E (1–5). Their structures determined by NMR spectroscopy, HR-ESI-MS, and ECD spectra. Hepatoprotection effects of a series of dibenzocyclooctadiene derivatives (1–68) were investigated against acetaminophen (APAP) induced HepG2 cells. Compounds 2, 10, 13, 21, 32, 41, 46, and 49 showed remarkable protective effects, increasing the viabilities to > 52.2% (bicyclol, 52.1 ± 1.3%) at 10 μM. The structure–activity relationships (SAR) for hepatoprotective activity were summarized, according to the activity results of dibenzocyclooctadiene derivatives. Furthermore, we found that one new dibenzocyclooctadiene lignan heilaohusuin B attenuates hepatotoxicity, the mechanism might be closely correlated with oxidative stress inhibition via activating the Nrf2 pathway.

The genus Kadsura comprises woody vine plants belonging to the family Schisandraceae. Species are found mostly in Northern Thailand and widely consumed by the local population. Occurrences of these wild fruits are rare as they only grow naturally in forest areas. Nutritive values of Kadsura spp. remain unclear, leading to improper management for food applications. Nutritional composition of Kadsura spp. was evaluated to promote sustainable conservation. Nutritive values in different fruits parts (exocarp, mesocarp, seed and core) of two Kadsura species as Kadsura coccinea (Lem.) A.C. Sm. and Kadsura heteroclita (Roxb.) Craib, from Chiang Rai Province, Thailand were assessed. When comparing nutritional contents based on per 100 g dry weight, results suggested that K. coccinea exhibited higher carbohydrate (1–2 times), sugar (1–2 times) and vitamin C (3–4 times) contents than K. heteroclita, while the latter possessed higher fat (1–2 times), protein (1.6–1.9 times), and dietary fiber (1.5–1.8 times) contents. Considering each fruit part, the mesocarp (the only edible fruit part) and exocarp of both species provided high dietary fiber (11.6–20.9% recommended dietary fiber) and vitamin C (as high as 73% recommended per day) but were low in energy (30–40 kcal/100 g fresh weight), protein (0.6–1.2% recommended per day), fat (0.5–1.8% recommended per day) and sugar (2.4–5.4% recommended per day). Interestingly, seed contained higher energy (1–2 times), protein (2–3 times) and fat (4–50 times) than the other fruit parts. Results support the potential consumption of Kadsura spp. as a healthy fruit that can be used for future food applications. Seed and exocarp from Kadsura spp. also showed potential for new product development., Food analysis, Nutrition, Kadsura coccinea (Lem.) A.C. Sm., Kadsura heteroclita (Roxb.) Craib, Conservative plant, Fruit parts, Nutritive values.

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.

Kadsuraols A-C (1-3), which are tetrahydrocyclobutaphenanthrofuranone-type lignans with a new carbon skeleton comprising a four-membered ring across C-1'-C-8, have been isolated from the roots of Kadsura longipedunculata. Their structures and absolute configurations were unambiguously determined using nuclear magnetic resonance, X-ray diffraction crystallography, DP4+ calculations, and computed and experimental electronic circular dichroism spectra. Kadsuraol C (3) exhibited hepatoprotective activity against N-acetyl- p-aminophenol (APAP)-induced toxicity. The compounds showed no cytotoxicity at 10 μM in a zone assay.

Plants in genus Kadsura, belong to the Schisandraceae family including genus Schisandra and genus Kadsura, revealed folk efficacy and medicinal application in the treatment of rheumatoid arthritis and gastroenteric disorders for a long history. Previous study indicated that plants from genus Kadsura mainly contain lignans, triterpenoids and essential oils, and showed the active compounds were lignans and triterpenoids. Among all compounds from Schisandraceae family, the triterpenoids between the genus Schisandra and genus Kadsura had obvious differences. In this paper, we reviewed 214 triterpenoids and their pharmacological activities reported from genus Kadsura in the past 30 years (from 1987 to 2017), aiming to provide reference for further study. Keywords: Kadsura, Triterpenoids, Structures, Classifications, Pharmacological activities

The plants of the genus Kadsura are widely distributed in China, South Korea, and Japan. Their roots and stems are traditionally used to treat blood diseases and pain. The main bioactive constituents of Kadsura longipedunculata comprise highly oxygenated triterpenoids. Schiartane-type nortriterpenoids showed anti-HIV, anti-HBV, and cytotoxic bioactivities. For such compounds, the absolute configuration influences the bioactivities, and hence its unambiguous determination is essential. In this work, the absolute configurations of three highly oxygenated schiartane-type nortriterpenoids were unequivocally assigned using X-ray, ECD, and J-based configuration analysis and HSQC overlay data.The ethanol extract of Kadsura longipedunculata Finet et Gagnep was purified by column chromatography using silica, Sephadex LH-20, and ODS as substrates. To help assign the absolute configuration of schiartane-type nortriterpenoids, X-ray diffraction analysis, ECD experiment compared to ab initio computed data, DP4+ analysis, HSQC overlay, NOESY, and J-based configuration analysis were carried out. Hetero- and homo-nuclear coupling constants were extracted from HETLOC experiments.Three new highly oxygenated triterpenoids, micrandilactone I (1), micrandilactone J (2), and 22,23-di-epi-micrandilactone J (3) were isolated. Their 2D structures were solved using NMR and HRESIMS data and their absolute configurations were elucidated using X-ray diffraction analysis, ECD experimental results compared to ab initio computed spectra, HSQC overlay, DP4+, NOESY, and J-based configuration analysis. Micrandilactone I (1) and 22,23-di-epi-micrandilactone J (3) showed moderate hepatoprotective activity against APAP-induced toxicity in HepG2 cells with cell survival rates of 53.0 and 50.2%, respectively, at 10μM (bicyclol, 49.0%), while micrandilactone J (2) was inactive.This is the first comprehensive stereochemical assignment of a non-crystalline schiartane-type nortriterpenoid like 3. This general protocol may contribute towards solving the problems hampering the assignment of the absolute configurations of other members of this class of nortriterpenoids.

Objective: To identify Kadsura interior (Dian Ji Xue Teng, Schisandraceae) by using DNA barcoding.

Two new tetrahydrobenzocyclooctabenzofuranone lignans (1-2), a new dibenzocyclooctadiene lignan (3) and three new schiartane-type triterpenoids (4-6), together with six known compounds (7-12), were isolated from the roots of Kadsura longipedunculata. Their structures were elucidated by extensive NMR and HRESIMS spectroscopic data analysis. The absolute configurations of these compounds were determined by comparison of the experimental and calculated ECD spectra. Compound 12 exhibited moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with cell survival rates of 53.04%.

The fermentation of Kadsura angustifolia with an endophytic fungus, Penicillium ochrochloron SWUKD4.1850 yielded five additional undescribed oxygenated terpenoids, kadanguslactones A-E, together with ten known compounds. Their structures were established by the extensive 1D, 2D-NMR, HR-ESI-MS, CD and X-ray crystallography data analysis. Kadanguslactone A is the first example of 1,30-cyclo-3,4; 9,10-disecocycloartanes that combine a five-membered lactone ring A with a cyclopentane ring B consisting of C-1, C-4, C-5, C-10, C-30. Kadanguslactone B was a rare highly oxygenated 18-norschiartane-type bisnortriterpenoid with spirocyclis rings F and G, whereas kadanguslactone C was an uncommon henrischinin-type schitriterpenoid containing a unique 3-one-2-oxabicyclo [3,2,1]-octane motif. The cytotoxicity against HepG2 cell line of all compounds were evaluated. Except nigranoic acid, all other metabolites have been first found in unfermented K. angustifolia, suggesting that main functional ingredients from K. angustifolia may be converted by P. ochrochloron SWUKD4.1850 into highly oxygenated terpenoids. This study provided a fascinating prospective for setting up alternative processing techniques to enhance the functionality and utility of Chinese herbal medicine.

Four new dibenzocyclooctadiene lignans, named heilaohusus A-D (1–4), one new arylnaphthalene lignan named heilaohusu E (5), and seven known analogues (6–12) were isolated from the roots of Kadsura coccinea. Their structures and configurations were elucidated by a combination of HR-ESI-MS, 1H NMR, 13C NMR, HSQC, HMBC, NOESY and CD spectra. Among the known compounds, compounds 6 and 8–12 were isolated from this plant for the first time. All of compounds were evaluated for their cytotoxicity activities, compounds 3, 6 and 7 showed weak cytotoxicity against four human cancer cell lines (HepG-2, HCT-116, BGC-823 and Hela) with IC50 values range from 13.04 to 21.93 μM. Compounds 1 and 7 demonstrated potential anti-RA (rheumatoid arthritis) activity against RA-FLS cell line with IC50 values of 14.57 and 11.70 μM, respectively.

In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name “Xuetong”. This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1–6), along with five known triterpenoids (7–11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 μM.

In the present work, we take advantage of the characteristic NMR signal (δC-10 = 96.0–99.9) for guiding the isolation of schinortriterpenoids (SNTs) from n-butanol fraction of stems of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name “Xuetong”. This effort resulted in the identification of three unreported 3,4:9,10-disecocycloartane triterpenoids xuetongdilactones A-C and three undescribed SNTs xuetongdilactones D-F, along with two known SNTs, namely, wuweizidilactone B and micrandilactone B. The structures of the unreported compounds were established based on 1D, and 2D NMR, HRESIMS, and ECD spectroscopic data analysis. The absolute stereochemistry of xuetongdilactone A was determined by X-ray diffraction analysis along with ECD calculation. The antioxidant and cytotoxic activities were evaluated for all the isolated compounds.

As part of our continual efforts to exploit &lsquo, Tujia Ethnomedicine&rsquo, for their pharmacophoric functionalities, we herein investigated Kadsura heteroclita collected from a deep Wulin mountain area in northern Hunan province. The current study resulted in the isolation of three new sesquiterpenes: 6&alpha, 9&alpha, 15-trihydroxycadinan-4-en-3-one (1), (+)-3,11,12-trihydroxycalamenene (2), (&ndash, )-3,10,11,12-tetrahydroxy-calamenene (3), along with four known sesquiterpenes (4&ndash, 7), and a cytochalasin H (8). Their chemical structures were elucidated by 1D-, and 2D-NMR spectroscopy, and HRESI-MS, CD spectrometry. The antioxidant, and cytotoxic activities of the compounds were evaluated. Compound 8 exhibited a strong antioxidant effect with an IC50 value of 3.67 &micro, M on isolated human polymorphonuclear cells or neutrophils.

Among 15 plant methanol extracts, Piper kadsura stem extract (PkSE) showed the strongest larvicidal activity against Aedes albotictus. Larvicidal activities of P. kadsura stem extract were 100 % and 80 % at 0.01 and 0.005 mg/mL concentrations, respectively. Two isobutyl amides, pellitorine and chingchengenamide A, and one neolignan, piperenone, were isolated as active compounds from PkSE. Larvicidal activities of chingchengenamide A, piperenone, and pellitorine were 100 %, 100 %, and 87.5 % at 0.005 mg/mL concentration, respectively, and 100 %, 67.5 %, and 15.0 % at 0.0025 mg/mL. Cellulose nanocrystal (CNC)-stabilized Pickering emulsion of PkSE was developed, and its larvicidal activity was slightly higher than that of pure PkSE. Acute oral and dermal toxicity of PkSE toward rat, Rattus norvegicus, was >2000 mg/kg body weight. Acute contact toxicity of PkSE to honeybee was >100 μg/bee. The no observed effect concentration (NOEC) of PkSE to Oryzias latipes was 0.031 mg/mL.

Phytochemical investigations on the fresh fruits of Kadsura coccinea (Lem.) A. C. Sm. have led to the isolation of fourteen undescribed 2,2′-cyclolignans named heilaohuguosus A-N, four undescribed aryltetrahydronaphthalene lignans, heilaohuguosus O-R and one tetrahydrofuran lignan, heilaohuguosu S, with twenty-seven previously described lignan analogues. Their structures and absolute configurations of heilaohuguosus A-S were established by spectroscopic methods including 1D and 2D-NMR techniques and CD experiments. All isolated compounds were evaluated for their hepatoprotective activity against APAP-induced toxicity in HepG-2 cells, four 2,2′-cyclolignans, heilaohuguosus A and L, tiegusanin I and kadsuphilol I showed good hepatoprotective activities against APAP toxicity in HepG-2 cells with cell survival rates of 53.5 ± 1.7%, 55.2 ± 1.2%, 52.5 ± 2.4%, and 54.0 ± 2.2% (positive control bicyclol, 52.1 ± 1.3%) at 10 μM, respectively.

Ethnopharmacological relevance Kadsura heteroclita (Roxb.) Craib (traditionally known as “Xue Tong”) is an important member of the economically and medicinally important plant family Schisandraceae. “Xue Tong” is an imperative ingredient of the Tujia ethnomedicine, traditionally used for the treatment of rheumatoid arthritis (RA), hepatitis, and muscles and joint spasm. The plant is known to be a rich source of lignans and triterpenoids. These classes of natural products have been known to possess various pharmacological activities. Aim of review This review was motivated by the importance of K. heteroclita in traditional Chinese medicine (TCM). It aims to compile the available information on its botanical distribution and description, traditional uses, phytochemistry, pharmacological activities, toxicity, and quality control to provide a solid base for further research and development. Materials and methods Relevant literature was collected by several scientific databases including PubMed, CNKI, Scifinder, The Plant List, Google Scholar, Baidu Scholar, Books (Tujia pharmaceutical records, Guangxi Chinese herbal medicine, Hunan pharmaceutical records and Field identification manual of Chinese herbal medicine) and other literature sources (Flora of China, Pharmacopoeia of the People’s Republic of China) which helped in collecting maximum data about the studied species. Results Traditional uses of K. heteroclita have proven its medicinal importance, providing a rationale for scientific research. Phytochemical studies on the stem of K. heteroclita resulted in the identification of 187 chemical constituents, among which lignans and triterpenoids are the predominant groups. The isolates and crude extracts have been found to exhibit a wide spectrum of in vivo and in vitro pharmacological activities such as anti-RA, anti-inflammatory and analgesic, hepatoprotection, anti-HIV, anti-cancer and anti-HBV. Schisanlactone E (xuetongsu), a triterpenoid, is one of the major components of K. heteroclita exhibiting anti-cancer, neuroprotective and anti-neuroinflammation activities. Interestingly and luckily, this plant has been found to be safe and non-toxic within the therapeutic dose range. Conclusion Pharmacological investigations have validated the use of K. heteroclita in traditional Chinese medicine (TCM). Literature review has demonstrated that lignans and triterpenoids are possibly responsible for most of the biological activities exhibited by this plant. To conclude, this plant shows immense potential for the discovery of more potent bioactive secondary metabolites and therefore further phytochemical and biological studies on other parts of K. heteroclita need to be conducted and more compounds need to be tested regarding their biological activities to completely explore its value as a tremendously important medicinal plant species.

The stems and roots of Kadsura species have been used as the folk medicine in Traditional Chinese medicine (TCM) and have good traditional efficacy and medicinal application with a long history. Among these species, K. coccinea, K. heteroclita and K. longipedunculata are the most widely distributed species in the regions of south and southwest China. Owing to their similar appearance, the crude drugs are often confusedly used by some folk doctors, even some pharmaceutical factories. To discriminate the crude drugs, haplotype analysis based on cpDNA markers and ITS was firstly employed in this study. Generic delimitation, interspecific interrelationships, and the identification of medicinal materials between K. longipedunculata and K. heteroclita remained unresolved by the existing molecular fragments. The original plant could be identified through the morphological character of flower, fruit and leaf. However, in most situation collectors have no chance to find out these characters due to lack of reproductive organs, and have no experience with the minor difference and transitional variation of leaf morphology. The chemical characterization show that the chemometric of chemical composition owned higher resolution to discriminate three herbs of Kadsura species. In conclusion, this integrative approach involving molecular phylogeny, morphology and chemical characterization could be applied for authentication of the Kadusra. Our study suggests the use of this comprehensive approach for accurate characterization of this closely related taxa as well as identifying the source plant and confused herbs of TCM.

The first complete chloroplast genome (cpDNA) sequence of Kadsura interior was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 153,201 bp in length, contains a large single-copy region (LSC) of 85,774 bp and a small single-copy region (SSC) of 18,077 bp, which were separated by a pair of inverted repeats (IR) regions of 24,673 bp each. The genome contains 129 genes, including 85 protein-coding genes, 8 ribosomal RNA genes, and 37 transfer RNA genes. The overall GC content of the whole genome is 39.6%, . The further phylogenomic analysis showed that K. interior and Kadsura coccinea clustered in a clade in Schisandraceae family.

A phytochemical investigation of the stems of Kadsura interior has led to an isolation of four new lignans, named kadsutherin E–H (1–4), together with two known lignans (5–6). The structures of the four new compounds were established on the basis of comprehensive spectroscopic analyses. Compounds 1–6 exhibited inhibition against adenosine diphosphate (ADP) induced platelet aggregation. Among the isolated compounds, kadsutherin F (2) showed the strongest anti-platelet aggregation activity with an inhibition of 49.47%.

Highly oxygenated schitriterpenoids are interesting for study of their structures, bioactivities and synthesis. From Kadsura angustifolia fermented by an associated symbiotic endophytic fungus, Penicillium sp. SWUKD4.1850, nine undescribed triterpenoids, kadhenrischinins A-H, and 7β-schinalactone C together with four known triterpenoids, henrischinins A and B, schinalactone C and nigranoic acid were isolated and established by the extensive 1D-, 2D-NMR, HR-ESI-MS and ECD data analysis. Except nigranoic acid, all these metabolites have been first detected in non-fermented K. angustifolia. Structurally, kadhenrischinins A-D belong to the relatively rare class of highly oxygenated schitriterpenoids that contain a unique 3-one-2-oxabicyclo [3,2,1]-octane motif, while kadhenrischinins E-H feature a cyclopentane ring in a side chain rarely found in the family Schisandraceae. These results indicated that fermentation of K. angustifolia with SWUKD4.1850 induced the production of highly oxygenated schitriterpenoids from nigranoic acid, which provided a guidance to obtain desired compounds from those plants initially thought not to produce. This is the first report on the fermentation of K. angustifolia medical plant and the first discovery of highly oxygenated schitriterpenoids by microbial technology.

Chloroplast genomes of plants are highly conserved in both gene order and gene content, are maternally inherited, and have a lower rate of evolution. Chloroplast genomes are considered to be good models for testing lineage-specific molecular evolution. In this study, we use Schisandraceae as an example to generate insights into the overall evolutionary dynamics in chloroplast genomes and to establish the phylogenetic relationship of Schisandraceae based on chloroplast genome data using phylogenomic analysis. By comparing three Schisandraceae chloroplast genomes, we demonstrate that the gene order, gene content, and length of chloroplast genomes in Schisandraceae are highly conserved but experience dynamic evolution among species. The number of repeat variations were detected, and the Schisandraceae chloroplast genome was revealed as unusual in having a 10 kb contraction of the IR due to the genome size variations compared with other angiosperms. Phylogenomic analysis based on 82 protein-coding genes from 66 plant taxa clearly elucidated that Schisandraceae is a sister to a clade that includes magnoliids, monocots, and eudicots within angiosperms. As to genus relationships within Schisandraceae, Kadsura and Schisandra formed a monophyletic clade which was sister to Illicium.

Objective To find new triterpenoids from the stems of Kadsura heteroclite. Methods The constituents were isolated and purified by various column chromatographies. Their structures were elucidated mainly on the basis of 1D (1H-, l3C-, and DEPT), 2D (HSQC, HMBC, and ROESY) NMR and mass spectral analysis, also compared with literature data. Results Four triterpenoids were isolated and identified as 3-ethyl manwuweizate (1), 26-methyl manwuweizate (2), manwuweizic acid (3), and anwuweizonic acid (4). Conclusion Compounds 1 and 2 are new triterpenoids.

Five 3,4-seco-cycloartane triterpenoids were isolated from the stems of Kadsura ananosma, two of which had rearranged 5/6 consecutive carbocycle rings C/D (trivially named ananosins A (1) and B (2)), one had a migrated CH3-18 (named ananosins C (3)), and two were analogs, ananosins D (4) and E (5). Their structures were characterized by comprehensive spectroscopic analysis, especially using 2D NMR spectra. A biogenetic pathway to 1 was proposed. These 5 compounds, together with 5 known analogs isolated from the same origin, were evaluated for their cytotoxicity against HL-60, SMMC-7721, A-549, PANC-1, and SK-BR-3 human cancer cells, but were inactive.

Thirty-three metabolites including five phenalenone derivatives (1–5), seven cytochalasins (6–12), thirteen butenolides (13–25), and eight phenyl derivatives (26–33) were isolated from Aspergillus sp. CPCC 400735 cultured on rice. The structures of all compounds were elucidated by NMR, MS, and CD experiments, of which 1–5 (asperphenalenones A–E), 6 (aspochalasin R), and 13 (aspulvinone R) were identified as new compounds. Specifically, asperphenalenones A–E (1–5) represent an unusual structure composed of a linear diterpene derivative linked to a phenalenone derivative via a C–C bond. Compounds 1, 4, 10, and 26 exhibited anti-HIV activity with IC50 values of 4.5, 2.4, 9.2, and 6.6 μM, respectively (lamivudine 0.1 μM; efavirenz, 0.4 × 10–3 μM).

Background and Aims Resin is a defence against herbivores and a floral reward in a few African and South American species whose bee pollinators collect it for nest construction. Here we describe a new role for floral resin from the Asian genus Kadsura (Schisandraceae). Kadsura tepals tightly cover a globe formed by carpels (in females) or near-fused stamens with fleshy connectives (in male flowers of most, but not all species). Methods We carried out field observations at four sites in China and used pollinator behavioural assays, chemical analyses and time-calibrated insect and plant phylogenies to investigate the specificity of the interactions and their relationship to floral structure. Key Results Nocturnal resin midges (Resseliella, Cecidomyiidae) walk around on the flowers’ sexual organs to oviposit, thereby transferring pollen and wounding tissues. The larvae then develop in resin-filled chambers. Male and female floral scents are dominated by α-pinene, while the resinous exudate is dominated by caryophyllene. As revealed by barcoding of multiple midge larvae per flower species, the mutualisms are species specific and appear to have evolved over the past 6–9 million years. Conclusions Resin feeding, not pollen or ovule feeding, by midge larvae explains the abundant Kadsura exudates, highlighting the poorly known world of nocturnal flower–fly interactions.

Background Cambial variations in lianas of Piperaceae in Taiwan have not been studied previously. The stem anatomy of seven Piper species from Taiwan was examined to document cambial variations and better distinguish the species when leaves are absent. Results A key for the seven species is provided, based on the internal stem anatomy. The seven Piper species climb via adventitious roots, and in cross section, the stems were generally eccentric and oblate, although a transversely elliptic stem was found in P. kadsura (Choisy) Ohwi and P. sintenense Hatus. A cambial variant with secondary growth of external primary vascular bundles and xylem in plates was observed in all species except Piper betle L., which developed another cambium variant with xylem furrowed deeply by parenchyma proliferation. The sclerenchymatous ring surrounding the medullary vascular bundles was always continuous except in P. betle, where it was discontinuous. Mucilage canals varied from absent to present in the center of the pith, or present in the pith and inner cortex. Different sizes of vessels dispersed throughout the stem were ring or diffuse porous. The numbers of medullary and peripheral vascular bundles were distinctive and the widths of rays were noticeably different in each species. Differences in the growth rate of the medullary vascular bundles produced two development types of vascular bundles, although in both types, the peripheral vascular bundles gradually lengthen and become separated from each other by wide rays. Conclusions We documented the internal stem anatomy of six previously unstudied species of Piper, including three endemic species, P. kwashoense Hayata, P. sintenense, and P. taiwanense Lin and Lu, and found that P. betle had deeply furrowed xylem, which had not been reported for the species before. The descriptions and photographs of seven Piper species will also provide a basis for further morphological studies. Electronic supplementary material The online version of this article (doi:10.1186/s40529-017-0172-z) contains supplementary material, which is available to authorized users.

Kadsura (Schisandraceae) comprises ca. 16 species and widely distributes in eastern Asia. Many species in the genus were used as important medicinal plants in China and other Asian countries. In pr...

Schisanlactone E (SE) is a major triterpene obtained from the plants of genus Kadsura. The aim of this research was to investigate the transformed metabolites of SE by fungi and evaluate the bioactivities of these products. After screening 10 strains of filamentous fungi, Cunninghamella blakesleana AS 3.970 was chosen as a potent organism to be used for the biotransformation of SE. 13 metabolites were obtained and determined to be new compounds through the use of spectroscopic data, including UV, 1D-, 2D-NMR, and HR-ESIMS. Furthermore, in an in vitro bioassay, metabolites 7 and 9 showed moderate inhibitory effects on the nitric oxide production in LPS-induced macrophages with IC50 values of 16.73, 5.91 μM, respectively; 9 could inhibit the proliferation of acetaldehyde-induced HSC-T6 cells, with the IC50 value of 21.4 μM. Preliminary findings on the structure–activity relationships for these metabolites were also discussed.

Aim To study the chemical constituents of the roots and stem bark of Kadsura coccinea . Method Compounds were isolated by column chromatography on silica gel and Sephadex LH-20, and finally purified by prep-HPLC. Their structures were elucidated by extensive spectroscopic methods, including 1D- and 2D-NMR, and HR-ESI-MS. Results Two compounds were determined as (7′ S ,8′ S ,8 R )-(8β,8′α)-dimethyl-4,4′-dihydroxy-5,3′-dimethoxy-5′-cyclolignan glucoside ( 1 ) and micrandiactone H ( 2 ), respectively. Conclusion Compunds 1 and 2 are new and neither showed inhibitory effects on nitric oxide (NO) production in lipopolysaccharide-induced RAW264.7 macrophages.

Genus Kadsura Kaempf. ex Juss. includes important medicinal plants widely used in the south and southwest of China. The stems and roots are effective in activating blood and resolving stasis, promoting qi circulation to relieve pain, dispelling wind and eliminating dampness, in which lignans and triterpenoids are the major bioactive constituents. Here we summarized the chemical constituents isolated from genus Kadsura Kaempf. ex Juss., which would provide a primary and strategic platform for further exploiting the medicinal value and resources of genus Kadsura Kaempf. ex Juss.

This article describes 221 new triterpenoids especially schinortriterpenoids, published from February 2008 through July 2013 as constituents of the family Schisandraceae. The article discusses their source, biological activity, synthetical studies, stereochemistry aspects and chemotaxonomy significance. Applications of hyphenated techniques to the qualitative and quantitative analysis of schinortriterpenoids are also reviewed, together with advances in microbial transformation and synthetic studies.

Highly oxygenated nortriterpenoids are the principle bioactive chemical constituents isolated from plants of the genera Schisandra and Kadsura. The stereochemistry of these molecules remains a highly challenging problem to solve. To establish the stereochemistry and develop a general nuclear magnetic resonance-electric circular dichroism-computational approach to solve these complex metabolites, we reviewed the published methods to solve the stereochemistry of these triterpenoids. A key goal of this review is to provide a protocol to solve the problems hampering the assignment of the relative absolute configurations of other members of this natural product class.

Kadsura marmorata has been used in traditional Chinese medicine as one of the major ingredients for the treatment of bronchial asthma, eczema, and acute and chronic infection due to either viruses or bacteria. The purpose of this study was to determine the immunomodulatory activities of the Kadsura polysaccharide (KPS) that was isolated and purified from the fruit of K. marmorata, designated as KPSIII and has a molecular weight of 130,406. The immunomodulatory effects of KPSIII were evaluated in vitro on chicken lymphocytes and macrophages. The results indicated that KPSIII could stimulate the cell proliferation of chicken T-lymphocytes, B-lymphocytes, and peritoneal macrophages and could significantly enhance cytokine secretion. Moreover, KPSIII regulated cytokine expression in T-lymphocytes and peritoneal macrophages. This study suggests that KPSIII has potential effects on regulating the immune system and might be an immunotherapeutic agent in treating various immunity-related diseases in chickens.

Three new dibenzocyclooctadiene lignans, kadusurain A–C (1–3), together with two known compounds kadsuphilin A (4) and B (5), were isolated from an EtOAc fraction of the 80 % acetone extract of Kadsura coccinea (Lem.) A. C. Smith. Their structures were established by 1D and 2D NMR techniques, and mass spectroscopy. Anti-proliferative effect of isolated compounds was evaluated against four human tumor cell lines (A549, HCT116, HL-60, and HepG2), and it was found that compound 1 exhibited significant antiproliferative effects with IC50 values ranging from 1.05 to 12.56 μg/ml.

Seven new unusual dibenzocyclooctadiene lignans, neglignans A-G (1-7), together with 16 known dibenzocyclooctadiene lignans, were isolated from the stems of Schisandra neglecta. Compounds 1 and 2 are the first dibenzocyclooctadiene lignans bearing a carboxyl group at C-4, and compounds 3 and 4 are the first 7,8-seco-dibenzocyclooctadiene lignans found from Nature. The new compounds (1-7) and several of the known compounds were evaluated for their anti-HIV activity and cytotoxicity. Compounds 2 and 6 showed anti-HIV-1 activities with therapeutic index values greater than 50, and compound 4 showed cytotoxicity against the NB4 and SHSY5Y cancer cell lines with IC50 values of 2.9 and 3.3 mu M, respectively.

In this study, response surface methodology and central composite design based on single-factor experiments were applied to the optimization of the extraction parameters (extraction time, extraction temperature, and solid-liquid ratio) of polysaccharides from Kadsura marmorata fruits. The extraction temperature and solid–liquid ratio affected the extraction yield significantly. The optimal conditions included a solid–liquid ratio of 1:27 (mass/volume), an extraction time of 3 h and an extraction temperature of 98 °C. Under these conditions, the maximal yield of crude Kadsura polysaccharide (KPS) was 2.7735 ± 0.068%, which agreed with model predictions. Five major fractions, KPS I, KPS II, KPS III, KPS IV and KPS V, were obtained by diethylaminoethyl (DEAE) cellulose-52 column chromatography. The main fraction, KPS III-1, was isolated from KPS III by Sephadex G-100 column chromatography. Preliminary characterization of KPS III-1 by gas chromatography indicated that it was composed mainly of xylose and galacturonic acid.

The ability of the endophytic fungus Umbelopsis dimorpha SWUKD3.1410 to transform the triterpene nigranoic acid (3, 4-secocycloarta-4(28), 24-(Z)-diene-3, 26-dioic acid; 1) was investigated. Co-culture of nigranoic acid with U. dimorpha SWUKD3.1410 yielded six major products, including a new triterpene (2) and 5 known compounds (3–7). Their structures were identified by the extensive 1D, 2D NMR and HR-ESI-MS Data analysis, and by comparison with those reported data. Among them, 2–4 were transformed from nigranoic acid (1), while 5–7 were derived from the culture medium stimulated by the substrate. On the basis of the structures of 2–4, it was proposed that the transformative process probably involved isomerase and hydroxylase, in which the former was rare in fungi. Additionally, all the compounds (1–7) were evaluated for their cytotoxic activity. As a result, compounds 1, 3–5 exhibited weak cytotoxicity against the tested cell lines, while others showed no cytotoxicity.

Fourteen new rearranged 6/6/5/6-fused triterpenoid acids, namely, kadcoccine acids A–N (1–14), were isolated from an EtOAc-soluble extract of the stems of Kadsura coccinea. Their structures were characterized mainly by analyzing 1D and 2D NMR and HRESIMS data and were shown to feature a rare 14(13→12)-abeo-lanostane skeleton. Compounds 7 and 8 represented the first examples of a 5-substituted 2(5H)-furanone motif on the C-17 side chain of this skeleton. The absolute configurations of C-23 for compounds 1, 7, and 8 were determined by comparison of their experimental electronic circular dichroism spectra. All the isolates were screened for their in vitro cytotoxicity against six human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW-480, and HeLa), and compounds 2 and 8 exhibited weak inhibitory effects with IC50 values ranging from 3.11 to 7.77 μM.

Piper kadsura is a vine-like medicinal plant which is widely used in clinical treatment. However, P. kadsura is often substituted by other materials in the markets, thereby causing health risks. In this study, 38 P. kadsura samples and eight sequences from GenBank, including a closely-related species and common adulterants were collected. This study aimed to identify an effective DNA barcode from four popular DNA loci for P. kadsura authentication. The success rates of PCR amplification, sequencing, and sequence acquisition of matK were 10.5%, 75%, and 7.9%, respectively; for rbcL they were 89.5%, 8.8%, and 7.9%, respectively; ITS2 rates were 86.8%, 3.0%, and 2.6%, respectively, while for psbA-trnH they were all 100%, which is much higher than for the other three loci. The sequences were aligned using Muscle, genetic distances were computed using MEGA 5.2.2, and barcoding gap was performed using TAXON DNA. Phylogenetic analysis showed that psbA-trnH could clearly distinguish P. kadsura from its closely related species and the common adulterant. psbA-trnH was then used to evaluate the fake proportions of P. kadsura. Results showed that 18.4% of P. kadsura samples were fake, indicating that adulterant species exist in the Chinese markets. Two-dimensional DNA barcoding imaging of P. kadsura was conducted, which was beneficial to the management of P. kadsura. We conclude that the psbA-trnH region is a powerful tool for P. kadsura identification and supervision in the current medicine markets.

In this study, a high-speed counter-current chromatography (HSCCC) separation method target guided by centrifugal ultrafiltration with high-performance liquid chromatography-mass spectrometry (CU-LC-MS) was proposed. This method was used to analyze α-amylase inhibitors from Kadsura longipedunculata extract. According to previous screening with CU-LC-MS, two screened potential α-amylase inhibitors was successfully isolated from Kadsura longipedunculata extract using HSCCC under the optimized experimental conditions. The isolated two target compounds (with purities of 92.3% and 94.6%) were, respectively, identified as quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) based on the MS, UV, and 1H-NMR spectrometry data. To verify the inhibition of screened compounds, the inhibitory activities of quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) on α-amylase were tested, and it demonstrated that the experimental IC50 values of quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) were 28.8 and 12.5 μmol/L. These results proved that the hyphenated technique using CU-LC-MS and HSCCC was a rapid, competent, and reproductive method to screen and separate potential active compounds, like enzyme inhibitors from the extract of herbal medicines.

Kadcoccinin A (1), a cage-like sesquiterpenoid possessing a tricyclo[4.4.0.0(3,10)]decane scaffold, and the biosynthetically related kadcoccinin B (2) were isolated from the stems of Kadsura coccinea. Their structures and absolute configurations were determined from extensive spectroscopic analysis and quantum chemical calculations. Additionally, their cytotoxic and antifungal effects were initially evaluated, and a plausible biosynthetic pathway was proposed.

Eleven new dibenzocyclooctadiene lignans, polysperlignans A-K (1-11), and eight known analogues (12-19) were isolated from the stems of Kadsura polysperma. Their structures and absolute configurations were established using a combination of MS, NMR, CD, and single-crystal X-ray diffraction techniques. Selected compounds were evaluated for activity against beta-amyloid- or hydrogen peroxide-induced neurotoxicity on PC12 cells, and 1, 2, 4, 5, 13, and 16 showed statistically significant neuroprotective effects in these in vitro assays.

The organogenesis of staminate and carpellate flowers of Schisandra chinensis (Schisandraceae) was investigated with scanning electron microscopy, with observations on the development of tepals reported for the first time. The results showed that there is no interval between the initiation of the last tepal and that of the first stamen or carpel, and that the shapes of tepal, stamen, and carpel primordia are similar. The tepals and stamens of staminate flowers are initiated acropetally in a continuous spiral Fibonacci phyllotaxis, with no carpel structures observed; the filaments are not connate. The organogenesis of the carpellate flowers is similar to that of the staminate flowers, but with no evidence of stamen development. The carpels are ascidiate without postgenital fusion. Three androecial characters of Schisandra and Kadsura are discussed in a phylogenetic context. The subglobose or obovoid androecium of Schisandrapropinqua and Schisandra plena may be homologous with that in sections Kadsura and Sarcocarpon. The plesiomorphic form of the androecium within the two genera is likely to be elongate with more than ten free stamens.

Fourteen new dibenzocyclooctadiene lignans, ananolignans A-N (1-14), together with five known compounds, were isolated from the seeds of Kadsura ana iosma. The structures and absolute configurations of 1-14 were established using a combination of spectroscopic methods including 1D- and 2D-NMR and CD techniques. The biological activity of the isolated lignans was evaluated, and ananolignan F (6) and ananolignan L (12) showed significant neuroprotective effects in an in vitro assay.

A petroleum ether extract of Kadsura longipedunculata enhanced the GABA-induced chloride current (I(GABA)) by 122.5±0.3% (n=2) when tested at 100 μg/ml in Xenopuslaevis oocytes expressing GABA A receptors (α(1)β(2)γ(2S) subtype) in two-microelectrode voltage clamp measurements. Thirteen compounds were subsequently identified by HPLC-based activity profiling as responsible for GABA A receptor activity and purified in preparative scale. 6-Cinnamoyl-6,7-dihydro-7-myrceneol and 5,6-dihydrocuparenic acid were thereby isolated for the first time. The determination of the absolute stereochemistry of these compounds was achieved by comparison of experimental and calculated ECD spectra. All but one of the 13 isolated compounds from K. longipedunculata potentiated I(GABA) through GABA A receptors composed of α(1)β(2)γ(2S) subunits in a concentration-dependent manner. Potencies ranged from 12.8±3.1 to 135.6±85.7 μM, and efficiencies ranged from 129.7±36.8% to 885.8±291.2%. The phytochemical profiles of petroleum ether extracts of Kadsura japonica fruits (114.1±2.6% potentiation of I(GABA) at 100 μg/ml, n=2), and Schisandra chinensis fruits (inactive at 100 μg/ml) were compared by HPLC-PDA-ESIMS with that of K. longipedunculata.

Illiciaceae and Schisandraceae, together with other members of Austrobaileyales have been identified as one of the earliest diverging lineages of angiosperms, within the ANITA grade The specialized Illiciaceae and Schisandraceae comprise a clade defined by apomorphic characters including pollen grains with three or six colpate apertures. In both these families, pollen apertures and exine sculpture were found to be very informative when considered in the context of recent understanding of evolutionary patterns In the current study, pollen grains of 21 taxa from Illicraceae and Schisandraceae were investigated. These data, together with palynological data for taxa previously studied, were mapped into recent molecular phylogenetic trees to re-evaluate the existing classification and phylogenetic relationships in the two families Palynological data were found to be relatively congruent with recent molecular phylogenies, while traditional delimitations of infra-generic taxa were somewhat conflicting and did not reflect phylogeny and evolution The evolution of pollen morphology in the two families, together with other members of Austrobaileyales, is discussed in comparison with the molecular phylogenies (C) 2009 Elsevier GmbH. All rights reserved