Research progress on chemical constituents from Chloranthus plants and their biological activities / 中国中药杂志

The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.

Chemical constituents of sesquiterpenes from Chloranthus multistachys / 中国中药杂志

With repeated silica gel, octadecyl silica(ODS), and Sephadex LH-20 column chromatography, normal-phase and reverse-phase high performance liquid chromatography(HPLC), etc., a pair of new enantiomers and 5 known compounds were separated from the 95% ethanol extract of Chloranthus multistachys. These compounds were identified by the nuclear magnetic resonance spectroscopy(including 1 D-NMR and 2 D-NMR), single-crystal X-ray diffraction, circular dichroism(CD) spectroscopy, mass spectrometry(MS), and some other methods as(1R,4R,5R,8S,10R)-chloraeudolide H(1 a),(1S,4S,5S,8R,10S)-chloraeudolide H(1 b), hydroxyisogermafurenolide(2), 4α-hydroxy-5α,8β(H)-eudesm-7(11)-en-8,12-olide(3), chloraniolide A(4), chlorantene D(5), 4α,8β-dihydroxy-5α(H)-eudesm-7(11)-en-8,12-olide(6). Compounds 1 a and 1 b are a pair of new eudesmane-type sesquiterpene enantiomers, and compounds 2-4 were isolated from C. multistachys for the first time.

A new sesquiterpene from Chloranthus henryi / 中国中药杂志

Eight sesquiterpenes were isolated and purified from the ethanol extract of Chloranthus henryi by column chromatographies over silica gel, ODS and Sephadex LH-20,and preparative HPLC. Their chemical structures were established by spectral data and physiochemical properties as(1S,6S,8S,10R)-8-ethoxy-10-methoxychlomultin C(1),tianmushanol(2),multistalide A(3),myrrhterpenoid N(4),1α,9α-dihydroxy-8,12-expoxy-eudesma-4,7,11-trien-6-one(5),4β,10α-aromadendranediol(6),oplopanone(7),10α-hydroxycadinan-4-en-3-one(8). Among them, compound(1) was a new compound, and compounds 2-8 were isolated from Chloranthus henryi for the first time.

Studies on chemical constituents of Chloranthus fortunei / 中草药

Objective: To study the antitumor constituents from Chloranthus fortunei. Methods: Various chromatographic techniques and spectroscopic methods were applied to investigate the chemical constituents from C. fortunei, and some of the compounds were screened for their antitumor activities by MTT method. Results: Sixteen compounds were obtained from the whole plants of C. fortunei and identified as rosmarinic acid (1), 2’-hydroxy-4,3’,4’,6’-tetramethoxychalcone (2), flavokawain A (3), cycloshizukaol A (4), atractylenolide III (5), 4β-hydroxy-8,12-epoxyeudesma-7,11-diene-1,6-dione (6), (8α)-6,8-dihydroxycadina-7 (11),10 (15)-dien-12-oic acid γ-lactone (7), curcolonol (8), 11-hydroxyldrim-8,12-en-14-oic acid (9), friedelin (10), isovanillic acid (11), 6β-hydroxystigmast-4-en-3-one (12), 3,4-dihydroxybenzoic acid (13), shikimic acid (14), scopolin (15) and N-acetyltyramine 1-O-β-D-glucoside (16). Compounds 4 and 5 showed weak cytotoxicity with IC50 ranged from 46 to 85 μmol/L. Conclusion: Compounds 2, 10, 11, and 13-15 are obtained from the genus Chloranthus for the first time and compounds 1-3 and 6-16 are isolated from C. fortunei for the first time. Some sesquiterpenoids from C. fortunei exhibited weak antitumor activities.

A pair of enantiomeric sesquiterpenoids with neuroprotective effects from Chloranthus henryi / 药学学报

An ethanol extract of Chloranthus henryi (Chloranthaceae) was subjected to various chromatographic procedures including silica gel column chromatography, MCI column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Five purified sesquiterpenes analyzed by spectroscopic analyses (MS, IR, NMR) and single crystal X-ray diffraction were elucidated as (1S,6S,8R)-8-ethoxychlomultin C (1a), (1R,6R,8S)-8-ethoxychlomultin C (1b), (+)-phaeocaulin D (2), atractylenolide Ⅰ (3), and 8-β-ethoxyasterolid (4). Compounds 1a and 1b were a new pair of sesquiterpene enantiomers and compounds 2-4 were isolated from this plant for the first time. Compounds 1a, 1b, 2 and 3 increased cell viability in H2O2-treated PC12 cells from (43.41 ± 1.59) % to (61.71 ± 7.56) %, (66.05 ± 5.61) %, (74.34 ± 3.32) % and (69.58 ± 5.02) % at 10 μmol·L-1, respectively.

Mechanisms of Toxicity and Cardiotoxicity of Alcohol Extract from Root, Stem and Leaf of Chloranthus Serratus / 法医学杂志

Objective To compare the differences of cardiotoxicity of alcohol extract from root, stem and leaf of Chloranthus serratus in the rats, and discuss preliminarily its mechanism of toxicity. Methods Rats were randomly divided into four groups: blank, root alcohol, stem alcohol and leaf alcohol, with 8 in each group. After 14 days of continuous intragastric administration, the body mass change curves were drawn. The cardiac coefficient was calculated. The contents of creatine kinase （CK）, creatine kinase isoenzyme （CK-MB）, lactate dehydrogenase （LDH） and α-hydroxybutyrate dehydrogenase （α-HBDH） as well as the content changes of oxidative stress indexes - total superoxide dismutase （T-SOD） and malondialdehyde （MDA） in the serum of rats were detected. The cardiac pathomorphology changes in the rats were observed. The expression of intercellular adhesion molecule （ICAM-1） and heme oxygenase （HO-1） in myocardial tissue was detected. Results Body mass growth rate： stem alcohol group was the smallest, followed by leaf alcohol group. The difference of cardiac coefficient of every group had no statistical significance （P>0.05）. The myocardial tissues of stem alcohol group suffered the most serious damage, followed by the leaf alcohol group. The contents of CK, CK-MB, LDH and α-HBDH in stem alcohol group increased （P<0.05）. The increase of MDA content and decrease of T-SOD content in stem alcohol group had statistical significance compared with the blank group and root alcohol group, while the leaf alcohol group only had statistical significance in the decrease of T-SOD content compared with the blank group （P<0.05）. The positive expression of ICAM-1 enhanced and the expression of HO-1 protein decreased in every group after the intervention of different extracts. The change trend was stem alcohol > leaf alcohol > root alcohol group. Conclusion The alcohol extract from the stem has the highest cardiotoxicity, followed by the leaf extract, and its mechanism of toxicity may be related to oxidative stress.

Transcriptomic analyses of Chloranthus japonicus by RNA-seq / 中草药

Objective To obtain the transcriptome dataset of Chloranthus japonicas. Methods Using the Illumina HiSeqTM 2000 150PE, a rhizome transcriptome of C. japonicus was generated, followed by systemic bioinformatics analyses. Results A total of 68 458 750 high quality clean reads were produced by the transcriptome sequencing. Trinity de novo assembling resulted in a total of 56 096 unigenes with an average length of 801 nt. BLAST analysis indicated that 25 773 (45.94%), 17 801 (31.73%), 16 082 (28.67%), and 9 649 (17.20%) unigenes were successfully annotated in the NR, Swiss-port, KOG, and KEGG databases, respectively. All unigenes were classified into three major groups by GO, including biological process, cellular component, and molecular function, and then, grouped into 40 subgroups. And 131 KEGG standard pathways were designated, 16 of which were defied as the secondary metabolism. Further analysis revealed that a total of 170 unigenes were involved in the biosynthesis of mono-, di-, sesqui-, or triterpene. Meantime, 1 887 unigenes were predicted to contain protein coding sequences. Totally 54 families of transcription factors of higher plant were identified. Using MISA prediction, 8 987 simple sequence repeats (SSRs) were obtained, among which the di-nucleotide SSRs were abundant with 5 948 (66.2%), whereas the penta-nucleotide SSRs were relatively less, accounting for 1.3%. Conclusion The transcriptome of C. japonicus rhizome was generated by RNA-seq along with the identification of unigenes implicated in various terpenes biosynthesis, which will provide a fundamental basis for secondary metabolism pathway dissections and their regulatory mechanisms in this plant species.

Chemical constituents from aerial parts of Chloranthus angustifolius / 中草药

Objective: To study the chemical constituents from the aerial parts of Chloranthus angustifolius. Methods: The chemical constituents were isolated by various chromatography techniques and their structures were elucidated on the basis of physiochemical properties and spectrascopic analysis. Results: Eight compounds were isolated and identified as 1-acetoxy-2,3,4,5- tetrahydroxy-5-p-metoxyphenylpentane (1), (E)-5-(4-methoxyphenyl) pent-4-ene-1,2,3-trihydroxyamyl (2), isofraxidin (3), (-)-dihydrodehydrodiconiferyl alcohol (4), (±)-erythro-guaiacyl-glycerol-β-O-4'-dihydroconiferyl ether (5), (-)-rosiridol (6), (4S)-p-menth-1-ene-4,7-diol (7), and loliolide (8), respectively. Conclusion: Compounds 1 and 2, named chloranthus pentitol and chloranthus enol, are two new p-methoxyphenyl pentitol derivatives, while compounds 3-8 are obtained from C. angustifolius for the first time.

Chemical constituents from Chloranthus japonicus / 中成药

AIM To study the chemical constituents from Chloranthus japonicus Sieb..METHODS The ethyl acetate fraction of 95％ ethanol extract from C.japonicus was isolated and purified by silica,Sephadex LH-20,ODS and PHPLC column,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Ten compounds were isolated and identified as p-hydroxyphenethyl (1),diisooctanephthalate (2),diisobutylphthalat (3),umbelliferone (4),ursolic acid (5),7α-hydroxysitosterol (6),chloranthalactone E (7),chloranthalactone B (8),apigenin (9),3-Sitosterol (10).CONCLUSION Compounds 1-3,6 are isolated from genus Chloranthus for the first time,compounds 4,5,9 are first isolated from this plant.

Sesquiterpenes with anti-metastasis breast cancer activity from Chloranthus henryi / 中国中药杂志

To study sesquiterpenes with anti-metastasis breast cancer activity from Chloranthus henryi, ten sesquiterpenes ,zedoarofuran (1), chlorajapolide D (2), 4β, 8β-dihydroxy-5α(H)-eudesm-7(11)-en-8, 12-olide (3), curcolonol (4), lasianthuslactone A (5), chlomultin C (6), (1E,4Z)-8-hydroxy-6-oxogermacra-1(10), 4, 7(11) -trieno-12, 8-lactone (7), shizukanolide E (8) , shizukanolide F (9) , 9α-hydroxycurcolonol (10), and five bis-sesquiterpenes, shizukaol B (11), shizukaol C (12) , cycloshizukaol A (13) , sarcandrolide B (14) , henriol A(15), were isolated by using different kinds of column chromatography methods from the ethyl acetate part of Ch.henryi and their structures were identified based on spectroscopic methods. Compounds 2, 8, 9, and 10 were obtained from the genus Chloranthus for the first time. Compounds 2, 5, 8-10, 12,and 14 were obtained from this plant for the first time. Some isolated compounds were subjected to evaluate the anti-metastasis breast cancer activity by using pharmacological methods, and only compounds 4, 11, and 12 were potent active.

Chemical constituents in lindenane-type sesquiterpene dimers in roots of Chloranthus multistachys / 中草药

Objective: To study the chemical constituents contained in the ethanol extracts from the roots of Chloranthus multistachys. Methods: Twelve compounds were separated from the roots of C. multistachys and their structures were identified by using various chromatographic techniques. Results: The structures of the 12 lindenane-type sesquiterpene dimmers from the chloroform and ethyl acetate extract in the roots of C. multistachys were identified on the basis of physicochemical properties and spectral data as 9-O-β-glucopyranosylcycloshizukaol A (1), cycloshizukaol A (2), shizukaol B (3), shizukaol C (4), shizukaol D (5), shizukaol F (6), shizukaol G (7), chloramultiol B (8), sarcandrolide B (9), sarglabolide I (10), 8-O-methyltianmushanol (11), and henriol B (12). Conclusion: Compounds 1, 7, and 9-12 are isolated from the roots C. multistachys for the first time and compounds 9 and 10 are obtained from the plants of Chloranthus Sw. for the first time.

Extraction Process Optimization of Total Flavonoids from Chloranthus Japonicus sieb by Box-Behnken Re-sponse Surface Methodology / 中国药师

Objective:To optimize the extraction process of total flavonoids from Chloranthus japonicus sieb by Box-Behnken re-sponse surface methodology. Methods:The independent variables were the ethanol concentration ( X1 ) , liquid-solid ratio ( X2 ) and extraction time ( X3 ) , the dependent variable was the extraction amount of total flavonoids ( Y) , and the extraction process was opti-mized by Box-Behnken response surface methodology. Results: The results showed that the optimal extraction conditions for total fla-vonoids from Chloranthus japonicus sieb were as follows: the ethanol concentration was 54. 8%, the liquid-solid ratio was 13. 6, and the extraction time was 2. 0 h. The verified extraction process parameters of three batches showed that the relative error between the ex-perimental values and those predicted from the regression model was -2. 34%. Conclusion:The optimal extraction process parameters are simple and more convenient with higher precision for the extraction of total flavonoids from Chloranthus japonicus sieb.

Study on chemical constituents from Chloranthus multistachys / 中国中药杂志

To investigate the chemical constituents from the shoots of Chloranthus multistachys.All compounds wereisolated by using a combination of various chromatographic techniques including silica gel, ODS, Sephadex LH-20, reversed-phase HPLC, and other methods.Their structures were elucidated by the nuclear magnetic resonance (NMR), mass spectrometry, and other modernspectroscopies.As a result, 19 compounds were isolated from the shoots of C.multistachys and identified as zederoneepoxide(1), chlomultin C(2), curcolonol(3), sarcaglaboside A(4), zedoarofuran(5), (1E,4Z)-8-hydroxy-6-oxogermacra-1(10), 4,7(11)-trieno-12,8-lactone(6), chloranoside A(7), istanbulin A(8), (8α)-6,8-dihydroxycadina-7(11),10(15)-dien-12-oicacid-γ-lactone(9), codonolactone(10), lasianthuslactone A(11), 12,15-epoxy-5αH,9βH-labda-8(17),13-dien-19-oicacid(12), 12R,15-dihydroxylabda-8(17),13E-dien-19-oicacid(13), N-transcinnamoyltyramine(14), trans-N-p-coumaroyltyramine(15), dibutyl phthalate (16), flavokawain A(17), bergenin(18), and enedione(19).Compounds 1, 2, 4, 7-10, 12-19 were isolated from C.multistachys for the first time and compounds 14-19 were obtained from the genus Chloranthus for the first time.

Chemical constituents from roots of Chloranthus serratus / 中草药

Objective: To study chemical constituents contained in the ethanol extracts from the roots of Chloranthus serratus. Methods: Fifteen compounds were separated from the roots of M. serratus by using various chromatographic techniques. Results: Their structures were identified on the basis of physicochemical properties and spectral data as 1α, 9α-dihydroxy-8,12-expoxy-eudesma-4,7,11-trien-6-one (1), 1β, 5α-guaiane-4β, 10α-diol-6-one (2), zedoalactone E (3), multistalactone C (4), 1β, 8β-dihydroxy-eudesman-3,7(11)-dien-8α, 12-olide (5), 1β, 8β-dihydroxy-eudesman-4(15), 7(11)-dien-8α, 12 olide (6), sobrerol (7), umbelliferone (8), isofraxidin (9), 5-methoxy-6,7-methylene-dioxy coumarin (10), trans-N-p-coumaroyl tyramine (11), N-trans-feruloyl tyramin (12), N-cis-feruloyl tyramin (13), catechin (14), and 7-hydroxy-5,8-dimethoxyflavanone (15). Conclusion: Compounds 2,5-7,10,14 an 15 are obtained from the plants of Chloranthus Sw. for the first time, and compounds 1,3, and 4 are isolated from C. serratus for the first time.

Sequences analysis and pattern recognition of ITS in Sarcandra glabra from different areas / 中草药

Objective: To study the ribosomal DNA internal transcribed spacer (rDNA-ITS) sequences of Sarcandra glabra from different areas and five plants in Chloranthus Swartz, and to provide pattern recognition and thread for the species identification of S. glabra. Methods: The ITS sequences of 18 populations of S. glabra and six populations of Chloranthus spicatus were amplified by PCR with universal primer of ITS and sequenced, and the ITS sequences of the other plants in Chloranthus Swartz were searched in GeneBank. Data were analyzed by ClustalX 2.1, and a cluster analysis was presented by UPGMA. Results: The semblance of ITS sequences of S. glabra from different areas was 99%. The total mutation rate of ITS1 sequence (2.7%) was higher than that of ITS2 sequence (1.4%). However, compared with other plants in Chloranthus Swartz, the total mutation rate of ITS2 sequence (20.3%-22.7%) was higher than that of ITS1 sequence (15.9%-18.3%). The cluster analysis showed that there was little variation among the 18 populations of S. glabra, but there was significant difference with the five plants of Chloranthus Swartz. Conclusion: ITS sequence can be used to identify the plants from different areas and in different genus, ITS sequence of S. glabra has several specified information sites to identify the five plants in Chloranthus Swartz, with significantly different cluster analyseis, and is the active molecular marker for the species identification of S. glabra and plants in Chloranthus Swartz.