Mining Therapeutic Efficacy from Treasure Chest of Biodiversity and Chemodiversity: Pharmacophylogeny of Ranunculales Medicinal Plants.

Ranunculales, comprising of 7 families that are rich in medicinal species frequently utilized by traditional medicine and ethnomedicine, represents a treasure chest of biodiversity and chemodiversity. The phylogenetically related species often have similar chemical profile, which makes them often possess similar therapeutic spectrum. This has been validated by both ethnomedicinal experiences and pharmacological investigations. This paper summarizes molecular phylogeny, chemical constituents, and therapeutic applications of Ranunculales, i.e., a pharmacophylogeny study of this representative medicinal order. The phytochemistry/metabolome, ethnomedicine and bioactivity/pharmacology data are incorporated within the phylogenetic framework of Ranunculales. The most studied compounds of this order include benzylisoquinoline alkaloid, flavonoid, terpenoid, saponin and lignan, etc. Bisbenzylisoquinoline alkaloids are especially abundant in Berberidaceae and Menispermaceae. The most frequent ethnomedicinal uses are arthritis, heat-clearing and detoxification, carbuncle-abscess and sore-toxin. The most studied bioactivities are anticancer/cytotoxic, antimicrobial, and anti-inflammatory activities, etc. The pharmacophylogeny analysis, integrated with both traditional and modern medicinal uses, agrees with the molecular phylogeny based on chloroplast and nuclear DNA sequences, in which Ranunculales is divided into Ranunculaceae, Berberidaceae, Menispermaceae, Lardizabalaceae, Circaeasteraceae, Papaveraceae, and Eupteleaceae families. Chemical constituents and therapeutic efficacy of each taxonomic group are reviewed and the underlying connection between phylogeny, chemodiversity and clinical uses is revealed, which facilitate the conservation and sustainable utilization of Ranunculales pharmaceutical resources, as well as developing novel plant-based pharmacotherapy.

In silico approach in reveal traditional medicine plants pharmacological material basis.

In recent years, studies of traditional medicinal plants have gradually increased worldwide because the natural sources and variety of such plants allow them to complement modern pharmacological approaches. As computer technology has developed, in silico approaches such as virtual screening and network analysis have been widely utilized in efforts to elucidate the pharmacological basis of the functions of traditional medicinal plants. In the process of new drug discovery, the application of virtual screening and network pharmacology can enrich active compounds among the candidates and adequately indicate the mechanism of action of medicinal plants, reducing the cost and increasing the efficiency of the whole procedure. In this review, we first provide a detailed research routine for examining traditional medicinal plants by in silico techniques and elaborate on their theoretical principles. We also survey common databases, software programs and website tools that can be used for virtual screening and pharmacological network construction. Furthermore, we conclude with a simple example that illustrates the whole methodology, and we present perspectives on the development and application of this in silico methodology to reveal the pharmacological basis of the effects of traditional medicinal plants.

In silico Approach for Anti-Thrombosis Drug Discovery: P2Y1R Structure-Based TCMs Screening.

Cardiovascular diseases (CVDs), including thrombosis, which is induced by platelet aggregation, are the leading cause of mortality worldwide. The P2Y1 receptor (P2Y1R) facilitates platelet aggregation and is thus an important potential anti-thrombotic drug target. The P2Y1R protein structure contains a binding site for receptor antagonist MRS2500 within its seven-transmembrane bundle, which also provides suitable pockets for numerous other ligands to act as nucleotide antagonists of P2Y1R. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) comprises 499 Chinese Pharmacopoeia-registered herbs and the structure information for 29,384 ingredients. In silico docking of these compounds into the P2Y1R protein structure within the MRS2500 pocket can identify potential antithrombotic drugs from natural medicinal plants. Docking studies were performed and scored to evaluate ligand-binding affinities. In this study, a total of 8987 compounds from Traditional Chinese Medicine (TCM) were filtered by Lipinski's rule of five, and their ideal oral-intake properties were evaluated. Of these, 1656 compounds distributed in 443 herbs docked into the P2Y1R-MRS2500 structure in 16,317 poses. A total of 38 compounds were ranked with a DockScore above 70, and these may have significant potential for development into anti-thrombosis drugs. These computational results suggested that licorice (Glycyrrhiza uralensis Fisch), cimicifugae (Cimicifuga foetida L.), and ganoderma (Ganoderma lucidum Karst) and their chemical constituents, which have not previously been widely used for anti-thrombosis, may have unexpected effects on platelet aggregation. Moreover, two types of triterpene scaffolds summarized from 10 compounds were distributed in these three herbs and also docked into P2Y1R. These scaffold structures may be utilized for the development of drugs to inhibit platelet aggregation.

[Spectrum-effect relationship between anti-HIV 1 activities and ultra-performance liquid chromatography fingerprints of Rheum species].

OBJECTIVE: To study the relationship between ultra-performance liquid chromatography (UPLC) fingerprints of Rheum species and their anti-HIV 1 activities. METHOD: Twenty two samples of 16 species belonging to genus Rheum from various sources were collected and analyzed in this study. Firstly they were assayed for the HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) activity. Secondly the fingerprints were established by an optimized UPLC method. Sample was analyzed by UPLC-TOF-MS/MS to identify major peaks. The possible relationship between UPLC fingerprints and anti-HIV 1 activities of Rheum species were deduced by mathematical statistics method. RESULT: Samples of R. austral, R. austral, R. hotaoense exhibited good anti-HIV 1 activities with IC50 < or = 0.2 mg x L(-1). The correlation of anti-HIV 1 activities and fingerprints showed that three compounds were the main bioactive components, and their retention times were 4.74, 7.99, 21.18 min, respectively. CONCLUSION: Compounds in Rheum species with possible anti-HIV 1 activities were deduced by spectrum-effect relationship study. This study supported for study of medicinal plants in Rheum.

Two new antioxidant diarylheptanoids from the fruits of Alpinia oxyphylla.

Two new diarylheptanoids, 1-(3',5'-dihydroxy-4'-methoxyphenyl)-7-phenyl-3-heptanone (1) and 1-(2',4'-dihydroxy-3'-methoxyphenyl)-7-(4″-methoxyphenyl)-3-heptanone (2), along with known diarylheptanoid yakuchinone A (3), and five flavanoids, tectochrysin (4), chrysin (5), izalpinin (6), kaempferol 7, 4'-dimethyl ether (7), and kaempferide (8) were isolated from the fruits of Alpinia oxyphylla Miq. Their structures were determined by means of spectroscopic methods. Antioxidant activities of all the isolated compounds were evaluated using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Compounds 1-3 and 6-8 exhibited potent antioxidant activities in the DPPH assay.

Cis-aconitic anhydride ethyl ester and phenolic compounds from the seeds of Alisma orientale.

From the seeds of Alisma orientale, cis-aconitic anhydride ethyl ester and cis-2,4,5-trihydroxycinnamic acid were isolated, together with nine known phenolic compounds and a megastigmane sesquiterpene. All compounds are reported for the first time from Alisma species.

[Effective components against HIV-1 replicative enzymes isolated from plants].

Plant active components characterized of many different structures and activities on multiple targets, have made them to be the important sources of inhibitors on HIV-1. For finding leading compounds with new structure against HIV-1, three key HIV-1 replicative enzymes (reverse transcriptase, protease and integrase) were used as screening models. The in vitro activities of 45 plant derived components isolated from Schisandraceae, Rutaceae and Ranunculaceae were reported. Within twelve triterpene components isolated, eight compounds were found to inhibit HIV-1 protease, in these eight active compounds, kadsuranic acid A (7) and nigranoic acid (8), inhibited both HIV-1 protease and integrase; Among fifteen lignans, meso-dihydroguaiaretic acid (15) and kadsurarin (16) were active on HIV-1 reverse transcriptase, and 4, 4-di(4-hydroxy-3-methoxyphenly)-2, 3-dimethylbutanol (13) active on HIV-1 integrase. All of the six alkaloids, seven flavones, and five others compounds were not active or only with low activities against HIV-1 replicative enzymes. Further studies of the triterpene components showing strong inhibitory activities on HIV-1 were warranted.

[Argument on the correct Chinese name of genus Kadsura Kaempf.ex Juss].

Family Schisandraceae is composed of two genera Schisandra and Kadsura, which are quite different in regard to the used part and medical function. Traditionally, the fruits of Schisandra plants were called 'Wuweizi' used as tonic for neurasthenia, antitussive, and sedative agents. The stems and roots of Kadsura plants, with names related to 'XueTeng', possess activating blood circulation and eliminating stasis and are used for the treatment of rheumatism, fractures and irregular menstruation. The dried fruit of Schisandra chinensis was recorded in Chinese Pharmacopoeia (2010 Edition) as 'Wuweizi', while the dried fruit of S. sphenanthera was recorded as an official origin of 'Nanwuweizi'. Historically, there was no evidence that the fruits of Kadsura plants were substituted as 'Wuweizi' either in ancient literatures or contemporary marketing. However, genus Kadsura is still popularly called 'Nanwuweizi' and plant K. longipedunculata is regarded as the origin of 'Nanwuweizi', thus this will cause confusion as well as misunderstanding of genus Kadsura. The authors recommended, therefore, the Chinese name of genus Kadsura should be 'Lengfantengshu' and K. longipedunculata with the name of 'Lengfanteng' in order to guarantee the drug authenticity.

Two new lignans from Schisandra henryi.

Two new lignans, henricines A (1) and B (2), were isolated along with the eight known lignans, ganshisandrine (3), wulignan A(2) (4), epiwulignan A(1) (5), deoxyschisandrin (6), wulignan A(1) (7), epischisandrone (8), schisantherin A (9), and schisandrol A (10), from the stems of Schisandra henryi. The structures of the new compounds were elucidated based on the spectral analysis, including 1D and 2D NMR experiments.

[Chemical study on ethyl acetate portion of Ehretia thyrsiflora, boraginaceae species of Kudingcha].

OBJECTIVE: To investigate the chemical constituents of Ehretia thyrsiflora. METHOD: Compounds were isolated by using silica gel, Sephadex LH-20 and RP-C18 chromatography; their structures were elucidated by means of spectral data analysis. RESULT: Seven compounds were isolated and identified as methyl rosmarinate (1), caffeic acid (2), quercetin (3), kampferol (4), kaempferol 3-O-alpha-D-arabinoside (5), quercetin 3-O-alpha-D-arabinoside (6), and p-hydroxy benzoic acid (7). CONCLUSION: All these compounds were isolated from E. thyrsiflora for the first time. Compounds 2-7 were isolated from genus Ehretia for the first time.

[Chemical constituents from stems of Schisandra propinqua].

OBJECTIVE: To study the chemical constituents in the stems of Schisandra propinqua and evaluate their effects on proliferation of vascular smooth muscle cells (VSMCs) in vitro by MTT assay. METHOD: The compounds were isolated and purified by various column chromatographic techniques and their structures were elucidated on the basis of spectral analysis (ESI-MS, 1H-NMR, 13C-NMR). RESULT: Five compounds were isolated and identified as galgravin (1), veraguensin (2), octadecanoic acid 2, 3-dihydroxypropyl ester (3), hexadecanoic acid 2, 3-dihydroxypropy ester (4), tetracosanoic acid 2, 3-dihydroxypropyl ester (5). CONCLUSION: All the compounds were isolated for the first time from the plant. 1, 2, 5 showed inhibiting effects on vascular smooth muscle cell (VSMCs) proliferation in vitro.

Psoralenoside and isopsoralenoside, two new benzofuran glycosides from Psoralea corylifolia.

Two new benzofuran glycosides, called psoralenoside and isopsoralenoside, were isolated from the fruits of Psoralea corylifolia, together with nine known compounds. Their structures were elucidated by detailed spectral analyses including extensive two dimensional (2D) NMR spectra.

New lignans and cytotoxic constituents from Schisandra propinqua.

The CHCl (3) extract from the stems of Schisandra propinqua (Wall.) Baill exhibited significant cytotoxic activity against cancer cell lines. Subsequent fractionation procedures led to the isolation of four new dibenzocyclooctadiene lignans, propinquanins A - D, along with two known lignans, schisantherin I and heteroclitin A, and three known triterpenoids, isoschisandrolic acid, schisandrolic acid and schisandronic acid. Their structures, including absolute stereochemistry, were elucidated through analyses of NMR data and CD spectra. The isolated compounds were tested for their cytotoxic activity in several tumor cell lines with the MTT assay. Propinquanin B ( 2) was significantly cytotoxic (IC (50) values < 10 microM) in HL-60 and Hep-G2 tumor cell lines. Cell cycle analysis and Hoechst 33 258 staining assay suggested that one possible mechanism of cytotoxic activity by 2 might be related to the induction of apoptosis.

Establishment of HPLC-DAD-MS fingerprint of fresh Houttuynia cordata.

A HPLC-DAD-MS fingerprint method of fresh Houttuynia cordata THUNB. was developed basing on the consistent chromatographic features among 11 batches of authentic samples. Major chemical components including phenolic compounds, flavones and alkaloids were simultaneously analyzed. Eleven common peaks in the fingerprint were chosen and identified by comparing their UV and ESI-MS data with the authentic compounds. The unique properties of this HPLC-DAD-MS fingerprint were successfully applied to analyze and differentiate samples from different geographical origins, processing methods and various medicinal parts of H. cordata. The results showed that these variations will give rise to differences in identities and/or abundance of chemical compounds, indicating that a comprehensive quality evaluation of those major ingredients in H. cordata is critical to assess and represent its overall quality.