- Phthalides: Distribution in Nature, Chemical Reactivity, Synthesis, and Biological Activity. [Review]
- PCProg Chem Org Nat Prod 2017; 104:127-246
- Phthalides are a relatively small group of natural compounds confined to several plant families and some genera of fungi and liverworts. They are divided into two structural groups, the monomeric and...
Phthalides are a relatively small group of natural compounds confined to several plant families and some genera of fungi and liverworts. They are divided into two structural groups, the monomeric and dimeric phthalides, and known mainly as bioactive constituents of different plant species used traditionally for medicinal purposes in Asia, Europe, and North America.The first reports on the chemistry of phthalides appeared at the end of the nineteenth century, in which they were identified as the odor constituents of the essential oil of celery (Apium graveolens) by Ciamician and Silber (1897). In the first half of the last century, phthalides were isolated from Cnidium officinale and Ligusticum acutilobum, species widely used in Asian traditional medicine, and from Levisticum officinale, a species used as food and condiment. Throughout the second part of the twentieth century, phthalides have been characterized from several plant families, namely Asteraceae, Leguminosae, Orchidaceae and Rutaceae, among others, but mainly from the Umbelliferae (syn Apiaceae) family, and the major contributors have been the following species used in traditional medicine: Ligusticum chuanxiong (Chinese name: Chuanxiong), Angelica sinensis (Chinese name: Danggui), Cnidium officinale (Japanese name: Senkyu), Angelica acutiloba (Japanese name: Toki), and Ligusticum porteri (Hispanic name: Oshá). Phthalides are also constituents of several genera of fungi, such as Penicillium, Alternaria and Pestalotiopsis, and some liverworts.Different chromatographic, spectrometric, and two-dimensional nuclear magnetic resonance (NMR) techniques have been used for the isolation and structural characterization of phthalides in extracts, and for assessing the quality of plant material containing this type of compound. Isotopic labeling has established the biosynthesis of phthalides via linkage of acetate units forming polyketide intermediates.Chemical transformations of monomeric phthalides have included oxidation, reduction, addition, elimination, and cycloaddition reactions, and treatments with Lewis acids of (Z)-ligustilide have afforded linear dimers. Some intramolecular condensations and differentiated cyclizations of the dimeric phthalides have been carried out, providing evidences for the particular chemical reactivity of these compounds.Several structural modifications of phthalides have been carried out subjecting them to microbial transformations by different species of bacteria, fungi and algae, and these included resolutions of racemic mixtures and oxidations, among others.The [π4s + π2s] and [π2s + π2s] cycloadditions of (Z)-ligustilide for the synthesis of dimeric phthalides have been reported, and different approaches involving cyclizations, Alder-Rickert reactions, Sharpless asymmetric hydroxylations, or Grignard additions have been used for the synthesis of monomeric phthalides. The use of phthalides as building blocks for divergent oriented synthesis has been proven.Many of the naturally occurring phthalides display different biological activities including antibacterial, antifungal, insecticidal, cytotoxic, and anti-inflammatory effects, among many others, with a considerable recent research on the topic. In the case of compounds isolated from the Apiaceae, the bioactivities correlate with the traditional medicinal uses of the natural sources. Some monomeric phthalides have shown their ability to attenuate certain neurological diseases, including stroke, Alzheimer's and Parkinson's diseases.The present contribution covers the distribution of phthalides in nature and the findings in the structural diversity, chemical reactivity, biotransformations, syntheses, and bioactivity of natural and semisynthetic phthalides.
- Rapid Authentication of the Herbal Medicine Plant Species Aralia continentalis Kitag. and Angelica biserrata C.Q. Yuan and R.H. Shan Using ITS2 Sequences and Multiplex-SCAR Markers. [Journal Article]
- MMolecules 2016 Feb 29; 21(3):270
- Accurate identification of the plant species that are present in herbal medicines is important for quality control. Although the dried roots of Aralia continentalis (Araliae Continentalis Radix) and ...
Accurate identification of the plant species that are present in herbal medicines is important for quality control. Although the dried roots of Aralia continentalis (Araliae Continentalis Radix) and Angelica biserrata (Angelicae Pubescentis Radix) are used in the same traditional medicine, namely Dok-Hwal in Korean and Du-Huo in Chinese, the medicines are described differently in the national pharmacopeia. Further confusion arises from the distribution of dried Levisticum officinale and Heracleum moellendorffii roots as the same medicine. Medicinal ingredients from all four plants are morphologically similar, and discrimination is difficult using conventional methods. Molecular identification methods offer rapidity and accuracy. The internal transcribed spacer 2 (ITS2) region of the nuclear ribosomal RNA gene (rDNA) was sequenced in all four plant species, and the sequences were used to design species-specific primers. Primers for each species were then combined to allow sample analysis in a single PCR reaction. Commercial herbal medicine samples were obtained from Korea and China and analyzed using the multiplex assay. The assay successfully identified authentic medicines and also identified inauthentic or adulterated samples. The multiplex assay will be a useful tool for identification of authentic Araliae Continentalis Radix and/or Angelicae Pubescentis Radix preparations in Korea and China.
- Development of SCAR Markers Based on Improved RAPD Amplification Fragments and Molecular Cloning for Authentication of Herbal Medicines Angelica sinensis, Angelica acutiloba and Levisticum officinale. [Journal Article]
- NPNat Prod Commun 2015; 10(10):1743-7
- Molecular cloning from DNA fragments of improved RAPD amplification of Angelica sinensis, Angelica acutiloba and Levisticum officinale, provided novel sequence-characterized amplified region (SCAR) m...
Molecular cloning from DNA fragments of improved RAPD amplification of Angelica sinensis, Angelica acutiloba and Levisticum officinale, provided novel sequence-characterized amplified region (SCAR) markers A13, A23, A1-34 and A1-0 whose sequences were deposited in the GenBank database with the accession numbers KP641315, KP641316, KP641317 and KP641318, respectively. By optional PCR amplification, the SCAR markers A13 and A23 are Levisticum officinale-specific, whereas the SCAR marker A1-34 is Angelica acutiloba-specific, and the SCAR marker A1-0 is Angelica sinensis-specific. These diagnostic SCAR markers may be useful for genetic authentications, for ecological conservation of all three medicinal plants and as a helpful tool for the genetic authentication of adulterant samples.
- Identification of species and materia medica within Angelica L. (Umbelliferae) based on phylogeny inferred from DNA barcodes. [Journal Article]
- MEMol Ecol Resour 2015; 15(2):358-71
- DNA barcodes have been increasingly used in authentication of medicinal plants, while their wide application in materia medica is limited in their accuracy due to incomplete sampling of species and a...
DNA barcodes have been increasingly used in authentication of medicinal plants, while their wide application in materia medica is limited in their accuracy due to incomplete sampling of species and absence of identification for materia medica. In this study, 95 leaf accessions of 23 species (including one variety) and materia medica of three Pharmacopoeia-recorded species of Angelica in China were collected to evaluate the effectiveness of four DNA barcodes (rbcL, matK, trnH-psbA and ITS). Our results showed that ITS provided the best discriminatory power by resolving 17 species as monophyletic lineages without shared alleles and exhibited the largest barcoding gap among the four single barcodes. The phylogenetic analysis of ITS showed that Levisticum officinale and Angelica sinensis were sister taxa, which indicates that L. officinale should be considered as a species of Angelica. The combination of ITS + rbcL + matK + trnH-psbA performed slight better discriminatory power than ITS, recovering 23 species without shared alleles and 19 species as monophyletic clades in ML tree. Authentication of materia medica using ITS revealed that the decoction pieces of A. sinensis and A. biserrata were partially adulterated with those of L. officinale, and the temperature around 80 °C processing A. dahurica decoction pieces obviously reduced the efficiency of PCR and sequencing. The examination of two cultivated varieties of A. dahurica from different localities indicated that the four DNA barcodes are inefficient for discriminating geographical authenticity of conspecific materia medica. This study provides an empirical paradigm in identification of medicinal plants and their materia medica using DNA barcodes.
- [Comparison on content of ligustilides in different danggui samples]. [Journal Article]
- ZZZhongguo Zhong Yao Za Zhi 2013; 38(17):2838-43
- Bioactivity of Danggui is linked to the content of ligustilide, but the relationship between ligustilide with herb shape, cultivating areas and plant species is still unknown. The relationship was in...
Bioactivity of Danggui is linked to the content of ligustilide, but the relationship between ligustilide with herb shape, cultivating areas and plant species is still unknown. The relationship was investigated by quantifying on the amounts of Z-ligustilide and E-ligustilide by HPLC-DAD-MS method, and then comparing the content of ligustilides (the sum of Z-ligustilide and E-ligustilide) among forty-four various "Danggui" samples containing thirty Chinese Danggui (CDG), six Japanese Danggui (JDG), four Korea Danggui (KDG) and four European Danggui (EDG). Results showed that the content of ligustilides in CDG samples (Angelica sinensis) was in the range of 5.63-24.53 mg x g(-1) with the mean of 11.02 mg x g(-1) (n = 30). Ligustilides amounts were varied among samples cultivated in different areas in China, i. e. 13.90 mg x g(-1) (n = 6) in Yannan, 12.51 mg x g(-1) (n = 6) in Sichuan and 10.04 mg x g(-1) (n = 13) in Gansu. It was also found that ligustilides content was related to the shape, color and fragrance of herb, e. g. the relative larger amount of ligustilides was in the small main root, long rootlet and perfumed sample. Further, ligustilides contents were estimated to be 1.00 mg x g(-1) (n = 6) in JDG samples (A. acutiloba and A. acutiloba var. sugiyamae) and 2.78 mg x g(-1) (n = 2) in EDG samples (lovage root, Levisticum officinale). However, ligustilides could not be detected in the four KDG samples (A. gigas) and two EDG samples (angelica root, A. archangelica). It has been concluded that ligustilide is significant variant among plant species, which may result in the variety of bioactivity and therapeutic effect.
- Molecular systematics of Angelica and allied genera (Apiaceae) from the Hengduan Mountains of China based on nrDNA ITS sequences: phylogenetic affinities and biogeographic implications. [Journal Article]
- JPJ Plant Res 2009; 122(4):403-14
- Maximum parsimony, maximum likelihood, and Bayesian analyses of nuclear ribosomal DNA internal transcribed spacer sequences were used to infer the phylogenetic affinities and historical biogeography ...
Maximum parsimony, maximum likelihood, and Bayesian analyses of nuclear ribosomal DNA internal transcribed spacer sequences were used to infer the phylogenetic affinities and historical biogeography of Angelica and its allies (Apiaceae tribe Selineae), with emphasis on those species of Angelica and Peucedanum endemic to the Hengduan Mountains of south-central China. Results of these analyses corroborate a monophyletic Angelica (Angelica sensu stricto) upon the inclusion of Coelopleurum, Czernaevia, and one of two examined species of Ostericum, but with the exclusion of several species previously attributable to Angelica. Angelica oncosepala and A. likiangensis arise within the genus Heracleum in tribe Tordylieae; the former is recognized under its original name, Heracleum oncosepalum. Angelica sinensis, A. tianmuensis and A. paeoniifolia arise within the Sinodielsia clade of previous circumscription, closely related to Levisticum officinale. Angelica anomala is a sister group to Ostericum grosseserratum in the previously delimited Acronema clade. Angelica apaensis and A. decursiva, taxa whose phylogenetic affinities have previously been controversial, are confirmed within Angelica. Northeast Asia (including Japan, northeast China, Korea and adjacent areas of Russia), Western Europe, and North America are inferred to be ancestral areas of Angelica based on optimal solutions of a dispersal-vicariance analysis, with the Hengduan Mountains likely providing a refugium for Angelica during the latter part of the Tertiary.
- A bioassay using Artemia salina for detecting phototoxicity of plant coumarins. [Journal Article]
- PMPlanta Med 1999; 65(8):715-8
- Artemia salina (brine shrimp) has been successfully used for toxicity testing, and a screening test for phototoxicity has been developed based on this method. The ability of the method to test the ph...
Artemia salina (brine shrimp) has been successfully used for toxicity testing, and a screening test for phototoxicity has been developed based on this method. The ability of the method to test the phototoxic potential of seven known compounds was investigated. Athamantin (an angular furanocoumarin) and umbelliferone (a simple coumarin) showed no phototoxicity, while linear furanocoumarins exhibited phototoxic activity in the following order: psoralen > bergapten > peucedanin > xanthotoxin. The applicability of this method was also tested in screening the phototoxicity of plant material. Six plants from Apiaceae [Aegopodium podagraria L., Anethum graveolens L., Angelica archangelica L., Levisticum officinalis Koch, Petroselinum crispum (P. Mill) A. W. Hill., and Peucedanum palustre (L.) Moench] and one from Rutaceae (Ruta graveolens L.) were selected, all of them known to contain furanocoumarins. Extracts from leaves collected at different times during the growth period were used in the screening. Our results were in accordance with the furanocoumarin content of these plants and with the results of other phototoxicity tests. The Artemia salina method proved to be rapid, simple and inexpensive, and is therefore ideal in the initial biological screening of large numbers of samples for simultaneous detection of both toxicity and phototoxicity.
- [Phospholipid components of danggui]. [Journal Article]
- ZZZhongguo Zhong Yao Za Zhi 1991; 16(12):741-2, 763
- This paper deals with the phospholipid components in Danggui (Angelica sinensis and Levisticum officinale) by using thin-layer chromatographic scanning and the corrective method of absorbance proport...
This paper deals with the phospholipid components in Danggui (Angelica sinensis and Levisticum officinale) by using thin-layer chromatographic scanning and the corrective method of absorbance proportional coefficient. Seven known and two unknown phospholipid components were separated and determined. The authors have compared the composition of phospholipids for six Danggui samples.
- [Studies on the components of essential oils. II. Comparison of the major constituents of the essential oil from two species of Dang gui (Angelica sinensis (Oliv.) Diels and Levisticum officinale Koch (author's transl)]. [Journal Article]
- YXYao Xue Xue Bao 1979; 14(10):617-23