An overview on the chemistry, pharmacology and anticancer properties of tetrandrine and fangchinoline (alkaloids) from Stephania tetrandra roots.

Tetrandrine (TET) and fangchinoline (FAN) are dominant bisbenzylisoquinoline (BBIQ) alkaloids from the roots of Stephania tetrandra of the family Menispermaceae. BBIQ alkaloids comprise two benzylisoquinoline units linked by oxygen bridges. The molecular structures of TET and FAN are exactly the same, except that TET has a methoxy (-OCH3) group, while FAN has a hydroxyl (-OH) group at C7. In this overview, the current knowledge on the chemistry, pharmacology and anticancer properties of TET and FAN have been updated. The focus is on colon and breast cancer cells, because they are most susceptible to TET and FAN, respectively. Against colon cancer cells, TET inhibits cell proliferation and tumor growth by inducing apoptosis and G1 cell cycle arrest, and suppresses adhesion, migration and invasion of cells. Against breast cancer cells, FAN inhibits cell proliferation by inducing apoptosis, G1-phase cell cycle arrest and inhibits cell migration. The processes involve various molecular mechanisms and signaling pathways. Some insights on the ability of TET and FAN to reverse multi-drug resistance in cancer cells and suggestions for future research are provided.

Phenolic constituents and anticancer properties of Morus alba (white mulberry) leaves.

Flavonoids are by far the most dominant class of phenolic compounds isolated from Morus alba leaves (MAL). Other classes of compounds are benzofurans, phenolic acids, alkaloids, coumarins, chalcones and stilbenes. Major flavonoids are kuwanons, moracinflavans, moragrols and morkotins. Other major compounds include moracins (benzofurans), caffeoylquinic acids (phenolic acids) and morachalcones (chalcones). Research on the anticancer properties of MAL entailed in vitro and in vivo cytotoxicity of extracts or isolated compounds. Flavonoids, benzofurans, chalcones and alkaloids are classes of compounds from MAL that have been found to be cytotoxic towards human cancer cell lines. Further studies on the phytochemistry and anticancer of MAL are suggested. Sources of information were PubMed, PubMed Central, ScienceDirect, Google, Google Scholar, J-Stage, PubChem and China National Knowledge Infrastructure.

Ursolic acid: An overview on its cytotoxic activities against breast and colorectal cancer cells.

Ursolic acid (UA) is a pentacyclic triterpene of the ursane type. As a common chemical constituent among species of the family Lamiaceae, UA possesses a broad spectrum of pharmacological properties. This overview focuses on the anticancer properties of UA against breast cancer (BC) and colorectal cancer (CRC) that are most common among women and men, respectively. In vitro studies have shown that UA inhibited the growth of BC and CRC cell lines through various molecular targets and signaling pathways. There are several in vivo studies on the cytotoxic activity of UA against BC and CRC. UA also inhibits the growth of other types of cancer. Studies on structural modifications of UA have shown that the -OH groups at C3 and at C28 are critical factors influencing the cytotoxic activity of UA and its derivatives. Some needs for future research are suggested. Sources of information were from ScienceDirect, Google Scholar and PubMed.

Casticin from Vitex species: a short review on its anticancer and anti-inflammatory properties.

This short review provides an update of the anticancer and anti-inflammatory properties of casticin from Vitex species. Casticin is a polymethylflavone with three rings, an orthocatechol moiety, a double bond, two hydroxyl groups and four methoxyl groups. Casticin has been isolated from various tissues of plants in the Vitex genus: fruits and leaves of V. trifolia, aerial parts and seeds of V. agnus-castus and leaves of V. negundo. Studies have reported the antiproliferative and apoptotic activities of casticin from Vitex species. The compound is effective against many cancer cell lines via different molecular mechanisms. Studies have also affirmed the anti-inflammatory properties of casticin, with several molecular mechanisms identified. Other pharmacological properties include anti-asthmatic, tracheospasmolytic, analgesic, antihyperprolactinemia, immunomodulatory, opioidergic, oestrogenic, anti-angiogenic, antiglioma, lung injury protection, rheumatoid arthritis amelioration and liver fibrosis attenuation activities. Clinical trials and commercial use of the casticin-rich fruit extract of V. agnus-castus among women with premenstrual syndrome were briefly discussed.

Apocynaceae species with antiproliferative and/or antiplasmodial properties: a review of ten genera.

Apocynaceae is a large family of tropical trees, shrubs and vines with most species producing white latex. Major metabolites of species are triterpenoids, iridoids, alkaloids and cardenolides, which are known for a wide range of biological and pharmacological activities such as cardioprotective, hepatoprotective, neuroprotective, anti-inflammatory, anticancer and antimalarial properties. Prompted by their anticancer and antimalarial properties, the current knowledge on ten genera (Allamanda, Alstonia, Calotropis, Catharanthus, Cerbera, Dyera, Kopsia, Nerium, Plumeria and Vallaris) is updated. Major classes of metabolites are described using some species as examples. Species with antiproliferative (APF) and/or antiplasmodial (APM) properties have been identified. With the exception of the genus Dyera, nine genera of 22 species possess APF activity. Seven genera (Alstonia, Calotropis, Catharanthus, Dyera, Kopsia, Plumeria and Vallaris) of 13 species have APM properties. Among these species, Alstonia angustiloba, Alstonia macrophylla, Calotropis gigantea, Calotropis procera, Catharanthus roseus, Plumeria alba and Vallaris glabra displayed both APF and APM properties. The chemical constituents of these seven species are compiled for assessment and further research.

Phytochemistry, pharmacology, and clinical trials of Morus alba.

The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties.

Phytochemistry and pharmacology of ornamental gingers, Hedychium coronarium and Alpinia purpurata: a review.

In this review, the phytochemistry and pharmacology of two ornamental gingers, Hedychium coronarium (butterfly ginger) and Alpinia purpurata (red ginger), are updated, and their botany and uses are described. Flowers of H. coronarium are large, showy, white, yellow or white with a yellow centre and highly fragrant. Inflorescences of A. purpurata are erect spikes with attractive red or pink bracts. Phytochemical investigations on the rhizomes of H. coronarium generated research interest globally. This resulted in the isolation of 53 labdane-type diterpenes, with little work done on the leaves and flowers. Pharmacological properties of H. coronarium included antioxidant, antibacterial, antifungal, cytotoxic, chemopreventive, anti-allergic, larvicidal, anthelminthic, analgesic, anti-inflammatory, anti-urolithiatic, anti-angiogenic, neuro-pharmacological, fibrinogenolytic, coagulant and hepatoprotective activities. On the contrary, little is known on the phytochemistry of A. purpurata with pharmacological properties of antioxidant, antibacterial, larvicidal, cytotoxic and vasodilator activities reported in the leaves and rhizomes. There is much disparity in terms of research effort within and between these two ornamental gingers.

Antiproliferative activity of Vallaris glabra Kuntze (Apocynaceae).

BACKGROUND: Our earlier study on the antiproliferative (APF) activity of leaf extracts of ten Apocynaceae species showed that leaves of Vallaris glabra possessed strong and broad-spectrum properties. MATERIALS AND METHODS: In this study, sequential extracts of leaves, flowers and stems, and fractions and isolated compounds from dichloromethane (DCM) leaf extract of V. glabra were assessed for APF activity using the sulphorhodamine B (SRB) assay. Apoptotic effect of MDA-MB-231 cancer cells treated with DCM leaf extract of V. glabra was studied using Hoechst 33342 dye and caspase colorimetry. RESULTS: Both DCM extracts of leaves and flowers possessed broad-spectrum APF activity against HT-29, MCF-7, MDA-MB-231 and SKOV-3 cancer cells. From DCM leaf extract, stearic acid (SA) and ursolic acid (UA) were isolated by column chromatography, and identified by NMR and MS analyses. APF activity of SA from DCM leaf extract displayed weak inhibitory activity and scientific literature showed UA has anticancer properties against those cancer cells used in this study. MDA-MB-231 cancer cells treated with DCM leaf extract and stained with Hoechst 33342 dye provided evidence that the extract had an apoptotic effect on the cells. Caspase colorimetry showed that the apoptotic effect involved activation of caspase-8, -9 and -3, but not caspase-6. CONCLUSION: The potential of V. glabra as a candidate species for anticancer drugs warrants further investigation.

Caffeoylquinic acids in leaves of selected Apocynaceae species: Their isolation and content.

BACKGROUND: Three compounds isolated from the methanol (MeOH) leaf extract of Vallaris glabra (Apocynaceae) were those of caffeoylquinic acids (CQAs). This prompted a quantitative analysis of their contents in leaves of V. glabra in comparison with those of five other Apocynaceae species (Alstonia angustiloba, Dyera costulata, Kopsia fruticosa, Nerium oleander, and Plumeria obtusa), including flowers of Lonicera japonica (Japanese honeysuckle), the commercial source of chlorogenic acid (CGA). MATERIALS AND METHODS: Compound were isolated by column chromatography, and identified by NMR and MS analyses. CQA content of leaf extracts was determined using reversed-phase HPLC. RESULTS: From the MeOH leaf extract of V. glabra, 3-CQA, 4-CQA, and 5-CQA or CGA were isolated. Content of 5-CQA of V. glabra was two times higher than flowers of L. japonica, while 3-CQA and 4-CQA content was 16 times higher. CONCLUSION: With much higher CQA content than the commercial source, leaves of V. glabra can serve as a promising alternative source.

Antiproliferative and phytochemical analyses of leaf extracts of ten Apocynaceae species.

BACKGROUND: The anticancer properties of Apocynaceae species are well known in barks and roots but less so in leaves. MATERIALS AND METHODS: In this study, leaf extracts of 10 Apocynaceae species were assessed for antiproliferative (APF) activities using the sulforhodamine B assay. Their extracts were also analyzed for total alkaloid content (TAC), total phenolic content (TPC), and radical scavenging activity (RSA) using the Dragendorff precipitation, Folin-Ciocalteu, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, respectively. RESULTS: Leaf extracts of Alstonia angustiloba, Calotropis gigantea, Catharanthus roseus, Nerium oleander, Plumeria obtusa, and Vallaris glabra displayed positive APF activities. Extracts of Allamanda cathartica, Cerbera odollam, Dyera costulata, and Kopsia fruticosa did not show any APF activity. Dichloromethane (DCM) extract of C. gigantea, and DCM and DCM:MeOH extracts of V. glabra showed strong APF activities against all six human cancer cell lines. Against breast cancer cells of MCF-7 and MDA-MB-231, DCM extracts of C. gigantea and N. oleander were stronger than or comparable to standard drugs of xanthorrhizol, curcumin, and tamoxifen. All four extracts of N. oleander were effective against MCF-7 cells. Extracts of Kopsia fruticosa had the highest TAC while those of Dyera costulata had the highest TPC and RSA. Extracts of C. gigantea and V. glabra inhibited the growth of all six cancer cell lines while all extracts of N. oleander were effective against MCF-7 cells. CONCLUSION: Extracts of C. gigantea, V. glabra, and N. oleander therefore showed great promise as potential candidates for anticancer drugs. The wide-spectrum APF activities of these three species are reported for the first time and their bioactive compounds warrant further investigation.

Assessment of antiproliferative and antiplasmodial activities of five selected Apocynaceae species.

BACKGROUND: Studies have shown that the barks and roots of some Apocynaceae species have anticancer and antimalarial properties. In this study, leaf extracts of five selected species of Apocynaceae used in traditional medicine (Alstonia angustiloba, Calotropis gigantea, Dyera costulata, Kopsia fruticosa and Vallaris glabra) were assessed for antiproliferative (APF) and antiplasmodial (APM) activities, and analysed for total alkaloid content (TAC), total phenolic content (TPC) and radical-scavenging activity (RSA). As V. glabra leaf extracts showed wide spectrum APF and APM activities, they were further screened for saponins, tannins, cardenolides and terpenoids. METHODS: APF and APM activities were assessed using the sulphorhodamine B and lactate dehydrogenase assays, respectively. TAC, TPC and RSA were analysed using Dragendorff precipitation, Folin-Ciocalteu and DPPH assays, respectively. Screening for saponins, tannins, cardenolides and terpenoids were conducted using the frothing, ferric chloride, Kedde and vanillin-H2SO4 tests, respectively. RESULTS: Leaf extracts of A. angustiloba, C. gigantea and V. glabra displayed positive APF activity. Dichloromethane (DCM) extract of C. gigantea, and DCM and DCM:MeOH extracts of V. glabra showed strong APF activity against all six human cancer cell lines tested. DCM extract of A. angustiloba was effective against three cancer cell lines. Against MCF-7 and MDA-MB-231 cell lines, DCM extract of C. gigantea was stronger than standard drugs of xanthorrhizol, curcumin and tamoxifen. All five species were effective against K1 strain of Plasmodium falciparum and three species (C. gigantea, D. costulata and K. fruticosa) were effective against 3D7 strain. Against K1 strain, all four extracts of V. glabra displayed effective APM activity. Extracts of D. costulata were effective against 3D7 strain. Selectivity index values of extracts of A. angustiloba, C. gigantea and V. glabra suggested that they are potentially safe for use to treat malaria. Extracts of K. fruticosa had the highest TAC while D. costulata had the highest TPC and RSA. Phytochemical screening of extracts of V. glabra also showed the presence of terpenoids, tannins and saponins. CONCLUSIONS: Leaf extracts of C. gigantea and V. glabra showed great promise as potential candidates for anticancer drugs as they inhibited the growth of all six cancer cell lines. Against K1 strain of P. falciparum, all four extracts of V. glabra displayed effective APM activity. The wide spectrum APF and APM activities of V. glabra are reported for the first time and this warrants further investigation into its bioactive compounds.