An Overview of Chemical Constituents, Medicinal Properties, Clinical Trials, and Patents of Twigs of Morus alba(Ramulus Mori)

The rich chemical constituents and diverse pharmacological properties of Ramulus Mori(RM) or the twig of Morus alba with evidence supported by clinical trials and patents are reviewed. Known as Sangzhi in Chinese, RM is widely used in traditional Chinese medicine to treat gout, arthritis, and rheumatism. Chemical constituents include flavonoids, benzofurans, alkaloids, stilbenes, chalcones, phenolic acids, and coumarins. Bioactivities of RM include antidiabetic, anti-obesity, anti-inflammatory, antityrosinase, neuroprotective, antioxidant, hepatoprotective, cytoprotective, renoprotective, antihyperuricemic, analgesic, antifungal, DNA protective, anticancer, gastroprotective, cardioprotective, anti-hair aging, anti-arthritic, and antiplatelet aggregation properties. The most active compounds from RM are mulberrin, oxyresveratrol, and mulberroside A. All four clinical trials on RM are focused on the treatment of diabetes. The patents entail using RM extracts as cosmetics for skin whitening and as agents for hypoglycemia. Topics for further research on RM are suggested.

An overview of flavonoids from Sophora flavescens(kushen)with some emphasis on the anticancer properties of kurarinone and sophoraflavanone G

In this overview,the current knowledge of the constituents of flavonoids isolated from the roots of Sophora flavescens(kushen)is updated.Flavonoids consist of several classes,such as flavanones,flavonols,chalcones,isoflavones,biflavonoids,flavanols,and flavones.The most common compounds are kurarinone(KRN),sophoraflavanone G(SFG),2′-methoxykurarinone,kuraridine,isoxanthohumol,and formononetin.KRN and SFG are two major flavanones with more vital anticancer properties than other flavonoids.From the literature,the cytotoxic values of KRN and SFG are variable and depend on the type of cancer cells tested.The anticancer activities of these two flavonoids involve different molecular mechanisms.Clinical trials are needed before anticancer drugs from KRN and SFG can be developed.

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 Pub Med,Pub Med Central, Science Direct, Google, Google Scholar, J-Stage, Pub Chem and China National Knowledge Infrastructure.

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.

Phenolic constituents from the root bark of Morus alba with emphasis on morusin and its anti-cancer properties

The root bark of Morus alba L. or white mulberry is widely used as traditional medicine in China, Japan and Korea. Major classes and types of phenolic compounds isolated from the root bark are flavonoids(kuwanons, morusin, cyclomorusin and sanggenons), benzofurans(moracins and mulberrofurans), and stilbenoids(mulberrosides). Some of the flavonoids and benzofurans are products of Diel-Alder type adducts. Other classes of compounds include triterpenes, phenolic acids and coumarins. Morusin, a prenylated flavonoid, was first isolated from the root bark of M. alba, and later from the leaf, stem bark and twig of the plant. The potent anti-cancer properties of morusin have attracted much attention with research on-going and new findings being published. The compound inhibits angiogenesis, tumour progression and tumour migration, and triggers apoptosis, cell cycle arrest and autophagy in colorectal, cervical, prostate, breast, hepatoma, pancreatic, glioblastoma, gastric, ovarian and lung cancer cell lines. The anti-cancer activities of morusin are executed via various molecular targets and signalling pathways. It is anticipated that on-going in vitro studies will progress gradually to in vivo studies using animal models before efforts towards drug development can be initiated for clinical trials.

Alpinia zerumbet, a ginger plant with a multitude of medicinal properties： An update on its research findings

In this review, the botany and uses of Alpinia zerumbet(yan shan jiang) are described, and the current knowledge of its phytochemistry, pharmacological properties, and clinical trials is summarized. An important ginger crop in East Asia, A. zerumbet has many uses, both medicinal and non-medicinal. Leaves are used to produce essential oils and herbal teas. Rhizomes are consumed as spices, and stem fibers are made into paper, fabrics, and handicrafts. In Brazil, tea from A. zerumbet leaves is believed to have hypotensive, diuretic, and anti-ulcerogenic properties. This species possesses many medicinal properties due to its chemical constituents, including flavonoids, phenolic acids, phenylpropanoids, kava pyrones, sterols, and terpenoids. Extracts of A. zerumbet display antioxidant, antimicrobial, insecticidal, anthelmintic, tyrosinase and melanogenesis inhibitory, anti-atherogenic, anti-aging, anti-glycation, integrase and neuraminidase inhibitory, lifespan prolongation, hair growth promotion, anticancer, antidepressant, anxiolytic, anti-obesity, analgesic, anti-inflammatory, hypolipidemic, anti-ulcerogenic, anti-platelet, osteoblastic, osteogenic, thrombolytic, and cardiac arrhythmogenic activities. Essential oils of A. zerumbet leaves have antimicrobial, larvicidal, antinociceptive, hypotensive, vasorelaxant, myorelaxant, antispasmodic, antidepressant, anxiolytic, anti-neuraminidase, anti-atherogenic, anti-aging, anti-melanogenic, anti-tyrosinase, cytoprotective, cardiodepressive, antipsychotic, analgesic, anti-inflammatory, and tissue healing activities. Clinical trials conducted in Brazil showed that extracts of A. zerumbet have hypotensive and diuretic effects whereas topical application of the essential oil has positive therapeutic effects on patients with fibromyalgia. Spanning two continents of Asia and South America, A. zerumbet is truly a multi-purpose ginger plant with promising medicinal properties.

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.

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.

Matrine, oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities

In the present review,we updated current information on the chemistry,contents,and anticancer properties of matrine(MT),oxymatrine(OMT),and compound Kushen injection(CKI).The anticancer properties were focused on lung,breast,and liver cancer cells because they are most susceptible.Sources of information were from Google,Google Scholar,PubMed,PubMed Central,Science Direct,PubChem,J-Stage,Directory of Open Access Journals(DOAJ),and China National Knowledge Infrastructure(CNKI).Reference was also made on botanical websites,such as Flora of China and World Flora Online.MT and OMT are dominant quinolizidine alkaloids from the roots of Sophora flavescens(Kushen)of the family Fabaceae.Against lung,breast,and liver cancer cells,MT and OMT inhibit cell proliferation;induce cell cycle arrest,apoptosis,and autophagy;restrict angiogenesis;and inhibit cell metastasis,invasion,and migration.The processes involve various molecular targets and signaling pathways.CKI is a traditional Chinese medicine(TCM)composed of root extracts of S.flavescens and Smilax glabra(Baituling)of the family Smilacaceae.With MT and OMT as major components,CKI has been approved for the treatment of cancer in China more than 20 years ago.In recent years,systematic reviews and meta-analysis have been undertaken to evaluate the anticancer effects of CKI.When CKI is used alone and in combination with chemotherapy of western medicine,there is much to be learned concerning their interactions besides their individual and integrated efficacy.Some perspectives of MT,OMT,and CKI are discussed,and their suggestions for future research are provided.

Cerbera are coastal trees with promising anticancer properties but lethal toxicity： A short review

In this short review, the current knowledge on the chemical constituents and anticancer properties of Cerbera odollam and Cerbera manghas is updated with some description of their botany and uses. Although these two closely-related coastal tree species have overlapping geographical distribution, they can be distinguished by the eye colour of flowers and the shape of fruits. Chemical constituents of C. odollam and C. manghas include lignans, iridoids, terpenoids, cardiac glycosides(cardenolides), flavonoids, phenolic acids and steroids. Cardiac glycosides of cerberin, dehydrocerberin, neriifolin, tanghinin, deacetyltanghinin and tanghinigenin possess promising anticancer properties with apoptotic activities. However, these cardiac glycosides are also cardiotoxic. Fatal cases of suicides by ingesting Cerbera fruits or seeds have been reported in India and Sri Lanka. In two suicide cases, one in Taiwan and another in the United States, the patients recovered completely. In New Caledonia, four death-threatening cases of poisoning(two were fatal) occurred through consuming toxic coconut crabs. Taken together, both C. odollam and C. manghas are endowed with cardiac glycosides, which have useful pharmacological properties but lethal toxicity.

A synopsis on flavonoids from the roots of Scutellaria baicalensis with some insights on baicalein and its anti-cancer properties

Flavones are the most dominant type of flavonoids isolated from the roots of Scutellaria baicalensis(Radix Scutellariae), which is a traditional medicinal plant in East Asian countries, including China, Japan and Korea.Most of the flavones are derivatives with methoxyl and hydroxyl groups, and they include baicalein, baicalin, chrysin, norwogonin, oroxylin A and wogonin.Baicalein possesses anti-cancer activities against a wide spectrum of human cancer cells by inducing apoptosis and cell cycle arrest, and by inhibiting angiogenesis, metastasis and inflammation.Some examples of the effects of baicalein on apoptosis, cell cycle arrest and metastasis are presented with discussion on the molecular targets and pathways.Studies on the structure-activity relationships of flavonoid cytotoxicity towards human cancer cells show that the potent cytotoxic activities of baicalein can be attributed to its-OH groupsat C5, C6 and C7(triple hydroxylation) of ring A, carbonyl group at C4 of ring C, and C2–C3 double bond of ring C.Studies on structural modifications of baicalein have shown that the configurations at C6 of ring A are critical factors influencing its anti-proliferative activity.Considering the remarkable anti-cancer properties, the future prospects for developing baicalein into an anti-cancer drug are promising.

Nobiletin and tangeretin(citrus polymethoxyflavones): an overview on their chemistry, pharmacology and cytotoxic activities against breast cancer

The fruit peel of Citrus species(Chenpi),particularly those of mandarin oranges,is a useful source of food and medicine in China.Flavonoids from the citrus fruit peel are mainly polymethoxyflavones(PMFs),of which nobiletin and tangeretin are the most abundant components.In the present review,we summarized the cytotoxic activities of these two PMFs to breast cancer cells.Studies have reported that these two compounds inhibit the growth of breast cancer cells by inducing apoptosis,cytostatic cell death and cell cycle arrest,or by inhibiting cell proliferation,metastasis and tumour angiogenesis,depending on the molecular subtypes of breast cancer.In vitro and in vivo cytotoxic activities involve different molecular targets and signalling pathways.Analyses on the structure-activity relationship(SAR)of nobiletin and tangeretin have shown that the presence of a methoxy group at C8 and a hydroxyl group at C3 or C5 are essential for anti-proliferative activity.Some future perspectives and research needs are suggested.Sources of information are from Pub Med,Pub Med Central,Science Direct,Google Scholar,J-Stage,Pub Chem and CNKI using keyword search.

An overview of Pu-erh tea and its health-promoting effects of lipid-lowering and anti-obesity

As a dark tea,Pu-erh tea(PET)is produced from sun-dried leaves of Camellia sinensis var.assamica mainly in Yunnan Province of China.Many microorganisms are involved in the fermentation of PET.Among them,Aspergillus niger is most important.It is believed that the longer the preservation period,the better is the quality and taste of PET,which is commercially available as loose,compressed or instant tea leaves.Chemical components of PET include flavones,flavanols,flavonols,phenolic acids,alkaloids and methylxanthines.In this overview,the lipid-lowering and anti-obesity effects of PET were discussed based on animal models and human trials,and our study provided some insights into possible mechanisms of bioactive compounds,such as theabrownin,catechins,lovastatin and gallic acid.Other bioactivities of PET and some information on Fuzhuan brick tea were also included.Sources of information cited were from Google Scholar,Pub Med,Pub Med Central,Science Direct,J-Stage,Pub Chem,Directory of Open Access Journals(DOAJ),and China National Knowledge Infrastructure(CNKI).

Genipin and geniposide from Gardenia jasminoides:An overview of their anti-cancer and other pharmacological properties

Genipin and geniposide are iridoids from the fruits of Gardenia jasminoides.Both compounds have a methyl acetate(-COOCH_(3))group at C4 and a hydroxyl(-OH)group at C10.As an iridoid glucoside with a glucose moiety at C1,geniposide is also known as genipin-1-O-β-D-glucoside.Without the glucose moiety,genipin is an iridoid and the aglycone of geniposide.The-OH group at C1 of genipin is responsible for its cytotoxic effects.Geniposide without the-OH group at C1 lacks the cytotoxic effects.There are more publications on the anti-cancer properties of genipin than geniposide.Studies have reported the potentiation of genipin when used in combination with anti-cancer drugs.The anti-cancer properties of geniposide have been investigated using human intestinal microflora that hydrolyzes geniposide to genipin.Both genipin and geniposide exert antiproliferative and apoptotic activities via different molecular targets and pathways.Other pharmacological properties of genipin and geniposide include antidepressant,antidiabetic,anti-inflammatory,anti-obesity,anti-thrombotic,hepatoprotective,and neuroprotective activities.Future research on genipin and geniposide is suggested.