Phytochemistry Reviews (v.14, #3)

Phytochemicals in medicine and food by Jianbo Xiao (317-320).

Nutritional composition, physiological functions and processing of lotus (Nelumbo nucifera Gaertn.) seeds: a review by Yi Zhang; Xu Lu; Shaoxiao Zeng; Xuhui Huang; Zebin Guo; Yafeng Zheng; Yuting Tian; Baodong Zheng (321-334).
Nelumbo nucifera Gaertn. has a relatively wide geographical distribution and biological diversity; various lotus parts have excellent food and medicinal values. Lotus seeds, which are currently the oldest known plant seeds, contain many functional ingredients. They can be eaten raw or cooked, and are often added to foods as ingredients or supplements. Many naturally occurring ingredients isolated from lotus seeds are certified to be multiple functional compounds, such as polyphenols, protein, polysaccharides. Proteins and carbohydrates are the main nutrients of lotus seeds. Low fat content and good proportion of amino acids confer to lotus seeds unique nutritional values that have attracted increasing attention around the world: multiple studies have assessed the functional components of lotus seeds. The bioactivity of ingredients from lotus seeds in vitro and in vivo include antioxidant activity, hypoglycemic, immunomodulatory, antibacterial, anti-inflammatory, analgesic effects as well as gastrointestinal regulation. Lotus seeds show prospective application in function food area and traditional medicine research. Furthermore, structure–activity relationship of functional compounds from lotus seeds will attracts much more interests in recent years. This work briefly reviews the nutrition composition, physiological functions and processing methods of lotus seeds, describing the impact of the latter on nutrient preservation. In addition, this review addresses the recent progresses made in this area and discusses the potential applications and limitations.
Keywords: Nelumbo nucifera Gaertn.; Semen nelumbinis ; Nutrition composition; Physiological activity; Products

Thymus L. is one of the most important and polymorphic genera of the Lamiaceae family, comprises ca. 250 species distributed across the Eurasian continent, North and East Africa, and southern Greenland, but the great majority of the indigenous species is found in the area that surrounds the Mediterranean region. Thymus species can potentially be used as the medicinal or aromatic herbs in the pharmaceutical and food industries. The essential oils of Thymus species are characterized by a high chemical variability due to different intrinsic (genetic variation) and extrinsic (ecological and environmental aspects) factors. Despite broad scientific interest in the biology, taxonomy, chemotypes, and related biological activity of secondary metabolites of Thymus species, there is a general lack of information regarding this genus from Balkan. The aim of the present review was to comprise the literature in order to document essential oil constituents that characterize different Thymus species from Balkan Peninsula. Essential oil composition of 45 Thymus taxa from ten countries was summarized. In addition, it discusses the reported biological activities of Thymus species, with particular focus on their antimicrobial and antioxidant properties. Cultivation of rare species, monitoring, and standardization of their essential oils, as well as direct studies on cellular and animal models are needed to assess whole spectrum of biological properties of essential oils of Thymus species.
Keywords: Thymus L.; Balkan Peninsula; Essential oil composition; Antimicrobial activity; Antioxidant activity

Saussurea medusa, source of the medicinal herb snow lotus: a review of its botany, phytochemistry, pharmacology and toxicology by Jia-Yi Fan; Hu-Biao Chen; Lin Zhu; Hong-Li Chen; Zhong-Zhen Zhao; Tao Yi (353-366).
Saussurea medusa Maxim. is a plant source of the traditional medicine known as “snow lotus” which has been recorded in many ethnopharmacy books, including: Herbal Communications, Flora Tibet, National Herbal Compendium, and Crystal beads Materia Medica, This plant is also a medicinal plant source of Gaode-Subage, a Mongolian folk medicine. The review summarizes the traditional uses and current knowledge concerning the botany, phytochemistry, pharmacological effects, toxicology studies and clinical applications of S. medusa. These could guide the priorities and direction of the future research. Information on S. medusa was gathered from e-literature found on the internet using SCI Finder, Google Scholar, Web of science, PubMed, CNKI, and the Wanfang database, and from printed material (books, theses, etc.) found in libraries. Additionally, information was also obtained from some local herb gatherers, herbal peddler and herbalist. More than 70 chemical compounds have been isolated, including apigenin, quercetin, rutin, arctigenin, saussureoside A, and saussureoside B. Modern pharmacological studies have found that S. medusa has anti-inflammatory, analgesic, anti-fungal, anti-tumor, anti-anoxia, anti-oxidation, and anti-fatigue effects. This plant also benefits the uterus, cardiovascular system, intestines, tracheal smooth muscle, and immune system. S. medusa is an important traditional herbal medicine with a broad spectrum of therapeutic efficacies. It has the reputation of non-toxic. Due to the low source of the original plant, experiment of cell culture of S. medusa can improve the output of the medicine. Further studies can lead to the development of new drugs and therapeutics from this medical plant for various diseases.
Keywords: Saussurea medusa ; Botany; Phytochemistry; Pharmacological effects

New advances in chemical defenses of plants: researches in calceolariaceae by Carlos L. Cespedes; Pedro M. Aqueveque; José G. Avila; Julio Alarcon; Isao Kubo (367-380).
Evidences about the biosynthesis of secondary metabolites from plants point to constitutive or induce chemical defense generated for protection against to different phytopathogenic attack. Calceolaria spp. is regarded both as a notorious weed and as a popular ornamental garden plant and have medicinal application. Some taxa of the America distributed Calceolaria genus are toxic to insects, fungi and several bacteria strains, and its effect has been associated with the presence of phenolics. Calceolaria spp. produces a number of iridoids, flavonoids, naphthoquinones and phenylpropanoids that have been shown to possess interesting biological activities. All these aspects are considered in this review to allow an evaluation of the potential for utilization of the large biodiversity of Calceolaria available. An up-to-date of the phytochemistry and biological activities of several members of the Calceolariaceae family is show. New iridoids, flavonoids and phenylpropanoids for these Calceolaria species have been isolated, identified and tested for their antifeedant, igr, insecticidal, antimicrobial, anticancer, proteinase, tyrosinase, and acetylcholinesterase inhibitory activities. Until now mixtures of flavonoids have been found to be potent insecticides and fungicides, followed by phenylpropanoids mixtures and iridoids showed to be antifeedant and in some cases repellent and attractant. Dose-dependent experiments shows that flavonoids are insecticidal against S. frugiperda and D. melanogaster at early growth stages. Bactericidal and fungicidal activity showed that dunnione (a naphthoquinone) have potent activity as fungistatic and fungicidal. O-methylflavonols, and different mixtures of them were very effective fungistatic. However, fungistatic quercetin and dunnione both combined with sublethal amount of kaempferol and gallic acid showed a strong fungicidal activity against phytopathogenic strains. Additionally, naphthoquinones possess a promissory activity as anticancer.
Keywords: Biological activity; Calceolariaceae; Naphthoquinones; Insecticidal; Antimicrobial; Anticancer

Advance on the benefits of bioactive peptides from buckwheat by Xiaoli Zhou; Lang Wen; Zongjie Li; Yiming Zhou; Yingjiao Chen; Yuan Lu (381-388).
Buckwheat is a kind cereal mainly grown in cold plateau and mountainous districts. The seeds and food production made from buckwheat demonstrated great nutritional value and protective effects towards various kinds of disease. In this review, the antibacterial, trypsin inhibiting, antitumor, hypocholesterol, hypotensive and antidiabetic effects of buckwheat proteins and their enzyme hydrolysates were summarized and discussed. Many naturally occurring peptides isolated from buckwheat seeds are certified to be multiple functional compounds, such as buckwheat antimicrobial peptides, trypsin inhibitors, antitumor proteins, hypotensive peptides and antioxidant peptides. Besides its trypsin inhibiting activity upon proteases, buckwheat trypsin inhibitors also revealed antimicrobial activity towards fungi, Gram-positive and Gram-negative bacteria and antitumor activity against various kinds of cancer cells. The antitumor effects and the trypsin inhibiting activity are related with the special active site of the peptide molecules, while the hypolipidemic property and the hypotensive activity are most probably associating with the unique amino acids composition of buckwheat proteins, for the reason that the hydrolyzed small peptides still possess the relevant activity. Buckwheat peptides show prospective application in function food area and traditional medicine research. And structure–activity relationship of peptides attracts much more interests in recent years.
Keywords: Buckwheat; Antimicrobial peptides; Trypsin inhibitors; Antitumor proteins; Hypotensive peptides

Secondary metabolites have diverse functions into plants. These functions are products of the coevolution which result in synthesis of constitutive and/or induced chemical defense generated for protection against to different phytopathogenic attack. Many phytochemical studies are biodirected with the aim of finding biopesticides of botanical origins. Some taxa of Americas such as Rhamnaceae family are toxic to insects, fungi and several bacteria strains, and these effects has been associated with the presence of alkaloids, phenolics and terpenes. The natural compounds that have been isolated represent a valuable resource for future studies of plant chemical defense and the role of these substances in chemical ecology. Here are show recent advances in the phytochemistry and biological activities of selected members of Rhamnaceae from Latin-America.
Keywords: Rhamnaceae; Cyclopeptidealkaloids; Condalia; Talguenea; Discaria; Triterpenes; Insecticidal activity

Solanesol: a review of its resources, derivatives, bioactivities, medicinal applications, and biosynthesis by Ning Yan; Yanhua Liu; Daping Gong; Yongmei Du; Huaibao Zhang; Zhongfeng Zhang (403-417).
Solanesol, which mainly accumulates in solanaceous crops, including tobacco, tomato, potato, eggplant, and pepper plants, is a long-chain polyisoprenoid alcohol compound with nine isoprene units. Chemical synthesis of solanesol is difficult; therefore, solanesol is primarily extracted from solanaceous crops, particularly tobacco leaves. In plants, solanesol exists in both free and esterified forms, and its accumulation is influenced by genetic and environmental factors. Solanesol is widely used in the pharmaceutical industry as an intermediate for the synthesis of ubiquinone drugs, such as coenzyme Q10 and vitamin K2. Solanesol possesses antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, and anti-ulcer activities, and solanesol derivatives also have anti-oxidant and antitumour activities, in addition to other bioactivities. Solanesol derivatives can also be used for the treatment of cardiovascular disease, osteoporosis, acquired immune deficiency syndrome, and wound healing. Solanesol biosynthesis occurs in plastids of higher plants via the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway. The key enzymes in solanesol biosynthesis, including 1-deoxy-d-xylulose-5-phosphate synthase, 1-deoxy-d-xylulose-5-phosphate-reductoisomerase, isopentenyl pyrophosphate isomerase, and solanesyl diphosphate synthase, are also important regulators of the MEP pathway, and their overexpression is favourable for downstream metabolic flow, further promoting the synthesis of downstream metabolites, such as solanesol. Future studies should determine the pharmacokinetic properties of solanesol and its derivatives and investigate the metabolic pathways and regulatory mechanisms mediating solanesol biosynthesis, metabolic and genetic engineering of solanesol, the synthetic biology of solanesol, and the physiological role of solanesol. In the present review, we systematically summarise current knowledge on solanesol resources, derivatives, bioactivities and medicinal applications, metabolic pathways, and key biosynthetic enzymes.
Keywords: Bioactivities; Biosynthesis; Derivatives; Medicinal application; Resources; Solanesol

Cosmetic potential of Southeast Asian herbs: an overview by Radhakrishnan Narayanaswamy; Intan Safinar Ismail (419-428).
Herbs and spices have been used in retaining and boosting human beauty since time immemorial. Herbal cosmetic has growing demand in the worldwide market and is an invaluable gift of Mother Nature. In the present review, the focus is on the cosmetic herbs of Southeast Asian countries namely Malaysia, Cambodia, Laos, Myanmar [Burma], Thailand, Vietnam, Brunei, East Timor, Indonesia, Philippines and Singapore in highlighting both traditional and scientific knowledge or background of the selected potential herbs. The available literature was searched in the following scientific database such as PubMed, Google Scholar, Science Direct and Springer for publications and patents. In view of traditional uses, herbs like Allium sativum, Aloe vera, Centella asiatica, Curcuma longa, Hibiscus rosa-sinensis, Lawsonia inermis and Tamarindus indica L. were classified as need of special mention. Many herbs have been scientifically evaluated for their cosmetic potentials such as anti-aging, anti-acne, melanogenic and anti-tyrosinase activities. The great void remains for a systematic study, thorough review of scientific report that provides a basis for the use of specific herbs due to their efficacy as cosmetics. In addition, two of the Malay herbs; Labisia pumila (Kacip Fatimah) and Ficus deltoidea (Mas cotek), are proposed to be clinically studied for their safety in cosmetic application aspects wherein the need for safety evaluation and fruitful application of herbal cosmetics were emphasized.
Keywords: Malaysian herbs; Traditionally use; Herbal cosmetics; Topical applications

Current status of CPT and its analogues in the treatment of malignancies by Guohua Hu; David Zekria; Xun Cai; Xiaoling Ni (429-441).
Camptothecin (CPT) is a kind of terpene indole alkaloid which was firstly isolated from native Chinese happy tree Camptotheca acuminata and owns a unique anti-tumor mechanism by inhibiting Topo I. Being approved by FDA, the camptothecin derivatives, irinotecan and topotecan, are extensively used for the treatment of various cancers throughout the world. In the past decades, pharmacology of CPT and its analogues has been well documented. This review will focus on different human malignancies with demonstrated clinical efficacy of CPT analogues.
Keywords: Analogues; Camptothecin; Chemotherapy; Malignancies

Edible freshwater macrophytes: a source of anticancer and antioxidative natural products—a mini-review by Tsun-Thai Chai; Keng-Fei Ooh; Yixian Quah; Fai-Chu Wong (443-457).
Edible freshwater macrophytes (EFM) are edible, macroscopic freshwater plants, many of which are also used as traditional/folk medicine. This mini-review highlights phytochemical and pharmacological evidence pertaining to anticancer and antioxidative natural products derived from EFM, with special attention to Centella asiatica (Indian pennywort), Nelumbo nucifera (sacred lotus), Nasturtium officinale (watercress), Ipomoea aquatica (water spinach) and Ludwigia adscendens (water primrose). Current knowledge gaps and further research opportunities are also discussed. EFM is a promising source of anticancer and antioxidative natural products which warrants more extensive exploration. More research is needed before such natural products can be exploited for application in food and medicine.
Keywords: Centella asiatica ; Ipomoea aquatica ; Ludwigia adscendens ; Nasturtium officinale ; Nelumbo nucifera

Interactions between soy isoflavones and other bioactive compounds: a review of their potentially beneficial health effects by Meng-Lei Xu; Jingbo Liu; Chunyi Zhu; Yu Gao; Songning Zhao; Wenchao Liu; Yan Zhang (459-467).
We review the recent literature on the protective effects of soy isoflavones and other bioactive components. We review the effect of combinations of three soy isoflavones, daidzein, genistein, and glycitein and examine the interactions of individual soy isoflavones with other compounds such as vitamins, trace elements, chemotherapeutics, and phytoestrogens. We further review the effect of whole isoflavones and other compounds and discuss these effects when assessing the risks associated with various environmental and food compounds.
Keywords: Soy isoflavone; Genistein; Daidzein; Glycitein; Health

Phytochemical analysis of isoflavonoids using liquid chromatography coupled with tandem mass spectrometry by Kanumuri Siva Rama Raju; Naveen Kadian; Isha Taneja; M. Wahajuddin (469-498).
Isoflavonoids are the biologically active secondary metabolites of plants that are being used for several health promoting and restoring effects mediated through different pathways. Isoflavonoids are structurally similar to estrogens due to which also known as phytoestrogens and have shown potent estrogenic and anti-estrogenic activity. Association with large biological activity lead to the need of rapid, sensitive and precise quantitation of different isoflavonoids in different plant extracts, food materials and biological matrices as the biological activities mainly depends on the quantities and nature of isoflavonoids present in them. The characterisation, standardisation and quantification of herbal extracts or food products require techniques that are highly selective, sensitive and also provide mass measurement precisions and structural information. Liquid chromatography with tandem mass spectroscopy has made it possible to analyse and characterize several constituents and their metabolites in a single run along with high selectivity and sensitivity. In this review, we have summarised the application of LC–MS/MS for the identification and quantification of isoflavonoids reported for various plant extracts and food products along with their general extraction procedures and factors affecting extraction providing a view towards the conditions used for their analysis. The most suitable and widely acceptable extraction solvent system for the isoflavonoids is methanol or ethanol in combination with water ranging from 40 to 60 % organic solvent based on the type of tissues and the isoflavonoids to be extracted by different extraction techniques. ESI ionization with Q-TOF MS was the most useful detection system for the characterisation and quantification of the diverse isoflavonoids with molecular insights.
Keywords: LC–MS/MS; Isoflavonoids; Phytoestrogens; Extraction; Polyphenols

Brick dark tea is a unique brick-formed tea compressed from the older, coarse and rough leaves and branches of Camellia sinensis var. sinensis and C. sinensis var. assamica mainly in Hunan, Sichuan and Yunnan provinces in China. Researches on brick dark tea have become increasingly popular owing to its special health benefits. A series of biochemical reactions occur during the special production—microbial fermentation stage and multitudinous components have been detected. Many of the functional components have been isolated and identified from brick dark tea. In this paper, modern manufacturing techniques about different kinds of brick dark tea and their effects on transformation of the chemical constituents, as well as the chemical components were reviewed and discussed.
Keywords: Brick dark tea (BDT); Fuzhuan brick tea (FBT); Processing; Chemical components; Biochemical conversion

Biosynthesis and biotechnological production of anti-cancer drug Camptothecin by Guoyin Kai; Chao Wu; Liyuan Gen; Liqiang Zhang; Lijie Cui; Xiaoling Ni (525-539).
Camptothecin (CPT) is a kind of modified monoterpene indole alkaloid firstly identified from woody plant Camptotheca acuminata, and its semisynthetic CPT analogs irinothecan and topothecan are clinically used for the treatment of various cancers throughout the world. However, the extraction of CPT from limited natural CPT-producing plant resources couldn’t meet the rapidly increasing market need. The development of plant metabolic engineering provides one alternative way to increase CPT yield by genetic manipulation, which relies on in-depth understanding of the CPT biosynthesis pathway. Several attempts have been also made to obtain CPT by biotechnological approaches such as cell suspensions, endophytic fungi, hairy roots, elicitation as well as metabolic engineering in the past decade. Here, recent advances in knowledge of biosynthesis of CPT, gene isolation, molecular regulation, production improvement and biotechnological methods are summarized and future perspectives are also discussed in this review.
Keywords: Biosynthesis; Camptothecin; Endophytes; Gene cloning; Hairy root; Metabolic engineering

Influence of Agrobacterium oncogenes on secondary metabolism of plants by Tatiana V. Matveeva; Sophie V. Sokornova; Ludmila A. Lutova (541-554).
The transgenic hairy root cultures have revolutionized the role of tissue culture of plants in the production of secondary metabolites. It was shown that hairy roots often exhibit about the same or higher biosynthetic capacity for secondary metabolite production comparing to their normal roots. Using this methodology, a big number of chemical compounds has been synthesized. The role of single rol genes in secondary metabolite production was studied. Stimulatory effect on the production of secondary metabolites has been shown for genes rolA, rolB, rolC. These genes are present in naturally trasgenic Linaria and Nicotiana plants that are discussed as a model for study of possible evolutionary function of rol genes in the control of secondary metabolites.
Keywords: T-DNA; rol genes; Secondary metabolism