Purification of citrus limonoids and their differential inhibitory effects on human cytochrome P450 enzymes

Recent studies demonstrated that citrus limonoids and flavonoids possess numerous health promoting properties. In the present study, glucosides of limonoids and flavonoids were purified from citrus molasses and limonoid aglycones from citrus seeds. Glucosides were separated on styrene (divinylbenzene), Q‐sepharose resins with increasing concentration of sodium chloride. A pH‐dependent cold precipitation was carried out for the isolation of naringin in large quantity. Major aglycones such as limonin and nomilin were isolated from seeds by direct crystallization and minor limonoids were purified by vacuum liquid chromatography. The structures of the isolated compounds were confirmed by NMR spectra. Individual limonoids were tested for O‐dealkylase and hydroxylase activities of human cytochrome P450 (CYP) isoenzymes such as CYP1A2, CYP1B1, CYP3A4 and CYP19, using ethoxyresorufin, methoxyresorufin and dibenzylfluorescein as substrates. Partial to high inhibition of CYPs was observed in dose‐dependent assays. Significant (P < 0.001) reductions in enzyme activities were observed with purified compounds above 2 µmol. Kinetic analyses indicated that limonin glucoside inhibited CYP19 competitively (IC₅₀, 7.1 µ mol L^?1), whereas Nomilinic acid glucoside inhibited it noncompetitively (IC₅₀, 9.4 µ mol^?1). Nomilinic acid glucoside was the most potent limonoid, with an overall IC₅₀ of < 10 µ mol, for all the enzymes tested. The differential inhibition of CYPs can be ascribed to structural variations of the limonoid nucleus. Limonoid inhibition of key CYPs involved in carcinogenesis supports growing evidence that citrus limonoids act as anticancer agents. Copyright © 2007 Society of Chemical Industry     

Biochemistry and biological functions of citrus limonoids

Abstract

Limonoids are one of bitter principles in citrus juices. Excessive bitterness lowers the quality and value of citrus juices. Nomilin is considered to be the precursor of all other limonoids accumulated in Citrus and related species. It is biosynthesized from acetate via the terpenoid biosynthetic pathway in the phloem region of stems and then translocated to the leaves, fruit tissues, peels, and seeds where it is further metabolized to other limonoids. The citrus limonoid aglycones are then glucosidated by limonoid UDP‐D‐glucose transferase in maturing fruit tissues and seeds. These limonoid glucosides are accumulated in such high concentrations that they are one of major secondary metabolites in citrus fruit tissues, and they play an important role in fruit quality and possibly in human health. Research on creation of transgenic citrus trees that produce fruits free of the limonoid bitterness problem is in progress. Limonoids have been shown to induce glutathione S‐transferase activity and inhibit the formation of certain chemically induced carcinogenesis in laboratory animals. Some of the limonoids possess antifeedant activity against insects, suggesting that one of the biological functions of limonoids in plants is pest control. The citrus limonoids are unique for many species and varieties, and make excellent taxonomic markers. Thus, limonoids are important citrus constituents to citrus growers, processors, breeders, and the consumer.     

Limonoids as cancer chemopreventive agents

Nutritional research on the health benefits of substances in plant foods has recently advanced to a new stage. The research frontier has moved from study of classical vitamin deficiency diseases to study of the thousands of phytochemicals that may have important physiological effects. Recent research suggests that citrus fruit consumers may be getting another health benefit from orange juice and other citrus products called limonoids, which appear to possess substantial anticancer activity. Limonoids are highly oxidized triterpenes present in Rutaceae and Maliaceae families. Several citrus limonoids have recently been subjected to anticancer screening utilizing laboratory animals and human breast cancer cells. The experimental results described that citrus limonoids may provide substantial anticancer actions. The compounds have been shown to be free of toxic effects in animal models, so potential exists for the use of limonoids against human cancer in either natural fruits, in citrus fortified with limonoids, or in purified forms of specific limonoids. Although the initial studies are very promising they have been conducted primarily with in vitro cell culture and animal models. Thus, research is needed to determine whether the limonoids may be useful in preventing or treating cancer in humans. Copyright © 2005 Society of Chemical Industry     

类柠檬苦素生物转化与脱苦研究进展

类柠檬苦素中柠檬苦素的苦味是世界柑橘属果汁加工业的一大障碍,类柠檬苦素生物脱苦法是目前改善苦味的首选方法。本文主要概述类柠檬苦素的结构与分类、自然生物转化与“后苦”现象、酶法脱苦、固定化细胞脱苦和基因工程脱苦等方面的国内外研究进展。     

Chemical constituents and biological research on plants in the genus Curcuma

Curcuma, a valuable genus in the family Zingiberaceae, includes approximately 110 species. These plants are native to Southeast Asia and are extensively cultivated in India, China, Sri Lanka, Indonesia, Peru, Australia, and the West Indies. The plants have long been used in folk medicine to treat stomach ailments, stimulate digestion, and protect the digestive organs, including the intestines, stomach, and liver. In recent years, substantial progress has been achieved in investigations regarding the chemical and pharmacological properties, as well as in clinical trials of certain Curcuma species. This review comprehensively summarizes the current knowledge on the chemistry and briefly discusses the biological activities of Curcuma species. A total of 720 compounds, including 102 diphenylalkanoids, 19 phenylpropene derivatives, 529 terpenoids, 15 flavonoids, 7 steroids, 3 alkaloids, and 44 compounds of other types isolated or identified from 32 species, have been phytochemically investigated. The biological activities of plant extracts and pure compounds are classified into 15 groups in detail, with emphasis on anti-inflammatory and antitumor activities.     

p‐Coumaric acid and its conjugates: dietary sources,pharmacokinetic properties and biological activities

p‐Coumaric acid (4‐hydroxycinnamic acid) is a phenolic acid that has low toxicity in mice (LD₅₀ = 2850 mg kg^?1 body weight), serves as a precursor of other phenolic compounds, and exists either in free or conjugated form in plants. Conjugates of p‐coumaric acid have been extensively studied in recent years due to their bioactivities. In this review, the occurrence, bioavailability and bioaccessibility of p‐coumaric acid and its conjugates with mono‐, oligo‐ and polysaccharides, alkyl alcohols, organic acids, amine and lignin are discussed. Their biological activities, including antioxidant, anti‐cancer, antimicrobial, antivirus, anti‐inflammatory, antiplatelet aggregation, anxiolytic, antipyretic, analgesic, and anti‐arthritis activities, and their mitigatory effects against diabetes, obesity, hyperlipaemia and gout are compared. Cumulative evidence from multiple studies indicates that conjugation of p‐coumaric acid greatly strengthens its biological activities; however, the high biological activity but low absorption of its conjugates remains a puzzle. © 2015 Society of Chemical Industry     

Interactions between phytochemicals from fruits and vegetables: Effects on bioactivities and bioavailability

The combinations of two or more phytochemicals bring about changes in the ultimate biological effects and/or the bioavailability of each component. A number of mixtures of pure bioactive compounds or phytochemical-containing plant extracts provide synergy with regard to antioxidant status, anti-inflammation, anti-cancer and chemoprevention of several oxidative stress and metabolic disorders in vitro. The biological activities of food phytochemicals depend upon their bioaccessibility and bioavailability which can be affected by the presence of other food components including other bioactive constituents. The interactions between phytochemicals during intestinal absorption could result in changes in the bioavailability of the compounds, which in turn affects the intensity of their bioactivities. This paper provides an overview of combined biological effects of phytochemical mixtures derived from fruits and vegetables with a focus on anti-oxidative, anti-inflammatory and anti-carcinogenic activities. The bioavailability impairment or enhancement caused by the co-consumption of dietary phytochemicals is also discussed. Finally, research gaps for future studies on phytochemical interactions are identified.     

柠檬苦素类似物的研究进展综述

研究表明柠檬苦素类似物具有多种生物活性,其在抗癌、抗炎、镇痛、除虫、抗氧化性、调节血糖等方面具有作用。因此,柠檬苦素类似物的研究受到越来越多的重视。本文就柠檬苦素类似物的提取、纯化、分析和生物活性等方面作了简单概述。     

Nutrient components,health benefits,and safety of litchi (Litchi chinensis Sonn.): A review

Litchi (Litchi chinensis Sonn.) is a tropical to subtropical fruit that is widely cultivated in more than 20 countries worldwide. It is normally consumed as fresh or processed and has become one of the most popular fruits because it has a delicious flavor, attractive color, and high nutritive value. Whole litchi fruits have been used not only as a food source but also for medicinal purposes. As a traditional Chinese medicine, litchi has been used for centuries to treat stomach ulcers, diabetes, cough, diarrhea, and dyspepsia, as well as to kill intestinal worms. Both in vitro and in vivo studies have indicated that whole litchi fruits exhibit antioxidant, hypoglycemic, hepatoprotective, hypolipidemic, and antiobesity activities and show anticancer, antiatherosclerotic, hypotensive, neuroprotective, and immunomodulatory activities. The health benefits of litchi have been attributed to its wide range of nutritional components, among which polysaccharides and polyphenols have been proven to possess various beneficial properties. The diversity and composition of litchi polysaccharides and polyphenols have vital influences on their biological activities. In addition, consuming fresh litchi and its products could lead to some adverse reactions for some people such as pruritus, urticaria, swelling of the lips, swelling of the throat, dyspnea, or diarrhea. These safety problems are probably caused by the soluble protein in litchi that could cause anaphylactic and inflammatory reactions. To achieve reasonable applications of litchi in the food, medical and cosmetics industries, this review focuses on recent findings related to the nutrient components, health benefits, and safety of litchi.     

Chemical profiling of Punica granatum peels from Jordan using LC–MS/MS and study on their biological activities

A paucity of local information concerning the chemical profiles and biological activities of extracts obtained from less-studied P. granatum peel of Jordanian origin was considered in this study for the first time. Fractionation of the crude ethanol extracts was performed because of their higher phenolic and flavonoid contents compared to the water and acetone extracts. The chemical compositions of the respective samples, that is, extracts/fractions were identified by LC–MS/MS, and the elemental content of the raw materials was also analysed using atomic absorption spectrometry. Antioxidant activities of extracts and fractions were evaluated against DPPH and ABTS radical scavenging assays, and the antibacterial activities were investigated by disc diffusion method and MIC (Minimum Inhibitory Concentration). The LC–MS/MS results correlated strongly with the total phenolic and flavonoid contents, where ethanol displayed higher efficacy for extracting bioactive ingredients. Overall, a total of 19 phenolics were detected in the ethanolic peel extract of P. granatum. All of the analysed extracts showed strong antioxidant activities. Fractionation of ethanolic extracts resulted in fractions with almost similar chemical LC–MS/MS profiles, but the relative proportion of constituents was different. All fractions showed lower intensities of antioxidant capacities than crude extracts, highlighting the superiority of some components, either individually or combined, as well as their relative proportion on the biological activity of each fraction. The results of the present study emphasise the need to further explore the effect of putative interactions among plant bioactive ingredients and focus on possible interactions with drugs along with foods.     

甜橙皮渣中柠檬苦素类似物提取工艺研究

以硫酸调节的酸性水为提取剂,采用单因素实验和正交实验探讨了料液比、提取温度、时间和提取剂pH对甜橙皮渣中柠檬苦素类似物提取的影响,并确定了最佳的工艺参数为温度65℃、时间1.5h、提取剂pH为4、料液比1∶12,在该工艺路线下提取柠檬苦素类似物的得率为1.19mg/g(鲜重)。     

柠檬皮中柠檬苦素对根霉的抑菌活性和机理

通过测定柠檬皮中柠檬苦素对根霉的最小抑菌浓度(MIC)、最小杀菌浓度(MBC)、孢子萌发抑制率、菌丝萌发抑制率确定其抑菌活性,根据测定各因素对抑菌活性的影响确定抑菌活性的稳定性;并通过扫描电镜观察和测定根霉细胞外碱性磷酸酶(AKP)含量和蛋白质含量,菌丝体的总糖含量,分析柠檬皮中柠檬苦素对根霉的抑菌机理。结果表明:柠檬皮中柠檬苦素对根霉的最低抑菌浓度(MIC)和最小杀菌浓度(MBC)分别为1250、5000 μg/mL;对根霉孢子萌发的抑制效果更强,对孢子萌发和菌丝生长抑制的EC₅₀值分别为918.34和1707.31 μg/mL。柠檬苦素对根霉的抑菌活性不受温度和明胶的影响;pH为4时,抑菌活性最强;Fe³⁺、Fe²⁺均能显著(p<0.05)提高柠檬苦素的抑菌活性。柠檬苦素能使根霉的糖、蛋白质、AKP等胞内物质渗出;扫描电镜观察也发现经柠檬苦素处理的根霉孢子凹陷和皱缩严重,且溶出物明显;菌丝出现断裂扭曲、变形、变细。因此,柠檬苦素能破坏根霉的细胞壁和细胞膜的完整性,使胞内物质渗出,菌丝体和孢子变形,从而使根霉生长代谢受到影响。     

柑橘中类柠檬苦素的提取、分离纯化及检测技术研究进展

柑橘是世界第一大类水果，每年有大量的柑橘加工副产品产生，这些副产品中含有丰富的类柠檬苦素化合物，具有抗肿瘤、抗炎、抗病毒等多种生理作用，已被应用于食品、医药和农业等领域。开发高效的类柠檬苦素提取、分离纯化技术，研发快速的类柠檬苦素分析检测方法，有着重要的理论和实践价值。本文介绍了柑橘中类柠檬苦素结构特征及含量，重点综述了类柠檬苦素的提取、分离纯化及检测技术。总结发现新兴技术如超声辅助、超临界流体提取类柠檬苦素的提取效率较好，联合应用大孔树脂吸附、高速逆流色谱、制备型高效液相色谱法分离效果好。在检测技术方面，液相色谱是柑橘中类柠檬苦素使用最广泛的分析方法，可以准确检测出柑橘中所含类柠檬苦素的种类和含量，但高效、绿色、快速的前处理技术和便捷、高通量的检测技术还有待开发。本文为柑橘中类柠檬苦素的深入研究和综合开发利用提供参考,为促进柑橘副产物资源的利用提供依据。     

Application and bioactive properties of proteins and peptides derived from hen eggs: opportunities and challenges

Several proteins and peptides that are released in vitro and/or in vivo from hen eggs are biologically active and have a variety of functional properties in humans beyond normal nutrition, for which extensive studies have been performed. This review focuses on their biological activities, including antihypertensive, antioxidant, antimicrobial, antiadhesive, immunomodulatory and antithrombotic activities and enhancement of mineral absorption. These proteins and peptides have been shown to regulate the nervous system, cardiovascular system, immune system and gastrointestinal system. The potential application and future directions of research on these bioactive peptides and proteins in the food industry are also addressed. © 2014 Society of Chemical Industry     

陈皮表面微生物及其转化黄酮类物质的研究进展

陈皮是传统中药材,药食两用,具有“理气健脾,燥湿化痰”等功效,富含黄酮类、挥发油类、生物碱类、柠檬苦素类、微量元素等。其活性成分以黄酮类化合物为主,具有多种药理活性,包括抗炎、抗氧化、抗血栓、抗菌、抗病毒、降血糖、降血脂等,被广泛应用到食品和保健品等诸多领域。但是由于黄酮类化合物溶解性差、生物利用率低,限制其应用,随着生物技术的不断发展,微生物转化黄酮以及其他活性物质已成为国内外研究热点。已有报道对陈皮的活性成分的结构特征、生物活性,以及陈皮中微生物及其转化黄酮类化合物进行了深入系统的研究。该研究综述了陈皮表面微生物及其转化黄酮类物质的研究进展,为微生物转化陈皮活性黄酮的开发及应用提供参考。     

Arbutus species (Ericaceae) as source of valuable bioactive products

Abstract

In addition to nutrients, plant foods contain compounds that may provide additional health benefits improving the quality of life. Species from Arbutus genus (Ericaceae) represent a promising source of healthy phytochemicals. Bioactive compounds including such as anthocyanins, iridoids, phenols, triterpenes, sterols, and fatty acids are reported from Arbutus species. Some Arbutus species revealed promising biological activities including antioxidant, anti-inflammatory, anti-proliferative, anti-diabetic, and antimicrobial activities, and deserve for that reason further consideration for new drug discovery. However, only few species are investigated scientifically for their chemical profile and biological activities. The aim of this article is to summarize the current knowledge of the components and biological properties of Arbutus species common in Mediterranean area, as well as the future prospects on their applications as potentially valuable products.     

Phenol‐Based Antioxidants and the In Vitro Methods Used for Their Assessment

Abstract: In recent years, much interest has been observed in the field of phenol‐based antioxidants. As a result of this, many analytical methods have been developed for the purpose of the quantification of phenolic and polyphenolic antioxidant capacities in biological materials. Many of these methods have been altered for application toward the in vitro assessment of antioxidant activities in animal and human model systems as well as in vivo. Due to the varied applicability and usage, methods for the assessment of phenol antioxidant capacities have become so widespread that they are often misused. It is the intent of this work to review the chemistry behind the antioxidant activity of phenolics as well as summarize the many methods applicable for the measurement of in vitro phenolic antioxidant capacity.     

Sulfated modification of polysaccharides: Synthesis,characterization and bioactivities

BackgroundPolysaccharides are a kind of biological macromolecular substance with multiple biological effects. Natural polysaccharides derived from plants and fungi are known as ideal raw food supplements for health food and pharmaceuticals due to their few side effects. Sulfated modification could significantly improve structure characteristics, promote bioactivities, and even add new bioactivities to polysaccharides. Thus, sulfated polysaccharides are increasingly causing more attention, as they have been proved to possess a variety of biological activities, including antioxidant, anticancer, and immunoregulatory, and anticoagulant activities. Furthermore, recent advances in synthesis, characterization and bioactivities of sulfated polysaccharides can promote its application in the food industry or pharmaceutics.Scope and approachThis paper reviewed the main methods of sulfated modification, structural changes and the bioactivities of sulfated polysaccharide derivatives. We have comprehensively discussed biological activities of sulfated polysaccharides, emphatically the effects of sulfated group, composition, functional groups, as well as their replaced position on the bioactivities of sulfated polysaccharides, in order to reveal the potential mechanism of sulfation on bioactivities of polysaccharides.Key findings and conclusionsThis paper reviewed the recent research in the sulfated modification of polysaccharides and provided future directions for research in this area. There are many methods for sulfated modification, such as chlorosulfonic acid-pyridine method, concentrated sulfuric acid method, and sulfur trioxide-pyridine method, which could improve anti-coagulant, anti-oxidative, immunoregulation, anti-tumor, and anti-virus activities of polysaccharides. Sulfated modification could change bioactivities of polysaccharides due to their effects on structure characteristics. DS, monosaccharide compositions, replaced position of sulfated groups were considered to contribute to their bioactivities promotion. Further studies are required to explore the application of sulfated polysaccharides in pharmaceutical and food industries.     

Health benefits of anthocyanins and molecular mechanisms: Update from recent decade

Anthocyanins are one of the most widespread families of natural pigments in the plant kingdom. Their health beneficial effects have been documented in many in vivo and in vitro studies. This review summarizes the most recent literature regarding the health benefits of anthocyanins and their molecular mechanisms. It appears that several signaling pathways, including mitogen-activated protein kinase, nuclear factor κB, AMP-activated protein kinase, and Wnt/β-catenin, as well as some crucial cellular processes, such as cell cycle, apoptosis, autophagy, and biochemical metabolism, are involved in these beneficial effects and may provide potential therapeutic targets and strategies for the improvement of a wide range of diseases in future. In addition, specific anthocyanin metabolites contributing to the observed in vivo biological activities, structure–activity relationships as well as additive and synergistic efficacy of anthocyanins are also discussed.     

Designing novel industrial and functional foods using the bioactive compounds from Nigella sativa L. (black cumin): Biochemical and biological prospects toward health implications

Nigella sativa is one of the nutraceuticals that has gained popularity and studied extensively in recent decades as it is considered a safe medicinal plant for use as a dietary supplement. N. sativa contains a wide variety of bioactive substances, which include polyphenols, volatile oils (thymoquinone and p-cymene), proteins, and peptides. The biological attributes of N. sativa include antioxidant, antimicrobial, antifungal, anti-inflammatory, anticancer, antidiabetic, antihypertensive, hypolipidemic, and antioxidant activities, which have potential applications for the prevention of a variety of chronic diseases. In the food industry, N. sativa improves the sensory qualities, shelf life, strength, and freshness of foods, such as bread, pizza, biscuits, cookies, and cakes. This review discusses the industrial use of N. sativa, which includes processing technologies to enhance its health-promoting properties as well as the isolation of nutraceutical components.