桉属间苯三酚-萜烯类化合物及其抗肿瘤作用机制研究进展

间苯三酚-萜烯为桉属Eucalyptus L.Herit植物中天然存在的主要活性成分,具有独特的聚酮-二萜骨架,抗癌活性显著,是抗癌先导化合物的潜在来源。综述桉属植物抗癌活性天然间苯三酚-萜烯类化合物的结构、作用机制,为间苯三酚-萜烯类抗癌新药的研发提供参考。     

金莲花属植物研究概况

我国金莲花属(Trollius)药用植物有16种,7个变种,具有清热、解毒、消肿等功效,用于治疗急慢性扁桃体炎、急性中耳炎、慢性支气管炎和尿路感染等疾病。通过查阅中国知网、万方数据库、百度学术和Pub Med等多个数据库中关于金莲花属植物从1972年到2019年的文献资料,整理归纳了我国金莲花属药用植物的栽培种植、质量控制方法、提取纯化工艺、化学成分、药理作用、药动和代谢等方面的内容。栽培种植研究,主要集中在种子处理和组织培养体系的建立;质量控制方面,主要以荭草苷和总黄酮为指标;提取纯化工艺研究,主要为总黄酮类成分的提取纯化;化学成分方面,目前从该属植物中分离得到的主要化合物有100多个,包括黄酮类、有机酸类、生物碱类、香豆素类和苯乙素类等,其中黄酮类单体80个,有机酸类单体12个,生物碱类单体3个,香豆素类单体4个,苯乙素类单体14个;药理作用方面,主要为药材粗提物的体外实验;药动和代谢方面的资料主要集中在黄酮单体成分的研究。     

Some South African Rubiaceae Tree Leaf Extracts Have Antimycobacterial Activity Against Pathogenic and Non‐pathogenic Mycobacterium Species

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Many plant species contain antimycobacterial compounds, which may serve as template molecules for new anti‐TB drugs. The Rubiaceae family is the largest family of trees in southern Africa, and preliminary evidence revealed antimycobacterial activity in several species of the genus, motivating further studies. Leaf extracts of 15 tree species from the Rubiaceae family were screened for antimycobacterial activity against pathogenic M. tuberculosis and non‐pathogenic Mycobacterium smegmatis, Mycobacterium aurum and Mycobacterium bovis BCG (Bacillus Calmette‐Guérin) using a twofold serial microdilution assay. Cytotoxicity was determined using a tetrazolium‐based colorimetric assay against C3A liver cells and Vero kidney cells. Minimum inhibitory concentration values as low as 0.04 mg/mL against M. smegmatis and M. tuberculosis were recorded. Activity against M. aurum was the best predictor of activity against pathogenic M. tuberculosis (correlation coefficient = 0.9). Bioautography indicated at least 40 different antimycobacterial compounds in the extracts. Cytotoxicity of the extracts varied, and Oxyanthus speciosus had the most promising selectivity index values. Copyright © 2015 John Wiley & Sons, Ltd.     

Xanthine Oxidase Inhibitory Activity of Hungarian Wild‐Growing Mushrooms

Mushrooms represent a remarkable and yet largely unexplored source of new, biologically active natural products. In this work, we report on the xanthine oxidase (XO) inhibitory activity of 47 wild‐growing mushrooms native to Hungary. Aqueous and organic (n‐hexane, chloroform, and 50% methanol) extracts of selected mushrooms from different families were screened for their XO inhibitory activities. Among the 188 extracts investigated, the chloroform and 50% methanol fractions proved to be the most effective. Some species exhibited high inhibitory activity, e.g., Hypholoma fasciculare (IC₅₀ = 67.76 ± 11.05 µg/mL), Suillus grevillei (IC₅₀ = 13.28 ± 1.58 µg/mL), and Tricholoma populinum (IC₅₀ = 85.08 ± 15.02 µg/mL); others demonstrated moderate or weak activity. Additional studies are warranted to characterize the compounds responsible for the XO inhibitory activity of mushroom extracts. Copyright © 2014 John Wiley & Sons, Ltd.     

Chemical Composition and Antioxidant,Antinociceptive, and Anti‐inflammatory Activities of Four Amazonian Byrsonima Species

Species of the Byrsonima genus are widely used in Brazil, especially for the treatment of gastrointestinal disorders. However, species from the Amazonian region are still poorly studied. Thus, we studied the antioxidant, antinociceptive, and anti‐inflammatory activities of for Amazonian species, Byrsonima crispa , Byrsonima duckeana , Byrsonima garcibarrigae , and Byrsonima incarnata . Phenolic composition was determined by chemical and chromatographic methods. The aqueous extracts were evaluated in DPPH^?, ABTS^+?, and superoxide (O₂^??) tests, LPS‐activated macrophage assay, and formalin test. All species contained a high phenolic and flavonoid content. We identified 15 phenolic compounds, including phenolic acids, hydroxycinnamic acids, flavonoids, and catechins. The extracts showed high antioxidant activity and were more active than quercetin at inhibiting nitric oxide release in the LPS‐activated macrophage assay. B. duckeana and B. garcibarrigae showed higher in vivo antinociceptive and anti‐inflammatory activities. B. garcibarrigae presented significant effect on the early phase of the formalin test, pointing to an antinociceptive mechanism distinct from traditional anti‐inflammatory medicines. In conclusion, the pharmacological potential of these species is closely related to their flavonoid‐rich chemical composition, which seems to act through antioxidant mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.     

Antimycobacterial Activity and Low Cytotoxicity of Leaf Extracts of Some African Anacardiaceae Tree Species

Treatment of tuberculosis (TB) is a challenge because of multidrug‐resistant and extremely drug‐resistant strains of Mycobacterium tuberculosis. Plant species contain antimicrobial compounds that may lead to new anti‐TB drugs. Previous screening of some tree species from the Anacardiaceae family revealed the presence of antimicrobial activity, justifying further investigations. Leaf extracts of 15 Anacardiaceae tree species were screened for antimycobacterial activity using a twofold serial microdilution assay against the pathogenic Mycobacterium bovis and multidrug resistant M. tuberculosis and rapidly growing mycobacteria, Mycobacterium smegmatis, Mycobacterium fortuitum and Mycobacterium aurum. The vaccine strain, M. bovis and an avirulent strain, H37Ra M. tuberculosis, were also used. Cytotoxicity was assessed using a colorimetric assay against Vero kidney, human hepatoma and murine macrophage cells. Four out of 15 crude acetone extracts showed significant antimycobacterial activity with minimum inhibitory concentration varying from 50 to 100 µg/mL. Searsia undulata had the highest activity against most mycobacteria, followed by Protorhus longifolia. M. fortuitum was the strongest predictor of activity against multidrug‐resistant TB (correlation coefficient = 0.65). Bioautography against M. aurum and M. fortuitum worked well as indicators of the Rf values of active compounds yielding strong zones of inhibition. The leaf extracts of S. undulata and P. longifolia had more than ten different antimycobacterial compounds and had low cytotoxicity with LC₅₀ values above 100 µg/mL. Copyright © 2016 John Wiley & Sons, Ltd.     

Antiulcerogenic Activities of the Extracts and Isolated Flavonoids of Euphorbia cuneata Vahl

The total alcohol extracts of Euphorbia cuneata Vahl.(Euphorbiaceae) were screened for antiulcerogenic activity using an ethanol‐induced ulcer model at doses of 125, 250 and 500 mg/kg. The extracts possessed antiulcerogenic activity in a dose‐dependent manner. Four flavonoidal compounds were isolated and identified as naringenin, aromadendrin, apigenin and 4'‐O‐methoxy‐luteolin‐7‐O‐rhamnoglucoside, each demonstrating antiulcerogenic activity with curative ratios ranging from 75.78% to 88.23%. In addition, the alcohol extracts and isolated compounds were shown to scavenge the 1,1‐diphenyl,2‐picrylhydrazyl radical by different ratio, with the most effective being 4'‐O‐methoxy‐luteolin‐7‐O‐rhamnoglucoside (91.14%). The antioxidant activity of the alcohol extracts and the isolated compounds may explain the antiulcerogenic properties. No side effects were observed on either liver or kidney functions. Copyright © 2012 John Wiley & Sons, Ltd.     

Phenolic‐Linked Biochemical Rationale for the Anti‐Diabetic Properties of Swertia chirayita (Roxb. ex Flem.) Karst.

The crude extract of Swertia chirayita, an important medicinal plant of Nepal, is locally used for many diseases including type 2 diabetes. In this study, crude aqueous and 12% ethanol solution extracts of S. chirayita collected from nine districts of Nepal were analyzed for anti‐diabetic‐linked anti‐hyperglycemia potential using in vitro biochemical assays. There was moderate‐to‐high positive correlation between antioxidant activity and total phenolic content of both extracts and moderate‐to‐high α‐glucosidase inhibitory activity. Although the anti‐diabetic property of S. chirayita is mainly attributed to the phytochemical swerchirin present in its hexane fraction, we propose that the crude extract of this plant used in local healing also has anti‐hyperglycemia potential. The crude extracts indicated the presence of three main phytochemicals mainly mangiferin, swertiamarin, and amarogentin and their derivatives. Among the standard compounds (mangiferin, swertiamarin, and amarogentin), mangiferin showed α‐glucosidase and 2,2‐diphenyl‐1‐picrylhydrazyl radical inhibitory activity indicating anti‐hyperglycemia potential. Copyright © 2012 John Wiley & Sons, Ltd.     

Screening of medicinal plants from Iranian traditional medicine for acetylcholinesterase inhibition

To find new herbal compounds with an acetylcholinesterase (AChE) inhibitory effect, this study focused on herbal drugs and resins which have been used in Iranian traditional medicine for the treatment of cognitive disorders. Forty drugs were selected from authoritative written documents of Iranian traditional medicine. Each drug was extracted by accelerated solvent extraction using dichloromethane followed by methanol. The 80 extracts were screened for AChE inhibitory activity by a TLC bioautography method. The inhibiting effect of the 32 most active extracts was measured by a microplate colorimetric assay. Due to the best activity, the seeds of Peganum harmala L. were investigated in detail. From the TLC bioautography assay the alkaloids harmaline and harmine were identified as active compounds. This result was confirmed by means of HPLC‐DAD. The IC₅₀ values were 41.2 μg/mL for the methanol extract, 95.5 μg/mL for the dichloromethane extract, 8.4 μg/mL for harmaline and 10.9 μg/mL for harmine. The concentrations of active compounds in the extracts were determined by a fast and precise HPLC method. As the amounts of harmaline and harmine in the extracts were correlated with the IC₅₀ values of the extracts, it can be concluded that these two alkaloids are responsible for the AChE inhibitory activity of P. harmala. Copyright © 2011 John Wiley & Sons, Ltd.     

In Vitro Inhibition of the Transcription Factor NF‐κB and Cyclooxygenase by Bamboo Extracts

Several bamboo species have been used in traditional medicine for the treatment of inflammatory conditions. The present study evaluates the in vitro anti‐inflammatory properties of the traditionally used bamboo species Phyllostachys nigra (Lodd.) Munro and Sasa veitchii (Carr.) Rehder to explore their future research opportunities and therapeutic potential as anti‐inflammatory agents. The extracts were evaluated for their potential inhibitory activity at the level of NF‐κB‐induced gene expression and suppression of cyclooxygenase (COX)‐1 and COX‐2 enzyme activities, representative pharmacological targets for the anti‐inflammatory action of glucocorticoids and non‐steroidal anti‐inflammatory drugs, respectively. The activity of P. nigra (Lodd.) Munro and S. veitchii (Carr.) Rehder was compared with bamboo species without traditional anti‐inflammatory indications. High‐performance liquid chromatography with diode‐array detection and liquid chromatography–tandem mass spectrometry analyses were performed to phytochemically characterize the extracts. P. nigra (Lodd.) Munro leaf extract potently inhibited NF‐κB‐induced gene expression, while S. veitchii (Carr.) Rehder leaf extract exerted a selective COX‐2 inhibition. The crude extracts consistently showed a more potent bioactivity than the solid phase extraction fractions. P. nigra (Lodd.) Munro and S. veitchii (Carr.) Rehder both exert anti‐inflammatory properties, but act via a different molecular mechanism. Copyright © 2013 John Wiley & Sons, Ltd.     

The Hypoglycemic and Synergistic Effect of Loganin,Morroniside, and Ursolic Acid Isolated from the Fruits of Cornus officinalis

Hypoglycemic activity‐guided separation of ethanol extracts from the fruits of Cornus officinalis Sieb. et Zucc (CO) led to the isolation of loganin, morroniside, and ursolic acid. The antidiabetic capacity of CO extracts and related compounds was further investigated in diabetes mellitus mice. The results suggested that both CO extracts and pure compounds could ameliorate diabetes‐associated damages and complications. Oral administration of loganin and morroniside decreased fasting blood glucose levels in diabetes mellitus mice. Ursolic acid exhibited the highest reactive oxygen species scavenging activity and α‐glucosidase inhibitory activity. Notably, we noticed an interesting synergistic effect between loganin and ursolic acid. Given these favorable hypoglycemic properties, C. officinalis, a food and medicinal plant in China, may be used as a valuable food supplement for the treatment of diabetes mellitus. Copyright © 2015 John Wiley & Sons, Ltd.     

Therapeutic Potential of Polyphenols from Epilobium Angustifolium (Fireweed)

Epilobium angustifolium is a medicinal plant used around the world in traditional medicine for the treatment of many disorders and ailments. Experimental studies have demonstrated that Epilobium extracts possess a broad range of pharmacological and therapeutic effects, including antioxidant, anti‐proliferative, anti‐inflammatory, antibacterial, and anti‐aging properties. Flavonoids and ellagitannins, such as oenothein B, are among the compounds considered to be the primary biologically active components in Epilobium extracts. In this review, we focus on the biological properties and the potential clinical usefulness of oenothein B, flavonoids, and other polyphenols derived from E. angustifolium. Understanding the biochemical properties and therapeutic effects of polyphenols present in E. angustifolium extracts will benefit further development of therapeutic treatments from this plant. Copyright © 2016 John Wiley & Sons, Ltd.     

Toxicity of Anthraquinones: Differential Effects of Rumex Seed Extracts on Rat Organ Weights and Biochemical and Haematological Parameters

The genus Rumex and related species such as Rheum and Polygonum are widely used as medicinal herbs and foods. They contain anthraquinones (AQ) such as emodin and chrysophanol as active ingredients, and there is concern about the toxicity of these compounds. This study evaluated the chronic effects of Rumex patientia seed aqueous and ethanolic extracts, in male and female rats separately, on organ weights and over 30 haematological, biochemical and histological parameters, immediately after 14‐week administration and after a further period of 15 days without drug treatment. Adverse changes were associated with long‐term AQ administration, and these focussed on the liver, lung and kidney, but after 15‐day convalescence, most had reverted to normal. In general, male rats appeared to be more susceptible than female rats at similar doses. The water extract produced no irreversible changes, which may reflect the lower dose of the AQ constituents or the presence of different ancillary compounds, and supports the traditional method of extracting Rumex seeds with water. In conclusion, ethanolic extracts of R. patientia caused irreversible pathological changes at very high doses (4000mg/kg), but lower doses and aqueous extracts produced either non‐significant or reversible changes. Long‐term administration of high doses of AQ extracts over a long period of time should be avoided until further assurances can be given, and given other existing reports of reproductive toxicity, should be avoided altogether during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.     

Mutagenic and antimutagenic effects of hexane extract of some Astragalus species grown in the eastern Anatolia region of Turkey

Medical plants and their various extracts have been occasionally used in the treatment of many diseases. Astragalus is one of those medical plants and it has several biological activities. In the present study, the hexane extracts of six Astragalus species, which are grown in the eastern Anatolia region of Turkey, were isolated, and their mutagenic and antimutagenic properties were investigated by using Salmonella typhimurium TA1535, TA1537 and Escherichia coli WP2uvrA tester strains at 0.05, 0.5 and 5 μg/plate concentrations. Known mutagens sodium azide (NaN₃), 9‐Aminoacridine (9‐AA) and N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) were used to determine antimutagenic properties of hexane extracts. The results showed that all hexane extracts, investigated in the present study, can be considered genotoxically safe because they do not have mutagenic activity at the tested concentrations. But, a great many of them have antimutagenic activity against 9‐Aminoacridine known as a model intercalator agent. The inhibition rates obtained from the antimutagenicity assays ranged from 27.51% (A. macrocephalus – 0.05 μg/plate) to 54.39% (A. galegiformis – 5 μg/plate). These activities are valuable toward an extension of the employ of these drugs as new phytotherapeutic or preservative ingredients. Copyright © 2009 John Wiley & Sons, Ltd.     

Promising in vitro antioxidant,anti‐acetylcholinesterase and neuroactive effects of essential oil from two non‐psychotropic Cannabis sativa L. biotypes

The aim of this study was to compare the micro‐morphological features of two different non‐drug Cannabis sativa L. biotypes (Chinese accession G‐309 and one fibrante variety) and to evaluate the phytochemical profile as well as some biological properties of the essential oils (EOs) obtained by hydrodistillation of dried flowering tops. After a micro‐morphological evaluation by scanning electron microscopy, the phytochemical composition was analysed by GC–FID and GC–MS analyses. Antioxidant and anti‐acetylcholinesterase properties were investigated by several in vitro cell‐free assays, while neuroactive effects were evaluated on mouse cortical neuronal as well as human iPS cell‐derived central nervous system cells grown on MEA chips. Both EOs showed strong antioxidant properties mainly attributable to the high content of hydroxylated compounds as well as significant anti‐acetylcholinesterase activities (IC₅₀ 74.64 and 57.31 μg/ml for Chinese accession and fibrante variety, respectively). Furthermore, they showed a concentration‐dependent inhibition of spontaneous electrical activity of human and mouse neuronal networks, with the fibrante variety, which showed the best activity (MFR, IC₅₀ 0.71 and 10.60 μg/ml, respectively). The observed biological activities could be due to a synergic effect between terpenes and phytocannabinoids, although in vivo studies, which clarify the molecular mechanism, are still lacking.     

Screening of selected food and medicinal plant extracts for pancreatic lipase inhibition

Lipids are important components in human nutrition; however, their increased intake contributes to the development of obesity and can lead to multiple long‐term complications. Pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) is a key enzyme for the absorption of dietary triglycerides. Interference with fat hydrolysis results in the reduced utilization of ingested lipids, therefore inhibition of lipases decreases fat absorption. Extracts from 106 species of medicinal plants, vegetables and fruits were screened for potential lipase inhibitory activity. p‐Nitrophenylpalmitate and 5‐bromo‐4‐chloro‐3‐indoxylpalmitate were used as substrates in an in vitro test with crude porcine pancreatic lipase. Bearberry (Arctostaphylos uva‐ursi), garden pea (Pisum sativum), Norway spruce (Picea abies) and large‐leaved lime (Tilia platyphyllos) extracts were the most active. Additionally, the activity of selected extracts with removed polyphenols was measured. Extracts of bearberry, garden pea and large‐leaved lime are a promising source for developing functional foods or isolating active compounds. Copyright © 2008 John Wiley & Sons, Ltd.     

Phytochemical Characterization,Antibacterial, Acetylcholinesterase Inhibitory and Cytotoxic Properties of Cryptostephanus vansonii,an Endemic Amaryllid

Cryptostephanus vansonii I. Verd., an endemic Amaryllidaceae species from Zimbabwe, was evaluated for its acetylcholinesterase (AChE) inhibitory and cytotoxicity properties using Ellman's colorimetric method and the tetrazolium‐based colorimetric assay against Vero monkey kidney cells, respectively. The plant extracts were also evaluated for their antibacterial activity against five bacteria. Furthermore, phytochemical profiles of the extracts were determined using ultra‐high performance liquid chromatography coupled with tandem mass spectrometry analysis. A plant part‐dependent AChE inhibitory activity was observed, in the order, root > rhizome > basal leaf > leaf. Overall, C. vansonii extracts exhibited better antibacterial activity against Gram‐negative compared with Gram‐positive bacteria. Cytotoxic effects were not detected in Vero monkey kidney cell lines suggesting the possible absence of toxophores in C. vansonii extracts. Similar to the trend in biological activity, a distinct plant part‐dependent variation in hydroxybenzoates, hydroxycinnamates and flavonoids was observed in the plant extracts. In addition, 5‐hydroxymetylfurfural and eucomic acid were detected in the different plant parts of C. vansonii. The results of the present study provide valuable AChE inhibition activity, toxicological and phytochemical profiles of C. vansonii. Further studies on isolation of bioactive compounds and their subsequent evaluation in other pharmacological and toxicological model systems are required. Copyright © 2017 John Wiley & Sons, Ltd.     

Acetylcholinesterase Inhibition,Antioxidant, Antiinflammatory,Antimicrobial and Phytochemical Properties of Huernia hystrix

Huernia species are typical famine‐food plants consumed in southern Ethiopia. H. hystrix is a heavily exploited ethnomedicinal succulent plant traded in traditional medicine systems especially on South Africa's eastern seaboard. This study investigated the acetylcholinesterase (AChE) inhibition, antioxidant, antiinflammatory and antimicrobial properties of extracts obtained from the stems and roots of this plant. At the same concentration level (625.0, 312.5 or 156.3 µg/mL), the whole plant extract showed higher AChE inhibitory activity when compared with the stem and root extracts; a finding suggesting the presence of AChE inhibitors acting additively or synergistically in the whole plant extract. The roots showed strong antioxidant activity (in DPPH and β‐carotene assays) comparable to that of butylated hydroxytoluene (BHT), indicating the presence of potent antioxidant compound(s) that can be exploited as alternatives for use in the food and cosmetic industries and/or as nutraceuticals. All the petroleum ether (PE) (except root PE) and dichloromethane (DCM) extracts demonstrated good inhibitory activity (> 70%) in cyclooxygenase (COX‐1 and COX‐2) assays at a 0.25 µg/μL concentration. Most of the extracts showed broad‐spectrum inhibitory and lethal activities against the microorganisms used in this study. The observed biological activities might be due to the iridoid, phenolic and flavonoid contents of the plants. Copyright © 2011 John Wiley & Sons, Ltd.     

Cytotoxic activity of marine macro‐algae on Artemia salina (Brine shrimp)

A total of 22 ethanol extracts of seaweed species (13 brown, 6 green and 3 red) collected from the Karachi coast were investigated for brine shrimp cytotoxicity. Of all the species, only six namely Stoechospermum marginatum, Sargassum swartzii, S. binderi, Spatoglossum asperum, Stokeyia indica (brown) and Caulerpa racemosa (green) showed significant activity. n‐Hexane‐soluble fractions of the ethanol extract of S. marginatum and S. swartzii were found to be responsible for the activity, whereas the methanol‐soluble fractions of S. asperum and S. binderi were most active. The water extract of S. indica and C. racemosa exhibited the most prominent activity (LC₅₀ value below 70 µg/mL) when compared with the ethanol extracts and their fractions. Cytotoxic activity may be due to the compounds differing in polarity. Copyright© 1999 John Wiley & Sons, Ltd.     

Plants of the Melaleuca Genus as Antimicrobial Agents: From Farm to Pharmacy

Plants belonging to Melaleuca genus (Myrtaceae family) are native to Oceania, where they have been used for ages by Aborigine people in Australian traditional medicine, mainly because of their broad‐spectrum antimicrobial activity. Although, M. linariifolia, M. dissitiflora, and other species of Melaleuca can also be used, the tea tree oil, an essential oil obtained from M. alternifolia shows the longest history of medicinal uses. Tea tree oil contains for the 80–90% several monoterpenes (terpinen‐4‐ol, α‐terpinene, 1,8‐cineol, p‐cymene, α‐terpineol, α‐pinene, terpinolene, limonene, and sabinene). Sesquiterpenes and aromatic compounds further compose this oil. The essential oil of Melaleuca spp. has been reported to possess effective antibacterial and antifungal properties in vitro. In particular, data show that 1,8‐cineol, terpinen‐4‐ol and methyl eugenol play the key role in mediating this oil's antimicrobial activity. Copyright © 2017 John Wiley & Sons, Ltd.