Pharmacological mechanisms of black cohosh in Sprague-Dawley rats

Background

Studies indicate that extracts and purified components from black cohosh inhibit the growth of human breast cancer cells, but the molecular targets and signaling pathways have not yet been defined.

Purpose

This study examines the pharmacological mechanisms and toxicological effects in the short term of the herb black cohosh on female Sprague–Dawley rats.

Materials and methods

To assess effects on gene activity and lipid content, we treated female Sprague–Dawley rats with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 or 0 mg/kg. Four animals for each group were sacrificed at 1, 6 and 24 h after treatment; liver tissue and serum samples were obtained for gene expression and lipid analysis.

Results

Microarray analysis of rat liver tissue indicated that black cohosh markedly downregulated mitochondrial oxidative phosphorylation genes. Phospholipid biosynthesis and remodeling, PI3-Kinase and sphingosine signaling were upregulated, driven largely by an upregulation of several isoforms of phospholipase C. Hierarchical clustering indicated that black cohosh clustered with antiproliferative compounds, specifically tubulin binding vinca alkaloids and DNA alkylators. In support of this, black cohosh repressed the expression of cyclin D1 and ID3, and inhibited the proliferation of HepG2, p53 positive, liver cancer cells. Black cohosh reduced the level of free fatty acids at 6 and 24 h and triglycerides at 6 h in the serum, but increased the free fatty acid and triglyceride content of the treated livers at 24 h.

Conclusion

Our results suggest that black cohosh warrants further study for breast cancer prevention and therapy.     

交让木属植物中生物碱类化合物的研究进展

生物碱广泛存在于自然界,是科学家们研究最早的一类有生物活性的天然有机化合物.随着植化分离和结构鉴定手段的提高,越来越多的生物碱类化合物被从交让木属植物中分离鉴定出来,近年来已鉴定80余种化合物.为了更好地开发和利用本属植物,作者在查阅国内外文献的基础上就这一领域的研究进展进行了综述.     

Failure of black cohosh (Actaea racemosa L.) rhizome transplants: potential causes and forest farming implications

Black cohosh (Actaea racemosa L.) rhizomes are harvested extensively from eastern North American forests and sold worldwide for treatment of menopausal symptoms. While forest farming is encouraged to reduce wild-harvest impacts, little information is available to aid landowners in successfully cultivating black cohosh. This study examined survival and multi-year growth of 200 black cohosh rhizomes collected from an Appalachian deciduous forest and transplanted to a similar forest type. By the second year after transplant, fewer than 40 % of rhizomes produced above-ground growth and mean rhizome biomass declined by more than 50 %. Shoot biomass was the greatest predictor of below-ground biomass; however, leaf area provided a reasonable, non-destructive means of estimating this commercially-important biomass. Our results suggest that pre-transplant rhizome condition is particularly important to transplant success. Low biomass, lack of roots, and fungal infection all were associated with reduced plant survival. Based on this and associated studies, we recommend careful site selection for propagation, including circumneutral or lime-amended soils and light to moderate shading. Well-drained soil appears particularly important to discourage fungal infection. Understanding conditions for successful transplanting of black cohosh rhizomes can improve forest farming and contribute to sustainable management of this and other non-timber forest products.     

Unbiased evaluation of bioactive secondary metabolites in complex matrices

The majority of bioactive principles in a complex matrix such as natural products and botanical medicines are secondary rather than primary metabolites. In addition to being chemically diverse, the bioactivity of an ethnobotanical can comprise from one to several bioactive compounds, present in a complex mixture. Conventional discovery efforts utilize bioassay-guided fractionation (BGF) to isolate individual active compounds. When applied to complex natural products, BGF is often challenged by an apparent loss of activity during fractionation, resulting in weakly active isolated compounds. Metabolomic analysis can potentially complement existing the BGF paradigm by capturing the chemical complexity of the metabolites. The proposed biochemometric approach establishes a link between the chemistry of a secondary metabolome and a deserved health impact, using a high-throughput, high-resolution capable biological endpoint. The proof of principle is demonstrated for the anti-tuberculosis (TB) activity of the Alaskan ethnobotanical, Oplopanax horridus. Biochemometric analysis identified the 100 most active constituents from thousands of metabolites in the active extract by means of 2D orthogonal chromatography using countercurrent and GC-MS methods. Previously isolated O. horridus phytoconstituents were used as reference markers of known structure and bio (in)activity. Positive correlations allowed distinction of anti-TB actives from inactive compounds. A total of 29 bioactives from 3 main structural classes were assigned based on MS data. Biochemometric analysis is a new tool for the standardization of herbal medicines and ethnobotanicals, as well as for drug discovery from nature. The method can assign multiple active compounds in complex mixtures without their prior isolation or structure elucidation, while still providing an interface to structural information.     

植物多酚(英文)

从普遍存在的绿原酸到分子量在500—20000范围之间的多酚组分(即植物单宁)植物多酚的变化是很复杂的。从广义上讲,多酚主要可分为两类,即原花色素和以倍酸和(或)六羟基联苯甲酸和它们的衍生物为基础的聚酯化合物。如早期文献报道的,前者相当于凝缩类单宁,而后者则是水解单宁。作为植物的二次代谢物它们具有一些不同的分子特性。它们不仅具有多种多样酚基,而且还有一种和各种天然大分子即蛋白、多糖和核酸以及代谢物如生物碱结合成可逆复合物的倾向。根据这些性质,历史上按“伞”命名法称之为植物单宁。文中还讨论了植物多酚结构的变化因素,以及它们与其它物质的结合。     

OPLC and AMD, recent techniques of planar chromatography: their interest for separation and characterization of extractive and synthetic compounds

It is always important for the chemist to have good methods of separation, characterization and quantitative evaluation for one or several compounds resulting from a chemical reaction or an extraction procedure. In this domain the chromatographic techniques are choice methods, in particular Over Pressured Layer Chromatography (OPLC) and Automated Multiple Development (AMD). They are relatively recent methods whose use is unfortunately not yet generalized although they give very clean separation. In this paper we present numerous examples of the use of these two new types of planar chromatographies and especially the results we have obtained in the field of natural products on a wide variety of different structures: coumarins, flavonoids, anthocyanins, alkaloids and essential oils.     

红树属植物内生真菌多样性及其代谢产物研究进展

红树林是生长在热带和亚热带潮间带河口地带的耐盐植物群落,分布在南纬30°与北纬30°之间,具有盐胁迫、高矿物组成、强还原性、频繁的潮汐等特征,也使植物对营养、空间的竞争异常激烈,特殊生境使红树林植物内生真菌多样性丰富,必然会造成不同于其他生态系统的良好生物活性、独特化学结构的活性功能分子。红树属是红树林植物中分布较广泛的一个属,包括8个种,分别是红海榄、红树、红茄苳、美洲红树、Rhizophora harrisonii、R.racemosa、树冬红树和萨摩红树。迄今为止,从红树属分离出内生真菌类群已达23目41科64属,其中对拟盘多毛孢属、青霉属和毛霉属的内生真菌代谢产物研究的最为广泛;从红树属内生真菌中分离鉴定出195种天然产物,包括生物碱类、萜类化合物、香豆素类、色酮类化合物、醌类化合物、杂氧蒽醌类化合物、肽类、酚酸类化合物、内酯类等化合物,从红树属植物中发现许多结构新颖的次生代谢产物,从中国南海红树林红茄苳内生拟盘多毛孢真菌中发现一系列罕见的具有亲脂性取代基的新色酮类化合物pestalotiopsones A-F (107—112),从拟盘多毛孢属JCM2A4中发现2个具有柔性结构的补身烷型倍半萜-环青霉醛酸的新骨架化合物pestalotiopens A和B (83, 84)。此外,许多化合物显示出良好的抗肿瘤、抗菌和抗氧化等生物活性,如化合物pestalpolyol 1(119)具有很强的抑制作用,对小鼠淋巴瘤L5178Y细胞的半抑制浓度(half maximal inhibitory concentration,IC₅₀)值为4.10μmol·L^-1。从内生真菌毛霉QEN-189中分离到的吲哚生物碱rhizovarins A,B和F(46, 47, 50)对肺癌细胞A549抑制作用强,IC₅₀值分别为11.5、6.3和9.2μmol·L^-1,对白血病细胞HL-60有强抑制作用,IC₅₀值为9.6、5和7μmol·L^-1。     

Ageratum conyzoides L. (Asteraceae)

Ageratum conyzoides L., is an annual herb with a long history of traditional medicinal uses in many countries in the world, especially in the tropical and subtropical regions. A wide range of chemical compounds including alkaloids, flavonoids, chromenes, benzofurans and terpenoids have been isolated from this species. Extracts and metabolites from this plant have been found to possess pharmacological and insecticidal activities. The comprehensive account of the chemical constituents and the biological activities are presented in this review such that the potential use of this plant either in pharmaceutics or as an agricultural resource can be evaluated.     

Antifungal activity of the methanolic extract and alkaloids of Glaucium oxylobum

The methanolic extract and total alkaloids of the aerial parts of Glaucium oxylobum exhibited good activity against Microsporum gypseum, Microsporum canis, Trichophyton mentagrophytes and Epidermophyton floccosum. Four alkaloids, dicentrine, glaucine, protopine, and alpha-allocryptopine, were identified as the compounds responsible for the antifungal activity of this plant.     

Discussion of a well-designed clinical trial which did not demonstrate effectiveness: UIC center for botanical dietary supplements research study of black cohosh and red clover

The performance of a clinical trial for pharmaceutical agents is usually undertaken only after there is likely benefit demonstrated from the use of the putative agent. The consideration of botanical products as pharmaceutical agents must similarly go through a rigorous evaluation process. The present work reviews the recently published phase II study evaluating the effectiveness of black cohosh and red clover in a randomized trial with conjugated equine estradiol/medroxyprogesterone acetate and placebo for the treatment of menopausal symptoms. We analyze the possible reasons why this study failed to show benefit for either botanical product in reducing menopause-related vasomotor symptoms.     

Tongkat Ali (Eurycoma longifolia Jack): A review on its ethnobotany and pharmacological importance

Eurycoma longifolia Jack is an herbal medicinal plant of South-East Asian origin, popularly recognized as ‘Tongkat Ali.’ The plant parts have been traditionally used for its antimalarial, aphrodisiac, anti-diabetic, antimicrobial and anti-pyretic activities, which have also been proved scientifically. The plant parts are rich in various bioactive compounds (like eurycomaoside, eurycolactone, eurycomalactone, eurycomanone, and pasakbumin-B) among which the alkaloids and quassinoids form a major portion. Even though toxicity and safety evaluation studies have been pursued, still a major gap exists in providing scientific base for commercial utilization and clearance of the Tongkat Ali products with regard to consumer's safety. The present review aims at reviewing the research works undertaken till date, on this plant in order to provide sufficient baseline information for future works and for commercial exploitation.     

生物碱在植物保护管理中的应用

生物碱是一类重要植物次生代谢物,本文述及生物碱在植物保护管理中的应用,包括生物碱对有害昆虫、有害微生物、有害植物等有害生物管理上的研究进展。     

Phytochemical and antimicrobial characterization of Macleaya cordata herb

Macleaya cordata (plume poppy) is a source of bioactive compounds, mainly isoquinoline alkaloids which are used in phytopreparations with anti-inflammatory and antimicrobial activities. In this study, the alkaloids sanguinarine, chelerythrine, their dihydro derivatives, protopine and allocryptopine and phenolics, gallic, protocatechuic, p-hydroxybenzoic, m-hydroxybenzoic, gentisic, p-coumaric, caffeic, ferulic and sinapic acids were determined in extracts prepared from M. cordata aerial part, seeds, and seed capsules using HPLC with UV detection and/or LC/MS with electrospray ionization. The highest content of sanguinarine and chelerythrine was found in capsules. Protopine and allocryptopine were major alkaloids in leaves including footstalks. The seed oil contained dihydrosanguinarine, dihydrochelerythrine and twelve fatty acids of which linoleic, oleic, palmitic and stearic acids predominated. In addition, sanguinarine reductase, a key enzyme in sanguinarine/dihydrosanguinarine equilibrium in plants, was found for the first time, in the soluble proteins of leaves. Finally, extracts were tested for antimicrobial activity using the microdilution method on standard reference bacterial strains.     

植物次生代谢产物及影响其积累的因素研究综述

植物次生代谢产物在植物生命活动的许多方面均起着重要作用。其种类繁多,目前研究主要集中于萜类、酚类、含氮有机物以及炔类、有机酸等。次生代谢产物的合成和积累受遗传(基因)控制,受树龄、季节(生长发育阶段)的影响,不同种源的同一植物在相同的环境下生长也存在差异,光照强度、光质、温度、水分、养分等环境因子亦会对次生代谢产物的积累产生重要影响。研究这些因素对植物次生代谢产物积累的影响,对为提高其产量而进行的栽培措施具有指导意义,有助于缓解有限的次生代谢物产量与人类越来越大的需求之间的矛盾。     

松材线虫病感病松树中致萎毒性物质的研究

本研究用我国自然感染松材线虫病的15年生以上黑松和马尾松以及人工感染松材线虫病的3年生黑松的木质组织进行萃以和粗提纯，方法为高压蒸煮法和氯仿碱法。生物测定结果显示，有致萎活性的毒性物质仅存在于自然感病未死的黑松和马尾松以及人工感病未死的黑松木质组织中。自然感病死后1年的黑松和马尾松以及健康松树不中含有这些毒性物质。通过气相色谱－质谱联用仪（GC／MS System）对上述木质组织萃取物作定性分析发现，自然感病未死的黑松、马尾松和人工感病未死的黑松有致萎活性的萃取物中均含苯乙酸和2－甲氧基肉桂酸，自然感病死后1年的松树和健康松树中则无。而在健康松树和感病松树中都发现有苯甲醛存在。表明毒性物质与苯乙酸和2－甲氧基肉桂酸有关，苯甲醛则是松树正常的代谢产物。苯乙酸和2－甲氧基肉桂酸均为酚类化合物，是植物体内重要的次生物质。说明感病松树中的毒性物质是松树组织由于松材线虫侵染而产生的异常代谢产物，应称之为致萎毒性物质。     

植物生物碱的杀虫作用及应用

植物生物碱是植物在与昆虫协同进化过程中形成的一大类具有防御功能的次生代谢物质,在害虫综合治理中具有非常重要的作用。本文对植物生物碱的杀虫作用方式、作用机理和作为杀虫剂、昆虫拒食剂、驱避剂、产卵忌避剂的应用以及作为先导化合物在新农药创制中的作用做了综述,并对植物生物碱的研究前景进行了展望,提出了今后研究和开发应用中注意的问题。     

Urinary metabolites of isorhynchophylline in rats and their neuroprotective activities in the HT22 cell assay

Isorhynchophylline is one of the major alkaloids from the Uncaria hook possessing the effects of lowered blood pressure, vasodilatation and protection against ischemia-induced neuronal damage. However, the metabolic pathway of isorhynchophylline has not been fully reported yet. In this paper, the metabolism of isorhynchophylline was investigated in rats. Five metabolites were isolated by using solvent extraction and repeated chromatographic methods, and identified by spectroscopic methods including UV, MS, NMR and CD experiments. Three new compounds were identified as 5-oxoisorhynchophyllic acid-22-O-β-D-glucuronide (M1), 17-O-demethyl-16,17-dihydro isorhynchophylline (M2) and 5-oxoisorhynchophyllic acid (M4) together with two known compounds isorhynchophylline (M0) and rhynchophylline (M3). Possible metabolic pathways of isorhynchophylline are proposed. Furthermore, the activity assay for all the metabolites showed that isorhynchophylline (M0) exhibited potent neuroprotective effects against glutamate-induced HT22 cell death. However, little or weak neuroprotective activities were observed for M1–M4. Our present study is important to further understand its metabolic fate and disposition in humans.     

Identification of non-alkaloid acetylcholinesterase inhibitors from Ferulago campestris (Besser) Grecescu (Apiaceae)

Inhibition of Acetylcholinesterase (AChE) is still considered as a strategy for the treatment of neurological disorders such as Alzheimer's disease. Many plant derived alkaloids (such as galantamine and rivastigmine) are known for their AChE inhibitory activity. Recently, other classes of natural compounds such as terpenoids, sesquiterpene glycosides and coumarins have been studied as new AChE inhibitors, with the aim to discover less toxic compounds compared to alkaloidal ones. The Ferulago campestris roots dichloromethane extract was used for a bioassay-guided fractionation for the search of AChE inhibitors. Three coumarin derivatives (umbelliprenin 1, coladonin 2 and coladin 3), three daucane ester derivatives (siol anisate 4, ferutinin 5 and 1-acetyl-5-angeloyl lapiferol 6), two phenol derivatives (2-epilaserine 7 and epielmanticine 8) and one polyacetylene (9-epoxyfalcarindiol 9) were isolated by the bioassay-guided approach. Their structures were characterized on the basis of spectral methods (1D and 2D NMR, and MS spectroscopy). All the isolated compounds were able to inhibit the AChE (IC₅₀ 1.2–0.1 mM) although at higher doses if compared to galantamine (6.7 μM) measured in the same conditions. The most active compounds were the daucane derivative siol anisate 4 and the epielmanticine 8, with IC₅₀ of 0.172 and 0.175 mM respectively.     

Enzyme-assistant extraction (EAE) of bioactive components: a useful approach for recovery of industrially important metabolites from seaweeds: a review

Over the years, the biological activities of seaweeds could have gained a considerable research interest because of their specific functional compounds, which may not be available in land plants. Thus, efforts at discovery of novel metabolites from seaweeds over the past years have yielded a considerable amount of new active compounds. In addition, studies about the extraction of active compounds from natural products have attracted special attention in the last recent years. Potent biologically active compounds of seaweeds have been demonstrated to play a significant role in prevention of certain degenerative diseases such as cancer, inflammation, arthritis, diabetes and hypertension. Therefore, seaweed derived active components, whose immense biochemical diversity looks like to become a rich source of novel chemical entities for the use as functional ingredients in many industrial applications such as functional foods, pharmaceuticals and cosmeceuticals. Thus, the interest in the extraction of active compounds from seaweeds is obvious. However, the physical and chemical barriers of the plant material become the key drawbacks of such extraction process. Therefore, enhanced release and recovery of active compounds attached to the cells have been addressed. Taken together, the aim of this communication is to discuss the potential use of enzyme treatment as a tool to improve the extraction efficiency of bioactive compounds from seaweeds.     

Contrasting impact of whole-tree-harvesting on chemical quality of plant foliage in coastal versus inland forest

Whole-tree-harvesting (WTH) is gaining support as a means to obtain more bioenergy from forests. One aspect that is scarcely addressed is its impact on the chemical quality of post-harvest plant growth, which may initiate ecological cascade effects through, for example, altered patterns of herbivory and decomposition. We measured C:N ratios and phenolic compounds in foliage from birch Betula spp. that had grown naturally after WTH and conventional harvest (CH) on two boreal sites in inland and more coastal Norway, three or five years after harvest. We found that carbon concentrations were higher after WTH compared to CH on the near-coastal site in spring and summer, but not on the inland site. The only observed change in nitrogen concentration after WTH was that it was lower compared to CH on the near-coastal site in autumn. In line with these changes, the C:N ratio was higher with WTH throughout the season on the near-coastal site, ostensibly favouring production or accumulation of plant defence metabolites. Expectedly, we observed altered concentrations of several phenolic compounds with WTH, particularly at the near-coastal site. Further studies are needed to clarify patterns, but our data strongly suggest that sustainability assessments of WTH should not ignore impact on plant chemical quality, and its potential consequences for trophic interactions.