Seco-terpenoids and other constituents from Elateriospermum tapos

Two new taraxerane triterpenes, 2,3-seco-taraxer-14-ene-2,3,28-trioic acid 2,3-dimethyl ester ( 1) and 2,3-seco-taraxer-14-ene-2,3,28-trioic acid 3-methyl ester ( 2), along with two known triterpenes, hopenol B and aleuritolic acid, and five known flavonoids, putraflavone, kaempferol, sequoiaflavone, amentoflavone, and ginkgetin, were isolated from the leaves of Elateriospermum tapos. The stem extract yielded a new cleistanthane diterpene, 2,3-seco-sonderianol ( 3), three known triterpenes, lupeol, lupeol acetate, and 3-acetylaleuritolic acid, and three known diterpenes, yucalexin B-22, yucalexin P-15, and yucalexin P-17. The structures of these compounds were established on the basis of their spectroscopic data. Compound 1 was cytotoxic against NCI-H187 and BC cell lines and also showed in vitro antimycobacterial activity against Mycobacterium tuberculosis.     

Picea mariana polyphenolic extract inhibits phlogogenic mediators produced by TNF-α-activated psoriatic keratinocytes: Impact on NF-κB pathway

Ethnopharmacological relevance

Picea mariana ((Miller) Britton, Sterns, and Poggenburg; Pinaceae) bark has been traditionally used by North American natives for treating topical inflammations. It has been also suggested to improve various inflammatory skin disorders like Psoriasis vulgaris. Extracts from this bark storage protein contain polyphenolic compounds which have well-known antiinflammatory activities. Based on the capacity of polyphenolic compounds to modulate functions of normal human keratinocytes, this study was set up to decipher the mechanisms of action of a chemically characterized polyphenolic extract from Picea mariana bark (BS-EAc_f) on lesional keratinocytes of skin with psoriasis vulgaris, a disease driven by the immune system in which TNF-α plays a significant role.

Materials and methods

BS-EAc_f corresponds to the ethyl acetate soluble fraction from the hot water extract of Picea mariana bark. BS-EAc_f effects were evaluated in normal human (NHK) and psoriatic (PK) keratinocytes stimulated by TNF-α. Cell viability was assessed by lactate deshydrogenase release and propidium iodide (PI) staining. The mechanisms of action of BS-EAc_f in keratinocytes were investigated by flow cytometry, ELISAs, RT-PCR and western blot analyses.

Results

PK exhibited a higher response to TNF-α than NHK regarding the ICAM-1 expression and the production of NO, IL-6, IL-8, fractalkine and PGE₂, whereas BS-EAc_f significantly inhibited this TNF-α-induced increase at concentrations without causing keratinocyte toxicity. Additionally, this extract significantly inhibited the TNF-α-induced release of elafin and VEGF by PK and NHK. Since TNF-α activation of most of these factors is dependent on the NF-κB pathway, this latter was studied in TNF-α-activated PK. BS-EAc_f inhibited the TNF-α-induced phosphorylation and degradation of total IκBα as well as phosphorylation of NF-κB p65.

Conclusions

The ethyl acetate fraction from Picea mariana bark extract showed inhibitory effects of cytokines, chemokines, adhesion molecules, nitric oxide and prostaglandins produced by keratinocytes under TNF-α activation through down-regulating the NF-κB pathway. This study demontrated that this extract could be a potential antiinflammatory agent capable of improving psoriatic skin.     

Antiplasmodial triterpenes from twigs of Gardenia saxatilis

Ten triterpenes (1-10) were isolated and identified from the twigs of Gardenia saxatilis (Rubiaceae) and were subjected to antiplasmodial evaluation against the parasite Plasmodium falciparum. The first six compounds, lupenone (1), lupeol (2), betulinic acid (3), oleanolic acid (4), ursolic acid (5), and winchic acid (27-O-feruloyloxybetulinic acid) (6) were inactive in the assay. The other four compounds, messagenic acid A (7) and messagenic acid B (8), the 27-O-p-(Z)- and 27-O-p-(E)-coumarate esters of betulinic acid, and a mixture of uncarinic acid E (27-O-p-(E)-coumaroyloxyoleanolic acid) (9) and 27-O-p-(E)-coumaroyloxyursolic acid (10) exhibited antiplasmodial activity, with the IC50 values of 1.5, 3.8 and 2.9 microg/ml, respectively. The results indicated that the p-coumarate moieties at the 27-position, both the cis and trans isomers, contributed to antiplasmodial activity. Introduction of a methoxyl group to the 3-position of the p-coumarate moiety to give a ferulate moiety resulted in loss of activity.     

Investigation of Grewia bicolor Juss

Grewia bicolor is a small tree, parts of which are used in Sudanese traditional medicine for treating pustulent skin lesions, internally on indication of a delayed afterbirth and sometimes as a tranquilizer. A phytochemical investigation of Grewia bicolor gave the following results: the petroleum ether extract afforded beta-sitosterol and beta-sitosterol- and triterpene esters, and the triterpenes lupeol and betulin. The methanol extract afforded: beta-sitosterol-glucoside and three alkaloids, harman, 6-methoxyharman and 6-hydroxyharman. The latter is the main alkaloid. The methanol extract shows activity against gram-positive and gram-negative organisms and causes a strong contraction of the isolated rat uterus which can be blocked by methysergide.     

A glycosyl analogue of diacylglycerol and other antiinflammatory constituents from Inula viscosa

Some extracts from Inula viscosa were examined for acute antiinflammatory activity in vivo. Three flavonoids: rhamnocitrin (1), 7-O-methylaromadendrin (3), and 3-O-acetylpadmatin (4); a sesquiterpene lactone, inuviscolide (2); a sesquiterpene acid, ilicic acid (5); and a digalactosyl-diacylglycerol, inugalactolipid A (6), were isolated from the CH2Cl2 extract, identified by spectroscopic methods, and characterized as the topical antiinflammatory principles of this species. All these compounds proved to be effective against 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in mice, although lacking activity against arachidonic acid-induced edema. In addition, compounds 5 and, markedly, 6 showed notable effects on a multiple-dose murine chronic dermatitis model. This is the first attempt to establish a rationale concerning the documented use of the plant on various skin diseases.     

Antiinflammatory activity of coumarins from Ligusticum lucidum Mill. subsp. cuneifolium (Guss.) Tammaro (Apiaceae)

Four coumarin derivatives [selidinin 1, (+)-praeruptorin A 2, visnadin 3 and (R)-(+)-7-(2',3'-epoxy-3'-methylbutoxy)-coumarin 4] were isolated from the aerial parts of Ligusticum lucidum Mill. subsp. cuneifolium (Guss.) Tammaro (Apiaceae). This is the first report on the identification of these compounds in the Ligusticum genus. Their topical antiinflammatory activity was evaluated as the inhibition of croton oil-induced ear dermatitis in mice. Each compound (0.3 μmol/cm(2) ) induced a significant oedema reduction and compound 4 exerted an effect similar to that of the equimolar dose of the reference drug indomethacin.     

Antiinflammatory effects of a red orange extract in human keratinocytes treated with interferon‐gamma and histamine

Red oranges are an important component of the so‐called Mediterranean diet and they have been used by traditional medicine for their health protective properties, particularly to heal sore throat and cough, suggesting an interesting antiinflammatory activity. The purpose of this study was to evaluate the antiinflammatory activity of a red orange (Citrus sinensis varieties: Moro, Tarocco, Sanguinello) complex (ROC), characterized by high levels of anthocyanins, flavanones, hydroxycinnamic acids and ascorbic acid, on the human keratinocyte line NCTC 2544 exposed to interferon‐gamma (IFN‐γ) and histamine. The expression of immunomodulatory membrane molecules such as inter‐cellular adhesion molecule‐1 (ICAM‐1) by Western blot analysis, and the release of chemokines such as monocyte chemoattractant protein‐1 (MCP‐1) and interleukin‐8 (IL‐8) through ELISA kits, were determined. ICAM‐1 modulates the permanence and activation of T lymphocytes in the epidermis. MCP‐1 is a specific chemoattractant for monocytes and dendritic cells. IL‐8 is important for the recruitment of both neutrophils and T lymphocytes. Addition of ROC at different concentrations together with IFN‐γ and histamine induced a dose‐dependent inhibition of ICAM‐1 expression and MCP‐1 and IL‐8 release. ROC shows interesting antiinflammatory properties in human keratinocyte cells NCTC 2544. This natural complex could have a topical employment and mitigate the consequences of some skin pathologies. Copyright © 2009 John Wiley & Sons, Ltd.     

Differentiation- and apoptosis-inducing activities by pentacyclic triterpenes on a mouse melanoma cell line

In a study to investigate the relationship between the chemical structure and the differentiation-inducing activity of pentacyclic triterpenes, several lupane, oleanane, and ursane triterpenes were prepared and their effects on B16 2F2 melanoma cell differentiation and growth were examined. Eleven lupane triterpenes used in this study acted on the melanoma cells as a melanogen, but no induction of melanogenesis of B16 2F2 cells by oleanane and ursane was detected. The differences at C-17 of the lupane series and acetylation of the OH group at C-3 did not markedly influence their activities. However, the ED(50) value for up-regulation of melanin biosynthesis was markedly decreased by the oxidation of the OH group at C-3 of lupeol (1). Betulinic acid (11), its methyl ester (12), lup-28-al-20(29)-ene-3beta-ol (9), and lup-28-al-20(29)-en-3-one (10) inhibited B16 2F2 cell proliferation by induction of apoptosis. These findings suggested that the carbonyl group at C-17 might be essential for the apoptotic effects of these compounds on B16 2F2 cells.     

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??OBJECTIVE To study the chemical constituents of Microtropis triflora Merr. et Freem. METHODS The compounds were isolated and purified by various chromatographic technigues such as silica gel, Sephadex LH-20, and pre-HPLC. Their structures were identified on the basis of chemical properties and spectral analysis. RESULTS Ten triterpenes were isolated and elucidated as 3, 25-epoxy-1??, 3??, 11??, 12, 23, 25-hexahydroxy-urs-12-en(1), ??-amyrin(2), ??-amyrin palmitate(3), 3??-hydroxy-11-oxo-olean-12-enyl-3-palmitate(4), lupeol(5), friedelin(6), 3-oxo-28-friedelanoic acid(7), oleanolic acid(8), salaspermic acid(9), and orthosphenic acid(10). CONCLUSION Compound 1 is a new compound and has cytotoxic activity against Bcap37 and SMMC7721 cells with IC₅₀ values of 27.86 and 11.38 ??g??mL^-1, respectively.     

A study on major chemical components of Uvaria grandiflora]

OBJECTIVE: To make clear the chemical constituents of Uvaria grandiflora (Annonaceae). METHODS: Purification was performed using sephadex LH-20 permeation and silica gel chromatography. Structures of the purified components were determined on the basis of 1H, 13C NMR analysis and also by comparison with those of authentic compounds. RESULTS: Two major triterpenes, suberosol and lupeol, were identified. CONCLUSION: This paper is the first report on the identification of suberosol and lupeol from the gunus Uvaria.     

Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models

Eryngium foetidum L. (Apiaceae) is a Caribbean endemic plant, used in folk medicine for the treatment of several antiinflammatory disorders. A preliminary phytochemical study showed that the hexane extract is rich in terpenic compounds. Chromatographic fractionation of this extract yielded: alpha-cholesterol, brassicasterol, campesterol, stigmasterol (as the main component, 95%) clerosterol, beta-sitosterol, delta 5-avenasterol, delta (5)24-stigmastadienol and delta 7-avenasterol. The topical antiinflammatory activity of the hexane extract and of stigmasterol was evaluated by auricular oedema, induced by 12-0-tetradecanoylphorbol acetate (TPA), in the mouse, using single and multiple applications of the phlogistic agent. Both reduced the oedema in a similar proportion in the two model assays (acute and chronic). Meloperoxidase activity was strongly reduced by both the extract and the compound, in the acute but not the chronic model. These results indicate that the leaves of Eryngium foetidum L may be effective against topical inflammation processes. Stigmasterol also exerts a significant topical antiinflammatory activity although it cannot be considered to be a major antiinflammatory agent, therefore other bioactive components are probably involved in the activity of the hexane extract.     

Antidermatophytic triterpenoids from Syzygium jambos (L.) Alston (Myrtaceae)

Chemical investigation of the EtOAc extract of the stem bark of Syzygium jambos (L.) Alston (Myrtaceae) afforded a number of known triterpenes such as friedelin, beta-amyrin acetate, betulinic acid and lupeol. Friedelin was submitted to a Baeyer-Villiger oxidation, and was also reduced with LiAlH(4) to give the known friedelolactone and friedelanol, respectively. These compounds were identified by comparison of NMR spectral data with those from the literature. The EtOAc extract and the isolated compounds were tested for their antidermatophytic activity against three dermatophyte species: Microsporum audouinii, Trichophyton mentagrophytes and Trichophyton soudanense, commonly found in Cameroon. Betulinic acid and friedelolactone were the most active compounds, and the most sensitive fungi were Trichophyton soudanense and Trichophyton mentagrophytes.     

地胆草三萜成分的研究

 目的分离鉴定地胆草的化学成分,为PC-12细胞活性筛选提供样品。方法用体积分数80%工业酒精提取,硅胶柱色谱分离纯化,根据理化性质和光谱分析确定结构。结果分得8个三萜类成分,分别为无羁萜酮(friedlin,E-6),表无羁萜醇(epifriedlinol,E-7),羽扇豆醇(lupeol,E-8),羽扇豆醇乙酸酯(lupeol acetate,E-9),乌苏酸(ursolic acid,E-10),乌苏-12-烯-3β-十七酸酯(ursa-12-ene-3β-heptadecanoate,E-11),桦木酸(betulinic acid,E-12),30-羟基羽扇豆醇(30-hydroxylupeol,E-13)。结论化合物E-11为一个新的天然产物;化合物E-6,E-10,E-12,E-13为首次从该属植物中得到。     

Cucurbitane triterpenes from the fruiting bodies and cultivated mycelia of Leucopaxillus gentianeus

A reinvestigation of the fruiting bodies of the mushroom Leucopaxillus gentianeus, allowed the isolation of two minor cucurbitane triterpenes, namely, cucurbitacin D (5) and the new metabolite 16-deoxycucurbitacin B (6). The latter compound lacks an oxygenated substituent at C-16, an unprecedented structural feature among congeners of cucurbitacin B. The cucurbitanes present in the fruiting bodies were compared with those extracted from mycelia grown on the modified Melin-Norkans (MMN) culture medium. Cucurbitacins B (1) and D (5), as well as leucopaxillones A (3) and B (4), were isolated from both sources; in contrast, 16-deoxycucurbitacin B (6) and a mixture of fatty acid esters of cucurbitacin B (2) were absent in the mycelia. A new triterpene, 18-deoxyleucopaxillone A (7), was isolated from the mycelia, but was not detected in the fruiting bodies. The antiproliferative activity of the isolated triterpenes was determined against the NCI-H460 human tumor cell line, in comparison with the antitumor compound topotecan, a well-known topoisomerase I inhibitor.     

Pomegranate as a cosmeceutical source: pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells

Pomegranate (Punica granatum) is an ancient fruit with exceptionally rich ethnomedical applications. The peel (pericarp) is well regarded for its astringent properties; the seeds for conferring invulnerability in combat and stimulating beauty and fertility. Here, aqueous fractions prepared from the fruit's peel and fermented juice and lipophilic fractions prepared from pomegranate seeds were examined for effects on human epidermal keratinocyte and human dermal fibroblast function. Pomegranate seed oil, but not aqueous extracts of fermented juice, peel or seed cake, was shown to stimulate keratinocyte proliferation in monolayer culture. In parallel, a mild thickening of the epidermis (without the loss of ordered differentiation) was observed in skin organ culture. The same pomegranate seed oil that stimulated keratinocyte proliferation was without effect on fibroblast function. In contrast, pomegranate peel extract (and to a lesser extent, both the fermented juice and seed cake extracts) stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 (MMP-1; interstitial collagenase) production by dermal fibroblasts, but had no growth-supporting effect on keratinocytes. These results suggest heuristic potential of pomegranate fractions for facilitating skin repair in a polar manner, namely aqueous extracts (especially of pomegranate peel) promoting regeneration of dermis, and pomegranate seed oil promoting regeneration of epidermis.     

Cytotoxic principles from Ventilago leiocarpa

Three new anthraquinones, islandicin 4-methyl ether (1), 1,2,6-trihydroxy-7,8-dimethoxy-3-methylanthraquinone (2), and 2-hydroxyemodin 1-methyl ether (3) as well as two known triterpenoids [taraxerol (4), lupeol (5)], six anthraquinones [chrysophanol (6), islandicin (8), parietin (9), emodin (10), catenarin (11), skyrin (15)], a 2,3-dihydroflavonol [(+)-aromadendrin (12)], two benzisochromanquinones [ventiloquinone K (13) and ventiloquinone I (14)], and stigmasterol (7) were isolated from Ventilago leiocarpa. The cytotoxicity of these compounds to various tumor cell lines was evaluated, and compound 15 significantly suppressed growth of HeLa, Vero, K562, Raji, Wish, and Calu-1 tumor cell lines. With the exception of K562 cells, the proliferation of other tumor cell lines was inhibited by compounds 3 and 10.     

Anti-inflammatory activity of lupeol and lupeol linoleate in rats

Two pentacyclic triterpenes, namely lupeol and lupeol linoleate, were investigated for their anti-inflammatory, antinociceptive, anti-pyretic and ulcerogenic properties in comparison with the commonly used non-steroidal anti-inflammatory drug, indomethacin in rats. Lupeol, lupeol linoleate and indomethacin showed a reduction in paw swelling by 39, 58 and 35%, respectively, in adjuvant arthritis. Triterpenes were devoid of any antinociceptive, anti-pyretic and ulcerogenic actions. However, indomethacin exhibited a positive response to these properties. These results suggest that the mechanism of action of triterpenes is different from the non-steroidal anti-inflammatory drug.     

Ethyl acetate fraction of Radix rubiae inhibits cell growth and promotes terminal differentiation in cultured human keratinocytes

Ethnopharmacological relevance

In Chinese medicine practice, Radix rubiae, the dry root of Rubia cordifolia L. is commonly used for the treatment of psoriasis.

Aim of the study

Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes. Our previous studies identified Radix rubiae to have potent antiproliferative action on cultured HaCaT keratinocytes and to induce keratinocyte differentiation in mouse tail model. The present study aimed to investigate whether Radix rubiae could also induce terminal differentiation in cultured human keratinocytes.

Methods and results

The cornified envelope (CE) formation assay showed that ethyl acetate (EA) fraction of Radix rubiae significantly accentuated the CE formation, a well-recognized marker of terminal differentiation, in cultured HEK and HaCaT cells in a dose and time dependent manner. Western blot analyses demonstrated that EA fraction of Radix rubiae at a concentration of 3.2 μg/ml significantly increased transglutaminase type I and involucrin expression in both HEK and HaCaT keratinocytes after 96 h treatment, a response similar to that of Ca²⁺ positive control. Moreover, the expression level of cytokeratin 5/14, which is specifically related to cell proliferation, was significantly downregulated while terminal differentiation markers cytokeratin 1/10 were markedly increased by Radix rubiae treatment in both HEK and HaCaT cells.

Conclusion

The present experimental findings unequivocally confirmed the keratinocyte terminal differentiation promoting capacity of Radix rubiae, and strongly suggest that Radix rubiae is a promising antipsoriatic agent warranting further clinical development for psoriasis treatment.     

Biologically active steroid from the green alga Ulva lactuca

The marine green alga, Ulva lactuca, was shown to contain 3-O-beta-D glucopyranosyl-stigmasta-5,25-dien. The structure of the compound was established on the basis of its spectroscopic data and it was extracted for the first time from this alga. The topical antiinflammatory activity of this compound was examined using the mouse ear oedema assay as an experimental model of topical inflammation. Also, the antimicrobial activity of the isolated compound was tested against 10 various microorganisms (G+, G-, fungi and yeast strains).     

Potential antipsoriatic agents: lapacho compounds as potent inhibitors of HaCaT cell growth.

A number of lapacho compounds, representing the most common constituents of the inner bark of Tabebuia impetiginosa, together with some synthetic analogues, were evaluated in vitro against the growth of the human keratinocyte cell line HaCaT. With an IC(50) value of 0.7 microM, beta-lapachone (4) displayed activity comparable to that of the antipsoriatic drug anthralin. 2-Acetyl-8-hydroxynaphtho[2,3-b]furan-4,9-dione (7), which was prepared in a four-step synthesis from 2,8-dihydroxy-1, 4-naphthoquinone, was the most potent inhibitor among the known lapacho-derived compounds and inhibited cell growth with an IC(50) value of 0.35 microM. Furthermore, other active constituents of lapacho inhibited keratinocyte growth, with IC(50) values in the range of 0.5-3.0 microM. However, as already observed with anthralin, treatment of HaCaT cells with these potent lapacho compounds also caused remarkable damage to the plasma membrane. This was documented by leakage of lactate dehydrogenase into the culture medium, which significantly exceeded that of the vehicle control. Because of their potent activity against the growth of human keratinocytes, some lapacho-derived compounds appear to be promising as effective antipsoriatic agents.