Downregulation of iNOS expression in rat mesangial cells by special extracts of Harpagophytum procumbens derives from harpagoside-dependent and independent effects.

Special extracts from the roots of Harpagophytum procumbens (Devil's Claw) are used in the supportive treatment of inflammatory diseases, and the iridoid derivative harpagoside is thought to be the active principle. To investigate, whether Harpagophytum extracts may also be useful therapeutics in the treatment of inflammatory kidney diseases, we studied the effects of two different extracts containing 8.9% (extract 1) and 27% harpagoside (extract 2), respectively, on IL-1beta-induced nitric oxide (NO) formation as well as transcriptional regulation of inducible NO synthase (iNOS) in rat renal mesangial cells. We observed a concentration-dependent suppression of nitrite formation by about 80%, which was due to an inhibition of iNOS expression. Moreover, a reduction of iNOS promoter activity and nuclear NF-kappaB translocation was observed, indicating that the extracts interfere with the transcriptional activation of iNOS. Three further Harpagophytum extracts containing about 2% harpagoside did not inhibit NO formation suggesting, that only extracts with a high harpagoside content elicit iNOS inhibition. However, pure harpagoside was only inhibitory at concentrations between 0.3 and 1 mg/ml, which is much higher than the harpagoside content present in an effective concentration of the total extracts. Moreover, a harpagoside-free extract 1 also markedly inhibited iNOS expression, indicating that other extract constituents are involved in this effect. Extract 1 exerted a strong antioxidative effect, whereas no such effect could be demonstrated for harpagoside. Together, these data show that special Harpagophytum extracts may represent potential antiinflammatory drugs in the treatment of glomerular inflammatory diseases.

Hyperforin, possibly the major non-nitrogenous secondary metabolite of Hypericum perforatum L.

An overview of the constituents of Hypericum perforatum is given, with special emphasis on the acylphloroglucinol hyperforin. Previous work on the chemistry of hyperforin and on other components derived from hyperforin in H. perforatum is reviewed. A new optimized method of isolating hyperforin on a large scale is presented, including full spectroscopic characterization of the isolate.

Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility.

Efforts leading to the identification of hyperforin as an antidepressive component of therapeutically used alcoholic hypericum extracts are described and discussed. Initially, the effects of this unique and major constituent of the herb were detected in peripheral organs using in vitro models and an extract was obtained by supercritical extraction of the herb by carbon dioxide. These extracts are highly enriched in hyperforin (38.8%) and are devoid of hypericines and numerous other components of alcoholic extracts. Studies with such an extract and with isolated hyperforin indicated that this acylphloroglucinol derivative can inhibit serotonin-induced responses and uptake of this neurotransmitter in peritoneal cells. Assuming that the effects of hyperforin were due to its actions on serotoninergic 5-HT3/5-HT4 receptors, further studies were conducted to investigate its effects on the CNS. These efforts revealed its antidepressant activity in the behavioral despair test and led to the working hypothesis that hyperforin and serotoninergic mechanisms are involved in the antidepressant activities of alcoholic hypericum extracts. The observations made during this study also indicate that hyperforin is the major, but not the only antidepressive component of alcoholic extracts.

Antiviral and antiphlogistic activities of Hamamelis virginiana bark.

A crude hydroalcoholic extract from Hamamelis virginiana bark was subjected to ultrafiltration (UF) with a cut-off limit of 3 kDa to obtain a higher and a lower molecular weight fraction. Characterisation of the fractions was attempted with TLC, HPLC, acidic hydrolysis, and chromatography over Sephadex LH-20. The UF-concentrate was shown to consist mainly of oligomeric to polymeric proanthocyanidins (PA). This fraction was found to exhibit significant antiviral activity against Herpes simplex virus type 1 (HSV-1). In addition, the UV-concentrate displayed radical scavenging properties, inhibited alpha-glucosidase as well as human leukocyte elastase (HLE), and exhibited strong antiphlogistic effects in the croton oil ear edema test in the mouse. With the exception of the antioxidant potential and the inhibition of HLE-action the lower molecular fraction possessed weaker activities and contained mainly hamamelitannin, catechin, and further, unidentified constituents.

Five new prenylated p-hydroxybenzoic acid derivatives with antimicrobial and molluscicidal activity from Piper aduncum leaves.

Five new prenylated benzoic acid derivatives, methyl 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxybenzoate (1), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-hydroxybenzoate (2), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (3), methyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (4), and 4-hydroxy-3-(3-methyl-2-butenyl)-5-(3-methyl-2-butenyl)-benzoic acid (5) were isolated from the dried leaves of Piper aduncum L. (Piperaceae). Together with the new metabolites, four known prenylated benzoic acid derivatives, 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (6), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (nervogenic acid, 7), methyl 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoate (8), and methyl 4-hydroxy-3-(3-methyl-2-butenyl)-benzoate (9) as well as, dillapiol (10), myristicin, and the three sesquiterpenes humulene, caryophyllene epoxide, and humulene epoxide were isolated. Compounds 7, 8, and 9 are reported as natural products for the first time. The structures of the isolates were elucidated by spectroscopic methods, mainly 1D-and 2D-NMR spectroscopy. Isolates 4-7, 9, and 10 were molluscicidal while 2, 5-7, and 9 displayed significant antibacterial activities.

A novel amino acid glycoside and three amino acids from Allium sativum.

A novel amino acid glycoside (-)-N-(1'-deoxy-1'-beta-D-fructopyranosyl)-S-allyl-L-cysteine sulfoxide [1], was isolated from a hydrophilic extract of the leaves of Allium sativum (Alliaceae), together with three known compounds: (+)-S-allyl-L-cysteine sulfoxide [2],(+)-S-methyl-L-cysteine sulfoxide [3], and (+)-S-(trans-1-propenyl)-L-cysteine sulfoxide [4]. The latter two substances were isolated for the first time from garlic. The structure elucidation of 1 was performed by extensive chemical, spectroscopic (ir, fabms, 1D and 2D(1)H- and (13)C-nmr measurements) and chromatographic experiments. For the first time, detailed nmr data and the unambiguous assignment of all (13)C-nmr data for compounds 2-4 were reported. Compound 1, the amino acid glycoside, revealed a significant inhibition of in vitro platelet aggregation induced by ADP and epinephrine, whereas none of the amino acids tested displayed any activity.

New phenolic glucosides from the leaves of Eurya tigang.

Three new compounds, 6'-O-coumaroyl-1'-O-[2-(4-hydroxyphenyl)ethyl]-beta-D-glucopyra nos ide [1] (eutigoside A), 6'-O-coumaroyl-1'-O-[2-(1-hydroxy-4-oxo-2,5-cyclohexadien-1- yl)ethyl]-beta-D-glucopyranoside [2] (eutigoside B), and 6'-O-cinnamoyl-1'-O-[2-(1-hydroxy-4-oxo-2,5-cyclohexadien-1-yl)eth yl]- beta-D-glucopyranoside [3] (eutigoside C) have been isolated from the leaves of Eurya tigang, along with other known compounds (afzelin, quercitrin, p-coumaric acid, methyl-alpha-D-fructofuranoside, isorengyol, and euryanoside). Their structures were determined by chemical and spectroscopic methods (uv, ir, ms, 1H-1H COSY, and 1H-13C COSY).

The pregnane glycoside marsdekoiside A from Marsdenia koi.

A new pregnane glycoside, marsdekoiside A was isolated from the stems of Marsdenia koi (Asclepiadaceae) and its structure was elucidated from chemical and spectral data as 12-cinnamoyl-dihydrosarcostin-3-O-methyl-6-deoxy-beta-D-allopyr ano syl-(1----4)-O-beta-D-oleandropyranosyl-(1----4)-O-beta-D-++ +cymar opyranoside.

Indole alkaloids with in vitro antiproliferative activity from the ammoniacal extract of Nauclea orientalis.

Nine angustine-type alkaloids were isolated from ammoniacal extracts of Nauclea orientalis L. (Rubiaceae). Three of them, 10-hydroxyangustine and the two diastereoisomeric 3,14-dihydroangustolines, have not been described in the literature thus far. The structures of the isolates were determined with spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy. The compounds were found to exhibit in vitro anti-proliferative activity against the human bladder carcinoma T-24 cell line and against EGF (epidermal growth factor)-dependent mouse epidermal keratinocytes. By using overpressure layer chromatography, it was shown that minor quantities of these alkaloids occur in dried Nauclea orientalis leaves. The use of ammonia in the extraction process results in a significant increase in the formation of angustine-type alkaloids from strictosamide-type precursors.

DNA as an affinity probe useful in the detection and isolation of biologically active natural products.

A simplified hplc system is described for the detection of compounds capable of binding to DNA. Compounds known to interact with DNA were found to invoke a positive response with this system, and the concentration-dependence and sensitivity were determined. When applied to 17 randomly selected plant extracts, five elicited a positive response and, of these, four were subsequently found to be cytotoxic with cultured KB or P-388 cells. As described in a companion paper, one of these extracts (derived from Albizia amara) has been further processed and found to contain a group of structurally-unique macrocyclic alkaloids that demonstrate a variety of biological activities. Therefore, this approach should prove a value in facilitating the identification of plant extracts that contain substances capable of binding to DNA and the subsequent activity-directed fractionation for the procurement of active principles. As a prescreen or monitor, these relatively uncomplicated hplc procedures can be used in laboratories not prepared to perform more complicated or costly bioassay techniques. Thus, the pool of potentially active novel chemical substances to be considered for more advanced testing could be increased.

New indole alkaloid glycosides from Nauclea orientalis.

Two new indole alkaloid glycosides, 10-hydroxystrictosamide and 6'-O-acetylstrictosamide, as well as the known alkaloids strictosamide and vincosamide were isolated from the leaves of Nauclea orientalis L. The structures of the isolated compounds were determined using spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy.

Studies on the antifertility components from Marsdenia koi.

By random screening test, Marsdenia koi was found to have antifertility activity on SD rat. From MeOH extracts of this plant two steroidal glycosides, marsdekoiside A and B, were isolated, and their structures were elucidated on the basis of spectral evidence and by comparison of the hydrolysis products with the authentic samples. Both are newly identified compounds, and marsdekoiside A has good antifertility activity.

Furanoid lignans from Larrea tridentata.

From the leaves and stems of Larrea tridentata six new furanoid lignans, compounds 1-6, have been isolated and their structures determined through interpretation of physical and spectroscopic properties. The use of 1D and 2D nOe experiments was of particular importance in assigning the stereochemistry.