€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARZNEIMITTEL-FORSCHUNG***** Winterhoff H Gumbinger HG Vahlensieck U Kemper FH Schmitz H Behnke B Endocrine effects of Lycopus europaeus L. following oral application. In: Arzneimittelforschung (1994 Jan) 44(1):41-5 ISSN: 0004-4172 Lycopus extracts are used in folk medicine for the treatment of hyperthyroid symptoms. Diverse effects on the pituitary thyroidal system as well as on the pituitary gonadal system could be confirmed in experimental studies. But till now endocrine effects of Lycopus extracts in experimental animals were observed after parenteral application only. Therefore in this investigation an ethanolic extract of Lycopus europaeus was applied orally to rats, diverse endocrine parameters were measured between 3 and 24 h later and the effects compared to an i.p. treated group. The plant extract given p.o. caused a long lasting (for a period of more than 24 h) decrease of T3 levels, presumably as a consequence of a reduced peripheral T4 deiodination. A pronounced reduction of T4 and thyroid stimulating hormone (TSH) concentrations was observed 24 h after application of the test solution by gavage. The luteinizing hormone (LH) decrease as well as the TSH decrease, which was pronounced in spite of reduced T4 and T3 levels indicate a central point of attack of the plant extract. Differences in the biological activity in dependence on the route of application may be explained e.g. by differences in absorption of plant constituents. Registry Numbers: 6893-02-3 (Triiodothyronine) 7488-70-2 (Thyroxine) 9002-71-5 (Thyrotropin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ENDOCRINOLOGY***** Auf'mkolk M Ingbar JC Amir SM Winterhoff H Sourgens H Hesch RD Ingbar SH Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. In: Endocrinology (1984 Aug) 115(2):527-34 ISSN: 0013-7227 The present studies were undertaken to explore the mechanism by which, as previous studies have shown, freeze-dried aqueous extracts (FDE) of plants of the species Lycopus virginicus and Lycopus europaeus, Melissa officinalis (Laminaceae), and Lithospermum officinale (Boraginaceae) have the ability to inhibit at least many of the effects of exogenous and endogenous TSH on the thyroid gland. To this end, we have examined the in vitro effects of FDE from these plants on the ability of bovine TSH (bTSH) to both bind to human thyroid plasma membranes (TPM) and activate adenylate cyclase therein. FDE of these four species produced a dose-related, ultimately complete, inhibition of the binding of 125I-labeled bTSH when studied at 4 C in a 20 mM Tris-HCl-0.5% BSA buffer, pH 7.45. Half-maximum inhibition of bTSH binding was produced by approximately 50 mU/ml bTSH and only about 10-30 micrograms/ml of the four active FDE. When studied in Tris-BSA-50 mM NaCl buffer at 37 C, these FDE remained inhibitory to bTSH binding, but their potency was decreased to about one fifth of that seen in the absence of NaCl. The binding of [125I]hCG to rat testis membranes was also inhibited by all of these FDE, but no effect on the binding of [125I]insulin to crude rat liver membranes was observed. In concentrations as high as 1 mg/ml, FDE of Verbena officinalis (Verbenaceae), which belongs to the same order (Tubiflorae) as the other plants, but exhibits no antithyrotropic or antigonadotropic activity in vivo, had no effect on either the binding of bTSH to thyroid membranes or the binding of hCG to rat testis membranes. No inhibition of [125I]bTSH binding occurred when TPM were preincubated with the four active FDE, washed, and then incubated with [125I]bTSH in medium devoid of FDE. Hence, the inhibition of [125I]bTSH binding seen when labeled hormone and active FDE were added together was not due to irreversible binding of FDE to TPM or damage to the TSH receptor. When [125I]bTSH was incubated with the active FDE in Tris-BSA and the mixture was chromatographed on Sephadex G-100 using the same buffer, [125I]bTSH was shifted from an apparent mol wt of 30,000 and eluted at the void volume. Direct binding of [125I]bTSH in fractions from the new, large molecular peak was nil. Addition of a large excess of unlabeled bTSH during preincubation prevented the shift in the elution pattern of [125I] bTSH produced by these FDE.(ABSTRACT TRUNCATED AT 400 WORDS) Registry Numbers: EC 4.6.1.1 (Adenyl Cyclase) 9002-71-5 (Thyrotropin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANNALES PHARMACEUTIQUES FRANCAISES***** Lamaison JL Petitjean-Freytet C Carnat A [Rosmarinic acid, total hydroxycinnamic derivatives and antioxidant activity of Apiaceae, Borraginaceae and Lamiceae medicinals] Teneurs en acide rosmarinique, en derives hydroxycinnamiques totaux et activite antioxydante chez les Apiacees, les Borraginacees et les Lamiacees medicinales. In: Ann Pharm Fr (1990) 48(2):103-8 ISSN: 0003-4509 (Published in French) A number of medicinal species of the Apiaceae, Borraginaceae and Lamiaceae families present high rosmarinic acid and total hydroxycinnamic derivative contents. Species of genera Sanicula (Apiaceae), Lycopus, Melissa, Mentha, Origanum and Salvia (Lamiaceae) contain rosmarinic acid in large amount, more than 3%, based on dry weight. The antioxidant activity of hydroalcoholic extracts, on DPPH, is partly in relation with the hydroxycinnamic derivative content. Registry Numbers: 537-15-5 (rosmarinic acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARZNEIMITTEL-FORSCHUNG***** Winterhoff H Gumbinger HG Vahlensieck U Kemper FH Schmitz H Behnke B Endocrine effects of Lycopus europaeus L. following oral application. In: Arzneimittelforschung (1994 Jan) 44(1):41-5 ISSN: 0004-4172 Lycopus extracts are used in folk medicine for the treatment of hyperthyroid symptoms. Diverse effects on the pituitary thyroidal system as well as on the pituitary gonadal system could be confirmed in experimental studies. But till now endocrine effects of Lycopus extracts in experimental animals were observed after parenteral application only. Therefore in this investigation an ethanolic extract of Lycopus europaeus was applied orally to rats, diverse endocrine parameters were measured between 3 and 24 h later and the effects compared to an i.p. treated group. The plant extract given p.o. caused a long lasting (for a period of more than 24 h) decrease of T3 levels, presumably as a consequence of a reduced peripheral T4 deiodination. A pronounced reduction of T4 and thyroid stimulating hormone (TSH) concentrations was observed 24 h after application of the test solution by gavage. The luteinizing hormone (LH) decrease as well as the TSH decrease, which was pronounced in spite of reduced T4 and T3 levels indicate a central point of attack of the plant extract. Differences in the biological activity in dependence on the route of application may be explained e.g. by differences in absorption of plant constituents. Registry Numbers: 6893-02-3 (Triiodothyronine) 7488-70-2 (Thyroxine) 9002-71-5 (Thyrotropin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CHROMATOGRAPHY. A***** Wojciechowski H Gumbinger HG Vahlensieck U Winterhoff H Nahrstedt A Kemper FH Analysis of the components of Lycopus europaeus L. in body fluids during metabolism studies. Comparison of capillary electrophoresis and high-performance liquid chromatography. In: J Chromatogr A (1995 Nov 24) 717(1-2):261-70 During pharmacokinetic studies with extracts obtained from medicinally used plants, analysis in body fluids is mainly performed by HPLC, an established separation method. In this paper high- performance capillary electrophoresis (HPCE) is investigated for its ability to separate such complex extracts. Crude extracts of Lycopus europaeus L. (Lamiaceae) are traditionally used against mild forms of hyperthyroidism. The metabolism of a 70% ethanolic extract with respect to some of its individual main components (rosmarinic and caffeic acid, luteolin-7-glucoside) and a mixture of the pure compounds were investigated using isolated perfused rat liver. After solid-phase extraction metabolites were determined using HPCE and HPLC separation techniques. A buffer solution composed of 0.05 mol l- 1 Na2HPO4 at pH 7.0 with 30% acetonitrile was found to be the most suitable electrolyte for HPCE separation. The best mobile phase for isocratic HPLC was 0.03% TFA-acetonitrile (82:18, v/v). Data obtained with HPCE are in good accordance with those from HPLC; HPCE, however, is clearly more rapid and simple to perform. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACEUTICA ACTA HELVETIAE***** Lamaison JL Petitjean-Freytet C Carnat A [Medicinal Lamiaceae with antioxidant properties, a potential source of rosmarinic acid] Lamiacees medicinales a proprietes antioxydantes, sources potentielles d'acide rosmarinique. In: Pharm Acta Helv (1991) 66(7):185-8 ISSN: 0031-6865 (Published in French) Hydroalcholic extracts from four native medicinal Lamiaceae, Lycopus europaeus L., Melissa officinalis L., Origanum vulgare L. and Prunella vulgaris L. have shown significant antioxidative activities, by free radical scavenger effect on DPPH, compared with those of Rosmarinus officinalis L. and Salvia officinalis L. extracts. The antioxidative activity was partly in relation to the rosmarinic acid content. The major hydroxycinnamic compound, quantitatively determinated by HPLC, was present in large amount. The content in Prunella vulgaris L. spikes average 6.1%, based on dry weight. Registry Numbers: 537-15-5 (rosmarinic acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Gumbinger HG Winterhoff H Wylde R Sosa A On the influence of the sugar moiety on the antigonadotropic activity of luteoline glycosides. In: Planta Med (1992 Feb) 58(1):49-50 ISSN: 0032-0943 Luteolin-7-glucoside and luteolin-7-glucuronide were isolated from Lycopus europaeus L. (Lamiaceae) and identified by 1H- and 13C-NMR spectroscopy. Luteolin-7-glucuronide proved to be active against PMSG in vitro as well as in vivo, whereas the other flavone glycosides occurring in the plant were completely inactive. Registry Numbers: 29741-10-4 (luteolin-7-glucuronide) 5373-11-5 (luteolin-7-glucoside) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Nahrstedt A Albrecht M Wray V Gumbinger HG John M Winterhoff H Kemper FH Structures of compounds with antigonadotropic activity obtained by in vitro oxidation of caffeic acid. In: Planta Med (1990 Aug) 56(4):395-8 ISSN: 0032-0943 Two new cyclolignan derivatives were isolated by HPLC from the mixture of substances obtained after oxidation of caffeic acid with KMnO4. Their structures were elucidated by spectroscopic methods as 2,3-dicarboxy-6,7-dihydroxy-1-(3', 4'-dihydroxy)-phenyl-1, 2- dihydronaphthalene (1) and 3-carboxy-6,7-dihydroxy-1-(3', 4'- dihydroxy)-phenylnaphthalene (2). Compounds 1 and 2 exhibit antigonadotropic activity as do the extracts of crude drugs of Lycopus europaeus and Lithospermum officinale after oxidation by plant enzymes. Registry Numbers: 121242-02-2 (KS IV) 130752-21-5 (KS I) 331-39-5 (caffeic acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€