Serotonergic mechanisms are involved in antidepressant-like effects of bisbenzylisoquinolines liensinine and its analogs isolated from the embryo of Nelumbo nucifera†Gaertner seeds in mice.

OBJECTIVES: We attempted to ascertain if bisbenzylisoquinoline alkaloids, liensinine and isoliensinine from Nelumbo nucifera Gaertner have antidepressant-like effects and compare the effects with those previously obtained by their analogue neferine. METHODS: Using mice, the forced swimming test (FST) was carried out after treatment with liensinine, isoliensinine and neferine. KEY FINDINGS: Liensinine and isoliensinine elicited antidepressant-like effects in mice after the FST. Anti-immobility effects of liensinine and isoliensinine were antagonized by the 5-hydroxytryptamine1 A (5-HT1 A ) receptor antagonist WAY 100635, but not by the α1 -adrenoceptor antagonist prazosin. The anti-immobility effects of liensinine, isoliensinine and neferine were blocked by pretreatment with p-chlorophenylalanine (PCPA), which depletes serotonin (5-HT). CONCLUSIONS: These data suggest that liensinine and isoliensinine from Nelumbo nucifera Gaertner have antidepressant-like effects and that antidepressant-like effects of liensinine and its analogues are closely related to serotonergic mechanisms.

Bisbenzylisoquinoline Alkaloids from Nelumbo nucifera.

From the embryos of the seeds of Nelumbo nucifera, three bisbenzylisoquinoline alkaloids, nelumboferine and nelumborines A and B, were isolated along with four known compounds, neferine, liensinine, isoliensinine and anisic acid. The structures of the new alkaloids were determined mainly by spectroscopic methods.

Antidepressant-like effects of neferine in the forced swimming test involve the serotonin1A (5-HT1A) receptor in mice.

The effects of neferine, an alkaloid of Nelumbo nucifera Gaertner embryos, on immobility in the forced swimming test, which is used to evaluate antidepressants, were investigated in mice. The administration of neferine from 25 to 100 mg/kg i.p. elicited anti-immobility effects in mice. The molecular dose effects of neferine in the forced swimming test were almost equal to those of the typical antidepressants maprotiline and imipramine. The involvement of the 5-HT receptor subtypes was also studied using 5-HT receptor antagonists. Anti-immobility effects of neferine are antagonized by the serotonin1A (5-HT1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). However, the 5-HT1B receptor antagonist, 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl] benzamide dihydrochloride (GR 55562), the 5-HT2 receptor antagonist, 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY 53857), the 5-HT3 receptor antagonist, ondansetron and the 5-HT4 receptor antagonist, 4-amino-5-chloro-2-methoxy-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205,557) did not affect the anti-immobility effects of neferine. The anti-immobility effect of the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetaralin (8-OH-DPAT) was also antagonized by WAY 100635. Furthermore, co-administration of subactive doses of neferine (10 mg/kg) and 8-OH-DPAT (0.1 mg/kg) produced synergistic antidepressant-like effects. These results suggest that neferine shows antidepressant-like effects in mice similar to typical antidepressants and that these effects are mediated by the 5-HT1A receptor. Therefore, the central effects of neferine are likely to be linked to serotonergic neurotransmission.

Effects of extracts and neferine from the embryo of Nelumbo nucifera seeds on the central nervous system.

The effects of embryos of the seeds of Nelumbo nucifera on the central nervous system were studied in mice. MeOH extracts of embryos of Nelumbo nucifera seeds significantly inhibited locomotor activity in mice. The MeOH extract was successively partitioned between H(2)O and n-hexane, between H(2)O and CHCl(3), and between H(2)O and n-BuOH. CHCl(3) extracts strongly inhibited locomotor activity in mice, although other extracts had no effect on locomotor activity. The main alkaloid of CHCl(3) extracts, neferine, dose-dependently inhibited locomotor activity in mice. Neferine induced hypothermia in mice and apparently potentiated thiopental-induced sleeping time. An anxiolytic, diazepam, decreased locomotor activity, rectal temperature and enhanced sleep elicited by thiopental, similar to neferine. In addition, neferine and diazepam showed anti-anxiety effects in the elevated plus maze test. Neferine did not affect muscle coordination by the rota-rod test. Neferine did not affect strychnine- nor picrotoxin-induced seizure. In contrast, diazepam had apparent muscle relaxant and anti-convulsant effects. These results suggest that neferine has several central effects and that neferine may participate in the efficacy of the sedative effects of embryos of the seeds of Nelumbo nucifera. The mechanisms of the sedative effects of neferine are not similar to those of diazepam.

Phenolic and iridoid glycosides from Strychnos axillaris.

Five phenolic glycosides 1-5 and an iridoid glucoside 6 were isolated, together with 22 known compounds, from the dried barks and woods of Strychnosaxillaris. Their structures were determined by application of spectroscopic (NMR, MS) and chemical methodologies.

Secoiridoid glucosides from Strychnos spinosa.

Three new secoiridoid glucosides, stryspinoside (1) and strychosides A (2) and B (3), were isolated, together with 23 known compounds, from the dried branches of Strychnos spinosa. The structures of the new compounds were determined by spectroscopic means.

[Deep vein thrombosis caused by pelvic lymphocyst following radical prostatectomy: a case report].

A 66-year-old man was admitted with distal edema of his right leg. He had undergone radical prostatectomy and pelvic lymphadenectomy for prostatic cancer 23 days previously. Abdominal computed tomography (CT) showed a lymphocyst (4.5 x 3.0 cm) along the right pelvic wall compressing the right external iliac vein. CT with contrast medium showed thrombus formation (about 9 cm) in the distal portion of the right external iliac vein and femoral vein. An inferior vena cava filter was placed to prevent pulmonary embolism, and anticoagulation with warfarin was started. One week later, CT showed shrinkage of the lymphocyst and thrombus in the vein, as well as a large thrombus trapped in the filter. Follow-up CT taken 2 months later revealed marked reduction of the lymphocyst and absence of thrombus in both the vein and filter. A lymphocyst, also known as a lymphocele, is a complication of radical pelvic surgery. Most lymphocysts are asymptomatic and regress spontaneously, but may lead to deep vein thrombosis and pulmonary embolism, usually a few weeks after surgery. Careful observation is needed even after discharge from hospital.

Indole alkaloids and other constituents of Rauwolfia serpentina.

From the dried roots of Rauwolfia serpentina were isolated five new indole alkaloids, N(b)-methylajmaline (1), N(b)-methylisoajmaline (2), 3-hydroxysarpagine (3), yohimbinic acid (4), isorauhimbinic acid (5), a new iridoid glucoside, 7-epiloganin (6), and a new sucrose derivative, 6'-O-(3,4,5-trimethoxybenzoyl)glomeratose A (7), together with 20 known compounds. The structures of the new compounds were determined by spectroscopic and chemical means. The inhibitory activities of the selected alkaloids on topoisomerase I and II and their cytotoxicity against the human promyelocytic leukemia (HL-60) cell lines were assessed.

Three isocoumarins and a benzofuran from the cultured lichen mycobionts of Pyrenula sp.

The spore-derived mycobionts of the lichen Pyrenula sp. were cultivated on a malt-yeast extract medium supplemented with 10% sucrose. The investigation of their metabolites resulted in isolation of four compounds, three isocoumarins and a biogenetically related benzofuran; their structures were determined by spectroscopic methods.

Flavonoid glycosides from Adina racemosa and their inhibitory activities on eukaryotic protein synthesis.

From the dried leaves, flowers, and twigs of Adina racemosa, five new flavonoid glycosides, quercetin 3-O-alpha-l-rhamnopyranosyl(1-->6)-(3-O-trans-p-coumaroyl)-beta-d-galactopyranoside (1), quercetin 3-O-alpha-l-rhamnopyranosyl(1-->6)-[(4-O-trans-p-coumaroyl)-alpha-l-rhamnopyranosyl(1-->2)]-(4-O-trans-p-coumaroyl)-beta-d-galactopyranoside (2), kaempferol 3-O-alpha-l-rhamnopyranosyl(1-->6)-[(4-O-trans-p-coumaroyl)-alpha-l-rhamnopyranosyl(1--> 2)]-(4-O-trans-p-coumaroyl)-beta-d-galactopyranoside (3), quercetin 3-O-alpha-l-rhamnopyranosyl(1-->6)-[(4-O-trans-p-coumaroyl)-alpha-l-rhamnopyranosyl(1-->2)]-(3-O-trans-p-coumaroyl)-beta-d-galactopyranoside (4), and quercetin 3-O-alpha-l-rhamnopyranosyl(1-->6)-[(4-O-trans-caffeoyl)-alpha-l-rhamnopyranosyl(1-->2)]-(3-O-trans-p-coumaroyl)-beta-d-galactopyranoside (5), and eight known compounds were isolated. The structures of the new compounds were determined by spectroscopic and chemical means. Their inhibitory activities on protein synthesis were assessed. The new glycosides were found to be inhibitors of eukayrotic, but not prokaryotic, protein synthesis.

Two triterpenoid saponins from Neonauclea sessilifolia.

From the dried roots of Neonauclea sessilifolia (Rubiaceae), two new triterpenoid saponins, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-quinovopyranosyl quinovic acid (1) and 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-quinovopyranosyl pyrocincholic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (2), were isolated, together with five known saponins. The structures of the new saponins were determined by spectroscopic and chemical means.

Six secoiridoid glucosides from Adina racemosa.

Six novel secoiridoid glucosides, adinosides A (1), B (2), C (3), D (4), E (5), and grandifloroside 11-methyl ester (6) were isolated, together with 27 known compounds, from the dried leaves, flowers, and twigs of Adina racemosa. The structures of the new compounds were determined by spectroscopic (NMR, MS) and chemical means.

Characterization of a cAMP-dependent protein kinase catalytic subunit from rainbow trout spermatozoa.

The cyclic AMP-dependent phosphorylation of proteins is essential for the initiation of sperm motility in salmonid fishes. This study isolated cDNA for the catalytic subunit of a cAMP-dependent protein kinase (PKA-C) from rainbow trout testis. The deduced amino acid sequence shows 75-80% identity to sequences previously reported in other organisms. However, the N-terminal regions of PKA-C from the testis as well as ovary in the trout appear slightly shorter than those from other tissues, suggesting that small PKA-C might be specific to germ cells. An immunofluorescence study using polyclonal antibody against trout testis PKA-C shows that it localizes along sperm flagellum. Furthermore, immunoelectron microscopy revealed that PKA-C is anchored to the outer arm dynein of flagellar axonemes. These results suggest that PKA-C is involved in regulating the flagellar motility of sperm via phosphorylation of a subunit of the outer arm dynein.

Two chromone-secoiridoid glycosides and three indole alkaloid glycosides from Neonauclea sessilifolia.

From the dried roots of Neonauclea sessilifolia, two new chromone-secoiridoid glycosides, sessilifoside and 7"-O-beta-D-glucopyranosylsessilifoside, and three novel indole alkaloid glycosides, neonaucleosides A, B, and C, were isolated along with the main known glycosides, 5-hydroxy-2-methylchromone-7-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside, sweroside, loganin, grandifloroside, and quinovic acid 3 beta-O-beta-D-quinovopyranoside-28-O-beta-D-glucopyranoside. The structures of these new glycosides were determined by spectroscopic and chemical means. Neonaucleoside A and its C-3 epimer were prepared from secologanin and tryptamine.

Flavonoid glycosides from Rhazya orientalis.

Six new flavonoid glycosides, quercetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(4-O-trans-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (1), quercetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(3-O-trans-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (2), isorhamnetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(4-O-trans-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (3), isorhamnetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(3-O-trans-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (4), isorhamnetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(4-O-cis-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (5), and isorhamnetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(4-O-trans-feruloyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (6), were isolated from the dried aerial parts of Rhazya orientalis. The structures of 1-6 were determined by spectroscopic and chemical means.

Tetrahydroisoquinoline-monoterpene glycosides from Cephaelis acuminata.

From the dried roots of Cephaelis acuminata, five tetrahydroisoquinoline-monoterpene glycosides, 2-O-beta-D-glucopyranosyldemethylalangiside, demethylisoalangiside, 6"-O-beta-D-glucopyranosylipecoside, 6"-O-alpha-D-glucopyranosylipecoside and (4R)-4-hydroxyipecoside, were isolated. The structures of these glycosides were determined by spectroscopic and chemical means.