Study on regulatory effect of Kaixin San on endogenous melatonin biosynthesis in rat depression model / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of Kaixin San on the rate-limiting enzyme in biosynthesis of melatonin (MT) and pineal body in rat depression model.</p><p><b>METHOD</b>The unpredictable chronic mild stress was used to establish the rat depression model for 21 days. The rats were divided into the normal control group, the model group, Kaixin San low, medium and high dose groups (KXS 65, 130, 260 mg x kg x d(-1)) and the trazodone group. All groups were administered at 30 min after modeling each day. Rats were sacrificed and the pineal glands were isolated immediately after acquisition tail venous blood at 2:00a. m on the 22nd day. The plasma was analyzed for melatonin content by using a rat metabolic panel Milliplex kit. The pineal glands were analyzed for AANAT and HIOMT mRNA levels by Real-time quantitative PCR and for AANAT and HIOMT activity by a radiometric assay simultaneously.</p><p><b>RESULT</b>The plasma MT concentration, expression of AANT and HIOMT mRNA, activity of AANAT in rat pineal glands of the model group were significantly lower than the control group (P < 0.05), but the activity of HIOMT showed not change. Compared with the model group, all of Kaixin San groups showed increase in MT concentration in plasma (P <0. 05) , with the medium dose group revealing the highest level. Besides, the medium dose group displayed significant increase in AANAT, HIOMT mRNA level and AANAT activity (P < 0.05), but no increase in HIOMT activity.</p><p><b>CONCLUSION</b>Kaixin San can regulate AANAT activity of pineal bodyand regulate MT biosynthesis in rat depression model.</p>

Genetic transformation of Nicotiana tabacum L. by Agrobacterium tumefaciens carrying genes in the melatonin biosynthesis pathway and the enhancement of antioxidative capability in transgenic plants / 生物工程学报

Arylalkylamine N-acetyltransferase (AANAT) and Hydroxyindole O-methyltransferase(HIOMT) are the key regulation enzymes in the melatonin biosynthesis pathway in mammals. The AANAT and HIOMT genes were constructed into a binary plant expression vector YXu55. Using leaf strips as the recipiences, we efficiently transformed tobacco (Nicotiana tabacum) variety qinyan 95 by the Agrobacterium mediated method. After gradient selection with gentamycin, a number of transgenic plants were regenerated. Southern blot and RT-PCR analyses showed that the AANAT-HIOMT genes were integrated into the genome of the transgenic plants and the target genes could express at the level of RNA transcription. By RP-HPLC, we measured the melatonin contents in transgenic plants. The results showed that the melatonin level in YXu55 (containing the gentamycin-resistance gene, the AANAT gene and HIOMT gene) transgenic plants were much higher than those in pZP122 (control containing only the gentamycin-resistance gene) transgenic plants and nontransgenic plants. The content of melatonin in pZP122 transgenic plants was nearly the same as that in nontransgenic plants. Physiological determination of antioxidative characteristics demonstrated that 1) the capacity of total antioxidation, 2) the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) and 3) the content of glutathione (GSH) were increased in YXu55 transgenic plants containing the AANAT-HIOMT genes as compared to the control plants (pZP122 or nontransgenic plants). At the same time, malonaldehyde (MDA) content did not appear remarkably difference between transgenic plants and nontransgenic plants. The above mentioned facts indicate enhancement of melatonin levels in YXu55 transgenic plants might help to reduce damage by oxidative stress.

Efeito neuroprotetor da melatonina e N-acetilserotonina na epileptogênese e no controle de crises em animais submetidos ao modelo da pilocarpina / Neuroprotector effect of melatonin and N-acetilserotonin in the epileptogenesis and in the control of seizures in animals submitted to the pilocarpine model

PURPOSE: The aim of this research was to study the effects of treatment with melatonin and N-acetilserotonin in the development of pilocarpina model of epilepsy in adult male rats. METHODS: Part I - The animals were divided in 4 groups: SALINE - animals that received only saline; SE - animals submitted to status epilepticus (SE); NAS + SE - animals that received pre-treatment with N-acetylserotonin and were submitted to SE and MEL + SE - animals that received pre-treatment with melatonin and were submitted to SE. Part II - The animals were divided in 6 groups: SALINE - animals that received only saline; SE - animals submitted to status epilepticus (SE); PX + SE - animals submitted to pinealectomy and to SE 7 days later; SH + SE - animals submitted to sham-surgery and to SE 7 days later; SE + NAS - animals submitted to SE and treated with N-acetylserotonin (2,5 mg/kg), 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h and 48 h after the SE and SE + MEL - animals submitted to SE and treated with melatonin (2,5 mg/kg), 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h and 48 h after the SE. Following the treatment the animals were continuously video-recorded for 60 days. The behavioral parameters were observed: latency for the SE in minutes, latency for the first spontaneous seizures (ie, duration of the silent period), number of spontaneous seizures during the chronic period and mortality. Five animals per group were perfused for neo-Timm assay. RESULTS: Part I - The animals treated with melatonin and N-acetylserotonin presented an increased of latency for the status epilepticus and decreased number of spontaneous seizures during the chronic period when compared to SE group. The mortality was reduced 100 percent in animals treated with melatonin and theses animals presented a minor mossy fibers sprouting. Part II - The latency for the first spontaneous seizures and mortality were similar in all groups. The animals treated with melatonin presented...

Melatonin and N-acetyl-serotonin cross the red blood cell membrane and evoke calcium mobilization in malarial parasites

The duration of the intraerythrocytic cycle of Plasmodium is a key factor in the pathogenicity of this parasite. The simultaneous attack of the host red blood cells by the parasites depends on the synchronicity of their development. Unraveling the signals at the basis of this synchronicity represents a challenging biological question and may be very important to develop alternative strategies for therapeutic approaches. Recently, we reported that the synchrony of Plasmodium is modulated by melatonin, a host hormone that is synthesized only during the dark phases. Here we report that N-acetyl-serotonin, a melatonin precursor, also releases Ca2+ from isolated P. chabaudi parasites at micro- and nanomolar concentrations and that the release is blocked by 250 mM luzindole, an antagonist of melatonin receptors, and 20 mM U73122, a phospholipase C inhibitor. On the basis of confocal microscopy, we also report the ability of 0.1 æM melatonin and 0.1 æM N-acetyl-serotonin to cross the red blood cell membrane and to mobilize intracellular calcium in parasites previously loaded with the fluorescent calcium indicator Fluo-3 AM. The present data represent a step forward into the understanding of the signal transduction process in the host-parasite relationship by supporting the idea that the host hormone melatonin and N-acetyl-serotonin generate IP3 and therefore mobilize intracellular Ca2+ in Plasmodium inside red blood cells.

Pineal serotonin N - acetyltransferase and hydroxyindole - 0 - methyltransferase activities in vizcacha (Lagostomus maximus maximus) maintained under various photoperiods

Este trabajo tiene como propósito estudiar las actividades de las enzimas NAT y HIOMT en glándula pineal de vizcacha, bajo distintos regímenes de iluminación. La actividad de NAT presentó marcada variación diaria en los animales mantenidos en condiciones de LD 12:12, permaneciendo descendida durante las horas de iluminación y siendo máxima en oscuridad. En oscuridad permanente aumenta significativamente y se anulan las variaciones diarias de NAT. La actividad de HIOMT en pineal de vizcachas mantenidas en LD 12:12 no presentó ritmos diarios; en iluminación la actividad desciende, no recuperándose en la etapa de oscuridad. En el lote de oscuridad permanente se observó un marcado aumento, mientras que en iluminación permanente descendió a 1/7 de los valores encontrados en oscuridad. En iluminación natural día-noche la HIOMT recuperó su actividad en las horas de oscuridad. Concluimos que en este roedor la actividad de las enzimas estudiadas es afectada por la luz, siendo la HIOMT la más sensible