Effects of mitragynine from Mitragyna speciosa Korth leaves on working memory

Aim of the study: Mitragyna speciosa Korth from Rubiaceae family is a tropical plant indigenous to Southeast Asia particularly in Thailand, Peninsular of Malaysia and Indonesia. The leaves have been used by natives for their opium-like effect and cocaine-like stimulant ability to combat fatigue and enhance tolerance to hard work. However there is no scientific information about the effect of mitragynine on the cognitive performances. This study is designed to examine the working memory effects of mitragynine which is extracted from Mitragyna speciosa mature leaves. Materials and methods: The cognitive effect was studied using object location task and the motor activity in open-field test. Mitragynine 5, 10 and 15. mg/kg and were administered by intraperitoneal (IP) for 28 consecutive days and evaluated on day 28 after the last dose treatment. Scopolamine was used as the control positive drug. Results: In this study there is prominent effects on horizontal locomotor activity was observed. Mitragynine significantly reduced locomotor activity in open-field test compared with vehicle. In object location task mitragynine (5, 10 and 15. mg/kg) did not showed any significances discrimination between the object that had changed position than the object that had remain in a constant position. Conclusion: Our results suggest that chronic administration of mitragynine can altered the cognitive behavioral function in mic

Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression.

Mitragyna speciosa Korth. leaves have been used for decades as a traditional medicine to treat diarrhea, diabetes and to improve blood circulation by natives of Malaysia, Thailand and other regions of Southeast Asia. Mitragynine is the major active alkaloid in the plant. To date, the role of mitragynine in psychological disorders such as depression is not scientifically evaluated. Hence, the present investigation evaluates the antidepressant effect of mitragynine in the mouse forced swim test (FST) and tail suspension test (TST), two models predictive of antidepressant activity and the effect of mitragynine towards neuroendocrine system of hypothalamic- pituitary-adrenal (HPA) axis by measuring the corticosterone concentration of mice exposed to FST and TST. An open-field test (OFT) was used to detect any association of immobility in the FST and TST with changes in motor activity of mice treated with mitragynine. In the present study, mitragynine at dose of 10 mg/kg and 30 mg/kg i.p. injected significantly reduced the immobility time of mice in both FST and TST without any significant effect on locomotor activity in OFT. Moreover, mitragynine significantly reduced the released of corticosterone in mice exposed to FST and TST at dose of 10 mg/kg and 30 mg/kg. Overall, the present study clearly demonstrated that mitragynine exerts an antidepressant effect in animal behavioral model of depression (FST and TST) and the effect appears to be mediated by an interaction with neuroendocrine HPA axis systems

Determination of mitragynine bound opioid receptors

Mitragyna Speciosa Korth from Rubiaceae family is a tropical plant indigenous to Southeast Asia particularly in Thailand, Peninsular of Malaysia and Indonesia. The leaves have been used by natives for their opium-like effect and cocaine-like stimulant ability to combat fatigue and enhance tolerance to hard work. This study is designed to examine the binding affinity and selectivity of mitragynine towards opioid receptors namely µ-, δ-, and κ-receptors and the density of those opioid receptors in brain tissues, spinal cord, duodenum, ileum and vas deferens. Our results suggest that mitragynine has a high affinity to the 9-opioid receptors and brain has the highest density of opioid receptors

AntiHepatitis C Virus Activity of Alectryon serratus Leaves Extract

Hepatitis C Virus (HCV) has infected approximately 2-3% (130-170 million) of the world's population. No vaccine is available to prevent HCV infection. Investigation of anti-HCV agent is thus deemed necessary. Various plants have been explored for their anti-HCV activity. A. serratus is a member of Sapindaceae family, which fruit and seed were traditionally used as insecticide. Anti-HCV activity tested on A.serratus leaves extract has been done. The result showed that leaves extract exhibited anti-HCV with IC50 value of 14.9 μg/ml and 9.8 μg/ml against HCV J6/JFH1 and JFH1a, respectively. The cytotoxicity assay results showed that A.serratus leaves extract was not toxic and has CC50 >100 μg/ml. Mode of action experiment results suggested that A.serratus extract inhibited HCV at the post-entry step. Further fractionation of leaves extract by open column chromatography resulted in 4 fractions. Only Fraction 1 (AP-5F.1) exhibited anti-HCV with IC50 value of 1.2 μg/ml against HCV JFH1a. Separation of AP-5F.1 by open column chromatography resulted in 15 fractions. Fraction number 13 (AP-5F.1.13) exhibited anti-HCV with IC50 value of 0.43 μg/ml against HCV JFH1a. Separation of AP-5F.1.13 by semi preparative-HPLC resulted in isolate identified by TLC and LC-MS method as chlorophyll derivate. There was a possibility that chlorophyll derivate has participated in performing the anti-HCV activity of fractions and extract besides the other compounds contained. In this study, we concluded that A. serratus leaves extract, AP-5F.1, and AP-5F.1.13 exhibited anti-HCV activity against JFH1a virus

ANTIHEPATITIS C VIRUS ACTIVITY OF INDONESIAN MAHOGANY (TOONA SURENI)

 Objective: Toona sureni (Indonesian mahogany) is a member of Meliaceae family and locally known as suren. Previous study reported that T. sureni leaves extract exhibited antiviral activity with 50% inhibitory concentration (IC50) value of 13.9 ± 1.6 μg/ml against hepatitis C virus (HCV) J6/JFH1. Cytotoxicity analysis of T. sureni leaves extract did not reveal any cytotoxicity effect; therefore, further study was taken to investigate the active substances from the extract.Methods: Bioassay-guided isolation of anti-HCV was conducted using Huh-7.5 cells infected with HCV J6/JFH1 in the presence of extracts, fractions, or compounds from the plant.Results: Ethyl acetate fraction (Fr E) exhibited high anti-HCV activity with IC50 value of 1.7 μg/ml. Further, separation of Fr E by open column chromatography resulted in nine sub-fractions (sub-Fr E1-E9). Sub-Fr E3 and E4 have IC50 value of 29.90 μg/ml and 7.68 μg/ml, respectively. Polyphenols compounds have been isolated from sub-Fr E3 and E4. The structures have been determined to be ethyl gallate (1), methyl gallate (2), catechin (3), gallic acid (4), and quercetin 3-O-rhamnoside (5). Among the isolated compounds, gallic acid showed to possess strong anti-HCV activity with IC50 value of 15.9 μg/ml.Conclusion: T. sureni and its isolated compound, gallic acid, may be good candidates to develop for alternative and/or complementary agents of anti-HCV infection

Effects of Mitragynine from Mitragyna Speciosa Korth. Leaves on Working Memory in Mice

Repeated exposure to opiates can lead to deficits in cognitive function. A study in 2000 reported that opioid users have the risk for the brain damage. In the present study,we examined the working memory effects of mitragynine extracted from Mitragyna speciosa mature leaves using object location task and the motor activity in open field test. Mitragynine of the dose 5, 10 and 15 mg/kg were administered intraperitoneally (IP) to mice for 28 consecutive days and evaluated on day 28 after the last dose treatment. Scopolamine was used as the positive control drug. After the completion of behavioral study, mice were sacrificed and the brain was used to evaluate any changes in hippocampal morphology and in the expression of N-Methyl-D-aspartic Acid Receptors-1 (NMDAR1) by using immunohistochemical method. It was observed, that the administration of mitragynine significantly reduced the locomotor acitivity in open-field test compared with vehicle ( p 0.05). The analysis of the results obtained indicated that mice with cognitive impairment will spend more time exploring the familiar object than the novel one. An absence of any difference in the exploration of the two objects during the second phase can be interpreted as a memory deficit. Histological study did not show any morphological changes but immunohistochemical study showed down-regulation in the expression of NMDAR1. Our results suggested that chronic administration of mitragynine may alter the cognitive behavioral function in mice, while preserving the brain morphology

Mouse strain specificity of DAAO inhibitors‐mediated antinociception

Abstract D‐Amino acid oxidase (DAAO) specifically catalyzes the oxidative deamination of neutral and polar D‐amino acids and finally yields byproducts of hydrogen peroxide. Our previous work demonstrated that the spinal astroglial DAAO/hydrogen peroxide (H2O2) pathway was involved in the process of pain and morphine antinociceptive tolerance. This study aimed to report mouse strain specificity of DAAO inhibitors on antinociception and explore its possible mechanism. DAAO inhibitors benzoic acid, CBIO, and SUN significantly inhibited formalin‐induced tonic pain in Balb/c and Swiss mice, but had no antinociceptive effect in C57 mice. In contrast, morphine and gabapentin inhibited formalin‐induced tonic pain by the same degrees among Swiss, Balb/c and C57 mice. Therefore, mouse strain difference in antinociceptive effects was DAAO inhibitors specific. In addition, intrathecal injection of D‐serine greatly increased spinal H2O2 levels by 80.0% and 56.9% in Swiss and Balb/c mice respectively, but reduced spinal H2O2 levels by 29.0% in C57 mice. However, there was no remarkable difference in spinal DAAO activities among Swiss, Balb/c and C57 mice. The spinal expression of glutathione (GSH) and glutathione peroxidase (GPx) activity in C57 mice were significantly higher than Swiss and Balb/c mice. Furthermore, the specific GPx inhibitor D‐penicillamine distinctly restored SUN antinociception in C57 mice. Our results reported that DAAO inhibitors produced antinociception in a strain‐dependent manner in mice and the strain specificity might be associated with the difference in spinal GSH and GPx activity

Anti Hepatitis C virus activity screening on Harpullia arborea extracts and isolated compound

Hepatitis C is a major healthcare problem worldwide. Available therapy for hepatitis C treatment is very expensive and probably not be accessible for all patients. Regarding to this reason, the development of safe and inexpensive antiviral drugs is required. Natural products as a source of new drugs are potential to study. Some antiHCV substances from plants were obtained (Wahyuni, 2013; Adianti, 2014; Aoki, 2014). Harpullia arborea (tulip wood tree) is a member of Sapindaceae family commonly known as kayu pacat in Indonesia (Basuni, 1997). Traditionally, watery exudates from barks and fruits is used as leech repellant, oil extracted from seeds is a source of antirheumatics (Singh, 2011). H.arborea seeds extract also shown antibacterial activities against various strains of bacteria. H.arborea seeds contain glycosides, steroids, saponins and resins (Gowri, 2009). A norhopane triterpenoid also isolated from the leaves of H.arborea (Poovapatthanachart, 2008). This study was conducted to determine antiHCV activity of H.arborea extracts and isolated compound