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Effects of mitragynine from Mitragyna speciosa Korth leaves on working memory

Apryani E, Hidayat MT, Moklas MA, Fakurazi S, Idayu NF

J Ethnopharmacol, 2010 Jun 16;129(3):357-60.
PMID: 20371280 DOI: 10.1016/j.jep.2010.03.036

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 mice.
Therapeutic potential of Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in rats

Sharifudin SA, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P

Pharm Biol, 2013 Mar;51(3):279-88.
PMID: 23043505 DOI: 10.3109/13880209.2012.720993

Moringa oleifera Lam. (Moringaceae) is a rich source of essential minerals and antioxidants; it has been used in human and animal nutrition. The leaves and flowers are being used by the population with great dietary importance.
Fulltext Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system

Shamima AR, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P

Int J Mol Sci, 2012;13(9):11427-42.
PMID: 23109863 DOI: 10.3390/ijms130911427

Cannabinoids and opioids systems share numerous pharmacological properties and antinociception is one of them. Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system. In the present study, the action of MG was investigated as the antinociceptive agent acting on Cannabinoid receptor type 1 (CB1) and effects on the opioids receptor. The latency time was recorded until the mice showed pain responses such as shaking, licking or jumping and the duration of latency was measured for 2 h at every 15 min interval by hot plate analysis. To investigate the beneficial effects of MG as antinociceptive agent, it was administered intraperitoneally 15 min prior to pain induction with a single dosage (3, 10, 15, 30, and 35 mg/kg b.wt). In this investigation, 35 mg/kg of MG showed significant increase in the latency time and this dosage was used in the antagonist receptor study. The treated groups were administered with AM251 (cannabinoid receptor-1 antagonist), naloxone (non-selective opioid antagonist), naltrindole (δ-opioid antagonist) naloxonazine (μ(1)-receptor antagonist) and norbinaltorpimine (κ-opioid antagonist) respectively, prior to administration of MG (35 mg/kg). The results showed that the antinociceptive effect of MG was not antagonized by AM251; naloxone and naltrindole were effectively blocked; and norbinaltorpimine partially blocked the antinociceptive effect of MG. Naloxonazine did inhibit the effect of MG, but it was not statistically significant. These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.
Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression

Idayu NF, Hidayat MT, Moklas MA, Sharida F, Raudzah AR, Shamima AR, et al.

Phytomedicine, 2011 Mar 15;18(5):402-7.
PMID: 20869223 DOI: 10.1016/j.phymed.2010.08.011

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.
Antinociceptive and anti-inflammatory effects of the ethanol extract of Alpinia conchigera rhizomes in various animal models

Sulaiman MR, Zakaria ZA, Mohamad AS, Ismail M, Hidayat MT, Israf DA, et al.

Pharm Biol, 2010 Aug;48(8):861-8.
PMID: 20673172 DOI: 10.3109/13880200903302820

Alpinia conchigera Griff. (Zingiberaceae), locally known to the Malays as "lengkuas ranting", is native to Peninsular Malaysia. The Malays traditionally used it to treat infection and rashes, and as a health drink. This study evaluated the analgesic and anti-inflammatory activities of the ethanol extract of A. conchigera rhizomes in mice and rats, respectively. The analgesic activity was elucidated using the acetic acid-induced writhing test, hot plate test, and formalin test, while the anti-inflammatory activity was determined using carrageenan-induced paw edema. The extract (30, 100, and 300 mg/kg) given intraperitoneally (i.p.) exhibited antinociceptive and anti-inflammatory activities in all tests used. The range of percentage of analgesia obtained for all doses of extract in the writhing test was 50-92%, and in the early and late phases of the formalin test was 25-62% and 63-98%, respectively. In addition, naloxone (5 mg/kg) given subcutaneously (s.c.) was found to reverse the extract (300 mg/kg)-induced antinociceptive activity in the writhing, hot plate, and formalin tests. Based on the results obtained, it can be concluded that the ethanol extract of A. conchigera rhizomes possessed a peripheral and central antinociceptive activity that was mediated, in part, via the opioid receptor, as well as anti-inflammatory activity.
Antinociceptive and anti-inflammatory activities of the aqueous extract of Kaempferia galanga leaves in animal models

Sulaiman MR, Zakaria ZA, Daud IA, Ng FN, Ng YC, Hidayat MT

J Nat Med, 2008 Apr;62(2):221-7.
PMID: 18404328 DOI: 10.1007/s11418-007-0210-3

This study was performed to determine the antinociceptive and anti-inflammatory activities of aqueous extract of Kaempferia galanga leaves using various animal models. The extract, in the doses of 30, 100, and 300 mg/kg, was prepared by soaking (1:10; w/v) the air-dried powdered leaves (40 g) in distilled water (dH(2)O) for 72 h and administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot-plate and formalin tests, with activity observed in all tests occurring in a dose-dependent manner. Furthermore, the antinociceptive activity of K. galanga extract was significantly (P < 0.05) reversed when prechallenged with 10 mg/kg naloxone. The extract also produced a significantly (P < 0.05) dose-dependent anti-inflammatory activity when assessed using the carrageenan-induced paw-edema test. In conclusion, this study demonstrated that K. galanga leaves possessed antinociceptive and anti-inflammatory activities and thus supports the Malay's traditional uses of the plant for treatments of mouth ulcer, headache, sore throat, etc.
Fulltext The combination of mitragynine and morphine prevents the development of morphine tolerance in mice

Fakurazi S, Rahman SA, Hidayat MT, Ithnin H, Moklas MA, Arulselvan P

Molecules, 2013 Jan 04;18(1):666-81.
PMID: 23292329 DOI: 10.3390/molecules18010666

Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.