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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.
Fulltext Involvement of monoaminergic system in the antidepressant-like effect of aqueous extract of Channa striatus in mice

Saleem AM, Taufik Hidayat M, Jais AM, Fakurazi S, Moklas MA, Sulaiman MR, et al.

Eur Rev Med Pharmacol Sci, 2013;17(15):2019-22.
PMID: 23884821

BACKGROUND: In our previous study, the aqueous extract of Channa striatus (family: Channidae) fillet (AECSF) showed an antidepressant-like effect in mice. However, the mechanism of the antidepressant-like effect is unknown.
AIM: The objective of this study was to explore the involvement of monoamines in the antidepressant-like effect of AECSF in mice.
MATERIALS AND METHODS: AECSF was prepared by steaming the fillets of C. striatus. The male ICR mice were pretreated with various monoaminergic antagonists viz., p-chlorophenylalanine (100 mg/kg, i.p.), prazosin (1 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.), SCH23390 (0.05 mg/kg, s.c.) and sulpiride (50 mg/kg, i.p.) followed by treatment with AECSF and tested in tail suspension test (TST). Two-way ANOVA with Tukey test were used at p < 0.05 for significance.
RESULTS: The pretreatments with p-chlorophenylalanine, prazosin and yohimbine, but not with SCH23390 and sulpiride, were able to reverse the antidepressant-like effect of AECSF in TST.
CONCLUSIONS: The antidepressant-like effect of AECSF may be mediated through the serotonergic and noradrenergic systems and not through the dopaminergic system.
Antidepressant-like effect of aqueous extract of Channa striatus fillet in mice models of depression

Saleem AM, Taufik Hidayat M, Mat Jais AM, Fakurazi S, Moklas M, Sulaiman MR, et al.

Eur Rev Med Pharmacol Sci, 2011 Jul;15(7):795-802.
PMID: 21780549

Channa (C.) striatus (Malay-Haruan), is a fresh water snakehead fish, consumed as a rejuvenating diet in post-parturition period in local Malay population. The aqueous extract of C. striatus fillet (AECSF) was reported to act through serotonergic receptor system in a previous study. There is no scientific report on neuropharmacological effects of C. striatus. Based on these data, the antidepressant-like effect of C. striatus was evaluated in mice models of depression.
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.
Anatomical variations of median nerve formation, distribution and possible communication with other nerves in preserved human cadavers

Mat Taib CN, Hassan SN, Esa N, Mohd Moklas MA, San AA

Folia Morphol (Warsz), 2016 09 26;76(1):38-43.
PMID: 27665953 DOI: 10.5603/FM.a2016.0045

Formation, distribution and possible communication of the median nerve are essential to know in treatment and surgeries of various conditions of injuries e.g. repair or reconstruction of the median nerve post traumatic accident. In the present study, 44 upper limbs were dissected. Root forming the median nerve, the median nerve in relation with the axillary artery and communication of the median nerve with other nerves were noted.
Fulltext Possible Epigenetic Role of Vitexin in Regulating Neuroinflammation in Alzheimer's Disease

Yahaya MAF, Zolkiffly SZI, Moklas MAM, Hamid HA, Stanslas J, Zainol M, et al.

J Immunol Res, 2020;2020:9469210.
PMID: 32258178 DOI: 10.1155/2020/9469210

Alzheimer's disease (AD) has been clinically characterized by a progressive degeneration of neurons which resulted in a gradual and irreversible cognitive impairment. The accumulation of Aβ and τ proteins in the brain contribute to the severity of the disease. Recently, vitexin compound has been the talk amongst researchers due to its pharmacological properties as anti-inflammation and anti-AD. However, the epigenetic mechanism of the compound in regulating the neuroinflammation activity is yet to be fully elucidated. Hence, this review discusses the potential of vitexin compound to have the pharmacoepigenetic property in regulating the neuroinflammation activity in relation to AD. It is with hope that the review would unveil the potential of vitexin as the candidate in treating AD.
Fulltext Lipid lowering effect of antioxidant alpha-lipoic Acid in experimental atherosclerosis

Amom Z, Zakaria Z, Mohamed J, Azlan A, Bahari H, Taufik Hidayat Baharuldin M, et al.

J Clin Biochem Nutr, 2008 Sep;43(2):88-94.
PMID: 18818758 DOI: 10.3164/jcbn.2008051

Accumulating data demonstrated that hypercholesterolemia and oxidative stress play an important role in the development of atherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group N, HCD and ALA (n = 6). Group N (normal control) was fed with normal chow, the rest (HCD and ALA) were fed with 100 g/head/day of 1% cholesterol rich diet to induce hypercholesterolemia. Four point two mg/body weight of alpha lipoic acid was concomintantly supplemented to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks. Blood sampling was taken from the ear lobe vein at the beginning, week 5 and week 10. Plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. At the end of the experiment, the animals were sacrificed and the aorta were excised for intimal lesion analysis. The plasma total cholesterol (TC) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the HCD group (p<0.05). Similarly, low level of MDA (p<0.05) in ALA group was observed compared to that of the HCD group showing a significant reduction of lipid peroxidation activity. Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to HCD group. These findings suggested that alpha lipoic acid posses a dual lipid lowering and anti-atherosclerotic properties indicated with low plasma TC and LDL levels and reduction of athero-lesion formation in hypercholesterolemic-induced rabbits.
Plasmodium berghei ANKA Infection in ICR Mice as a Model of Cerebral Malaria

Basir R, Rahiman SF, Hasballah K, Chong W, Talib H, Yam M, et al.

Iran J Parasitol, 2012;7(4):62-74.
PMID: 23323093

Animal models with various combination of host-parasite have long been employed to study malaria pathogenesis. Here, we describe the combination of Plasmodium berghei ANKA infection in inbred ICR mice as a model of cerebral malaria (CM).
Fulltext Biological Properties of Tinospora crispa (Akar Patawali) and Its Antiproliferative Activities on Selected Human Cancer Cell Lines

Zulkhairi A, Abdah MA, M Kamal NH, Nursakinah I, Moklas MA, Hasnah B, et al.

Malays J Nutr, 2008 Sep;14(2):173-87.
PMID: 22691774 MyJurnal

The antioxidant and anti-proliferative activity of the aqueous crude extract of Tinospora crispa stem was investigated. The proximate composition of its stem and leaves was determined. Proximate analysis revealed that T. crispa contains - protein: leaves = 4.7%, stem = 1.2%; fat: leaves = 1.5%, stem = 0.43%; carbohydrate: leaves = 11.8%, stem = 19.4%; ash: leaves = 2.7%, stem = 1.1%; moisture: leaves = 79.3%, stem = 77.9%; fibre: leaves = 1.59%, stem = 0.65%; and energy: leaves = 1.59%, stem = 0.65%. The antioxidant activity of the extract prepared at various temperatures and incubation time was evaluated to determine the optimum extraction procedure. Based on DPPH and TBA tests, the preparation of the extract at 60oC for 6 hours was established as the best possible method as it demonstrated the highest inhibition percentage. The extract was tested against brine shrimp to evaluate its toxicity and no significant toxicity was recorded since the IC50 value was more than 1000 μg/ml. The extract produced moderate anti-proliferative activity on selected human cancer cell lines (IC50 MCF-7: 107 μg/ml, HeLa: 165 μg/ml, Caov-3: 100 μg/ml, and HepG2: 165 μg/ml). The findings from this study suggest that T. crispa has the potential to be a source of natural antioxidants and nutrients, besides having a moderate anti-proliferative effect on selected human cancer cell lines.
Fulltext Modulation of interleukin-18 release produced positive outcomes on parasitaemia development and cytokines production during malaria in mice

Basir R, Hasballah K, Jabbarzare M, Gam LH, Abdul Majid AM, Yam MF, et al.

Trop Biomed, 2012 Sep;29(3):405-21.
PMID: 23018504 MyJurnal

The involvement of interleukin-18 (IL-18) and the effects of modulating its release on the course of malaria infection were investigated using Plasmodium berghei ANKA infection in ICR mice as a model. Results demonstrated that plasma IL-18 concentrations in malarial mice were significantly elevated and positively correlated with the percentage parasitaemia development. Significant expressions of IL-18 were also observed in the brain, spleen and liver tissues. Slower development of parasitaemia was observed significantly upon inhibition and neutralization of IL-18, whereas faster development of parasitaemia was recorded when the circulating levels of IL-18 were further augmented during the infection. Inhibition and neutralization of IL-18 production also resulted in a significant decrease of plasma concentrations of pro-inflammatory cytokines (TNFα, IFNγ, IL-1α and IL-6), whereas the anti-inflammatory cytokine, IL-10, was significantly increased. Augmenting the release of IL- 18 during the infection on the other hand resulted in the opposite. Early mortality in malarial mice was also observed when the circulating levels of IL-18 were further augmented. Results proved the important role of IL-18 in immune response against malaria and suggest that IL-8 is pro-inflammatory in nature and may involve in mediating the severity of the infection through a pathway of elevating the pro-inflammatory cytokine and limiting the release of anti-inflammatory cytokine.