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Background: Resistance training has been widely used in various sports and improves competition performance, especially in swimming. Swimming performance is highly dependent on muscle strength, especially short distances. For adolescent athletes, the existing literature has bound to prove that resistance training is undoubtedly bound to improve swimmers' performance. Objectives: This study adopts a systematic literature review to (1) examine the effects of resistance training on the performance of adolescent swimmers, and (2) summarize their training methods and intensity. Methods: The literature search was undertaken in five international databases: the SCOUPS, PubMed, EBSCOhost (SPORTDiscus), CNKL, Web of Science. The searches covered documents in English and Chinese published until 30th December 2020. Electronic databases using various keywords related to “strength training” and “adolescent swimmers” were searched. Sixteen studies met the inclusion and exclusion criteria where the data was then systematically reviewed using the PRISMA guideline. Furthermore, the physical therapy evidence database (PEDro) scale was used to measure each study's scientific rigor. Results: This review found that to improve the swimming performance of adolescents, two types of resistance training were used, specifically in water and on land, where both types of training can improve swimming performance. In addition, training with two types of resistance machines were better in the water than with one equipment. Resistance training can improve the swimming performance of adolescent swimmers at 50 m, 100 m, 200 m and 400 m distances. However, most studies only focused on the swimming performance at 50 m and 100 m lengths. A low-intensity, high-speed resistance training programme is recommended for adolescent swimmers to obtain the best training results. Conclusion: Water or land resistance training can improve the swimming performance. Given that both types of exercises have their stren

The present study evaluated the effect of Centella asiatica L. Urban (CA) extracts on ultrastructure and oxidative stress parameters on chronic unpredictable mild stress (CUMS) rat’s hippocampi. Rats were divided into six groups (n=6) and treated as follows: Group 1, Unstressed + normal saline (control); Group 2, CUMS + normal saline (Model); Group 3, CUMS + Flx (10 mg/kg) (FLX); Groups 4, CUMS + CA (200 mg/kg) (CA 200); Group 5, CUMS + CA (400 mg/kg) (CA 400) and Group 6, CUMS + CA (800 mg/kg) (CA 800). Nine different stressors were administered to the rats for 8 weeks consecutively, with concurrent administration of fluoxetine or CA. The hippocampi of the rats were evaluated by transmission electron microscopy (TEM) and oxidative stress biomarkers were also determined. Qualitative TEM results showed defective mitochondria, nucleus, myelin sheaths and reduced numbers of synapses in CUMS rats as well as increased oxidative stress biomarkers. Administration of CA prevented some of the structural and biochemical aberrations observed in response to stress in a manner comparable with fluoxetine, a selective serotonin-reuptake inhibitor. Conclusively, CA ameliorates structural defects induced by CUMS in the rat hippocampus, with a potential therapeutic importance in the treatment of stress and depression.

Background: Cannabis and its extracts are now being explored due to their huge health benefits. Although, the effect they elicit, whether on humans or rodents, may vary based on the age of the animal/subject and or the time in which the extract is administered. However, several debates exist concerning the various medical applications of these compounds. Nonetheless, their applicability as therapeutics should not be clouded based on their perceived negative biological actions. Methods: Articles from reliable databases such as Science Direct, PubMed, Google Scholar, Scopus, and Ovid were searched. Specific search methods were employed using multiple keywords: ''Medicinal Cannabis; endocannabinoid system; cannabinoids receptors; cannabinoids and cognition; brain disorders; neurodegenerative diseases''. For the inclusion/exclusion criteria, only relevant articles related to medicinal Cannabis and its various compounds were considered. Results: The current review highlights the role, effects, and involvement of Cannabis, cannabinoids, and endocannabinoids in preventing selected neurodegenerative diseases and possible amelioration of cognitive impairments. Furthermore, it also focuses on Cannabis utilization in many disease conditions such as Alzheimer's and Parkinson's disease among others. Conclusion: In conclusion, the usage of Cannabis should be further explored as accumulating evidence suggests that it could be effective and somewhat safe, especially when adhered to the recommended dosage. Furthermore, in-depth studies should be conducted in order to unravel the specific mechanism underpinning the involvement of cannabinoids at the cellular level and their therapeutic applications.

Pathophysiology of postpartum depression (PPD) has been associated with many factors, such as neuroendocrine, neuroinflammation and neurotransmitter changes. Fish oil (FO) improves PPD both in humans and animals. However, little is known with regards to its pharmacology on a PPD-like rat model. Hence, the current study aimed at investigating the effects of FO on a PPD-like rat model. Female rats were induced with PPD-like symptoms and then randomly divided into six groups (n = 6) for two experimental protocols. Protocol 1 consisted of PPD-like rats (2 mL distilled water), PPD-like + FO (9 g/kg/d) and PPD-like + Fluoxetine (FLX) (15 mg/kg/d) groups of rats, whereas Protocol 2 consisted of PPD-like rats (2 mL distilled water) + PCPA (p-chlorophenylalanine) 150 mg/kg, PPD-like + FO (9 g/kg/d) + PCPA 150 mg/kg and PPD-like + FLX (15 mg/d) + PCPA 150 mg/kg groups of rats, respectively. All treatments were administered orally for 10 days postpartum, except PCPA, which was given intraperitoneally. Prior to euthanasia, the antidepressant-like effect of the FO was evaluated using the forced swimming test (FST) and open field test (OFT) on day 10 postpartum. Biochemical analysis of serotonin, serotonin metabolite and serotonin turnover from their prefrontal cortex and hippocampus were also measured. The results showed that FO decreased immobility time and increased swimming time significantly, but not climbing time in FST. Further, it also decreased serotonin metabolite and turnover significantly in the hippocampus of the PPD-like rats. In contrast, administration with PCPA reversed all the outcomes. The antidepressant-like effects of FO were found to be similar with that of FLX. Thus, it can be concluded that FO exerts its antidepressant-like effects in PPD-like rats through modulation of serotonergic system.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl3-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl3 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats’ was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl3 exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl3 improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations.

Background: The nootropic or simply known as smart drug is a common term given to any compound that is responsible for enhancing mental capability or performance. Alzheimer's disease is characterized clinically by lose of cognitive abilities and pathologically by two hallmark lesions, neurofibrillary tangles and senile plaques. It is unfortunate that AD has no cure yet. In this review attempt has been made to elucidate the general views on AD pathogenic hypotheses and common nootropics being used in AD research. Methods: Articles from credible scientific data bases such as Sciencdirect, Scopus Pubmed, and Google scholar were searched and retrieved using keywords nootropics', Alzheimer's disease', amyloid beta hypotheses', tau hypotheses', cholinergic hypotheses', oxidative stress' and cognitive impairments'. Results: The nootropics act as Ca-channel blockers, AChE inhibitors, glysine antagonists, antioxidants, serotonergic, dopaminergic and glutamic acid receptors antagonists. Conclusion: Based on the available literature searched, there is no doubts the nootropics are attenuating cognitive deficits in both preclinical and clinical studies on AD.

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent, while aluminium is a known neurotoxin linked to pathogenesis of AD. The combined administration of rats with d-gal and aluminium chloride (AlCl3) is considered to be an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explored the protective effects of CA on cognition and brain ultrastructure in d-gal and AlCl3 induced rats. Materials and methods: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl’s staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes. Results: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil. Conclusion: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA.

Alzheimer's disease (AD) is the most frequent and multifactorial form of dementia, characterised by multiple cognitive impairments and personality changes. Different methods including chemicals have been used to induce AD-like symptoms in rodent in order to screen many therapeutic drugs for a variety of cognitive dysfunctions. Articles from reliable databases such as Google Scholar, Science Direct, PubMed, Scopus, and Ovid were searched and retrieved with the following descriptors: 'Alzheimer's Disease', Cognitive impairments', Neurotoxins that induce AD', Alzheimerogenic chemicals', excitotoxins', Amyloid beta', neurofibrillary tangles. A number of chemicals have been studied to develop an animal model of AD on the basis of their mechanism of action for cognitive dysfunctions. Some of such chemicals are Heavy metals, Scopolamine, Ethanol, Colchicine, Streptozotocin, Lipopolysaccharide, and Okadaic acid among others, with a view to understanding the pathogenesis of this devastating disease. The purpose of this review is to put forward some AD pathophysiology including AD causative theories and also highlight some Alzheimerogenic chemicals for the purpose of enriching our existing knowledge. It is worth mentioning that not all the biochemical, histopathological, cognitive and behavioural abnormalities can be recapitulated. Nonetheless, experimental models of AD produced by chemicals offer insights to unravelling the pathogenesis of the disease.

Cognitive impairments and cholinergic dysfunctions have been well reported in old age disorders including Alzheimer’s disease (AD). d-galactose (D-gal) has been reported as a senescence agent while aluminium act as a neurotoxic metal, but little is known about their combined effects at different doses. The aim of this study was to establish an animal model with cognitive impairments by comparing the effects of different doses of co-administrated D-gal and aluminium chloride (AlCl3). In this study male albino wistar rats were administered with D-gal 60 mg/kg.bwt intra peritoneally (I.P) injected and AlCl3 (100, 200, or 300 mg/kg.bwt.) was orally administered once daily for 10 consecutive weeks. Performance of the rats were evaluated through behavioural assessments; Morris water maze (MWM) and open field tests (OFT); histopathological examination was performed on the hippocampus; moreover biochemical measurements of acetylcholinesterase (AChE) and hyperphosphorylated tau protein (p-tau) were examined. The results of this experiment on rats treated with D-gal 60 + AlCl3 200 mg/kg.bwt showed near ideal cognitive impairments. The rats exhibited an obvious memory and learning deficits, marked neuronal loss in hippocampus, showed increase in AChE activities and high expression of p-tau within the tissues of the brain. This study concludes that D-gal 60 + AlCl3 200 mg/kg.bwt as the ideal dose for mimicking AD like cognitive impairments in albino wistar rats. It is also crucial to understand the pathogenesis of this neurodegenerative disease and for drug discovery.

Ergogenic aids usage by athletes is a common scenario that can be seen in any level of athletes and any types of sports nowadays. Ergogenic aids can range from drugs, food, hormone, mechanical aid and herbs. Traditionally, ergogenic aids can be classified into categories namely: physiological, psychological, mechanical, pharmacological and nutrition. Despite all these classification, all ergogenic aids had one common purpose, which is to improve physical performance. Herbs consumption as ergogenic aids had been practiced since years ago by athletes as either nutritional or pharmacological aids. Using herbs as physical performance booster has gained popularity since it was claimed safer and natural. One of local herb that gets attention as energy booster is Ficus deltoidea (Mas Cotek). Ficus deltoidea had been used traditionally to restore energy. Few studies had reveal that Ficus deltoidea had medicinal properties such anti-nociceptive, antioxidant, wound healing enhancer and blood glucose regulation properties. There is no direct study on Ficus deltoidea as energy booster or ergogenic aids, but this medicinal value might be beneficial to increase athlete’s physical performance. Ergogenic aids, especially those that been produce using herbs, rarely have scientific evidence to determine its effectiveness, safety, dosage and mechanism of action. Ergogenic aids were normally marketed with claims and report as their reference, not scientific evidence. The most frequent claim used by traders is that ergogenic aids can increase and sustain body’s energy. This review will discuss on how ergogenic aids might help athletes to increase their physical performance and possibility of using Ficus deltoidea as ergogenic aids based on its medicinal properties.

Medicinal herbalism has become popular because of its documented efficacy, synergistic interactions against complex conditions and lesser side effects. CA (CA) is a traditional Ayurveda medicine widely used in India, China, and Malaysia and across countries in south-eastern Asia for treating a range of diseases. The whole plant or its parts (leaf or roots) are used for medicinal purpose and its chemical constituents have been proven scientifically to have neuro-protective, wound healing, anti-inflammatory and antioxidants activities. In this review we have retrieved and evaluated available literatures on neuro-therapeutic properties of CA on neurotoxic and transgenic models of Alzheimer’s diseases (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). The extract was found to have neuroprotective ability through modifying a key signaling pathways and events concerned with neuro-degeneration. Further research is required to discover more bioactive compounds of CA and their exact mode of action.

This study evaluated the antidepressant-like effect of lipid extract of C. striatus in chronic unpredictablemild stress (CUMS)model of depression in male rats and its mechanism of action. The animals were subjected to CUMS for six weeks by using variety of stressors. At the end of CUMS protocol, animals were subjected to forced swimming test (FST) and open field test followed by biochemical assay. The CUMS protocol produced depressive-like behavior in rats by decreasing the body weight, decreasing the sucrose preference, and increasing the duration of immobility in FST. The CUMS protocol increased plasma corticosterone and decreased hippocampal and prefrontal cortex levels of monoamines (serotonin, noradrenaline, and dopamine) and brain-derived neurotrophic factor. Further, the CUMS protocol increased interleukin-6 (in hippocampus and prefrontal cortex) and nuclear factor-kappa B (in prefrontal cortex but not in hippocampus).The lipid extract of C. striatus (125, 250, and 500mg/kg) significantly (

Erythroxylum cuneatum has been traditionally proven to possess beneficial properties in treating drug addiction and other illness. Due to less information on this plant, this elusive plant was investigated further to evaluate the in vivo toxicity profile of the plant and to investigate the effect of E. cuneatum on cognitive performance in rats. Two different extracts were produced from the leaves of E. cuneatum which were aqueous and alkaloid extracts. Acute in vivo toxicity test was evaluated in ICR mice to determine their medium lethal dose 50 value. In the in-vivo toxicity study, aqueous extract showed the almost similar toxic effect as alkaloid extract which was 416.86 mg/kg for alkaloid extract and 316.23 mg/kg for aqueous extract. These findings suggesting that aqueous and alkaloid extracts showed toxic effects at the high dose, thus safe at a low dose. Working memory task using novel object discrimination test (NOD) was performed for the determination of neurobehavioral profiles. In the NOD test, alkaloid-treated rats did not show any significant discrimination between the familiar and novel object (P > 0.05); thus it can be interpreted as not induce a memory defi cit. It can also be postulated that the extract has no effect on memory and learning neither improvises nor impairs the cognitive function. In conclusion, since E. cuneatum does not show any impairment on cognitive, its pharmacological properties could be further investigated without significant changes in cognitive performance.

Punica granatum L. (pomegranate) is commonly known for its traditional use as a food supplement and for its medicinal values. P. granatum methanolic pulp and peel extract were investigated for its antidepressant activities on mice model of depression using tail suspension test (TST) and forced swimming test (FST). P. granatum pulp and peel extract were administered at doses of 25 and 50 mg/kg intraperitoneally, respectively while fluoxetine (20 mg/kg) was administered intraperitoneally as the standard drug. The results showed that P. granatum pulp extract at 25 mg/kg significantly exhibited antidepressant activity in both TST and FST which able to reduce the immobility time, similar to fluoxetine, a recognized antidepressant drug. It is concluded that P. granatum methanolic extract has the ability as antidepressant-like agent. Further research is required to investigate the exact pharmacological mechanism of action of this fruit.

Haruan fish is a fresh water carnivorous fish popularly known in tropical countries like Malaysia, Thailand and Indonesia. The aqueous extract of the fish contains omega-3 fatty acids, namely, eicosapentaenoic acids (EPA) and deicosahexaenoic acids (HA). These fatty acids possess cytotoxic effects. Here we study the cytotoxic effects of the extract on neuroblastoma cancer cell line, SK-N-SH cells, MTI assay, phase contrast microscopy and flow cytometry were the methods used to determine the cytotoxic effects of the extract. For MTT assay, the cells were treated with different concentrations of the extract range from 3.125 µg/ml to 100 µg/ml. For the phase contrast microscopy and flow cytometry, 100 µg/ml of the extract was adopted as the concentration used for the treatment of the cells prior to observation and recording of results. From MTT assay, cell visibility of 68.8% were recorded, indicating lack of cytotoxic effect. The result for phase contrast microscopy showed no clear different between treated and control group, supporting the MTT result. However, flow cytometry results indicates significant (P < 0.05) apoptosis when control cells were compared with treated ones. Aqueous haruan fish extract possess mild cytotoxic effects on SK-N-SH cells.

Cobalt-60 (Co-60) is a relatively new source for the application of high-dose rate (HDR) brachytherapy. Radiation dose to the rectum is often a limiting factor in achieving the full prescribed dose to the target during brachytherapy of cervical cancer. The aim of this study was to measure radiation doses to the rectum in-vivo during HDR Co-60 brachytherapy. A total of eleven HDR brachytherapy treatments of cervical cancer were recruited in this study. A series of diodes incorporated in a rectal probe was inserted into the patient's rectum during each brachytherapy procedure. Real-time measured rectal doses were compared to calculated doses by the treatment planning system (TPS). The differences between calculated and measured dose ranged from 8.5% to 41.2%. This corresponds to absolute dose differences ranging from 0.3 Gy to 1.5 Gy. A linear relationship was observed between calculated and measured doses with linear regression R2 value of 0.88, indicating close association between the measured and calculated doses. In general, absorbed doses for the rectum as calculated by TPS were observed to be higher than the doses measured using the diode probe. In-vivo dosimetry is an important quality assurance method for HDR brachytherapy of cervical cancer. It provides information that can contribute to the reduction of errors and discrepancies in dose delivery. Our study has shown that in-vivo dosimetry is feasible and can be performed to estimate the dose to the rectum during HDR brachytherapy using Co-60.

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.

Mitragyna speciosa, a plant from Rubiaceae family, was reported to have an opium-like effect and their coca-like stimulative ability to combat fatigue and enhance tolerance to hard work. There are lack of information regarding to the effect of Mitragyna speciosa on cognitive and behavioural performances. Therefore the project was conducted to observe the effect of Mitragyna speciosa on cognitive behavior of rats and mice. Mitragyna speciosa in methanol extract form and aqueous extract form with same dosage distributions were used; 10 mg/kg, 30 mg/kg, and 100 mg/kg. Four tests were conducted to observe the behavioural changes of the animal namely locomotor, cognitive performances, anxiety and rotarod performance. Results showed that all dosage of treatment reduced locomotor and impaired cognitive performance significantly. Study showed that Mitragyna speciosa induce sedative effect in dose dependant manner. Interestingly, Mitragyna speciosa increased the time spent in open arm of plus maze indicating low anxiety level of the rodent. As conclusion, Mitragyna speciosa caused sedative effect, impairment in working memory, and possess anxiolytic properties.

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.

Background and Objectives: 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. Materials and Methods: AECSF was prepared by steaming the fillets as described previously. Antidepressant activity was studied in male ICR mice using forced swimming test (FST) and tail suspension test (TST). Open-field test was used to evaluate any psychomotor stimulant activity. AECSF was administered intraperitoneally at the concentrations of 30%, 40% and 50% w/v at the dosage of 10 ml/kg. Amitriptyline (10 mg/kg) was used as positive control. Results: All the three concentrations of AECSF (30%, 40% and 50% w/v) significantly reduced the immobility time (p < 0.001) in FST and TST. All the three concentrations of AECSF (30%, 40% and 50% w/v) significantly (p < 0.001) reduced locomotor activity in a dose-dependent manner in open-field test. Conclusions: AECSF produced significant reduction of immobility time in both FST and TST. Amitriptyline produced a significant reduction of immobility time in both FST and TST similar to previous findings. The AECSF produced a dose-dependent decrease in locomotor activity in the open-field test. This hypolocomotion effect indicated the absence of any psychomotor stimulant activity thereby supporting the antidepressant-like effect of the AECSF. The pharmacological mechanisms of the observed antidepressant-like effect and hypolocomotion effect are not understood from our study. Hence, further studies are required.

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.

The present invention relates to methods and compositions to counter the side effects of analgesic treatments with opioids such as morphine. Provided are novel treatment regimes comprising the administration of mitragynine for the prevention, reversal and/or delay of the progression and/or development of a tolerance of a subject against the pharmaceutical effects of an opiate. Also comprised by the present invention are therapeutic means for the treatment of severe or chronic pain using a combination of mitragynine and opiates, as well as pharmaceutical compositions comprising the compounds of the present invention.

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

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 300mg/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 5092%, and in the early and late phases of the formalin test was 2562% and 6398%, respectively. In addition, naloxone (5mg/kg) given subcutaneously (s.c.) was found to reverse the extract (300mg/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.

Introduction: Hypercholesterolemia is the major cause of cardiovascular disturbances. The influence of Tinospora crispa on atherosclerotic plaque formation in rabbits fed with high cholesterol diet was investigated. Methods: Thirty male New Zealand White rabbits were divided into 6 groups. The negative control (NC) and positive control (PC) groups were used as a negative and positive (0.5% cholesterol) control. The simvastatin control (SC) group was given a high cholesterol diet (HCD) with 5mg/kg simvastatin. Treatment groups T150 and T450 were given HCD with supplementation of 150,300 and 450mg/kg of T.crispa extract respectively for 10 weeks. Blood was collected from ear vein for plasma analysis while the aortas were excised and examined microscopically. Results: Comparison within groups showed that PC, T300 and T450 had a significant increase (p<0.05) in total cholesterol level throughout the study. The groups supplemented with T.crispa (T150, T300 and T450) were significantly higher (p<0.05) in high density lipoprotein (HDL) level by 10.7-fold, significantly higher (p<0.05) in total antioxidant activity and had a significantly lower (p<0.05) LDL level compared to PC at week 10. At week 10, T450 had significantly highest (p<0.05) glutathione peroxidase and superoxide dismutase levels compared to PC. No foam cell formation was visible in the aorta of rabbits,in groups NC,SC and T450. However , there was visible foam cell formation in the aorta of groups PC, T150 and T300. Conclusion: This study suggest that supplementation of 450mg/kg of T.crispa extract would be able to reduce or retard the progression of atherosclerotic plaque development induced by dietary cholesterol.

OBJECTIVES: To determine the anti-inflammatory and antinociceptive activities of Mitragyna speciosa Korth methanol extract in rodents. Materials and METHODS: Anti-inflammatory activity was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma tests in rats. Antinociceptive activity was measured using the writhing test and the hot plate test in mice, and the formalin test in rats. All drugs and extracts were diluted in dH(2)O and administered through the intraperitoneal route. Results were analyzed using one-way ANOVA followed by Dunnett's test for multiple comparisons among groups. RESULTS: Results showed that intraperitoneal administration of the extract at doses of 100 and 200 mg/kg produced significant dose-dependent activity in all of the nociceptive models evaluated (p < 0.05). With the formalin test, the antinociceptive activity in mice was inhibited only at the highest dose of the extract (200 mg/kg). The study also showed that intraperitoneal administration of the methanol extract of M. speciosa (100 and 200 mg/kg) significantly and dose-dependently suppressed the development of carrageenan-induced rat paw edema (p < 0.05). In the chronic test, however, significant reduction in granulomatous tissue formation in rats was observed only at the highest dose of the methanol extract of M. speciosa (200 mg/kg, p < 0.05). CONCLUSION: The present study suggests the presence of potent antinociceptive and anti-inflammatory principles in the extract, supporting its folkloric use for the treatment of these conditions.

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.

There is accumulating data demonstrated 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 K, AT and ALA (n=6). While group K was fed with normal chow and acted as a control, the rest fed with 100 g/head/day with 1% high cholesterol diet to induce hypercholesterolemia. 4.2 mg/body weight of alpha lipoic acid was supplemented daily 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 of the study, week 5 and week 10 and plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. Animals were sacrificed at the end of the study and the aortas were excised for intimal lesion analysis. The results showed a significant reduction of lipid peroxidation index indicated with low MDA level (p<0.05) in ALA group compared to that of the AT group. The blood total cholesterol (TCHOL) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the AT group (p<0.05). Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to that of AT group. These findings suggested that apart from its antioxidant activity, alpha lipoic acid may also posses a lipid lowering effect indicated with low plasma TCHOL and LDL levels and reduced the athero-lesion formation in rabbits fed a high cholesterol diet.

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 (dH2O) 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.