A pinboard by
Oritoke Aluko

Assistant Lecturer, Federal University of Technology, Akure, Nigeria


The pre and post synaptic modulations offered by methyl jasmonate in rats' brains are being studied.

My research focus in neuroscience is the study of the relationship between stress and pathogenesis of neuropsychiatric disorders, and testing a variety of anti-stress natural and synthetic compounds to ameliorate the impact of stressors on brain functions. I primarily study the effects of chronic stress on behavioral alterations, markers of oxidative stress, levels of expressions of neurochemical substrates, regional expression of pre-and post-synaptic markers of neurotransmitters involved in stress response. Partially extracted and identified local natural compounds are investigated for their ability to reduce or inhibit oxidative stress and neuroinflammation and thus may be beneficial as alternatives for the treatment of stress-induced neurodegenerative disorders prevalent in my community.

Currently, I am investigating methyl jasmonate, which is a natural plant hormone synthesized and released by plants when exposed to stressors. Methyl jasmonate was originally obtained from the beautiful flower, Jasminum grandiflorum, but is now available in synthetic form. Methyl jasmonate is considered to be safe, as it is present in food, fruits, and vegetables such as rice and tomatoes. We hypothesize that methyl jasmonate will perform the same stress-modulatory function in humans, as it does in plants.

This investigation is being carried out in rodents such as mice and rats, and utilizing a model of chronic stress called the unpredictable chronic mild stress paradigm. This model mimics the way humans undergo stress in an unpredictable manner. The rodents are exposed to different stressors at varying times and duration in the day. This is done for 28 consecutive days along with various doses of the treatment.

Thereafter, the rodents are tested for various behaviors such as stability, locomotion, memory, anxiety, and depression. Blood samples are also taken for measurement of glucose, corticosterone and lipid levels. The brains are removed for biochemical analysis such as the levels of various markers of oxidative stress. The histological examinations of various regions of the brain identified to be involved in stress response for the possible modulatory effects of methyl jasmonate on dendritic spines, neurochemical substrates, neurotransmitter level, and receptor substrates. Western blotting, immunohistochemistry, and Golgi staining techniques are being utilized to obtain the results.


Effects of Methyl Jasmonate on Acute Stress Responses in Mice Subjected to Forced Swim and Anoxic Tests.

Abstract: Methyl jasmonate (MJ) is an anti-stress hormone released by plants in response to external stressors and aids adaptation to stress. In this study, we evaluated the anti-stress activity of MJ using the forced swim endurance test (FSET) and anoxic tolerance test in mice. Male Swiss mice were given MJ (25-100 mg/kg, i.p) 30 min before the FSET and anoxic test were carried out. The first occurrence of immobility, duration of immobility, time spent in active swimming, and latency to exhaustion were assessed in the FSET. The onset to anoxic convulsion was measured in the anoxic tolerance test. MJ significantly (p < 0.05) delayed the first occurrence of immobility and shortened the period of immobility, which indicates anti-stress property. MJ also increased the time spent in active swimming and prolonged the latency to exhaustion, which further suggests anti-stress activity. In addition, it also exhibited anti-stress property as evidenced by prolonged latency to first appearance of anoxic convulsions. The results of this study suggest that MJ demonstrated anti-stress activity and may be useful as an energizer in times of body weakness or exhaustion. Although more studies are necessary before concluding on how MJ exerts its anti-stress activity, the present data suggest an action similar to adaptogens in boosting energy and resilience in the face of stress.

Pub.: 04 Feb '16, Pinned: 24 Apr '18

Stress relaxant and antioxidant activities of acid glycoside from Spondias mangifera fruit against physically and chemically challenged albino mice.

Abstract: Stress relaxant and antioxidant activities of ethanolic extract of fruit Spondias mangifera (EEFSM) and its isolated compound (Sm-01) were evaluated. The structure of Sm-01 was also elucidated.EEFSM at two different doses of 100 and 200 mg/kg (bw)/day and Sm-01 at dose of 10 mg/kg (bw)/day were screened for in vivo stress relaxant activity using anoxia stress tolerance, swimming endurance and cyclophosphamide-induced immune suppression model and in vitro antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) model. The levels of Hb, red blood cell (RBC) and white blood cell (WBC) along with organ and body weights suppressed by cyclophosphamide were estimated. The structure of Sm-01 was elucidated by spectroscopy (ultraviolet, infrared, (1)H-nuclear magnetic resonance [NMR],(13) C-NMR and mass spectrometry) and chemical analyses.Sm-01 was structurally elucidated as propan-1,2-dioic acid-3-carboxyl-β-D-glucopyranosyl-(6'→1")-β-D-glucofuranoside. It was found that EEFSM and Sm-01 significantly increased the anoxia stress tolerance, swimming endurance and duration of stay on rotarod and normalized the levels of Hb, RBC, and WBC along with altered organ and body weights suppressed by cyclophosphamide. EEFSM and Sm-01 also exhibited significant antioxidant activity against DPPH free radical at the concentrations of 0.05, 0.5, and 1.0 mg/mL with obtained IC50 of 0.32 and 0.15 mg/mL, respectively.These findings demonstrated that extract and Sm-01 both possess significant stress relaxant and antioxidant activities favoring its use as adaptogens. The activities of the extract may be due to the Sm-01.

Pub.: 10 Mar '16, Pinned: 24 Apr '18

Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium.

Abstract: Medical application of Panax ginseng was first found in "Shen-Nong Herbal Classic"around 200 AD Panax quinquefolium was first introduced in "Essential of Materia Medica" in 1694 in China. The most important bioactive components contained in P ginseng and P quinquefolium are ginseng saponins (GS). The contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which was lower in P quinquefolium. After steaming for several hours, the total GS will decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase, while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation, especially in P quinquefolium, is high. P ginseng and P quinquefolium are general tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS) activities, but the effect of the latter is weaker. Thus, for the higher contents of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it. Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax, antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus, for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better than P quinquefolium. For anticancer effects, P quinquefolium is better.

Pub.: 23 Aug '08, Pinned: 24 Apr '18

Effect of Scoparia dulcis on noise stress induced adaptive immunity and cytokine response in immunized Wistar rats.

Abstract: Noise acts as a stressor and is reported to have impact on individual health depending on nature, type, intensity and perception. Modern medicine has no effective drugs or cure to prevent its consequences. Being an environmental stressor noise cannot be avoided; instead minimizing its exposure or consuming anti-stressor and adaptogens from plants can be considered.The present study was carried out to evaluate the anti-stressor, adaptogen and immunostimulatory activity of Scoparia dulcis against noise-induced stress in Wistar rat models.Noise stress in rats was created by broadband white noise generator, 100 dB A/4 h daily/15 days and S. dulcis (200 mg/kg b.w.) was administered orally. 8 groups of rats were used consisting of 6 animals each; 4 groups for unimmunized and 4 groups for immunized. For immunization, sheep red blood cells (5 × 10(9) cells/ml) were injected intraperitoneally.Sub-acute noise exposed rats showed a significant increase in corticosterone and IL-4 levels in both immunized and unimmunized rats whereas lymphocytes, antibody titration, soluble immune complex, IL-4 showed a marked increase with a significant decrease in IL-2, TNF-α, IFN-γ cytokines only in unimmunized rats. Immunized noise exposed rats presented increased leukocyte migration index and decreased foot pad thickness, IL-2, TNF-α, IFN-γ with no changes in the lymphocytes.S.dulcis (SD) has normalized and prevented the noise induced changes in cell-mediated and humoral immunity and it could be the presence of anti-stressor and immuno stimulant activity of the plant.

Pub.: 06 Feb '17, Pinned: 24 Apr '18

Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals.

Abstract: Adaptogens are stress-response modifiers that increase an organism's nonspecific resistance to stress by increasing its ability to adapt and survive. The classical reductionist model is insufficiently complex to explain the mechanistic aspects of the physiological notion of "adaptability" and the adaptogenic activity of adaptogens. Here, I demonstrate that (1) the mechanisms of action of adaptogens are impossible to rationally describe using the reductionist concept of pharmacology, whereas the network pharmacology approach is the most suitable method; and (2) the principles of systems biology and pharmacological networks appear to be more suitable for conceptualizing adaptogen function and are applicable to any phytochemical. Molecular targets, signaling pathways, and networks common to adaptogens have been identified. They are associated with stress hormones and key mediators of the regulation of homeostasis. In this context, the mechanisms of action of adaptogens are specifically related to stress-protective activity and increased adaptability of the organism. Consequently, adaptogens exhibit polyvalent beneficial effects against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer, and other aging-related diseases. Current and potential uses of adaptogens are mainly related to stress-induced fatigue and cognitive function, mental illness, and behavioral disorders. Their prophylactic use by healthy subjects to ameliorate stress and prevent age-related diseases appears to be justified. It is very unlikely that the pharmacological activity of any phytochemical is specific and associated only with one type of receptor, particularly adaptogenic compounds, which affect key mediators of the adaptive stress response at intracellular and extracellular levels of communication.

Pub.: 24 Jun '17, Pinned: 24 Apr '18

Immunopotentiating significance of conventionally used plant adaptogens as modulators in biochemical and molecular signalling pathways in cell mediated processes.

Abstract: Natural products are of great surge in the identification of chemopreventive agents and biologically active molecules for the development of new promising therapeutic agents. These agents influence the cascade of biochemical and molecular signalling pathways involved in numerous physiological and pathological processes. The natural agents combat the dogma associated with the most dreaded, unconquered health concern and a multigenic disease- cancer. A category of plants known as adaptogens maintain perturbed homoeostasis, augment adaptations to noxious stimuli (exposure to cold, heat, pain, general stress, infectious organisms) and offer endurance to attenuate several disorders in human beings. The well known adaptogens and immunomodulators such as Rhodiola rosea, Withania somnifera, Tinospora cordifolia, Bacopa monnieri, Emblica officinalis, Glycyrrhiza glabra, Asparagus racemosus, Ocimum sanctum and Panax notoginseng claimed to have significant antioxidant and anticarcinogenic properties due to the presence of various biologically active chemical compounds. Their immunopotentiating activity is mediated through the modulation of T-cell immunity biochemical factors, transcription factors, some genes and factors associated with tumor development and progression. The combinatory formulation of active immunostimulating constituents from these plants may provide better homeostasis. These immunostimulant factors suggest their potential therapeutic significance in adjuvant or supportive therapy in cancer treatment.

Pub.: 04 Oct '17, Pinned: 24 Apr '18

Alterations in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in post-pubertal rats after neonatal excitotoxic lesions of the ventral hippocampus.

Abstract: Neonatal ventral hippocampal (nVH) lesions in rats result in adult onset of a number of behavioral and cognitive abnormalities analogous to those seen in schizophrenia, including hyperresponsiveness to stress and psychostimulants and deficits in working memory, sensorimotor gating and social interaction. Molecular and neurochemical alterations in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of nVH-lesioned animals suggest developmental reorganization of these structures following neonatal lesions. To determine whether nVH lesions lead to neuronal morphological changes, we investigated the effect of nVH lesion on dendritic structure and spine density of pyramidal neurons of the PFC and medium spiny neurons of the NAcc. Bilateral ibotenic acid-induced lesion of the VH was made in Sprague-Dawley pups at postnatal day 7 (P7); and at P70, neuronal morphology was quantified by modified Golgi-Cox staining. The results show that length of basilar dendrites and branching and the density of dendritic spines on layer 3 pyramidal neurons were significantly decreased in rats with nVH lesions. Medium spiny neurons from the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. The data, comparable to those observed in the PFC of schizophrenic patients, suggest that developmental loss of excitatory projections from the VH may lead to altered neuronal plasticity in the PFC and the NAcc that may contribute to the behavioral changes in these animals.

Pub.: 10 May '05, Pinned: 24 Apr '18

Stress, glucocorticoids and glutamate release: effects of antidepressant drugs.

Abstract: Stressful life events impact on memory, cognition and emotional responses, and are known to precipitate mood/anxiety disorders. It is increasingly recognized that stress and its neurochemical and endocrine mediators induce changes in glutamate synapses and circuitry, and this in turn modify mental states. Half a century after the monoamine hypothesis, it is widely accepted that maladaptive changes in excitatory/inhibitory circuitry have a primary role in the pathophysiology of mood/anxiety disorders. The neuroplasticity hypothesis posits that volumetric changes consistently found in limbic and cortical areas of depressed subjects are in good part due to remodeling of neuronal dendritic arbors and loss of synaptic spines. A considerable body of work, carried out with in vivo microdialysis as well as alternative methodologies, has shown that both stress and corticosterone treatment induce enhancement of activity-dependent glutamate release. Accordingly, results from preclinical studies suggest that stress- and glucocorticoid-induced enhancement of glutamate release and transmission plays a main role in the induction of maladaptive cellular effects, in turn responsible for dendritic remodeling. Additional recent work has showed that drugs employed for therapy of mood/anxiety disorders (antidepressants) prevent the enhancement of glutamate release induced by stress. Understanding the action of traditional drugs on glutamate transmission could be of great help in developing drugs that may work directly at this level.

Pub.: 22 Jun '11, Pinned: 24 Apr '18

Adolescent female rats exhibiting activity-based anorexia express elevated levels of GABA(A) receptor α4 and δ subunits at the plasma membrane of hippocampal CA1 spines.

Abstract: Activity-based anorexia (ABA) is an animal model for anorexia nervosa that has revealed genetic links to anxiety traits and neurochemical characteristics within the hypothalamus. However, few studies have used this animal model to investigate the biological basis for vulnerability of pubertal and adolescent females to ABA, even though the great majority of the anorexia nervosa cases are females exhibiting the first symptoms during puberty. GABAergic inhibition of the hippocampus strongly regulates anxiety as well as plasticity throughout life. We recently showed that the hippocampal CA1 of female mice undergo a dramatic change at puberty onset--from expressing virtually none of the nonsynaptic α4βδ GABA(A) receptors (GABARs) prepubertally to expressing these GABARs at ~7% of the CA1 dendritic spine membranes at puberty onset. Furthermore, we showed that this change underlies the enhanced modulation of anxiety, neuronal excitability, and NMDA receptor-dependent synaptic plasticity in the hippocampus by the stress neurosteroid, THP (3α-OH-5α[β]-pregnan-20-one or [allo]pregnanolone). Here, we used quantitative electron microscopy to determine whether ABA induction in female rats during adolescence also elevates the expression of α4 and δ subunits of α4βδ GABARs, as was observed at puberty onset for mice. Our analysis revealed that rats also exhibit a rise of α4 and δ subunits of α4βδ GABARs at puberty onset, in that these subunits are detectable at ~6% of the dendritic spine membranes of CA1 pyramidal cells at puberty onset (postnatal day 32-36; P32-36) but this drops to about 2% by P40-P44. The levels of α4 and δ subunits at the CA1 spines remained low following exposure of females to either of the two environmental factors needed to generate ABA--food restriction and access to a running wheel for 4 days--from P40 to P44. This pattern contrasted greatly from those of ABA animals, for which the two environmental factors were combined. Within the hippocampus of ABA animals, 12% of the spine profiles were labeled for α4, reflecting a sixfold increase, relative to hippocampi of age-matched (P44) control females (p < 0.005). Concurrently, 7% of the spine profiles were labeled for δ, reflecting a 130% increase from the control values of 3% (p = 0.01). No measurable change was detected for spine size. The observed magnitude of increase in the α4 and δ subunits at spines is sufficient to increase both tonic inhibition of hippocampus and anxiety during stress, thereby likely to exacerbate hyperactivity and weight loss.

Pub.: 04 Jan '12, Pinned: 24 Apr '18

Structural and functional characterization of dendritic arbors and GABAergic synaptic inputs on interneurons and principal cells in the rat basolateral amygdala.

Abstract: The basolateral amygdala (BLA) is a complex brain region associated with processing emotional states, such as fear, anxiety, and stress. Some aspects of these emotional states are driven by the network activity of synaptic connections, derived from both local circuitry and projections to the BLA from other regions. Although the synaptic physiology and general morphological characteristics are known for many individual cell types within the BLA, the combination of morphological, electrophysiological, and distribution of neurochemical GABAergic synapses in a three-dimensional neuronal arbor has not been reported for single neurons from this region. The aim of this study was to assess differences in morphological characteristics of BLA principal cells and interneurons, quantify the distribution of GABAergic neurochemical synapses within the entire neuronal arbor of each cell type, and determine whether GABAergic synaptic density correlates with electrophysiological recordings of inhibitory postsynaptic currents. We show that BLA principal neurons form complex dendritic arborizations, with proximal dendrites having fewer spines but higher densities of neurochemical GABAergic synapses compared with distal dendrites. Furthermore, we found that BLA interneurons exhibited reduced dendritic arbor lengths and spine densities but had significantly higher densities of putative GABAergic synapses compared with principal cells, which was correlated with an increased frequency of spontaneous inhibitory postsynaptic currents. The quantification of GABAergic connectivity, in combination with morphological and electrophysiological measurements of the BLA cell types, is the first step toward a greater understanding of how fear and stress lead to changes in morphology, local connectivity, and/or synaptic reorganization of the BLA.

Pub.: 05 Jun '15, Pinned: 24 Apr '18

Gallic Acid Protects 6-OHDA Induced Neurotoxicity by Attenuating Oxidative Stress in Human Dopaminergic Cell Line

Abstract: Gallic acid is one of the most important polyphenolic compounds, which is considered an excellent free radical scavenger. 6-Hydroxydopamine (6-OHDA) is a neurotoxin, which has been implicated in mainly Parkinson’s disease (PD). In this study, we investigated the molecular mechanism of the neuroprotective effects of gallic acid on 6-OHDA induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that 6-OHDA induced cytotoxicity in SH-SY5Y cells was suppressed by pre-treatment with gallic acid. The percentage of live cells (90%) was high in the pre-treatment of gallic acid when compared with 6-OHDA alone treated cell line. Moreover, gallic acid was very effective in attenuating the disruption of mitochondrial membrane potential, elevated levels of intracellular ROS and apoptotic cell death induced by 6-OHDA. Gallic acid also lowered the ratio of the pro-apoptotic Bax protein and the anti-apoptotic Bcl-2 protein in SH-SY5Y cells. 6-OHDA exposure was up-regulated caspase-3 and Keap-1 and, down-regulated Nrf2, BDNF and p-CREB, which were sufficiently reverted by gallic acid pre-treatment. These findings indicate that gallic acid is able to protect the neuronal cells against 6-OHDA induced injury and proved that gallic acid might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress and apoptosis.

Pub.: 18 Apr '18, Pinned: 24 Apr '18

Exposure to Far Infrared Ray Protects Methamphetamine-Induced Behavioral Sensitization in Glutathione Peroxidase-1 Knockout Mice via Attenuating Mitochondrial Burdens and Dopamine D1 Receptor Activation

Abstract: Evidence indicates that stress conditions might lead to drug dependence. Recently, we have demonstrated that exposure to far infrared ray (FIR) attenuates acute restraint stress via induction of glutathione peroxidase-1 (GPx-1) gene. We investigated whether FIR affects methamphetamine (MA)-induced behavioral sensitization and whether FIR-mediated pharmacological activity requires interaction between dopamine receptor and GPx-1 gene. We observed that MA treatment significantly increased GPx-1 expression in the striatum of wild-type (WT) mice. Interestingly, exposure to FIR potentiated MA-induced increase in GPx-1 expression. This phenomenon was also observed in animals receiving MA with dopamine D1 receptor antagonist SCH23390. However, dopamine D2 receptor antagonist sulpiride did not affect MA-induced GPx-1 expression. FIR exposure or SCH23390, but not sulpiride, significantly attenuated MA-induced behavioral sensitization. Exposure to FIR significantly attenuated MA-induced dopamine D1 receptor expression, c-Fos induction and oxidative burdens. FIR-mediated antioxidant effects were also more pronounced in mitochondrial- than cytosolic-fraction. In addition, FIR significantly attenuated against MA-induced changes in mitochondrial superoxide dismutase and mitochondrial GPx activities, mitochondrial transmembrane potential, intramitochondrial Ca2+ level, mitochondrial complex-I activity, and mitochondrial oxidative burdens. The attenuation by FIR was paralleled that by SCH23390. Effects of FIR or SCH23390 were more sensitive to GPx-1 KO than WT mice, while SCH23390 treatment did not exhibit any additive effects on the protective activity mediated by FIR, indicating that dopamine D1 receptor constitutes a molecular target of FIR. Our result suggests that exposure to FIR ameliorates MA-induced behavioral sensitization via possible interaction between dopamine D1 receptor and GPx-1 gene.

Pub.: 23 Apr '18, Pinned: 24 Apr '18

Methyl jasmonate attenuated lipopolysaccharide-induced depressive-like behaviour in mice.

Abstract: Depression is a recurrent neuropsychiatric disorder that affects millions of individuals worldwide and impact negatively on the patients' social functions and quality of life. Studies have shown that i.p injection of lipopolysaccharide (LPS) induces depressive-like behavior in rodents via induction of oxidative stress and neuroinflammation. Methyl jasmonate (MJ), an isolated compound from jasmine plant has gained reputation in aromatherapy for treatment of depression, nervousness and memory deficits. This study was designed to evaluate the effects of MJ on LPS-induced depressive-like behavior in mice. Mice were given MJ (5-20 mg/kg), imipramine (10 mg/kg) or vehicle (10 mL/kg) intraperitoneally for 7 consecutive days. On day 7, treatment was carried out 30 min prior to i.p injection of LPS (830 μg/kg). Twenty four hours after LPS administration, tail suspension, forced swim and sucrose preference tests were carried out. Thereafter, serum corticosterone levels were determined using ELISA. The levels of malondialdehyde (MDA), glutathione (GSH) and tumor necrosis factor-alpha (TNF-α) were determined in brain tissue homogenates. LPS significantly increased immobility time in the tail suspension and forced swim tests when compared with vehicle (p < 0.05), which indicates depressive-like syndromes. However, the increased immobility time was significantly reduced by MJ (5-20 mg/kg) when compared with LPS-treated group. LPS administration also altered the levels of MDA, GSH, corticosterone and TNF alpha in mice, which was significantly reversed by MJ. These findings suggest that attenuation of LPS-induced depressive-like behavior by MJ may be related to suppression of oxidative stress and release of TNF alpha.

Pub.: 26 Jun '17, Pinned: 24 Apr '18

Antidepressant-like effect of tetrahydroisoquinoline amines in the animal model of depressive disorder induced by repeated administration of a low dose of reserpine: behavioral and neurochemical studies in the rat.

Abstract: Animal models are widely used to study antidepressant-like effect in rodents. However, it should be mentioned that pharmacological models do not always take into account the complexity of the disease process. In the present paper, we demonstrated that repeated but not acute treatment with a low dose of reserpine (0.2 mg/kg i.p.) led to a pharmacological model of depression which was based on its inhibitory effect on the vesicular monoamine transporter 2, and monoamines depleting action in the brain. In fact, we observed that chronic treatment with a low dose of reserpine induced a distinct depressive-like behavior in the forced swim test (FST), and additionally, it produced a significant decrease in the level of dopamine, noradrenaline, and serotonin in the brain structures. 1,2,3,4-Tetrahydroisoquinoline (TIQ) and its close methyl derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) are exo/endogenous amines present naturally in the mammalian brain which demonstrated a significant antidepressant-like effect in the FST and the reserpine model of depression in the rat. Both compounds, TIQ and 1MeTIQ, administered chronically in a dose of 25 mg/kg (i.p.) together with reserpine completely antagonized reserpine-produced depression as assessed by the immobility time and swimming time. Biochemical data were in agreement with behavioral experiments and demonstrated that chronic treatment with a low dose of reserpine in contrast to acute administration produced a significant depression of monoamines in the brain structures and impaired their metabolism. These neurochemical effects obtained after repeated reserpine (0.2 mg/kg i.p.) in the brain structures were completely antagonized by joint TIQ or 1MeTIQ (25 mg/kg i.p.) administration with chronic reserpine. A possible molecular mechanism of action of TIQ and 1MeTIQ responsible for their antidepressant action is discussed. On the basis of the presented behavioral and biochemical studies, we suggest that both compounds may be effective for the therapy of depression in clinic as new antidepressants which, when administered peripherally easily penetrate the blood-brain barrier, and as endogenous compounds may not have adverse side effects.

Pub.: 11 Jan '14, Pinned: 24 Apr '18

Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis.

Abstract: Geniposide as the major active component of Gardenia jasminoides Ellis has neuroprotective activity. This study elucidated the potential antidepressant-like effect of geniposide and its related mechanisms using a depression rat model induced by 3 consecutive weeks of chronic unpredictable mild stress (CUMS). Sucrose preference test, open field test (OFT) and forced swimming test (FST) were applied to evaluate the antidepressant effect of geniposide. Adrenocorticotropic hormone (ACTH) and corticosterone (CORT) serum levels, adrenal gland index and hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression were measured to assess the activity of hypothalamus-pituitary-adrenal (HPA) axis. Hypothalamic glucocorticoid receptor α (GRα) mRNA expression and GRα protein expression in hypothalamic paraventricular nucleus (PVN) were also determined by real-time PCR and immunohistochemistry, respectively. We found that geniposide (25, 50, 100mg/kg) treatment reversed the CUMS-induced behavioral abnormalities, as suggested by increased sucrose intake, improved crossing and rearing behavior in OFT, shortened immobility and prolonged swimming time in FST. Additionally, geniposide treatment normalized the CUMS-induced hyperactivity of HPA axis, as evidenced by reduced CORT serum level, adrenal gland index and hypothalamic CRH mRNA expression, with no significant effect on ACTH serum level. Moreover, geniposide treatment upregulated the hypothalamic GRα mRNA level and GRα protein expression in PVN, suggesting geniposide could recover the impaired GRα negative feedback on CRH expression and HPA axis. These aforementioned therapeutic effects of geniposide were essentially similar to fluoxetine. Our results indicated that geniposide possessed potent antidepressant-like properties that may be mediated by its effects on the HPA axis.

Pub.: 29 Apr '15, Pinned: 24 Apr '18