Adv Pharmacol Sci
· 2012 · PMID 22848211
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St. John's Wort herb extracts often contain undesirable or volitional polysaccharides. As polysaccharides exhibit structure-dependent biological functions in the present study water-soluble polysaccharides were extracted...St. John's Wort herb extracts often contain undesirable or volitional polysaccharides. As polysaccharides exhibit structure-dependent biological functions in the present study water-soluble polysaccharides were extracted from herb material, fractionated by anion exchange chromatography into four main polysaccharide fractions (denominated as Hp1, Hp2, Hp3 and Hp4) and characterized by HPAEC-PAD, CE, IR and GC-MS. Biological activity on human skin keratinocytes and fibroblasts was assessed by investigation of their effect on proliferation, metabolism, cytotoxicity, apoptosis and differentiation. The underlying mechanisms were investigated in gene expression studies. Polysaccharide fraction Hp1 was mainly composed of β-D-glucose. Hp2, Hp3 and Hp4 contained pectic structures and arabinogalactan proteins varying in composition and quantity. Polysaccharides of Hp1 induced the keratinocyte differentiation by inhibiting the gene expression of the epidermal growth factor and insulin receptor. While the collagen secretion of fibroblasts was stimulated by each polysaccharide fraction only Hp1 stimulated the synthesis. The fibroblast proliferation was reduced by Hp1 and increased by Hp4. This effect was related to the influence on genes that referred to oxidative stress, metabolism, transcription processes and extracellular proteins. In conclusion polysaccharides have been shown as biologically active ingredients of aqueous St. John's Wort extracts with a relation between their structural characteristics and function.
Brenchat A, Rocasalbas M, Zamanillo D
… +3 more, Hamon M, Vela JM, Romero L
Adv Pharmacol Sci
· 2012 · PMID 22761612
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No study has ever examined the effect of 5-HT(7) receptor agonists on nociception by using 5-HT(7) receptor knockout mice. Basal sensitivity to noxious heat stimuli and formalin-induced nociception in both phase I and II...No study has ever examined the effect of 5-HT(7) receptor agonists on nociception by using 5-HT(7) receptor knockout mice. Basal sensitivity to noxious heat stimuli and formalin-induced nociception in both phase I and II of the formalin test did not differ in 5-HT(7) receptor knockout mice and paired wild-type controls. Similarly, there was no significant difference in basal body temperature between both genotypes. Subcutaneous administration of 5-HT(7) receptor agonists AS-19 (10 mg/kg), E-57431 (10 mg/kg), and E-55888 (20 mg/kg) significantly reduced formalin-induced licking/biting behavior during the phase II of the test in wild-type but not in 5-HT(7) receptor knockout mice. At these active analgesic doses, none of the three 5-HT(7) receptor agonists modified the basal body temperature neither in wild-type nor in 5-HT(7) receptor knockout mice. However, a significant decrease in body temperature was observed at a higher dose (20 mg/kg) of AS-19 and E-57431 in both genotypes. Our data strongly suggest that the 5-HT(7) receptor agonists AS-19, E-57431, and E-55888 produce antinociception in the formalin test by activating 5-HT(7) receptors. These results also strengthen the idea that the 5-HT(7) receptor plays a role in thermoregulation, but by acting in concert with other receptors.
Adv Pharmacol Sci
· 2012 · PMID 22761611
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The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is...The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models.
Froeliger B, Crowell Beckham J, Feldman Dennis M
… +2 more, Victoria Kozink R, Joseph McClernon F
Adv Pharmacol Sci
· 2012 · PMID 22719754
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There is evidence that individuals with posttraumatic stress disorder (PTSD) may smoke in part to regulate negative affect. This pilot fMRI study examined the effects of nicotine on emotional information processing in sm...There is evidence that individuals with posttraumatic stress disorder (PTSD) may smoke in part to regulate negative affect. This pilot fMRI study examined the effects of nicotine on emotional information processing in smokers with and without PTSD. Across groups, nicotine increased brain activation in response to fearful/angry faces (compared to neutral faces) in ventral caudate. Patch x Group interactions were observed in brain regions involved in emotional and facial feature processing. These preliminary findings suggest that nicotine differentially modulates negative information processing in PTSD and non-PTSD smokers.
Shilpi JA, Islam ME, Billah M
… +5 more, Islam KM, Sabrin F, Uddin SJ, Nahar L, Sarker SD
Adv Pharmacol Sci
· 2012 · PMID 22666237
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Mangrove plants are specialised plants that grow in the tidal coasts of tropic and subtropic regions of the world. Their unique ecology and traditional medicinal uses of mangrove plants have attracted the attention of re...Mangrove plants are specialised plants that grow in the tidal coasts of tropic and subtropic regions of the world. Their unique ecology and traditional medicinal uses of mangrove plants have attracted the attention of researchers over the years, and as a result, reports on biological activity of mangrove plants have increased significantly in recent years. This review has been set out to compile and appraise the results on antinociceptive, anti-inflammatory, and antipyretic activity of mangrove plants. While the Web of Knowledge, Google Scholar, and PubMed were the starting points to gather information, other pieces of relevant published literature were also adequately explored for this purpose. A total of 29 reports on 17 plant species have been found to report such activities. While 19 reports were on the biological activity of the crude extracts, 10 reports identified the active compound(s) of various chemical classes of natural products including terpenes, steroids, and flavonoids. This review finds that antinociceptive, anti-inflammatory, and antipyretic activity appears to be widespread in mangrove plants.
Nadia ME, Nazrun AS, Norazlina M
… +3 more, Isa NM, Norliza M, Ima Nirwana S
Adv Pharmacol Sci
· 2012 · PMID 22611381
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Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develo...Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-α. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis.
Mokondjimobe E, Longo-Mbenza B, Akiana J
… +4 more, Ndalla UO, Dossou-Yovo R, Mboussa J, Parra HJ
Adv Pharmacol Sci
· 2012 · PMID 22611380
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Background. The objectives were (i) to evaluate the impact of acute pulmonary tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity...Background. The objectives were (i) to evaluate the impact of acute pulmonary tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A prospective followup of 40 adults (21 males; mean age of 34.7 ± 5.8 years) with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n = 1) developed a transient and benign ADR at day 30 without interruption of anti-TB treatment. Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0-day 60, there was a significant, negative, and independent association between GGT and AST. Conclusion. The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR.
Adv Pharmacol Sci
· 2012 · PMID 22536226
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Despite decades of basic and clinical research, our understanding of how benzodiazepines tend to lose their efficacy over time (tolerance) is at least incomplete. In appears that tolerance develops relatively quickly for...Despite decades of basic and clinical research, our understanding of how benzodiazepines tend to lose their efficacy over time (tolerance) is at least incomplete. In appears that tolerance develops relatively quickly for the sedative and anticonvulsant actions of benzodiazepines, whereas tolerance to anxiolytic and amnesic effects probably does not develop at all. In light of this evidence, we review the current evidence for the neuroadaptive mechanisms underlying benzodiazepine tolerance, including changes of (i) the GABA(A) receptor (subunit expression and receptor coupling), (ii) intracellular changes stemming from transcriptional and neurotrophic factors, (iii) ionotropic glutamate receptors, (iv) other neurotransmitters (serotonin, dopamine, and acetylcholine systems), and (v) the neurosteroid system. From the large variance in the studies, it appears that either different (simultaneous) tolerance mechanisms occur depending on the benzodiazepine effect, or that the tolerance-inducing mechanism depends on the activated GABA(A) receptor subtypes. Importantly, there is no convincing evidence that tolerance occurs with α subunit subtype-selective compounds acting at the benzodiazepine site.
Aljamal-Naylor R, Wilson L, McIntyre S
… +4 more, Rossi F, Harrison B, Marsden M, Harrison DJ
Adv Pharmacol Sci
· 2012 · PMID 22505883
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The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung i...The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung injury, extracellular matrix-integrin interactions are altered and this leads to signalling alteration and mechanical missensing. The missensing, secondary to matrix alteration and cell surface receptor alterations, leads to increased cellular stiffness, injury, and death. We have identified a monoclonal antibody against β1 integrin which caused matrix remodelling and enhancement of cell survival. The antibody acts as an allosteric dual agonist/antagonist modulator of β1 integrin. Intriguingly, this antibody reversed both functional and structural tissue injury in an animal model of degenerative disease in lung.
Adv Pharmacol Sci
· 2012 · PMID 22461789
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An attempt to find pharmacological therapies to treat stroke patients and minimize the extent of cell death has seen the failure of dozens of clinical trials. As a result, stroke/cerebral ischemia is the leading cause of...An attempt to find pharmacological therapies to treat stroke patients and minimize the extent of cell death has seen the failure of dozens of clinical trials. As a result, stroke/cerebral ischemia is the leading cause of lasting adult disability. Stroke-induced cell death occurs due to an excess release of glutamate. As a consequence to this, a compensatory increased release of GABA occurs that results in the subsequent internalization of synaptic GABA(A) receptors and spillover onto perisynaptic GABA(A) receptors, resulting in increased tonic inhibition. Recent studies show that the brain can engage in a limited process of neural repair after stroke. Changes in cortical sensory and motor maps and alterations in axonal structure are dependent on patterned neuronal activity. It has been assumed that changes in neuronal excitability underlie processes of neural repair and remapping of cortical sensory and motor representations. Indeed, recent evidence suggests that local inhibitory and excitatory currents are altered after stroke and modulation of these networks to enhance excitability during the repair phase can facilitate functional recovery after stroke. More specifically, dampening tonic GABA inhibition can afford an early and robust improvement in functional recovery after stroke.
Chen X, de Haas S, de Kam M
… +1 more, van Gerven J
Adv Pharmacol Sci
· 2012 · PMID 22363345
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Various α(2,3) subtype selective partial GABA-A agonists are in development to treat anxiety disorders. These compounds are expected to be anxiolytic with fewer undesirable side effects, compared to nonselective GABA-A a...Various α(2,3) subtype selective partial GABA-A agonists are in development to treat anxiety disorders. These compounds are expected to be anxiolytic with fewer undesirable side effects, compared to nonselective GABA-A agonists like benzodiazepines. Several α(2,3) subtype selective and nonselective GABA-A agonists have been examined in healthy volunteers, using a battery addressing different brain domains. Data from five placebo-controlled double-blind studies were pooled. Lorazepam 2 mg was the comparator in three studies. Three α(2,3)-selective GABAA agonists (i.e., TPA023, TPACMP2, SL65.1498), one α(1)-selective GABAA agonists (zolpidem), and another full agonist (alprazolam) were examined. Pharmacological selectivity was assessed by determination of regression lines for the change from baseline of saccadic-peak-velocity- (ΔSPV-) relative effect, relative to changes in different pharmacodynamic endpoints (ΔPD). SPV was chosen for its sensitivity to the anxiolysis of benzodiazepines. Slopes of the ΔSPV-ΔPD relations were consistently lower with the α(2,3) selective GABA-A agonists than with lorazepam, indicating that their PD effects are less than their SPV-effects. The ΔSPV-ΔPD relations of lorazepam were comparable to alprazolam. Zolpidem showed relatively higher impairments in ΔPD relative to ΔSPV, but did not significantly differ from lorazepam. These PD results support the pharmacological selectivity of the α(2,3)-selective GABA-A agonists, implying an improved therapeutic window.
Imanishi T, Hossain MM, Suzuki T
… +3 more, Xu P, Sato I, Kobayashi H
Adv Pharmacol Sci
· 2012 · PMID 22319525
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Anticholinesterases (antiChEs) are used to treat Alzheimer's disease. The comparative effects of two antiChEs, methanesulfonyl fluoride (MSF) and donepezil, on the extracellular levels of ACh in the hippocampus were inve...Anticholinesterases (antiChEs) are used to treat Alzheimer's disease. The comparative effects of two antiChEs, methanesulfonyl fluoride (MSF) and donepezil, on the extracellular levels of ACh in the hippocampus were investigated by in vivo microdialysis in freely moving rats. MSF at 1 and 2 mg/kg produced a dose-dependent increase in ACh efflux from 10 min to at least 3 hrs after injection. At 2 mg/kg, the increase was still present at 24 hr. Donepezil at 1 mg/kg showed a similar but smaller effect, and, paradoxically, 2 mg/kg showed no consistent effect. MSF at 1 and 2 mg/kg decreased acetylcholinesterase activity in the hippocampus to 54.8 and 20.1% of control, respectively. These results suggest that MSF is a suitable candidate for the treatment of Alzheimer's disease.
Adv Pharmacol Sci
· 2011 · PMID 22242019
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No study has ever examined the effect of vitamin C with metformin on fasting (FBS) and postmeal blood glucose (PMBG) as well as glycosylated hemoglobin (HbA1c) in the treatment of type 2 diabetes mellitus (DM). The goal...No study has ever examined the effect of vitamin C with metformin on fasting (FBS) and postmeal blood glucose (PMBG) as well as glycosylated hemoglobin (HbA1c) in the treatment of type 2 diabetes mellitus (DM). The goal was to examine the effect of oral vitamin C with metformin on FBS, PMBG, HbA1c, and plasma ascorbic acid level (PAA) with type 2 DM. Seventy patients with type 2 DM participated in a prospective, double-blind, placebo-controlled, 12-week study. The patients with type 2 DM were divided randomly into placebo and vitamin C group of 35 each. Both groups received the treatment for twelve weeks. Decreased PAA levels were found in patients with type 2 diabetes mellitus. This level was reversed significantly after treatment with vitamin C along with metformin compared to placebo with metformin. FBS, PMBG, and HbA1c levels showed significant improvement after 12 weeks of treatment with vitamin C. In conclusion, oral supplementation of vitamin C with metformin reverses ascorbic acid levels, reduces FBS, PMBG, and improves HbA1c. Hence, both the drugs in combination may be used in the treatment of type 2 DM to maintain good glycemic control.
Adv Pharmacol Sci
· 2012 · PMID 22235200
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Leaf methanol extract of C. orbiculata L. was investigated for antinociceptive and anti-inflammatory activities using acetic acid writhing and hot-plate tests and carrageenan-induced oedema test in mice and rats, respect...Leaf methanol extract of C. orbiculata L. was investigated for antinociceptive and anti-inflammatory activities using acetic acid writhing and hot-plate tests and carrageenan-induced oedema test in mice and rats, respectively. C. orbiculata (100-400 mg/kg, i.p.) significantly inhibited acetic acid-induced writhing and significantly delayed the reaction time of mice to the hot-plate-induced thermal stimulation. Paracetamol (300 mg/kg, i.p.) significantly inhibited the acetic acid-induced writhing in mice. Morphine (10 mg/kg, i.p.) significantly delayed the reaction time of mice to the thermal stimulation produced with hot plate. Leaf methanol extract of C. orbiculata (50-400 mg/kg, i.p.) significantly attenuated the carrageenan-induced rat paw oedema. Indomethacin (10 mg/kg, p.o.) also significantly attenuated the carrageenan-induced rat paw oedema. The LD(50) value obtained for the plant species was greater than 4000 mg/kg (p.o.). The data obtained indicate that C. orbiculata has antinociceptive and anti-inflammatory activities, justifying the folklore use of the plant species by traditional medicine practitioners in the treatment of painful and inflammatory conditions. The relatively high LD(50) obtained shows that C. orbiculata may be safe in or nontoxic to mice.
Alnamer R, Alaoui K, Bouidida el H
… +2 more, Benjouad A, Cherrah Y
Adv Pharmacol Sci
· 2012 · PMID 22162677
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We evaluate the sedative and hypnotic activities of the methanolic and aqueous extract of Lavandula officinalis L. on central nervous system (CNS). In this study, the effect of the methanolic and aqueous extracts of this...We evaluate the sedative and hypnotic activities of the methanolic and aqueous extract of Lavandula officinalis L. on central nervous system (CNS). In this study, the effect of the methanolic and aqueous extracts of this plant was investigated in a battery of behavioural models in mice. Stems and flowers of Lavandula officinalis L. have several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including insomnia. The methanolic extract produced significant sedative effect at the doses of 200, 400, and 600 mg/kg (by oral route), compared to reference substance diazepam (DZP), and an hypnotic effect at the doses of 800 and 1000 mg/kg while the treatment of mice with the aqueous extract at the doses of 200 and 400 mg/kg via oral pathway significantly reduced in both the reestablishment time and number of head dips during the traction and hole-board tests. In conclusion, these results suggest that the methanolic and aqueous extracts of Lavandula officinalis possess potent sedative and hypnotic activities, which supported its therapeutic use for insomnia.
Nazrun AS, Norazlina M, Norliza M
… +1 more, Nirwana SI
Adv Pharmacol Sci
· 2012 · PMID 22162676
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There is growing evidence that inflammation may be one of the causal factors of osteoporosis. Several cytokines such as IL-1, IL-6, RANKL, OPG, and M-CSF were implicated in the pathogenesis of osteoporosis. These cytokin...There is growing evidence that inflammation may be one of the causal factors of osteoporosis. Several cytokines such as IL-1, IL-6, RANKL, OPG, and M-CSF were implicated in the pathogenesis of osteoporosis. These cytokines are important determinants of osteoclast differentiation and its bone resorptive activity. Anticytokine therapy using cytokine antagonists such as IL-receptor antagonist and TNF-binding protein was able to suppress the activity of the respective cytokines and prevent bone loss. Several animal studies have shown that vitamin E in the forms of palm-derived tocotrienol and α-tocopherol may prevent osteoporosis in rat models by suppressing IL-1 and IL-6. Free radicals are known to activate transcription factor NFκB which leads to the production of bone resorbing cytokines. Vitamin E, a potent antioxidant, may be able to neutralise free radicals before they could activate NFκB, therefore suppressing cytokine production and osteoporosis. Vitamin E has also been shown to inhibit COX-2, the enzyme involved in inflammatory reactions. Of the two types of vitamin E studied, tocotrienol seemed to be better than tocopherol in terms of its ability to suppress bone-resorbing cytokines.
Cuevas VM, Calzado YR, Guerra YP
… +4 more, Yera AO, Despaigne SJ, Ferreiro RM, Quintana DC
Adv Pharmacol Sci
· 2011 · PMID 22162675
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Effects of GSE and vitamins C and E on aspirin- and ethanol-induced gastric ulcer and associated increases of lipid peroxidation in rats were compared. Two experiments were conducted. Rats were randomized into eight grou...Effects of GSE and vitamins C and E on aspirin- and ethanol-induced gastric ulcer and associated increases of lipid peroxidation in rats were compared. Two experiments were conducted. Rats were randomized into eight groups: a negative control and seven groups that received aspirin or ethanol for ulcer induction: one positive control (vehicle) and six with VC, VE, or GSE (25 and 250 mg/kg). Ulcer indexes and gastric levels of malondialdehyde (MDA) were quantified. VC, VE, and GSE (25 and 250 mg/kg) decreased aspirin, and ethanol-induced ulcers and MDA values compared with positive control group. The magnitude of aspirin ulcer reduction was comparable for all treatments, and MDA decrease with GSE was higher than with VC and tended to be greater, albeit none significantly, than with VE. GSE was more effective than VC and VE for lowering the ethanol ulcers, while the decrease of MDA levels with GSE was greater than with VC, but comparable to that achieved with VE. GSE protected against ethanol-induced gastric ulcers more effectively than VC or VE, while its protection against aspirin ulcers was comparable for all treatments. GSE produced the greatest reductions of gastric MDA in both models.
Nickolls S, Mace H, Fish R
… +16 more, Edye M, Gurrell R, Ivarsson M, Pitcher T, Tanimoto-Mori S, Richardson D, Sweatman C, Nicholson J, Ward C, Jinks J, Bell C, Young K, Rees H, Moss A, Kinloch R, McMurray G
Adv Pharmacol Sci
· 2011 · PMID 22162674
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GABA(A) receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia. However...GABA(A) receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia. However, this approach is prone to a range of side effects including sedation, cognitive impairment, and abuse as a consequence of the widespread influence of GABA. The ability to make subtype selective low-efficacy benzodiazepine compounds, which potentiate the action of GABA at specific α subunits, has the potential to reduce this side effect profile. In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM) L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models. We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated.