Band 28, Heft 5

Alzheimer’s disease (AD) is related to increasing age. It is mainly characterized by progressive neurodegenerative disease, which damages memory and cognitive function. Natural products offer many options to reduce the progress and symptoms of many kinds of diseases, including AD. Meanwhile, natural compound structures, including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, have anti-inflammatory, antioxidant, anti-amyloidogenic, and anticholinesterase activities. In this review, we summarize the pathogenesis and targets for treatment of AD. We also present several medicinal plants and isolated compounds that are used for preventing and reducing symptoms of AD.

Background: The root bark of Anthocleista djalonensis A. Chev. (Loganiaceae) is widely used in traditional medicine in Northern Cameroon to treat epilepsy and related conditions, such as migraine, insomnia, dementia, anxiety, and mood disorders. Methods: To investigate the anticonvulsant effects and the possible mechanisms of this plant, an aqueous extract of Anthocleista djalonensis (AEAD) was evaluated by using animal models of bicuculline-, picrotoxin-, pilocarpine-, and pentylenetetrazole-induced convulsions. Their effects on brain γ-aminobutyric acid (GABA) concentration and GABA-T activity were also determined. Results: This extract significantly protected mice against bicuculline-induced motor seizures. It provided 80% protection against picrotoxin-induced tonic-clonic seizures, and strongly antagonized convulsions induced by pilocarpine. AEAD also protected 100% of mice against pentylenetetrazole-induced seizures. Flumazenil, a central benzodiazepine receptor antagonist and FG7142, a partial inverse agonist in the benzodiazepine site of the GABA A receptor complex, were found to have an inhibitory effect on the anticonvulsant action of AEAD in pentylenetetrazole test. Finally, the brain GABA concentration was significantly increased and GABA-T activity was inhibited by AEAD. Conclusions: The effects of Anthocleista djalonensis suggested the presence of anticonvulsant properties that might involve an action on benzodiazepine and/or GABA sites in the GABA A receptor complex or by modulating GABA concentration in the central nervous system (CNS).

Background: Stroke can result in body temperature sensitivity changes. This study analyzed abnormal temperature perception of patients with stroke and the use of vasoactive drugs. Methods: A cross-sectional retrospective study was carried out consisting of 100 patients (55.6±12.9 years old), from both genres, with either hemorrhagic or ischemic stroke, with unilateral hemiplegia or hemiparesis. Subjects had axillary temperature and different temperature sensitivities of the limbs measured using a visual analog scale (VAS). Information on the use of medical drugs was collected in clinical records. Results: In total, 64 patients reported body temperature alterations, and 62 patients stated they feel cold in the affected side. They reported 6.12±2.44 cm alteration for the upper limb and 6.72±2.44 cm for the lower limb in the VAS. Some 86 different drugs were identified in the 85 medical records available. There was a prevalence of a group of drugs formed by the β-blockers, dopamine agonists, dopamine reuptake Inhibitors, tricyclic antidepressants (TCAs) and another group formed by the selective serotonin reuptake inhibitors. Conclusions: Most of the subjects reported a sensation of cold in the affected limbs. The β-blockers, dopamine agonists, dopamine reuptake inhibitors, and TCAs seem to be related to this sensation, however, due to the number of uncontrolled variables that may be related to these drugs and the possible role of nitric oxide, it was not possible to establish precise relations regarding the use of a specific group of drugs and the cold sensation in the affected limbs, as reported by the patients.

Background: Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH. This necessitates the need for potent combinatorial therapies to improve cardiac acclimatization at high altitudes. We hypothesize that a combinatorial therapy comprising preconditioning to mild aerobic treadmill exercise and supplementation with nanocurcumin formulation (NCF) consisting of nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) might improve cardiac adaptation at high altitudes. Methods: Adult Sprague-Dawley rats pre-conditioned to treadmill exercise and supplemented with NCF were exposed to cHH (7620 m altitude corresponding to pO 2 ~8% at 28±2°C, relative humidity 55%±1%) for 3 weeks. The rat hearts were analyzed for changes in markers of oxidative stress (free radical leakage, lipid peroxidation, manganese-superoxide dismutase [MnSOD] activity), cardiac injury (circulating cardiac troponin I [TnI] and T [cTnT], myocardial creatine kinase [CK-MB]), metabolic damage (lactate dehydrogenase [LDH] and acetyl-coenzyme A levels, lactate and pyruvate levels) and bio-energetic insufficiency (ATP, p-AMPKα). Results: Significant modulations (p≤0.05) in cardiac redox status, metabolic damage, cardiac injury and bio-energetics were observed in rats receiving both NCF supplementation and treadmill exercise-preconditioning compared with rats receiving only one of the treatments. Conclusions: The combinatorial therapeutic strategy showed a tremendous improvement in cardiac acclimatization to cHH compared to either exercise-preconditioning or NCF supplementation alone which was evident from the effective modulation in redox, metabolic, contractile and bio-energetic homeostasis.

Background: Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. Methods: Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation. Mitochondrial antioxidant status such as mitochondrial superoxide dismutase, glutathione peroxidase, and reduced glutathione; adenosine triphosphate level; and lipid peroxidation were measured. The activities of Krebs cycle enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, III, and IV in kidney mitochondria were also determined. Results: Administration of P. rimosus (250 mg/kg b.wt) once daily for 30 days, significantly (p<0.05) enhanced the activities of Krebs cycle dehydrogenases, mitochondrial electron transport chain complexes, and ATP level. Further, P. rimosus had significantly protected the renal mitochondrial antioxidant status and lipid peroxidation. Conclusions: The results of the study concluded that by limiting the extent of renal mitochondrial damage in the hyperglycemic state, P. rimosus alleviated nephrotoxicity.

Background: This study was carried out to evaluate the antioxidant and hepatoprotective effects of Vaccinium arctostaphylos (V.a) methanolic extract on carbon tetrachloride (CCl 4 )-induced acute liver injury in Wistar rats. Methods: Total phenolic and total flavonoid contents as well as antioxidant activity of V.a were determined. Extracts of V.a at doses of 200 and 400 mg/kg were administered by oral gavage to rats once per day for 7 days and then were given an intraperitoneal injection of 1 mL/kg CCl 4 (1:1 in olive oil) for 3 consecutive days. Serum biochemical markers of liver injury, oxidative markers, as well as hydroxyproline (HP) content and histopathology of liver were evaluated. Results: The obtained results showed that V.a had strong antioxidant activity. Treatment of rats with V.a blocked the CCl 4 -induced elevation of serum markers of liver function and enhanced albumin and total protein levels. The level of hepatic HP content was also reduced by the administration of V.a treatment. Histological examination of the liver section revealed that V.a prevented the occurrence of pathological changes in CCl 4 -treated rats. Conclusions: These findings suggested that V.a may be useful in the treatment and prevention of hepatic injury induced by CCl 4 .

Background: Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF 2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated. Methods: Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation. Results: The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1β. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF 2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B 2 . Conclusions: Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B 2 excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.

Background: The objective of the study was to evaluate the antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. Methods: In the present study, the dried leaves of P. imbricatum were subjected to extraction with ethanol, and then it was fractioned by chloroform and pet ether solvent. Antidiarrheal effects were tested by using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal transit test. Antinociceptive activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test. Results: The standard drug loperamide (5 mg/kg) showed significant (p<0.001) inhibitory activity against castor oil-induced diarrhea, in which all the examined treatments decreased the frequency of defecation and were found to possess an anti-castor oil-induced enteropooling effect in mice by reducing both weight and volume of intestinal content significantly, and reducing the propulsive movement in castor oil-induced gastrointestinal transit using charcoal meal in mice. The results showed that the ethanol extract of P. imbricatum leaves has significant dose-dependent antinociceptive activity, and among its two different fractions, the pet ether fraction significantly inhibited the abdominal writhing induced by acetic acid and the licking times in formalin test at both phases. Conclusions: These findings suggest that the plant may be a potential source for the development of a new antinociceptive drug and slightly suitable for diarrhea, as it exhibited lower activity. Our observations resemble previously published data on P. imbricatum leaves.

Background: Fenugreek ( Trigonella foenum - graecum ) seeds and onion ( Allium cepa ) are independently known to have antidiabetic effects through different mechanisms. The beeneficial influence of a combination of dietary fenugreek seeds and onion on hyperglycemia and its associated metabolic abnormalities were evaluated in streptozotocin-induced diabetic rats. Methods: Diabetes was experimentally induced with streptozotocin and diabetic rats were fed with 10% fenugreek or 3% onion or their combination for 6 weeks. Results: These dietary interventions significantly countered hyperglycemia, partially improved peripheral insulin resistance and impaired insulin secretion, reduced β-cell mass and markedly reversed the abnormalities in plasma albumin, urea, creatinine, glycated hemoglobin and advanced glycation end products in diabetic rats. These beneficial effects were highest in the fenugreek+onion group. Diabetic rats with these dietary interventions excreted lesser glucose, albumin, urea and creatinine, which were accompanied by improved body weights compared with the diabetic controls. These dietary interventions produced ameliorative effects on pancreatic pathology as reflected by near-normal islet cells, restored glycogen and collagen fiber deposition in diabetic rats. Conclusions: This study documented the hypoglycemic and insulinotropic effects of dietary fenugreek and onion, which were associated with countering of metabolic abnormalities and pancreatic pathology. It may be strategic to derive maximum nutraceutical antidiabetic benefits from these functional food ingredients by consuming them together.

Background: Desmodium adscendens extract (DAE) is used traditionally in Ghana for the management of psychosis. The present study aimed at providing pharmacological evidence for its ethnomedical use by testing the hypothesis that an ethanolic extract of Desmodium adscendens may possess antipsychotic properties. Methods: The primary behavioral effects of DAE on the central nervous system of mice were investigated using Irwin’s test paradigm. Novelty-induced and apomorphine-induced locomotor and rearing behaviors in mice were explored in an open-field observational test system. Apomorphine-induced cage climbing test in mice was used as the antipsychotic animal model. The ability of DAE to induce catalepsy and enhance haloperidol-induced catalepsy was also investigated in mice. Results: The DAE produced sedation, cholinergic-, and serotonergic-like effects in mice when evaluated using the Irwin’s test. No lethality was observed after 24 h post-treatment. The LD 50 in mice was estimated to be greater than 3000 mg/kg. The DAE significantly decreased the frequency of novelty- and apomorphine-induced rearing and locomotor activities in mice. It also significantly lowered the frequency and duration of apomorphine-induced climbing activities in mice. It did not induce any cataleptic event in naïve mice but only significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. Conclusions: The ethanolic extract of Desmodium adscendens exhibited antipsychotic-like activities in mice. Motor side effects are only likely to develop at higher doses of the extract.