Effects of curcumin and γ-oryzanol solid dispersion on the brain of middle-aged rats.

Oxidative stress is one of the major factors that contributes to brain deterioration in the elderly. Oxidation causes molecular alterations, structural damage, and brain dysfunction, which includes cognitive impairment. Memory loss can begin in middle-aged individuals, so prevention of brain deterioration before aging is important. Several studies have reported that curcumin and γ-oryzanol exhibits anti-oxidant and anti-inflammatory properties. However, curcumin and γ-oryzanol exhibit low aqueous solubility. Thus, a solid dispersion technique was used to prepare curcumin and γ-oryzanol to enhance their solubility and stability. This study aims to evaluate the effects and mechanisms of γ-oryzanol solid dispersion (GOSD) and curcumin solid dispersion (CURSD) on learning and memory in six groups of male rats (n=5/group). Group one was the adult control consisting of 6-week old male rats, and the remaining five groups consisted of 42-week (middle-aged) male rats. The groups were labeled as the control group, the GO group (GOSD 10 mg/kg·BW), the Cur group (CURSD 50 mg/kg·BW), the GO-LCur group (GOSD 10 mg/kg·BW plus CURSD 25 mg/kg·BW), and the GO-HCur group (GOSD 10 mg/kg·BW plus CURSD 50 mg/kg·BW). Substances were administrated by oral gavage once daily for 42 consecutive days. The GO-HCur group exhibited significantly increased learning and memory performance in a Morris water maze and in reacting to a spontaneous tendency novel object test. The rats also exhibited decreased levels of lipid peroxidation, increased superoxide dismutase levels, glutathione peroxidase levels, catalase activity, and enhanced c-Fos expression both in the hippocampus and prefrontal cortex. The results indicated that GOSD 10 mg/kg plus CURSD 50 mg/kg was able to enhance learning and memory performance in the middle-aged rats.

Anti-nociceptive effects of ECa 233 a standardized extract of Centella asiatica (L.) Urban on chronic neuropathic orofacial pain in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: ECa 233 is a standardized extract of Centella asiatica (L.) Urban, a herb traditionally used to treat a number of diseases including neurological disorders. Accordingly, ECa 233 showed benefits on animal models of cognitive deficits, chronic stress and Parkinson's disease. Analgesic activity of ECa 233 was shown in Tail's flick test in rodent and relieving aphthous ulcer pain in man. Moreover, acute and sub-chronic toxicity testing in rodents and pharmacokinetic study in healthy volunteers, clinical trial phase I demonstrated good safety profiles of ECa 233. AIM OF THE STUDY: This study aims to evaluate the anti-nociceptive effects of ECa 233 and its synergistic effect with gabapentin on chronic neuropathic orofacial pain after 3 weeks infraorbital nerve chronic constriction injury in mice. The peripheral and central nociceptive activities are also examined. MATERIALS AND METHODS: Chronic neuropathic orofacial pain was induced by 3 weeks infraorbital nerve chronic constriction injury. Mice were treated with ECa 233 (30, 100 and 300 mg/kg) and gabapentin (10 mg/kg) by oral gavage starting on day 21 and going on for 14 consecutive days. Mechanical hyperalgesia and allodynia were measured on day 7, 14, 21, 28 and 35 after infraorbital nerve chronic constriction injury. At the end of the experiment, mice were observed for the sedative effect using the locomotor activity, the calcitonin gen-related peptide in trigeminal ganglion and c-fos expression in trigeminal nucleus caudalis were investigated after euthanasia. RESULTS: Infraorbital nerve chronic constriction injury gradually induced marked ipsilateral mechanical hyperalgesia and allodynia. The maximum hyperalgesia and allodynia response presented on day 21 and the response was remained constant until day 35. Treatment with either 300 mg/kg ECa 233 or 10 mg/kg gabapentin were able to attenuate mechanical hyperalgesia and allodynia. The downregulation of calcitonin gen-related peptide on ipsilateral trigeminal ganglion were observed in ECa 233 at 100 and 300 mg/kg and 10 mg/kg gabapentin-treated groups. The c-fos expression on ipsilateral trigeminal nucleus caudalis was also decreased in 300 mg/kg ECa 233 and 10 mg/kg gabapentin-treated groups. CONCLUSION: ECa 233 reduced hyperalgesia and allodynia by modulating the peripheral calcitonin gen-related peptide expression consequently alleviate the nociceptive activity in trigeminal nucleus caudalis. Further clinical trial to proof ECa 233's efficacy in neuropathic pain in man as well as possible attributable mechanism of action should be further investigated.

Neuroprotective effect of Asparagus racemosus root extract via the enhancement of brain-derived neurotrophic factor and estrogen receptor in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Asparagus racemosus (AR) is well known as an Ayurvedic rasayana which used traditionally by Ayurvedic practitioners for nervous disorders and prevent aging. In our previous study it was found that ethanol AR root extract can improve learning and memory impairment, induced by an ovariectomy, but the extract's mechanisms as a neuroprotective property are still unknown. AIM OF THE STUDY: This study aimed to examine the effects and mechanisms of ethanol AR root extract on the alteration of brain-derived neurotrophic factor (BDNF) and estrogen receptor (ER) subtypes in ovariectomized (OVX) rats. MATERIALS AND METHODS: Adult female Wistar rats were divided into five groups, 4 groups underwent ovariectomy, and one group was designed to be the sham control group. Two groups were gavaged with propylene glycol for sham, and a second group similarly prepared for OVX. Two further groups of OVX rats were gavaged once daily, one group with 100 mg/kg b.w. of ethanol AR root extract and the second group with 1000 mg/kg b.w. of ethanol AR root extract. The fifth group was gavaged once daily with 0.1 mg/kg b.w. of 17α-ethynylestradiol (EE). BDNF, ERα and ERß expression were evaluated by western blot analysis. RESULTS: The western blot analysis revealed that the OVX rats showed a significant decrease in BDNF and a down-regulation of ERα and ERß in the frontal cortex and hippocampus. It was also demonstrated that EE and AR root extract increased BDNF, ERα and ERß in the frontal cortex and hippocampus of ovariectomized rats. CONCLUSIONS: Based on these results, the enhancement of BDNF and ERs up-regulation may be involved in the neuroprotective effects of ethanol AR root extract in ovariectomized rat.

Inhibitory effects of Tabernaemontana divaricata root extract on oxidative stress and neuronal loss induced by amyloid ß25-35 peptide in mice.

In Alzheimer's disease, there are numerous amyloid plaques, neurofibrillary tangles, and neuronal loss in several brain areas. Oxidative stress is involved in the mechanisms of Aß-peptide induced neurotoxicity by the generation of free radical oxidative stress that may lead to neurodegeneration. Tabernaemontana divaricata has various medical properties in Thai folklore medicine including prevent forgetfulness or improve memory. The present study aimed to investigate the effects of T. divaricata root extract (TDE) on Aß25-35 peptides induced neuronal loss and oxidative stress in mice. Male ICR mice were administered with vehicle or TDE (250, 500, and 1000 mg/kg b.w., p.o.) for 28 consecutive days. Then, these mice were given a single intracerebroventricular (i.c.v.) injection of Aß25-35 or phosphate buffer saline (PBS) (10 µg/mouse). The novel object recognition (NOR) test was used to determine memory disturbance. In addition, the neuronal cells in the cerebral cortex and hippocampus were measured by using crystal violet staining and lipid peroxidation was determined by measuring the formation of thiobarbituric acid reactive substances. An i.c.v. injection of Aß25-35 peptides could significantly induce memory impairment, increase level of lipid peroxidation including the neuronal loss in CA3 of hippocampus. However, the mice pretreated with TDE could prevent the memory loss, neuronal loss and decrease lipid peroxidation. These results suggest the potential therapeutic value in dementia of TDE through its antioxidant property.

The effects of Tabernaemontana divaricata root extract on amyloid beta-peptide 25-35 peptides induced cognitive deficits in mice.

UNLABELLED: ETHNOPHAMACOLOGICAL RELEVANCE: Tabernaemontana divaricata (TD), a Thai medicinal herb, has been widely used as an analgesic, sedative, or a cough syrup. Moreover, it has been used in traditional rejuvenation remedies as for preventing forgetfulness and improving the memory. AIM OF STUDY: The present study aimed to determine the effect of TD on Abeta25-35 peptides induced cognitive deficits and acetylcholinesterase activity in mice. MATERIALS AND METHODS: Mice were pretreated with TDE (250, 500 and 1,000 mg/kg body weight) for 28 days and then received i.c.v. injection of Abeta25-35 peptides. Cognitive performance was evaluated using the Morris water maze (MWM) and step-down avoidance test. The Ellman's colorimetric method was used to investigate the levels of cortical and hippocampal AChE activity. RESULTS: Abeta25-35 peptides induced the memory impairment and the increased levels of cortical and hippocampal AChE activity. The consumption of TDE significantly improved the memory impairment and attenuated the brain levels of AChE activity induced by Abeta25-35 peptides. CONCLUSIONS: These findings suggest that subchronic administration of TDE might prevent the Abeta25-35 peptides induced memory deficits by decreasing the AChE activity level. Therefore TDE could potentially be one of nootropic supplements for those elderly people suffering from dementia such as the AD patients.