Analysis of bioactive compounds in cinnamon leaves and preparation of nanoemulsion and byproducts for improving Parkinson's disease in rats.

Introduction: Cinnamomum osmophloeum Kanehira (C. osmophloeum), a broad-leaved tree species of Taiwan, contains phenolic acids, flavonoids, and phenylpropanoids such as cinnamaldehyde and cinnamic acid in leaves. Many reports have shown that the cinnamon leaf extract possesses anti-inflammatory, hypoglycemic, hypolipidemic and neuroprotective functions. This study aims to analyze bioactive compounds in C. osmophloeum (cinnamon leaves) by UPLC-MS/MS and prepare hydrosol, cinnamon leaf extract and cinnamon leaf nanoemulsion for comparison in improving Parkinson's disease (PD) in rats. Methods: After extraction and determination of total phenolic and total flavonoid contents, cinnamaldehyde and the other bioactive compounds were analyzed in cinnamon leaves and hydrosol by UPLC-MS/MS. Cinnamon leaf nanoemulsion was prepared by mixing a suitable proportion of cinnamon leaf extract, soybean oil, lecithin, Tween 80 and deionized water, followed by characterization of particle size and polydispersity index by dynamic light scattering analyzer, particle size and shape by transmission electron microscope, encapsulation efficiency, as well as storage and heating stability. Fifty-six male Sprague-Dawley rats aged 8 weeks were divided into seven groups with group 1 as control (sunflower oil) and group 2 as induction (2 mg/kg bw rotenone in sunflower oil plus 10 mL/kg bw saline), while the other groups including rotenone injection (2 mg/kg bw) followed by high-dose of 60 mg/kg bw (group 3) or low-dose of 20 mg/kg bw (group 4) for tube feeding of cinnamon leaf extract or cinnamon leaf nanoemulsion at the same doses (groups 5 and 6) every day for 5 weeks as well as group 7 with rotenone plus hydrosol containing 0.5 g cinnamon leaf powder at a dose of 10 mL/kg bw. Biochemical analysis of brain tissue (striatum and midbrain) was done to determine dopamine, α-synuclein, tyrosine hydroxylase, superoxide dismutase, catalase, glutathione peroxidase and malondialdehyde contents by using commercial kits, while catalepsy performed by bar test. Results and discussion: An extraction solvent of 80% ethanol was found to be the most optimal with a high yield of 15 bioactive compounds being obtained following UPLC analysis. A triple quadrupole tandem mass spectrometer with electrospray ionization mode was used for identification and quantitation, with cinnamaldehyde present at the highest amount (17985.2 µg/g). The cinnamon leaf nanoemulsion was successfully prepared with the mean particle size, zeta potential, polydispersity index and encapsulation efficiency being 30.1 nm, -43.1 mV, 0.149 and 91.6%, respectively. A high stability of cinnamon leaf nanoemulsion was shown over a 90-day storage period at 4 and heating at 100 for 2 h. Animal experiments revealed that the treatments of cinnamon leaf extract, nanoemulsion and hydrosol increased the dopamine contents from 17.08% to 49.39% and tyrosine hydroxylase levels from 17.07% to 25.59%, while reduced the α-synuclein levels from 17.56% to 15.95% in the striatum of rats. Additionally, in the midbrain of rats, an elevation of activities of superoxide dismutase (6.69-16.82%), catalase (8.56-16.94%), and glutathione peroxidase (2.09-16.94%) was shown, while the malondialdehyde content declined by 15.47-22.47%. Comparatively, the high-dose nanoemulsion exerted the most pronounced effect in improving PD in rats and may be a promising candidate for the development of health food or botanic drug.

Utilizing Cerebral Perfusion Scan and Diffusion-tensor MR Imaging to Evaluate the Effect of Hyperbaric Oxygen Therapy in Carbon Monoxide-induced Delayed Neuropsychiatric Seqeulae- A Case Report and Literature Review.

PURPOSE: Detection of regional cerebral blood flow (rCBF) and/or brain magnetic resonance imaging (MRI) has been used to investigate functional defect of brain caused by carbon monoxide (CO) poisoning. In this report, we attempted to demonstrate the correlation of changes in brain singlephoton emission computed tomography (SPECT) and diffusion-tensor MR image (DTI) with functional improvement of severe delayed neuropsychiatric sequelae (DNS) after CO intoxication during the treatment of hyperbaric oxygen therapy (HBOT). CASE REPORT: The patient had normal activities of daily life after he recovered from acute CO poisoning. One month later, he presented symptoms of declined cognitive functioning, aphasia, apraxia, dysphagia, muscle rigidity, urine and fecal incontinence. After one course of HBOT, these symptoms improved significantly and the patient could regain most of his previous functioning. The patient's improvement was evidenced by increased rCBF in Brodmann areas 7, 8, 11 and 40, as well as higher mean fractional anisotropy (FA) value of DTI. CONCLUSION: Although the efficacy of HBOT in DNS patients is still needed to be evaluated in large clinical study, these data suggest that HBOT may be the choice to improve DNS efficiently and shorten the duration of suffering with favorable outcome.

Cancer risks among the users of ergot-derived dopamine agonists for Parkinson's disease, a nationwide population-based survey.

BACKGROUND: Factors of cancer occurrence among Parkinson disease patients are still not well known, although genetic predilection has been investigated. The aim of this study is to evaluate the medication effect of dopamine agonists of Parkinson disease on incidence of cancers from the Taiwan National Health Insurance Research Database. METHODS: We conducted a population-based nested case-control study by using the resources of the Taiwanese National Health Insurance from 1996 to 2000 and analyzed the prevalence of cancer among patients with Parkinson disease. A nested analysis was then implemented among those patients with both Parkinson disease and cancer, focusing separately on the use of ergot- and nonergot-derived-dopamine agonists. RESULTS: We reviewed 6211 patients with Parkinson's disease and found 329 patients with cancer. The ergot-derived dopamine agonists users were associated with an increased odds ratio for cancer, compared with nonergot-derived dopamine agonist users, with an adjusted odds ratio of 2.16 (95% confidence interval, 1.55-2.99). Among all the cancer types, we observed the higher occurrence of liver cancer among the ergot-derived dopamine agonist users. CONCLUSION: The association of ergot-derived-dopamine agonist use and cancers, especially the liver cancers, has provided us the information to further understand the drug-cancer interaction. We hope this result would prompt further investigations on the risk and benefit of the dopamine agonists use among the Parkinson's disease patients.

Effects of repetitive hyperbaric oxygen treatment in patients with acute cerebral infarction: a pilot study.

The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This prospective study assessed the efficacy and safety of HBOT as adjuvant treatment on 46 acute ischemic stroke in patients who did not receive thrombolytic therapy. The HBOT group (n = 16) received conventional medical treatment with 10 sessions of adjunctive HBOT within 3-5 days after stroke onset, while the control group (n = 30) received the same treatment but without HBOT. Early (around two weeks after onset) and late (one month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. The baseline clinical characteristics were similar in both groups. Both early and late outcomes of the HBOT group showed significant difference (P ≤ 0.001). In the control group, there was only significant difference in early outcome (P = 0.004). For early efficacy, there was no difference when comparing changes of NIHSS scores between the two groups (P = 0.140) but there was statistically significant difference when comparing changes of NIHSS scores at one month (P ≤ 0.001). The HBOT used in this study may be effective for patients with acute ischemic stroke and is a safe and harmless adjunctive treatment.

Improvement of clinical outcome and cerebral perfusion in a patient of atherosclerotic cerebral infarction after repetitive hyperbaric oxygen treatment--a case report and literature review.

This is a case report of hyperbaric oxygen therapy (HBO2T) for ischemic stroke. HBO2T should be the potential or additional treatment (with thrombolytic therapy) for ischemic stroke according to the preclinical and clinical studies. Hereby, we present a 56-year-old Chinese man with vascular risk factors. He had an acute ischemic stroke on the left corona radiata, with right hemiparesis and dysarthria resulting from atherosclerosis. The patient could not get thrombolytic treatment because the time to ER was in excess of five hours. He experienced great improvement after the general course of HBO2T; this was evaluated with standard rating scales for stroke research and cerebral perfusion images, including brain-computed tomography perfusion (CTP) and single-photon emission computed tomography (SPECT). Although few clinical trials showed a negative result, we suggest that further trials on HBO2T are still needed. Meanwhile, we emphasize the importance of HBO2T protocol and the selection of a suitable patient, which may influence the outcome.

Ganoderma tsugae extract inhibits expression of epidermal growth factor receptor and angiogenesis in human epidermoid carcinoma cells: In vitro and in vivo.

We examined the anti-angiogenic effects of Ganoderma tsugae methanol extract (GTME) on human epidermoid carcinoma A-431 cells. Our data indicate that GTME inhibits the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in vitro and in vivo, and also inhibits the capillary tube formation of human umbilical vein endothelial cells (HUVECs). We also show that the suppression of VEGF expression by GTME can be restored by treatment with EGF. These results suggest that GTME inhibits VEGF expression via the suppression of EGFR expression, resulting in the downregulation of VEGF secretion from epidermoid carcinoma A-431 cells. These findings reveal a novel role for G. tsugae in inhibiting EGFR and VEGF expression, which are important for tumor angiogenesis and growth. Thus, GTME may provide a potential therapeutic approach for anti-tumor treatment.