Curcumin, as a pleiotropic agent, improves doxorubicin-induced nephrotic syndrome in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a phenolic compound extracted from the rhizome of turmeric (Curcuma longa L.), has been reported to have broad biological functions including potent antioxidant and renoprotective effects. It has been reported that Curcumin has a certain protective effect on the kidney. However, its mechanism of action needs further study. AIM OF THE STUDY: The present research aims at investigating the therapeutic effects and its underlying mechanism of curcumin on NS. MATERIALS AND METHODS: The conditionally immortalized mouse podocyte cell line was utilized to evaluate the podocyte-protective effect of curcumin and its effects on NF-κB pathway and Nrf2/ARE pathway in podocyte in vitro. Furthermore, the DOX-induced NS rats were utilized to investigate the therapeutic effects and its underlying mechanism of curcumin against NS in vivo. RESULTS: The consequences of this study revealed that curcumin activated Nrf2, inhibited NF-κB pathway and up-regulated podocin in DOX-induced podocyte. Further research results showed that curcumin can considerably alleviate proteinuria and improve hypoalbuminemia in NS rats, and lower blood lipid levels to alleviate hyperlipidemia in NS rats, indicating that curcumin has significant therapeutic effects on rat NS. Further observation by electron microscopy and detection showed that curcumin can improve renal function and podocyte injury, which may be related to the repairment of mRNA expression and podocin protein. Interestingly, the results of the blood rheology test showed that curcumin can effectively reduce whole blood viscosity (WBV) and plasma viscosity (PV), and reduce hematocrit (Hct). In addition, the oxidative stress state of kidney in NS rats was considerably reversed by curcumin, which may be achieved by activating Nrf2 and increasing the expression of antioxidant enzymes HO-1, NQO-1. We also found that NF-κB pathway is activated in the kidney of NS rats, and curcumin can inhibit the activation of NF-κB by down-regulating the expression of NF-κB p65, reducing the level of p-IκBα and up-regulating the expression of IκBα. CONCLUSION: These findings suggest that curcumin, as a multifunctional agent, exerts a protective effect on DOX-induced nephrotic syndrome in rats, which provides a pharmacological basis for the further development of curcumin and also provides a basis for the advantages of multi-targeted drugs in the processing of NS.

Amyloid ß protein injection into medial septum impairs hippocampal long-term potentiation and cognitive behaviors in rats.

The specific loss of cholinergic neurons and the progressive deficits of cognitive function are the most primary characteristics of Alzheimer's disease (AD). Although the neurotoxicity of amyloid ß protein (Aß) in AD has been investigated extensively, it is still unclear whether the Aß aggregated in the medial septum (MS), a major cholinergic nucleus projecting to the hippocampus, could affect hippocampal synaptic plasticity and further impair the memory behaviors. The present study investigated the effects of Aß injection into the MS on hippocampal long-term potentiation (LTP) and cognitive behaviors of rats by using Morris water maze (MWM), Y maze and in vivo hippocampal LTP recording. The effects of kainic acid (KA), an agent with specific neurotoxicity to GABAergic neurons, were also observed. The results showed that: (1) Intra-MS injection of Aß25-35, not KA, impaired spatial learning and memory of rats in classical and reversal MWM tests; (2) Both Aß25-35 and KA impaired novelty-seeking behavior of rats in Y maze; (3) Intra-MS injection of Aß25-35, not KA, suppressed in vivo hippocampal LTP in the CA1 region of rats; (4) Both Aß25-35 and KA did not affect the motor ability in behavioral tests and the hippocampal paired-pulse facilitation (PPF) in electrophysiological recording. These results indicate that intra-MS injection of Aß could impair spatial memory, cognitive flexibility and exploratory motivation, as well as hippocampal LTP in rats, suggesting that the cholinergic neurons in the MS and the septo-hippocampal projection could be important targets of neurotoxic Aß, and the specific damage of cholinergic neurons in the MS is likely responsible for the impairments of hippocampal synaptic plasticity and cognitive function in AD.

Davunetide improves spatial learning and memory in Alzheimer's disease-associated rats.

Memory loss and cognition decline are the main clinical manifestations of Alzheimer's disease (AD). Amyloid ß protein (Aß) aggregated in the brain is one of the key pathological characteristics of AD and responsible for the deficits in learning and memory. It is reported that davunetide, an octapeptide derived from activity-dependent neuroprotective protein (ADNP), inhibited Aß aggregation and Aß-induced neurotoxicity. To further characterize the neuroprotective roles of davunetide and its possible mechanism, the present study investigated the effects of davunetide on Aß1-42-induced impairments in spatial memory, synaptic plasticity and hippocampal AKT level. In Morris water maze (MWM) test, bilateral intrahippocampal injection of Aß1-42 significantly increased escape latency and decreased target quadrant swimming time of rats, while three weeks of intranasal application of davunetide reversed the Aß1-42-induced learning deficits and memory loss in a dose-dependent manner. In vivo field potentiation recording showed that Aß1-42 suppressed long-term potentiation (LTP) of excitatory postsynaptic potential (fEPSP) in the hippocampal CA1 region of rats, while davunetide effectively blocked the suppression of LTP, without affecting paired-pulse facilitation (PPF). Western blotting experiments showed a significant decrease in the level of hippocampal p-AKT (Ser473), not total AKT, in Aß1-42 only group, which was mostly antagonized by davunetide treatment. These findings demonstrate that davunetide, probably by enhancing PI3K/AKT pathway, plays an important positive role in attenuating Aß1-42-induced impairments in spatial memory and synaptic plasticity, suggesting that davunetide could be an effective therapeutic candidate for the prevention and treatment of neurodegenerative disease such as AD.

Characteristics of Agraphia in Chinese Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment.

BACKGROUND: Patients with Alzheimer's disease (AD) manifest progressive decline in writing abilities. Most studies on agraphia in AD have been performed in the alphabetic system, such as English. However, these findings may not be applicable to other written language systems. The unique features of the Chinese written script could affect the patterns of agraphia in Chinese AD patients. The aim of this study was to explore the features of writing errors in Chinese patients with AD and amnestic mild cognitive impairment (a-MCI), as well as to study the relationship between their writing errors and neuropsychological functions. METHODS: In this study, we performed an observational study in a group of subjects including 17 AD patients, 14 patients with a-MCI, and 16 elderly healthy controls. We analyzed the writing errors in these subjects and also studied the relationship between their writing errors and neuropsychological functions. RESULTS: Our study showed that in patients whose mother tongue is Chinese, writing ability was comparatively well preserved in the MCI phase but significantly impaired when the disease progressed to the stage of AD. The writing errors showed corresponding increase with the severity of cognition decline, both in the types of errors and rate of occurrence. Analysis of the writing errors showed that word substitution and unintelligible words were the most frequent error types that occurred in all the three study groups. The occurrence rate of unintelligible words was significantly higher in the AD group compared with the a-MCI group (P = 0.024) and control group (P = 0.018). In addition, the occurrence rates of word substitution were also significantly higher in AD (P = 0.013) and a-MCI groups (P = 0.037) than that of control group. However, errors such as totally no response, visuospatial impairment, paragraph agraphia, ideograph, and perseverative writing errors were only seen in AD group. Besides, we also found a high occurrence rate of visuoconstructional errors (13.3%) in our AD group. CONCLUSIONS: Our study confirmed that agraphia is an important feature in patients with AD. The writing error profile in patients whose native language is Chinese was unique compared to patients using the alphabetic language system.

DNA binding, cytotoxicity and apoptosis induction activity of a mixed-ligand copper(II) complex with taurine Schiff base and imidazole.

A novel binuclear copper(II) complex (complex 1) with taurine Schiff base and imidazole has been synthesized and structurally characterized by single crystal X-ray diffraction, elemental analysis, ESI-MS spectrometry, UV-vis and IR spectroscopy. Single-crystal analysis revealed that 1 displays the sulfonate-bridged dinuclear copper(II) centers. Both copper atoms are five-coordinated and exhibit slightly distorted square pyramidal geometries. Each of copper atom is surrounded by three oxygen atoms and one nitrogen atom from different taurine Schiff base ligands, and one nitrogen atom from one imidazole ligand. The interaction between 1 and calf thymus DNA (CT-DNA) was investigated by UV-vis, fluorescence, circular dichroism (CD) spectra and agarose gel electrophoresis. The experimental results indicated that 1 could bind to CT-DNA via an intercalative mode and show efficient cleavage activity. In addition, 1 showed an antitumor effect on cell cycle and apoptosis. Flow cytometric analysis revealed that MGC-803 cells were arrested in the S phase after treatment with 1. Fluorescence microscopic observation indicated that 1 could induce apoptosis of MGC-803 cells.

What Is Important During the Selection of Traditional Chinese Medicine (TCM) in a Health Care Reimbursement or Insurance System?" Critical Issues of Assessment from the Perspective of TCM Practitioners.

OBJECTIVE: Complementary and alternative medicine (CAM) has gained increasing popularity over the last several decades internationally, leading to an increasing interest from decision makers and researchers as to how to assess the effectiveness of CAM. The attempts, however, have been unsatisfactory. The most important reason is a lack of attention to the theoretical characteristics of CAM, which are completely different from those of allopathic medicine or biomedicine. This study attempted to survey expert Traditional Chinese Medicine (TCM) practitioners in China to elucidate critical issues when assessing the effectiveness of TCM. METHODS: A questionnaire (with 20 close-ended and 2 open-ended questions) about the influencing factors of measuring the cost and effectiveness of TCM was distributed to TCM practitioners who had been working in the field of research for at least 5 years and had published at least one related scientific article in the last 5 years. Internal consistency test was performed for all questions to verify the reliability of the questionnaire. Principal-component analysis was performed for remaining items after Kaiser-Meyer-Olkin (KMO) index and Bartlett's test of sphericity. A linear combination model was then built to evaluate the contribution of various factors involved for the selection of TCM into the health care reimbursement or insurance system. RESULTS: Of 429 questionnaires issued, 137 were returned from respondents from 31 medical and research institutions, giving a recovery rate of 31.93%. Internal consistency coefficient obtained was 0.745, indicating good reliability of this measurement scale, and the data passed the KMO test and Bartlett's test of sphericity (KMO index = 0.691). In addition, eight common factors were extracted after the rotation of principal-component analysis with a cumulative variance of 70.92%. CONCLUSIONS: Our findings suggested that factors to be considered during the selection of TCM in health care reimbursement or insurance system include patient preference, long-term outcomes, comparative study of alternative options between TCM and allopathic medicine or biomedicine, pharmacoeconomic evaluation results and the overall economic burden of patients, and side effects of TCM. In addition, the TCM experts stressed the need of cost-effectiveness assessment of the expensive TCM of similar therapeutic functions during the selection process. Moreover, during the evaluation of health-related quality of life of TCM, they warned to avoid overexaggeration of their roles and that the generic scale should be modified according to the clinical circumstances.

Evaluation of impact on health-related quality of life and cost effectiveness of Traditional Chinese Medicine: a systematic review of randomized clinical trials.

BACKGROUND: Traditional Chinese Medicine (TCM), an important part of health care in China and with increased popularity worldwide, has received extensive attention from governments at all levels. With the current emphasis on clinical efficacy and cost-effectiveness, TCM, as indeed do all other treatments, requires rigorous evidence to be considered in reimbursement decision-making. Nevertheless, despite the fact that TCM treatment has always been considered to possess the advantage of improving the health-related quality of life (HRQOL) of patients, there is a lack of systematic study about available evidence to assess the impact of TCM treatments on HRQOL of patients. OBJECTIVES: The current study aimed to perform a review of available literature to evaluate whether sufficient evidence existed to allow an assessment of the impact on HRQOL and cost effectiveness of TCM treatments. This information would support a recommendation for wider use of TCM in the clinical setting as well as its consideration for reimbursement. METHODS: A structured search was performed using data sources including MEDLINE,(®) Cumulative Index for Allied Health and Nursing (CINAHL), PubMed, Cochrane database, EBSCO, SciSearch, Embase, and Google Scholar from 2000 to 2010. The search was supplemented with manual search after relevant articles were retrieved. RESULTS: After culling, a total 31 articles covering a range of TCM therapies applied to a variety of conditions were retrieved. The measurement tools used in these studies to assess impact in patient's HRQOL were mainly SF-36-based scales, but the results of HRQOL/patient preference studies were inconsistent and inconclusive. Of the 10 articles of cost-effectiveness evaluation of TCM treatments, the majority reported that TCM treatments resulted in better outcomes at a higher cost, but the incremental cost-effectiveness ratio was below the usually recommended thresholds. The overall results showed acupuncture and t'ai chi to be the most studied TCM-related therapies. CONCLUSIONS: The current review showed that there is a relative lack of cost-effectiveness research in TCM. For those few empirical research available, the major emphasis is for acupuncture or t'ai chi showing the acceptance of these branches of TCM that are better understood by the scientific community. The current results also showed the need for studies with better designs and longer duration to ascertain the actual impact of TCM on patients' HRQOL as well as a need for a generic HRQOL instrument that is specific for TCM.