Neuroprotective effect of epigallocatechin-3-gallate against beta-amyloid-induced oxidative and nitrosative cell death via augmentation of antioxidant defense capacity.

Arch Pharm Res. 2009 Jun; 32(6): 869-81Kim CY, Lee C, Park GH, Jang JHbeta-Amyloid (Abeta) peptide, a major component of senile plaques has been regarded to play a crucial role in the development and neuropathogenesis of Alzheimer's disease (AD). Increasing data from in vitro and in vivo studies indicate that Abeta-induced damages in neurons and glia are mediated via nitrosative as well as oxidative stress. Therefore, recent researches have been focused on searching for dietary and herbal manipulations to protect against the Abeta-induced oxidative and/or nitrosative cell death. Epigallocatechin-3-gallate (EGCG), one of these candidates is a major polyphenolic compound present in green tea and has been reported to exhibit potent antioxidant and anti-inflammatory properties. In the present study, we have investigated the effect of EGCG against Abeta-induced oxidative and/or nitrosative cell death in BV2 microglia. Abeta treatment led to apoptosis in BV2 cells as revealed by DNA fragmentation, perturbation of mitochondrial transmembrane potential, and alterations in the expression of apoptosis-regulator Bcl-2 family proteins. EGCG pretreatment effectively ameliorated Abeta-induced cytotoxicity and manifestation of proapoptotic signals. Furthermore, BV2 cells exposed to Abeta underwent nitrosative stress as shown by the increased expression of inducible nitric oxide synthase (iNOS) and subsequent production of nitric oxide (NO) and peroxynitrite, which were effectively suppressed by EGCG pretreatment. To elucidate a molecular mechanism underlying the neuroprotective effect of EGCG, we have examined the cellular metabolism of reduced glutathione (GSH) with antioxidant properties. EGCG treatment fortified cellular GSH pool through elevated mRNA expression of gamma-glutamylcysteine ligase (GCL), the rate limiting enzyme in the glutathione biosynthesis. These results suggest that EGCG may have preventive and/or therapeutic potential in AD patients by augmenting cellular antioxidant defense capacity and attenuating Abeta-mediated oxidative and/or nitrosative cell death.

Differential effect of Shenmai injection, a herbal preparation, on the cytochrome P450 3A-mediated 1'-hydroxylation and 4-hydroxylation of midazolam.

Chem Biol Interact. 2009 Aug 14; 180(3): 440-8Xia C, Sun J, Wang G, Shang L, Zhang X, Zhang R, Wang X, Hao H, Xie LShenmai injection (SMI), one of the most popular herbal preparations, is widely used for the treatment of coronary atherosclerotic cardiopathy and viral myocarditis. The purpose of this study was to investigate the effect of Shenmai injection (SMI) on the CYP3A-mediated metabolism of midazolam (MDZ). The present study demonstrated that SMI could significantly inhibit MDZ 4-hydroxylation but activate its 1'-hydroxylation in human liver microsomes (HLMs), rat liver microsomes (RLM) and recombinant human CYP3A4 and CYP3A5. The opposing effect of SMI was characterized by the kinetic change of increasing Vmax/Km for MDZ 1'-hydroxylation and decreasing Vmax/Km for MDZ 4-hydroxylation in HLM and RLM. The presence of SMI enhanced the inhibition of ketoconazole on MDZ 4-hydroxylation but weakened or reversed its inhibition on MDZ 1'-hydroxylation in HLM. After single or multiple pretreatment with SMI, the ratios of AUC(4-OH MDZ)/AUC(MDZ) in rats were significantly decreased, while the ratios of AUC(1'-OH MDZ)/AUC(MDZ) were increased. Among the major components in SMI, total ginsenoside (TG), ophiopogon total saponins (OTS), ophiopogon total flavone (OTF), ginsenoside Rd, ophiopogonin D and ophiopogonone A exhibited significant inhibition on both 4-hydroxylation and 1'-hydroxylation of MDZ in HLM and RLM, while no activation on MDZ metabolism was observed in the presence of these major constituents alone or together. To further explore the responsible components, 3 mL of SMI was loaded on a solid phase extraction (SPE) C18 cartridge and then separated by different concentrations of methanol. The fractions eluted with 60% and 90% methanol both showed significant activation on MDZ 1'-hydroxylation in HLM, but the fraction eluted with 30% methanol had no such effect. The results indicated that the activation of SMI on MDZ 1'-hydroxylation might be mainly resulted from the lipid-soluble components in SMI.

Prevalence of Polypharmacy, Polyherbacy, Nutritional Supplement Use and Potential Product Interactions among Older Adults Living on the United States-Mexico Border: A Descriptive, Questionnaire-Based

Drugs Aging. 2009; 26(5): 423-36Loya AM, González-Stuart A, Rivera JOThe use of multiple medications, herbs or nutritional supplements can lead to adverse consequences, particularly in the elderly. A significant consequence resulting from polypharmacy, polyherbacy and nutritional supplement use is the potential for interactions to occur among the various products. The primary objective of this study was to estimate the prevalence of polypharmacy, polyherbacy, nutritional supplement use and potential product interactions among older adults living on the US-Mexico border. This was a descriptive study that involved the administration of a bilingual (English/Spanish) questionnaire to a convenience sample of adults aged >/=60 years recruited from senior centres located within the most populated US-Mexico border region from June 2005 to March 2006. Participant demographics were collected in addition to information about current use of prescription medications, over-the-counter (OTC) medications, herbal products and nutritional supplements (i.e. nutraceuticals and vitamins or minerals). The outcomes measured were the number of prescription medications, OTC medications, herbal products, vitamins/minerals and nutraceuticals per participant. Furthermore, the number of potential interactions and major interactions between drugs, herbal products and nutritional supplements were identified for each participant. Additionally, product use patterns between men and women and among locations within the border region were compared. One-hundred-and-thirty participants (mean age 71.4 years) were recruited to complete the questionnaire. The prevalence of polypharmacy among all participants was 72.3% (n = 94), with 38.5% (n = 50) taking five or more concomitant medications (major polypharmacy). Twenty-one participants (16.2%) in the study sample reported taking two or more herbal products (polyherbacy). Thirty-four participants (26.2%) reported taking two or more vitamin/mineral supplements and nine (6.9%) reported using two or more nutraceuticals. Participants living on the US side of the border had higher rates of major polypharmacy, polyherbacy and use of nutritional supplements than those living on the Mexican side of the border. Overall, there were no significant differences in medication, herbal product and nutritional supplement use patterns between men and women. Evaluation of potential interactions revealed that 46.2% (n = 60) of participants were at risk of having at least one potential drug-drug interaction. Regarding drug and herbal product-supplement interactions, 31.5% (n = 41) of participants were at risk of having at least one possible interaction. The prevalence of polypharmacy among older adults living on the US side of the border was similar to national trends (estimates suggest that one-quarter to one-half of US adults aged >/=65 years take five or more medications). However, polypharmacy was less common in older adults living on the Mexican side of the border. Additionally, herb use was higher in older adults living on the US-Mexico border than has been reported in national surveys of US adults, which indicate that less than one-quarter of adults have used a herbal product within the previous 12 months. Furthermore, this study demonstrated that older adults living on the US side of the border consumed more herbs and nutritional supplements than their Mexican counterparts. In addition to describing product use patterns on the border, these findings suggest that almost half of the older adult participants were at risk for a potential drug-drug interaction, with approximately one-third having a potential interaction between their medications, herbs or nutritional supplements.

Simultaneous characterization of quaternary alkaloids, 8-oxoprotoberberine alkaloids, and a steroid compound in Coscinium fenestratum by liquid chromatography hybrid ion trap time-of-flight mass spect

J Pharm Biomed Anal. 2009 May 30; Deevanhxay P, Suzuki M, Maeshibu N, Li H, Tanaka K, Hirose SSimultaneous characterization of quaternary alkaloids, 8-oxoprotoberberine alkaloids, and a steroid compound in Coscinium fenestratum was successfully performed by liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LC/IT-TOF MS). A total of 32 compounds, including 2 benzylisoquinoline alkaloids, 3 aporphine alkaloids, 12 quaternary protoberberine alkaloids, 10 8-oxoprotoberberine alkaloids, 3 tetrahydroprotoberberine alkaloids, and a steroid compound were simultaneously separated and characterized by matching the empirical molecular formulae with those published in literature and the multi-stage mass spectrometry (MS(n)) data obtained using structural information from IT, accurate mass measurement obtained from TOF MS, and HPLC separation. A total of 20 compounds, including 4 novel natural products were identified or tentatively identified for the first time from Coscinium fenestratum. In the positive-ion mode, 8-oxoprotoberberines produced [M+H](+) and [M+Na](+); the fragmentation of 8-oxodihydroprotoberberines produced [M+H-CH(3)] (+), [M+H-CH(3)-CH(3)](+), and [M+H-CH(3)-CH(3)-CO](+), while 8-oxotetrahydroprotoberberines generated [M+H-CH(3)](+), [M+H-CH(3)-CH(3)](+), [M+H-CH(3)-H](+), and iminium ions from the cleavage of the protoberberine skeleton. The method can be applied for the analysis of 8-oxoberberine and other alkaloids in Coptis japonica, Phellodendron amurense, and other herbal medicines.