The effects of decision aids for genetic counselling among people considering genetic testing: A systematic review.

AIM: To assess the effectiveness of decision aids for genetic counsellees to improve their conflicts in decision-making and psychological well-being when considering genetic tests for inherited genetic diseases, and their knowledge about these tests and their genetic risks. DESIGN: Systematic review. DATA SOURCES: Six electronic databases (PubMed, MEDLINE, OVID Nursing, APA PsycINFO, EMBASE and CINAHL) were searched from inception to May 2022. REVIEW METHODS: Only randomised controlled trials that examined the effect of decision aids for information provision centring genetic testing on outcomes including decisional conflicts, informed choice making, knowledge on genetic risks or genetic tests, and psychological outcomes among participants who had undergone genetic counselling were included. Their risk of bias was assessed using the Version 2 of the Cochrane risk of bias tool for randomised trials. Results were presented narratively. The review was conducted according to the PRISMA checklist. RESULTS: Eight included studies examined the effect of booklet-based, computer-based, film-based or web-based decision aids on individuals considering genetic testing for their increased cancer risks. Despite contrasting findings across studies, they showed that decision aids enable genetic counsellees to feel more informed in decision-making on genetic tests, although most showed no effect on decisional conflict. Knowledge of genetic counsellees on genetic risks and genetic tests were increased after the use of decision aids. Most studies showed no significant effect on any psychological outcomes assessed. CONCLUSIONS: Review findings corroborate the use of decision aids to enhance the effective delivery of genetic counselling, enabling genetic counsellees to gain more knowledge of genetic tests and feel more informed in making decisions to have these tests. RELEVANCE TO CLINICAL PRACTICE: Decision aids can be used to support nurse-led genetic counselling for better knowledge acquisition and decision-making among counsellees. NO PATIENT OR PUBLIC CONTRIBUTION: Patient or public contribution is not applicable as this is a systematic review.

Association of single nucleotide polymorphisms of cytochrome P450 enzymes with experience of vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients: a systematic review.

BACKGROUND: Adjuvant endocrine therapies are known to induce undesirable adverse effects such as vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients. Drugs used in these therapies are often metabolised by cytochrome P450 (CYP) enzymes, in which their metabolising activities can be modified by single nucleotide polymorphisms (SNP) in CYP genes and CYP genotypes. This review aims to explore whether SNPs or genotypes of CYP are associated with the occurrence, frequency and severity of vasomotor, vaginal and musculoskeletal symptoms in breast cancer patients on adjuvant endocrine therapies. METHODS: A literature review was conducted using five electronic databases, resulting in the inclusion of 14 eligible studies, and their findings were presented narratively. Selected items from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist were used for critical appraisal of the reporting quality of the included studies. RESULTS: Most of the included studies showed that SNPs or genotypes of CYP that modify its metabolising activity have no effect on the occurrence, frequency or severity of vasomotor symptoms, including hot flashes. One study showed no correlation of these genetic variations in CYP with musculoskeletal symptoms, and no data were available on the association between such genetic variations and vaginal symptoms. CONCLUSIONS: Overall, genetic variations in CYP have no effect on the experience of hot flashes among breast cancer patients. We recommend exploration of the link between the active metabolites of chemotherapeutic drugs and the molecules shown to affect the occurrence or severity of hot flashes, and the establishment of the relationship between such genetic variations and patients' experience of musculoskeletal and vaginal symptoms. Subgroup analyses based on patients' duration of adjuvant endocrine therapies in such studies are recommended.

Genetics and epigenetics of autism: A Review.

Autism is a developmental disorder that starts before age 3 years, and children with autism have impairment in both social interaction and communication, and have restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. There is a strong heritable component of autism and autism spectrum disorder (ASD) as studies have shown that parents who have a child with ASD have a 2-18% chance of having a second child with ASD. The prevalence of autism and ASD have been increasing during the last 3 decades and much research has been carried out to understand the etiology, so as to develop novel preventive and treatment strategies. This review aims at summarizing the latest research studies related to autism and ASD, focusing not only on the genetics but also some epigenetic findings of autism/ASD. Some promising areas of research using transgenic/knockout animals and some ideas related to potential novel treatment and prevention strategies will be discussed.

Adequacy of Using a Three-Item Questionnaire to Determine Zygosity in Chinese Young Twins.

The present study examined the adequacy of a three-item parent questionnaire in determining the zygosity of young Chinese twins and whether there was any association between parent response accuracy and some demographic variables. The sample consisted of 334 pairs of same-sex Chinese twins aged from 3 to 11 years. Three scoring methods, namely the summed score, logistic regression, and decision tree, were employed to evaluate parent response accuracy of twin zygosity based on single nucleotide polymorphism (SNP) information. The results showed that all three methods achieved high level of accuracy ranging from 91 to 93 % which was comparable to the accuracy rates in previous Chinese twin studies. Correlation results also showed that the higher the parents' education level or the family income was, the more likely parents were able to tell correctly that their twins are identical or fraternal. The present findings confirmed the validity of using a three-item parent questionnaire to determine twin zygosity in a Chinese school-aged twin sample.

Hypotheses on the Potential of Rice Bran Intake to Prevent Gastrointestinal Cancer through the Modulation of Oxidative Stress.

Previous studies have suggested the potential involvement of oxidative stress in gastrointestinal cancers. In light of this, research efforts have been focused on the potential of dietary antioxidant intake to prevent gastrointestinal cancer through the modulation of oxidative stress. Rice bran, a by-product of rice milling, has been shown to contain an abundance of phytochemicals, which are dietary antioxidants. To date, a number of studies have shown the antioxidative effect of rice bran intake, and some demonstrated that such an effect may contribute to gastrointestinal cancer prevention, largely through the antioxidative properties of rice bran phytochemicals. In addition, these phytochemicals were shown to provide protection against cancer through mechanisms linked to oxidative stress, including ß-catenin-mediated cell proliferation and inflammation. The present article provides an overview of current evidence for the antioxidative properties of rice bran and its phytochemicals, and for the potential of such properties in cancer prevention through the oxidative-stress-linked mechanisms mentioned above. The article also highlights the need for an evaluation of the effectiveness of rice bran dietary interventions among cancer survivors in ameliorating oxidative stress and reducing the level of gastrointestinal cancer biomarkers, thereby establishing the potential of such interventions among these individuals in the prevention of cancer recurrence.

Novel Strategies on Personalized Medicine for Breast Cancer Treatment: An Update.

Breast cancer is the most common cancer type among women worldwide. With breast cancer patients and survivors being reported to experience a repertoire of symptoms that are detrimental to their quality of life, the development of breast cancer treatment strategies that are effective with minimal side effects is therefore required. Personalized medicine, the treatment process that is tailored to the individual needs of each patient, is recently gaining increasing attention for its prospect in the development of effective cancer treatment regimens. Indeed, recent studies have identified a number of genes and molecules that may be used as biomarkers for predicting drug response and severity of common cancer-associated symptoms. These would provide useful clues not only for the determination of the optimal drug choice/dosage to be used in personalized treatment, but also for the identification of gene or molecular targets for the development of novel symptom management strategies, which ultimately would lead to the development of more personalized therapies for effective cancer treatment. In this article, recent studies that would provide potential new options for personalized therapies for breast cancer patients and survivors are reviewed. We suggest novel strategies, including the optimization of drug choice/dosage and the identification of genetic changes that are associated with cancer symptom occurrence and severity, which may help in enhancing the effectiveness and acceptability of the currently available cancer therapies.

Home environmental influences on children's language and reading skills in a genetically sensitive design: Are socioeconomic status and home literacy environment environmental mediators and moderators?

This twin study examined how family socioeconomic status (SES) and home literacy environment (HLE) contributes to Chinese language and reading skills. It included 312 Chinese twin pairs aged 3 to 11. Children were individually administered tasks of Chinese word reading, receptive vocabulary and reading-related cognitive skills, and nonverbal reasoning ability. Information on home environment was collected through parent-reported questionnaires. Results showed that SES and HLE mediated shared environmental influences but did not moderate genetic influences on general language and reading abilities. Also, SES and HLE mediated shared environmental contributions to receptive vocabulary and syllable and rhyme awareness, but not orthographic skills. The findings of this study add to past twin studies that focused on alphabetic languages, suggesting that these links could be universal across languages. They also extend existing findings on SES and HLE's contributions to reading-related cognitive skills.

Study of Genetic Association With DCDC2 and Developmental Dyslexia in Hong Kong Chinese Children.

BACKGROUND: Doublecortin domain-containing 2 (DCDC2) is a doublecortin domain-containing gene family member and the doublecortin domain has been demonstrated to bind to tubulin and enhance microtubule polymerization. It has been associated with developmental dyslexia and this protein family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. OBJECTIVES: The objective of the study is to find out if there is any association of genetic variants of DCDC2 with developmental dyslexia in Chinese children from Hong Kong. METHODS: The dyslexic children were diagnosed as developmental dyslexia (DD) using the Hong Kong Test of Specific Learning Difficulties in Reading and Writing (HKT-SpLD) by the Department of Health, Hong Kong. Saliva specimens were collected and their genotypes of DCDC2 were studied by DNA sequencing or TaqMan Real Time PCR Assays. RESULTS: The most significant marker is rs6940827 which is associated with DD with nominal p-value (0.011). However, this marker did not remain significant after multiple testing corrections and the adjusted p-value from permutation test was 0.1329. Using sliding window haplotype analysis, several haplotypes were found to be nominally associated with DD. The smallest nominal p values was 0.0036 (rs2996452-rs1318700, C-A). However, none of the p values could withstand the multiple testing corrections. CONCLUSION: Despite early findings that DCDC2 is a strong candidate for developmental dyslexia and that some of the genetic variants have been linked to brain structure and functions, our findings showed that DCDC2 is not strongly associated with dyslexia.

Generalist genes and cognitive abilities in Chinese twins.

This study considered how far nonverbal cognitive, language and reading abilities are affected by common genetic influences in a sample of 312 typically developing Chinese twin pairs aged from 3 to 11 years. Children were individually given tasks of Chinese word reading, receptive vocabulary, phonological memory, tone awareness, syllable and rhyme awareness, rapid automatized naming, morphological awareness and orthographic skills, and Raven's Colored Progressive Matrices. Factor analyses on the verbal tasks adjusted for age indicated two factors: Language as the first factor and Reading as the second factor. Univariate genetic analyses indicated that genetic influences were substantial for nonverbal cognitive ability and moderate for language and reading. Multivariate genetic analyses showed that nonverbal cognitive ability, language and reading were influenced by shared genetic origins, although there were specific genetic influences on verbal skills that were distinct from those on nonverbal cognitive ability. This study extends the Generalist Genes Hypothesis to Chinese language and reading skills, suggesting that the general effects of genes could be universal across languages.

Association of genetic polymorphisms with psychological symptoms in cancer: A systematic review.

Cancer patients suffer from a repertoire of symptoms, including such psychological and psychiatric symptoms as anxiety, depression, and posttraumatic stress. Exploration of genetic factors that modify the risk and severity of these symptoms may facilitate the development of personalised care plans for managing these symptoms. This review aims to provide an overview on the variations in genes that may contribute to the occurrence and severity of anxiety, depression, and posttraumatic stress disorder (PTSD) among cancer patients. Literature search was performed in nine English and Chinese electronic databases, and extracted data are presented narratively. The reporting quality of the included studies was assessed using selected items of The STrengthening the REporting of Genetic Association (STREGA) checklist. Twenty-nine studies were included in the review. Most studies involved breast cancer patients, while patients of other cancer types appeared to be understudied. A number of studies reported the association between genes involved in inflammatory pathways and depression and anxiety. Other genes found to show associations with anxiety, depression, and PTSD among cancer patients are those involved in neurotrophic signalling, serotonergic signalling, regulation of stress response, antioxidation, dopamine catabolism and cellular apoptosis, despite some inconsistencies in findings between studies. Our review highlighted a need for further research for enhancing our knowledge on the association between genetic variations and anxiety, depression, and PTSD of patients of various cancer types. Future studies examining such associations in patients of various cancers should utilise standardised instruments for outcome assessments and stratify the patients based on their age for analysis.

Association of the rs3743205 variant of DYX1C1 with dyslexia in Chinese children.

BACKGROUND: Dyslexia is a learning disability that is characterized by difficulties in the acquisition of reading and spelling skills independent of intelligence, motivation or schooling. Studies of western populations have suggested that DYX1C1 is a candidate gene for dyslexia. In view of the different languages used in Caucasian and Chinese populations, it is therefore worthwhile to investigate whether there is an association of DYX1C1 in Chinese children with dyslexia. METHOD AND RESULTS: Eight single nucleotide polymorphisms (SNPs) were genotyped from three hundred and ninety three individuals from 131 Chinese families with two which have been reported in the literature and six tag SNPs at DYX1C1. Analysis for allelic and haplotypic associations was performed with the UNPHASED program and multiple testing was corrected using false discovery rates. We replicated the previously reported association of rs3743205 in Chinese children with dyslexia (p(corrected) = 0.0072). This SNP was also associated with rapid naming, phonological memory and orthographic skills in quantitative trait analysis. CONCLUSION: Our findings suggest that DYX1C1 is associated with dyslexia in people of Chinese ethnicity in Hong Kong.

Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients.

CYP2C9 and VKORC1 genotypes could be used to predict warfarin requirement. The objective was to develop and validate a warfarin dosing algorithm using genetic, clinical and demographic data of Chinese patients from an anticoagulation clinic in Hong Kong. Blood samples were collected from 100 patients on stable maintenance dose of warfarin, recruited from an anticoagulation clinic, for genotyping CYP2C9 and VKORC1. Clinical and demographic data were obtained by face-to-face interview and medical chart review. Data of 80 patients (study cohort) were randomly selected for deriving a dosing algorithm. Comparison between predicted dose and actual stable doses was conducted in a validation cohort (n = 20). Sixty-nine (69%) of all 100 patients were homozygous for VKORC1 1173-TT, 25 (25%) were VKORC1 1173-CT heterozygotes and six (6%) were homozygous for VKORC1 1173-CC. 6 (6%) patients were CYP2C9 1*/3* and 94 (94%) were CYP2C9 1*/1*. CYP2C9 and VKORC1 genotype, age, weight and vitamin K intake were identified by stepwise regression modelling to produce the best model for estimating warfarin dose (R (2) = 68%, P < 0.001). In the validation cohort (n = 20), actual stable dose was significantly associated with predicted dose (R = 0.6, P = 0.005). Five of 11 (45.6%) and 5/9 (55.6%) patients whose mean warfarin requirements were ≤ 3 mg/day and >3 mg/day, respectively, were within <20% of actual doses. In conclusion, a genotype-guided dosing algorithm for warfarin therapy was developed for Chinese patients to explain 68% of dosage variation. The predicted doses differed from the actual doses by no more than 20% in 50% of patients.

Combination of absolute pitch and tone language experience enhances lexical tone perception.

Absolute pitch (AP), a unique ability to name or produce pitch without any reference, is known to be influenced by genetic and cultural factors. AP and tone language experience are both known to promote lexical tone perception. However, the effects of the combination of AP and tone language experience on lexical tone perception are currently not known. In the current study, using behavioral (Categorical Perception) and electrophysiological (Frequency Following Response) measures, we investigated the effect of the combination of AP and tone language experience on lexical tone perception. We found that the Cantonese speakers with AP outperformed the Cantonese speakers without AP on Categorical Perception and Frequency Following Responses of lexical tones, suggesting an additive effect due to the combination of AP and tone language experience. These findings suggest a role of basic sensory pre-attentive auditory processes towards pitch encoding in AP. Further, these findings imply a common mechanism underlying pitch encoding in AP and tone language perception.

Associations of the growth hormone receptor (GHR) gene polymorphisms with adiposity and IGF-I activity in adolescents.

OBJECTIVE: To explore the genetic effect of the GH receptor (GHR) on obesity and related metabolic parameters in Hong Kong Chinese adolescents. CONTEXT: Obesity is a growing global epidemic. Increasing evidence suggests that the GH-IGF-I axis plays an important role in regulating adiposity and insulin sensitivity. DESIGN: We examined the associations of genetic variants of GHR with serum IGF-I and IGFBP-3 levels as well as obesity-related metabolic traits in Hong Kong Chinese adolescents. PATIENTS: Nine hundred and eighty-one randomly selected Hong Kong Chinese adolescents from 14 schools. MEASUREMENTS: We genotyped 17 single nucleotide polymorphisms (SNP) at GHR and measured serum IGF-I and IGFBP-3 levels as well as obesity-related metabolic traits including fasting plasma glucose, insulin and lipid levels. RESULTS: There were significant associations between rs4410646 and the body composition (P = 0.0044) and blood pressure factor scores (P = 0.00017). Carriers of the CC genotype had lower body mass index, percentage body fat, waist and hip circumferences than AC and AA genotype carriers (P = 0.00030-0.0094). There was also association between rs7703713 and the IGF-I activity factor score (P = 0.0033). The GA and AA carriers of rs7703713 had higher serum IGF-I, higher serum IGFBP-3 and higher IGF-I/IGFBP-3 molar ratio (P = 0.00069-0.025). Haplotype analysis did not increase the significance of associations. CONCLUSION: Our results support the role of GHR gene polymorphisms in modulating adiposity and IGF-I activity in adolescents. Examination of interactions of these SNPs with lifestyle, environmental and perinatal factors may provide further insights into their long-term effects on obesity and metabolic risks.

Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen.

PURPOSE: To review recent pharmacogenomics studies on breast cancer patients undergoing tamoxifen therapy, highlighting how our knowledge on cytochrome P450 2D6 (CYP2D6) can help to guide the development of adjuvant therapies for these patients. METHODS: A comprehensive literature search was conducted. Articles reporting findings pertaining to the effect of CYP2D6 on the therapeutic efficacy of tamoxifen, those reporting how targeting CYP2D6 could inform tamoxifen-based therapy development, and those on the tamoxifen effects on cell lines and animal models were included in the review. RESULTS: With CYP2D6 being the primary enzyme for tamoxifen metabolism, single-nucleotide polymorphisms (SNPs) in this gene were one of the determinants in the rate of tamoxifen metabolism, thereby potentially having an effect on the efficacy of tamoxifen-based therapies. Our review indicates the potential effectiveness of targeting these SNPs, including those for the CYP2D6*10 allele (c. 100C > T), in modifying the level of tamoxifen metabolism. These findings suggest the importance of pharmacogenomics research in our understanding of the efficacy of adjuvant therapies. However, the involvement of multiple enzymes in tamoxifen metabolism, dietary factors, ethnic differences in gene frequencies, and patients' compliance to tamoxifen therapies in studies do present challenges in pharmacogenomics research. CONCLUSIONS: Pharmacogenomics could play important roles in mediating the advancement of tamoxifen-based adjuvant therapies. Research efforts should be directed towards the exploration of further SNPs of CYP2D6 that affect tamoxifen metabolism, as well as epigenetic changes in CYP2D6, enabling the design of precision medicine and confirming clinical validity in the use of pharmacogenomics for tamoxifen.

Over-expression of SUMO-1 induces the up-regulation of heterogeneous nuclear ribonucleoprotein A2/B1 isoform B1 (hnRNP A2/B1 isoform B1) and uracil DNA glycosylase (UDG) in hepG2 cells.

Sumoylation is one of the post-translational modifications that governs many cellular activities, including subcellular localization targeting, protein-protein interaction, and transcriptional activity regulation. SUMO E3 ligases are responsible for substrate specificity determination in which PIAS is the largest E3 family that consists of five members in human; they are PIAS1, PIAS3, PIASx alpha, PIASx beta, and PIASy. Several studies showed that all these PIAS genes are highly expressed in testis but only a few reports have discussed their expression pattern in other tissues. Though liver is a multifunctional organ and one would expect to find regulation of cellular functions by sumoylation, the identified sumoylation substrates are scarce and few of them correlate with liver cancer. In this report, we have found that PIASx alpha, PIASx beta, and PIASy are highly expressed in liver as well as testis by tissue distribution studies. We thus aimed to identify any SUMO-1 related proteins in liver cancer cells by two-dimensional gel electrophoresis and mass spectrometry. Two up-regulated proteins, heterogeneous nuclear ribonucleoprotein A2/B1 isoform B1 (hnRNP A2/B1 isoform B1) and uracil DNA glycosylase (UDG), have been identified in the EGFP-SUMO-1 over-expressing HepG2 cells. The up-regulation is suggested to be mediated via changes at the translational level or protection from degradation by western blotting and RT-PCR.

Andrographolide up-regulates cellular-reduced glutathione level and protects cardiomyocytes against hypoxia/reoxygenation injury.

Recent studies revealed that the herb Andrographis paniculata possesses cardioprotective activities. Using neonatal rat cardiomyocytes, the cardioprotective actions of several diterpene lactones derived from A. paniculata including andrographolide, 14-deoxyandrographolide, 14-deoxy-11,12-didehydroandrographolide, and sodium 14-deoxyandrographolide-12-sulfonate were investigated. Pretreatment with andrographolide but not with the other compounds protected the cardiomyocytes against hypoxia/ reoxygenation injury and up-regulated the cellular-reduced glutathione (GSH) level and antioxidant enzyme activities. The cardioprotective action of andrographolide was found to coincide in a time-dependent manner with the up-regulation of GSH, indicating the important role of GSH. The cardioprotective action of andrographolide was also completely abolished by buthionine sulfoximine, which acts as a specific gamma-glutamate cysteine ligase (GCL) inhibitor to deplete cellular GSH level. It was subsequently found that the mRNA and protein levels of the GCL catalytic subunit (GCLC) and modifier subunit (GCLM) were up-regulated by andrographolide. Luciferase reporter assay also demonstrated that andrographolide activated both the GCLC and the GCLM promoters in the transfected rat H9C2 cardiomyocyte cell line. The 12-O-tetradecanoylphorbo-13-acetate response element or the antioxidant response element may be involved in the transactivating actions of andrographolide on the GCLC and GCLM promoters. The present study pinpoints andrographolide as a cardioprotective principle in A. paniculata and reveals its cytoprotective mechanism.

Development of human single-chain antibodies against SARS-associated coronavirus.

The outbreak of severe acute respiratory syndrome (SARS), caused by a distinct coronavirus, in 2003 greatly threatened public health in China, Southeast Asia as well as North America. Over 1,000 patients died of the SARS virus, representing 10% of infected people. Like other coronaviruses, the SARS virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. The spike protein of SARS virus consists of 1,255 amino acid residues and can be divided into two sub-domains, S1 and S2. The S1 domain mediates the binding of the virus to its receptor angiotensin-converting enzyme 2, which is abundantly distributed on the surface of human lung cells. The S2 domain mediates membrane fusion between the virus and the host cell. Hence two strategies can be used to block the infection of the SARS virus, either by interfering with the binding of the S1 domain to the receptor or by blocking the fusion of the virus with the cell membrane mediated by the S2 domain. Several antibodies against the S1 domain have been generated and all of them are able to neutralize the virus in vitro and in vivo using animal models. Unfortunately, point mutations have been identified in the S1 domain, so that the virus isolated in the future may not be recognized by these antibodies. As no mutation has been found in the S2 domain indicating that this region is more conserved than the S1 domain, it may be a better target for antibody binding. After predicting the immunogenicity of the epitopes of the S2 domain, we chemically synthesized two peptides and also expressed one of them using a recombinant DNA method. We screened a phage displaying library of human single-chain antibodies (ScFv) against the predicted epitopes and obtained a human ScFv which can recognize the SARS virus in vitro.

Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via a prooxidant mechanism.

OBJECTIVES: Baicalin and its aglycone baicalein are the major flavonoid components of the root of Scutellaria baicalensis. Recent studies have shown that they can attenuate oxidative stress in various in vitro models as they possess potent antioxidant activities. This study investigated alternative protective mechanisms of baicalein in a cardiomyocyte model. METHODS: Neonatal rat cardiomyocytes pretreated with the test compound were subjected to hypoxia/reoxygenation. The extent of cellular damage was accessed by the amount of released lactate dehydrogenase RESULTS: Pretreatment with baicalein up to 10 microM reduced lactate dehydrogenase release significantly (P<0.001), while pretreatment with baicalin up to 100 microM was ineffective. The cardioprotective effect of baicalein is not due to its antioxidant effect, because an adverse effect rather than a protective effect was observed when baicalein was present during hypoxia. Cotreatment with N-acetylcysteine attenuated the protective effect of baicalein and concomitantly increased intracellular reactive oxygen species level and the cytotoxic effect of baicalein, but N-acetylcysteine alone did not have such effects. In addition, cotreatment with catalase, but not superoxide dismutase or mannitol, reversed the cardioprotective effect of baicalein, suggesting the involvement of hydrogen peroxide in the cardioprotective mechanism. The NAD(P)H:quinone oxidoreductase inhibitors dicoumarol and chrysin also abolished the cardioprotective effect of baicalein. While pretreatment with baicalein did not increase antioxidant enzyme activities, it alleviated calcium accumulation in cardiomyocytes undergoing simulated ischemia. CONCLUSION: These results highlight the important role of hydrogen peroxide produced during the auto-oxidation of baicalein in the cardioprotective effect of baicalein.

A comparative study on aqueous root extracts of Pueraria thomsonii and Pueraria lobata by antioxidant assay and HPLC fingerprint analysis.

The roots of Pueraria thomsonii and Pueraria lobata are officially recorded in Chinese Pharmacopoeia under the same name Radix Puerariae. However, the aqueous root extract of Pueraria lobata showed more potent antioxidant activity than that of Pueraria thomsonii. A qualitative HPLC method was developed to compare the chemical profiles of Pueraria thomsonii and Pueraria lobata, which revealed four major common peaks (daidzein 1, daidzin 2, puerarin 3 and 5-hydroxypuerarin 4) and two major different peaks (3-hydroxypuerarin 5 and 3'-methoxypuerarin 6) in their chromatograms. Semi-quantitative analysis showed that the contents of 1-3 in Pueraria lobata are about three, three, and five times higher than those of Pueraria thomsonii, respectively. The higher contents of isoflavonoids in Pueraria lobata were inferred to be responsible for its more potent antioxidant activity as compared with that of Pueraria thomsonii. The HPLC method developed in this study and chemical markers 1-6 can be used for the rapid identification and evaluation of Radix Puerariae herbs and their aqueous supplements, and the results of this investigation support the use of Pueraria lobata and Pueraria thomsonii in the clinic application and as dietary supplement, respectively.