Yubi-Wakka Test for Sarcopenia Screening in the Community: Comparative Agreement, Diagnostic Performance and Validity with Calf Circumference Measurements.

BACKGROUND: Screening tools such as calf circumference (CC) and Yubi-wakka (finger-ring) test have been recognized as effective tools by Asian Working Group for Sarcopenia 2019 (AWGS'19) for sarcopenia screening but their comparative agreement, diagnostic performance and validity are unclear. OBJECTIVES: This study aims to determine: (i)agreement between calf and finger-ring circumference, (ii)diagnostic performance for low muscle mass and AWGS'19 sarcopenia diagnosis, (iii)correlation with muscle mass, strength, and physical performance, and (iv)association with frailty, life space mobility and physical activity. METHODS: We studied 187 healthy community-dwelling older adults (mean age=66.8+7.0years) from the GERILABS-2 study. CC was measured via (i) both calves in sitting and standing positions, and (ii) Yubi-wakka test by encircling the thickest part of the non-dominant calf with index fingers and thumbs of both hands. We performed Cohen's kappa to check for agreement, area under receiver operating characteristic curve (AUC) to compare diagnostic performance, partial correlations adjusted for age and gender to compare convergent validity, and logistic regression to determine predictive validity for outcome measures. RESULTS: Sarcopenia prevalence was 24.0% (AWGS'19). Yubi-wakka identified 16.6% of participants as screen-positive ("smaller"), showing moderate agreement only with non-dominant sitting CC measurements (k=0.421,p<0.001) and having lower diagnostic performance in determining low muscle mass (AUC=0.591 vs 0.855-0.870,p<0.001; sensitivity=57.1% vs 75.5-90.8%; specificity=58.4% vs 70.8-80.9%) and sarcopenia diagnosis (AUC=0.581 vs 0.788-0.818,p<0.001; sensitivity=55.6% vs 57.5-71.8%; specificity=74.4% vs 75.6-88.9%) compared to CC measurements. Yubi-wakka correlated significantly with muscle mass, grip strength and knee extension but not physical performance. When adjusted for age, gender and hypertension, Yubi-wakka was significantly associated with frailty (OR=3.96,95%CI:1.09-14.38), life space mobility (OR=2.38,95%CI:1.08-5.24) and physical activity (OR=2.50,95%CI:1.07-5.86). DISCUSSION AND CONCLUSIONS: Yubi-wakka provides a self-administered, low-cost and practicable community screening tool for sarcopenia. Our study affirmed the convergent and predictive validity of Yubi-wakka, albeit with lower sensitivity and specificity in diagnostic performance compared to CC measurements.

Singapore Clinical Practice Guidelines For Sarcopenia: Screening, Diagnosis, Management and Prevention.

OBJECTIVES: To present the local evidence and final recommendations of the Clinical Practice Guidelines workgroup convened by the Chapter of Geriatricians and the Society for Geriatric Medicine Singapore. The aim is to develop contextualized evidence-based recommendations that facilitate adoption of the Asian Working Group for Sarcopenia (AWGS) 2019 consensus into current practice in Singapore. METHODS: The workgroup drew upon the AWGS'2019 consensus, updated literature review of Singapore studies till 31 Dec 2020, and evidence from recent systematic reviews. From 40 local studies included for data extraction, we constructed evidence tables organized as: definition and epidemiology; diagnosis and evaluation; and treatment and intervention. Twenty recommendations - case-finding, diagnosis, treatment, prevention, research - were developed, and graded for strength and quality using the GRADE approach. Consensus from an expert panel(N=23) was achieved after two rounds of the modified Delphi process. RESULTS: The local prevalence of sarcopenia among community-dwelling older adults ranged from 13.6% to 25%. Most studies adopted the AWGS'2019 and AWGS'2014 criteria. Reported case finding tools include SARC-F, calf circumference (CC) and SARC-CalF. Gender-specific AWGS cut-offs for appendicular skeletal mass were used to define low muscle mass. Different protocols and dynamometers were used to assess handgrip strength, whilst gait speed and 5-times chair stand were commonly used to assess physical performance. RECOMMENDATIONS: We conditionally recommend a case-finding approach in at-risk older adults using validated case-finding tools. Screen-positive individuals should be assessed for 'possible sarcopenia' and underlying causes. For diagnosis, we conditionally recommend using the AWGS'2019 algorithm, and dual-energy X-ray absorptiometry when necessary to determine low lean mass for a confirmatory diagnosis of sarcopenia. For treatment, we strongly recommend resistance-based exercises and conditionally recommend a quality protein-rich diet/protein supplementation, with Vitamin D supplementation for insufficiency (<30 micrograms/L). For prevention, we recommend regular resistance-based physical activity and adequate protein intake (≥1.0g/kg bodyweight). We encourage more research to address local evidence gaps.

Social Frailty and Executive Function: Association with Geriatric Syndromes, Life Space and Quality of Life in Healthy Community-Dwelling Older Adults.

BACKGROUND: Despite emerging evidence about the association between social frailty and cognitive impairment, little is known about the role of executive function in this interplay, and whether the co-existence of social frailty and cognitive impairment predisposes to adverse health outcomes in healthy community-dwelling older adults. OBJECTIVES: We aim to examine independent associations between social frailty with the MMSE and FAB, and to determine if having both social frailty and cognitive impairment is associated with worse health outcomes than either or neither condition. METHODS: We studied 229 cognitively intact and functionally independent community-dwelling older adults (mean age= 67.2±7.43). Outcome measures comprise physical activity; physical performance and frailty; geriatric syndromes; life space and quality of life. We compared Chinese Mini Mental State Examination (CMMSE) and Chinese Frontal Assessment Battery (FAB) scores across the socially non-frail, socially pre-frail and socially frail. Participants were further recategorized into three subgroups (neither, either or both) based on presence of social frailty and cognitive impairment. Cognitive impairment was defined as a score below the educational adjusted cut-offs in either CMMSE or FAB. We performed logistic regression adjusted for significant covariates and mood to examine association with outcomes across the three subgroups. RESULTS: Compared with CMMSE, Chinese FAB scores significantly decreased across the social frailty spectrum (p<0.001), suggesting strong association between executive function with social frailty. We derived three subgroups relative to relationship with socially frailty and executive dysfunction: (i) Neither, N=140(61.1%), (ii) Either, N=79(34.5%), and (iii) Both, N=10(4.4%). Compared with neither or either subgroups, having both social frailty and executive dysfunction was associated with anorexia (OR=4.79, 95% CI= 1.04-22.02), near falls and falls (OR= 5.23, 95% CI= 1.10-24.90), lower life-space mobility (odds ratio, OR=9.80, 95% CI=2.07-46.31) and poorer quality of life (OR= 13.2, 95% CI= 2.38-73.4). CONCLUSION: Our results explicated the association of executive dysfunction with social frailty, and their synergistic relationship independent of mood with geriatric syndromes, decreased life space and poorer quality of life. In light of the current COVID-19 pandemic, the association between social frailty and executive dysfunction merits further study as a possible target for early intervention in relatively healthy older adults.

Disentangling the Relationship between Frailty and Intrinsic Capacity in Healthy Community-Dwelling Older Adults: A Cluster Analysis.

BACKGROUND: Frailty and intrinsic capacity (IC) are distinct but interrelated constructs. Uncertainty remains regarding how they are related and interact to influence health outcomes. We aim to understand the relationship between frailty and IC by identifying subgroups based on frailty criteria and IC domains and studying one-year outcomes. METHODS: We studied 200 independent community-dwelling older adults (mean age 67.9±7.9 years, Modified Barthel Index (MBI) score 99±2.6). Frailty was defined by modified Fried criteria. Scores (range: 0-2) were assigned to individual IC domains (cognition, psychological, locomotion, and vitality) to yield a total IC score of 8. To identify subgroups, two-step cluster analysis was performed with age, frailty and IC domains. Cluster associations with one-year outcomes (frailty, muscle strength (grip strength, repeated chair stand test), physical performance (gait speed, Short Physical Performance Battery), function (MBI) and quality-of-life (EuroQol (EQ)-5D)) were examined using multiple linear regression adjusted for age, gender and education. RESULTS: Three distinct clusters were identified - Cluster 1: High IC/Robust (N=74, 37%); Cluster 2: Intermediate IC/Prefrail (N=73, 36.5%); and Cluster 3: Low IC/Prefrail-Frail (53, 26.5%). Comparing between clusters, IC domains, cognition, depressive symptoms, nutrition, strength and physical performance were least impaired in Cluster 1, intermediate in Cluster 2 and most impaired in Cluster 3. At one year, the proportion transitioning to frailty or remaining frail was highest in Cluster 3 compared to Cluster 2 and Cluster 1 (39% vs 6.9% vs 2.8%, P<0.001). Compared to Cluster 1, Cluster 3 experienced greatest declines in grip strength (ß=-4.1, P<.001), MBI (ß=-1.24, P=0.045) and EQ-5D utility scores (ß=-0.053, P=0.005), with Cluster 2 intermediate between Cluster 1 and Cluster 3. CONCLUSIONS: Amongst independent community-dwelling older adults, IC is complementary to frailty measures through better risk-profiling of one-year outcomes amongst prefrail individuals into intermediate and high-risk groups. The intermediate group merits follow-up to ascertain longer-term prognosis.

Grip Strength Criterion Matters: Impact of Average Versus Maximum Handgrip Strength on Sarcopenia Prevalence and Predictive Validity for Low Physical Performance.

IMPORTANCE: Muscle strength has been elevated to the forefront of sarcopenia diagnosis, with handgrip strength the preferred measure. Extant handgrip protocols adopt different handgrip strength (HGS) criteria. Paucity of direct comparison studies assessing the impact of HGS criterion on prevalence of sarcopenia and predictive validity on physical performance contributes to the lack of standardisation of HGS criteria in sarcopenia diagnosis. OBJECTIVES: Our study aims to compare the effect of average (HGSave) versus maximum (HGSmax) HGS criterion on: (1) prevalence of low HGS and sarcopenia; and (2) association with physical performance at baseline and at 2 years. METHODS: We recruited 200 community dwelling, cognitively intact, and functionally independent older adults. Muscle strength, physical performance measures, cognitive tests and nutritional assessments were performed. Short Physical Performance Battery (SPPB) was administered at baseline and at 2 years. We compared HGSave and HGSmax to assess the prevalence of low HGS and sarcopenia. Univariate analysis was performed comparing baseline characteristics between low and normal groups for each HGS criterion. Significantly different variables were included in logistic regression analysis to examine association of low HGS and SPPB at baseline. Predictive validity of low HGS for SPPB<10 at 2 years was examined by performing logistic regression analysis for HGSave and HGSmax. RESULTS: The prevalence of low HGS and sarcopenia incorporating HGSave criterion is 40% and 33% respectively, whereas that of HGSmax criterion is 21% and 19.5% respectively. There is moderate agreement between the 2 HGS criteria for sarcopenia diagnosis (kappa=0.604) and poorer agreement for low HGS (kappa=0.570). There was no significant association with baseline SPPB for both HGS criteria. At 2 years, only low HGSmax was significantly associated with low SPPB (adjusted OR 3.91, 95% CI 1.24 - 12.33). CONCLUSION: Our study demonstrates that HGS criteria matters in diagnosis of sarcopenia and we support extant HGS protocols using HGSmax criterion in view of better predictive validity for poor physical performance.

Muscle Strength Definitions Matter: Prevalence of Sarcopenia and Predictive Validity for Adverse Outcomes Using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) Criteria.

BACKGROUND: EWGSOP2 criteria for sarcopenia recommends the use of either handgrip strength (GS) or 5-times repeated chair stand test (RCS) as a muscle strength measure. We aim to compare the impact of different muscle strength definitions on sarcopenia prevalence and predictive validity for 2-year outcomes, using the EWGSOP2 clinical algorithm. METHODS: We studied 200 community-dwelling older adults, comparing sarcopenia prevalence using three muscle strength definitions: 1) maximum GS (Asian Working Group cutoffs); 2) RCS-1 (standard cutoff >15s); and 3) RCS-2 (ROC-derived cutoff >12.5s). Two-year outcomes include: 1) Incident frailty (modified Fried criteria); 2) Physical performance [Short Physical Performance Battery (SPPB) score <10]; and 3) Quality of life [EuroQol-5 dimension (EQ-5D) <25th percentile]. We performed logistic regression on 2-year outcomes adjusted for age, gender, cognition and mood. RESULTS: Prevalence of confirmed sarcopenia was 14.5%, 4% and 9% for GS, RCS-1 and RCS-2 respectively. For 2-year outcomes (N=183), RCS-2 predicted incident frailty (OR: 5.7, 95% CI 1.4-22.8, p=0.013), low SPPB (OR: 4.4, 95% CI 1.4-13.1, p=0.009), and trended towards predicting low QOL (OR: 2.1, 95% CI 0.9-4.9, p=0.095). In contrast, GS and RCS-1 did not predict frailty nor low QOL, but predicted low SPPB only (GS: OR 3.8, 95% CI 1.3-10.6, p=0.01; RCS-1: OR: 8.8, 95% CI 2.2-35.0, p=0.002). CONCLUSIONS: Sarcopenia prevalence varies with muscle strength definitions, with GS being significantly higher vis-à-vis RCS definitions. Our results also support the use of population-specific over standard cutoffs for RCS to obtain intermediate estimates of sarcopenia prevalence and the best predictive validity for two-year outcomes.

Obesity Definitions in Sarcopenic Obesity: Differences in Prevalence, Agreement and Association with Muscle Function.

BACKGROUND: Sarcopenic obesity (SO) is associated with poorer physical performance in the elderly and will increase in relevance with population ageing and the obesity epidemic. The lack of a consensus definition for SO has resulted in variability in its reported prevalence, poor inter-definitional agreement, and disagreement on its impact on physical performance, impeding further development in the field. While sarcopenia definitions have been compared, the impact of obesity definitions in SO has been less well-studied. OBJECTIVES: To compare 3 widely-adopted definitions of obesity in terms of SO prevalence, inter-definitional agreement, and association with muscle function. DESIGN: Cross-sectional. SETTING: GERILABS study, Singapore Participants: 200 community-dwelling, functionally-independent older adults. MEASUREMENTS: We utilized three commonly-used definitions of obesity: body mass index (BMI), waist circumference (WC) and DXA-derived fat mass percentage (FM%). Sarcopenia was defined using Asian Working Group for Sarcopenia criteria. For muscle function, we assessed handgrip strength, gait speed and Short Physical Performance Battery (SPPB). Subjects were classified into 4 body composition phenotypes (normal, obese, sarcopenic and SO), and outcomes were compared between groups. RESULTS: The prevalence rate for SO was lowest for BMI (0.5%) compared to FM% (10.0%) and WC (10.5%). Inter-definitional agreement was lowest between BMI and WC (κ=0.364), and at best moderate between FM% and WC (κ=0.583). SO performed the worst amongst body composition phenotypes in handgrip strength, gait speed and SPPB (all p<0.01) only when defined using WC. In regression analyses, SO was associated with decreased SPPB scores (ß=-0.261, p=0.001) only for the WC definition. CONCLUSION: There is large variation in the prevalence of SO across different obesity definitions, with low-to-moderate agreement between them. Our results corroborate recent evidence that WC, and thus central obesity, is best associated with poorer muscle function in SO. Thus, WC should be further explored in defining obesity for accurate and early characterization of SO among older adults in Asian populations.

Serum Myostatin and IGF-1 as Gender-Specific Biomarkers of Frailty and Low Muscle Mass in Community-Dwelling Older Adults.

OBJECTIVES: (i) To investigate serum myostatin (absolute and normalized for total body lean mass (TBLM)) and IGF-1 as biomarkers of frailty and low relative appendicular skeletal muscle mass (RASM) in older adults, and; (ii) to examine gender differences in the association of serum myostatin and IGF-1 levels with frailty and low RASM. DESIGN: Cross-sectional study. SETTING: The "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and predicting frailty and functional decline in community-dwelling Asian older adults Study" (GERI-LABS) study in Singapore. PARTICIPANTS: 200 subjects aged 50 years and older residing in the community. MEASUREMENTS: Frailty was assessed using the modified Fried criteria. Low RASM was defined using cutoffs for height-adjusted appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry as recommended by the Asian Working Group for Sarcopenia. Comorbidities, cognitive and functional performance, physical activity and nutritional status were assessed. Blood samples collected included serum myostatin, insulin-like growth factor 1 (IGF-1) and markers of inflammation (total white cell count, CRP, IL-6 and TNFaR1). Subjects were classified into 4 groups: Frail/Prefrail with low RASM (Frail/Low RASM), Frail/Prefrail with normal RASM (Frail/Normal RASM), Robust with low RASM (Robust/Low RASM) and Robust with normal RASM (Robust/Normal RASM). RESULTS: 63 (32%) subjects were classified as Frail/Low RASM, 53 (27%) Frail/Normal RASM, 28 (14%) Robust/Low RASM and 56 (28%) Robust/Normal RASM respectively. Frail/Low RASM subjects were older and had lower BMI compared to Frail/Normal RASM and robust subjects. Mean (SE) normalized myostatin levels were higher in Frail/Low RASM compared to Frail/Normal RASM subjects (1.0 (0.04) versus 0.84 (0.05) ng/ml/kg, P=0.01). Median (IQR) IGF-1 level was lower amongst Frail/Low RASM subjects compared to Frail/Normal RASM subjects (102.3, (77.7, 102.5) vs 119.7 (82.7, 146.0) ng/ml, P=0.046). No differences in myostatin or IGF-1 were observed among robust individuals with or without low muscle mass. In adjusted multinomial logistic regression models with Robust/Normal RASM as the reference group, myostatin (P=0.05) and IGF-1 (P=0.043) were associated with Frail/Low RASM status in the whole cohort. When stratified by gender, myostatin was significantly associated with Frail/Low RASM status in men only (P=0.03). In women, serum IGF-1 was associated with Frail/Low RASM status (P=0.046), but not myostatin (P=0.53). CONCLUSION: Serum myostatin, normalized for TBLM in men and IGF-1 in women are potential biomarkers for frail individuals with low RASM, and may identify a target group for intervention.

Stage-Specific Relationship between Frailty and Cognitive Impairment in a Specialist Memory Clinic Setting.

BACKGROUND: It is unclear if the complex relationship between physical frailty and cognition varies across the severity of cognitive impairment. OBJECTIVES: We therefore aimed to explore if there are stage-specific differences in the relationship between frailty and cognitive impairment. DESIGN: Cross-sectional study. SETTING: A specialist Memory Clinic setting. PARTICIPANTS: Mild cognitive impairment (MCI) and mild-moderate Alzheimer's disease (AD) community-dwelling subjects. MEASUREMENTS: We obtained data on demographics, multimorbidity, cognition-related measures, nutrition, neuroimaging measures, muscle mass, Vitamin D level, apolipoprotein - e (APOE) status and physical performance measures. Frailty measures of gait speed, hand grip strength, question on exhausation and weight loss, classified subjects according to the Buchmann criteria into non-frail and frail categories. RESULTS: Forty-five MCI, 64 mild AD and 13 moderate AD subjects (total n=122) were studied. The prevalence of frailty for MCI, mild AD and moderate AD was 35.6%, 21.9% and 46.2% respectively, indicating a u-shaped trend. Significant differences were noted in fatigue, grip strength and gait speed frailty sub-items. Significant correlation of frailty with cognition were noted in mild-moderate AD (Spearman's coefficient 0.26, p<0.05) but not in MCI (0.01, p=0.6). No other differences in multimorbidity, Vitamin D, APOE, nutritional measures, white matter lesions were observed. Sarcopenia interestingly had an inverse stage-specific relationship unlike frailty. CONCLUSIONS: Our results suggest a U-shaped relationship between frailty and cognition, characterized by initial dissociation with cognitive impairment and subsequent convergence at later stages. Future studies incorporating immune markers and endocrine pathways with longitudinal follow-up could potentially elucidate intermediary mechanisms in the frailty cascade.

SEB-3, a CRF receptor-like GPCR, regulates locomotor activity states, stress responses and ethanol tolerance in Caenorhabditis elegans.

The CRF (corticotropin-releasing factor) system is a key mediator of the stress response. Alterations in CRF signaling have been implicated in drug craving and ethanol consumption. The development of negative reinforcement via activation of brain stress systems has been proposed as a mechanism that contributes to alcohol dependence. Here, we isolated a gain-of-function allele of seb-3, a CRF receptor-like GPCR in Caenorhabditis elegans, providing an in vivo model of a constitutively activated stress system. We also characterized a loss-of-function allele of seb-3 and showed that SEB-3 positively regulates a stress response that leads to an enhanced active state of locomotion, behavioral arousal and tremor. SEB-3 also contributed to acute tolerance to ethanol and to the development of tremor during ethanol withdrawal. Furthermore, we found that a specific CRF(1) receptor antagonist reduced acute functional tolerance to ethanol in mice. These findings demonstrate functional conservation of the CRF system in responses to stress and ethanol in vertebrates and invertebrates.

Taok2 controls behavioral response to ethanol in mice.

Despite recent advances in the understanding of ethanol's biological action, many of the molecular targets of ethanol and mechanisms behind ethanol's effect on behavior remain poorly understood. In an effort to identify novel genes, the products of which regulate behavioral responses to ethanol, we recently identified a mutation in the dtao gene that confers resistance to the locomotor stimulating effect of ethanol in Drosophila. dtao encodes a member of the Ste20 family of serine/threonine kinases implicated in MAP kinase signaling pathways. In this study, we report that conditional ablation of the mouse dtao homolog, Taok2, constitutively and specifically in the nervous system, results in strain-specific and overlapping alterations in ethanol-dependent behaviors. These data suggest a functional conservation of dtao and Taok2 in mediating ethanol's biological action and identify Taok2 as a putative candidate gene for ethanol use disorders in humans.

Molecular authentication of Panax ginseng species by RAPD analysis and PCR-RFLP.

In order to develop convenient and reproducible methods for the identification of ginseng drugs at a DNA level, randomly amplified polymorphic DNA (RAPD) and PCR-restriction fragment length polymorphism (PCR-RFLP) analyses were applied within Panax species. To authenticate Panax ginseng among ginseng populations, RAPD analysis was carried out using a 20 mer-random primer. The similarity coefficients among the DNA of ginseng plants analyzed were low, ranging from 0.197 to 0.491. In addition, by using PCR-RFLP analysis, very different fingerprints were obtained within Korean ginseng plants. These results suggest that these methods are able to authenticate the concerned Panax species. Broader application of this approach to authenticate other morphologically similar medicinal materials is rationalized.

Inhibitory action of water soluble fraction of Terminalia chebula on systemic and local anaphylaxis.

We investigated the effects of the water soluble fraction of Terminalia chebula (Combretaceae) (WFTC) on systemic and local anaphylaxis. WFTC administered 1h before compound 48/80 injection inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.01-1.0 g/kg. When WFTC was administered 5 or 10 min after compound 48/80 injection, the mortality also decreased in a dose-dependent manner. Passive cutaneous anaphylaxis was inhibited by 63.5+/-7.8% by oral administration of WFTC (1.0 g/kg). When WFTC was pretreated at concentrations ranging from 0.005 to 1.0 g/kg, the serum histamine levels were reduced in a dose-dependent manner. WFTC (0.01-1.0 mg/ml) also significantly inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. However, WFTC (1.0 mg/ml) had a significant increasing effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that WFTC may possess a strong antianaphylactic action.

Effect of allergina on mast cell-mediated allergic reactions.

The herbal formulation ALLERGINA has been used against allergic inflammation disease for generations, and still occupies an important place in traditional medicine in Korea. In this study, we investigated the effect of ALLERGINA by oral administration in mast cell-mediated anaphylaxis responses. ALLERGINA dose-dependently inhibited compound 48/48-induced systemic anaphylaxis with doses of 10(-2) to 5 g/kg 1 h before orally administered. Of special note, ALLERGINA inhibited systemic anaphylaxis completely with doses of 1 g/kg and 5 g/kg. ALLERGINA (1 g/kg) also inhibited passive cutaneous anaphylaxis by 84%. ALLERGINA dose-dependently inhibited histamine release from rat peritoneal mast cells. When ALLERGINA (0.01 mg/ ml) was added, ALLERGINA inhibited the production of tumor necrosis factor-alpha and interleukin-6, 80% and 26%, respectively in anti-dinitrophenyl IgE antibody-stimulated mast cells. Our studies provide evidence that ALLERGINA may be beneficial in the treatment of allergic inflammation diseases.

Effect of Vitex rotundifolia on immediate-type allergic reaction.

We investigated the effect of aqueous extract of Vitex rotundifolia (L.) (Verbenaceae) fruits (VRFE) on the immediate-type allergic reactions in vivo and in vitro. VRFE (10(-4)-1.0 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80. When VRFE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. VRFE (5x10(-1) and 1.0 g/kg) inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. VRFE (10(-3)-1.0 mg/ml) also dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 or anti-DNP IgE. Moreover, VRFE (10(-3) mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results suggest that VRFE may be beneficial in the regulation of immediate-type allergic reaction.

Benzo[c]phenanthridine alkaloids from Corydalis incisa.

Six benzo[c]phenanthridine alkaloids, corynoline (1), acetylcorynoline (2), corynoloxine (3), luguine (4), 6-oxocorynoline (5), and 12-hydroxycorynoloxine (6) were isolated from the aerial parts of Corydalis incisa, and 6 was isolated for the first time from nature. The structure was elucidated by NMR techniques.