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1.  Herbal Treatment for Osteoporosis: A Current Review 
Osteoporosis is an aging problem. The declining bone mineral density (BMD) enhances the chances of fractures during minor falls. Effective pharmaceuticals are available for a rapid improvement of BMD. However, hormonal treatment gives serious complications, and bisphosphonates may lead to odd fractures of long bones, resulting from excessive rigidity of the cortical components. Many medicinal herbs used in Traditional Chinese Medicine, known as kidney tonics, have been tested for their effects on bone metabolism in the laboratory and clinically. Three of these, viz. Herba epimedii (淫羊藿, Yín Yáng Huò), Fructus ligustri lucidi (女貞子, Nǚ Zhēn Zi), and Fructus psoraleae (補骨脂, Bǔ Gǔ Zhī) were chosen to form a herbal formula, ELP. ELP was tested on in vitro platforms and was shown to have both osteoblastic and anti- osteoclastic action. ELP tested on ovariectomized rats also showed BMD protection. ELP was then put on a placebo- controlled randomized clinical trial. BMD protection was obvious among those women with the onset of menopause beyond 10 years (P < 0.05). A general protective trend was observed among all women under trial (P > 0.05). Although a thorough literature review on the herbal treatment effects did not give convincing answers to the use of Chinese herbs in osteoporosis, our study supports more research and trials in this area, while we are looking for safe and effective agents to keep the bone metabolism in a balanced state.
PMCID: PMC3924968  PMID: 24716161
Bone mineral density; Herbal treatment; Osteoporosis
2.  Muscle-Based Pharmacokinetic Modeling of Marrow Perfusion for Osteoporotic Bone in Females  
BioMed Research International  2014;2014:620925.
The pharmacokinetic model has been widely used in tissue perfusion analysis, such as bone marrow perfusion. In the modeling process, the arterial input function is important to guarantee the reliability of the fitting result. However, the arterial input function is variable and hard to control, which makes it difficult to compare results across different studies. The purpose of this study was to establish a muscle-based pharmacokinetic model for bone marrow perfusion without using arterial input function. Erector spinae muscle around the vertebral body was selected as the reference region. The study was carried out in elderly females with different bone mineral densities (normal, osteopenia, and osteoporosis). Quantitative parameters were extracted from the pharmacokinetic model. Parameter Ktrans,BM (contrast agent extravasation rate constants for blood perfusion of the bone marrow) showed a significant reduction in subjects with lower bone mineral density, which is consistent with previous studies. However, muscle perfusion parameters remained unchanged among different groups. The results indicated that the muscle-based model was stable for bone marrow perfusion modeling. Additionally, nonsignificant change in muscle parameters indicated that the diminished perfusion is only a local rather than a systematic change in the bone marrow for osteoporosis.
PMCID: PMC4070517
3.  Efforts to Achieve Healthy Aging 
Longevity is a blessing as long as good health is not lost. However, the tendency to have a decline on normal physiological activities is inevitable because of the natural processes of degeneration at all levels: molecular, cellular and organic. Hence, the elderly people frequently suffer from cardiovascular problems and skeletal deteriorations that gradually develop to disabilities. Awareness of factors leading to unhealthy aging has led to the formation of different professional groups that aim at the maintenance of health of aging community. The approach tends to be target orientated for the European and US groups, aiming at hormonal replacements and detoxification. In contrast, the oriental groups have been keeping their traditional belief of prevention and internal balance, using nutritional arrangements and non-strenuous exercise as means of maintaining health.
PMCID: PMC3046017  PMID: 21614158
chinese medicine; aging
4.  Quality of life assessment in clinical research on Chinese medicine: Early experience and outlook 
Patients’ own account of the clinical progress is particularly important in situations of pain control, mental disturbances, and chronic problems. Chinese medicine does not directly target against a symptom or pathology, but emphasizes the maintenance of harmony between the vital forces of an individual. To achieve the harmony, usually long-termed treatment is required by consideration of the changing seasons and subject’s constitution nature. With such unique requirements in Chinese medicine, the assessment of the quality of life becomes most important. There are obvious similarities between different systems of medical care. Hence the general domains of the quality of life should fit all patients, whether they are receiving conventional, modern medical care on alternative, Chinese medical care. Like different clinical research categories, specific areas (eg, cancer, women’s problems) would need special additions of assessment. Chinese medicine is based on a uniquely different philosophy and the approach is not deductive, but individualized treatment is an essential requirement. The symptom/syndrome descriptions and interpretation are different from modern western medicine. Health-related quality of life is not sufficient for clinical trials using Chinese medicine, especially when Chinese medicine experts serve as chief investigators. Early attempts to develop an additional system to cover the need for Chinese medicine have been scanty. A lot of effort needs to be given before a practical instrument taking care of both the general domains of common interests and special feelings on health, relevant to Chinese medicine, could be established and made available. Users of Chinese medicine have to rely on generally acceptable yard-sticks with the addition of self-reporting symptoms unique to Chinese medicine.
PMCID: PMC2770405  PMID: 19920969
alternative medicine; Chinese medicine; quality of life
5.  Cognitive deficit is associated with phase advance of sleep–wake rhythm, daily napping, and prolonged sleep duration—a cross-sectional study in 2,947 community-dwelling older adults 
Age  2012;35(2):479-486.
This study aims to examine the phase advance of sleep–wake rhythm, napping habit, nocturnal sleep duration, prolonged sleep latency and insomnia and their relationship with cognitive function. This is a cross-sectional study. Participants in this study are 2,947 community-dwelling adults older than 65 years old. Measurements of mini-mental examination (MMSE) score, go-to-bed time, wake-up time, nocturnal sleep duration, prolonged sleep latency, napping, and insomnia were done. The mean (standard deviation) nocturnal sleep hours was 7.96 (1.39) h. Twenty-one percent and 16.2% of the participants complained of prolonged sleep latency longer than 1 h and insomnia, respectively. Fifty-six percent of the participants napped once or more than once weekly. With advancing age, the participants reported longer sleep duration (p < 0.001), went to bed earlier, and woke up earlier, which were significant both before and after adjustment. The participants who had lower MMSE score went to bed earlier and woke up earlier, which were statistically significant both before and after adjustment. An inverted U-shaped relationship was observed between MMSE score and napping frequency, p for tend 0.026.The MMSE score decreased when the sleep duration prolonged from 7 h to ≧10 h (p for trend 0.006). No trend was observed from the sleep duration <4 up to 7.9 h (p for trend 0.500). Modest age-independent phase advance of the sleep–wake rhythm is associated with lower cognitive function. Whether this is a manifestation of early pre-clinical dementia and whether its recognition with early stabilization can slow cognitive decline remain elusive.
PMCID: PMC3592949  PMID: 22215376
Phase advance; Sleep/wake rhythm; Sleep duration; Dementia; Cognitive decline; Napping; Insomnia; Prolonged sleep latency
6.  Prevalence and gender difference of lumbar disc space narrowing in elderly Chinese men and women: Mr. OS (Hong Kong) and Ms. OS (Hong Kong) studies 
Arthritis and rheumatism  2013;65(4):1004-1010.
Mr. OS (Hong Kong) and Ms. OS (Hong Kong) represent the first large scale prospective population based studies conducted on bone health in elderly (≥65 yrs) Chinese men (n=2000) and women (n=2000). The current study investigated the prevalence of lumbar disc space narrowing (DSN) in these subjects, and identified the potential relationship between DSN and gender, bone mineral density (BMD), and other demographic and clinical data.
On lumbar lateral radiographs, L1/L2-L4/L5 disc space was classified to 4 categories: 0= normal; 1= mild narrowing; 2= moderate narrowing; 3= severe narrowing. Demographic and clinical data between subjects with and without sum of DSN score ≥ 3 were compared.
DSN was more common in elderly women than in men. The average DSN score for the four discs was 2.71±2.21 for men, and 3.08±2.50 for women (P<0.0001). For the three age groups of 65~69, 70~79, ≥80 (yrs), average DSN score increased with increasing age in both men and women, and to a greater degree in women than men. Average DSN score difference between women and men was 0.12, 0.40, and 0.90 respectively in the three age groups. For both men and women, DSN ≥ 3 was associated with older age, higher spine and hip BMD, low back pain, and restricted leg mobility.
Prevalence and severity of DSN is higher in elderly women than elderly men. With increasing age, DSN progresses at a greater rate in females than males. DSN ≥ 3 is associated with higher spine and hip BMD.
PMCID: PMC3618501  PMID: 23335175
lumbar; disc; gender; elderly; bone mineral density
7.  Systematic Review of Chinese Medicine for Miscarriage during Early Pregnancy 
Background. Miscarriage is a very common complication during early pregnancy. So far, clinical therapies have limitation in preventing the early pregnancy loss. Chinese Medicine, regarded as gentle, effective, and safe, has become popular and common as a complementary and alternative treatment for miscarriages. However, the evidence to support its therapeutic efficacy and safety is still very limited. Objectives and Methods. To summarize the clinical application of Chinese Medicine for pregnancy and provide scientific evidence on the efficacy and safety of Chinese medicines for miscarriage, we located all the relevant pieces of literature on the clinical applications of Chinese Medicine for miscarriage and worked out this systematic review. Results. 339,792 pieces of literature were identified, but no placebo was included and only few studies were selected for systematic review and conducted for meta-analysis. A combination of Chinese medicines and Western medicines was more effective than Chinese medicines alone. No specific safety problem was reported, but potential adverse events by certain medicines were identified. Conclusions. Studies vary considerably in design, interventions, and outcome measures; therefore conclusive results remain elusive. Large scales of randomized controlled trials and more scientific evidences are still necessary to confirm the efficacy and safety of Chinese medicines during early pregnancy.
PMCID: PMC3933529  PMID: 24648851
8.  Ten Years' Research on a Cardiovascular Tonic: A Comprehensive Approach—From Quality Control and Mechanisms of Action to Clinical Trial 
Objective. Mortality arising from cardiovascular pathologies remains one of the highest. Maintenance of cardiovascular health therefore remains a universal concern. Interventional therapies and medications have made impressive advances, but preventive measures would be of the same importance. Method. Ten years' search for a simple herbal formula has resulted in a two-herb combination, consisting of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix. The formula has been studied extensively on cardiovascular biological platforms and then put on three clinical trials. Results. In the laboratory, the formula was found to have the biological effects of anti-inflammation, anti-oxidation, anti-foam cell formation on vascular endothelium, and vasodilation. Clinical trials using ultrasonic carotid intima thickness as a surrogate marker showed very significant benefits. No significant adverse effects were encountered. Conclusion. It is therefore recommended that the herbal formula could be used as an adjuvant therapy in cardiac patients under treatment or as a preventive agent among the susceptible.
PMCID: PMC3845704  PMID: 24324512
9.  Inferior physical performance tests in 10,998 men in the MrOS study is associated with recurrent falls 
Age and Ageing  2012;41(6):740-746.
Background: recurrent fallers are at especially high risk for injuries.
Objective: to study whether tests of physical performance are associated with recurrent falls.
Subjects: a total of 10,998 men aged 65 years or above.
Methods: questionnaires evaluated falls sustained 12 months preceding testing of grip strength, timed stand, 6-m walk and 20-cm narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.01 is a statistically significant difference.
Results: in comparison to both occasional fallers and non-fallers, recurrent fallers performed more poorly on all the physical ability tests (all P < 0.001). A score below −2 standard deviations (SDs) in the right-hand grip strength test was associated with an odds ratio of 2.4 (95% CI 1.7, 3.4) for having had recurrent falls compared with having had no fall and of 2.0 (95% CI 1.3, 3.4) for having had recurrent falls compared with having had an occasional fall.
Conclusion: low performance in physical ability tests are in elderly men associated with recurrent falls.
PMCID: PMC3476829  PMID: 22923607
falls; men; muscle; older people; physical performance tests; recurrent
10.  The Aqueous Extract of Rhizome of Gastrodia elata Protected Drosophila and PC12 Cells against Beta-Amyloid-Induced Neurotoxicity 
This study aims to investigate the neuroprotective effect of the rhizome of Gastrodia elata (GE) aqueous extract on beta-amyloid(Aβ)-induced toxicity in vivo and in vitro. Transgenic Drosophila mutants with Aβ-induced neurodegeneration in pan-neuron and ommatidia were used to determine the efficacy of GE. The antiapoptotic and antioxidative mechanisms of GE were also studied in Aβ-treated pheochromocytoma (PC12) cells. In vivo studies demonstrated that GE (5 mg/g Drosophila media)-treated Drosophila possessed a longer lifespan, better locomotor function, and less-degenerated ommatidia when compared with the Aβ-expressing control (all P < 0.05). In vitro studies illustrated that GE increased the cell viability of Aβ-treated PC12 cells in dose-dependent manner, probably through attenuation of Aβ-induced oxidative and apoptotic stress. GE also significantly upregulated the enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase, leading to the decrease of reactive oxidation species production and apoptotic marker caspase-3 activity. In conclusion, our current data presented the first evidence that the aqueous extract of GE was capable of reducing the Aβ-induced neurodegeneration in Drosophila, possibly through inhibition of apoptosis and reduction of oxidative stress. GE aqueous extract could be developed as a promising herbal agent for neuroprotection and novel adjuvant therapies for Alzheimer's disease.
PMCID: PMC3794658  PMID: 24174977
11.  Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor Blockade 
Pharmaceuticals  2013;6(8):1039-1054.
NMDA receptor (NMDA-R) is an important molecular entity governing a wide range of functions in the central nervous system. For example, the NMDA-R is involved in memory and cognition, and impairment of both (as in Alzheimer’s Disease) is attributed to NMDA-mediated neurotoxicity. With greater understanding of the NMDA-R structure, antagonists with varying degrees of binding-site and subtype selectivity have been developed and put into clinical use. Discovery of target-specific Chinese herbs have also been made in parallel. This article provides an overview of the known active sites on the NMDA-R, followed by a discussion of the relevant herbs and their constituents. Experimental evidence supporting the inhibitory role of the herbal compounds on the NMDA-R is highlighted. For some of the compounds, potential research directions are also proposed to further elucidate the underlying mechanisms of the herbs. It is envisaged that future investigations based on the present data will allow more clinically relevant herbs to be identified.
PMCID: PMC3817734  PMID: 24276380
NMDA receptor; antagonist; herb; Chinese medicine
12.  The effectiveness of acupuncture on the sleep quality of elderly with dementia: a within-subjects trial 
Elderly with dementia are often afflicted with sleep problems. Recent studies have suggested that acupuncture may be a feasible alternative to traditional sleep medicine for treating sleep disturbance. This study investigated the effectiveness of acupuncture on sleep quality of elderly with dementia.
Patients and methods
Nineteen elders with dementia were followed through a control period and an acupuncture treatment period, each lasting 6 weeks. Outcome measures were subjects’ sleep quality and cognitive function. Sleep parameters were recorded by wrist actigraphy. Cognitive function was assessed by the Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-Cog). Pretests and posttests were conducted immediately before and after the control and treatment periods. Changes in the outcome measures between control and treatment periods were compared.
Wilcoxon signed rank tests revealed that the subjects gained significantly more resting time and total sleep time in the treatment period than in the control period (P < 0.05). A nonsignificant trend for improvement in sleep efficiency was observed. Improvement in cognitive function was not statistically significant. A total of 86% of the subjects completed the treatment regime.
Results reveal that acupuncture was effective in improving some domains of sleep quality of elderly with dementia, and the subjects showed acceptance towards the intervention. Strengths and limitations of the present study as well as suggestions for further studies were considered.
PMCID: PMC3736969  PMID: 23940415
acupuncture; sleep disturbance; patients with dementia
13.  The Known Immunologically Active Components of Astragalus Account for Only a Small Proportion of the Immunological Adjuvant Activity When Combined with Conjugate Vaccines 
Planta medica  2010;77(8):817-824.
The 95% ethanol extract of Astragalus has been demonstrated to have potent activity as an immunological adjuvant when administered with vaccines of various types. We endeavor here to identify the components of this extract that are responsible for this adjuvant activity. Mice were immunized with KLH conjugated to cancer carbohydrate antigens globo H and GD3 and cancer peptide antigen MUC1 combined with different Astragalus fractions or with commercially available Astragalus saponins and flavonoids. The antibody responses against cancer antigens and KLH were quantitated in ELISA assays, and toxicity was calculated by weight loss. Astragalosides II and IV were the most active components, but the toxicity of these two differed dramatically. Astragaloside II was the most toxic Astragalus component with 5–10% weight loss at a dose of 500 µg while astragaloside IV showed no weight loss at all at this dose, suggesting that astragaloside IV might be utilized as an immunological adjuvant in future studies. Several flavonoids also had significant adjuvant activity. However, when the activities of these known immunologically active components of Astragalus (and of endotoxin) are calculated based on the extent of their presence in the 95% ethanol extract, they provide only a small proportion of the immunological activity. This raises the possibility that additional uniquely active components of Astragalus may contribute to adjuvant activity, or that the adjuvant activity of Astragalus is greater than the activity of the sum of its parts.
PMCID: PMC3711077  PMID: 21128203
Astragalus membranaceus; Leguminosae; botanicals; conjugate vaccine; cancer vaccine; astragalosides; saponin
14.  Inferior physical performance test results of 10,998 men in the MrOS Study is associated with high fracture risk 
Age and Ageing  2012;41(3):339-344.
Background: most fractures are preceded by falls.
Objective: the aim of this study was to determine whether tests of physical performance are associated with fractures.
Subjects: a total of 10,998 men aged 65 years or above were recruited.
Methods: questionnaires evaluated falls sustained 12 months before administration of the grip strength test, the timed stand test, the six-metre walk test and the twenty-centimetre narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.05 is a statistically significant difference.
Results: fallers with a fracture performed worse than non-fallers on all tests (all P < 0.001). Fallers with a fracture performed worse than fallers with no fractures both on the right-hand-grip strength test and on the six-metre walk test (P < 0.001). A score below –2 standard deviations in the right-hand-grip strength test was associated with an odds ratio of 3.9 (95% CI: 2.1–7.4) for having had a fall with a fracture compared with having had no fall and with an odds ratio of 2.6 (95% CI: 1.3–5.2) for having had a fall with a fracture compared with having had a fall with no fracture.
Conclusion: the right-hand-grip strength test and the six-metre walk test performed by old men help discriminate fallers with a fracture from both fallers with no fracture and non-fallers.
PMCID: PMC3335372  PMID: 22314696
falls; fractures; men; old; physical performance tests; elderly
16.  Stachyose: One of the Active Fibroblast-proliferating Components in the Root of Rehmanniae Radix (地黃 dì huáng)  
This study aimed to investigate and compare the fibroblast-proliferating activities of different Rehmanniae Radix (RR) samples and its chemical components using human normal fibroblast cells Hs27. Those active components were quantified in differently treated RR samples using UPLC so as to correlate activity with component content. Our results showed that dried RR aqueous extract exhibited the most potent fibroblast-proliferating activity. Stronger effect was observed when ethanol with heating was applied in the extraction process. Stachyose and verbascoside were demonstrated for their first time to exhibit significant stimulatory effects on fibroblast proliferation. However, the proliferating effect of dried RR extract did not correlate with the stachyose content, and verbascoside was not responsible for the fibroblast proliferative effect of RR since it was undetectable in all samples. In conclusion, stachyose only contributed in part to the activity of RR, suggesting that other active components might be present and yet to be found.
PMCID: PMC3942900  PMID: 24716137
Rehmanniae Radix; Rehmannia glutinosa; Stachyose; Verbascoside; Fibroblast proliferation
17.  Chemical and Genetic Assessment of Variability in Commercial Radix Astragali (Astragalus spp.) by Ion Trap LC-MS and Nuclear Ribosomal DNA Barcoding Sequence Analyses 
Radix Astragali (Huangqi) has been demonstrated to have a wide range of immunopotentiating effects and has been used as an adjuvant medicine during cancer therapy. Identity issues in the collection of Radix Astragali exist because many sympatric species of Astragalus occur in the northern regions of China. In order to assess the quality, purity, and uniformity of commercial Radix Astragali, 44 samples were purchased from herbal stores in Hong Kong and New York City. The main constituents, including four isoflavonoids and three saponins were quantitatively determined by liquid chromatography mass spectrometry (LC-MS). There was significant sample-to-sample variability in the amounts of the saponins and isoflavonoids measured. Furthermore, DNA barcoding utilizing the variable nuclear ITS spacer regions of the 44 purchased Radix Astragali samples were sequenced, aligned and compared. Eight polymorphic point mutations were identified which separated the Radix Astragali samples into three groups. These results indicate that the chemical and genetic variability that exists among Radix Astragali medicinal products is still a consistency and quality issue for this herbal. Two-way ANOVA analysis showed significant effect on the contents of the seven tested compounds when both phylogenetic and geographic (i.e. point of purchase) factors considered. Therefore, chemical profiles determined by LC-MS and DNA profiles in ITS spacer domains could serve as barcode markers for quality control of Radix Astragali.
PMCID: PMC3058609  PMID: 21322556
18.  Inhibitory effects of salviae miltiorrhizae radix (danshen) and puerariae lobatae radix (gegen) in carbachol-induced rat detrusor smooth muscle contractility 
Both danshen (D) and gegen (G) have proven relaxant effects on vascular smooth muscle, thus their potential bladder inhibitory effects have impending interests in urology. The aim of this study was to demonstrate the novel effects of D and G on detrusor smooth muscle contractility. Urothelium-intact (+UE) and urothelium-denuded (-UE) detrusor strips were isolated from the rat. Isometric tension was measured using a myograph system. Carbachol (CCh) was used to pre-contract the detrusor strips prior to stepwise relaxation by adding extracts of D, G, and a DG (7:3) formulation. Tonic relaxation level and phasic contractile activity under the herbal treatments were analyzed. There was no difference in the herbal effects between +UE and -UE strips. D alone induced a much smaller relaxation than G alone or DG. G alone also suppressed phasic amplitude but not phasic frequency while DG suppressed both parameters. D and G acted synergistically to yield the observed effects on detrusor smooth muscle. The findings showed that the DG formulation were able to relax the detrusor as well as suppress phasic contractions, both actions important in maintaining normal bladder filling and urine storage processes. Hence DG may have new application in the management of bladder disorders.
PMCID: PMC3312461  PMID: 22461955
Detrusor smooth muscle; contractility; danshen; gegen; Chinese medicine
19.  Effects of height loss on morbidity and mortality in 3145 community-dwelling Chinese older women and men: a 5-year prospective study 
Age and Ageing  2010;39(6):699-704.
Background: height loss beginning in mid-life and post-menopausal period was associated with adverse health outcomes. However, height loss occurring after old age has been little studied. We examined how height loss was related to bone mineral density (BMD) change, fracture incidence and cause-specific mortality in older adults.
Methods: the stature and BMD of 3145 community-dwelling men and women aged ≥65 were measured at baseline and after 4 years. All fracture and cause-specific mortality events were searched in a territory-wide clinical information database and death registry.
Results: twenty-five (1.6%) men and 64 (4.0%) women lost >2 cm after 4 years. In women, the BMD decline was faster in the rapid height losers (adjusted difference = 4.18%, P < 0.001). There was no corresponding difference observed in men. Rapid height loss was associated with excess all fractures and hip fractures (adjusted HR for all fractures = 2.86, P < 0.001; adjusted HR for hip fractures = 4.74, P < 0.01) in women but only hip fractures (adjusted HR = 4.93, P < 0.05) in men. The all-cause (adjusted HR = 3.43, P < 0.01) and respiratory disease mortality (adjusted HR = 5.64, P < 0.05) were higher in men with rapid height loss, whereas those in women were insignificant.
Conclusions: modest height loss occurring after old age, >2 cm in 4 years, was associated with excess hip fracture, total and respiratory disease mortality in older men. In women, it was associated with excess BMD decline, all fractures and hip fractures but not mortality. Further research is needed to determine the usefulness of regular stature measurement as an indicator of bone health in the primary-care setting in older adults.
PMCID: PMC2956531  PMID: 20817934
height loss; mortality; fractures; osteoporosis; elderly
20.  Immunostimulatory activities of polysaccharide extract isolated from Curcuma longa 
Several curcuminoids and sesquiterpenoids isolated from Curcuma longa (CL) have been shown to have many pharmacological activities. In the present study, the immunomodulatory activities of the polar fractions of CL hot water extracts were investigated using human peripheral blood mononuclear cells (PBMC). Our results showed that the high polarity fraction of the hot water extract exhibited stimulatory effects on PBMC proliferation as shown in [methyl-3H]-thymidine incorporation assay. In an attempt to isolate the active components responsible for the activities, further partition with ethyl-acetate, n-butanol and ethanol, progressively were performed. The cytokine productions (TGF-β, TNF-α, GM-CSF, IL-1α, IL-5, IL-6, IL-8, IL-10 and IL-13, etc.) have been modulated by a polysaccharide-enriched fraction as shown in ELISA and cytokine protein array. The proportion of CD14 positive stained PBMC was increased by such fraction. The composition of monosaccharide of the active fraction has been determined by GC-MS and gel permeation chromatography. The immunostimulatory effects of Curcuma longa polysaccharides on PBMC were shown for the first time. The findings revealed the potential use of Curcuma longa crude extract (containing curcuminoids and polysaccharides) as an adjuvant supplement for cancer patients, whose immune activities were suppressed during chemotherapies.
PMCID: PMC2917522  PMID: 20609432
Curcuma longa; immunostimulatory; peripheral blood mononuclear cells; polysaccharide
21.  The Ethanol Extract of Fructus trichosanthis Promotes Fetal Hemoglobin Production via p38 MAPK Activation and ERK Inactivation in K562 Cells 
Pharmacological stimulation of fetal hemoglobin (HbF) expression may be a promising approach for the treatment of beta-thalassemia. In this study, the effects of Fructus trichosanthis (FT) were investigated in human erythroleukemic K562 cells for their gamma-globin mRNA and HbF-induction activities. The role of signaling pathways, including extracellular regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), was also investigated. It was found that the ethanol extract of FT significantly increased gamma-globin mRNA and HbF levels, determined by real-time reverse transcription polymerase chain reaction and enzyme linked immunosorbent assay, respectively, in dose- and time-dependent manner. Total Hb (THb) levels were also elevated in the concentrations without cytotoxicity (<80 μg mL−1). Pre-treatment with p38 MAPK inhibitor SB203580 blocked the stimulatory effects of FT extract in total and HbF induction. In contrast, no change in HbF was observed when treated with ERK inhibitor PD98059. Furthermore, FT ethanol extract activated p38 MAPK and inhibited ERK signaling pathways in K562 cells, as revealed in western blotting analysis. In addition, SB203580 significantly abolished p38 MAPK activation when the cells were treated with FT. In summary, the ethanol extract of FT was found to be a potent inducer of HbF synthesis in K562 cells. The present data delineated the role of ERK and p38 MAPK signaling as molecular targets for pharmacologic stimulation of HbF production upon FT treatment.
PMCID: PMC3163070  PMID: 21876711
22.  Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa 
The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent.
PMCID: PMC2910176  PMID: 20438793
Turmerone; Breast cancer; Apoptosis; Immunomodulatory; Peripheral blood mononuclear cells
23.  Chinese herbal medicine research in eczema treatment 
Chinese Medicine  2011;6:17.
Eczema is a chronic relapsing atopic dermatitis (AD) associated with pruritus, sleep disturbance and poor quality of life of the patient. Treatment of eczema includes use of emollient, topical and systemic antimicrobial agents, corticosteroid or immunomodulating agents. Many patients also seek alternative treatments such as dietary avoidance, supplementation or both. This article reviews the basic pathophysiology of eczema and clinical trials involving Chinese medicine in the treatment of eczema. Research reports on Chinese herbal medicine for eczema were retrieved from PubMed and the Cochrane Database for Systematic Reviews for this review. Only a few RCTs demonstrated the efficacy (or lack of efficacy) of Chinese medicinal herbs in treating atopic eczema. Further larger scale trials are warranted.
PMCID: PMC3110124  PMID: 21527032
24.  Suppression of low-density lipoprotein oxidation, vascular smooth muscle cell proliferation and migration by a herbal extract of Radix Astragali, Radix Codonopsis and Cortex Lycii 
Atherosclerosis is a major cause of death in developed world. Atherosclerosis is characterized by low-density lipoprotein deposition in the arterial wall which ultimately begets the formation of lesions. Rupture of lesions finally leads to clinical events such as heart attack and stroke. Atherosclerosis is a complication associated with diabetes. In patients with diabetes, the risk of atherosclerosis is three to five folds greater than in non-diabetics. Our previous study showed that a herbal extract of Radix Astragali, Radix Codonopsis and Cortex Lycii, namely SR10, could improve glucose homeostasis both in vitro and in vivo. In this study, we want to further investigate the efficacy of SR10 in treating atherosclerosis.
The inhibitory effect of SR10 on low-density lipoprotein oxidation was investigated using free radical-induced erythrocyte hemolysis model and copper ion-induced low-density lipoprotein oxidation model. Since vascular smooth muscle cell proliferation and migration are important processes in atherogenesis, we also examined the effect of SR10 in inhibiting these events.
Our results showed that SR10 inhibited erythrocyte hemolysis with IC50 value at 0.25 mg/ml and significantly prolonged low-density lipoprotein oxidation in vitro. SR10 attenuated platelet derived growth factor-BB-induced vascular smooth muscle cell proliferation by promoting cell cycle arrest at G0/G1 phase as well as inhibiting vascular smooth muscle cell migration.
The potential application of SR10 in treating atherosclerosis has been implied in this study. Animal model will be needed to further verify the efficacy of SR10 in future.
PMCID: PMC3107819  PMID: 21513503
Atherosclerosis; vascular smooth muscle cell; proliferation; migration
25.  Survival in Older Men May Benefit From Being Slightly Overweight and Centrally Obese—A 5-Year Follow-up Study in 4,000 Older Adults Using DXA 
Whether overweight in old age is hazardous remains controversial. Body mass index (BMI) overestimates adiposity and fails to measure central adiposity. We used dual-energy x-ray absorptiometry (DXA) to measure adiposity and hypothesized that overall adiposity, distribution of adiposity, and muscle mass might individually affect survival.
We recruited 2000 men and 2000 women aged 65 years or older. Baseline BMI, waist–hip ratio (WHR), body fat index (BFI = total body fat/height square), relative truncal fat (RTF = trunk fat/total body fat), and body muscle mass index (BMMI = total body muscle mass/height square) were measured. Mortality was ascertained by death registry after 63.3 (median) months.
Two hundred and forty-two men and 78 women died. In men, mortality hazard ratio (HR) decreased consistently by 0.85 (p < .005), 0.86 (p < .005), and 0.86 (p < .005) per every quintile increase in BMI, BFI, and BMMI, respectively. A J-shaped relationship was observed in central adiposity (RTF and WHR) quintiles; the minimum values were at the 3rd WHR quintile (0.92–0.94) and 4th RTF quintile (mean WHR, 0.94). When RTF was tested with BFI, both high and low central adiposity were unfavorable while general adiposity became marginally insignificant (p = 0.062). When BFI and BMMI were tested together, increasing adiposity rather than muscle mass favored survival (BFI quintile, HR 0.97, p .015; BMMI quintile, HR 1.00, p .997).
Older men were resistive to hazards of overweight and adiposity; and mild-grade overweight, obesity, and even central obesity might be protective. This may bear significant implication on the recommended cutoff values for BMI and WHR in the older population.
PMCID: PMC2796879  PMID: 19628635
mortality; adiposity; BMI; muscles

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