Clara B S Lau

The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Publications (80)201.21 Total impact

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    ABSTRACT: Preclinical ResearchSchisandrae Chinensis Fructus (SCF), the fruit of Schisandra chinensis (Turcz.) Baill. (family Schisandraceae) is traditionally used as a tonic and antidiabetic agent in Asia. In this study, SCF was investigated for its effects on sodium glucose cotransporters 1 and 2 (SGLT 1 and 2) expressed in a COS-7 cell line for its specificity in inhibiting SGLT2, which is a novel mechanism to screen for potential antidiabetic agents. Using a bioassay-guided fractionation, we then tried to isolate and identify the active fraction(s)/component(s). The ethanol extract of SCF at a concentration of 1 mg/mL significantly inhibited 89% of SGLT1 and 73% of SGLT2 activities in a [14C]-α-methyl-d-glucopyranoside ([14C]-AMG) uptake assay. Fractionation of the ethanol extract yielded nine fractions, of which F8, at a concentration of 1 mg/mL, was specific in inhibiting SGLT 2 (42% inhibition, P < 0.001), without inhibiting SGLT 1. Using LC/MS-MS, three compounds, deoxyschisandrin, schisandrin B (γ-schisandrin) and schisandrin were identified in F8 and their amounts quantified. However, subsequent evaluation in the [14C]-AMG uptake assay showed that these three compounds failed to inhibit SGLT 2 activity indicating that the SGLT active component(s) from SCF have yet to be identified.
    Drug Development Research 12/2014; · 0.87 Impact Factor
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    ABSTRACT: We investigated the effect of a Chinese 2-herb formula (NF3) on the enumeration and angiogenic differentiation of endothelial progenitor cells (EPCs) in diabetic foot ulcer rats.
    Journal of Diabetes 10/2014; · 2.94 Impact Factor
  • Pancreas 10/2014; 43(7):1126-1128. · 2.95 Impact Factor
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    ABSTRACT: Objectives The aims of this study were to identify the active ingredients from Portulaca oleracea L. (PO) that could provide synergism with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) and their possible mechanisms of resistance inhibition.Methods High-speed counter-current chromatography (HSCCC) coupled with gas chromatography-mass spectrometry and a panel of laboratory MRSA strains were used for checkerboard and efflux inhibitory assays.Key findingsLinoleic and oleic acids were identified from HSCCC fraction 18 of PO with synergistic antibacterial activity when combined with erythromycin against RN4220/pUL5054. Ethidium bromide efflux inhibitory studies revealed that linoleic and oleic acids may interfere the activity of MsrA pump. By comparing among a panel of linoleic and oleic acids analogues, unsaturated fatty acids in salt form with cis configuration and an increase in number of double bonds were found to further increase the antibacterial activity when used alone or in combination with antibiotics.Conclusion This study reported for the first time that two active ingredients, namely linoleic and oleic acids, were identified from PO with synergistic antibacterial activity when combined with erythromycin against MRSA RN4220/pUL5054 and possibly act by inhibiting the efflux pumps of the bacteria cells.
    Journal of Pharmacy and Pharmacology. 10/2014;
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    ABSTRACT: Thiol-containing antioxidant systems play an important role in regulating cellular redox homeostasis. Several anti-cancer agents act by targeting these systems by inducing the production of reactive oxygen species (ROS). Our earlier studies have shown that Eriocalyxin B (EriB), a diterpenoid isolated from Isodon eriocalyx, possesses anti-pancreatic tumour activities in vitro and in vivo. The present study further demonstrated that only thiol-containing antioxidants, N-acetylcysteine (NAC) or dithiothreitol (DTT), inhibited EriB-induced cytotoxicity and apoptosis. EriB suppressed the glutathione and thioredoxin antioxidant systems, thus increasing the intracellular ROS levels and regulating the MAPK, NFκB pathways. Treatment with EriB depleted the intracellular thiol-containing proteins in CAPAN-2 cells. In vivo studies also showed that EriB treatment (2.5 mg/kg) reduced the pancreatic tumour weights significantly in nude mice with increased superoxide levels. Taken together, our results shed important new light on the molecular mechanisms of EriB acting as an apoptogenic agent and its therapeutic potential for pancreatic cancer.
    Current Molecular Medicine 07/2014; 14(5). · 4.20 Impact Factor
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    ABSTRACT: Bitter melon, the fruit of Momordica charantia L. (Cucurbitaceae), is a widely-used treatment for diabetes in traditional medicine systems throughout the world. Various compounds have been shown to be responsible for this reputed activity, and, in particular, cucurbitane triterpenoids are thought to play a significant role. The objective of this study was to investigate the gastrointestinal transport of a triterpenoid-enriched n-butanol extract of M. charantia using a two-compartment transwell human intestinal epithelial cell Caco-2 monolayer system, simulating the intestinal barrier. Eleven triterpenoids in this extract were transported from the apical to basolateral direction across Caco-2 cell monolayers, and were identified or tentatively identified by HPLC-TOF-MS. Cucurbitane triterpenoids permeated to the basolateral side with apparent permeability coefficient (P app) values for 3-β-7-β,25-trihydroxycucurbita-5,23(E)-dien-19-al and momordicines I and II at 9.02 × 10(-6), 8.12 × 10(-6), and 1.68 × 10(-6) cm/s, respectively. Also, small amounts of these triterpenoids were absorbed inside the Caco-2 cells. This is the first report of the transport of the reputed antidiabetic cucurbitane triterpenoids in human intestinal epithelial cell monolayers. Our findings, therefore, further support the hypothesis that cucurbitane triterpenoids from bitter melon may explain, at least in part, the antidiabetic activity of this plant in vivo.
    Planta Medica 07/2014; 80(11):907-11. · 2.35 Impact Factor
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    ABSTRACT: Endothelial cells were crucially involved in wound healing angiogenesis, restoring blood flow to wound tissues. Our previous study demonstrated that the Chinese 2-herb formula (NF3) possessed significant wound healing effect in diabetic foot ulcer rats with promising in vitro pro-angiogenic effects on human umbilical vein endothelial cells (HUVEC). Here we presented the comparative global proteome analysis of NF3-treated HUVEC in static or scratch conditions, screening the comprehensive molecular targets in governing the pro-angiogenic response in wound healing. Our results suggested PAI-1, specifically down-regulated in static condition and ANXA1 and ANXA2, up-regulated in scratch condition, as principal proteins which were responsible for the pro-angiogenesis in wound healing. We also identified a panel of cytoskeleton regulatory proteins in static and scratch condition, mediating the migratory behavior of NF3-treated HUVEC. The key proteins in static state included MYL9, SPAST, TPM2 and VIM while that in scratch state contained LMNA, TPM1, TPM2 and VIM. In addition, NF3 was shown to regulate transcription and translation, cell-cell interaction and ROS defense in HUVEC. Proliferation and migration assays further confirmed the identified principal proteins PAI-1 and ANXA2 which are responsible for NF3-induced pro-angiogenesis of HUVEC in wound healing. This was the first study on the global proteome expression of NF3-treated HUVEC with the identification of the differences at the molecular level, between static and scratch conditions involved in wound healing angiogenesis.This article is protected by copyright. All rights reserved
    Proteomics 07/2014; · 4.43 Impact Factor
  • European Journal of Integrative Medicine 02/2014; 6(1):129–130. · 0.56 Impact Factor
  • European Journal of Integrative Medicine 02/2014; 6(1):129. · 0.56 Impact Factor
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    ABSTRACT: The study objective was to evaluate the composition of a neutral and weakly acidic water-soluble extract from Echinacea purpurea (L.) Moench (EchNWA) previously shown to modify the course of influenza infection in a mouse model, and to assess potential immunomodulatory effects on human T-cells. This EchNWA extract was obtained from fresh aerial parts extracted with water, followed by ethanolic precipitation, and size-exclusion chromatography. The chemical profile of EchNWA was characterized by chromatography (size-exclusion, HPLC, GC-MS), and small molecule fingerprint analysis was performed by HPLC-PDA. Jurkat T-cells at high and low cell density were pretreated or not for 40min with doses of EchNWA, followed by activation with phorbol 12-myristate 13-acetate plus ionomycin (PMA+I). Interleukin-2 (IL-2) and interferon gamma (IFN-γ) cytokine secretion were measured by multi-cytokine bead immunoassay and assessed by Luminex technology. Expression of CD25 on T-cells was measured by flow cytometry. Results showed that EchNWA contains 80% polysaccharides, predominantly a 10kDa entity; phenolic compounds primarily cynarin, cichoric and caftaric acids, but no detectable alkylamides. T-cell cytokine production was absent without stimulation and was much less after PMA+I activation in high-density compared to low-density conditions. EchNWA mediated a strong dose-dependent enhancement of high-density T-cell production of IL-2 and IFN-γ response to PMA+I. EchNWA alone did not stimulate T-cells. EchNWA enhanced mean fluorescence intensity of IL-2 response in Jurkat T-cells activated by PMA+1 or ionomycin alone. Conversely EchNWA mediated slight but significant suppression of T-cell production of IFN-γ and reduced the percentage of CD25+ T-cells under low-density conditions. Conclusions are that polysaccharides in the EchNWA extract, but not phenolic compounds cause dose-related adjuvant effects on human T-cell cytokine responses characterized by enhancing and suppressing the effects that were regulated by T-cell density.
    International immunopharmacology 01/2014; · 2.21 Impact Factor
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    ABSTRACT: Export Date: 18 October 2014
    Journal of Agricultural and Food Chemistry. 01/2014; 62(39):9488-9498.
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    ABSTRACT: Chlorhexidine (CHX) is a widely used antimicrobial agent in dentistry. Herein, we report the synthesis of a novel mesoporous silica nanoparticle-encapsulated pure CHX (Nano-CHX), and its mechanical profile and antimicrobial properties against oral biofilms.
    PLoS ONE 01/2014; 9(8):e103234. · 3.53 Impact Factor
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    ABSTRACT: Chinese medicine is a common name for a collection of Chinese Materia Medica with therapeutic properties for medical treatment and healing. Similar to Western pharmaceuticals, Chinese medicines are not free of risk, and have the potential to cause adverse pregnancy outcomes and affect embryonic and fetal development. However, most clinical data concerning safety of maternal exposure to Chinese medicines during pregnancy are not available and the conclusion remains elusive. Some individual clinical trials of Chinese medicines reported some minor adverse effects during pregnancy, whereas few animal studies identified some adverse maternal and perinatal effects, as well as embryotoxic potentials. Basic research and mechanistic studies of the teratogenicity of Chinese medicines are still lacking. There is an urgent need for testing the safety of Chinese medicines before recommendation and commercialization. Until more reliable and scientific research data become available, clinicians should consider both the risks and benefits before recommending Chinese medicines to pregnant women. More systematic investigations of the safety implications of the use of Chinese medicines are highly recommended, in addition to more clinical trials with a larger sample size to confirm its safety during pregnancy. This review includes a critical overview of available clinical and experimental data and provides directions to study the safety issue of Chinese medicines for pregnancy. Birth Defects Research (Part C) 99:275-291, 2013. © 2013 Wiley Periodicals, Inc.
    Birth Defects Research Part C Embryo Today Reviews 12/2013; 99(4):275-91. · 4.44 Impact Factor
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    ABSTRACT: Danshen and Gegen are two commonly used Chinese herbal medicines for treatment of cardiovascular diseases. The aim of the present study was to elucidate the combination effects of these two herbs on cerebral vascular tone and their underlying mechanisms of actions. Basilar artery rings were obtained from rats and precontracted with U46619. Cumulative administrations of aqueous extracts of Danshen, Gegen, or the two herbs combined (DG; ratio 7:3) produced concentration-dependent relaxation of the artery rings. Statistical analysis on these findings produced a combination index (CI) of 1.041 at ED50, which indicates the two herbs produced additive vasodilator effects when used as a combined decoction. Removal of the endothelium had no effect on the vasodilator properties of Danshen, Gegen, and DG. However, their maximum effects (Imax) were significantly blunted by a KATP channel inhibitor glibenclamide, a non-selective K(+) channel inhibitor tetraethylammonium (TEA), and by a combination of K(+) channel inhibitors (glibenclamide+TEA+iberiotoxin+4-aminopyridine+barium chloride). In addition, Danshen, Gegen, and DG produced augmentation of KATP currents and inhibited Ca(2+) influx in vascular smooth muscle cells isolated from rat basilar arteries. Furthermore, these agents inhibited CaCl2-induced contraction in the artery rings. In conclusion, the present study showed that Danshen and Gegen produced additive vasodilator effects on rat cerebral basilar arteries. These effects were independent of endothelium-derived relaxant factors (EDRF), but required the opening of KATP channels and inhibition of Ca(2+) influx in the vascular smooth muscle cells. It is suspected that the cerebral vasodilator effects of Danshen and Gegen produced either on their own or in combination, can help patients with obstructive cerebrovascular diseases.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 11/2013; · 2.97 Impact Factor
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    ABSTRACT: Mast cells are believed to contribute to the pathogenesis of osteoporosis as their number is increased in osteoporotic bones. Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae are three Chinese herbs traditionally for tonifying the 'kidney system' and a herbal formula (ELP) containing the respective herbs at the weight ratio of 5 : 4 : 1 was shown to prevent osteoporosis. This study evaluated if suppression of mast cell accumulation and activity contribute to the anti-osteoporotic action of ELP. The herbs were boiled under reflux to produce the aqueous extract that was further concentrated under reduced pressure and lyophilized. An in-vivo rat osteoporosis model using hind limb unloading was employed for studying the accumulation of mast cells. The human mast cell line, LAD2, was employed to evaluate the mast cell modulating action of ELP. Mast cell number in the tibiae of hind limb unloaded rats increased significantly during the course of osteoporosis. ELP treatment (10 g/kg/day) prevented both osteoporosis and mast cell accumulation in these rats. Furthermore, ELP significantly inhibited histamine and tumour necrosis factor-α release from LAD2 cells. Mast cells contributed to hormone independent osteoporosis. The suppression of mast cell accumulation and activation may contribute to the anti-osteoporotic action of ELP.
    The Journal of pharmacy and pharmacology. 10/2013;
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    ABSTRACT: Herba Epimedii, an herb commonly used in East Asian medicine, is commonly used for treatment of impotence, osteoporosis and many inflammatory conditions in traditional Chinese medicine. Recent studies revealed that Herba Epimedii also has anti‐tumor or anti‐cancer activities, which may possibly be mediated through anti‐angiogenesis. This study aims to examine and confirm the anti‐angiogenic activity in the herb using both in vivo and in vitro approaches. The 95% ethanol extract and four subsequent fractions (n‐hexane, ethyl acetate (EA), n‐butanol and aqueous fractions) of Herba Epimedii were tested on the zebrafish model by the quantitative assay for endogenous alkaline phosphatase; then, the active fraction was further tested on Tg(fli1a:EGFP)y1 zebrafish embryos and human umbilical vein endothelial cells (HUVECs) for the anti‐angiogenic effects. In addition, the action mechanism of Herba Epimedii was further investigated on wild‐type zebrafish embryos and HUVECs. The EA fraction showed anti‐angiogenic effects in both in vivo and in vitro models. Further experiments demonstrated that it might affect angiogenesis by acting on multiple molecular targets in zebrafish embryos and ERK signaling pathway in HUVECs. In conclusion, Herba Epimedii can inhibit angiogenesis, which may be the mechanism for its anti‐inflammatory, anti‐tumor and anti‐cancer actions. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 09/2013; 27(9). · 2.40 Impact Factor
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    ABSTRACT: Pharmaceutical countermeasures to treat disuse osteoporosis are rarely studied. Pharmaceutical studies for the treatment and prevention of osteoporosis depend on the ovariectomized rat model, which is a suitable model for the disease in women. Disuse osteoporosis affects men and women, but there is lack of awareness and relevant pharmaceutical studies for this condition. The objectives of this study were to verify the validity of an unusual tail-suspension rat model in the induction of disuse osteoporosis and subsequent pharmaceutical treatments. This model was created by unloading the hind limbs of the rats in order to create a state of weightlessness in their hindlimb bones. Validation of the model was performed with non-suspended rats. This study included five groups of suspended rats fed with different agents, such as distilled water (control), high-, medium- and low-dose raloxifene and a bisphosphonate (alendronate). The experiment lasted for 28 days. Comparisons were made between the suspended control and treatment groups. Ovariectomized and sham‑operated rats were also included as a reference for bone changes during osteoporosis. Changes in bone mineral density (BMD) at the distal femur and proximal tibia, microarchitecture at the distal femur and biomechanical strength at the diaphyseal femur were studied. Reduction of BMD and deterioration of trabeculae were similar between the suspended control and ovariectomized rats. Loss of BMD induced by tail suspension was reduced most effectively by medium-dose raloxifene. Deterioration of trabecular microarchitecture was also prevented by raloxifene. The tail-suspension rat model is suitable for the study of disuse osteoporosis under the effects of various therapeutic agents. The preventive effects of raloxifene against bone loss under disuse conditions have been demonstrated using this model.
    Molecular Medicine Reports 08/2013; · 1.17 Impact Factor
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    ABSTRACT: This study aims to determine the effect of metronomic (0.0125 mg/kg twice a week for 4 weeks) zoledronic acid (ZOL) on cancer propagation and osteolysis against both metastatic and primary breast cancer in mice model. From our results, metronomic ZOL resulted in a significant reduction of tumor burden and did not promote lung or liver metastasis. The metronomic ZOL appeared to be more effective than the conventional regimen (0.1 mg/kg once in 4 weeks) in reducing breast cancer tumor burden, and regulating its movement to lung and liver. This dosing schedule of ZOL showed great potential against metastatic breast cancer.
    Cancer letters 07/2013; · 5.02 Impact Factor
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    ABSTRACT: Medicinal mushrooms have been traditionally used as food nutrient supplements in China for thousands of years. The present study aimed to evaluate the immunomodulatory activities of Ganoderma sinense (GS), an allied species of G. lucidum, using human peripheral blood mononuclear cells (PBMC). Our results showed that the polysaccharide-enriched fraction of GS hot water extract (400 μg/ml) exhibited significant stimulatory effects on PBMC proliferation. When the fruiting bodies of GS were divided into pileus and stipe parts and were separately extracted, the GS stipe polysaccharide-enriched fraction (50-400 μg/ml) showed concentration-dependent immunostimulating effects in PBMC. The productions of tumor necrosis factor-α, interleukin (IL)-10, and transforming growth factor -β were significantly enhanced by this fraction. In addition, the proportion of CD14(+) monocyte subpopulation within the PBMC was specifically increased. The IL-10 and IL-12 productions in monocyte-derived dendritic cells were significantly enhanced by GS stipe fraction. The composition of monosaccharides of this fraction was determined by ultra performance liquid chromatography and ion exchange chromatography. Our study demonstrated for the first time the immunostimulatory effects of GS stipe polysaccharide-enriched fraction on PBMC and dendritic cells. The findings revealed the potential use of GS (especially including the stipes of fruiting bodies) as adjuvant nutrient supplements for patients, who are receiving immunosuppressive chemotherapies.
    Nutrition and Cancer 07/2013; 65(5):765-74. · 2.70 Impact Factor
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    ABSTRACT: Introduction: Eczema is a common childhood atopic disease associated with chronicity and impaired quality of life. As there is no cure for this disease, treatment relies on topical and systemic anti-allergic or immunomodulating therapies. Topical corticosteroids, macrolide immunosuppressants and oral immunomodulating drugs have been the mainstay for the treatment of recalcitrant disease. However, in China as well as throughout Asia, the use of traditional and proprietary topical and herbal medicines is also popular. Areas covered: This article reviews the evidence for the anti-allergic effects of topical and oral forms of these medicinal. The authors also present and discuss the current methods of preparation and evaluation for these traditional and proprietary medications. Additionally, the authors present the novel delivery method of employing nanotechnology to deliver these herbal therapies. Expert opinion: Many herbal concoctions have had trials which have claimed therapeutic benefits for eczema. However, the scientific methods in these trials are often flawed and often not objective. In fact, the majority of these trials do not provide proof of objective efficacy for the anti-allergic effects claimed. It is felt that the delivery of herbal medication by nanotechnology has several crucial challenges that certainly need to be overcome for the optimal design of therapies for eczema, through optimizing material properties, methods of delivery and understanding the mechanisms of action.
    Expert Opinion on Drug Discovery 05/2013; · 2.30 Impact Factor

Publication Stats

623 Citations
201.21 Total Impact Points

Institutions

  • 2002–2014
    • The Chinese University of Hong Kong
      • Institute of Chinese Medicine
      Hong Kong, Hong Kong
  • 2013
    • Sun Yat-Sen University
      • School of Life Sciences
      Shengcheng, Guangdong, China
  • 2011–2012
    • The University of Hong Kong
      • Department of Biochemistry
      Hong Kong, Hong Kong
  • 2010
    • Zhejiang University
      Hang-hsien, Zhejiang Sheng, China