Biomedical subjects

K P Fung

Publications and source records attributed to K P Fung.

At least 19 recordsLinked to original sources

PubMed2006

Influence of an anti-diabetic foot ulcer formula and its component herbs on tissue and systemic glucose homeostasis.

Complications of diabetes impose major public health burdens worldwide. The positive effect of a Radix Astragali-based herbal preparation on healing diabetic foot ulcers in patients has been reported. Formula 1 is also referred as the 'Herbal drink to strengthen muscle and control swelling'. This formula contains six Chinese medical herbs, including Radix Astragali, Radix Rehmanniae, Rhizoma Smilacis Chinensis, Rhizoma Atractylodis Macrocephalae, Radix Polygoni Multiflori Preparata, and Radix Stephania Tetrandrae. Three of these herbs (Radix Astragali, Radix Rehmanniae, Rhizoma Atractylodis Macrocephalae) are commonly used in different anti-diabetic formulae of Chinese medicine. The objective of the current study is to use an interdisciplinary approach to test the hypothesis that Formula 1 and its components influence tissue and systemic glucose homeostasis. In vitro and in vivo models have been established including: (1) glucose absorption into intestinal brush border membrane vesicles (BBMV); (2) gluconeogenesis by H4IIE hepatoma cells; (3) glucose uptake by 3T3-L1 adipocytes and Hs68 skin fibroblasts; (4) normalization of glycaemic control in a diabetic rat model. The results of in vitro studies indicated that all herbal extracts can modify cellular glucose homeostasis. Since Formula 1 and Rhizoma Smilacis Chinensis extracts demonstrated potent effects on modifying glucose homeostasis in multiple tissues in vitro, they were further studied for their anti-diabetic activities in vivo using a streptozotocin (STZ)-induced diabetic rat model. The results showed that Formula 1 and Rhizoma Smilacis Chinensis extracts did not significantly improve oral glucose tolerance or basal glycaemia in diabetic rats. In conclusion, the anti-diabetic foot ulcer Formula 1 contains ingredients active in modifying tissue glucose homeostasis in vitro but these biological activities could not be associated with improved glycaemic control of diabetes in vivo.

3T3 Cells↗

PubMed2006

Macrophage activation by polysaccharide biological response modifier isolated from Aloe vera L. var. chinensis (Haw.) Berg.

A mannose-rich polysaccharide biological response modifier (BRM), derived from Aloe vera L. var. chinensis (Haw.) Berg., was demonstrated to be a potent murine B- and T-cell stimulator in our previous study. We here report the stimulatory activity of PAC-I on murine peritoneal macrophage. The polysaccharide when injected into mice enhanced the migration of macrophages to the peritoneal cavity. Peritoneal macrophage when treated by PAC-I in vitro had increased expression of MHC-II and FcgammaR, and enhanced endocytosis, phagocytosis, nitric oxide production, TNF-alpha secretion and tumor cell cytotoxicity. The administration of PAC-I into allogeneic ICR mice stimulated systemic TNF-alpha production in a dose-dependent manner and prolonged the survival of tumor-bearing mice. PAC-I is thus a potent stimulator of murine macrophage and the in vitro observed tumoricidal properties of activated macrophage might account for the in vivo antitumor properties of PAC-I. Our research findings may have therapeutic implications in tumor immunotherapy.

Aloe↗

PubMed2006

Polysaccharide biological response modifiers.

Biological response modifiers (BRMs) are substances which augment immune response. BRMs can be cytokines which are produced endogenously in our body by immune cells or derivatives of bacteria, fungi, brown algae, Aloe vera and photosynthetic plants. Such exogeneous derivatives (exogeneous BRMs) can be nucleic acid (CpG), lipid (lipotechoic acid), protein or polysaccharide in nature. The receptors for these exogeneous BRMs are pattern recognition receptors. The binding of exogeneous BRMs to pattern recognition receptors triggers immune response. Exogenous BRMs have been reported to have anti-viral, anti-bacterial, anti-fungal, anti-parasitic, and anti-tumor activities. Among different exogeneous BRMs, polysaccharide BRMs have the widest occurrence in nature. Some polysaccharide BRMs have been tested for their therapeutic properties in human clinical trials. An overview of current understandings of polysaccharide BRMs is summarized in this review.

Animals↗

PubMed2006

In vitro immunomodulatory activities of a newly concocted traditional Chinese medicine formula: VI-28.

Previous studies have suggested that Vigconic VI-28, an anti-aging traditional Chinese medicine (TCM) formula containing Radix Ginseng and Cornu Cervi Pantotrichum, possesses immunological efficacy. This in vitro study further investigated the immunomodulatory effects of the hot water extracts of VI-28. The study included (1) colorimetric 5-bromo-2'-deoxy-uridine proliferation ELISA for estimating mitogenicity in human peripheral blood mononuclear cells (PBMC), (2) immunofluorescence staining for measuring the expression of IL-2 receptor alpha (CD25) on lymphocytes, (3) cytometric bead array (CBA) for quantifying cytokine liberation from PBMC, and (4) intracellular immunophenotyping for macrophage phagocytosis and hydrogen peroxide (H(2)O(2)) production from monocytes. The results demonstrated that VI-28 (1) could dose-dependently inhibited the proliferation of unstimulated and lipopolysaccharide-activated PBMC but enhanced the proliferation of phytohemagglutinin-activated PBMC at concentrations of <1 mg/mL, (2) significantly augmented the expression of CD25 on lymphocytes at concentrations of 0.4 mg/mL or above (p < 0.05), (3) dose dependently (0.1-1.0 mg/mL) activated macrophage phagocytosis and monocyte synthesis of H(2)O(2) and (4) significantly increased the production of cytokines IL-8, IL-10, IL-12 and IL-1beta at various concentrations of VI-28 (p < 0.05). The results suggest that VI-28 is a potential immunomodulator which probably acts through the activation of lymphocytes and monocytes.

Cells, Cultured↗

PubMed2006

Immunomodulatory effects of a traditional Chinese medicine with potential antiviral activity: a self-control study.

Traditional Chinese medicine (TCM) has been used for prevention and treatment of severe acute respiratory syndrome (SARS) in Hong Kong during the outbreak in spring 2003. We investigated the immunomodulating effects of an innovative TCM regimen derived from two herbal formulas (Sang Ju Yin and Yu Ping Feng San) for treating febrile diseases. Thirty-seven healthy volunteers were given the oral TCM regimen daily for 14 days. Peripheral venous blood samples were taken on days 0, 15 and 29 for hematology, biochemistry and immunology tests, including the measurement of blood lymphocyte subsets and plasma T-helper lymphocyte types 1 and 2 cytokines and receptor. After 3 months, 23 of the volunteers participated in a control study without TCM treatment for the same time course of blood tests. Two volunteers withdrew on day 2, due to headache and dizziness. All others remained well without any side effects. No participants showed significant changes in their blood test results, except that the T-lymphocyte CD4/CD8 ratio increased significantly from 1.31 +/- 0.50 (mean +/- SD) on day 0 to 1.41 +/- 0.63 on day 15 (p < 0.02), and reduced to 1.32 +/- 0.47 on day 29 (p < 0.05). In the control study, there were no changes in the CD4/CD8 ratio. The transient increase in CD4/CD8 ratio was likely due to the TCM intake. We postulate that the administration of the innovative TCM may have beneficial immunomodulatory effects for preventing viral infections including SARS.

Adult↗

PubMed2005

In vitro anti-allergic activities of a newly concocted traditional Chinese medicine--the wheeze-relief formula.

Asthma is one of the most common chronic diseases worldwide. Western medications such as glucocorticoids are effective therapeutic agents but may be associated with side effects. Traditional Chinese medicine (TCM) has been used for treating allergic diseases with observable clinical benefits. The present study investigated whether a novel TCM concoction, the wheeze-relief formula (WRF), possesses in vitro anti-allergic activities. We measured the effects of WRF on the release of eosinophil cationic protein (ECP) by human eosinophils using fluorescence enzyme immunoassay, expression of chemokine receptor CCR3 and adhesion molecule CD49d on eosinophils using immunophenotyping, cytokine induction from peripheral blood mononuclear cells (PBMC) using cytometric bead array (CBA), and the gene expression of cytokines and cytokine receptors using cDNA expression array. Results demonstrated that WRF dose-dependently and significantly: (1) suppressed ECP release from eosinophils activated with granulocyte macrophage-colony stimulating factor (GM-CSF) and platelet activating factor (PAF); (2) inhibited the expression of CCR3 and CD49d on PAF-activated eosinophils; and (3) attenuated the production of tumor necrosis factor alpha and gene expression of IL-2 receptor chain alpha (CD25) on house dust mite (Der p 1) activated PBMC. The above results suggest a possible anti-allergic role of WRF and provide a biochemical basis for further clinical trial on human subjects.

Anti-Allergic Agents↗

PubMed2004

Inhibition of cell proliferation and the action mechanisms of arsenic trioxide (As2O3) on human breast cancer cells.

Arsenic trioxide (As(2)O(3)) is one of the arsenic compounds found in nature. As(2)O(3) has recently been used to treat patients suffering from retinoic acid receptor (AML). It is of clinical interest to investigate whether As(2)O(3) is also effective in treating solid tumors. Here, we report that As(2)O(3) exhibited inhibitory effects on the proliferation of human breast cancer MCF-7 cells in a dose- and time-dependent manner. The 50% inhibitory concentration (IC(50)) of As(2)O(3) in inhibiting proliferation of MCF-7 cells were 8, 1.8, and 1.2 microM upon 1-, 2-, and 3-day treatment, respectively. In elucidating the underlying action mechanisms, the results of experiments concerning DNA fragmentation and externalization indicated that As(2)O(3) exerted its action on MCF-7 cells via apoptosis, whereas the result of flow cytometry also indicated that As(2)O(3) could induce mitochondrial mediated cell-cycle arrest at G(1) phase. Further studies by Western blot analysis indicated that As(2)O(3) regulated apoptosis and the expression of cell-cycle-related proteins as it upregulated p53 protein level and downregulated bcl-2 protein level. Results in present study indicated that As(2)O(3) might also be a good candidate for treating breast cancer.

Antineoplastic Agents↗

PubMed2004

Cytotoxic activities of Coriolus versicolor (Yunzhi) extract on human leukemia and lymphoma cells by induction of apoptosis.

Coriolus versicolor (CV), also known as Yunzhi, is one of the commonly used Chinese medicinal herbs. Although recent studies have demonstrated its antitumour activities on cancer cells in vitro and in vivo, the exact mechanism is not fully elucidated. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized aqueous ethanol extract prepared from Coriolus versicolor on a B-cell lymphoma (Raji) and two human promyelocytic leukemia (HL-60, NB-4) cell lines using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. Cell death ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis. The present results demonstrated that CV extract at 50 to 800 microg/ml dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more than 90% (p < 0.01), with ascending order of IC50 values: HL-60 (147.3 +/- 15.2 microg/ml), Raji (253.8 +/- 60.7 microg/ml) and NB-4 (269.3 +/- 12.4 microg/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 microg/ml) when compared with a chemotherapeutic anticancer drug, mitomycin C (MMC), confirming the tumour-selective cytotoxicity. Nucleosome productions in HL-60, NB-4 and Raji cells were significantly increased by 3.6-, 3.6- and 5.6-fold respectively upon the treatment of CV extract, while no significant nucleosome production was detected in extract-treated WRL cells. The CV extract was found to selectively and dose-dependently inhibit the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.

Antineoplastic Agents↗

PubMed2004

Chemical and biological characterization of a polysaccharide biological response modifier from Aloe vera L. var. chinensis (Haw.) Berg.

Three purified polysaccharide fractions designated as PAC-I, PAC-II, and PAC-III were prepared from Aloe vera L. var. chinensis (Haw.) Berg. by membrane fractionation and gel filtration HPLC. The polysaccharide fractions had molecular weights of 10,000 kDa, 1300 kDa, and 470 kDa, respectively. The major sugar residue in the polysaccharide fractions is mannose, which was found to be 91.5% in PAC-I, 87.9% in PAC-II, and 53.7% in PAC-III. The protein contents in the polysaccharide fractions was undetectable. NMR study of PAC-I and PAC-II demonstrated the polysaccharides shared the same structure. The main skeletons of PAC-I and PAC-II are beta-(1-->4)-D linked mannose with acetylation at C-6 of manopyranosyl. The polysaccharide fractions stimulated peritoneal macrophages, splenic T and B cell proliferation, and activated these cells to secrete TNF-alpha, IL-1 beta, INF-gamma, IL-2, and IL-6. The polysaccharides were nontoxic and exhibited potent indirect antitumor response in murine model. PAC-I, which had the highest mannose content and molecular weight, was found to be the most potent biological response modifier of the three fractions. Our results suggested that the potency of aloe polysaccharide fraction increases as mannose content and molecular weight of the polysaccharide fraction increase.

Aloe↗

PubMed2004

Immunomodulatory effects of yun zhi and danshen capsules in health subjects--a randomized, double-blind, placebo-controlled, crossover study.

Immunostimulating polysaccharides extracted from the Chinese medicinal plant Yun Zhi (Coriolus versicolor) have been found to enhance various immunological functions, and Danshen (Salvia miltiorrhiza) to show beneficial effects on the circulatory system. In the present clinical study, we investigated if regular consumption of Yun Zhi and Danshen capsules could improve cellular immunity in healthy subjects. One hundred healthy subjects were recruited to take Yun Zhi (50 mg/kg body weight) plus Danshen (20 mg/kg body weight) or placebo capsules daily for four successive months and, after a 2-month wash-out period, crossover to take placebo or Yun Zhi plus Danshen capsules for four successive months. Flow cytometry was used to assess the lymphocyte subtypes and concentration of T helper (Th) cell cytokines in culture supernatant. Gene expression of cytokines and cytokine receptors of peripheral blood mononuclear cells (PBMC) was analyzed by cDNA expression array. Results showed that regular oral consumption of Yun Zhi-Danshen capsules could significantly elevate PBMC gene expression of interleukin (IL)-2 receptor, increase the percentage and absolute counts of T helper cell and ratio of CD4(+) (T helper)/CD8(+) (T suppressor and cytotoxic T) cell, and significantly enhance the ex vivo production of typical Th1 cytokine interferon-gamma from PBMC activated by phytohemagglutinin and lipopolysaccharide (all p<0.005). Such consumption had no adverse effects on liver and renal functions, and the biochemical bone profile. Therefore, regular consumption of Yun Zhi and Danshen could be beneficial for immunological functions by potential enhancement of cell-mediated immunity in healthy subjects without any adverse effects.

Adult↗

PubMed2004

Differential effect of Coriolus versicolor (Yunzhi) extract on cytokine production by murine lymphocytes in vitro.

Being one of the commonly used Chinese medicinal herbs, Coriolus versicolor (CV), also named as Yunzhi, was known to possess both anti-tumor and immunopotentiating activities. The present study aimed to investigate the in vitro immunomodulatory effect of a standardized ethanol-water extract prepared from CV on the proliferation of murine splenic lymphocytes using the MTT assay, and the production of six T helper (Th)-related cytokines using the enzyme-linked immunosorbent assay (ELISA) technique. The results showed that the CV extract significantly augmented the proliferation of murine splenic lymphocytes in a time- and dose-dependent manner, maximally by 2.4-fold. Moreover, the production of two Th1-related cytokines, including interleukin (IL)-2 and IL-12, in culture supernatants from the CV extract-activated lymphocytes was prominently upregulated at 48 and 72 h. Positive correlations were found between the levels of these two cytokines and the MTT-based proliferative response. In contrast, the production of two other Th1-related cytokines, including interferon (IFN)-gamma and IL-18, was significantly augmented only at 24 h, but not at 48 and 72 h. On the other hand, the levels of two Th2-related cytokines such as IL-4 and IL-6 were undetectable in the culture supernatants of lymphocytes treated with the CV extract. The CV extract was suggested to be a lymphocyte mitogen by differentially enhancing the production of Th1-related cytokines.

Animals↗

PubMed2004

Anti-cancer and pro-apoptotic effects of an herbal medicine and Saccharomyces cerevisiae product (CKBM) on human hepatocellular carcinoma HepG2 cells in vitro and in vivo.

Hepatocellular carcinoma is a major health problem worldwide. Different treatment strategies have been developed to cope with this problem. Herbal medicine is now widely studied in both Eastern and Western countries. In this study, we used both in vitro and in vivo model to illustrate the anti-tumor effect of a product, CKBM, consisting of herbal medicine and specially processed Saccharomyces cerevisiae. Dose-dependent anti-proliferation effect was observed on in vitro growth of human hepatoma HepG2 cells after 48 hours incubation with CKBM. At the 50% inhibitory concentration (IC50) no significant toxic effect was observed on normal human fibroblasts Hs68 and human liver WRL-68 cells. The results of morphological changes, detection of DNA fragmentation, flow cytometric analysis and Western blot analysis indicated that this anti-tumor effect of CKBM was mediated via the process of apoptosis. In addition, HepG2 cells- bearing nude mice model was used for in vivo anti-tumor study. Our results showed that 14-day treatment with 0.8 ml daily dosage of CKBM could inhibit 54.1% of tumor growth. The plasma activities of enzymes specific for heart and liver, namely creatine kinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase, remained at normal levels, indicated that CKBM did not produce toxicity to the host.

Animals↗

PubMed2004

Mitochondria-targeting drug oligomycin blocked P-glycoprotein activity and triggered apoptosis in doxorubicin-resistant HepG2 cells.

BACKGROUND: Mitochondria are key regulators in apoptosis. This suggests that a mitochondrion can be a target for cancer treatment. To examine the feasibility of this approach, we investigated the effect of oligomycin on the induction of apoptosis in drug-resistant cells. As a mitochondrion-targeting agent, oligomycin inhibits mitochondrial F0F1-ATPase. Of 37,000 molecules tested against the 60 human cancer cell lines of the National Cancer Institute, oligomycin is among the top 0.1% most cell line selective agents. METHODS: Changes in the doxorubicin (Dox) accumulation and mitochondrial potential (Deltapsim) in human hepatocarcinoma HepG2 and its derivative R-HepG2 with Dox resistance were determined by flow cytometry. P-glycoprotein (Pgp) expression and release of cytochrome c from mitochondria were analyzed by Western blot. Cytotoxicity was examined by DNA fragmentation and the alamar blue assay. RESULTS: R-HepG2 cells produced Pgp, showed drug resistance and accumulated less Dox when compared to their parent. In both cell lines, oligomycin depolarized Deltapsim, released cytochrome c and elicited DNA fragmentation. Moreover, oligomycin blocked Pgp activity and accumulated more Dox in R-HepG2. Combined treatment with Dox and oligomycin elicited more cell death. CONCLUSION: Our results suggest that oligomycin could bypass Dox resistance and trigger apoptosis in R-HepG2 cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Genomic characterisation of the severe acute respiratory syndrome coronavirus of Amoy Gardens outbreak in Hong Kong.

Severe acute respiratory syndrome (SARS) is a global health concern. In Hong Kong, two major outbreaks, one hospital based and the other in the Amoy Gardens apartments, were identified. The frequency of diarrhoea, admission to intensive care, and mortality differed significantly between the two outbreaks. We did genomic sequencing for viral isolates from five Amoy Gardens patients. The virus sequence was identical in four of these five patients. The sequence data from one hospital case and the four identical community cases had only three nucleotide differences. Alterations in the SARS coronavirus genome are unlikely to have caused the distinctive clinical features of the Amoy Gardens patients, and these results highlight the importance of non-viral genomic factors in this outbreak.

Base Sequence↗

PubMed2003

Reactive oxygen species mediate doxorubicin induced p53-independent apoptosis.

Doxorubicin (DOX) is a common anticancer drug. The mechanisms of DOX induced apoptosis and the involvement of reactive oxygen species (ROS) in apoptotic signaling were investigated in p53-null human osteosarcoma Saos-2 cells. Accumulation of pre-G1 phase cells and induction of DNA laddering, which are the hallmarks of apoptosis, were detected in cells at 48 h upon DOX treatment. Furthermore, DOX increased the intracellular hydrogen peroxide and superoxide levels, followed by mitochondrial membrane depolarization, cytochrome c release, caspase-3 activation, prior to DNA laddering in Saos-2 cells. In addition, DOX treatment also upregulated Bax and downregulated Bcl-2 levels in the cells. The role of ROS in DOX induced cell death was confirmed by the suppression effect of catalase on DOX induced ROS formation, mitochondrial cytochrome c release, procaspase-3 cleavage, and apoptosis in Saos-2 cells. The catalase treatment however only suppressed DOX induced Bax upregulation but had no effect on Bcl-2 downregulation. Results from the present study suggested that ROS might act as the signal molecules for DOX induced cell death and the process is still functional even in the absence of p53.

Antineoplastic Agents↗

PubMed2002

Circumvention of multidrug resistance and reduction of cardiotoxicity of doxorubicin in vivo by coupling it with low density lipoprotein.

Doxorubicin (Dox) was coupled into human low density lipoprotein (LDL) to form a complex LDL-Dox. In in vitro studies, the accumulation of LDL-Dox in human resistant hepatoma (R-HepG2) cells was found to be higher than that of free Dox in the cells, resulting in an increase of the cytotoxic effect on the cells. Moreover, in in vivo studies, under the same dosage of drugs (1 mg/kg), the anti-proliferative effect on the tumor cells of LDL-Dox in nude mice bearing R-HepG2 cells was higher than that of free Dox as evidenced by the larger reduction in tumor volumes and tumor weights in LDL-Dox treated group. Histological studies showed that LDL-Dox treatment did not cause any heart damage when compared with the control group. In contrast, Dox treatment caused disruption and vacuolization of myocardial filament. Plasma lactate dehydrogenase activity and plasma creatine kinase activity in nude mice bearing R-HepG2 cells were found to be elevated in the Dox-treated group but remained unchanged in LDL-Dox-treated group. The present studies indicate that when Dox is coupled with LDL, the multidrug resistance can be circumvented and the cardiotoxicity can be reduced.

Animals↗

PubMed2002

Mitochondrial targeting drug lonidamine triggered apoptosis in doxorubicin-resistant HepG2 cells.

Mitochondria play a crucial role in the induction and execution of apoptosis. Accordingly, recent suggestions have been made to use agents that directly act on mitochondria to trigger apoptosis so that drug-sensitive and-resistant tumour cells can be eliminated. To test this hypothesis, human hepatocarcinoma HepG2 and its derivative R-HepG2 with doxorubicin (Dox) resistance as a result of expression of P-glycoprotein were used to investigate the effect of lonidamine (LND), a new mitochondrial targeting drug, on the induction of apoptosis. Results from our study indicate that R-HepG2 cells were more sensitive to LND than parental cells in terms of cytotoxicity determined by alamar blue assay. Cell death induced by LND was associated with the hallmarks of apoptosis such as mitochondrial membrane depolarization, release of cytochrome c, phosphatidyl-serine externalization and DNA fragmentation. Moreover, combined treatment of cells with Dox and LND elicited more cell death. Taken together, our results suggest a potential use of LND as an anti-cancer drug to bypass drug resistance and to trigger tumour destruction through apoptosis in HepG2 and R-HepG2 cells.

Antineoplastic Agents↗

PubMed2002

Effect of arsenic trioxide on human hepatocellular carcinoma HepG2 cells: inhibition of proliferation and induction of apoptosis.

Arsenic trioxide (As(2)O(3)), a major ingredient of Traditional Chinese Medicine (TCM), is found to be an effective anticancer drug in acute promyelocytic leukemia (APL). The present study explored the use of As(2)O(3) on human hepatocellular carcinoma by in vitro study. The study showed that the clinically achievable concentration of As(2)O(3), i.e. 2 microM, inhibited the cell proliferation of human hepatocellular carcinoma cell line, HepG2, in a time-dependent manner. The mechanistic study showed that 2 microM of As(2)O(3) acted through induction of apoptosis in which caspase-3 was activated. The results also suggested that mitochondria did not take part in As(2)O(3)-induced apoptosis.

Antineoplastic Agents↗