Assoc. Prof. Xianqin Qu has gained her MD in China and PhD in Australia; her research focuses on the mechanism of insulin resistance and lipotoxicity contributing to metabolic syndrome, non-alcoholic fatty liver disease, type 2 diabetes, polycystic ovarian syndrome and infertility. In order to development of natural approaches to metabolic disease, she has also conducted experimental and clinical research on Chinese herbal medicine. She has been selected as a member of Advisory Committee on Complementary Medicine for Therapeutic Goods Administration Australia since 2010.
Can supervise: YES
- Pharmacology of Chinese Herbal Medicine
- Clinical subjects of Chinese Medicine
- Supervising Masters and senior undergraduate students' practice of Chinese herbal medicine
Chen, Y, Chen, H, Li, Y, Chen, Z, Wu, Y, McGowan, E, Qu, X, Sun, B & Lin, Y 2020, 'Chinese herbal medicine Guilu Erxian Jiao attenuates bone marrow suppression following chemotherapy in patients with advanced lung cancer', Translational Metabolic Syndrome Research.
In recent decades, a classic recipe in traditional Chinese medicine, Guilu erxian jiao (GEJ), has been used in the prevention and treatment of myelosuppression following cancer chemotherapy. However, the safety and efficacy of GEJ has not been studied. In the present study, we investigated the safety and efficacy of GEJ in the management of myelosuppression in a cohort of advanced lung adenocarcinoma patients who received 4 cycles of chemotherapy. Treatment with GEJ was compared to the conventional treatment with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF). The GEJ treatment group (38 patients) was orally administered GEJ whilst the control group (25 patients) were treated with PEG-rhG-CSF during the 4 cycles of chemotherapy. We found that GEJ was as safe as the recommended treatment, PEG-rhG-CSF . GEJ patients recovered from suppressed bone marrow in a much steadier approach, compared with the highly fluctuating changes observed in PEG-rhG-CSF treatment. Our data suggests that GEJ may be a better alternative to manage cancer chemotherapy-induced myelosuppression.
Cheng, J, Tan, Y, Zhou, J, Xiao, L, Johnson, M & Qu, X 2020, 'Green tea polyphenols ameliorate metabolic abnormalities and insulin resistance by enhancing insulin signalling in skeletal muscle of Zucker fatty rats', Clinical Science, vol. 134, no. 10, pp. 1167-1180.View/Download from: Publisher's site
©2020 The Author(s). In the present study, we evaluated the metabolic effects of green tea polyphenols (GTPs) in high-fat diet (HFD) fed Zucker fatty (ZF) rats, in particular the effects of GTP on skeletal muscle insulin sensitivity. Body weight, visceral fat, glucose tolerance, lipid profiles and whole-body insulin sensitivity were measured in HFD-fed ZF rats after 8-week-treatment with GTP (200 mg/kg of body weight) or saline (5 ml/kg of body weight). Zucker lean rats were studied as controls. Ex vivo insulin-mediated muscle glucose uptake was assessed. Immunoblotting was used to evaluate the expression of key insulin signalling proteins in skeletal muscle. GTP treatment attenuated weight gain (P<0.05) and visceral fat accumulation (27.6%, P<0.05), and significantly reduced fasting serum glucose (P<0.05) and insulin (P<0.01) levels. Homoeostasis model assessment of insulin resistance (HOMA-IR), a measure of insulin resistance, was lower (P<0.01) in GTP-treated animals compared with ZF controls. Moreover, insulin-stimulated glucose uptake by isolated soleus muscle was increased (P<0.05) in GTP-ZF rats compared with ZF-controls. GTP treatment attenuated the accumulation of ectopic lipids (triacyl- and diacyl-glycerols), enhanced the expression and translocation of glucose transporter-4, and decreased pSer612IRS-1 and increased pSer473Akt2 expression in skeletal muscle. These molecular changes were also associated with significantly decreased activation of the inhibitory (muscle-specific) protein kinase (PKC) isoform, PKC-θ. Taken together, the present study has shown that regular ingestion of GTP exerts a number of favourable metabolic and molecular effects in an established animal model of obesity and insulin resistance. The benefits of GTP are mediated in part by inhibiting PKC-θ and improving muscle insulin sensitivity.
Arhin, SK, Zhao, J, Ji, X, Shi, C, Tang, J, Gu, Y, Xi, H, Cheng, J, Qu, X, Shi, H, Jin, XL & Lv, JQ 2019, 'Multiple facilitated glucose transporters SLC2As are required for normal mouse preimplantation embryo development', American Journal of Translational Research, vol. 11, no. 6, pp. 3412-3425.
© 2019, E-Century Publishing Corporation. All rights reserved. Background: Glucose metabolism is an essential energy source for mammalian preimplantation embryonic development. Therefore, we aimed to analyze the expression of all 12 known glucose transporters (facilitated solute carrier family 2, Slc2a) during early mouse embryo development. Methods: Gene and protein expression of Slc2a transporters in oocytes and embryos were assessed by the TaqMan gene expression assay and confocal immunofluorescence, respectively. Results: Except for Slc2a2, the other 11 Slc2a transcripts were detected in oocytes. Transcripts of Slc2a1, Slc2a3, Slc2a4, and Slc2a8 were the most enriched and detected in preimplantation embryos. The transcription of other Slc2a isoforms was barely detectable or absent after fertilization; however, they were detected in blastocysts, except for Slc2a10 and Slc2a13. Embryo culture in the simple defined medium caused a reduction in transcription of Slc2a1, Slc2a3, Slc2a4, and Slc2a8 in blastocyst; yet, amino acids partially reversed this impaired transcription of Slc2a1 and Slc2a4. SLC2A1 and SLC2A4 proteins were detected at all embryonic stages with nuclear accumulation in the embryos at the early cleavage stage. SLC2A3 and SLC2A8 were not detected in embryos until the eight-cell stage. The cellular membrane localization of SLC2A1, SLC2A3, and SLC2A8 occurred after compaction and was characterized in blastocysts. SLC2A4 was evenly distributed in the cytoplasm and nuclei without its characteristic membrane localization. Indinavir sulfate (a SLC2A4 inhibitor) decreased the rate of development and prevented glucose utilization in embryos after compaction. These inhibitory activities were partially reversed by exogenous insulin. Conclusion: The results unveil distinct expression patterns of individual Slc2a glucose transporters during early embryo development. Taken together, they provide novel insights into the understanding and management of glucose m...
Ong, M, Cheng, J, Jin, X, Lao, W, Johnson, M, Tan, Y & Qu, X 2019, 'Paeoniflorin extract reverses dexamethasone-induced testosterone over-secretion through downregulation of cytochrome P450 17A1 expression in primary murine theca cells.', Journal of ethnopharmacology, vol. 229, pp. 97-103.View/Download from: Publisher's site
ETHNOPHARMACOLOGICAL RELEVANCE:Polycystic Ovarian Syndrome (PCOS) is a complex endocrine and reproductive disorder. A main hallmark includes increased androgen production. The root of Paeonia lactiflora Pall. (Bai Shao) is used in Chinese herbal medicine for reproductive disorders, however its effects and mechanisms on ovarian theca cells has not yet been fully elucidated. AIM OF THE STUDY:The aim of this study was to evaluate effect of paeoniflorin extract (PFE), the main constituents of Bai Shao, on androgen production in ovarian theca cells. MATERIALS AND METHODS:Primary murine theca cells were treated with concentrations of PFE (1-100 µg/mL) in the presence of dexamethasone (10 µM) with media-only treated cells used as the control. After 24 h, culture media was collected for biochemistry assays of testosterone and progesterone. Expression of key steroidogenic enzymes, cholesterol side-chain cleavage (CYP11A1) and 17α-hydroxylase (CYP17A1) was characterized using immunofluorescence staining, immunoblotting and qRT-PCR. RESULTS:Dexamethasone significantly enhanced testosterone secretion (P < 0.05 vs. the control cells). PFE reversed over-production of testosterone induced by dexamethasone in a dose-dependent manner. The treatment with PFE also normalized production of progesterone in dexamethasone-treated cells. Expression of CYP11A1 and CYP17A1 in the theca cells were visualised by immunofluorescence staining. All doses of PFE significantly inhibited CYP17A1 expression detected by immunoblotting, but only 100 µg/mL of PFE downregulated CYP11A1 expression and reduced CYP11A1 significantly in dexamethasone-treated theca cells. CONCLUSIONS:PFE may reduce over-secretion of testosterone in theca cells through downregulation of CYP17A1 and CYP11A1. These findings provide scientific evidence to treat ovarian hyperandrogenism with the root of Paeonia lactiflora Pall.
Chen, H, McGowan, E, Ren, N, Nassif, N, Lal, S, Qu, X & Lin, Y 2018, 'Nattokinase: A Promising Alternative in Prevention andTreatment of Cardiovascular Diseases', Biomarker Insights, vol. 13.View/Download from: Publisher's site
Cardiovascular disease (CVD) is the leading cause of death in the world, however our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, lipid lowering, anti-platelet and neuroprotective effects. This review covers the major pharmacological effects of NK with a focus on its clinical relevance to CVD. It outlines the advantages of NK and the outstanding issues pertaining to NK pharmacokinetics. Available evidence suggests that NK is a unique natural compound that possesses several key cardiovascular beneficial effects for CVD patients and is therefore an ideal drug candidate for the prevention and treatment of CVD. NK is therefore a promising alternative in the management of CVD.
Kamal, MA, Shakil, S, Nawaz, MS, Yu, QS, Tweedie, D, Tan, Y, Qu, X & Greig, NH 2017, 'Inhibition of butyrylcholinesterase with fluorobenzylcymserine, an experimental Alzheimer’s drug candidate: Validation of enzoinformatics results by classical and innovative enzyme kinetic analyses', CNS and Neurological Disorders - Drug Targets, vol. 16, no. 7, pp. 820-827.View/Download from: Publisher's site
© 2017 Bentham Science Publishers. Background: Selective butyrylcholinesterase (BuChE)-inhibition, increases acetylcholine (ACh) levels. In rodents, this inhibition is known to boost cognition. Also, this occurs without the typical unwanted adverse effects of acetylcholinesterase-inhibitors or AChE-Is. The novel compound, fluorobenzylcymserine (FBC), is derived from our effort to design a selective BuChE-inhibitor. Also, we wanted to check whether butyrylcholinesterase-inhibitors (BuChE-Is) possessed an edge over AChE-Is in Alzheimer’s disease (AD) in terms of efficacy and/or tolerance. Method: FBC was synthesized as reported earlier while enzymatic activity of BuChE was calculated by Ellman-technique. Molecular docking was performed using Autodock4.2. We applied classical as well as innovative analyses of enzyme-kinetics for exploring “FBC:human BuChE-interaction”. The mode of inhibition and kinetic parameters were also determined. Results: Docking results displayed two strong interacting sites for FBC. One of these binding sites was previously identified as a deep narrow groove having polar aromatic residues while a second site was identified during this study which displayed better interaction and was lined with aliphatic and sulphur containing residues. At low concentrations of BuChE, the IC 50 was found to be very low i.e. 4.79 and 6.10 nM for 12 and 36 μg, respectively, whereas it increased exponentially by increasing the units of BuChE. Conclusion: These analyses indicate that FBC is an interesting AD drug candidate that could provide a potent and partial mixed type of inhibition of human BuChE.
Ong, M, Peng, J, Jin, X & Qu, X 2017, 'Chinese Herbal Medicine for the Optimal Management of Polycystic Ovary Syndrome.', The American journal of Chinese medicine, vol. 45, no. 3, pp. 405-422.View/Download from: Publisher's site
Polycystic ovary syndrome (PCOS) is a complex heterogeneous disorder characterized by androgen excess and ovulatory dysfunction; it is now known to be closely linked to metabolic syndrome. Recent research suggests that insulin resistance plays an important role in the pathogenesis of PCOS which may lead to the excessive production of androgens by ovarian theca cells. Currently there is no single drug that can treat both the reproductive and metabolic complications of the disorder. Existing pharmaceutical agents such as hormonal therapies have been associated with side effects and are not appropriate for PCOS women with infertility. Additionally, insulin sensitizing agents useful for treating the metabolic abnormalities in PCOS have limited efficacy for treating reproductive aspects of the disorder. Chinese herbal medicines have a long history of treating gynaecological problems and infertility and therefore may be a novel approach to the treatment of PCOS. Current research demonstrates that the compounds isolated from herbs have shown beneficial effects for PCOS and when combined in an herbal formula can target both reproductive and metabolic defects simultaneously. Therefore, further investigation into Chinese herbal medicine in the treatment of PCOS is warranted.
Teng, B, Peng, J, Ong, M & Qu, X 2017, 'Successful Pregnancy after Treatment with Chinese Herbal Medicine in a 43-Year-Old Woman with Diminished Ovarian Reserve and Multiple Uterus Fibrosis: A Case Report.', Medicines, vol. 4, no. 1, pp. 1-5.View/Download from: Publisher's site
To highlight a natural approach to coexisting oligomenorrhea, subfertility, luteal phase insufficiency and multiple fibroids cohesively when in vitro fertilisation (IVF) has failed.A 43-year-old woman with diminished ovarian reserve and multiple uterine fibroids had previously been advised to discontinue IVF treatment. According to Chinese Medicine diagnosis, herbal formulae were prescribed for improving age-related ovarian insufficiency as well as to control the growth of fibroids. After 4 months of treatment, the patient's menstrual cycle became regula r and plasma progesterone one week after ovulation increased from 10.9 nmol/L to 44.9 nmol/L. After 6 months, she achieved a natural conception, resulting in a live birth of a healthy infant at an estimated gestational age of 40 weeks.The successful treatment with Chinese Herbal Medicine for this case highlights a natural therapy to manage infertility due to ovarian insufficiency and multiple fibroids after unsuccessful IVF outcome.
Lees, T, Nassif, N, Simpson, A, Shad-Kaneez, F, Martiniello-Wilks, R, Lin, Y, Jones, A, Qu, X & Lal, S 2017, 'Recent advances in molecular biomarkers for diabetes mellitus: a systematic review.', Biomarkers, vol. 22, no. 7, pp. 604-613.View/Download from: Publisher's site
CONTEXT: Diabetes is a growing global metabolic epidemic. Current research is focussing on exploring how the biological processes and clinical outcomes of diabetes are related and developing novel biomarkers to measure these relationships, as this can subsequently improve diagnostic, therapeutic and management capacity. OBJECTIVE: The objective of this study is to identify the most recent advances in molecular biomarkers of diabetes and directions that warrant further research. METHODS: Using a systematic search strategy, the MEDLINE, CINAHL and OVID MEDLINE databases were canvassed for articles that investigated molecular biomarkers for diabetes. Initial selections were made based on article title, whilst final inclusion was informed by a critical appraisal of the full text of each article. RESULTS: The systematic search returned 246 records, of which 113 were unique. Following screening, 29 records were included in the final review. Three main research strategies (the development of novel technologies, broad biomarker panels, and targeted approaches) identified a number of potential biomarkers for diabetes including miR-126, C-reactive protein, 2-aminoadipic acid and betatrophin. CONCLUSION: The most promising research avenue identified is the detection and quantification of micro RNA. Further, the utilisation of functionalised electrodes as a means to detect biomarker compounds also warrants attention.
Tan, Y, Kim, J, Cheng, J, Ong, M, Lao, W-G, Jin, X-L, Lin, Y-G, Xiao, L, Zhu, X-Q & Qu, X-Q 2017, 'Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats', World Journal of Gastroenterology, vol. 23, no. 21, pp. 3805-3805.View/Download from: Publisher's site
To investigate protective effects and molecular mechanisms of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats.
Male ZF rats were fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1c (SREBP1c).
Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain (10.1%, P = 0.052) and significantly lowered visceral fat (31.0%, P < 0.01). Compared with ZF-controls, GTP treatment significantly reduced fasting serum insulin, glucose and lipids levels. Reduction in serum ALT and AST levels (both P < 0.01) were observed in GTP-treated ZF rats. GTP treatment also attenuated the elevated TNFα and IL-6 in the circulation. The increased hepatic TG accumulation and cytoplasmic lipid droplet were attenuated by GTP treatment, associated with significantly increased expression of AMPK-Thr172 (P < 0.05) and phosphorylated ACC and SREBP1c (both P < 0.05), indicating diminished hepatic lipogenesis and triglycerides out flux from liver in GTP treated rats.
The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.
Kim, M-S, Ong, M & Qu, X 2016, 'Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?', WORLD JOURNAL OF GASTROENTEROLOGY, vol. 22, no. 1, pp. 8-23.View/Download from: Publisher's site
Lao, W, Jin, X, Tan, Y, Xiao, L, Padula, M, Bishop, D, Reedy, B, Ong, M, Kamal, M & Qu, X 2016, 'Characterisation of Bone Beneficial Components from Australian Wallaby Bone', Medicines, vol. 3, pp. 1-13.View/Download from: Publisher's site
Background: Osteoporosis is a condition in which the bones become brittle, increasing the risk of fractures. Complementary medicines have traditionally used animal bones for managing bone disorders, such as osteoporosis. This study aimed to discover new natural products for these types of conditions by determining mineral and protein content of bone extracts derived from the Australian wallaby. Methods: Inductively coupled plasma-mass spectrometry and Fourier transform infrared spectroscopic analysis were used for mineral tests, proteome analysis was using LC/MS/MS and the effects of wallaby bone extracts (WBE)s on calcium deposition and alkaline phosphatase activity were evaluated in osteogenic cells derived from adipose tissue-derived stem cells (ADSCs). Results: Concentrations of calcium and phosphorus were 26.21% and 14.72% in WBE respectively. Additionally, minerals found were wide in variety and high in concentration, while heavy metal concentrations of aluminium, iron, zinc and other elements were at safe levels for human consumption. Proteome analysis showed that extracts contained high amounts of bone remodelling proteins, such as osteomodulin, osteopontin and osteoglycin. Furthermore, in vitro evaluation of WBEs showed increased deposition of calcium in osteoblasts with enhanced alkaline phosphatase activity in differentiated adipose-derived stem cells. Conclusion: Our results demonstrate that wallaby bone extracts possess proteins and minerals beneficial for bone metabolism. WBEs may therefore be used for developing natural products for conditions such as osteoporosis and further investigation to understand biomolecular mechanism by which WBEs prevent osteoporosis is warranted.
Peng, J, Wang, P, Ge, H, Qu, X & Jin, X 2015, 'Effects of cordycepin on the microglia-overactivation-induced impairments of growth and development of hippocampal cultured neurons.', PLoS ONE, vol. 10, no. 5, pp. 1-10.View/Download from: Publisher's site
Microglial cells are normally activated in response to brain injury or immunological stimuli to protect central nervous system (CNS). However, over-activation of microglia conversely amplifies the inflammatory effects and mediates cellular degeneration, leading to the death of neurons. Recently, cordycepin, an active component found in Cordyceps militarisa known as a rare Chinese caterpillar fungus, has been reported as an effective drug for treating inflammatory diseases and cancer via unclear mechanisms. In this study, we attempted to identify the anti-inflammatory role of cordycepin and its protective effects on the impairments of neural growth and development induced by microglial over-activation. The results indicate that cordycepin could attenuate the lipopolysaccharide (LPS)-induced microglial activation, evidenced by the dramatically reduced release of TNF-α and IL-1β, as well as the down-regulation of mRNA levels of iNOS and COX-2 after cordycepin treatment. Besides, cordycepin reversed the LPS-induced activation of NF-κB pathway, resulting in anti-inflammatory effects. Furthermore, by employing the conditioned medium (CM), we found cordycepin was able to recover the impairments of neural growth and development in the primary hippocampal neurons cultured in LPS-CM, including cell viability, growth cone extension, neurite sprouting and outgrowth as well as spinogenesis. This study expands our knowledge of the anti-inflammatory function of cordycepin and paves the way for the biomedical applications of cordycepin in the therapies of neural injuries.
Qu, X & Ong, M 2015, 'Successful Treatment of Polycystic Ovarian Syndrome, Nonalcoholic Fatty Liver Disease and Infertility with Chinese Herbal Medicine: A Case Report', Endocrinology and Metabolic Syndrome, vol. 4, no. 3, pp. 1-3.View/Download from: Publisher's site
This case report details a 30 year old woman with hyperlipidemia, Nonalcoholic Fatty Liver Disease (NAFLD), Polycystic Ovarian Syndrome (PCOS) and infertility. Her impaired liver function has prevented the use of pharmaceutical drugs (statins and metformin). The patient therefore underwent two stages of Chinese herbal medicine treatment: the first formula to ameliorate hyperlipidemia and amenorrhea; and the second formula to improve ovarian dysfunction as well as glucose and lipid metabolism. Over 8 months of treatment, the patient achieved pregnancy and a natural birth without developing gestational diabetes. While the treatment of coexisting metabolic syndrome conditions is often complex and difficult, this case report highlights how Chinese herbal medicine may offer a successful treatment option for women with multiple metabolic abnormalities and associated infertility
Lao, W, Tan, Y, Jin, X, Xiao, L, Kim, JJY & Qu, X 2015, 'Comparison of Cytotoxicity and the Anti-Adipogenic Effect of Green Tea Polyphenols with Epigallocatechin-3-Gallate in 3T3-L1 Preadipocytes', AMERICAN JOURNAL OF CHINESE MEDICINE, vol. 43, no. 6, pp. 1177-1190.View/Download from: Publisher's site
Tan, Y, Jin, XL, Lao, W, Kim, J, Xiao, L & Qu, X 2015, 'Antiresistin RNA Oligonucleotide Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease in Mice through Attenuating Proinflammatory Cytokines', BIOMED RESEARCH INTERNATIONAL, vol. 2015.View/Download from: Publisher's site
Aliev, G, Shahida, K, Gan, SH, Firoz, C, Khan, A, Abuzenadah, AM, Kamal, W, Kamal, MA, Tan, Y, Qu, X & Reale, M 2014, 'Alzheimer disease and type 2 diabetes mellitus: the link to tyrosine hydroxylase and probable nutritional strategies.', CNS and Neurological Disorders - Drug Targets, vol. 13, no. 3, pp. 467-477.View/Download from: Publisher's site
Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) are chronic health disorders that affect millions of people around the world. According to recent studies, there are molecular similarities in the inflammatory pathways involved in both AD and T2DM, which opens a new avenue for researchers with different perspectives to target the cause of these diseases rather than their obvious symptoms. Several links between inflammation, cardiovascular disease, T2DM and central nervous system disorders such as AD and Parkinson's disease have been elucidated. Mutations in the hippocampal-β-amyloid precursor protein gene in genetically high-risk individuals have been shown to cause the early onset of AD symptoms. The overexpression of β-amyloid protein in the hippocampal region and the synaptotoxicity that occurs as a result have been considered a typical feature of AD and leads to neuronal loss and cognitive decline. However, the identity of the cellular components that cause the late onset of the disease seen in the majority of the cases is still unknown. Synaptic insults associated with neuronal dysfunction may involve several cascades and molecules, one of which has been hypothesized to be tyrosine hydroxylase (TH). The axons of the noradrenergic cells that project to the hippocampus appear to be affected by the β-amyloid protein, which subsequently contributes to TH loss in Alzheimer brain cells. In this review, we attempt to shed light on the important mechanisms involved in AD as well as T2DM such as inflammatory factors, abnormalities in the insulin signaling system and the possible role of the endocrine enzyme TH.
Kim, JJY, Tan, Y, Xiao, L, Sun, Y-L & Qu, X 2013, 'Green Tea Polyphenol Epigallocatechin-3-Gallate Enhance Glycogen Synthesis and Inhibit Lipogenesis in Hepatocytes', BIOMED RESEARCH INTERNATIONAL.View/Download from: Publisher's site
Tan, Y, Lao, W, Xiao, LH, Wang, Z, Wei, X, Kamal, M, Seale, JP & Qu, X 2013, 'Managing The Combination Of Nonalcoholic Fatty Liver Disease And Metabolic Syndrome With Chinese Herbal Extracts In High-fat-diet Fed Rats', Evidence-based Complementary And Alternative Medicine, vol. 2013, no. 1, pp. 1-10.View/Download from: Publisher's site
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MetS). The aim of the study was to evaluate the effects of Chinese herbal extracts from Salvia miltiorrhiza and Gardenia jasminoides (SGE) on the combination of NAFLD and MetS induced by a high-fat diet (HFD) in rats. After 6 weeks of HFD feeding, rats ( each group) were treated with saline, rosiglitazone (RSG), and SGE for 4 weeks. HFD rats were obese, hyperinsulinemic, hyperlipidemic and increased hepatic enzymes with the histological images of NAFLD. Treatment with SGE significantly reduced serum triglycerides (TG), nonesterified fatty acids and enhanced insulin sensitivity, and ameliorated the elevated serum hepatic enzymes compared with HFD-saline group. SGE treatment also attenuated hepatic TG by 18.5% (). Histological stains showed SGE decreased lipids droplets in hepatocytes () and normalized macrovesicular steatosis in HFD rats. Significant reduction of TNF-a and IL6 in adipose tissue was detected in SGE treated rats. The anti-inflammatory action may be, at least in part, the mechanism of SGE on MetS associated with NAFLD. This study discovered that SGE is capable of managing metabolic and histological abnormalities of NAFLD and MetS. SGE may be an optimal treatment for the combination of NAFLD and MetS.
Xiao, LH, Lao, W, Tan, Y & Qu, X 2012, 'In Vitro Investigation Of Anti-diabetic Effect Of Taxus Cuspidate Extracts By Ultrasound Assisted Method', The American Journal of Chinese Medicine, vol. 40, no. 6, pp. 1205-1215.View/Download from: Publisher's site
Extracting active components from Chinese medicinal herbs efficiently is a key step in the investigation of their pharmacological effects and modes of action. In this project, we compared the ultrasound-assisted method and the conventional solvent method
Tan, Y, Kamal, M, Wang, Z, Xiao, W, Seale, JP & Qu, X 2011, 'Chinese herbal extracts (SK0506) as a potential candidate for the therapy of the metabolic syndrome', Clinical Science, vol. 120, no. 7-8, pp. 297-305.View/Download from: Publisher's site
The metabolic syndrome has reached epidemic proportions worldwide, but currently there is a lack of effective therapies for this multifactorial endocrine disease. TCM (traditional Chinese medicine) has been utilized to treat a wide variety of diseases for centuries in the People's Republic of China, subsequently becoming a promising source for the development of new therapeutic agents. Chinese medicinal herbs Gynostemma pentaphyllum, Coptis chinensis and Salvia miltiorrhiza have been shown to have anti-atherosclerotic and antidiabetic properties. In this study, we have investigated the metabolic effects of a mixture of these three herbal extracts (SK0506) in a rodent model of the metabolic syndrome induced by an HFD (high-fat diet). SD (Sprague-Dawley) rats that were fed on an HFD for 4 weeks gained 33% more weight compared with chow-fed rats (P<0.05). Four weeks treatment with SK0506 prevented weight gain with decreased visceral fat (P<0.01 compared with vehicle treatment). SK0506 also significantly reduced plasma triacylglycerols (triglycerides), NEFAs (non-esterified fatty acids) and cholesterol. SK0506 exerted similar effects to RSG (rosiglitazone) on impaired glucose intolerance. SK0506 also significantly enhanced glucose uptake and glycogen synthesis in adipose tissue during hyperinsulinaemic euglycaemic clamp. Western blotting analysis revealed that SK0506 enhanced GLUT4 (glucose transporter 4) expression in adipose tissue, and RSG markedly up-regulated GLUT4 translocation in skeletal muscle. Overall, the present study has discovered that SK0506 can reverse several components of the metabolic syndrome primarily through acting on hyperlipidaemia and visceral obesity. The results from the present study suggest that it is worthwhile to conduct a randomized clinical trial to confirm the potential that SK0506 may be a new oral agent for treating the metabolic syndrome and preventing Type 2 diabetes.
Tan, Y, Sun, L, Kamal, M, Wang, X, Seale, J & Qu, X 2011, 'Suppression Of Retinol-binding Protein 4 With Rna Oligonucleotide Prevents High-fat Diet-induced Metabolic Syndrome And Non-alcoholic Fatty Liver Disease In Mice', Biochimica et Biophysica Acta, vol. 1811, no. 12, pp. 1045-1053.View/Download from: Publisher's site
Conflicting data have been reported regarding the role of retinol-binding protein (RBP4) in insulin resistance, obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). In this study, we used pharmacological methods to investigate the role
Kamal, M, Tan, Y, Seale, JP & Qu, X 2009, 'Targeting Buche-Inflammatory Pathway By Sk0506 To Manage Type 2 Diabetes And Alzheimer Disease', Neurochemical Research, vol. 34, no. 12, pp. 2163-2169.View/Download from: Publisher's site
Type 2 diabetes mellitus (T2DM) and Alzheimers disease (AD) affect a large percent of the population worldwide. Experimental studies have revealed that T2DM and AD share several molecular processes that underlie their respective degenerative pathology. Based on this information, we quantified TNF-?, IL-6 levels, serum glucose, serum triglyceride, hepatic triglyceride, serum AST, serum ALT and butyrylcholinesterase (BuChE) in various rat tissues. HFD was fed to rats resulting in increased body weight, fasting blood glucose, IL-6, TNF-? levels, hepatic triglyceride, serum AST, serum ALT and BuChE. SK0506 treatment significantly prevented weight gain induced by HFD feeding. SK0506, but not Rosiglitazone, significantly reduced serum and hepatic triglycerides levels. Treatment with SK0506 also ameliorated elevated levels of both inflammatory markers (TNF-? and IL-6) and serum liver enzymes (ALT and AST) significantly in HFD fed rats. BuChE activity also reduced in skeletal muscle and adipose tissues of rats treated by SK0506. In conclusion, current study has opened new potential avenues towards research for management of T2DM and AD by Chinese herbal extracts, SK0506.
Kim, JK, Xiao, H, Tan, Y, Wang, Z, Seale, JP & Qu, X 2009, 'The Effects And Mechanism Of Saponins Of Panax Notoginseng On Glucose Metabolism In 3T3-L1 Cells', The American Journal of Chinese Medicine, vol. 37, no. 6, pp. 1179-1189.View/Download from: Publisher's site
This study was carried out to determine the effect of saponins of Panax notoginseng (SPN), a naturally occurring cardiovascular agent, on: (1) glucose uptake, (2) GLUT4 translocation and (3) glycogen synthesis in 3T3-L1 adipocytes. Electrospray ionization-Mass spectrometry (ESI-MS) was used to determine the structural characterization of the major active components of SPN. 3T3-L1 adipocytes were cultured and treated with 100 nM insulin alone or with 10, 50 and 100 ?g/ml of SPN. [3H]2-deoxyglucose glucose uptake, GLUT4 immunofluorescence imaging and glycogen synthesis assay were carried out to determine the effects of SPN on glucose metabolism. Under insulin stimulation, SPN significantly increased glucose uptake in a dose-dependent manner; 50 ?g/ml of SPN increased glucose uptake by 64% (p < 0.001). Immunofluorescence imaging and analysis have revealed that 50 and 100 ?g/ml of SPN increased GLUT4 in the plasma membrane by 3-fold and 6-fold respectively (p < 0.001). Furthermore, the incorporation of D-[U-14C] glucose into glycogen was enhanced by 53% in 3T3-L1 cells treated with 100 ?g/ml of SPN (p < 0.01 vs. insulin stimulation alone). SPN, a naturally occurring agent used to treat ischemic cardio-cerebral vascular disease in China, enhanced insulin-stimulated glucose uptake and glycogen synthesis in adipocytes. The results of this study indicate that SPN may have a therapeutic potential for hyperglycaemia in type 2 diabetes.
Kamal, M, Qu, X, Yu, Q, Tweedie, D, Holloway, H, Li, Y, Tan, Y & Greig, N 2008, 'Tetrahydrofurobenzofuran cymserine, a potent butyrylcholinesterase inhibitor and experimental Alzheimer drug candidate, enzyme kinetic analysis', Journal Of Neural Transmission, vol. 115, no. 6, pp. 889-898.View/Download from: Publisher's site
Synaptic loss, particularly related to the forebrain cholinergic system, is considered to be an early event that leads to Alzheimer's disease (AD) and has led to the development of acetylcholinesterase inhibitors (AChE-Is) as the mainstay of treatment fo
Dang, L, Seale, JP & Qu, X 2007, 'Effects Of Hypocrellin A On Expression Of Vascular Endothelial Growth Factor And Endothelin-1 In Human Umbilical Endothelial Cells', American Journal Of Chinese Medicine, vol. 35, no. 4, pp. 713-723.View/Download from: Publisher's site
Increased endothelin-1 (ET-1), vascular endothelial growth factor (VEGF) and activation of protein kinase C (PKC) are co-contributors to endothelial hyperpermeability in diabetes. Several lines of evidence have suggested a hypothesis that activation of s
Donnelly, R, Wang, B & Qu, X 2006, 'Type 2 diabetes in China partnerships in education and research to evaluate new antidiabetic treatments', British Journal Of Clinical Pharmacology, vol. 61, no. 6, pp. 702-705.View/Download from: Publisher's site
There are 40 million people with diabetes in China, and the projected increase in the rates of obesity and premature cardiovascular disease is alarming. Most patients prefer to combine traditional Chinese medicine with Western medicine, but there is litt
Dang, L, Seale, JP & Qu, X 2005, 'High glucose-induced human umbilical vein endothelial cell hyperpermeability is dependent on protein kinase C activation and independent of the Ca2+-nitric oxide signalling pathway', Clinical And Experimental Pharmacology And Physiology, vol. 32, no. 9, pp. 771-776.View/Download from: Publisher's site
1. Endothelial barrier dysfunction plays a pivotal role in the pathogenesis of diabetic vascular complications. The precise molecular mechanisms by which hyperglycaemia causes the increased permeability in endothelial cells are not yet well understood. I
Dang, L, Seale, JP & Qu, X 2004, 'Reduction of high glucose and phorbol-myristate-acetate-induced endothelial cell permeability by protein kinase C inhibitors LY379196 and hypocrellin A', Biochemical Pharmacology, vol. 67, pp. 855-864.View/Download from: Publisher's site
Samuel, VT, Liu, Z, Qu, X, Elder, BD, Bilz, S, Befroy, D, Romanelli, AJ & Shulman, GI 2004, 'Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease', Journal Of Biological Chemistry, vol. 279, no. 1, pp. 32345-32353.View/Download from: Publisher's site
Short term high fat feeding in rats results specifically in hepatic fat accumulation and provides a model of non-alcoholic fatty liver disease in which to study the mechanism of hepatic insulin resistance. Short term fat feeding (FF) caused a ?3-fold increase in liver triglyceride and total fatty acyl-CoA content without any significant increase in visceral or skeletal muscle fat content. Suppression of endogenous glucose production (EGP) by insulin was diminished in the FF group, despite normal basal EGP and insulin-stimulated peripheral glucose disposal. Hepatic insulin resistance could be attributed to impaired insulin-stimulated IRS-1 and IRS-2 tyrosine phosphorylation. These changes were associated with activation of PKC-? and JNK1. Ultimately, hepatic fat accumulation decreased insulin activation of glycogen synthase and increased gluconeogenesis. Treatment of the FF group with low dose 2,4-dinitrophenol to increase energy expenditure abrogated the development of fatty liver, hepatic insulin resistance, activation of PKC-? and JNK1, and defects in insulin signaling. In conclusion, these data support the hypothesis hepatic steatosis leads to hepatic insulin resistance by stimulating gluconeogenesis and activating PKC-? and JNK1, which may interfere with tyrosine phosphorylation of IRS-1 and IRS-2 and impair the ability of insulin to activate glycogen synthase.
Dang, L, Seale, JP & Qu, X 2003, 'Protein Kinase C Inhibition Reverses High-glucose-induced Expression And Secretion Of Vascular Endothelial Growth Factor In Human Umbilical Vein Endothelial Cells.', Diabetologia, vol. 46, pp. 1-1.
Kim, JK, Fillmore, JJ, Gavrilova, O, Chao, L, Higashimori, T, Choi, H, Kim, H, Yu, C, Chen, Y, Qu, X, Haluzik, M, Reitman, ML & Shulman, GI 2003, 'Differential effects of rosiglitazone on skeletal muscle and liver insulin resistance in A-ZIP/F-1 fatless mice', Diabetes, vol. 52, no. 6, pp. 1311-1318.View/Download from: Publisher's site
Qu, X, Dang, L & Seale, JP 2003, 'Inhibitory effect of hypocrellin A on protein kinase C in liver and skeletal muscle of obese zucker rats', The American Journal of Chinese Medicine, vol. 31, no. 6, pp. 871-878.View/Download from: Publisher's site
Patig, D, Qu, X, Gray, S, Idirs, I, Wilkes, M & Seale, JP 2000, 'Possible Interactions Between Angiotensin II and Insulin: Effects on Glucose and Lipid Metabolosm in Vivo and in Vitro', Journal of Endocrinology, vol. 167, no. 0, pp. 525-531.
Patiag, D, Qu, X, Wilkes, M, Gray, S, Seale, JP & Donnelly, R 1999, 'Effects Of Angiotensin Ii And At(1) & At(2) Receptor Blockade On Glucose And Lipid Metabolism In Vivo And In Vitro.', Diabetologia, vol. 42, pp. 1-1.
Qu, X, Seale, JP & Donnelly, R 1999, 'Tissue And Isoform-selective Activation Of Protein Kinase C In Insulin-resistant Obese Zucker Rats - Effects Of Feeding', Journal Of Endocrinology, vol. 162, no. 2, pp. 207-214.View/Download from: Publisher's site
The mechanisms of insulin resistance in the obese Zucker rat have not been clearly established but increased diacylglycerol-protein kinase C (DAG-PKC) signalling has been associated with decreased glucose utilisation in states of insulin resistance and n
Qu, X, Seale, JP & Donnelly, R 1999, 'Tissue- And Isoform-specific Effects Of Aging In Rats On Protein Kinase C In Insulin-sensitive Tissues', Clinical Science, vol. 97, no. 3, pp. 355-361.View/Download from: Publisher's site
The mechanisms responsible for the age-related decline in insulin sensitivity have not been clearly identified, but activation of the diacylglycerol/protein kinase C (PKC) signalling pathway (often confined to individual isoforms of PKC) has recently bee
QU, X, SEALE, JP & DONNELLY, R 1999, 'Tissue- and isoform-specific effects of aging in rats on protein kinase C in insulin-sensitive tissues', Clinical Science, vol. 97, no. 3, pp. 355-361.View/Download from: Publisher's site
The mechanisms responsible for the age-related decline in insulin sensitivity have not been clearly identified, but activation of the diacylglycerol/protein kinase C (PKC) signalling pathway (often confined to individual isoforms of PKC) has recently been implicated in the pathogenesis of other insulin-resistant states in both humans and animal models. Fasting serum glucose, insulin and triacylglycerol (triglyceride) concentrations, and results of oral glucose tolerance tests, were compared in groups of 6-week-old (n = 8) and 6-month-old (n = 8) Sprague–Dawley rats. Insulin-responsive tissues (liver, soleus muscle and epididymal fat pad) were collected to compare levels of diacylglycerol, PKC enzyme activity and protein expression of individual PKC isoforms in cytosol and membrane fractions. The older group were heavier (556±14 g, compared with 188±7 g) and relatively insulin-resistant and hyperinsulinaemic (477±73 pM compared with 293±51 pM; P < 0.05) compared with young rats; they also had greater areas under the serum glucose (old, 20.3±1.1; young, 17.3±0.7 mmol·h-1·l-1) and insulin (old, 1254±76; young, 721±113 mmol·h-1·l-1) profiles following an oral glucose tolerance test, and significantly higher fasting triacylglycerol levels (old, 1.24±0.06 mM; young, 0.92±0.07 mM; P < 0.01). There were no age-related differences in diacylglycerol levels or PKC activity in muscle and liver, but membrane-associated PKC activity was 2.5-fold higher in the adipose tissue of older rats (101±19 compared with 40±5 pmol·min-1·mg-1 protein; P < 0.05) due to increased translocation of PKC-βI, -βII and -ε. Thus insulin resistance due to normal aging is associated with tissue- and isoform-specific changes in diacylglycerol/PKC signalling. In contrast with diabetes and dietary-induced insulin resistance, there were no changes in diacylglycerol/PKC signalling in skeletal muscle and liver, but isoform-specific translocation and higher PKC activity in adipose tissue ma...
Black, K, Qu, X, Seale, JP & Donnelly, R 1998, 'Metabolic Effects Of Thioctic Acid In Rodent Models Of Insulin Resistance And Diabetes', Clinical And Experimental Pharmacology And Physiology, vol. 25, no. 9, pp. 712-714.View/Download from: Publisher's site
1. The antioxidant thioctic acid (TA) has been used in the treatment of diabetic neuropathy and recent studies have suggested that TA also has pancreatic and peripheral effects that improve glucose transport and metabolism,In the present study, the metab
Donnelly, R & Qu, X 1998, 'Mechanisms Of Insulin Resistance And New Pharmacological Approaches To Metabolism And Diabetic Complications', Clinical And Experimental Pharmacology And Physiology, vol. 25, no. 2, pp. 79-87.View/Download from: Publisher's site
1. Resistance to insulin-mediated glucose transport and metabolism has been identified as a primary mechanism in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) and as a target for drug development, The aetiology of insulin resistance
Qu, X & Donnelly, R 1997, 'Is Insulin Resistance In The Spontaneously Hypertensive Rat Related To Changes In Protein Kinase C In Skeletal Muscle?', American Journal Of Hypertension, vol. 10, no. 9, pp. 1053-1057.View/Download from: Publisher's site
The mechanism of insulin resistance in the spontaneously hypertensive rat (SHR) has not been clearly identified, but protein kinase C (PKC) has been implicated as a mechanism of insulin resistance in obesity and diabetes mellitus and in a diet-induced (f
Qu, X, Cooney, G & Donnelly, R 1997, 'Short-term Metabolic And Haemodynamic Effects Of Gr79236 In Normal And Fructose-fed Rats', European Journal Of Pharmacology, vol. 338, no. 3, pp. 269-276.View/Download from: Publisher's site
The adenosine (A1) receptor agonist, GR79236 (N-[(1S,trans)-2-hydroxycyclopentyl]adenosine), inhibits catecholamine-induced lipolysis in vitro, but the short-term metabolic and haemodynamic effects have not been previously reported in the fructose fed mo