1.Research advances on the usage of traditional Chinese medicine for neuroprotection in glaucoma.
Xue-song MI ; E-mail: HRMASKF@HKUCC.HKU.HK. ; Jing-xiang ZHONG ; Raymond Chuen-Chung CHANG ; Kwok-Fai SO
Journal of Integrative Medicine 2013;11(4):233-240
Progressive loss of retinal ganglion cells (RGCs) and their axons is the main pathogenesis of glaucoma. The cause of glaucoma is not fully understood, but the neurodegeneration of glaucoma involves many mechanisms such as oxidative stress, glutamate toxicity and ischemia/reperfusion insult. In order to target these mechanisms, multiple neuroprotective interventions have been investigated to prevent the death of RGCs. Of note are some tonic herbs from the traditional Chinese medicine (TCM) pharmacopeia that have shown neuroprotective effects in glaucoma. TCM differs from Western medicine in that TCM exhibits complicated bioactive components, triggering many signaling pathways and extensive actions on vital organs. Modern scientific approaches have demonstrated some of their underlying mechanisms. In this review, we used Lycium barbarum and Ginkgo biloba as examples to elaborate the characteristics of TCM and their potential applications in neuroprotection in glaucoma.
Clinical Trials as Topic
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Drugs, Chinese Herbal
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therapeutic use
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Ginkgo biloba
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Glaucoma
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drug therapy
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Humans
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Medicine, Chinese Traditional
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Neuroprotective Agents
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therapeutic use
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Retinal Ganglion Cells
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pathology
2.Modulation of the suppressive effect of corticosterone on adult rat hippocampal cell proliferation by paroxetine.
Guang QIU ; Daiga M HELMESTE ; Asanka N SAMARANAYAKE ; Wui-Man LAU ; Tatia M C LEE ; Siu-Wa TANG ; Kwok-Fai SO
Neuroscience Bulletin 2007;23(3):131-136
OBJECTIVEThe literature has shown that cognitive and emotional changes may occur after chronic treatment with glucocorticoids. This might be caused by the suppressive effect of glucocorticoids on hippocampal neurogenesis and cell proliferation. Paroxetine, a selective serotonin reuptake transporter, is a commonly used antidepressant for alleviation of signs and symptoms of clinical depression. It was discovered to promote hippocampal neurogenesis in the past few years and we wanted to investigate its interaction with glucocorticoid in this study.
METHODSAdult rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine for 14 d. Cell proliferation in the dentate gyrus was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry.
RESULTSThe corticosterone treatment suppressed while paroxetine treatment increased hippocampal cell proliferation. More importantly, paroxetine treatment could reverse the suppressive effect of corticosterone on hippocampal cell proliferation.
CONCLUSIONThis may have clinic application in preventing hippocampal damage after glucocorticoid treatment.
Analysis of Variance ; Animals ; Bromodeoxyuridine ; metabolism ; Cell Count ; Cell Proliferation ; drug effects ; Corticosterone ; pharmacology ; Drug Interactions ; Hippocampus ; cytology ; Male ; Neural Inhibition ; drug effects ; Neurons ; drug effects ; Paroxetine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Serotonin Uptake Inhibitors ; pharmacology
3.Roles of paroxetine and corticosterone on adult mammalian ciliary body cell proliferation.
Hua WANG ; Benson W M LAU ; Suk-yu YAU ; Suk-yee LI ; Nelson LEUNG ; Ning-li WANG ; Siu-wa TANG ; Tatia M C LEE ; Kwok-fai SO
Chinese Medical Journal 2010;123(10):1305-1310
BACKGROUNDThe neurogenesis in retina of adult mammals is generally abolished, and this renders the retina lack of regenerative capacity. Despite this, there is a small population of nestin-positive cells in the ciliary epithelium which retains neurogenic potential. The present study aimed at investigating the effect of two drugs, corticosterone and paroxetine, on the cell proliferation of the ciliary body.
METHODSAdult Sprague-Dawley rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine treatment for 14 days. Cell proliferation in the ciliary body was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry. Co-labelling of BrdU and stem cell marker was used to phenotype the BrdU immunoreactive cells.
RESULTSCorticosterone treatment suppressed while paroxetine treatment increased the cell proliferation of the ciliary body. Co-labelling with cell markers revealed that the BrdU positive cells also showed nestin expression but not glial fibrillary acidic protein (GFAP).
CONCLUSIONSThe results illustrate that proliferation of retinal progenitor cells situated in ciliary body are subjected to regulation by selective serotonin reuptake inhibitors (SSRI) and corticosteroid, which is similar to our previous findings in neurogenic regions in central nervous system (CNS). Paroxetine treatment could reverse the suppressive effect of corticosterone on ciliary body cell proliferation. This provides information for future investigation of retinal stem cell biology and potential treatment of retinal degenerative diseases.
Adrenal Glands ; drug effects ; pathology ; Animals ; Body Weight ; drug effects ; Cell Proliferation ; drug effects ; Ciliary Body ; cytology ; drug effects ; Corticosterone ; pharmacology ; Immunohistochemistry ; In Vitro Techniques ; Male ; Organ Size ; drug effects ; Paroxetine ; pharmacology ; Rats ; Rats, Sprague-Dawley
4. Neuromodulation-Based Stem Cell Therapy in Brain Repair: Recent Advances and Future Perspectives
Ti-Fei YUAN ; Ti-Fei YUAN ; Kwok-Fai SO ; Ti-Fei YUAN ; Chun YAO ; Yongjun WANG ; Renjie CHAI ; Yan LIU ; Yi DONG ; Li ZHANG ; Kwok-Fai SO ; Li ZHANG ; Kwok-Fai SO ; Jieyu QI ; Renjie CHAI ; Chun YAO ; Yongjun WANG ; Yan LIU
Neuroscience Bulletin 2021;37(5):735-745
Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site, orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation. All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.
5.Anti-cancer activities of S-allylmercaptocysteine from aged garlic.
Yi LV ; Kwok-Fai SO ; Nai-Kei WONG ; Jia XIAO
Chinese Journal of Natural Medicines (English Ed.) 2019;17(1):43-49
While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract (AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine (SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.
Animals
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Antineoplastic Agents, Phytogenic
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chemistry
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pharmacology
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therapeutic use
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Apoptosis
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drug effects
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Cysteine
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analogs & derivatives
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chemistry
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pharmacology
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therapeutic use
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Disease Models, Animal
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Garlic
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chemistry
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Humans
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Molecular Structure
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Neoplasms
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drug therapy
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metabolism
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Signal Transduction
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drug effects
7.Melatonin alleviates alcoholic liver disease via EGFR-BRG1-TERT axis regulation.
Zhaodi CHE ; Yali SONG ; Chengfang XU ; Wei LI ; Zhiyong DONG ; Cunchuan WANG ; Yixing REN ; Kwok-Fai SO ; George L TIPOE ; Fei WANG ; Jia XIAO
Acta Pharmaceutica Sinica B 2023;13(1):100-112
Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.
8.Garlic-derived compound -allylmercaptocysteine inhibits hepatocarcinogenesis through targeting LRP6/Wnt pathway.
Jia XIAO ; Feiyue XING ; Yingxia LIU ; Yi LV ; Xiaogang WANG ; Ming-Tat LING ; Hao GAO ; Songying OUYANG ; Min YANG ; Jiang ZHU ; Yu XIA ; Kwok-Fai SO ; George L TIPOE
Acta Pharmaceutica Sinica B 2018;8(4):575-586
Whether and how garlic-derived -allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients (66.7% of 48 patients) and its over-expression only correlated with the over-expression of -catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.