Publications by authors named "Cheng-Fu Su"

7 Publications

  • Page 1 of 1

TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2.

Acta Pharmacol Sin 2021 Aug 20. Epub 2021 Aug 20.

Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.

Transcriptional factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, is generally regarded as a pro-survival factor. Here, we identify that besides its effect on autophagy induction, TFEB exerts a pro-apoptotic effect in response to the cyclopentenone prostaglandin 15-deoxy-∆--prostaglandin J2 (15d-PGJ2). Specifically, 15d-PGJ2 promotes TFEB translocation from the cytoplasm into the nucleus to induce autophagy and lysosome biogenesis via reactive oxygen species (ROS) production rather than mTORC1 inactivation. Surprisingly, TFEB promotes rather than inhibits apoptosis in response to 15d-PGJ2. Mechanistically, ROS-mediated TFEB translocation into the nucleus transcriptionally upregulates the expression of ATF4, which is required for apoptosis elicited by 15d-PGJ2. Additionally, inhibition of TFEB activation by ROS scavenger N-acetyl cysteine or inhibition of protein synthesis by cycloheximide effectively compromises ATF4 upregulation and apoptosis in response to 15d-PGJ2. Collectively, these results indicate that ROS-induced TFEB activation exerts a novel role in promoting apoptosis besides its role in regulating autophagy in response to 15d-PGJ2. This work not only evidences how TFEB is activated by 15d-PGJ2, but also unveils a previously unexplored role of ROS-dependent activation of TFEB in modulating cell apoptosis in response to 15d-PGJ2.
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http://dx.doi.org/10.1038/s41401-021-00711-7DOI Listing
August 2021

Qingyangshen mitigates amyloid-β and Tau aggregate defects involving PPARα-TFEB activation in transgenic mice of Alzheimer's disease.

Phytomedicine 2021 Oct 12;91:153648. Epub 2021 Jul 12.

Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address:

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs) is the key pathological hallmark of AD. Accumulating evidence suggest that impairment of autophagy-lysosomal pathway (ALP) plays key roles in AD pathology.

Purpose: The present study aims to assess the neuroprotective effects of Qingyangshen (QYS), a Chinese herbal medicine, in AD cellular and animal models and to determine its underlying mechanisms involving ALP regulation.

Methods: QYS extract was prepared and its chemical components were characterized by LC/MS. Then the pharmacokinetics and acute toxicity of QYS extract were evaluated. The neuroprotective effects of QYS extract were determined in 3XTg AD mice, by using a series of behavioral tests and biochemical assays, and the mechanisms were examined in vitro.

Results: Oral administration of QYS extract improved learning and spatial memory, reduced carboxy-terminal fragments (CTFs), amyloid precursor protein (APP), Aβ and Tau aggregates, and inhibited microgliosis and astrocytosis in the brains of 3XTg mice. Mechanistically, QYS extract increased the expression of PPARα and TFEB, and promoted ALP both in vivo and in vitro.

Conclusion: QYS attenuates AD pathology, and improves cognitive function in 3XTg mice, which may be mediated by activation of PPARα-TFEB pathway and the subsequent ALP enhancement. Therefore, QYS may be a promising herbal material for further anti-AD drug discovery.
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http://dx.doi.org/10.1016/j.phymed.2021.153648DOI Listing
October 2021

Resveratrol in Rodent Models of Parkinson's Disease: A Systematic Review of Experimental Studies.

Front Pharmacol 2021 22;12:644219. Epub 2021 Apr 22.

Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.

Parkinson's disease (PD) is a common neurodegenerative disease featured by progressive degeneration of nigrostriatal dopaminergic neurons (DA) accompanied with motor function impairment. Accumulating evidence has demonstrated that natural compounds from herbs have potent anti-PD efficacy in PD models. Among those compounds, resveratrol, a polyphenol found in many common plants and fruits, is more effective against PD. Resveratrol has displayed a potent neuroprotective efficacy in several PD animal models. However, there is still no systematic analysis of the quality of methodological design of these studies, nor of their results. In this review, we retrieved and analyzed 18 studies describing the therapeutic effect of resveratrol on PD animal models. There are 5 main kinds of PD rodent models involved in the 18 articles, including chemical-induced (MPTP, rotenone, 6-OHDA, paraquat, and maneb) and transgenic PD models. The neuroprotective mechanisms of resveratrol were mainly concentrated on the antioxidation, anti-inflammation, ameliorating mitochondrial dysfunction, and motor function. We discussed the disadvantages of different PD animal models, and we used meta-analysis approach to evaluate the results of the selected studies and used SYRCLE's risk of bias tool to evaluate the methodological quality. Our analytical approach minimized the bias of different studies. We have also summarized the pharmacological mechanisms of resveratrol on PD models as reported by the researchers. The results of this study support the notion that resveratrol has significant neuroprotective effects on different PD models quantified using qualitative and quantitative methods. The collective information in our review can guide researchers to further plan their future experiments without any hassle regarding preclinical and clinical studies. In addition, this collective assessment of animal studies can provide a qualitative analysis of different PD animal models, either to guide further testing of these models or to avoid unnecessary duplication in their future research.
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http://dx.doi.org/10.3389/fphar.2021.644219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100515PMC
April 2021

Traditional Chinese medicine compounds regulate autophagy for treating neurodegenerative disease: A mechanism review.

Biomed Pharmacother 2021 Jan 11;133:110968. Epub 2020 Nov 11.

Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region. Electronic address:

Neurodegenerative diseases (NDs) are common chronic diseases related to progressive damage of the nervous system. Globally, the number of people with an ND is dramatically increasing consistent with the fast aging of society and one of the common features of NDs is the abnormal aggregation of diverse proteins. Autophagy is the main process by which misfolded proteins and damaged organelles are removed from cells. It has been found that the impairment of autophagy is associated with many NDs, suggesting that autophagy has a vital role in the neurodegeneration process. Recently, more and more studies have reported that autophagy inducers display a protective role in different ND experimental models, suggesting that enhancement of autophagy could be a potential therapy for NDs. In this review, the evidence for beneficial effects of traditional Chinese medicine (TCM) regulate autophagy in the models of Alzheimer's disease (AD), Parkinson's disease (PD), and other NDs are presented and common autophagy-related mechanisms are identified. The results demonstrate that TCM which regulate autophagy are potential therapeutic candidates for ND treatment.
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http://dx.doi.org/10.1016/j.biopha.2020.110968DOI Listing
January 2021

Lignanamides with potent antihyperlipidemic activities from the root bark of Lycium chinense.

Fitoterapia 2017 Oct 8;122:119-125. Epub 2017 Sep 8.

School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, People's Republic of China; Collaborative Innovation Center for Respiratory Disease Diagnosis, Treatment and New Drug Research and Development of Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, People's Republic of China. Electronic address:

Seven new lignanamides, lyciumamides D-J (1-4 and 9-11), together with nine known analogues (5-8 and 12-16), were isolated from the root bark of Lycium chinense. The structures of the isolated compounds were elucidated on the basis of NMR spectroscopic and HRESIMS data. All isolated compounds were evaluated for antihyperlipidemic activities in HepG2 cells. The primary structure-activity relationships were discussed.
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http://dx.doi.org/10.1016/j.fitote.2017.09.004DOI Listing
October 2017

Antihyperlipidaemic and antioxidant effect of the total flavonoids in Selaginella tamariscina (Beauv.) Spring in diabetic mice.

J Pharm Pharmacol 2013 May 14;65(5):757-66. Epub 2013 Mar 14.

Henan University of Traditional Chinese Medicine, Zhengzhou, China.

Objectives: To investigate the antidiabetic, antihyperlipidaemic and antioxidant activity of total flavonoids in Selaginella tamariscina (Beauv.) Spring (TFST) in a mouse model of diabetes.

Methods: Normal mice, mice fed with a high-fat emulsion diet and streptozotocin (STZ)-induced diabetic mice were treated with TFST for 6 weeks. Serum glucose, insulin and lipid, hepatic steatosis, production of the protein visfatin and antioxidant indices were evaluated.

Key Findings: TFST significantly decreased the concentration of fasting blood glucose, total cholesterol, triglycerides and low-density-lipoprotein cholesterol, while it increased the levels of insulin and high-density-lipoprotein cholesterol in diabetic mice. TFST also improved the results of the oral glucose tolerance test to a certain degree. Furthermore, both the free fatty acid levels in the liver and hepatic steatosis were ameliorated by TFST treatment. These changes may be be associated with decreased production of visfatin. Administration of TFST also significantly decreased the levels of malondialdehyde, nitric oxide and inducible nitric oxide synthase and increased the content of glutathione and the activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the liver. No change in blood glucose levels were observed in the normal mice treated with TFST.

Conclusions: TFST showed an excellent effect in reducing the high blood glucose level but had no effect on normal blood glucose level. The antidiabetic activity of TFST could be explained by its antioxidant and antihyperlipidaemic activity, which finally elevated the insulin sensitivity of liver.
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http://dx.doi.org/10.1111/jphp.12035DOI Listing
May 2013

Consensus sequence L/PKSSLL mimics crucial epitope on Loop III of Taiwan cobra cardiotoxin.

Biochem Biophys Res Commun 2009 Sep 24;387(3):617-22. Epub 2009 Jul 24.

Institute of Biotechnology, National University of Kaohsiung, Kaohsiung 811, Taiwan.

Phage display is effective in screening peptides that mimic venom's neutralizing epitopes. A phage display cyclized heptapeptide library (C7C library) was panned with purified divalent antivenin IgG, which neutralizes Naja naja atra venom (NAV) and Bungarus multicinctus venom (BMV). The selected heptapeptide sequences were aligned with known protein sequences of NAV and BMV in GenBank. One of the four consensus sequences, L/PKSSLL, mimicked the crucial epitope on Loop III of Taiwan cobra cardiotoxin that is associated with the venom's lethal potency. In dot blot analysis, several clones showed varying reactivities for NAV monovalent antivenin and lesser cross-reactions with BMV monovalent antivenin. The KSSLLRN-carrying phage occurred four times in selected clones and showed the strongest reactivity to NAV monovalent antivenin. Furthermore, the QDSLLPS-carrying phage also presented significant dot blot signal, indicating that the SLL sequence shared by these two clones may be a crucial antibody-binding site.
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http://dx.doi.org/10.1016/j.bbrc.2009.07.097DOI Listing
September 2009
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