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1.
Int J Toxicol ; 38(5): 436-444, 2019.
Article in English | MEDLINE | ID: mdl-31342801

ABSTRACT

Triptolide is a major active ingredient isolated from the traditional Chinese herb Tripterygium wilfordii Hook F. However, its use in clinical practice is limited due to its severe hepatotoxicity. Autophagy, a highly conserved intracellular process, is essential for maintaining cytoplasmic homeostasis. Considering that abnormalities in autophagy are closely associated with drug-mediated hepatotoxicity, we applied human normal liver HL7702 cells to elucidate the roles of autophagy in triptolide-induced hepatotoxicity. Our study revealed that triptolide was cytotoxic to HL7702 cells. It markedly increased autophagosome formation and expression of autophagy-related proteins, namely Beclin1 and microtubule-associated protein 1 light chain 3II, and induced oxidative stress. These proautophagic effects were counteracted by pretreatment with N-acetylcysteine, a reactive oxygen species scavenger. Moreover, the pharmacological suppression of autophagy further exacerbated triptolide-elicited decrease in cell viability, increase in lactate dehydrogenase leakage, and activation of apoptosis proteases (caspase 3 and caspase 9). Our findings suggest that triptolide-induced oxidative stress consequently enhances autophagic activity, and autophagy is a cytoprotective mechanism against triptolide-induced cytotoxicity in HL7702 cells.


Subject(s)
Autophagy/drug effects , Diterpenes/toxicity , Hepatocytes/drug effects , Phenanthrenes/toxicity , Caspase 3/metabolism , Caspase 9/metabolism , Cell Line , Epoxy Compounds/toxicity , Glutathione/metabolism , Hepatocytes/metabolism , Hepatocytes/ultrastructure , Humans , Malondialdehyde/metabolism , Microscopy, Electron, Transmission , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism
2.
Chin J Integr Med ; 25(3): 233-240, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30178091

ABSTRACT

As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic process involved in cytoplasmic materials degradation. Autophagic dysfunction contributes to the pathologies of many human diseases, which makes it a promising therapeutic target. Recent studies have shown that triptolide exerts neuroprotection, anti-tumor activities, organ toxicity, and podocyte protection by modulating autophagy. This article highlights the current information on triptolide-modulated autophagy, analyzes the possible pathways involved, and describes the crosstalk between autophagy and apoptosis modulated by triptolide, in hope of providing implications for the roles of autophagy in pharmacological effects of triptolide and expanding its novel usage as an autophagy modulator.


Subject(s)
Autophagy/drug effects , Diterpenes/pharmacology , Phenanthrenes/pharmacology , Animals , Apoptosis/drug effects , Epoxy Compounds/pharmacology , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Neuroprotective Agents/pharmacology , Podocytes/drug effects
3.
BMC Complement Altern Med ; 16(1): 509, 2016 Dec 07.
Article in English | MEDLINE | ID: mdl-27927244

ABSTRACT

BACKGROUND: Chinese medicine Wuzi Yanzong pill (WZYZP) was firstly documented in ancient Chinese medical works "She Sheng Zhong Miao Fang" by Shi-Che Zhang in 1550 AD. The traditional herbal formula is widely used in treating nephrasthenia lumbago, prospermia, erectile dysfunction and male sterility. The present study was to explore the effects of WZYZP on ionizing irradiation-induced testicular damage in mice. METHODS: The pelvic region of male mice was exposed to X-rays for inducing testicular damage. The effects of WZYZP on testicular damage were evaluated in terms of testes weight, sperm quantity and motility, testes oxidative status and serum hormone levels. The alterations in testicular structure were examined by hematoxylin-eosin staining. Additionally, changes in proliferating cell nuclear antigen (PCNA) expression of testes were explored by western blot. RESULTS: Pelvic exposure to x-ray induced reduction in testes weight and sperm quality, along with oxidative stress and abnormal testicular architecture in testes. Oral administration of WZYZP for 3 weeks markedly increased testes weight, sperm quantity and motility, and attenuated testicular architecture damage. Meanwhile, WZYZP treatment significantly reversed the reduction of serum testosterone, and decreased testes malondialdehyde (MDA) and Oxidative stress index (OSI) relative to the radiated mice. Additionally, WZYZP effectively prevented the downregulation of PCNA expression in testes induced by x-ray irradiation. CONCLUSION: These findings suggest WZYZP exhibits ameliorating effects against ionizing irradiation-induced testicular damage in mice, which may be related to its antioxidation.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Infertility, Male/prevention & control , Radiation Injuries, Experimental/prevention & control , Testis/drug effects , Animals , Antioxidants/metabolism , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/pharmacology , Follicle Stimulating Hormone/blood , Infertility, Male/etiology , Luteinizing Hormone/blood , Male , Malondialdehyde/metabolism , Mice , Proliferating Cell Nuclear Antigen/metabolism , Radiation Injuries, Experimental/complications , Random Allocation , Sperm Count , Sperm Motility/drug effects , Testis/metabolism , Testosterone/blood , X-Rays/adverse effects
4.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(11): 2981-6, 2012 Nov.
Article in Chinese | MEDLINE | ID: mdl-23387162

ABSTRACT

To study the genuine soil of Astragalus menbranceus grows, FTIR spectrometry was used, which is accurate, simple and efficient and has high resolution. The genuine soils include six areas in Hunyuan of Shanxi province, three areas in Yingxian of Shanxi province, Fansi of Shanxi province, and Guyang of Inner Mongolia. Different growth years of two to five for each area were also studied. The results show that there are significant differences between Astragalus menbranceus soil FTIR spectrometry and general soil's, between soil of Astragalus menbranceus growth and radix codonopsitis growth, between different soil of Astragalus menbranceus growth, providing useful information for the area chose of Chinese herb cultural and transplantation.


Subject(s)
Astragalus propinquus/growth & development , Soil/chemistry , Spectroscopy, Fourier Transform Infrared/methods , Ecosystem , Spectrum Analysis
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