Publications by authors named "Li-Hong Shan"

18 Publications

  • Page 1 of 1

Designed, synthesized and biological evaluation of proteolysis targeting chimeras (PROTACs) as AR degraders for prostate cancer treatment.

Bioorg Med Chem 2021 Sep 26;45:116331. Epub 2021 Jul 26.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou 450001, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, PR China. Electronic address:

As a continuation of our research on developing potent and potentially safe androgen receptor (AR) degrader, a series of novel proteolysis targeting chimeras (PROTACs) containing the phthalimide degrons with different linker were designed, synthesized and evaluated for their AR degradation activity against LNCaP (AR+) cell line. Most of the synthesized compounds displayed moderate to satisfactory AR binding affinity and might lead to antagonist activity against AR. Among them, compound A16 exhibited the best AR binding affinity (85%) and degradation activity against AR. Due to the strong fluorescence properties of pomalidomide derivatives, B10 was found to be effectively internalized and visualized in LNCaP (AR + ) cells than PC-3 (AR-) cells. Moreover, the molecular docking of A16 with AR and the active site of DDB1-CRBN E3 ubiquitin ligase complex provides guidance to design new PROTAC degrons targeting AR for prostate cancer therapy. These results represent a step toward the development of novel and improved AR PROTACs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2021.116331DOI Listing
September 2021

Efficacy and Mechanism of a Chinese Classic Prescription of Yueju in Treating Nonalcoholic Steatohepatitis and Protecting Hepatocytes from Apoptosis.

Evid Based Complement Alternat Med 2020 29;2020:8888040. Epub 2020 Oct 29.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai 200433, China.

Yueju, a famous classic Chinese prescription, has been extensively used in treating depression syndromes for hundreds of years. Recent studies have reported that Yueju showed good effects in treating metabolic diseases, such as obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH), which leads to cirrhosis and severe cardiovascular diseases, is closely linked to obesity and abnormal lipid metabolism. In this study, Yueju could decrease the levels of alanine aminotransferase, aspartate transaminase, triglyceride, cholesterol, and low-density lipoprotein-C but increase the high-density lipoprotein-C in the serum of the NASH rat model induced by high-fat and high-cholesterol diet. Yueju could alleviate hepatosteatosis by increasing the phosphorylation of acetyl-CoA carboxylase and inhibiting the expression of fatty acid synthase and stearoyl-CoA desaturase 1. Yueju downregulated the expression of -smooth muscle actin and collagen type 1A1, ameliorating the liver fibrilization. Yueju could also protect the hepatocytes from apoptosis by upregulating antiapoptosis protein Bcl-2 and X-linked inhibitor of apoptosis protein and downregulating apoptotic proteins Bax and cleaved poly ADP-ribose polymerase. Thus, Yueju could improve liver function, regulate lipid metabolism, alleviate hepatosteatosis and fibrosis, and protect hepatocytes from apoptosis against NASH. Yueju may be used as an alternative effective medicine for NASH treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8888040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644301PMC
October 2020

Intestinal Microecology: An Important Target for Chinese Medicine Treatment of Non-alcoholic Fatty Liver Disease.

Chin J Integr Med 2020 Oct 10;26(10):723-728. Epub 2020 Jun 10.

Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, causing serious economic and medical burdens. Currently, Chinese medicine (CM) has become an important means in treating NAFLD in China. Intestinal microecology (IM) is an important part of the internal environment in the human body and is involved in the occurrence and development of NAFLD. In this paper, the authors systematically discuss the significance of IM in the pathogenesis of NAFLD and the current status of research on the CM treatment of NAFLD via IM regulation. In combination with our own research practice, we propose that IM is an important target for the treatment of NAFLD with CM and formulate plans for future research to target limitations existing in current studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11655-020-3268-3DOI Listing
October 2020

Salidroside and Curcumin Formula Prevents Liver Injury in Nonalcoholic Fatty Liver Disease in Rats.

Authors:
Hong-Shan Li

Ann Hepatol 2018 Aug;17(5):769-778

Introduction And Aim: Salidroside and curcumin (SC) formula could alleviate lipid deposition in high fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the mechanisms are still unknown, and the magnitude of potential therapeutic benefit remains understudied.

Material And Methods: The rats were treated with high fat diet for 14 weeks to induce NAFLD. The experiment was divided into control, model (NAFLD), SC formula and rosiglitazone groups (n = 7 in each group). Hematoxylin-eosin (H&E) staining was applied to detect liver morphological changes. Biochemical, metabolic indices and inflammation factors in liver tissue and serum were detected. Additionally, the activities of related enzymes were detected by enzyme-linked immunosorbent assay.

Results: In the established rat model, typical lipid deposition and liver steatosis were observed. Liver triglyceride, free fatty acids, sera alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, fasting insulin, fasting blood glucose and homeostasis model assessment of insulin resistance were elevated in model group. Liver malondialdehyde was significantly elevated, while superoxide dismutase was significantly decreased in model group, compared with control. Moreover, tumor necrosis factor-α and Interleukin-1 were significantly produced in model group, compared with control. As a mechanism, high fat diet decreased tissue AMP-activated protein kinase (AMPK), phosphorylated AMPK, carnitine palmitoyltransferase 1 and increased inacetyl-CoA carboxylase (ACCase), phosphorylated ACCase. Importantly, these abnormal changes caused by high fat diet were reduced by SC formula administration.

Conclusion: SC formula could ameliorate the injury caused by high fat diet. The effect was likely mediated via its influence on insulin resistance, lipid peroxidation injury and AMPK signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5604/01.3001.0012.3135DOI Listing
August 2018

[Effects of berberine on serum inflammatory factors and carotid atherosclerotic plaques in patients with acute cerebral ischemic stroke].

Zhongguo Zhong Yao Za Zhi 2016 Nov;41(21):4066-4071

Baoding No.1 Central Hospital, Baoding 071000, China.

This study aims to analyze the effect of berberine on serum inflammatory factors and carotid atherosclerotic plaques in ppatients with acute cerebral ischemic stroke(AIS). In the study, 120 patients with AIS were randomly divided into berberine group(n=60) and general group (n=60). The 60 cases in the general group were provided with general therapy according to the latest guidelines of diagnosis and treatment of AIS. The berberine group received berberine 300 mg(tid) in addition to the therapy of the general group. The levels of serum inflammatory factors, the nerve function defect grades and the indexes of carotid atherosclerosis plaques [including the total plaque area(TPA), intima-media thickness(IMT) and the number of unstable carotid atherosclerotic plaques] were measured and compared. The results indicated that the levels of serum inflammatory factors, the NIHSS(national institute of health stroke scales) cores and the indexes of carotid atherosclerosis plaques were not significantly different between the berberine groups of general group, with positive correlation between serum inflammatory factors and NIHSS scores(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine groups on 14 d were significantly lower than those on 1 d(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine group on 14 d were significantly lower than those of the general group(P<0.05). The TPA and the number of unstable carotid atherosclerotic plaques of the berberine groups on 90 d were significantly lower than those of general group, with significant differences(P<0.05). The IMT showed a downward trend, but with significant difference.The mRS(modified rankin scale) scores of the berberine group on 90 d were significantly lower, with a higher rate of short-term favorable prognosis (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. This study showed that berberine in addition to the general therapy can significantly lower the levels of serum MIF and IL-6, reduce the degree of carotid atherosclerosis to some extent and improve neurological impairment and the prognosis of patients with AIS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4268/cjcmm20162128DOI Listing
November 2016

New Non-Nucleocide NS5B Protein Inhibitors for the Treatment of Chronic Hepatitis C Infection.

Curr Top Med Chem 2016 ;16(12):1392-401

School of Pharmaceutical Sciences of Zhengzhou University, zhengzhou, China.

Hepatitis C virus is one of the major causative pathogens of chronic hepatitis and the second most common cause of hepatocellular cancer. The virally encoded NS5B RNA-dependent RNA polymerase is a vital component of the replicase complex that orchestrates the replication process leading to the production of progeny virus. In recent years, developing novel drugs to target NS5B polymerase has become one of the important strategies for the treatment of chronic hepatitis C infection. This review highlights the structure and scaffold of the non-nucleoside NS5B inhibitors represented in the past five years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568026616666151120113933DOI Listing
November 2016

Efficient three-component one-pot synthesis of steroidal polysubstituted anilines.

Steroids 2015 Dec 22;104:1-7. Epub 2015 Jul 22.

School of Pharmaceutical Sciences of Zhengzhou University and Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, No. 100, KeXue DaDao, Zhengzhou 450001, PR China. Electronic address:

An efficient and practical base-promoted cascade reaction has been developed to access steroidal polysubstituted anilines from simple precursors. The protocol reported herein achieved the formation of a benzene ring as well as three continuous C-C bonds in a single operation. The reaction mechanism was proposed on the basis of the key intermediate obtained. Besides, this method could be potentially employed for the synthesis of biphenyl compounds. The adjacent amine and nitrile groups existed in the final products have the potential for late stage functionalization, which would provide efficient access to steroidal compound collections with structural diversity and complexity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2015.07.005DOI Listing
December 2015

Discovery of novel steroidal pyran-oxindole hybrids as cytotoxic agents.

Steroids 2014 Oct 11;88:44-52. Epub 2014 Jun 11.

School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address:

A series of novel steroidal pyran-oxindole hybrids were efficiently synthesized in a single operation through the vinylogous aldol reaction of vinyl malononitrile 3 with substituted isatins involving the construction of C-C and C-O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC-7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu against T24 and MGC-803 cells with the IC50 values of 4.43 and 8.45 μM, respectively. Further mechanism studies indicated that compound 4i induced G2/M arrest and early apoptosis in a concentration- and time-dependent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2014.05.022DOI Listing
October 2014

Synthesis and antimicrobial activities of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives.

Bioorg Med Chem Lett 2014 Feb 7;24(4):1236-8. Epub 2013 Dec 7.

New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, No. 100, KeXue DaDao, Zhengzhou 450001, China. Electronic address:

A series of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives were synthesized in five steps from a common precursor, phthalic anhydride. Most of synthesized phthalazine derivatives showed inhibitory activity against Staphylococcus aureus. One of phthalazine derivatives 5l showed inhibitory activity against all tested bacterial and fungal strains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2013.12.010DOI Listing
February 2014

[The relationship of ultrastructure and function of hypothalamus-pituitary-adrenal axis in early stage of sepsis in rats].

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2011 May;23(5):286-9

Department of Intensive Care Unit, 309 Hospital of PLA, Beijing 100091.

Objective: To observe the changes in ultrastructure and function of hypothalamic-pituitary-adrenal axis (HPAA), and to approach the relationship between them in early stage of sepsis in rats.

Methods: Thirty male Sprague-Dawley (SD) rats were randomly divided into normal control group, sham group, sepsis group. The sepsis model was reproduced by cecal ligation and puncture (CLP). The rats were sacrificed after collection of blood at 6 hours after CLP, and the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in the plasma, and the corticotropin release hormone (CRH) in the tissue of hypothalamus were detected. The histopathological changes in HPAA were observed with transmission electron microscopy.

Results: The levels of ACTH and CORT in plasma, and the CRH in hypothalamus tissue of sepsis group were increased in the early stage of sepsis compared with the normal control group or sham group [ACTH (pmol/L): 5.78±0.36 vs. 1.94±0.31, 2.51±0.10; CORT (nmol/L): 88.48±4.47 vs. 22.02±1.62, 34.20±2.51; CRH (μg/L): 101.92±6.61 vs. 61.65±6.05, 66.65±4.03, P<0.05 or P<0.01]. The changes in ultrastructure of the hypothalamus, pituitary and adrenal were also found. In sepsis group, the ultrastructure of hypothalamus was as follows. Rough endoplasmic reticulum expansion and degranulation of rough endoplasmic reticulum, and swelling of Golgi complex were found. A large number of endocrine granules could be seen in ATCH cells in the pituitary with depletion of adrenal lipid droplets.

Conclusion: In septic rats, the HPAA was excessively activated, and ACTH and CORT in plasma, and CRH in hypothalamus were significantly increased in early stage of sepsis. The changes in ultrastructure of HPAA were obvious, and the change in function was closely related to the ultrastructural changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2011

[Effect of hepatitis B virus X gene on the expression of spastic paraplegia 21].

Zhonghua Gan Zang Bing Za Zhi 2010 Dec;18(12):920-3

The Infectious Disease Hospital of Ningbo, Ningbo 315010, China.

Objective: To investigate the effect of hepatitis B virus(HBV) X gene on the expression of SPG21.

Methods: The expressions of SPG21 mRNA and protein in HepG2 and HepG2.2.15 cells were tested by RT-PCR and western blot. HepG2 cells were co-transfected with reporter plasmid pGL3-SPG21 and plasmids carrying individual genes of HBV, the luciferase activity was measured and the expressions of SPG21 were detected by RT-PCR and western blot.

Results: The expressions of SPG21 mRNA and protein were higher in HepG2.2.15 cells than in HepG2 cells (0.36+/-0.06 vs 0.21+/-0.05, P value is less than 0.05). The activity of SPG21 in HepG2 cells transfected with pCMV-X was higher (875+/-27 vs 67+/-12, P value is less than 0.01) as compared to blank control group (transfected with pCMV-tag2B). HBV X gene enhanced SPG21 gene promoter activity, SPG21 mRNA expression and SPG21 protein production in HepG2 cells in a dose-dependent manner.

Conclusion: HBV X gene can specially activate SPG21 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2010.12.009DOI Listing
December 2010

[Effect of qushl huayu decoction on high-fat diet induced hepatic lipid deposition in rate].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2009 Dec;29(12):1092-5

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai.

Objective: To explore the intervention effect of Qushi Huayu Decoction (QHD) on high-fat diet induced hepatic lipid deposition and its dose-effect relationship in rats.

Methods: Fatty liver model of rats were established simply by 10 weeks of high-fat diet feeding, and starting from the 7th week of modeling, they were gastric perfused respectively with saline (model group), high-dose QHD (QHDh group), low-dose QHD (QHDI group) and polyene phosphatidylcholine (PP group) for successive 4 weeks. Liver pathology by electron microscope observation with HE staining and oil red staining; contents of triglyceride (TG) and free fatty acid (FFA) in liver tissue; and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and TG in rats were determined.

Results: In the model group, the significant hepatic steatosis and vesicle changes as well as severe accumulation of middle- and micro-sized fatty drops in the hepatocyte plasma were found under electron microscope; with TG and FFA contents in liver tissue elevated to 3.2 and 3.5 multiples of those in normal group respectively, but, the difference between them in serum levels of ALT, AST, TG and TC were not significant. Above-mentioned pathological changes in the QHDh, QHDI and PP groups were all ameliorated significantly with the hepatic TG decreased to 57.55%, 72.32% and 71.07%, and FFA decreased to 48.95%, 65.67%, 55.57% of those in model group respectively, especially the effect of QHDh in reducing TG was superior to that of QHDI and PP (P < 0.05).

Conclusion: QHD shows an evident fatty liver antagonizing effect in rats induced by high-fat diet in a dose-dependent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2009

[The role of adiponectin and adiponectin receptor 2 in the pathology of fatty liver].

Zhonghua Gan Zang Bing Za Zhi 2009 Nov;17(11):826-30

Institute of Liver Disease, Shuguang Hospital, Shanghai University of TCM, Shanghai 201203, China.

Objective: To investigate the role of adiponectin (ADP) and adiponectin receptor 2 (adipoR2) in pathology of fatty liver, and to investigate the effect of Chinese herbal decoction (Qushi Huayu Decoction, QHD) on fatty liver disease.

Methods: Two experimental fatty liver models were used. One was induced with high-fat diet for ten weeks, and the rats were divided into normal, model and QHD group, the QHD group was administrated with QHD during the last four weeks. The other experimental fatty liver model was induced by subcutaneous injection of carbon tetrachloride (CCl4) in combination with high-fat and low-protein diet for four weeks, and the rats were also divided into normal, model and QHD group, the QHD group was administrated with QHD during the last two weeks. The observation items include: (1) hepatic steatosis (H.E. staining); (2) serum ADP, hepatic triglyceride (TG), free fatty acid (FFA) and adipoR2; (3) correlation among serum ADP content, hepatic TG, FFA and adipoR2.

Results: (1) Serious hepatic steatosis, increased hepatic TG and FFA, decreased serum ADP and hepatic adipoR2 were observed in the two models (P less than 0.01). QHD administration significantly reduced the hepatic TG and FFA, and increased serum ADP and hepatic adipoR2 (P less than 0.01) in these two models. (2) Inverse correlation was observed between hepatic TG, FFA and serum ADP, hepatic adipoR2 in these two models.

Conclusion: (1) Decreased serum ADP and hepatic adipR2 may play important roles in pathological process of fatty liver. (2) QHD administration increased the serum ADP and hepatic adipoR2.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2009

Synthesis of 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives and their cytotoxic activities.

Bioorg Med Chem Lett 2009 Dec 14;19(23):6637-9. Epub 2009 Oct 14.

New Drug Research and Development Center of Zhengzhou University, Zhengzhou 450001, China.

A series of novel 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives were synthesized and characterized by NMR, HRMS. The pregnenolone (1) was first biotransformed by Mucor circinelloides var lusitanicus to 3beta, 7alpha, 11alpha-trihydroxy-pregn-5-en-20-one (3), then 3 was treated with various benzaldehydes to produce 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives. These derivatives showed remarkable activity against EC109 cells. The absolute configuration of 3 was also confirmed by signal-crystal X-ray analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2009.10.019DOI Listing
December 2009

[Effects of Qushi Huayu Decoction in prevention and treatment of fatty liver in rats based on adiponectin-free fatty acid pathway].

Zhong Xi Yi Jie He Xue Bao 2009 Jun;7(6):546-51

Institute of Liver Diseases of Shuguang Hospital, Key Laboratory for Liver-Kidney Disease Pattern of Ministry of Education, E-Institute of Shanghai Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Objective: To explore the effects of Qushi Huayu Decoction (QSHYD), a compound traditional Chinese herbal medicine, in prevention and treatment of non-alcoholic fatty liver disease (NAFLD) in rats.

Methods: Forty Wistar male rats were used to establish the NAFLD model by subcutaneous injection of carbon tetrachloride (CCl(4)) for 4 weeks (twice weekly) along with high-fat and low-protein diet for 2 weeks. After two-week administration, the rats were randomly divided into four groups: untreated group, high-dose QSHYD group, medium-dose QSHYD group and low-dose QSHYD group. Another six rats were used as normal control. After 2-week treatment, the following indexes were detected: (1) liver pathology; (2) contents of serum adiponectin (ADP) and liver triglyceride (TG); (3) concentrations of liver FFA, adiponectin receptor 2 (AdipoR2), malonyl-coenzyme A (malony1-CoA), AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACCase), fatty acid synthase (FAS) and carnitine palmitoyl transferase-1 (CPT-1).

Results: Compared with the normal group, there were physiological changes associated with hepatic steatosis and inflammation in liver tissues in the untreated group as observed by oil red O staining and HE staining. The TG, FFA, malony1-CoA, FAS, and ACCase concentrations in liver tissues in the untreated group were elevated significantly. While the contents of ADP in serum and AdipoR2, CPT-1 and AMPK in liver tissues in the untreated group were decreased markedly. The pathological damages in each QSHYD-treated group were significantly less than those in the untreated group. The TG and FFA contents in liver tissues in each QSHYD-treated group were significantly decreased. The FAS, ACCase and malonyl-CoA concentrations in liver tissues of the high QSHYD-treated group were reduced markedly as compared with the untreated group. High- and medium-dose of QSHYD could significantly increase ADP content in serum and AMPK, CPT-1 and AdipoR2 contents in liver tissues.

Conclusion: QSHYD can affect the ADP-FFA pathway by increasing the content of serum ADP, which may be one of its important mechanisms in preventing and treating NAFLD in rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3736/jcim20090610DOI Listing
June 2009

[Effects of Qushi Huayu Decoction on cathepsin B and tumor necrosis factor-alpha expression in rats with non-alcoholic steatohepatitis].

Zhong Xi Yi Jie He Xue Bao 2008 Sep;6(9):928-33

Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Objective: To study the mechanism of Qushi Huayu Decoction (QHD), a compound of traditional Chinese herbal medicine, in prevention and treatment of non-alcoholic steatohepatitis (NASH).

Methods: Thirty-five Wistar male rats were randomly divided into normal group, untreated group, QHD group and Ganle (diisopropylamine dichloroacetate) group. The rats except those in normal group were subcutaneously injected with carbon tetrachloride (CCl(4)) for 4 weeks (twice per week) and simultaneously fed with high-fat and low-protein diet for 2 weeks to induce NASH. Then, the rats were administrated with QHD, Ganle, or distilled water for 2 weeks, respectively. After harvest, alanine aminotransferase (ALT) activity and tumor necrosis factor-alpha (TNF-alpha) content in serum as well as triglyceride (TG) and free fatty acid (FFA) in liver tissue were evaluated, and relativity analysis among these parameters was performed. Cathepsin B (Ctsb), phospho-inhibitor kappa B (P-IkappaB), TNF-alpha protein expressions in liver tissue were assayed with western-blot. The expression and distribution of ctsb in liver tissue were observed with immunohistochemical method.

Results: The contents of TG, FFA and activity of ALT were significantly decreased in QHD group. While in the Ganle group, only the activity of ALT in serum was decreased significantly. Expressions of Ctsb, P-IkappaB and TNF-alpha proteins in liver tissues and serum TNF-alpha level were all enhanced in untreated group which, however, were significantly inhibited in the QHD group. And as expected, there were significant relativities among contents of TG in liver tissues and the content of FFA in liver tissue and activity of ALT in serum, content of TNF-alpha in serum and content of FFA in liver tissue and activity of ALT in serum.

Conclusion: The inhibiting effects of QHD on fat deposition and inflammation in liver are related with its inhibition on the "FFA-Ctsb-TNF-alpha" pathway of lipo-toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3736/jcim20080910DOI Listing
September 2008

Effect of JIANPI HUOXUE decoction on inflammatory cytokine secretion pathway in rat liver with lipopolysaccharide challenge.

World J Gastroenterol 2008 Mar;14(12):1851-7

Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528, Zhangheng Road, Shanghai 201203, China.

Aim: To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction (JHD) on cytokine secretion pathway in rat liver induced by lipopolysaccharide (LPS).

Methods: Twenty-four male SD rats were divided into normal group (n = 4), model group (n = 10) and JHD group (n = 10) randomly. Rats in model group and JHD group were administrated with normal saline or JHD via gastrogavage respectively twice a day for 3 d. One hour after the last administration, rats were injected with LPS via tail vein, 50 mug/kg. Simultaneously, rats in normal group were injected with equivalent normal saline. After LPS stimulation for 1.5 h, serum and liver tissue were collected. Pathological change of liver tissues was observed through hematoxylin-eosin (H.E.) staining. Tumor necrosis factor alpha (TNF-alpha) in serum were assayed by enzyme linked immunosorbent assay (ELISA). The protein expression of TNF-alpha, phosphorylated inhibit-kappaB (p-IkappaB) and CD68 in liver were assayed by Western blot. The distribution of CD68 protein in liver was observed through immunohistochemical staining. The mRNA expression of TNF-alpha, interleukin-6 (IL-6), CD14, toll-like receptor 2 (TLR2) and TLR4 in liver were assayed by real-time RT-PCR.

Results: Predominant microvesicular change, hepatocyte tumefaction and cytoplasm dilution were observed in liver tissues after LPS administration as well as obvious CD68 positive staining in hepatic sinusoidal. After LPS stimulation, serum TNF-alpha (31.35 +/- 6.06 vs 12225.40 +/- 9007.03, P < 0.05), protein expression of CD68 (1.13 +/- 0.49 vs 3.36 +/- 1.69, P < 0.05), p-IkappaB (0.01 +/- 0.01 vs 2.07 +/- 0.83, P < 0.01) and TNF-alpha (0.27 +/- 0.13 vs 1.29 +/- 0.37, P < 0.01) in liver and mRNA expression of TNF-alpha (1.96 +/- 2.23 vs 21.45 +/- 6.00, P < 0.01), IL-6 (4.80 +/- 6.42 vs 193.50 +/- 36.36, P < 0.01) and TLR2 (1.44 +/- 0.62 vs 4.16 +/- 0.08, P < 0.01) in liver were also increased significantly. These pathological changes were all improved in JHD group. On the other hand, TLR4 mRNA (1.22 +/- 0.30 vs 0.50 +/- 0.15, P < 0.05) was down-regulated and CD14 mRNA increased but not significantly after LPS stimulation.

Conclusion: JHD can inhibit cytokine secretion pathway induced by LPS in rat liver, which is probably associated with its regulation on CD68, p-IkappaB and endotoxin receptor TLR2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700410PMC
http://dx.doi.org/10.3748/wjg.14.1851DOI Listing
March 2008

[Microbial transformation of 4-ene-3-one steroids by Mucor racemosus].

Wei Sheng Wu Xue Bao 2007 Jun;47(3):540-3

College of Life Science and Technology, Heiloangiang August First Agricultural University, Daqing 163319, China.

A steroid-converting fungus isolated from soil samples, was identified as Mucor racemosus according to its morphological characters. The application of M. racemosus for biotransformation of 4-ene-3-one steroids had been investigated to obtain hydroxylated derivatives of 4-ene-3-one steroids. The substrates were incubated with M. racemosus in rotary shaker (220 rpm) culture for a period of four days at 27 degrees C. All of the fermentation media were exhaustively extracted with ethyl acetate and filtered to separate the both from the mycelium. The transformation products were separated on silica gel column chromatography. Each microbial metabolite was characterized by spectroscopic methods such as IR, MS and NMR. Fermentation of progesterone yielded 14alpha-hydroxypregn-4-en-3, 20-dione and 7alpha, 14alpha-dihydroxypregn-4-en-3, 20-dione. Incubation of androstenedione resulted in three transformation products: 14, 17-dihydroxyandrost-4-en-3-one, 14alpha, 17beta-dihydroxyandrost-4-en-3-one and 6alpha, 17beta-dihydroxyandrost-4-en-3-one. This fungus was found to biotransformation steroids. The results showed that the fermentation of 4-ene-3-one steroids with M. racemosus yielded mainly 14alpha-hydroxy steroids.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2007
-->