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1
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Taguchi D, Shirakami Y, Sakai H, Maeda T, Miwa T, Kubota M, Imai K, Ibuka T, Shimizu M. High-Fat Diet Delays Liver Fibrosis Recovery and Promotes Hepatocarcinogenesis in Rat Liver Cirrhosis Model. Nutrients 2024; 16:2506. [PMID: 39125385 PMCID: PMC11314319 DOI: 10.3390/nu16152506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/29/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
More effective treatments for hepatitis viral infections have led to a reduction in the incidence of liver cirrhosis. A high-fat diet can lead to chronic hepatitis and liver fibrosis, but the effects of lipid intake on liver disease status, including hepatitis C virus and alcohol, after elimination of the cause are unclear. To investigate the effects, we used a rat cirrhosis model and a high-fat diet in this study. Male Wistar rats were administered carbon tetrachloride for 5 weeks. At 12 weeks of age, one group was sacrificed. The remaining rats were divided into four groups according to whether or not they were administered carbon tetrachloride for 5 weeks, and whether they were fed a high-fat diet or control diet. At 12 weeks of age, liver fibrosis became apparent and then improved in the groups where carbon tetrachloride was discontinued, while it worsened in the groups where carbon tetrachloride was continued. Liver fibrosis was notable in both the carbon tetrachloride discontinuation and continuation groups due to the administration of a high-fat diet. In addition, liver precancerous lesions were observed in all groups, and tumor size and multiplicity were higher in the high-fat diet-fed groups. The expression of genes related to inflammation and lipogenesis were upregulated in rats fed a high-fat diet compared to their controls. The results suggest that a high-fat diet worsens liver fibrosis and promotes liver carcinogenesis, presumably through enhanced inflammation and lipogenesis, even after eliminating the underlying cause of liver cirrhosis.
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Affiliation(s)
| | - Yohei Shirakami
- Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
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Sorour A, Aly RG, Ragab HM, Wahid A. Structure Modification Converts the Hepatotoxic Tacrine into Novel Hepatoprotective Analogs. ACS OMEGA 2024; 9:2491-2503. [PMID: 38250371 PMCID: PMC10795119 DOI: 10.1021/acsomega.3c07126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 12/02/2023] [Accepted: 12/11/2023] [Indexed: 01/23/2024]
Abstract
The liver is responsible for critical functions such as metabolism, secretion, storage, detoxification, and the excretion of various compounds. However, there is currently no approved drug treatment for liver fibrosis. Hence, this study aimed to explore the potential hepatoprotective effects of chlorinated and nonchlorinated 4-phenyl-tetrahydroquinoline derivatives. Originally developed as tacrine analogs with reduced hepatotoxicity, these compounds not only lacked hepatotoxicity but also displayed a remarkable hepatoprotective effect. Treatment with these derivatives notably prevented the chemically induced elevation of hepatic indicators associated with liver injury. Additionally, the compounds restored the activities of defense antioxidant enzymes as well as levels of inflammatory markers (TNF-α and IL-6), apoptotic proteins (Bax and Bcl2), and fibrogenic mediators (α-SMA and TGF-β) to normal levels. Histopathologic analysis confirmed the hepatoprotective activity of tetrahydroquinolines. Furthermore, computer-assisted simulation docking results were highly consistent with those of the observed in vivo activities. In conclusion, the designed tacrine analogs exhibited a hepatoprotective role in acute liver damage, possibly through their antioxidative, anti-inflammatory, and antifibrotic effects.
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Affiliation(s)
- Amani
A. Sorour
- Department
of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Rania G. Aly
- Department
of Pathology, Faculty of Medicine, Alexandria
University, Alexandria 21521, Egypt
| | - Hanan M. Ragab
- Department
of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Ahmed Wahid
- Department
of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
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3
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Polysaccharide extract from Rosa laevigata fruit attenuates inflammatory obesity by targeting redox balance and gut interface in high-fat diet-fed rats. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2022.07.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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4
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Quan XX, Huang YY, Chen L, Yuan JQ. Traditional uses, phytochemical, pharmacology, quality control and modern applications of two important Chinese medicines from Rosa laevigata Michx.: A review. Front Pharmacol 2022; 13:1012265. [PMID: 36278229 PMCID: PMC9582767 DOI: 10.3389/fphar.2022.1012265] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 09/05/2022] [Indexed: 11/17/2022] Open
Abstract
Rosa laevigata Michx. is an ethnic medicine that have strong biological activities used in the traditional medicine system for the treatment of diabetes, nephropathy, myocardial damage, oxidative damage, liver damage and so on. Currently, The Chinese herb R. laevigata Michx. can be divided into two important medicines: Fructus R. laevigata and Radix R. laevigata, from which approximately 148 chemical components have been isolated, including flavonoids, lignans, polyphenols, steroids, triterpenoids, tannins as well as other components. Pharmacological studies have already confirmed that both of these herbs have antioxidant, anti-inflammatory, antiviral and anti-tumor activities, as well as renal protective, immunomodulatory, lipid-lowering, cardiovascular protective, bacteriostatic, and other pharmacological effects. Toxicological tests and quality control studies revealed the safety and nontoxicity of R. laevigata Michx. Therefore, this paper systematically summarizes the traditional uses, botanical, phytochemical, and pharmacology as well as the quality control and toxicology of Fructus and Radix, which in order to provide a comprehensive reference for its continued research.
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Affiliation(s)
- Xiao-Xiao Quan
- Scientific Experimental Center of Guangxi University of Chinese Medicine, Nanning, China
| | - Yuan-Yuan Huang
- Scientific Experimental Center of Guangxi University of Chinese Medicine, Nanning, China
| | - Lu Chen
- Guangxi Botanical Garden of Medicinal Plants, Nanning, China
| | - Jing-Quan Yuan
- Scientific Experimental Center of Guangxi University of Chinese Medicine, Nanning, China
- *Correspondence: Jing-Quan Yuan,
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Ko HM, Choi SH, Jee W, Lee SH, Park D, Jung JH, Lee BJ, Kim KI, Jung HJ, Jang HJ. Rosa laevigata Attenuates Allergic Asthma Exacerbated by Water-Soluble PM by Downregulating the MAPK Pathway. Front Pharmacol 2022; 13:925502. [PMID: 35837279 PMCID: PMC9274115 DOI: 10.3389/fphar.2022.925502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
Exposure to water-soluble particulate matter (WPM) containing heavy metals can cause severe inflammatory responses and trigger and exacerbate the onset of asthma. As a follow-up study of Rosa laevigata (RL), this study analyzed the therapeutic effects and mechanisms of oral and intratracheal administration of RL and demonstrated anti-inflammatory effects in asthma models. Worse T-helper cell type 2 (Th2)-related inflammatory and pro-inflammatory responses were observed after simultaneous challenge with ovalbumin (OVA) and WPM. To establish a model of asthma exacerbated by WPM, BALB/c mice were sensitized with OVA + aluminum hydroxide and challenged with OVA + WPM. To confirm the therapeutic efficacy of RL, it was administered both orally and intratracheally. Histopathological analysis of H&E staining confirmed that oral and intratracheal administration of RL alleviated inflammatory cell infiltration in the airways aggravated by OVA + WPM. RL effectively reduced the number of inflammatory cells obtained from the bronchoalveolar lavage fluid. In addition, enzyme-linked immunosorbent assay (ELISA) and multiplex analysis of serum samples confirmed that the administration of RL reduced the levels of immuno-globulin E (IgE), Th2-related cytokines, and pro-inflammatory cytokines. Furthermore, real-time PCR analysis of lung tissue samples confirmed that the release of MUC5AC (Mucin 5AC, Oligomeric Mucus/Gel-Forming) and pro-inflammatory cytokines was reduced by RL, and western blotting confirmed that the administration of RL reduced the phosphorylation of ERK and p38 in the MAPK pathway. In conclusion, oral and intratracheal administration of RL appears to have an anti-asthmatic effect by reducing the secretion of Th2-related cytokines, pro-inflammatory cytokines, and IgE by downregulating the MAPK pathway. Thus, RL has further demonstrated potential for development as an oral and inhaled therapeutic for asthma symptoms exacerbated by WPM exposure.
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Affiliation(s)
- Hyun Min Ko
- College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Seung-Han Choi
- College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Biological Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Wona Jee
- College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Seung-Hyeon Lee
- College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Doil Park
- College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Ji Hoon Jung
- College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Beom-Joon Lee
- Department of Biological Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
- Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Kwan-Il Kim
- Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Hee-Jae Jung
- Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Hyeung-Jin Jang
- College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea
- *Correspondence: Hyeung-Jin Jang,
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Liaqat M, Siddique K, Yousaf I, Bacha R, Farooq SMY, Gilani SA. Comparison between shear wave elastography and serological findings for the evaluation of fibrosis in chronic liver disease. J Ultrason 2021; 21:e186-e193. [PMID: 34540271 PMCID: PMC8438924 DOI: 10.15557/jou.2021.0030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 03/11/2021] [Indexed: 12/07/2022] Open
Abstract
Aim: In this study, we sought to examine the optimal cutoff values for predicting different stages of liver fibrosis, and to determine the level of agreement between shear wave elastography and aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4) scores in patients with chronic liver disease. Methodology: A descriptive, cross-sectional study was performed at the Radiology Department of Shaukat Khanum Memorial Hospital Lahore from 1 Jun 2019 until 1 June 2020. FIB-4 and APRI scores were determined by the following formula: FIB-4 = (age × AST) ÷ (platelet count × (√ (ALT)) and APRI = (AST÷AST upper limit of normal) ÷ platelet × 100. Data was analyzed with the help of SPSS version 24.0 and Microsoft Excel 2013. Results: Eighty individuals were conveniently selected, of which 62.5% were men and 37.5% were women. The mean age of the subjects was 43.47 SD ± 13.85 years. APRI and FIB-4 scores predicted F4 patients using the cutoff values of 0.47 (Sn. 72%, Sp. 70%) and 1.27 (Sn. 78%, Sp. 73%), respectively. The cutoff values of 0.46 for APRI and 1.27 for FIB-4 predicted F3–F4 patients (Sn. 74% and 77%; Sp. 76% and 76%), respectively. To predict F1–F4 compared to F0, the cutoff value was 0.34 (Sn. 68%, Sp. 75%) for APRI, while the cutoff value for FIB was 0.87 (Sn. 72%, Sp. 75%). The findings suggest that FIB-4 shows better diagnostic accuracy than APRI. Conclusion: This study provides optimal cutoff values for different groups of fibrosis patients for both serum markers. Also, the diagnostic accuracy of FIB-4 for predicting liver fibrosis was found to be superior to APRI in all disease stages.
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Affiliation(s)
| | | | | | - Raham Bacha
- Radiology, The University of Lahore, Pakistan
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Li BL, Yuan J, Wu JW. A Review on the Phytochemical and Pharmacological Properties of Rosa laevigata: A Medicinal and Edible Plant. Chem Pharm Bull (Tokyo) 2021; 69:421-431. [PMID: 33952852 DOI: 10.1248/cpb.c20-00743] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Rosa laevigata Michx., a medicinal and edible plant in China, has exerted a variety of medicinal values and health benefits. This present review aims to achieve a comprehensive and up-to-date investigation in the phytochemistry and pharmacology of R. laevigata. According to these findings in the literature, approximately 123 chemical ingredients covering triterpenoids, flavonoids, tannis, lignans and polysaccharides, have been characterized from various parts of this species. Among these isolates, 77 triterpenoids have been isolated and thus regarded as the primary and characteristic substance. Based on the chemical structures, most of the obtained triterpenoids can be classified into polyhydroxy triterpenoids and readily divided into four categories: ursane-type, oleanane-type, lupinane-type, as well as seco-triterpenoids. The crude extracts and the purified compounds have demonstrated various pharmacological effects in vitro and in vivo, such as antioxidant activity, immunomodulatory effect, anti-inflammatory effect, liver protection, kidney protection, cardiovascular protection, neuroprotective effect and improvement of diabetic cataract. Noticeably, these pharmacological results of R. laevigata provide evidences for its traditional uses. In addition, these different chemical ingredients existing in the title plant may have synergistic effects. In conclusion, the chemical profiles, including ingredients and structures, together with the modern pharmacological properties have been adequately summarized. These evidences have revealed this plant to be a valuable source for therapeutic foodstuff and more attention should be paid to a better utilization of this plant.
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Affiliation(s)
- Bai-Lin Li
- Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine
| | - Jie Yuan
- Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine
| | - Jie-Wei Wu
- Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine
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8
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Li H, Fang W, Wang Z, Chen Y. Physicochemical, biological properties, and flavour profile of Rosa roxburghii Tratt, Pyracantha fortuneana, and Rosa laevigata Michx fruits: A comprehensive review. Food Chem 2021; 366:130509. [PMID: 34339923 DOI: 10.1016/j.foodchem.2021.130509] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 06/11/2021] [Accepted: 06/27/2021] [Indexed: 01/24/2023]
Abstract
In China, three Rosaceae fruits with distinctive flavours and functions have recently been transformed from edible plants into standardised juice or beverage products. To enhance the development of these fruit products, the results and conclusions from various investigations of the chemical and biological properties of fruits should be summarised. Based on industrial advances, there are still some limitation in the research and development of these fruit products that need to be addressed. Therefore, in this report, we provided a comprehensive and rigorous review to summarise critical data from phytochemical and biological investigations and from flavour profiles and industrial development of these fruit products. Our goal is to provide insights into recent research findings in order to advance studies and developments of products of these flavourful fruits from a reasonable perspective.
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Affiliation(s)
- Huan Li
- Department of Biopharmaceuticals and Materials Engineering, Zhuhai Campus Zunyi Medical University, Zhuhai, Guangdong, China
| | - Wangyang Fang
- Department of Biopharmaceuticals and Materials Engineering, Zhuhai Campus Zunyi Medical University, Zhuhai, Guangdong, China
| | - Ze Wang
- Department of Biopharmaceuticals and Materials Engineering, Zhuhai Campus Zunyi Medical University, Zhuhai, Guangdong, China.
| | - Yang Chen
- Department of Biopharmaceuticals and Materials Engineering, Zhuhai Campus Zunyi Medical University, Zhuhai, Guangdong, China; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, China.
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9
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Abd Elkader HTAE, Abdou HM, Khamiss OA, Essawy AE. Anti-anxiety and antidepressant-like effects of astragaloside IV and saponins extracted from Astragalus spinosus against the bisphenol A-induced motor and cognitive impairments in a postnatal rat model of schizophrenia. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:35171-35187. [PMID: 33666843 DOI: 10.1007/s11356-021-12927-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 02/08/2021] [Indexed: 06/12/2023]
Abstract
Bisphenol A (BPA) is a chemical endocrine disruptor to which humans are often exposed in daily life. Postnatal administration of BPA results in schizophrenia (SCZ)-like behaviours in rats. The present study was designed to elucidate whether treatment with astragaloside IV (ASIV) or saponins extracted from Astragalus spinosus improves the neurobehavioural and neurochemical disturbances induced by BPA. Fifty-two juvenile (PND20) male Sprague Dawley rats were divided into four groups. The rats in Group I were considered the control rats, while the rats in Group II were orally administered BPA (125 mg/kg) daily from PND20 to adult age (PND117). The rats in the third and fourth groups were administered BPA (125 mg/kg/day) supplemented with astragaloside IV (80 mg/kg/d) on PND20 or A. spinosus saponins (100 mg/kg/d) from PND50 to PND117, respectively. Administration of ASIV and saponins extracted from Astragalus spinosus reversed the anxiogenic and depressive-like behaviours and the social defects that were observed in the rats treated with BPA alone. Additionally, these compounds improved memory impairments, restored dopamine (DA), serotonin (5-HT), and monoamine oxidase (MAO-A) levels and normalized Tph2 mRNA expression towards the control values. Taken together, it can be concluded that orally administered ASIV and A. spinosus saponins exhibit neuroprotective effects and that these compounds can be used as therapeutic strategies against BPA-induced neuropsychiatric symptoms in a rat model of SCZ.
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Affiliation(s)
| | - Heba Mohamed Abdou
- Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
| | - Omaima Ahmed Khamiss
- Department of Genetic Engineering and Biotechnology, Institute of Genetic Engineering and Biotechnology, Sadat City University, Sadat City, Egypt
| | - Amina Essawy Essawy
- Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
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10
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Sayed AM, Hassanein EH, Salem SH, Hussein OE, Mahmoud AM. Flavonoids-mediated SIRT1 signaling activation in hepatic disorders. Life Sci 2020; 259:118173. [DOI: 10.1016/j.lfs.2020.118173] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/18/2020] [Accepted: 07/27/2020] [Indexed: 02/07/2023]
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11
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Ren Y, Li HX, Zhou L, Lu ZM, Shi J, Geng Y, Xu ZH. Protective Effect of Spore Powder of Antrodia camphorata ATCC 200183 on CCl 4-Induced Liver Fibrosis in Mice. Nutrients 2020; 12:nu12092778. [PMID: 32932919 PMCID: PMC7551437 DOI: 10.3390/nu12092778] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 09/06/2020] [Accepted: 09/09/2020] [Indexed: 02/07/2023] Open
Abstract
Liver fibrosis is a pathological process with intrahepatic diffused deposition of the excess extracellular matrix, which leads to various chronic liver diseases. Drugs with high efficacy and low toxicity for liver fibrosis are still unavailable. Antrodia camphorata has antioxidant, antivirus, antitumor and anti-inflammation roles, and has been used to treat liver diseases in the population. However, the hepatoprotective effects of A. camphorata spores and the mechanisms behind it have not been investigated. In this study, we evaluate the hepatoprotective effect of spore powder of A. camphorata (SP, 100 mg/kg/day or 200 mg/kg/day) on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. SP groups reduced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities compared with the CCl4 group. SP also showed a decrease in hydroxyproline (Hyp) content in liver tissues. SP improved cell damage and reduced collagen deposition by H&E, Sirius red and Masson staining. Furthermore, SP down-regulated the mRNA levels of α-SMA and Col 1, and the protein expression of α-smooth muscle actin (α-SMA), collagen I (Col 1), tumor necrosis factor alpha (TNF-α), toll like receptor 4 (TLR4) and nuclear factor-Κb (NF-κB) p65. In summary, SP has an ameliorative effect on hepatic fibrosis, probably by inhibiting the activation of hepatic stellate cells, reducing the synthesis of extracellular matrix.
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Affiliation(s)
- Yilin Ren
- School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China; (Y.R.); (J.S.)
- National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China; (Z.-M.L.); (Z.-H.X.)
- Jiangsu Engineering Research Center for Bioactive Products Processing Technology, Jiangnan University, Wuxi 214122, China
| | - Hua-Xiang Li
- College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, China;
| | - Lingxi Zhou
- Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China;
| | - Zhen-Ming Lu
- National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China; (Z.-M.L.); (Z.-H.X.)
- Jiangsu Engineering Research Center for Bioactive Products Processing Technology, Jiangnan University, Wuxi 214122, China
| | - Jinsong Shi
- School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China; (Y.R.); (J.S.)
| | - Yan Geng
- School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China; (Y.R.); (J.S.)
- Correspondence: ; Tel.: +86-510-85918206
| | - Zheng-Hong Xu
- National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China; (Z.-M.L.); (Z.-H.X.)
- Jiangsu Engineering Research Center for Bioactive Products Processing Technology, Jiangnan University, Wuxi 214122, China
- Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China;
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Huang X, Chen W, Yan C, Yang R, Chen Q, Xu H, Huang Y. Gypenosides improve the intestinal microbiota of non-alcoholic fatty liver in mice and alleviate its progression. Biomed Pharmacother 2019; 118:109258. [DOI: 10.1016/j.biopha.2019.109258] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 07/19/2019] [Accepted: 07/19/2019] [Indexed: 01/02/2023] Open
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13
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Li X, Yao Q, Huang J, Jin Q, Xu B, Chen F, Tu C. Morin Hydrate Inhibits TREM-1/TLR4-Mediated Inflammatory Response in Macrophages and Protects Against Carbon Tetrachloride-Induced Acute Liver Injury in Mice. Front Pharmacol 2019; 10:1089. [PMID: 31616301 PMCID: PMC6763683 DOI: 10.3389/fphar.2019.01089] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Accepted: 08/26/2019] [Indexed: 12/29/2022] Open
Abstract
This study aims to investigate the protective effects of morin hydrate (MH) against acute liver injury induced by carbon tetrachloride (CCl4) in mice and to elucidate the possible molecular mechanism of action. Mice were pretreated with MH (50 mg/kg body weight) or vehicle by oral gavage once daily for 5 days, followed by intraperitoneal injection of a single dose of CCl4 (1 ml/kg in olive oil). Mice were sacrificed 24 h later; the blood and liver samples were harvested for analysis. We also used the model of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in vitro and examined the effects of MH and its mechanism of action on the inflammatory response. Our results revealed that MH remarkably attenuated liver histopathological alterations, serum transaminases, hepatocytes death, and inflammatory response induced by CCl4. Importantly, MH reduced expression of the triggering receptor expressed on myeloid cells-1 (TREM-1) and toll-like receptor 4 (TLR4) both in vivo and in vitro experiments. This inhibitory effect MH on expression of the TREM-1 and TLR4 in cell culture was further heightened after TREM-1 knockdown with small interfering RNA (siRNA). Moreover, MH dramatically suppressed the inhibitor of kappa B α (IκBα) degradation and subsequent nuclear factor-kappa B (NF-κB) p65 translocation into the nucleus and NF-κB-mediated cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6. Additionally, MH also ameliorated CCl4-induced oxidative stress by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in the injured livers. Taken together, MH has hepatoprotective activity, and this effect may be elicited by attenuating macrophage-mediated inflammatory responses via inhibition TREM-1/TLR4/NF-κB signaling and by regulating hepatic oxidative stress via enhancement Nrf2/HO-1 antioxidant pathway.
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Affiliation(s)
- Xi Li
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qunyan Yao
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiying Huang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China
| | - Qianwen Jin
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Beili Xu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Fangyuan Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chuantao Tu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
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Ou Z, Zhao J, Zhu L, Huang L, Ma Y, Ma C, Luo C, Zhu Z, Yuan Z, Wu J, Li R, Yi J. Anti-inflammatory effect and potential mechanism of betulinic acid on λ-carrageenan-induced paw edema in mice. Biomed Pharmacother 2019; 118:109347. [PMID: 31545273 DOI: 10.1016/j.biopha.2019.109347] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 08/05/2019] [Accepted: 08/07/2019] [Indexed: 12/24/2022] Open
Abstract
λ-Carrageenan (Carr), a seaweed polysaccharide, is used as a proinflammatory agent in research. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exerts immunomodulatory, antioxidant, anti-inflammatory, antitumor, anti-malarial and anti-HIV effects. The aim of this study was to investigate whether BA exerts anti-inflammatory effect against Carr-induced paw edema in mice, and how BA could mediate the expression of inflammation-associated MAPK-COX-2-PGE2 signal pathway. BA pretreatment significantly reduced the inflammatory response to Carr-induced paw edema, especially at 4 h after injection. BA reduced the serum levels of pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-5, IL-6, GM-CSF, KC, MCP-1 and PGE2 in Carr-treated mice, and increased those of anti-inflammatory cytokines, such as IL-12. It also increased SOD, CAT and GSH-Px activities, and GSH content, and reduced MDA content in the liver of Carr-treated mice. Besides, BA reduced neutrophil infiltration in the basal and subcutaneous layers of the paw of Carr-treated mice, decreased the expression of COX-2 protein, and reduced the phosphorylation of JNK, p38 and ERK1/2. These results indicated that the protective effect of BA on Carr-induced paw edema might be due to its alleviation of inflammatory response and inhibition of oxidative stress, possibly by inhibiting MAPK-COX-2-PGE2 signaling pathway activation.
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Affiliation(s)
- Zhaoping Ou
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China
| | - Jing Zhao
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China
| | - Lijuan Zhu
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China
| | - Lin Huang
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China
| | - Yurong Ma
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China
| | - Chaoyang Ma
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China
| | - Chenxi Luo
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China
| | - Zihan Zhu
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China
| | - Zhihang Yuan
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China; Hunan Co-innovation Center of Animal Production Safety, Changsha City, 410128, China
| | - Jing Wu
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China; Hunan Co-innovation Center of Animal Production Safety, Changsha City, 410128, China
| | - Rongfang Li
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China; Hunan Co-innovation Center of Animal Production Safety, Changsha City, 410128, China.
| | - Jine Yi
- College of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China; Hunan Co-innovation Center of Animal Production Safety, Changsha City, 410128, China.
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15
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Barghi M, Ashrafi M, Aminlari M, Namazi F, Nazifi S. The protective effect of Zataria multiflora Boiss essential oil on CCl 4 induced liver fibrosis in rats. Drug Chem Toxicol 2019; 44:229-237. [PMID: 30746963 DOI: 10.1080/01480545.2019.1571502] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Activation of hepatic stellate cells by free radicals is an initial step in the development of liver fibrosis. Zataria multiflora Boiss (ZM) essential oil as a natural product has antioxidant activity and maybe a suitable candidate for treatment or prevention of the disease. Thus, this study aims to evaluate the protective effect of ZM oil in CCl4 induced liver fibrosis. Male rats were divided into 5 groups, group C: control rats; CO: vehicle control group; CE: rats that received essential oil (500 µl/kg); F: fibrosis group, rat were intraperitoneally injected with CCl4 (1 mL/kg); FE: fibrosis rats that received both CCl4 and ZM essential oil as mentioned above. At the end of the 11th week, serum samples and liver tissues were collected for the evaluation of fibrosis markers, liver enzymes, oxidative stress parameters and histopathological studies. The results showed a significant increase in the activity of serum AST, ALT, total bilirubin, TGF-β1, hyaluronan, and hydroxyproline levels in serum and liver tissues in F group. Also, an abnormality in lipid profile and the existence of oxidative stress was found in serum and liver tissues in F group compared to the control groups. Our study showed that ZM essential oil could ameliorate mentioned parameters. Histopathological examinations confirmed the results of biochemical evaluations.
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Affiliation(s)
- Maryam Barghi
- Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Mahboobeh Ashrafi
- Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Mahmoud Aminlari
- Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Fateme Namazi
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Saeed Nazifi
- Department of Clinical Studies, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
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16
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Jia N, Lin X, Ma S, Ge S, Mu S, Yang C, Shi S, Gao L, Xu J, Bo T, Zhao J. Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice. Nutr Metab (Lond) 2018; 15:86. [PMID: 30555521 PMCID: PMC6282400 DOI: 10.1186/s12986-018-0323-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 11/26/2018] [Indexed: 02/07/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is a chronic and progressive liver disease with an increased risk of morbidity and mortality. However, so far no specific pharmacotherapy has been approved. Gynostemma pentaphylla (Thunb.) Makino (GP) is a traditional Chinese medicine that is widely used against hyperlipemia as well as hyperglycemia. This study aims to evaluate the effect of GP on NAFLD and explore the possible mechanism. Methods High-fat-diet induced NAFLD mice model were orally administrated with GP at dose of 11.7 g/kg or equivalent volume of distilled water once a day for 16 weeks. Body weight, food intake and energy expenditure were assessed to evaluate the general condition of mice. The triglycerides, total cholesterol content in the liver and liver histopathology, serum lipid profile and serum insulin level, fecal microbiome, hepatic microRNAs and relative target genes were analyzed. Results Mice in GP treatment group displayed improved hepatic triglycerides content with lower lipid droplet in hepatocyte and NAFLD activity score. Besides, GP treatment altered the composition of gut microbiota and the relative abundance of some of the key components that are implicated in metabolic disorders, especially phylum Firmicutes (Eubacterium, Blautia, Clostridium and Lactobacillus). Several hepatic microRNAs were downregulated by GP treatment such as miR-130a, miR-34a, miR-29a, miR-199a, among which the expression miR-34a was altered by more than four-fold compared to that of HFD group (3:14). The correlation analysis showed that miR-34a was strongly related to the change of gut microbiota especially phylum Firmicutes (R = 0.796). Additionally, the target genes of miR-34a (HNF4α, PPARα and PPARα) were restored by GP both in mRNA and protein levels. Conclusion Our results suggested that GP modulated the gut microbiota and suppressed hepatic miR-34a, which was associated with the amelioration of hepatic steatosis.
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Affiliation(s)
- Ning Jia
- 1Shandong University of Traditional Chinese Medicine, Jinan, 250355 China.,2Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021 China.,Shandong Provincial Key Laboratory of Institute of Endocrinology and Lipid Metabolism, Jinan, 250021 China.,Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021 China
| | - Xiaoyan Lin
- 6Department of Pathology, Shandong Provincial Hospital affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 China
| | - Shizhan Ma
- 2Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021 China.,Shandong Provincial Key Laboratory of Institute of Endocrinology and Lipid Metabolism, Jinan, 250021 China.,Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021 China
| | - Shujian Ge
- 7Department of Scientific Research, Shandong Provincial Hospital affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 China
| | - Shumin Mu
- 8Department of Endocrinology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014 China
| | - Chongbo Yang
- 2Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021 China.,Shandong Provincial Key Laboratory of Institute of Endocrinology and Lipid Metabolism, Jinan, 250021 China.,Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021 China
| | - Shulong Shi
- 1Shandong University of Traditional Chinese Medicine, Jinan, 250355 China.,2Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021 China.,Shandong Provincial Key Laboratory of Institute of Endocrinology and Lipid Metabolism, Jinan, 250021 China.,Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021 China
| | - Ling Gao
- Shandong Provincial Key Laboratory of Institute of Endocrinology and Lipid Metabolism, Jinan, 250021 China.,Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021 China.,5Scientific Center, Shandong Provincial Hospital affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 China
| | - Jin Xu
- 2Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021 China.,Shandong Provincial Key Laboratory of Institute of Endocrinology and Lipid Metabolism, Jinan, 250021 China.,Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021 China
| | - Tao Bo
- 5Scientific Center, Shandong Provincial Hospital affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 China
| | - Jiajun Zhao
- 1Shandong University of Traditional Chinese Medicine, Jinan, 250355 China.,2Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021 China.,Shandong Provincial Key Laboratory of Institute of Endocrinology and Lipid Metabolism, Jinan, 250021 China.,Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021 China
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17
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Wang Y, Guan M, Zhao X, Li X. Effects of garlic polysaccharide on alcoholic liver fibrosis and intestinal microflora in mice. PHARMACEUTICAL BIOLOGY 2018; 56:325-332. [PMID: 29969576 PMCID: PMC6130653 DOI: 10.1080/13880209.2018.1479868] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
CONTEXT Alcoholic liver fibrosis (ALF) is treatable and reversible consequence of liver disease. Intestinal microflora plays an important role in the progression of liver disease. Garlic (Allium sativum L. [Amaryllidaceae]) has been consumed as a traditional medicine to treat liver injury. OBJECTIVE To investigate the effects of garlic polysaccharide (GP) on ALF and intestinal microflora in mice. MATERIALS AND METHODS KM mice were orally administered with alcohol (56%, 6 mL/kg) for 30 d to establish ALF model, and divided into four groups together with control group (water only). Hugan tablet (60 mg/kg) or GP (250 and 150 mg/kg) were given 5 h after each dose of alcohol. Biochemical markers in serum and liver homogenate were determined with kits. Alteration of intestinal microflora, and protein expressions of TGF-β1, TNF-α and decorin were detected. RESULTS In GP-H group, ALT and AST decreased to 18.85 ± 4.71 U/L and 40.84 ± 7.89 U/L. MDA, TC, TG and LDL-C decreased to 2.32 ± 0.86 mmol/mg, 0.21 ± 0.12 mmol/L, 0.96 ± 0.31 mmol/L and 0.084 ± 0.027 mmol/L. SOD, GSH-Px and GSH increased to 118.32 ± 16.32 U/mg, 523.72 ± 64.20 U/mg and 0.56 ± 0.05 mg/g. Ratios of TGF-β1 and TNF-α decreased to 0.608 ± 0.170 and 1.057 ± 0.058, decorin increased to 2.182 ± 0.129. Lachnospiraceae and Lactobacillus increased, Facklamia and Firmicutes decreased with GP pretreatment. DISCUSSION AND CONCLUSIONS Intestinal microflora provides novel insight into the mechanisms of GP that may be used to treat ALF and intestinal microflora dysbiosis.
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Affiliation(s)
- Yuchuan Wang
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, PR China
| | - Min Guan
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, PR China
| | - Xin Zhao
- Department of Biotechonolgy, Dalian Medical University, Dalian, PR China
| | - Xinli Li
- Department of Biotechonolgy, Dalian Medical University, Dalian, PR China
- CONTACT Xinli Li Department of Biotechnology, Dalian Medical University, No. 9, West-Middle Section of Lvshun South Road, Dalian116044, Liaoning, PR China
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18
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Lv J, Bai R, Wang L, Gao J, Zhang H. Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells. BMC Pharmacol Toxicol 2018; 19:64. [PMID: 30326962 PMCID: PMC6192352 DOI: 10.1186/s40360-018-0255-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 10/01/2018] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND An increasing number of studies are investigating the effects of Chinese medicine on hepatic fibrosis, but only few studies have examined the anti-fibrogenic properties of Artesunate (ART). The aim of the present study was to explore the anti-fibrotic effects of ART on LX-2 cells, the human HSC cell line, and to determine potential molecular mechanisms via the focal adhesion kinase (FAK)/ protein kinase B (Akt)/ β-catenin pathway. METHODS LX-2 cells were stimulated with different concentration of ART (0, 12.5, 25 and 50 μg/ml) for 12, 24, 48 or 72 h, their proliferation was analyzed using the Cell Counting Kit-8 (CCK-8) assay. LX-2 cells were treated with different doses of ART (0, 12.5, 25 and 50 μg/ml) for 24 h, their apoptosis was measured using flow cytometry, the levels of mRNAs encoding collagen I or α-smooth muscle actin (α-SMA) were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the levels of key proteins in the FAK/Akt/β-catenin signaling pathway were assessed by western blotting. Specific inhibitors of FAK were added to the LX-2 cells cultures to explore the potential signaling. RESULTS Exposing LX-2 cells to ART efficiently inhibited their proliferation, significantly promoted early apoptosis in a dose-dependent manner, and markedly downregulated the mRNA expression of α-SMA and collagen I. In addition, ART, similar to FAK inhibitor PF562271 significantly inhibited the FAK/Akt/β-catenin signaling pathway by reducing the levels of phosphorylated FAK, Akt and GSK-3β. CONCLUSIONS Our present study shows that ART could regulate the proliferation, apoptosis and activation of LX-2. Meanwhile, the anti-fibrogenic mechanisms of ART was correlated with FAK/Akt/β-catenin pathway. Future research should verify and extend these findings, as well as explore other molecules and therefore serve as useful therapeutic targets.
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Affiliation(s)
- Jian Lv
- Department of Pharmacy, Renmin Hospital of Wuhan University, Zhang Zhidong Road, Wuhan, Hubei, 430060, People's Republic of China
| | - Ruidan Bai
- Department of Pharmacy, Renmin Hospital of Wuhan University, Zhang Zhidong Road, Wuhan, Hubei, 430060, People's Republic of China
| | - Li Wang
- Department of Pharmacy, Renmin Hospital of Wuhan University, Zhang Zhidong Road, Wuhan, Hubei, 430060, People's Republic of China
| | - Jiefang Gao
- Department of Pharmacy, Renmin Hospital of Wuhan University, Zhang Zhidong Road, Wuhan, Hubei, 430060, People's Republic of China
| | - Hong Zhang
- Department of Pharmacy, Renmin Hospital of Wuhan University, Zhang Zhidong Road, Wuhan, Hubei, 430060, People's Republic of China.
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19
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Karimi J, Mohammadalipour A, Sheikh N, Khodadadi I, Hashemnia M, Goudarzi F, Khanjarsim V, Solgi G, Hajilooi M, Bahabadi M, Kheiripour N, Hedayatyanfard K. Protective effects of combined Losartan and Nilotinib on carbon tetrachloride (CCl 4)-induced liver fibrosis in rats. Drug Chem Toxicol 2018; 43:468-478. [PMID: 30207194 DOI: 10.1080/01480545.2018.1504960] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Tyrosine kinase inhibitors (TKIs) have been developed as therapeutic compounds for inhibiting the progression of liver fibrosis. In the present study, the simultaneous treatment of Nilotinib (TKIs) and Losartan was studied. Forty rats were divided into eight groups of fibrosis induced by carbon tetrachloride (CCl4) and therapeutics (Nilotinib, Losartan, and combination therapy). In the end, serum parameters of the liver and gene expression analysis of transforming growth factor-β1, its receptors (TβRII), platelet-derived growth factor, its receptors (PDGFRβ), matrix metalloproteinases (MMP-2 and MMP-9), tumor necrosis factor-α, cytochrome P450 2E1, and collagen1 type 1 were performed. The oxidant/antioxidant factors were also analyzed. Histopathology analysis along with α-SMA immunohistochemistry and hydroxyproline evaluation was also conducted for a more in-depth study. The overall results indicated a better therapeutic effect of co-treatment of Nilotinib-Losartan in comparison with the treatment of each of them alone. Interestingly, some gene and protein factors and fibrotic indices were reduced even to the normal levels of the control group. The results of this study suggest that co-administration of these two combinations, strengthens their anti-fibrotic properties and, due to the routine use of these compounds against AML and blood pressure, these compounds can be used with caution against human liver fibrosis.
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Affiliation(s)
- Jamshid Karimi
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.,Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Adel Mohammadalipour
- Faculty of Pharmacy and Pharmaceutical Sciences, Department of Clinical Biochemistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nasrin Sheikh
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Iraj Khodadadi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mohammad Hashemnia
- Veterinary Medicine Faculty, Departments of Pathobiology, Razi University, Kermanshah, Iran
| | - Farjam Goudarzi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Vahid Khanjarsim
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ghasem Solgi
- Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mehrdad Hajilooi
- Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Majid Bahabadi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Nejat Kheiripour
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Keshvad Hedayatyanfard
- Faculty of Medicine, Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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20
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Yang YQ, Yan XT, Wang K, Tian RM, Lu ZY, Wu LL, Xu HT, Wu YS, Liu XS, Mao W, Xu P, Liu B. Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF-κB Signaling Pathways. Front Pharmacol 2018; 9:999. [PMID: 30210350 PMCID: PMC6124152 DOI: 10.3389/fphar.2018.00999] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 08/14/2018] [Indexed: 12/11/2022] Open
Abstract
Nrf2 (Nuclear Factor Erythroid 2 Related Factor 2) transcription factor not only regulates oxidative stress response, but also represses inflammation by regulating cytokines production and cross-talking with NF-κB signaling pathways. Nrf2 plays an essential role in liver injury induced by oxidative stress and inflammation. Triptriolide (T11) is a minor component of Tripterygium wilfordii Hook F. (TwHF), which can be obtained by hydrolysis reaction of triptolide (T9). The major purpose of this study is to clarify the regulating effects of T11 on oxidative stress and inflammation in vivo and in vitro. LPS-stimulated RAW 264.7 cells were used to verify the regulating effects of T11 on oxidative stress (ROS and Nrf2 signaling pathway) and inflammatory cytokines production (TNF-α, IL-6 and IL-1β). The antioxidant responsive element (ARE) luciferase assay was employed to evaluate Nrf2 activation effect of T11 in HEK-293T cells. Lipopolysaccharides (LPS) induced acute liver injury (ALI) in BALB/c mice were used to study the protective effects (ALT, AST, MDA, SOD, histopathology and neutrophils/macrophages filtration) and the underlying protection mechanisms of ALI amelioration (Nrf2 and NF-κB signaling pathway) of T11. Firstly, the results showed that T11 can not only effectively decrease the productions of inflammatory cytokines (TNF-α, IL-6 and IL-1β), ROS and NO in LPS-stimulated RAW 264.7 cells, but also further significantly increase the activity of Nrf2 in HEK-293T cells. Secondly, the results suggested that T11 could dramatically decrease the oxidative stress responses (SOD and MDA) and inflammation (histopathology, neutrophils/macrophages filtration, TNF-α, IL-6 and IL-1β production) in LPS-induced ALI in BALB/c mice. Finally, the results implied that T11 could dramatically increase Nrf2 protein expression and decrease p-TAK1, p-IκBα and NF-κB protein expression both in vivo and in vitro. In conclusion, our findings indicated that T11 could alleviate LPS induced oxidative stress and inflammation by regulating Nrf2 and NF-κB signaling pathways in vitro and in vivo, which offers a novel insights for the application of TwHF in clinical.
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Affiliation(s)
- Yi-Qi Yang
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiao-Teng Yan
- Affiliated Huai'an Hospital, Xuzhou Medical University, Huai'an, China
| | - Kai Wang
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Rui-Min Tian
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Zhao-Yu Lu
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Li-Lan Wu
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Hong-Tao Xu
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China
| | - Yun-Shan Wu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.,Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Xu-Sheng Liu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.,Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Wei Mao
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.,Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Peng Xu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.,Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Bo Liu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.,Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
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21
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Sheng RF, Jin KP, Yang L, Wang HQ, Liu H, Ji Y, Fu CX, Zeng MS. Histogram Analysis of Diffusion Kurtosis Magnetic Resonance Imaging for Diagnosis of Hepatic Fibrosis. Korean J Radiol 2018; 19:916-922. [PMID: 30174481 PMCID: PMC6082766 DOI: 10.3348/kjr.2018.19.5.916] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Accepted: 02/09/2018] [Indexed: 12/22/2022] Open
Abstract
Objective To investigate the diagnostic value of diffusion kurtosis imaging (DKI) histogram analysis in hepatic fibrosis staging. Materials and Methods Thirty-six rats were divided into carbon tetrachloride-induced fibrosis groups (6 rats per group for 2, 4, 6, and 8 weeks) and a control group (n = 12). MRI was performed using a 3T scanner. Histograms of DKI were obtained for corrected apparent diffusion (D), kurtosis (K) and apparent diffusion coefficient (ADC). Mean, median, skewness, kurtosis and 25th and 75th percentiles were generated and compared according to the fibrosis stage and inflammatory activity. Results A total of 35 rats were included, and 12, 5, 5, 6, and 7 rats were diagnosed as F0–F4. The mean, median, 25th and 75th percentiles, kurtosis of D map, median, 25th percentile, skewness of K map, and 75th percentile of ADC map demonstrated significant correlation with fibrosis stage (r = −0.767 to 0.339, p < 0.001 to p = 0.039). The fibrosis score was the independent variable associated with histogram parameters compared with inflammatory activity grade (p < 0.001 to p = 0.041), except the median of K map (p = 0.185). Areas under the receiver operating characteristic curve of D were larger than K and ADC maps in fibrosis staging, although no significant differences existed in pairwise comparisons (p = 0.0512 to p = 0.847). Conclusion Corrected apparent diffusion of DKI histogram analysis provides added value and better diagnostic performance to detect various liver fibrosis stages compared with ADC.
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Affiliation(s)
- Ruo-Fan Sheng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Kai-Pu Jin
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - He-Qing Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Hao Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Cai-Xia Fu
- MR Collaboration NEA, Siemens Ltd. China, Shanghai 201318, China
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
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22
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Li X, Zhu L, Wang B, Yuan M, Zhu R. Drugs and Targets in Fibrosis. Front Pharmacol 2017; 8:855. [PMID: 29218009 PMCID: PMC5703866 DOI: 10.3389/fphar.2017.00855] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 11/08/2017] [Indexed: 01/18/2023] Open
Abstract
Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, the majority of fibrosis treatment strategies are limited to specific diseases or organs. However, accumulating evidence demonstrates great similarities among fibroproliferative diseases, and more and more drugs are proved to be effective anti-fibrotic therapies across different diseases and organs. Here we comprehensively review the current knowledge on the pathological mechanisms of fibrosis, and divide factors mediating fibrosis progression into extracellular and intracellular groups. Furthermore, we systematically summarize both single and multiple component drugs that target fibrosis. Future directions of fibrosis drug discovery are also proposed.
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Affiliation(s)
- Xiaoyi Li
- Department of Gastroenterology, School of Life Sciences and Technology, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Lixin Zhu
- Department of Pediatrics, Digestive Diseases and Nutrition Center, State University of New York at Buffalo, Buffalo, NY, United States
- Genome, Environment and Microbiome Community of Excellence, State University of New York at Buffalo, Buffalo, NY, United States
| | - Beibei Wang
- Department of Gastroenterology, School of Life Sciences and Technology, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Meifei Yuan
- Center for Drug Discovery, SINO High Goal Chemical Technology Co., Ltd., Shanghai, China
| | - Ruixin Zhu
- Department of Gastroenterology, School of Life Sciences and Technology, Shanghai East Hospital, Tongji University, Shanghai, China
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Guo Y, Liang X, Meng M, Chen H, Wei X, Li M, Li J, Huang R, Wei J. Hepatoprotective effects of Yulangsan flavone against carbon tetrachloride (CCl 4)-induced hepatic fibrosis in rats. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2017; 33:28-35. [PMID: 28887917 DOI: 10.1016/j.phymed.2017.07.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 05/22/2017] [Accepted: 07/02/2017] [Indexed: 06/07/2023]
Abstract
BACKGROUND Yulangsan flavone (YLSF) was extracted from the root of Millettia pulchra Kurz var-laxior (Dunn) Z. Wei, which has been widely used for liver disease treatment in the Guangxi province of China. HYPOTHESIS/PURPOSE The study was conducted to demonstrate the hepatoprotective effects of YLSF against CCl4-induced hepatic fibrosis in rats, meanwhile revealing the potential mechanism. STUDY DESIGN Sprague-Dawley (SD) rats of both sexes were randomly divided into two groups: hepatic fibrosis group and normal control (NC) group. The rats in the hepatic fibrosis group were given 1 ml/kg 50% CCl4 (1:1 mixed with peanut oil), while those in the NC group were given 1 ml/kg normal saline (NS), both via intragastric administration. The established experimental rat model from the hepatic fibrosis group was confirmed by pathological inspection and randomly divided into five groups: three YLSF groups (20 mg/kg, 40 mg/kg and 80 mg/kg), a colchicine group (0.20 mg/kg) and a model group (10 ml/kg NS). All rats were treated with corresponding drugs or NS once a day for four consecutive weeks. Twenty-four hours after the last administration, blood serum and hepatic tissue were collected. METHODS The activities of ALT and AST in the serum and the levels of SOD, MDA, GSH and GSH-Px in hepatic tissue were analysed, the indexes of liver, spleen and thymus were counted, the degree of hepatic injury was examined using HE and Masson staining, and the mRNA expression of Col-1, TIMP-1 and TGF-β1 in hepatic tissues was detected. RESULTS Compared with the model group, experimental results showed that YLSF and colchicine could reduce the levels of AST, ALT and MDA, increase the levels of SOD, GSH and GSH-Px, enhance rat survivability, decrease the liver, spleen and thymus index, significantly lessen collagen deposition and tissue damage and down-regulate the mRNA expression of Col-1, TIMP-1 and TGF-β1. CONCLUSIONS Our findings confirm that YLSF has a certain curative effect on rats with liver fibrosis induced by CCl4, and its mechanism may include attenuating free radicals, inhibiting lipid peroxidation and accelerating extracellular matrix degradation by down-regulating expression of related genes.
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Affiliation(s)
- Youjia Guo
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China
| | - Xingmei Liang
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China
| | - Mingyu Meng
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China
| | - Hongxia Chen
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China
| | - Xiaojie Wei
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China
| | - Mingyan Li
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China
| | - Juman Li
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China
| | - Renbin Huang
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China.
| | - Jinbin Wei
- Department of Pharmacology, Guangxi Medical University, 22, Shuangyong Road, Nanning 530021, Guangxi, P.R. China
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Yan XF, Zhao P, Ma DY, Jiang YL, Luo JJ, Liu L, Wang XL. Salvianolic acid B protects hepatocytes from H 2O 2 injury by stabilizing the lysosomal membrane. World J Gastroenterol 2017; 23:5333-5344. [PMID: 28839433 PMCID: PMC5550782 DOI: 10.3748/wjg.v23.i29.5333] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Revised: 03/27/2017] [Accepted: 05/09/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the capability of salvianolic acid B (Sal B) to protect hepatocytes from hydrogen peroxide (H2O2)/carbon tetrachloride (CCl4)-induced lysosomal membrane permeabilization. METHODS Cell Counting Kit-8 assay was used to measure cell viability. Apoptosis and death were assayed through flow cytometry. BrdU incorporation was used to detect cell proliferation. Serum alanine aminotransferase activity and liver malondialdehyde (MDA) content were measured. Liver histopathological changes were evaluated using hematoxylin-eosin staining. Lysosomal membrane permeability was detected with LysoTracker Green-labeled probes and acridine orange staining. The levels of protein carbonyl content (PCC), cathepsins (Cat)B/D, and lysosome-associated membrane protein 1 (LAMP1) were evaluated through western blotting. Cytosol CatB activity analysis was performed with chemiluminescence detection. The mRNA level of LAMP1 was evaluated through quantitative real-time polymerase chain reaction. RESULTS Results indicated that H2O2 induced cell injury/death. Sal B attenuated H2O2-induced cell apoptosis and death, restored the inhibition of proliferation, decreased the amount of PCC, and stabilized the lysosome membrane by increasing the LAMP1 protein level and antagonizing CatB/D leakage into the cytosol. CCl4 also triggered hepatocyte death. Furthermore, Sal B effectively rescued hepatocytes by increasing LAMP1 expression and by reducing lysosomal enzyme translocation to the cytosol. CONCLUSION Sal B protected mouse embryonic hepatocytes from H2O2/CCl4-induced injury/death by stabilizing the lysosomal membrane.
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Al-Rasheed NM, Attia HA, Mohamad RA, Al-Rasheed NM, Al Fayez M, Al-Amin MA. Date fruits inhibit hepatocyte apoptosis and modulate the expression of hepatocyte growth factor, cytochrome P450 2E1 and heme oxygenase-1 in carbon tetrachloride-induced liver fibrosis. Arch Physiol Biochem 2017; 123:78-92. [PMID: 27960551 DOI: 10.1080/13813455.2016.1251945] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
CONTEXT Date fruits have protective effects against liver fibrosis; however their anti-apoptotic effects have not been investigated. OBJECTIVE To investigate the modulating effects of date fruits on pro- and anti-apoptotic markers, cytochrome P450 2E1 (CYP2E1) and hepatocyte growth factor (HGF) in liver fibrosis. MATERIALS AND METHODS Liver fibrosis was induced by injection of carbon tetrachloride (CCl4) for eight weeks. Date flesh extract (DFE) and pits extract (DPE) were taken daily concomitant with CCl4. Hepatocyte apoptosis was determined by measuring the expression of Fas, caspase-3, Bax, Bcl2 and hemeoxygenase-1 (HO-1). Hepatic levels of HGF and CYP2E1 were determined. RESULTS Treatment with DFE and DPE significantly attenuated the elevated levels of Fas, caspase 3, Bax and CYP2E1 induced by CCl4. In addition, they alleviated the reduction in Bcl2, HGF and HO-1, the cytoprotective and anti-apoptotic factors in liver. Conclusions DFE and DPE treatment can ameliorate liver fibrosis by inhibiting hepatocyte apoptosis.
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Affiliation(s)
- Nouf M Al-Rasheed
- a Department of Pharmacology and Toxicology , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia
| | - Hala A Attia
- a Department of Pharmacology and Toxicology , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia
- b Department of Biochemistry , College of Pharmacy, Mansoura University , Mansoura , Egypt , and
| | - Raeesa A Mohamad
- c Anatomy Department , Faculty of Medicine, King Saud University , Riyadh , Kingdom of Saudi Arabia
| | - Nawal M Al-Rasheed
- a Department of Pharmacology and Toxicology , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia
| | - Musaed Al Fayez
- c Anatomy Department , Faculty of Medicine, King Saud University , Riyadh , Kingdom of Saudi Arabia
| | - Maha A Al-Amin
- a Department of Pharmacology and Toxicology , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia
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Sheng RF, Wang HQ, Yang L, Jin KP, Xie YH, Chen CZ, Zeng MS. Diffusion kurtosis imaging and diffusion-weighted imaging in assessment of liver fibrosis stage and necroinflammatory activity. Abdom Radiol (NY) 2017; 42:1176-1182. [PMID: 27866239 DOI: 10.1007/s00261-016-0984-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
PURPOSE To investigate and compare the diagnostic value of diffusion kurtosis imaging (DKI) with diffusion-weighted imaging (DWI) in assessing and quantifying hepatic fibrosis. METHODS Thirty rats were divided into the control group (n = 6) and the fibrosis experimental groups (n = 6 per group) with CCl4 administration for 2, 4, 6, and 8 weeks. Liver fibrosis stage (S) and necroinflammatory activity grade (G) were histopathologically determined. DKI and DWI were performed; mean apparent diffusion (MD), mean kurtosis (MK), and apparent diffusion coefficient (ADC) values were calculated. DKI parameters were compared with ADC values according to G/S scores. RESULTS Strong inverse correlations were found between the degree of fibrosis and both MD and ADC (r = -0.840 and r = -0.760), while only weak correlation existed in MK (r = 0.405). ROC analyses demonstrated the AUC in MD, MK, and ADC of 0.862, 0.684, 0.817 for identifying mild and severe fibrosis, and 0.757, 0.675, 0.733 for non-cirrhosis and cirrhosis, respectively. The degree of fibrosis was significantly correlated with α-smooth muscle actin (α-SMA) (P < 0.0001); α-SMA had strong inverse correlation with MD (r = -0.723), moderate inverse correlation with ADC (r = -0.613), and very weak correlation with MK (r = 0.175). Additionally, MD was strongly correlated with the necroinflammatory activity (r = -0.758), ADC was moderately correlated (r = -0.492), and MK was weakly correlated (r = 0.254). CONCLUSION DKI may provide added information and serve as a valuable tool for the characterization and surveillance of liver fibrosis in a non-invasive manner.
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Affiliation(s)
- Ruo Fan Sheng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - He Qing Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Kai Pu Jin
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Yan Hong Xie
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Cai Zhong Chen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Meng Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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Cai Y, Lu D, Zou Y, Zhou C, Liu H, Tu C, Li F, Liu L, Zhang S. Curcumin Protects Against Intestinal Origin Endotoxemia in Rat Liver Cirrhosis by Targeting PCSK9. J Food Sci 2017; 82:772-780. [PMID: 28196290 DOI: 10.1111/1750-3841.13647] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 12/16/2016] [Accepted: 01/10/2017] [Indexed: 12/13/2022]
Abstract
Intestinal origin endotoxemia always occurs in severe liver injury. The aim of the current study was to test antiendotoxemia effect of curcumin on tetrachloride (CCl4 )-induced liver cirrhosis rats, and to elucidate the underlying molecular mechanism. Rat cirrhosis models were constructed with CCl4 subcutaneous injections with curcumin (200 mg/kg/d) administered via gavages for 12 wk until the rats were sacrificed. We found that the administration of curcumin improved the physiological condition pertaining to activity index and temperature, and ameliorated the liver injury in CCl4 -induced cirrhosis rats. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR) showed that curcumin could reduce c-reaction protein levels and inflammatory cytokine (TNF-α, IL-1β, IL-6, and CINC-1/IL-8) concentrations in peripheral serum and liver tissue. Furthermore, curcumin treatment decreased lipopolysaccharide (LPS) levels in peripheral vein, but not in portal vein. As low-density lipoprotein receptor (LDLR) is the important receptor on the surface of hepatocyte during LPS detoxification process, we used qRT-PCR, western blot, and immunohistochemistry (IHC), finding that curcumin significantly increased LDLR protein levels, but not gene levels in the liver tissues. We also tested proprotein convertase subtilisin/kexin type 9 (PCSK9), one negative regulator of LDLR, by qRT-PCR, western blot, and IHC. The results showed that PCSK9 significantly decreased both gene and protein levels in the rat liver tissues of curcumin treatment. Thus, we concluded that curcumin could function to protect against intestinal origin endotoxemia by inhibiting PCSK9 to promote LDLR expression, thereby enhancing LPS detoxification as one pathogen lipid through LDLR in the liver.
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Affiliation(s)
- Yu Cai
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
| | - Di Lu
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
| | - Yanting Zou
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
| | - Chaohui Zhou
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
| | - Hongchun Liu
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
| | - Chuantao Tu
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
| | - Feng Li
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
| | - Lili Liu
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
| | - Shuncai Zhang
- Dept. of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan Univ., 180 Fenglin Rd., Xuhui District, Shanghai, P.R. China
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Sande JA, Verjee S, Vinayak S, Amersi F, Ghesani M. Ultrasound shear wave elastography and liver fibrosis: A Prospective Multicenter Study. World J Hepatol 2017; 9:38-47. [PMID: 28105257 PMCID: PMC5220270 DOI: 10.4254/wjh.v9.i1.38] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 06/24/2016] [Accepted: 08/08/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the accuracy of shear wave elastography (SWE) alone and in combination with aminotransferase platelet ratio index (APRI) score in the staging of liver fibrosis.
METHODS A multicenter prospective study was conducted to assess the accuracy of SWE (medians) and APRI to predict biopsy results. The analysis focused on distinguishing the different stages of liver disease, namely, F0 from F1-4, F0-1 from F2-4, F0-2 from F3-4 and F0-3 from F4; F0-F1 from F2-F4 being of primary interest. The area under the receiver operating characteristic (AUROC) curve was computed using logistic regression model. The role of age, gender and steatosis was also assessed.
RESULTS SWE alone accurately distinguished F0-1 from F2-4 with a high probability. The AUROC using SWE alone was 0.91 compared to 0.78 for using the APRI score alone. The APRI score, when used in conjunction with SWE, did not make a significant contribution to the AUROC. SWE and steatosis were the only significant predictors that differentiated F0-1 from F2-4 with an AUROC of 0.944.
CONCLUSION Our study validates the use of SWE in the diagnosis and staging of liver fibrosis. Furthermore, the probability of a correct diagnosis is significantly enhanced with the addition of steatosis as a prognostic factor.
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Tao X, Sun X, Xu L, Yin L, Han X, Qi Y, Xu Y, Zhao Y, Wang C, Peng J. Total Flavonoids from Rosa laevigata Michx Fruit Ameliorates Hepatic Ischemia/Reperfusion Injury through Inhibition of Oxidative Stress and Inflammation in Rats. Nutrients 2016; 8:418. [PMID: 27399769 PMCID: PMC4963894 DOI: 10.3390/nu8070418] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Revised: 06/29/2016] [Accepted: 07/04/2016] [Indexed: 12/17/2022] Open
Abstract
The effects of total flavonoids (TFs) from Rosa laevigata Michx fruit against liver damage and cerebral ischemia/reperfusion (I/R) injury have been reported, but its action on hepatic I/R injury remains unknown. In this work, the effects and possible mechanisms of TFs against hepatic I/R injury were examined using a 70% partial hepatic warm ischemia rat model. The results demonstrated TFs decreased serum aspartate transaminase (AST), alanine aminotransferase (ALT), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) activities, improved liver histopathology and ultrastructure through hematoxylin-eosin (HE) staining and electron microscope observation. In addition, TFs significantly decreased malondialdehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which indicated that TFs alleviated oxidative stress caused by I/R injury. RT-PCR results proved that TFs downregulated the gene levels of inflammatory factors including interleukin-1 beta (IL-1β), interleukin-1 (IL-6), and tumor necrosis factor alpha (TNF-α). Further research indicated that TF-induced hepatoprotection was completed through inhibiting TLR4/MyD88 and activating Sirt1/Nrf2 signaling pathways. Blockade of the TLR4 pathway by TFs inhibited NF-κB and AP-1 transcriptional activities and inflammatory reaction. Activation of Sirt1/Nrf2 pathway by TFs increased the protein levels of HO-1 and GST to improve oxidative stress. Collectively, these findingsconfirmed the potent effects of TFs against hepatic I/R injury, which should be developed as a candidate for the prevention of this disease.
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Affiliation(s)
- Xufeng Tao
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
| | - Xiance Sun
- Department of Occupational and Environmental of Health, Dalian Medical University, No. 9 Western Section of Lushun South Road, Dalian 116044, China.
| | - Lina Xu
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
| | - Lianhong Yin
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
| | - Xu Han
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
| | - Yan Qi
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
| | - Youwei Xu
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
| | - Yanyan Zhao
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
| | - Changyuan Wang
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
| | - Jinyong Peng
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
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