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Wang Y, Sui Z, Wang M, Liu P. Natural products in attenuating renal inflammation via inhibiting the NLRP3 inflammasome in diabetic kidney disease. Front Immunol 2023; 14:1196016. [PMID: 37215100 PMCID: PMC10196020 DOI: 10.3389/fimmu.2023.1196016] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 04/26/2023] [Indexed: 05/24/2023] Open
Abstract
Diabetic kidney disease (DKD) is a prevalent and severe complications of diabetes and serves as the primary cause of end-stage kidney disease (ESKD) globally. Increasing evidence indicates that renal inflammation is critical in the pathogenesis of DKD. The nucleotide - binding oligomerization domain (NOD) - like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most extensively researched inflammasome complex and is considered a crucial regulator in the pathogenesis of DKD. The activation of NLRP3 inflammasome is regulated by various signaling pathways, including NF- κB, thioredoxin-interacting protein (TXNIP), and non-coding RNAs (ncRNA), among others. Natural products are chemicals extracted from living organisms in nature, and they typically possess pharmacological and biological activities. They are invaluable sources for drug design and development. Research has demonstrated that many natural products can alleviate DKD by targeting the NLRP3 inflammasome. In this review, we highlight the role of the NLRP3 inflammasome in DKD, and the pathways by which natural products fight against DKD via inhibiting the NLRP3 inflammasome activation, so as to provide novel insights for the treatment of DKD.
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Affiliation(s)
- Yan Wang
- Department of Nephrology, Peking University People’s Hospital, Beijing, China
| | - Zhun Sui
- Department of Nephrology, Peking University People’s Hospital, Beijing, China
| | - Mi Wang
- Department of Nephrology, Peking University People’s Hospital, Beijing, China
| | - Peng Liu
- Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital, Beijing, China
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Pfingstgraf IO, Taulescu M, Pop RM, Orăsan R, Vlase L, Uifalean A, Todea D, Alexescu T, Toma C, Pârvu AE. Protective Effects of Taraxacum officinale L. (Dandelion) Root Extract in Experimental Acute on Chronic Liver Failure. Antioxidants (Basel) 2021; 10:504. [PMID: 33804908 PMCID: PMC8063808 DOI: 10.3390/antiox10040504] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/19/2021] [Accepted: 03/22/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Taraxacum officinale (TO) or dandelion has been frequently used to prevent or treat different liver diseases because of its rich composition in phytochemicals with demonstrated effect against hepatic injuries. This study aimed to investigate the possible preventing effect of ethanolic TO root extract (TOERE) on a rat experimental acute on chronic liver failure (ACLF) model. METHODS Chronic liver failure (CLF) was induced by human serum albumin, and ACLF was induced in CLF by D-galactosamine and lipopolysaccharide (D-Gal-LPS). Five groups (n = 5) of male Wistar rats (200-250 g) were used: ACLF, ACLF-silymarin (200 mg/kg b.w./day), three ACLF-TO administered in three doses (200 mg, 100 mg, 50 mg/kg b.w./day). RESULTS The in vivo results showed that treatment with TOERE administered in three chosen doses before ACLF induction reduced serum liver injury markers (AST, ALT, ALP, GGT, total bilirubin), renal tests (creatinine, urea), and oxidative stress tests (TOS, OSI, MDA, NO, 3NT). Histopathologically, TOERE diminished the level of liver tissue injury and 3NT immunoexpression. CONCLUSIONS This paper indicated oxidative stress reduction as possible mechanisms for the hepatoprotective effect of TOERE in ACLF and provided evidence for the preventive treatment.
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Affiliation(s)
- Iulia Olimpia Pfingstgraf
- Department of Pathophysiology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (I.O.P.); (A.U.); (A.E.P.)
| | - Marian Taulescu
- Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania;
- Synevovet Laboratory, 021408 Bucharest, Romania
| | - Raluca Maria Pop
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania
| | - Remus Orăsan
- Department of Physiology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania;
| | - Laurian Vlase
- Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania;
| | - Ana Uifalean
- Department of Pathophysiology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (I.O.P.); (A.U.); (A.E.P.)
| | - Doina Todea
- Department of Pneumology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania;
| | - Teodora Alexescu
- 4th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania;
| | - Corina Toma
- Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania;
| | - Alina Elena Pârvu
- Department of Pathophysiology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (I.O.P.); (A.U.); (A.E.P.)
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Zhuang W, Yue L, Dang X, Chen F, Gong Y, Lin X, Luo Y. Rosenroot ( Rhodiola): Potential Applications in Aging-related Diseases. Aging Dis 2019; 10:134-146. [PMID: 30705774 PMCID: PMC6345333 DOI: 10.14336/ad.2018.0511] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 05/11/2018] [Indexed: 12/12/2022] Open
Abstract
Aging is a progressive accumulation of changes in the body, which increases the susceptibility to diseases such as Alzheimer's disease, Parkinson's disease, cerebrovascular disease, diabetes, and cardiovascular disease. Recently, Chinese medicinal herbs have been investigated for their therapeutic efficacy in the treatment of some aging-related diseases. Rhodiola, known as 'Hongjingtian' in Chinese, has been reported to have anti-aging activity. Here, we provide a comprehensive review about its origin, chemical constituents, and effects on aging-related diseases.
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Affiliation(s)
- Wei Zhuang
- 1Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
| | - Lifeng Yue
- 2Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xiaofang Dang
- 3Department of Pharmacy, Hospital of T.C.M.S Shijingshan District, Beijing 100043, China
| | - Fei Chen
- 1Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
| | - Yuewen Gong
- 4College of Pharmacy, University of Manitoba, Winnipeg R3E 0T5, Manitoba, Canada
| | - Xiaolan Lin
- 1Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
| | - Yumin Luo
- 5Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
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Hong HD, Kim JC, Lim TG, Song YR, Cho CW, Jang M. Mixing ratio optimization for functional complex extracts of Rhodiola crenulata, Panax quinquefolius, and Astragalus membranaceus using mixture design and verification of immune functional efficacy in animal models. J Funct Foods 2018; 40:447-454. [PMID: 32288793 PMCID: PMC7105012 DOI: 10.1016/j.jff.2017.11.038] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 11/23/2017] [Accepted: 11/25/2017] [Indexed: 12/03/2022] Open
Abstract
We aimed to identify the optimum mixing ratio for various ingredients to obtain complex extracts with high extract yields and immune-enhancing activity in animals. The extract yield and amounts of nitric oxide (NO) and interleukin (IL)-6 were set to maximum for modeling predictions. The predicted optimum values for the mixing ratio were 49.5% for Rhodiola crenulata, 26.1% for Astragalus membranaceus, and 24.4% for Panax quinquefolius, and the predicted response values were 31.5% yield, 13.4% NO production, and 6.1% IL-6 production; actual values were 35.3% yield, 14.7% NO, and 6.6% IL-6. The optimum mixing ratio extract (OMRE) was used for the animal experiments. Treating mice with OMRE at 200 mg/kg produced significant increases in spleen indexes and T-cell/B-cell proliferation. OMRE treatment increased IL-10 and IL-6 production in concanavalin A- and lipopolysaccharide-induced T- and B- lymphocytes, respectively. These results provide a basis for the development of functional extracts and drinks.
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Affiliation(s)
- Hee-Do Hong
- Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Jong-Chan Kim
- Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Tae-Gyu Lim
- Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Young-Ran Song
- Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Chang-Won Cho
- Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Mi Jang
- Korea Food Research Institute, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
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Lan KC, Chao SC, Wu HY, Chiang CL, Wang CC, Liu SH, Weng TI. Salidroside ameliorates sepsis-induced acute lung injury and mortality via downregulating NF-κB and HMGB1 pathways through the upregulation of SIRT1. Sci Rep 2017; 7:12026. [PMID: 28931916 PMCID: PMC5607272 DOI: 10.1038/s41598-017-12285-8] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 09/06/2017] [Indexed: 12/29/2022] Open
Abstract
Sepsis is a life-threatening medical condition. Salidroside, a substance isolated from Rhodiola rosea, possesses antioxidant and anti-inflammatory properties. The effect and mechanism of salidroside on sepsis-induced acute lung injury still remains to be well clarified. Here, we investigated the effect and mechanism of salidroside on septic mouse models and explored the role of salidroside-upregulated SIRT1. Salidroside inhibited the inflammatory responses and HMGB1 productions in bacterial lipopolysaccharide (LPS)-treated macrophages and mice. Salidroside could also reverse the decreased SIRT1 protein expression in LPS-treated macrophages and mice. Salidroside also alleviated the sepsis-induced lung edema, lipid peroxidation, and histopathological changes and the mortality, and improved the lung PaO2/FiO2 ratio in cecal ligation and puncture (CLP)-induced septic mice. Salidroside significantly decreased the serum TNF-α, IL-6, NO, and HMGB1 productions, pulmonary inducible NO synthase (iNOS) and phosphorylated NF-κB-p65 protein expressions, and pulmonary HMGB1 nuclear translocation in CLP septic mice. Moreover, sepsis decreased the SIRT1 protein expression in the lungs of CLP septic mice. Salidroside significantly upregulated the SIRT1 expression and inhibited the inflammatory responses in CLP septic mouse lungs. These results suggest that salidroside protects against sepsis-induced acute lung injury and mortality, which might be through the SIRT1-mediated repression of NF-κB activation and HMGB1 nucleocytoplasmic translocation.
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Affiliation(s)
- Kuo-Cheng Lan
- Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Sung-Chuan Chao
- Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Hsiao-Yi Wu
- Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chia-Lien Chiang
- Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ching-Chia Wang
- Departments of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Shing-Hwa Liu
- Departments of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.,Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Te-I Weng
- Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. .,Departments of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
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Erzhi Pill® Repairs Experimental Liver Injury via TSC/mTOR Signaling Pathway Inhibiting Excessive Apoptosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017. [PMID: 28638431 PMCID: PMC5468563 DOI: 10.1155/2017/5653643] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (γ-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression. However, the secretion of albumin, liver weight, and index of liver weight were elevated. Microscopic examination showed that EZP restored pathological liver injury. Meanwhile, Rheb and mammalian target of rapamycin (mTOR) activation were suppressed, and tuberous sclerosis complex (TSC) expression was elevated in liver tissues induced by 2-AAF/PHx and accompanied with lower-expression of Bax, Notch1, p70S6K, and 4E-EIF and upregulated levels of Bcl-2 and Cyclin D. Hepatoprotective effect of EZP was possibly realized via inhibiting TSC/mTOR signaling pathway to suppress excessive apoptosis of hepatocyte.
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Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking-Induced Liver Injury. Molecules 2016; 21:molecules21111490. [PMID: 27834881 PMCID: PMC6272831 DOI: 10.3390/molecules21111490] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 11/03/2016] [Accepted: 11/04/2016] [Indexed: 01/15/2023] Open
Abstract
The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion and mRNA expression of of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury.
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Yang ZR, Wang HF, Zuo TC, Guan LL, Dai N. Salidroside alleviates oxidative stress in the liver with non- alcoholic steatohepatitis in rats. BMC Pharmacol Toxicol 2016; 17:16. [PMID: 27075663 PMCID: PMC4831194 DOI: 10.1186/s40360-016-0059-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2015] [Accepted: 03/29/2016] [Indexed: 01/19/2023] Open
Abstract
Background Nonalcoholic steatohepatitis (NASH) is characterized by fat accumulation in the hepatocyte, inflammation, liver cell injury, and varying degrees of fibrosis, and can lead to oxidative stress in liver. Here, we investigated whether Salidroside, a natural phenolic antioxidant product, can protect rat from liver injury during NASH. Methods NASH model was established by feeding the male SD rats with high-fat and high-cholesterol diet for 14 weeks. Four groups of male SD rats including, normal diet control group, NASH model group, and Salidroside treatment group with150mg/kg and 300 mg/kg respectively, were studied. Salidroside was given by oral administration to NASH in rats from 9 weeks to 14 weeks. At the end of 14 weeks, liver and serum were harvested, and the liver injury, oxidative stress and histological features were evaluated. Results NASH rats exhibited significant increases in the following parameters as compared to normal diet control rats: fat droplets with foci of inflammatory cell infiltration in the liver. ALT, AST in serum and TG, TC in hepatocyte elevated. Oxidative responsive genes including CYP2E1 and Nox2 increased. Additionally, NASH model decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to NASH model group, treatment rats with Salidroside effectively reduced lipid accumulation, inhibited liver injury in a does-dependent manner. Salidroside treatment restored antioxidant enzyme levels, inhibited expression of CYP2E1 and Nox2 mRNA in liver, which prevented the initial step of generating free radicals from NASH. Conclusion The data presented here show that oral administration of Salidroside prevented liver injury in the NASH model, likely through exerting antioxidant actions to suppress oxidative stress and the free radical–generating CYP2E1 enzyme, Nox2 in liver.
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Affiliation(s)
- Ze-ran Yang
- Department of Gastroenterology, the first Affiliated Hospital of Dalian Medical University, 222, Zhongshan Road, Dalian, 116011, Liaoning Province, China
| | - Hui-fang Wang
- Department of Gastroenterology, the first Affiliated Hospital of Dalian Medical University, 222, Zhongshan Road, Dalian, 116011, Liaoning Province, China
| | - Tie-cheng Zuo
- Department of Gastroenterology, the first Affiliated Hospital of Dalian Medical University, 222, Zhongshan Road, Dalian, 116011, Liaoning Province, China
| | - Li-li Guan
- Department of Digestive Physiology, Dalian Medical University, Dalian, Liaoning Province, China
| | - Ning Dai
- Department of Gastroenterology, the first Affiliated Hospital of Dalian Medical University, 222, Zhongshan Road, Dalian, 116011, Liaoning Province, China.
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Pomari E, Stefanon B, Colitti M. Effects of Two Different Rhodiola rosea Extracts on Primary Human Visceral Adipocytes. Molecules 2015; 20:8409-28. [PMID: 25970041 PMCID: PMC6272273 DOI: 10.3390/molecules20058409] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 05/05/2015] [Accepted: 05/06/2015] [Indexed: 12/13/2022] Open
Abstract
Rhodiola rosea (Rro) has been reported to have various pharmacological properties, including anti-fatigue, anti-stress and anti-inflammatory activity. It is also known to improve glucose and lipid metabolism, but the effects of Rhodiola rosea on adipocyte differentiation and metabolism are not still elucidated. In this study the anti-adipogenic and lipolytic activity of two extracts of Rhodiola rosea, containing 3% salidroside (RS) or 1% salidroside and 3% rosavines (RR) on primary human visceral adipocytes was investigated. Pre-adipocytes were analyzed after 10 and 20 days of treatment during differentiation and after 7 days of treatment when they reached mature shape. The RS extract significantly induced higher apoptosis and lipolysis in comparison to control cells and to RR extract. In contrast, RR extract significantly reduced triglyceride incorporation during maturation. Differentiation of pre-adipocytes in the presence of RS and RR extracts showed a significant decrease in expression of genes involved in adipocyte function such as SLC2A4 and the adipogenic factor FGF2 and significant increase in expression of genes involved in inhibition of adipogenesis, such as GATA3, WNT3A, WNT10B. Furthermore RR extract, in contrast to RS, significantly down-regulates PPARG, the master regulator of adipogenesis and FABP4. These data support the lipolytic and anti-adipogenetic activity of two different commercial extracts of Rhodiola rosea in primary human visceral pre-adipocytes during differentiation.
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Affiliation(s)
- Elena Pomari
- Department of Agricultural and Environmental Sciences, University of Udine, via delle Scienze, 206, 33100 Udine, Italy.
| | - Bruno Stefanon
- Department of Agricultural and Environmental Sciences, University of Udine, via delle Scienze, 206, 33100 Udine, Italy.
| | - Monica Colitti
- Department of Agricultural and Environmental Sciences, University of Udine, via delle Scienze, 206, 33100 Udine, Italy.
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Saracyn M, Brytan M, Zdanowski R, Ząbkowski T, Dyrla P, Patera J, Wojtuń S, Kozłowski W, Wańkowicz Z. Hepatoprotective effect of nitric oxide in experimental model of acute hepatic failure. World J Gastroenterol 2014; 20:17407-17415. [PMID: 25516652 PMCID: PMC4265599 DOI: 10.3748/wjg.v20.i46.17407] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Revised: 07/08/2014] [Accepted: 09/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF).
METHODS: An experimental rat model of galactosamine-induced AHF was used. An inhibitor of NO synthase, nitroarginine methyl ester, or an NO donor, arginine, were administered at various doses prior to or after the induction of AHF.
RESULTS: All tested groups developed AHF. Following inhibition of the endogenous NO pathway, most liver parameters improved, regardless of the inhibitor dose before the induction of liver damage, and depending on the inhibitor dose after liver damage. Prophylactic administration of the inhibitor was more effective in improving liver function parameters than administration of the inhibitor after liver damage. An attempt to activate the endogenous NO pathway prior to the induction of liver damage did not change the observed liver function parameters. Stimulation of the endogenous NO pathway after liver damage, regardless of the NO donor dose used, improved most liver function parameters.
CONCLUSION: The endogenous NO pathway plays an important role in the development of experimental galactosamine-induced AHF.
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Ha H, Shim KS, Kim T, An H, Lee CJ, Lee KJ, Ma JY. Water extract of Acer tegmentosum reduces bone destruction by inhibiting osteoclast differentiation and function. Molecules 2014; 19:3940-54. [PMID: 24694651 PMCID: PMC6271087 DOI: 10.3390/molecules19043940] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Revised: 03/24/2014] [Accepted: 03/25/2014] [Indexed: 12/25/2022] Open
Abstract
The stem of Acer tegmentosum has been widely used in Korea for the treatment of hepatic disorders. In this study, we investigated the bone protective effect of water extract of the stem of Acer tegmentosum (WEAT). We found that WEAT inhibits osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclast differentiation. In osteoclast precursor cells, WEAT inhibited RANKL-induced activation of JNK, NF-κB, and cAMP response element-binding protein, leading to suppression of the induction of c-Fos and nuclear factor of activated T cells cytoplasmic 1, key transcription factors for osteoclast differentiation. In addition, WEAT inhibited bone resorbing activity of mature osteoclasts. Furthermore, the oral administration of WEAT reduced RANKL-induced bone resorption and trabecular bone loss in mice. Taken together, our study demonstrates that WEAT possesses a protective effect on bone destruction by inhibiting osteoclast differentiation and function.
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Affiliation(s)
- Hyunil Ha
- KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea
| | - Ki-Shuk Shim
- KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea
| | - Taesoo Kim
- KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea
| | - Hyosun An
- KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea
| | - Chung-Jo Lee
- KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea
| | - Kwang Jin Lee
- KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea
| | - Jin Yeul Ma
- KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea.
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Protective effect of danhong injection on acute hepatic failure induced by lipopolysaccharide and d-galactosamine in mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 2014:153902. [PMID: 24772178 PMCID: PMC3977120 DOI: 10.1155/2014/153902] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/24/2014] [Accepted: 02/11/2014] [Indexed: 12/15/2022]
Abstract
Acute hepatic failure (AHF), which leads to an extremely high mortality rate, has become the focus of attention in clinic. In this study, Danhong injection (DHI) was investigated to evaluate the preventive and protective effect on AHF induced by lipopolysaccharide (LPS) and D-galactosamine (GalN) in mice. For AHF induction, ICR mice were intraperitoneally injected with D-GalN (700 mg/kg) and LPS (20 μ g/kg). DHI was administrated twice, at 12 and 1 h, respectively, before D-GalN/LPS injection. After stimulation with D-GalN/LPS for 1 and 6 h, serum and livers were collected for analysis. We found that mice administrated with DHI displayed a higher survival rate, lower serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), glutathione S-transferase (GST), and tumor necrosis factor (TNF)- α . DHI inhibited the elevations of hepatic lipid peroxidation (malondialdehyde), caspase-8 activity, and mRNA expression levels of inflammatory cytokines (interleukin-1 β and interleukin-6) increased by D-GalN/LPS in the liver. Furthermore, liver histopathological analysis indicated that the DHI group showed markedly fewer apoptotic (TUNEL positive) cells and less pathological changes than those in the AHF model group. These results provide a novel insight into the pharmacological actions of DHI as a potential candidate for treating AHF.
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Salidroside attenuates LPS-stimulated activation of THP-1 cell-derived macrophages through down-regulation of MAPK/NF-kB signaling pathways. ACTA ACUST UNITED AC 2013; 33:463-469. [PMID: 23904362 DOI: 10.1007/s11596-013-1143-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 07/12/2013] [Indexed: 10/26/2022]
Abstract
Excessive activation of macrophages is implicated in various inflammatory injuries. Salidroside (Sal), one of the main bioactive components of Rhodiola Sachalinensis, has been reported to possess anti-inflammatory activities. This study aimed to examine the effect of Sal on the activation of macrophages and the possible mechanism. The lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage models were established. The changes in the inflammatory profiles of THP-1-derived macrophages were determined. The results showed that Sal significantly decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at both mRNA and protein levels in THP-1-derived macrophages, and the effect was dose-depedent. Moreover, NF-κB activation was significantly suppressed and the phosphorylation of ERK, p38 and JNK was substantially down-regulated after Sal treatment. The findings suggested that Sal can suppress the activation of LPS-stimulated PMA-differetiated THP-1 cells, as evidenced by the decreased expression of iNOS, COX2, IL-1β, IL-6 and TNF-α, and the mechanism involves the inhibition of NF-κB activation and the phosphorylation of the MAPK signal pathway.
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Protective effect of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice. Molecules 2011; 16:9912-24. [PMID: 22134398 PMCID: PMC6264537 DOI: 10.3390/molecules16129912] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2011] [Revised: 11/18/2011] [Accepted: 11/22/2011] [Indexed: 12/11/2022] Open
Abstract
It has been confirmed that diabetes mellitus (DM) carries increased oxidative stress. This study evaluated the effects of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice. After induction of diabetes, diabetic mice were administered daily doses of 50, 100 and 200 mg/kg salidroside for 28 days. Body weights, fasting blood glucose (FBG), serum insulin, TC (total cholesterol), TG (triglyceride), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured. Results showed that salidroside possessed hypoglycemic activity and protective effects against diabetes-induced oxidative stress, which could significantly reduce FBG, TC, TG and MDA levels, and at same time increase serum insulin levels, SOD, GPx and CAT activities. Therefore, salidroside should be considered as a candidate for future studies on diabetes.
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