scholarly journals Protective Effects of Oroxylin A against Doxorubicin-Induced Cardiotoxicity via the Activation of Sirt1 in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Wen-Bin Zhang ◽  
Yong-Fa Zheng ◽  
Yao-Gui Wu
Keyword(s):  
Inflammatory Diseases ◽  
Cardiac Injury ◽  
Life Quality ◽  
Sirtuin 1 ◽  
Heart Weight ◽  
Protective Effects ◽  
Oroxylin A ◽  
Beneficial Effects

Doxorubicin- (DOX-) related cardiac injury impairs the life quality of patients with cancer. This largely limited the clinical use of DOX. It is of great significance to find a novel strategy to reduce DOX-related cardiac injury. Oroxylin A (OA) has been identified to exert beneficial effects against inflammatory diseases and cancers. Here, we investigated whether OA could attenuate DOX-induced acute cardiotoxicity in mice. A single dose of DOX was used to induce acute cardiac injury in mice. To explore the protective effects, OA was administered to mice for ten days beginning from five days before DOX injection. The data in our study indicated that OA inhibited DOX-induced heart weight loss, reduction in cardiac function, and the elevation in myocardial injury markers. DOX injection resulted in increased oxidative damage, inflammation accumulation, and myocardial apoptosis in vivo and in vitro, and these pathological alterations were alleviated by treatment of OA. OA activated the sirtuin 1 (Sirt1) signaling pathway via the cAMP/protein kinase A, and its protective effects were blocked by Sirt1 deficiency. OA treatment did not affect the tumor-killing action of DOX in tumor-bearing mice. In conclusion, OA protected against DOX-related acute cardiac injury via the regulation of Sirt1.

scholarly journals FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dezhong Wang ◽  
Yuan Yin ◽  
Shuyi Wang ◽  
Tianyang Zhao ◽  
Fanghua Gong ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Metabolic Regulation ◽  
Cardiac Injury ◽  
Serum Levels ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cardiac Tissues ◽  
Beneficial Effects

AbstractAs a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

scholarly journals Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives

2021 ◽  
Vol 11 (5) ◽  
pp. 336
Author(s):  
Mohammed Ghiboub ◽  
Ahmed M. I. Elfiky ◽  
Menno P. J. de Winther ◽  
Nicola R. Harker ◽  
David F. Tough ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Inflammatory Diseases ◽  
Selective Inhibition ◽  
In Vivo Studies ◽  
Beneficial Effects ◽  
Domain Specific ◽  
Recent Advances ◽  
Autoimmune And Inflammatory Diseases

Histone deacetylases (HDACs) and bromodomain-containing proteins (BCPs) play a key role in chromatin remodeling. Based on their ability to regulate inducible gene expression in the context of inflammation and cancer, HDACs and BCPs have been the focus of drug discovery efforts, and numerous small-molecule inhibitors have been developed. However, dose-limiting toxicities of the first generation of inhibitors, which typically target multiple HDACs or BCPs, have limited translation to the clinic. Over the last decade, an increasing effort has been dedicated to designing class-, isoform-, or domain-specific HDAC or BCP inhibitors, as well as developing strategies for cell-specific targeted drug delivery. Selective inhibition of the epigenetic modulators is helping to elucidate the functions of individual epigenetic proteins and has the potential to yield better and safer therapeutic strategies. In accordance with this idea, several in vitro and in vivo studies have reported the ability of more selective HDAC/BCP inhibitors to recapitulate the beneficial effects of pan-inhibitors with less unwanted adverse events. In this review, we summarize the most recent advances with these strategies, discussing advantages and limitations of these approaches as well as some therapeutic perspectives, focusing on autoimmune and inflammatory diseases.

scholarly journals The Beneficial Effects of Morusin, an Isoprene Flavonoid Isolated from the Root Bark of Morus

2020 ◽  
Vol 21 (18) ◽  
pp. 6541
Author(s):  
Dong Wook Choi ◽  
Sang Woo Cho ◽  
Seok-Geun Lee ◽  
Cheol Yong Choi
Keyword(s):  
Inflammatory Diseases ◽  
Root Bark ◽  
Biological Processes ◽  
Functional Roles ◽  
Beneficial Effects ◽  
Biochemical Identification ◽  
Underlying Mechanisms ◽  
Clinical Potential

The root bark of Morus has long been appreciated as an antiphlogistic, diuretic and expectorant drug in Chinese herbal medicine, albeit with barely known targets and mechanisms of action. In the 1970s, the development of analytic chemistry allowed for the discovery of morusin as one of 7 different isoprene flavonoid derivatives in the root bark of Morus. However, the remarkable antioxidant capacity of morusin with the unexpected potential for health benefits over the other flavonoid derivatives has recently sparked scientific interest in the biochemical identification of target proteins and signaling pathways and further clinical relevance. In this review, we discuss recent advances in the understanding of the functional roles of morusin in multiple biological processes such as inflammation, apoptosis, metabolism and autophagy. We also highlight recent in vivo and in vitro evidence on the clinical potential of morusin treatment for multiple human pathologies including inflammatory diseases, neurological disorders, diabetes, cancer and the underlying mechanisms.

The Indispensable Value of Clinical Trials in the Modernization of Traditional Chinese Medicine: 12 Years' Experience at CUHK and Future Perspectives

2014 ◽  
Vol 42 (03) ◽  
pp. 587-604 ◽  
Author(s):  
Willmann Liang ◽  
David T. Yew ◽  
Kam Lun Hon ◽  
Chun Kwok Wong ◽  
Timothy C. Y. Kwok ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chinese Medicine ◽  
Herbal Medicines ◽  
Chinese Herbs ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Artery Disease ◽  
The Many

The last decade has seen a wealth of information reporting the beneficial effects of Chinese herbal medicines. While a lot more studies were done using in vitro and in vivo research platforms, much fewer investigations were conducted according to evidence-based requirements in clinical settings. The Institute of Chinese Medicine at the Chinese University of Hong Kong (CUHK) has had the opportunity to collaborate with clinicians over the years to initiate and conduct dozens of clinical trials investigating and verifying the therapeutic values of Chinese herbs in selected disease conditions. Of the many disorders, we chose to focus on those that are known for their difficulties achieving perfect results with conventional treatment methods. Examples include non-healing ulcers, allergic conditions, degenerative diseases and cancer. Protective effects of the herbs in such chronic diseases as coronary artery disease and osteoporosis were also part of our focus. Even in healthy individuals and those recovering from chemotherapy, Chinese herbs could help with the immune system and were studied in our clinical trials as well. This paper aims to highlight the important findings from these clinical studies while at the same time, stressing the indispensable value of clinical trials in modernizing the use of Chinese herbs in present-day medicine.

scholarly journals Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Yan ◽  
Si-Chi Xu ◽  
Chun-Yan Kong ◽  
Xiao-Yang Zhou ◽  
Zhou-Yan Bian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

scholarly journals Canagliflozin Attenuates Lipotoxicity in Cardiomyocytes and Protects Diabetic Mouse Hearts by Targeting the mTOR/HIF-1α Pathway

2020 ◽  
Author(s):  
Pengbo Sun ◽  
Yipei Ding ◽  
Jingyi Luo ◽  
Jin Zhong ◽  
Weidong Xie
Keyword(s):  
Inflammatory Responses ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Diabetic Mouse ◽  
Protective Effects ◽  
Pharmacological Mechanism ◽  
Beneficial Effects ◽  
Mtor Phosphorylation

Abstract BackgroundLipotoxicity plays an important role in the development of diabetic cardiomyopathy and heart failure (HF). Canagliflozin (CAN), a marketed sodium-glucose co-transporter 2 inhibitor, has significant beneficial effects on HF. However, the potential pharmacological mechanism is still unknown.MethodsIn this study, we evaluated the protective effects and mechanism of CAN in the hearts of a C57BL/6J diabetic mouse model induced by a high-fat diet/streptozotocin (HFD/STZ) for 12 weeks in vivo and using HL-1 cells (a type of mouse cardiomyocyte line) induced by palmitic acid (PA) in vitro.ResultsCAN could significantly alleviate lipid accumulation and inflammatory responses in the hearts of the HFD/STZ-induced diabetic mice. Furthermore, CAN significantly attenuated the inflammatory injury induced by PA in the HL-1 cells. In addition, CAN bound to the mammalian target of rapamycin (mTOR) and significantly inhibited mTOR phosphorylation and hypoxia inducible factor-1α (HIF-1α) expression.ConclusionCAN attenuated lipotoxicity in cardiomyocytes and protected diabetic mouse hearts by targeting the mTOR/HIF-1α pathway.

scholarly journals TRPM8 Deficiency Attenuates Liver Fibrosis Through S100A9-HNF4α Signaling

2022 ◽  
Author(s):  
Qiang Liu ◽  
Xiaohua Lei ◽  
Zhenyu Cao ◽  
Ju Zhang ◽  
Likun Yan ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Transient Receptor Potential ◽  
Inflammatory Diseases ◽  
Receptor Potential ◽  
Potential Effect ◽  
Protective Effects ◽  
Tissue Samples ◽  
Duct Ligation

Abstract Background Liver fibrosis represent a major global health care burden. Data emerging from recent advances have suggested TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis. Methods The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8−/− (KO) fibrotic mice after carbon tetrachloride (CCl4) or bile duct ligation (BDL) treatment. The role of TRPM8 was systematically evaluated using specimens obtained from the aforementioned animal models after various in vivo and in vitro experiments. Results Clinicopathological analysis has shown TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice, but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl4 and BDL treated TRPM8 KO mice. Strong regulatory linkage between S100A9 and HNF4α was also noticed in L02 cells underwent siRNA-mediated S100A9 knockdown and S100A9 overexpressing plasmid transfection. Lastly, alleviative effect of a selective TRPM8 antagonist was confirmed in vivo. Conclusion These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies and fibrosis through S100A9-HNF4α signaling mechanistically. M8-B might be a promising therapeutic candidate for liver fibrosis.

scholarly journals Colon Bioaccessibility and Antioxidant Activity of White, Green and Black Tea Polyphenols Extract after In Vitro Simulated Gastrointestinal Digestion

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1711 ◽  
Author(s):  
Giuseppe Annunziata ◽  
Maria Maisto ◽  
Connie Schisano ◽  
Roberto Ciampaglia ◽  
Patricia Daliu ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Inflammatory Diseases ◽  
Black Tea ◽  
Tea Polyphenols ◽  
Array Detector ◽  
Total Phenol Content ◽  
Beneficial Effects ◽  
Polyphenolic Extract

The beneficial effects of the tea beverage are well-known and mainly attributed to polyphenols which, however, have poor bioaccessibility and bioavailability. The purpose of the present study was the evaluation of colon bioaccessibility and antioxidant activity of tea polyphenolic extract. An 80% methanolic extract (v/v) of tea polyphenols was obtained from green (GT), white (WT) and black tea (BT). Simulated gastrointestinal (GI) digestion was performed on acid-resistant capsules containing tea polyphenolic extract. The main tea polyphenols were monitored by HPLC-diode-array detector (DAD) method; in addition, Total Phenol Content (TPC) and antioxidant activity were evaluated. After GI digestion, the bioaccessibility in the colon stage was significantly increased compared to the duodenal stage for both tea polyphenols and TPC. Similarly, the antioxidant activity in the colon stage was significantly higher than that in the duodenal stage. Reasonably, these results could be attributable in vivo to the activity of gut microbiota, which is able to metabolize these compounds, generating metabolites with a greater antioxidant activity. Our results may guide the comprehension of the colon digestion of polyphenols, suggesting that, although poorly absorbed in the duodenum, they can exert their antioxidant and anti-inflammatory activities in the lower gut, resulting in a novel strategy for the management of gut-related inflammatory diseases.

scholarly journals Osteocrin, a novel myokine, prevents diabetic cardiomyopathy via restoring proteasomal activity

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xin Zhang ◽  
Can Hu ◽  
Xiao-Pin Yuan ◽  
Yu-Pei Yuan ◽  
Peng Song ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Injury ◽  
Neonatal Rat ◽  
Protective Effects ◽  
Rat Cardiomyocytes ◽  
Proteasomal Activity ◽  
Virus Serotype

AbstractProteasomal activity is compromised in diabetic hearts that contributes to proteotoxic stresses and cardiac dysfunction. Osteocrin (OSTN) acts as a novel exercise-responsive myokine and is implicated in various cardiac diseases. Herein, we aim to investigate the role and underlying molecular basis of OSTN in diabetic cardiomyopathy (DCM). Mice received a single intravenous injection of the cardiotrophic adeno-associated virus serotype 9 to overexpress OSTN in the heart and then were exposed to intraperitoneal injections of streptozotocin (STZ, 50 mg/kg) for consecutive 5 days to generate diabetic models. Neonatal rat cardiomyocytes were isolated and stimulated with high glucose to verify the role of OSTN in vitro. OSTN expression was reduced by protein kinase B/forkhead box O1 dephosphorylation in diabetic hearts, while its overexpression significantly attenuated cardiac injury and dysfunction in mice with STZ treatment. Besides, OSTN incubation prevented, whereas OSTN silence aggravated cardiomyocyte apoptosis and injury upon hyperglycemic stimulation in vitro. Mechanistically, OSTN treatment restored protein kinase G (PKG)-dependent proteasomal function, and PKG or proteasome inhibition abrogated the protective effects of OSTN in vivo and in vitro. Furthermore, OSTN replenishment was sufficient to prevent the progression of pre-established DCM and had synergistic cardioprotection with sildenafil. OSTN protects against DCM via restoring PKG-dependent proteasomal activity and it is a promising therapeutic target to treat DCM.

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