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

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.

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

Journal of Personalized Medicine ◽

10.3390/jpm11050336 ◽

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.

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Targeting necroptosis as therapeutic potential in chronic myocardial infarction

Journal of Biomedical Science ◽

10.1186/s12929-021-00722-w ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Chanon Piamsiri ◽

Chayodom Maneechote ◽

Natthaphat Siri-Angkul ◽

Siriporn C. Chattipakorn ◽

Nipon Chattipakorn

Keyword(s):

Myocardial Infarction ◽

Therapeutic Potential ◽

Coronary Perfusion ◽

Beneficial Effects ◽

Cell Death Pathways ◽

Threatening Condition ◽

Underlying Mechanisms ◽

Novel Therapeutic Strategies

AbstractCardiovascular diseases (CVDs) are considered the predominant cause of morbidity and mortality globally. Of these, myocardial infarction (MI) is the most common cause of CVD mortality. MI is a life-threatening condition which occurs when coronary perfusion is interrupted leading to cardiomyocyte death. Subsequent to MI, consequences include adverse cardiac remodeling and cardiac dysfunction mainly contribute to the development of heart failure (HF). It has been shown that loss of functional cardiomyocytes in MI-induced HF are associated with several cell death pathways, in particular necroptosis. Although the entire mechanism underlying necroptosis in MI progression is still not widely recognized, some recent studies have reported beneficial effects of necroptosis inhibitors on cell viability and cardiac function in chronic MI models. Therefore, extensive investigation into the necroptosis signaling pathway is indicated for further study. This article comprehensively reviews the context of the underlying mechanisms of necroptosis in chronic MI-induced HF in in vitro, in vivo and clinical studies. These findings could inform ways of developing novel therapeutic strategies to improve the clinical outcomes in MI patients from this point forward.

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Antioxidant and Anti-Inflammatory Effects of Citrus Flavonoid Hesperetin: Special Focus on Neurological Disorders

Antioxidants ◽

10.3390/antiox9070609 ◽

2020 ◽

Vol 9 (7) ◽

pp. 609 ◽

Cited By ~ 2

Author(s):

Amjad Khan ◽

Muhammad Ikram ◽

Jong Ryeal Hahm ◽

Myeong Ok Kim

Keyword(s):

Neurodegenerative Disorders ◽

In Vitro Models ◽

Experimental Models ◽

Special Focus ◽

Neuroprotective Effects ◽

Beneficial Effects ◽

Wide Range ◽

Underlying Mechanisms

Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models.

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Ganoderma lucidum Polysaccharides as An Anti-cancer Agent

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171113121246 ◽

2018 ◽

Vol 18 (5) ◽

pp. 667-674 ◽

Cited By ~ 20

Author(s):

Didem Sohretoglu ◽

Shile Huang

Keyword(s):

Ganoderma Lucidum ◽

Water Soluble ◽

In Vivo Studies ◽

Beneficial Effects ◽

Anticancer Effects ◽

Bioactive Component ◽

Cancer Agent ◽

Underlying Mechanisms

The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms.

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LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-κB signaling

Clinical Science ◽

10.1042/cs20170198 ◽

2017 ◽

Vol 131 (17) ◽

pp. 2275-2288 ◽

Cited By ~ 10

Author(s):

Zhou Jiang ◽

Juan-Juan Qin ◽

Yaxing Zhang ◽

Wen-Lin Cheng ◽

Yan-Xiao Ji ◽

...

Keyword(s):

Inflammatory Response ◽

Inflammatory Diseases ◽

Chronic Inflammatory Disease ◽

Plaque Instability ◽

Atherosclerotic Lesions ◽

Bone Marrow Derived Cells ◽

Underlying Mechanisms ◽

Human And Mouse

Atherosclerosis is a chronic inflammatory disease. Leukocyte immunoglobulin-like receptor B4 (LILRB4) is associated with the pathological processes of various inflammatory diseases. However, the potential function and underlying mechanisms of LILRB4 in atherogenesis remain to be investigated. In the present study, LILRB4 expression was examined in both human and mouse atherosclerotic plaques. The effects and possible mechanisms of LILRB4 in atherogenesis and plaque instability were evaluated in LILRB4-/-ApoE-/- and ApoE-/- mice fed a high-fat diet (HFD). We found that LILRB4 was located primarily in macrophages, and its expression was up-regulated in atherosclerotic lesions from human coronary arteries and mouse aortic roots. LILRB4 deficiency significantly accelerated the development of atherosclerotic lesions and increased the instability of plaques, as evident by the increased infiltration of lipids, decreased amount of collagen components and smooth muscle cells. Moreover, LILRB4 deficiency in bone marrow derived cells promoted the development of atherosclerosis. In vivo and in vitro analyses revealed that the proinflammatory effects of LILRB4 deficiency were mediated by the increased activation of NF-κB signaling due to decreased src homolog 2 domain containing phosphatase (Shp) 1 phosphorylation. In conclusion, the present study indicates that LILRB4 deficiency promotes atherogenesis, at least partly, through reduced Shp1 phosphorylation, which subsequently enhances the NF-κB-mediated inflammatory response. Thus, targetting the ‘LILRB4-Shp1’ axis may be a novel therapeutic approach for atherosclerosis.

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Rosiglitazone Ameliorates Spinal Cord Injury via Inhibiting Mitophagy and Inflammation of Neural Stem Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2022/5583512 ◽

2022 ◽

Vol 2022 ◽

pp. 1-22

Author(s):

Qingqi Meng ◽

Zhiteng Chen ◽

Qingyuan Gao ◽

Liqiong Hu ◽

Qilong Li ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Neural Stem Cells ◽

Atp Production ◽

Beneficial Effects ◽

Cord Injury ◽

Underlying Mechanisms

Background. Neurodegenerative diseases, such as Alzheimer’s disease, and traumatic brain and spinal cord injury (SCI) are prevalent in clinical practice. Inhibition of hyperactive inflammation and proliferation of endogenous neural stem cells (NSCs) is a promising treatment strategy for SCI. Our previous studies demonstrated the beneficial effects of rosiglitazone (Rosi) on SCI, but its roles in inflammation inhibition and proliferation of NSCs are unknown. Methods. SCI in a rat model was established, and the effects of Rosi on motor functions were assessed. The effects of Rosi on NSC proliferation and the underlying mechanisms were explored in details. Results. We showed that Rosi ameliorated impairment of moto functions in SCI rats, inhibited inflammation, and promoted proliferation of NSCs in vivo. Rosi increased ATP production through enhancing glycolysis but not oxidative phosphorylation. Rosi reduced mitophagy by downregulating PTEN-induced putative kinase 1 (PINK1) transcription to promote NSC proliferation, which was effectively reversed by an overexpression of PINK1 in vitro. Through KEGG analysis and experimental validations, we discovered that Rosi reduced the expression of forkhead box protein O1 (FOXO1) which was a critical transcription factor of PINK1. Three FOXO1 consensus sequences (FCSs) were found in the first intron of the PINK1 gene, which could be potentially binding to FOXO1. The proximal FCS (chr 5: 156680169–156680185) from the translation start site exerted a more significant influence on PINK1 transcription than the other two FCSs. The overexpression of FOXO1 entirely relieved the inhibition of PINK1 transcription in the presence of Rosi. Conclusions. Besides inflammation inhibition, Rosi suppressed mitophagy by reducing FOXO1 to decrease the transcription of PINK1, which played a pivotal role in accelerating the NSC proliferation.

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Koumine Suppresses IL-1β Secretion and Attenuates Inflammation Associated With Blocking ROS/NF-κB/NLRP3 Axis in Macrophages

Frontiers in Pharmacology ◽

10.3389/fphar.2020.622074 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yufei Luo ◽

Bojun Xiong ◽

Haiping Liu ◽

Zehong Chen ◽

Huihui Huang ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammatory Diseases ◽

Inhibitory Effect ◽

Receptor Protein ◽

Mechanistic Study ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation ◽

Underlying Mechanisms

Koumine (KM), one of the primary constituents of Gelsemium elegans, has been used for the treatment of inflammatory diseases such as rheumatoid arthritis, but whether KM impacts the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome remains unknown. This study aimed to explore the inhibitory effect of KM on NLRP3 inflammasome activation and the underlying mechanisms both in vitro using macrophages stimulated with LPS plus ATP, nigericin or monosodium urate (MSU) crystals and in vivo using an MSU-induced peritonitis model. We found that KM dose-dependently inhibited IL-1β secretion in macrophages after NLRP3 inflammasome activators stimulation. Furthermore, KM treatment efficiently attenuated the infiltration of neutrophils and suppressed IL-1β production in mice with MSU-induced peritonitis. These results indicated that KM inhibited NLRP3 inflammasome activation, and consistent with this finding, KM effectively inhibited caspase-1 activation, mature IL-1β secretion, NLRP3 formation and pro-IL-1β expression in LPS-primed macrophages treated with ATP, nigericin or MSU. The mechanistic study showed that, KM exerted a potent inhibitory effect on the NLRP3 priming step, which decreased the phosphorylation of IκBα and p65, the nuclear localization of p65, and the secretion of TNF-α and IL-6. Moreover, the assembly of NLRP3 was also interrupted by KM. KM blocked apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and its oligomerization and hampered the NLRP3-ASC interaction. This suppression was attributed to the ability of KM to inhibit the production of reactive oxygen species (ROS). In support of this finding, the inhibitory effect of KM on ROS production was completely counteracted by H2O2, an ROS promoter. Our results provide the first indication that KM exerts an inhibitory effect on NLRP3 inflammasome activation associated with blocking the ROS/NF-κB/NLRP3 signal axis. KM might have potential clinical application in the treatment of NLRP3 inflammasome-related diseases.

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Silencing lncRNA TUG1 Alleviates LPS-Induced Mouse Hepatocyte Inflammation by Targeting miR-140/TNF

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.616416 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qing-Min Liu ◽

Li-Li Liu ◽

Xi-Dong Li ◽

Ping Tian ◽

Hao Xu ◽

...

Keyword(s):

Public Health Problem ◽

Immunofluorescence Assay ◽

Major Public Health Problem ◽

Inflammation Response ◽

Beneficial Effects ◽

Multiple Organs ◽

Underlying Mechanisms ◽

Lncrna Tug1

Hepatitis is a major public health problem that increases the risk of liver cirrhosis and liver cancer. Numerous studies have revealed that long non-coding RNAs (lncRNAs) exert essential function in the inflammatory response of multiple organs. Herein, we aimed to explore the effect of lncRNA TUG1 in LPS-induced hepatocyte inflammation response and further illuminate the underlying mechanisms. Mice were intraperitoneally injected with LPS, and the liver inflammation was evaluated. Microarray showed that lncRNA TUG1 was upregulated in LPS-induced hepatocyte inflammation. qRT-PCR and immunofluorescence assay indicated a significant increase of TUG1 in mice with LPS injection. Functional analysis showed that si-TUG1 inhibited LPS-induced inflammation response in mice liver, inhibited apoptosis level, and protected liver function. Then, we knock down TUG1 in normal human hepatocyte AML12. Consistent with in vivo results, si-TUG1 removed the injury of LPS on AML12 cells. Furthermore, TUG1 acted as a sponge of miR-140, and miR-140 directly targeted TNFα (TNF). MiR-140 or si-TNF remitted the beneficial effects of TUG1 on LPS-induced hepatocyte inflammation response both in vitro and in vivo. Our data revealed that deletion of TUG1 protected against LPS-induced hepatocyte inflammation via regulating miR-140/TNF, which might provide new insight for hepatitis treatment.

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

Nutrients ◽

10.3390/nu10111711 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1711 ◽

Cited By ~ 23

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.

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Antiseptic effect of vicenin-2 and scolymoside from Cyclopia subternata (honeybush) in response to HMGB1 as a late sepsis mediator in vitro and in vivo

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0021 ◽

2015 ◽

Vol 93 (8) ◽

pp. 709-720 ◽

Cited By ~ 4

Author(s):

Wonhwa Lee ◽

Eun-Kyung Yoon ◽

Kyung-Min Kim ◽

Dong Ho Park ◽

Jong-Sup Bae

Keyword(s):

Inflammatory Diseases ◽

Umbilical Vein ◽

High Mobility ◽

Nuclear Factor Κb ◽

Underlying Mechanisms ◽

And Migration ◽

Umbilical Vein Endothelial Cells ◽

Factor Α

Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, which are 2 active compounds from C. subternata that act against high mobility group box 1 (HMGB1)-mediated septic responses in human umbilical vein endothelial cells (HUVECs) and mice. The antiseptic activities of vicenin-2 and scolymoside were determined by measuring permeability, neutrophil adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice. According to the results, vicenin-2 and scolymoside effectively inhibited lipopolysaccharide-induced release of HMGB1, and suppressed HMGB1-mediated septic responses such as hyperpermeability, the adhesion and migration of leukocytes, and the expression of cell adhesion molecules. In addition, vicenin-2 and scolymoside suppressed the production of tumor necrosis factor-α and interleukin 6, and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by HMGB1. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

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