Polyphenols in Liubao Tea Can Prevent CCl4-Induced Hepatic Damage in Mice through Its Antioxidant Capacities

The present study investigated the preventive effect of polyphenols in Liubao tea (PLT) on carbon tetrachloride (CCl4)-induced liver injury in mice. The mice were initially treated with PLT, followed by induction of liver injury using 10 mL/kg CCl4. Then liver and serum indices, as well as the expression levels of related messenger RNAs (mRNAs) and proteins in liver tissues were measured. The results showed that PLT reduces the liver quality and indices of mice with liver injury. PLT also downregulates aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TGs), and malondialdehyde (MDA), and upregulates superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the sera of mice with liver injury. PLT also reduces serum levels of interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) cytokines in mice with liver injury. Pathological morphological observation also shows that PLT reduces CCl4-induced central venous differentiation of liver tissues and liver cell damage. Furthermore, qPCR and Western blot also confirm that PLT upregulates the mRNA and protein expressions of Gu/Zn-SOD, Mn-SOD, catalase (CAT), GSH-Px, and nuclear factor of κ-light polypeptide gene enhancer in B-cells inhibitor-α (IκB-α) in liver tissues, and downregulates the expression of cyclooxygenase 2 (COX-2) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). Meanwhile, PLT also raised the phosphorylated (p)-NF-κB p65 and cytochrome P450 reductase protein expression in liver injury mice. The components of PLT include gallic acid, catechin, caffeine, epicatechin (EC), epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), and epicatechin gallate (ECG), which possibly have a wide range of biological activities. Thus, PLT imparts preventive effects against CCl4-induced liver injury, which is similar to silymarin.

Download Full-text

Andrographolide, A Natural Antioxidant: An Update

Antioxidants ◽

10.3390/antiox8120571 ◽

2019 ◽

Vol 8 (12) ◽

pp. 571 ◽

Cited By ~ 12

Author(s):

Eugenie Mussard ◽

Annabelle Cesaro ◽

Eric Lespessailles ◽

Brigitte Legrain ◽

Sabine Berteina-Raboin ◽

...

Keyword(s):

Signaling Pathway ◽

Herbal Remedy ◽

Biological Activities ◽

Lung Infection ◽

Andrographis Paniculata ◽

Natural Antioxidant ◽

Nuclear Factor ◽

Wide Range ◽

Anti Cancer ◽

Antioxidant Mechanisms

Traditionally, Andrographis paniculata has been used as an herbal remedy for lung infection treatments. Its leaves contain a diterpenoid labdane called andrographolide responsible for a wide range of biological activities such as antioxidant, anti-inflammatory, and anti-cancer properties. This manuscript is a brief review of the antioxidant mechanisms and the regulation of the Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling pathway by andrographolide.

Download Full-text

Molecular Targets Involved in the Neuroprotection Mediated by Terpenoids

Planta Medica ◽

10.1055/a-0953-6738 ◽

2019 ◽

Vol 85 (17) ◽

pp. 1304-1315 ◽

Cited By ~ 4

Author(s):

Laura González-Cofrade ◽

Beatriz de las Heras ◽

Luis Apaza Ticona ◽

Olga M. Palomino

Keyword(s):

Therapeutic Potential ◽

Cell Damage ◽

Biological Activities ◽

Neuronal Cell ◽

Molecular Targets ◽

Research Activity ◽

Neuroprotective Effects ◽

Therapeutic Value ◽

Wide Range ◽

Drug Leads

AbstractNatural products and their derivatives represent the most consistently successful source of drug leads. Terpenoids, a structurally diverse group, are secondary metabolites widely distributed in nature, endowed with a wide range of biological activities such as antibacterial, anti-inflammatory, antitumoral, or neuroprotective effects, which consolidate their therapeutic value. During the last decades, and taking into consideration the prevalence of aging-related diseases, research activity into the neuroprotective effects of these types of compounds has increased enormously. Several signaling pathways involved in neuroprotection are targets of their mechanism of action and mediate their pleiotropic protective activity in neuronal cell damage. In the present review, molecular basis of the neuroprotection exerted by terpenoids is presented, focusing on preclinical evidence of the therapeutic potential of diterpenoids and triterpenoids on neurodegenerative disorders. By acting on diverse mechanisms simultaneously, terpenoids have been emphasized as promising multitarget agents.

Download Full-text

Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

Biomolecules ◽

10.3390/biom9080346 ◽

2019 ◽

Vol 9 (8) ◽

pp. 346 ◽

Cited By ~ 28

Author(s):

Aladaileh ◽

Abukhalil ◽

Saghir ◽

Hanieh ◽

Alfwuaires ◽

...

Keyword(s):

Nitric Oxide ◽

Dna Damage ◽

Liver Injury ◽

Oxidative Damage ◽

Biological Activities ◽

B Cell Lymphoma ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Quinone Acceptor

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

Download Full-text

Study on the Mechanism of Erucamide Mediating Anti-stress Liver Injury in Rats by Inhibiting Glycine Cleavage

10.21203/rs.3.rs-148552/v1 ◽

2021 ◽

Author(s):

Qin Cuiying ◽

Chuyu Feng ◽

Zhenfeng He ◽

Zhanle Wang ◽

Changyun Qin ◽

...

Keyword(s):

Gene Expression ◽

Liver Injury ◽

Cell Apoptosis ◽

Cell Damage ◽

Colorimetric Method ◽

Normal Group ◽

Sd Rats ◽

Glycine Cleavage ◽

Liver Tissues

Abstract Objectives: In order to research the erucamide effect on Stress-induced rats liver injury and potential mechanism of the protect effect.Methods: Stress-induced liver injury in SD rats was used as an in vivo model. Adult female SD rats were differentiated into three groups: Normal group, SLI(Stress-induced liver injury)-group and [SLI+Erucamide (95.4uM/Kg)]-treated group. In addition, the transcriptomes from 9 liver tissues were sequenced using an Illumina sequencing platform, screened the differentially expressed genes and related cell signal transduction pathways. Gene expression was measured by RT-qPCR. Furthermore, observe the pathological changes of rats liver tissues by HE staining , and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by microplate method. Human LO2 cells was used for in vitro model, the cells in the logarithmic growth phase were differentiated into normal group, corticosterone groups, erucamide, and glycine intervention groups. Corticosterone (300uM) was used to induce LO2 cell damage in vitro. And using tetrazolium (MTT) colorimetric method to determine and calculate cells viability. Hoechst 33342 staining was used to observe the morphology of hepatocyte apoptosis.Result: This study showed that erucamide has a significant effect on Stress-induced liver injury in rats, which is proved by HE staining test and ALT / AST detection experiment (p<0.05). The results of transcriptomes indicated that erucamide could inhibit the cleavage of glycine to prevent stress-induced liver injury in rats. Moreover, RT-qPCR results demonstrated that erucamide reduced the expression of DLD and AMT(p<0.05) genes in glycine cleavage system, thereby reducing glycine cleavage. Compared with the SLI group, erucamide inhibited UNC5B gene expression(p<0.05), which is related to cell apoptosis, indicating that erucamide can inhibit cell apoptosis. In addition, erucamide inhibited the expression of GPSM3 (p<0.05) and IGSF11 that are associated with inflammation. In addition, both erucamide and glycine could prevent the damage of LO2 hepatocytes induced by CORT. Erucamide and Glycine were effective in preventing Crot-induced LO2 cell damage.Conclusions: In this research, erucamide inhibits the cleavage of glycine to anti-stress liver injury in rats.

Download Full-text

Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/8284107 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Lu Xu ◽

Yifan Yu ◽

Rui Sang ◽

Jinxia Li ◽

Bingjie Ge ◽

...

Keyword(s):

Liver Injury ◽

Signaling Pathways ◽

Heme Oxygenase 1 ◽

Intragastric Administration ◽

Related Factor ◽

Nuclear Factor ◽

Protective Effects ◽

Histopathological Changes ◽

Liver Index ◽

Liver Tissues

Taraxasterol, a pentacyclic-triterpene compound, is one of the main active components isolated from the traditional Chinese medicinal herb Taraxacum. The objective of this study is to evaluate the protective effects of taraxasterol and its possible underlying mechanisms against ethanol-induced liver injury in mice. ICR mice were fed with Lieber-DeCarli diet containing 5% ethanol for 10 d and then challenged with a single dose of 20% ethanol (5 g/kg BW) by intragastric administration. The mice were intragastrically treated daily with taraxasterol (2.5, 5, and 10 mg/kg). Tiopronin was used as a positive control. The liver index was calculated, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in sera were detected. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) and the activity of superoxide dismutase (SOD) in the livers were measured. The histopathological changes of liver tissues were observed by hematoxylin and eosin (H&E) staining. The protein expression levels of hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (Nrf2), antioxidant protein heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) signaling pathway in liver tissues were detected by immunohistochemistry and Western blot methods. Taraxasterol significantly reduced the ethanol-induced increases of liver index, ALT, AST, and TG levels in sera and TG and MDA contents in the livers and hepatic ROS production and suppressed the ethanol-induced decreases of hepatic GSH level and SOD activity. Taraxasterol also significantly inhibited the secretion of proinflammatory cytokines TNF-α and IL-6 induced by ethanol. In addition, taraxasterol improved the liver histopathological changes in mice with ethanol-induced liver injury. Further studies revealed that taraxasterol significantly inhibited the ethanol-induced upregulation of CYP2E1, increased the ethanol-induced downregulation of Nrf2 and HO-1, and inhibited the degradation of inhibitory kappa Bα (IκBα) and the expression level of NF-κB p65 in liver tissues of ethanol-induced mice. These findings suggest that taraxasterol possesses the potential protective effects against ethanol-induced liver injury in mice by exerting antioxidative stress and anti-inflammatory response via CYP2E1/Nrf2/HO-1 and NF-κB signaling pathways.

Download Full-text

Pharmacologically potentials of different substituted coumarin derivatives

10.31221/osf.io/w6hdg ◽

2019 ◽

Cited By ~ 1

Author(s):

Chem Int

Keyword(s):

Benzene Ring ◽

Bioactive Compounds ◽

Biological Activities ◽

Pharmacological Properties ◽

Coumarin Derivatives ◽

Wide Range ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Coumarin Compounds

Coumarin and its derivatives are widely spread in nature. Coumarin goes to agroup as benzopyrones, which consists of a benzene ring connected to a pyronemoiety. Coumarins displayed a broad range of pharmacologically useful profile.Coumarins are considered as a promising group of bioactive compounds thatexhibited a wide range of biological activities like anti-microbial, anti-viral,antiparasitic, anti-helmintic, analgesic, anti-inflammatory, anti-diabetic, anticancer,anti-oxidant, anti-proliferative, anti-convulsant, and antihypertensiveactivities etc. The coumarin compounds have immense interest due to theirdiverse pharmacological properties. In particular, these biological activities makecoumarin compounds more attractive and testing as novel therapeuticcompounds.

Download Full-text

Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.18:176-182 ◽

2019 ◽

Vol 18 (2) ◽

pp. 176-182

Author(s):

Chen Weiyan ◽

Deng Wujian ◽

Chen Songwei

Keyword(s):

Acute Lung Injury ◽

B Cells ◽

Lung Injury ◽

Signaling Pathway ◽

Light Chain ◽

Cecal Ligation ◽

Nuclear Factor ◽

Kappa Light Chain ◽

Cecal Ligation And Puncture ◽

Light Chain Enhancer

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

Download Full-text

Synthesis, Characterization and Antiproliferative Activity Assessment of a Novel 1H-5-mercapto-1,2,4 Triazole Derivative

Revista de Chimie ◽

10.37358/rc.17.4.5544 ◽

2017 ◽

Vol 68 (4) ◽

pp. 745-747 ◽

Cited By ~ 1

Author(s):

Marius Mioc ◽

Sorin Avram ◽

Vasile Bercean ◽

Mihaela Balan Porcarasu ◽

Codruta Soica ◽

...

Keyword(s):

Antiproliferative Activity ◽

Biological Activities ◽

Cancer Cell Line ◽

Vascular Endothelial ◽

Triazole Derivative ◽

Activity Assessment ◽

Wide Range ◽

Specific Receptors ◽

Endothelial Growth Factor ◽

Selection Of

Angiogenesis plays an important function in tumor proliferation, one of the main angiogenic promoters being the vascular endothelial growth factor (VEGF) which activates specific receptors, particularly VEGFR-2. Thus, VEGFR-2 has become an essential therapeutic target in the development of new antitumor drugs. 1,2,4-triazoles show a wide range of biological activities, including antitumor effect, which was documented by numerous reports. In the current study the selection of 5-mercapto-1,2,4-triazole structure (1H-3-styryl-5-benzylidenehydrazino-carbonyl-methylsulfanil-1,2,4-triazole, Tz3a.7) was conducted based on molecular docking that emphasized it as suitable ligand for VEGFR-2 and EGFR1 receptors. Compound Tz3a.7 was synthesized and physicochemically and biologically evaluated thus revealing a moderate antiproliferative activity against breast cancer cell line MDA-MB-231.

Download Full-text

Potential Triazole-based Molecules for the Treatment of Neglected Diseases

Current Medicinal Chemistry ◽

10.2174/0929867324666170727103901 ◽

2019 ◽

Vol 26 (23) ◽

pp. 4403-4434 ◽

Cited By ~ 5

Author(s):

Susimaire Pedersoli Mantoani ◽

Peterson de Andrade ◽

Talita Perez Cantuaria Chierrito ◽

Andreza Silva Figueredo ◽

Ivone Carvalho

Keyword(s):

Effective Treatment ◽

Chagas Disease ◽

Medicinal Chemistry ◽

Biological Activities ◽

Neglected Diseases ◽

Triazole Derivatives ◽

Wide Range ◽

The World ◽

Great Relevance ◽

The Moment

Neglected Diseases (NDs) affect million of people, especially the poorest population around the world. Several efforts to an effective treatment have proved insufficient at the moment. In this context, triazole derivatives have shown great relevance in medicinal chemistry due to a wide range of biological activities. This review aims to describe some of the most relevant and recent research focused on 1,2,3- and 1,2,4-triazolebased molecules targeting four expressive NDs: Chagas disease, Malaria, Tuberculosis and Leishmaniasis.

Download Full-text

Heterocycle Compounds with Antimicrobial Activity

Current Pharmaceutical Design ◽

10.2174/1381612826666200206093815 ◽

2020 ◽

Vol 26 (8) ◽

pp. 867-904 ◽

Cited By ~ 2

Author(s):

Maria Fesatidou ◽

Anthi Petrou ◽

Geronikaki Athina

Keyword(s):

Heterocyclic Compounds ◽

Bacterial Infections ◽

Scientific Community ◽

Antimicrobial Agents ◽

Fungal Infections ◽

Biological Activities ◽

Literature Survey ◽

New Findings ◽

Wide Range ◽

Number Of Microorganisms

Background: Bacterial infections are a growing problem worldwide causing morbidity and mortality mainly in developing countries. Moreover, the increased number of microorganisms, developing multiple resistances to known drugs, due to abuse of antibiotics, is another serious problem. This problem becomes more serious for immunocompromised patients and those who are often disposed to opportunistic fungal infections. Objective: The objective of this manuscript is to give an overview of new findings in the field of antimicrobial agents among five-membered heterocyclic compounds. These heterocyclic compounds especially five-membered attracted the interest of the scientific community not only for their occurrence in nature but also due to their wide range of biological activities. Method: To reach our goal, a literature survey that covers the last decade was performed. Results: As a result, recent data on the biological activity of thiazole, thiazolidinone, benzothiazole and thiadiazole derivatives are mentioned. Conclusion: It should be mentioned that despite the progress in the development of new antimicrobial agents, there is still room for new findings. Thus, research still continues.

Download Full-text