scholarly journals Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Temidayo D. Popoola ◽  
Stephanie T. Guetchueng ◽  
Kenneth J. Ritchie ◽  
Olufunsho Awodele ◽  
Nicola M. Dempster ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Chemical Constituents ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Root Extract ◽  
Related Factor ◽  
Nitric Oxide Release ◽  
Anti Cancer ◽  
Fold Induction ◽  
Anti Inflammatory

Abstract Background Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. Methods Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2′,7′-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). Results Extracts up to 100 μg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 200 μg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. Conclusion As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

scholarly journals TERMINALIA CHEBULA: SUCCESS FROM BOTANY TO ALLOPATHIC AND AYURVEDIC PHARMACY

2016 ◽  
Vol 9 (5) ◽  
pp. 21
Author(s):  
Varun Garg ◽  
Barinder Kaur ◽  
Sachin Kumar Singh ◽  
Bimlesh Kumar
Keyword(s):  
Chemical Constituents ◽  
Present Review ◽  
Terminalia Chebula ◽  
Pharmacological Activities ◽  
Therapeutic Uses ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Anti Inflammatory

ABSTRACTTerminalia chebula (TC) is a unique herb having various therapeutic potentials as anti-inflammatory, antioxidant, anticancer, and digestant. It belongsto family Combretaceae. In the present review, an attempt has been made to decipher classification, chemical constituents, therapeutic uses, andpatents that have been reported for TC. Various pharmacological activities of TC that make it as potential medicine and its Ayurvedic formulationsare highlighted.Keywords: Terminalia chebula, Anti-oxidant, Anti-cancer, Ayurvedic formulations, Anti-oxidant.

scholarly journals Chemical Constituents of the Aerial Parts of Scoparia dulcis and Anti-cancer, Anti-inflammatory Activities

2019 ◽  
Vol 544 ◽  
pp. 012029
Author(s):  
Nguyen Ngoc Thanh Tin ◽  
Nguyen Dang Thanh Truc ◽  
Hoang Thi Thu Hang ◽  
Pham Thi Nhat Trinh ◽  
Tri Duc Lam ◽  
...  
Keyword(s):  
Chemical Constituents ◽  
Scoparia Dulcis ◽  
Aerial Parts ◽  
Anti Cancer ◽  
Anti Inflammatory

scholarly journals Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NFκB Signaling Pathways in Primary Splenocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Hsin-Ling Yang ◽  
Ting-Yu Yang ◽  
Yugandhar Vudhya Gowrisankar ◽  
Chun-Huei Liao ◽  
Jiunn-Wang Liao ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Ex Vivo ◽  
Root Extract ◽  
Piper Methysticum ◽  
Serum Lipase ◽  
Antioxidant Genes ◽  
Anti Inflammatory

Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 μM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1β protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA’s potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF-α/IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.

scholarly journals Tackling Chronic Inflammation with Withanolide Phytochemicals—A Withaferin A Perspective

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1107
Author(s):  
Emilie Logie ◽  
Wim Vanden Berghe
Keyword(s):  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Withaferin A ◽  
Related Factor ◽  
Nuclear Factor ◽  
Pharmaceutical Drugs ◽  
In Vivo Models ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory

Chronic inflammatory diseases are considered to be one of the biggest threats to human health. Most prescribed pharmaceutical drugs aiming to treat these diseases are characterized by side-effects and negatively affect therapy adherence. Finding alternative treatment strategies to tackle chronic inflammation has therefore been gaining interest over the last few decades. In this context, Withaferin A (WA), a natural bioactive compound isolated from Withania somnifera, has been identified as a promising anti-cancer and anti-inflammatory compound. Although the majority of studies focus on the molecular mechanisms of WA in cancer models, recent evidence demonstrates that WA also holds promise as a new phytotherapeutic agent against chronic inflammatory diseases. By targeting crucial inflammatory pathways, including nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2 related factor 2 (Nrf2) signaling, WA suppresses the inflammatory disease state in several in vitro and preclinical in vivo models of diabetes, obesity, neurodegenerative disorders, cystic fibrosis and osteoarthritis. This review provides a concise overview of the molecular mechanisms by which WA orchestrates its anti-inflammatory effects to restore immune homeostasis.

scholarly journals SUN-LB101 NRF2 Represses Obesity-Associated Adipose Tissue Inflammation in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yoko Yagishita ◽  
Akira Uruno ◽  
Thomas W Kensler ◽  
Masayuki Yamamoto
Keyword(s):  
Adipose Tissue ◽  
Myeloid Cell ◽  
Potential Effect ◽  
Luciferase Reporter ◽  
Standard Diet ◽  
Related Factor ◽  
Nrf2 Pathway ◽  
Pathway Activation ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory

Abstract Obesity is associated with type 2 diabetes, cardiovascular disease and increased incidence of cancer. Chronic inflammation, mainly emanating from adipose tissue, has been proposed to be one of the links between obesity and these pathologies. Thus, identification of new targets against obesity and especially obesity-induced inflammation is needed urgently. Transcription factor Nrf2 (NF-E2-related-factor-2) plays a central role in cytoprotective responses to oxidative and electrophilic stresses and also exerts anti-inflammatory effects in rodent models of inflammation. However, whether activation of Nrf2 signaling pathway influences obesity-associated inflammation in adipose tissue is not well established. To this end, we generated mice with systemic activation of the Nrf2 pathway (Keap1flox/–), as well as mouse models with tissue-specific Nrf2 pathway activation: adipocyte-specific (Fabp4Cre::Keap1flox/ flox) and myeloid cell-specific (LymCre::Keap1flox/ flox). These mice were exposed to a high-fat diet (HFD) 60% kcal fat regimen for 6-weeks or crossed into the db/db background. Keap1flox/– mice showed a dramatic decrease of the numbers of F4/80-positive macrophages in white adipose tissue (WAT). Interestingly, both Fabp4Cre::Keap1flox/ flox and LymCre::Keap1flox/ flox mice showed suppression of F4/80-positive macrophages in WAT as well, suggesting enhanced Nrf2 signaling in either adipocytes or myeloid cells might contribute to anti-inflammatory effects in WAT under the stress of HFD. Transcript levels of inflammatory markers, especially macrophage F4/80 and Cd68 and the chemokine Ccl2 were decreased in the WAT from Keap1flox/– mice on the standard diet and also in the WAT of Keap1flox/– mice in the db/db background. Pharmacological activation of the Nrf2 pathway by treatment with CDDO-Im also suppressed Ccl2 expression in WAT of HFD fed mice and db/db mice. As CCL2 is a key mediator of macrophage accumulation in adipose tissue, we further studied the potential effect of Nrf2 on the transcriptional regulation of Ccl2 using 3T3-L1 preadipocyte and RAW264.7 macrophage cell lines. Treatment of both lines with the small molecule inducer of Nrf2, diethyl maleate significantly suppressed LPS-induced expression of Ccl2. Analysis using luciferase reporter assay revealed that a Nrf2 binding site in the Ccl2 5’ flanking region from -235 to +85 contributed to gene silencing of Ccl2 by activation of Nrf2. Our findings suggest that the druggable Nrf2 pathway may be an effective target to combat obesity-associated inflammation in adipose tissue and its’ concomitant metabolic disorders. Supported by AMED BINDS JP19am0101001 (MY), 19H05649 (MY), 16KK0195 (AU), NIH R35 CA197222 (TWK), JSPS OT 290125 (YY).

scholarly journals Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiah Ning Tan ◽  
Shamin Mohd Saffian ◽  
Fhataheya Buang ◽  
Zakiah Jubri ◽  
Ibrahim Jantan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Clinical Studies ◽  
Glycogen Synthase ◽  
Chemical Constituents ◽  
Future Research ◽  
Prostaglandin E ◽  
Pharmacokinetic Studies ◽  
Related Factor ◽  
Anti Inflammatory

Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents.Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as “Gynura,” “antioxidant,” “anti-inflammatory,” or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English.Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species.Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

scholarly journals Nuclear Factor Erythroid 2 Related Factor 2 Activator JC-5411 Inhibits Atherosclerosis Through Suppression of Inflammation and Regulation of Lipid Metabolism

2020 ◽  
Vol 11 ◽  
Author(s):  
Xinhai Jiang ◽  
Yining Li ◽  
Weizhi Wang ◽  
Xiaowan Han ◽  
Jiangxue Han ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Related Factor ◽  
Nuclear Factor ◽  
Phenethyl Isothiocyanate ◽  
Aortic Sinus ◽  
Anti Inflammatory

Phenethyl isothiocyanate is widely present in cruciferous vegetables with multiple biological effects. Here we reported the antiatherogenic effects and the underlying mechanisms of JC-5411 (Phenethyl isothiocyanate formulation) in vitro and in vivo. Luciferase reporter assay showed that JC-5411 increased the activity of nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE). JC-5411 treatment significantly increased the protein expression of Nrf2 and its downstream target gene hemeoxygenase 1 (HO-1) in liver of apolipoprotein E deficient (ApoE−/−) mice. Importantly, JC-5411 treatment significantly reduced atherosclerotic plaque area in both en face aorta and aortic sinus when compared with model group in WD induced ApoE−/− mice. JC-5411 obviously decreased proinflammatory factors’ levels in serum of ApoE−/− mice, LPS stimulated macrophages and TNFα induced endothelial cells, respectively. JC-5411 significantly decreased the levels of total cholesterol (TC) and triglyceride (TG) in both serum and liver of ApoE−/− mice and hyperlipidemic golden hamsters. Mechanism studies showed that JC-5411 exerted anti-inflammatory effect through activating Nrf2 signaling and inhibiting NF-κB and NLRP3 inflammasome pathway. JC-5411 exerted regulating lipid metabolism effect through increasing cholesterol transfer proteins (ABCA1 and LDLR) expression, regulating fatty acids synthesis related genes (p-ACC, SCD1 and FAS), and increasing fatty acids β-oxidation (CPT1A) in vivo. Furthermore, JC-5411 treatment had a favorable antioxidant effect in ApoE−/− mice by increasing the antioxidant related genes expression. Taken together, we conclude that JC-5411 as a Nrf2 activator has anti-inflammatory, rebalancing lipid metabolism, and antioxidant effects, which makes it as a potential therapeutic agent against atherosclerosis.

scholarly journals Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 167
Author(s):  
Seyed Hossein Shahcheraghi ◽  
Fateme Salemi ◽  
Niloufar Peirovi ◽  
Jamshid Ayatollahi ◽  
Waqas Alam ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Glutamate Cysteine Ligase ◽  
Response Elements ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory ◽  
Molecular Aspects

Nuclear factor erythroid 2 p45-related factor (2Nrf2) is an essential leucine zipper protein (bZIP) that is primarily located in the cytoplasm under physiological conditions. Nrf2 principally modulates endogenous defense in response to oxidative stress in the brain.In this regard, Nrf2 translocates into the nucleus and heterodimerizes with the tiny Maf or Jun proteins. It then attaches to certain DNA locations in the nucleus, such as electrophile response elements (EpRE) or antioxidant response elements (ARE), to start the transcription of cytoprotective genes. Many neoplasms have been shown to have over activated Nrf2, strongly suggesting that it is responsible for tumors with a poor prognosis. Exactly like curcumin, Zinc–curcumin Zn (II)–curc compound has been shown to induce Nrf2 activation. In the cancer cell lines analyzed, Zinc–curcumin Zn (II)–curc compound can also display anticancer effects via diverse molecular mechanisms, including markedly increasing heme oxygenase-1 (HO-1) p62/SQSTM1 and the Nrf2 protein levels along with its targets. It also strikingly decreases the levels of Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1) protein.As a result, the crosstalk between p62/SQSTM1 and Nrf2 could be used to improve cancer patient response to treatments. The interconnected anti-inflammatory and antioxidative properties of curcumin resulted from its modulatory effects on Nrf2 signaling pathway have been shown to improve insulin resistance. Curcumin exerts its anti-inflammatory impact through suppressing metabolic reactions and proteins such as Keap1 that provoke inflammation and oxidation. A rational amount of curcumin-activated antioxidant Nrf2 HO-1 and Nrf2-Keap1 pathways and upregulated the modifier subunit of glutamate-cysteine ligase involved in the production of the intracellular antioxidant glutathione. Enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). A variety of in vivo, in vitro and clinical studies has been done so far to confirm the protective role of curcumin via Nrf2 regulation. This manuscript is designed to provide a comprehensive review on the molecular aspects of curcumin and its derivatives/analogs via regulation of Nrf2 regulation.

scholarly journals PML-Rara/Nrf2-Regulated Mir-125b Targets CEBPA and Influences Acute Promyelocytic Leukemia Cell Proliferation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2845-2845
Author(s):  
Zeng Chengwu ◽  
Yikai Zhang ◽  
Tianyu Qin ◽  
Lijian Yang ◽  
Shaohua Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Promyelocytic Leukemia ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Mapk Signaling ◽  
Promyelocytic Leukemia ◽  
Luciferase Reporter ◽  
Related Factor

Abstract Acute promyelocytic leukemia (APL) is characterized by the presence of PML-RARA fusion protein. The PML-RARA oncoprotein is known to be the initiating factor for APL development. We have previously found that miR-125b is highly expressed in APL and upregulated by PML-RARA. However, the molecular mechanisms by which PML-RARA controls miR-125b expression had been uncharacterized. In the present study, we further confirmed that expression of PML-RARA resulted in a significant increase in primary miR-125b expression, and we found that the nuclear transcription factor E2-related factor 2 (Nrf2) targeting genes (HO1) was also upregulated (Figure 1A). Consistently, HO1 and miR-125b are transcriptionally upregulated by proteasome inhibitor (MG132) which has been showed to activate Nrf2 (Figure 1B). Knockdown of Nrf2 can inhibit the effect of PML-RARA expression and MG132 (Figure 1C). Thus, these results indicated that Nrf2 may mediate PML-RARA-induced miR-125b expression. Furthermore, we demonstrated the importance of miR-125b in APL cell proliferation (Figure 1D), we showed that promoting leukemic cell grow is associated with AKT pathway and MAPK signaling (Figure 1E). Subsequent bioinformatic and RNA-seq data analysis (Figure 1F and G) identified CEBPA as a putative target of miR-125b, and we further experimentally verified using luciferase reporter constructs (Figure H). In conclusion, we identified the mechanisms responsible for the high expression and the function of miR-125b in APL, suggesting that the expression of miR-125b could be a primary oncogenic event in APL leukemogenesis. This study was supported by grants from the National Natural Science Foundation of China (No.81400102), the China Postdoctoral Science Foundation (No.2015M570751), and the Medical Scientific Research Foundation of Guangdong Province, China (A2015420). Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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