scholarly journals The cannabinoids – important therapeutic approach in the field of oncology

2021 ◽  
Vol 57 (2) ◽  
pp. 63-67 ◽  
Author(s):  
Nicoleta Mirela Blebea ◽  
◽  
Laura Adriana Bucur ◽  
Simona Negreș ◽  
◽  
...  
Keyword(s):  
Antineoplastic Agents ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Tumor Cell Lines ◽  
Common Cause ◽  
Oncological Diseases ◽  
Diagnosis Of Cancer ◽  
Anti Inflammatory

Oncological diseases are the most common cause of death worldwide, it is estimated that 25% of the population will face the diagnosis of cancer during life. Phytochemicals such as cannabinoids (CBs) have been used in various branches of medicine for their properties, and the discovery of the anti-tumor, anti-emetic and anti-inflammatory effects of some of these substances has encouraged their use in oncology. Phytocannabinoids, cannabidiol (CBD) and Δ-9-tetra-hydrocannabinol (THC), have numerous anti-emetic, analgesic, orexigenic, anti-inflammatory / immunosuppressive pharmacodynamic effects. In recent years, studies have been aimed at evaluating their efficacy as antineoplastic agents. Much in vivo and in vitro research has demonstrated the efficacy of CBs on certain tumor cell lines, highlighting their potential role in the complementary treatment of cancer. This paper suggests that exploring the molecular mechanisms induced by CBs in cancer cells may contribute to the development of effective treatments in oncological diseases.

scholarly journals Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 450
Author(s):  
Kensuke Mitsunari ◽  
Yasuyoshi Miyata ◽  
Tomohiro Matsuo ◽  
Yuta Mukae ◽  
Asato Otsubo ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Molecular Mechanisms ◽  
Prostatic Hyperplasia ◽  
Pathological Conditions ◽  
Urinary Tract Symptoms ◽  
Anti Inflammatory ◽  
Lower Urinary

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.

Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis

2016 ◽  
Vol 44 (03) ◽  
pp. 595-615 ◽  
Author(s):  
Tao Yu ◽  
Man Hee Rhee ◽  
Jongsung Lee ◽  
Seung Hyung Kim ◽  
Yanyan Yang ◽  
...  
Keyword(s):  
Panax Ginseng ◽  
Molecular Mechanisms ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Inhibitory Mechanisms ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Ginsenoside Rc

Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng’s various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that G-Rc may be a major component of KRG with useful anti-inflammatory properties due to its suppression of IRF-3 and AP-1 pathways.

scholarly journals Antioxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Citrus lumia Juice

2020 ◽  
Vol 11 ◽  
Author(s):  
Antonella Smeriglio ◽  
Marcella Denaro ◽  
Valeria D’Angelo ◽  
Maria Paola Germanò ◽  
Domenico Trombetta
Keyword(s):  
Ascorbic Acid ◽  
Acid Content ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Ascorbic Acid Content ◽  
Zebrafish Embryos ◽  
Anti Inflammatory ◽  
Dose Dependent

Citrus juices are a rich source of bioactive compounds with various and well-known health benefits. The aim of this study was to investigate the polyphenols and ascorbic acid content as well as to investigate the antioxidant, anti-inflammatory and anti-angiogenic properties of the juice of an ancient Mediterranean species, Citrus lumia Risso (CLJ). The antioxidant and anti-inflammatory activities were evaluated by several in vitro cell-free and cell-based assays, whereas two different in vivo models, the chick chorioallantoic membrane (CAM) and the zebrafish embryos, were used to characterize the anti-angiogenic properties. Twenty-eight polyphenols were identified by RP-LC-DAD-ESI-MS analysis (flavonoids 68.82% and phenolic acids 31.18%) with 1-caffeoyl-5-feruloylquinic acid and kaempferol 3′-rhamnoside, which represent the most abundant compounds (25.70 and 23.12%, respectively). HPLC-DAD analysis showed a high ascorbic acid content (352 mg/kg of CLJ), which contributes with polyphenols to the marked and dose-dependent antioxidant and anti-inflammatory properties observed. CLJ showed strong and dose-dependent anti-angiogenic activity as highlighted by the inhibition of blood vessel formation on CAMs and the decrease of endogenous alkaline phosphatase on zebrafish embryos. Moreover, within the concentration range tested, no dead or malformed embryos were recorded. Certainly, further studies are needed to investigate the molecular mechanisms underlying these promising biological effects, but considering the evidence of the present study, the use of CLJ as a ready-to drink safe prevention strategy for inflammatory-based diseases correlated to angiogenesis could be justified.

scholarly journals Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3

2020 ◽  
Author(s):  
Marion Lenoir ◽  
Rebeca Martin ◽  
Edgar Torres-Maravilla ◽  
Sead Chadi ◽  
Pamela González-Dávila ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Commensal Bacterium ◽  
Jnk Pathway ◽  
Faecalibacterium Prausnitzii ◽  
Anti Inflammatory

Abstract BackgroundThe commensal bacterium Faecalibacterium prausnitzii plays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown.MethodsA transcriptomic approach on human intestinal epithelial cells (HT-29) that were stimulated with TNF-α and exposed to F. prausnitzii culture supernatant (SN) was used. Modulation of the most upregulated gene after F. prausnitzii SN contact was validated both in vitro and in vivo.ResultsF. prausnitzii SN upregulates the expression of Dact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silenced Dact3 expression, the effect of F. prausnitzii SN was lost. Butyrate was identified as the F. prausnitzii effector responsible for Dact3 modulation. Dact3 upregulation was also validated in vivo in both healthy and inflamed mice treated with either F. prausnitzii SN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influences Dact3 expression.ConclusionsOur results provide new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacterium F. prausnitzii.*Contributed equally to this work

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.

An Appraisal of Current Pharmacological Perspectives of Sesamol: A Review

2020 ◽  
Vol 20 (11) ◽  
pp. 988-1000 ◽  
Author(s):  
Bellamkonda Bosebabu ◽  
Sri Pragnya Cheruku ◽  
Mallikarjuna Rao Chamallamudi ◽  
Madhavan Nampoothiri ◽  
Rekha R. Shenoy ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Biological Effects ◽  
Hepatoprotective Activity ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Pharmacological Effects ◽  
Bioactive Constituents ◽  
Anti Inflammatory

Sesame (Sesamum indicum L.) seeds have been authenticated for its medicinal value in both Chinese and Indian systems of medicine. Its numerous potential nutritional benefits are attributed to its main bioactive constituents, sesamol. As a result of those studies, several molecular mechanisms are emerging describing the pleiotropic biological effects of sesamol. This review summarized the most interesting in vitro and in vivo studies on the biological effects of sesamol. The present work summarises data available from Pubmed and Scopus database. Several molecular mechanisms have been elucidated describing the pleiotropic biological effects of sesamol. Its major therapeutic effects have been elicited in managing oxidative and inflammatory conditions, metabolic syndrome and mood disorders. Further, compelling evidence reflected the ability of sesamol in inhibiting proliferation of the inflammatory cell, prevention of invasion and angiogenesis via affecting multiple molecular targets and downstream mechanisms. Sesamol is a safe, non‐toxic chemical that mediates anti‐inflammatory effects by down‐regulating the transcription of inflammatory markers such as cytokines, redox status, protein kinases, and enzymes that promote inflammation. In addition, sesamol also induces apoptosis in cancer cells via mitochondrial and receptor‐mediated pathways, as well as activation of caspase cascades. In the present review, several pharmacological effects of sesamol are summarised namely, antioxidant, anti-cancer, neuroprotective, cardioprotective, anti-inflammatory, hypolipidemic, radioprotective, anti-aging, anti-ulcer, anti-dementia, anti-depressant, antiplatelet, anticonvulsant, anti-anxiolytic, wound healing, cosmetic (skin whitening), anti-microbial, matrix metalloproteinase (MMPs) inhibition, hepatoprotective activity and other biological effects. Here we have summarized the proposed mechanism behind these pharmacological effects.

scholarly journals The Review of in Vitro and in Vivo Studies over the Glycyrrhizic Acid as Natural Remedy Option for Treatment of Allergic Asthma

2019 ◽  
Author(s):  
Saloomeh Fouladi ◽  
Mohsen Masjedi ◽  
Mazdak Ganjalikhani Hakemi ◽  
Nahid Eskandari
Keyword(s):  
Allergic Asthma ◽  
Molecular Mechanisms ◽  
Glycyrrhizic Acid ◽  
Data Bank ◽  
In Vivo Studies ◽  
Th2 Cells ◽  
Antitumor Effects ◽  
Anti Inflammatory

Allergic asthma is the most common type of allergy which have become increasingly prevalent in all around the world. Airway eosinophilic inflammation is a major feature of allergic asthma. Glycyrrhiza uralensis (licorice) is one of the regular herbs in traditional Chinese medicine (TCM) as it has many effects on the immune system such as anti-inflammatory and immune regulatory activity; antiviral and antitumor effects. This review focuses on the "licorice” components, mainly glycyrrhizic acid (GA) and derivatives structure that evaluate its effects on the allergic asthma. We performed searching articles in Pubmed, Web of Science, and Scopus data bank from 1990 to 2017. The search syntax were: "glycyrrhizin" OR " glycyrrhizic acid" OR " glycyrrhizinic acid" OR" glycyrrhiza glabra" OR " liquorice root" OR "G. glabra" OR "glycyrrhizic Acid" AND "allergic asthma" OR "bronchial asthma" OR "asthma, bronchial" OR "airway hyper-responsiveness" OR "airway inflammation".   Several molecular mechanisms and inflammatory mediators may possibly be responsible for efficacy of glycyrrhizin. Some in vitro studies indicated to the fact that possible mechanisms of anti-inflammatory effects could be through reduction of pro-inflammatory mediator's synthesis that motivates eosinophil, basophils and mast cells to release cytokines for the differentiation of T helper cells into Th2 cells to secrete interleukins. Furthermore, some transcription factors such as NF-κB, STAT6 and HDAC2 go between modulations of anti-asthmatic effects. The last but not the least it can be said that glycyrrhizin is potentially a good herbal drug with the lower most adverse effects for asthma treatment.

scholarly journals Anti-Inflammatory and Immunosuppressive Effects of the A2AAdenosine Receptor

2011 ◽  
Vol 11 ◽  
pp. 320-339 ◽  
Author(s):  
Gillian R. Milne ◽  
Timothy M. Palmer
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Current Evidence ◽  
Receptor Subtypes ◽  
Protective Effects ◽  
Stress Injury ◽  
Anti Inflammatory

The production of adenosine represents a critical endogenous mechanism for regulating immune and inflammatory responses during conditions of stress, injury, or infection. Adenosine exerts predominantly protective effects through activation of four 7-transmembrane receptor subtypes termed A1, A2A, A2B, and A3, of which the A2Aadenosine receptor (A2AAR) is recognised as a major mediator of anti-inflammatory responses. The A2AAR is widely expressed on cells of the immune system and numerousin vitrostudies have identified its role in suppressing key stages of the inflammatory process, including leukocyte recruitment, phagocytosis, cytokine production, and immune cell proliferation. The majority of actions produced by A2AAR activation appear to be mediated by cAMP, but downstream events have not yet been well characterised. In this article, we review the current evidence for the anti-inflammatory effects of the A2AAR in different cell types and discuss possible molecular mechanisms mediating these effects, including the potential for generalised suppression of inflammatory gene expression through inhibition of the NF-κB and JAK/STAT proinflammatory signalling pathways. We also evaluate findings fromin vivostudies investigating the role of the A2AAR in different tissues in animal models of inflammatory disease and briefly discuss the potential for development of selective A2AAR agonists for use in the clinic to treat specific inflammatory conditions.

scholarly journals Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6073
Author(s):  
Laily Rahmawati ◽  
Nur Aziz ◽  
Jieun Oh ◽  
Yo Han Hong ◽  
Byoung Young Woo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Raw264.7 Cells ◽  
Acute Gastritis ◽  
Anti Inflammatory

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.

In VitroandIn VivoProtective Effects of Flavonoid-Enriched Lotus Seedpod Extract on Lipopolysaccharide-Induced Hepatic Inflammation

2019 ◽  
Vol 47 (01) ◽  
pp. 153-176 ◽  
Author(s):  
Hsien-Chun Tseng ◽  
Pei-Min Tsai ◽  
Ying-Hsiang Chou ◽  
Yueh-Chun Lee ◽  
Hui-Hsuan Lin ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Pyrrolidine Dithiocarbamate ◽  
Hepatic Inflammation ◽  
Traditional Chinese Herbal Medicine ◽  
Anti Inflammatory ◽  
Lotus Seedpod

Endotoxin lipopolysaccharide (LPS) plays an important role in the acceleration of hepatic inflammation. Natural medicinal plants that can prevent inflammation by targeting LPS have potential therapeutic clinical application. The aim of the study is to examine the anti-inflammatory effects of lotus seedpod extract (LSE), used as a traditional Chinese herbal medicine with hemostasis function and for eliminating bruise, on the LPS-induced hepatic inflammation and its underlying molecular mechanisms in vitro and in vivo. In vitro, LSE and its purified compound (-)-epigallocatechin (EGC) dose-dependently inhibited the expressions of pro-inflammatory cytokines and mediators, including tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-6, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), without affecting cell viability in LPS-stimulated human hepatoma cell line HepG2. Molecular studies showed the anti-LPS effect of HLP or EGC might be mediated via downregulation of Toll-like receptor 4. (TLR4)-mediated both NF-[Formula: see text]B and p38 signaling, as demonstrated by the usage of pyrrolidine dithiocarbamate (PDTC), a specific NF-[Formula: see text]B inhibitor. In vivo, LPS-induced hepatic inflammation was significantly ameliorated in LSE-fed mice as gauged by dose-dependent inhibition of serum levels of biochemical markers of liver damage, the changes of hepatic lobular architecture and the secretion of pro-inflammatory mediators, as well as induction of anti-oxidant enzymes. As a result, our data presented the first evidence of EGC-enriched LSE as an anti-inflammatory agent in LPS-stimulated HepG2 cells and mice, and these findings may open interesting perspectives to the strategy in treatment for hepatic inflammation.

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