scholarly journals Herbal Medicines for the Treatment of Nonalcoholic Steatohepatitis: Current Scenario and Future Prospects

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Ravirajsinh Jadeja ◽  
Ranjitsinh V. Devkar ◽  
Srinivas Nammi
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Metabolic Disorders ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Herbal Medicines ◽  
Experimental Models ◽  
Treatment Schedule ◽  
Herbal Extracts ◽  
Current Scenario

Nonalcoholic steatohepatitis (NASH) is a multifactorial disease and has close correlations with other metabolic disorders. This makes its treatment difficult using a single pharmacological drug. Use of plant extract/decoction or polyherbal formulation to treat various liver diseases is very well mentioned in various traditional systems of medicine (Ayurveda, Japanese or traditional Chinese Medicine, and Kampo medicine). Medicinal herbs are known for their multifaceted implications and thus can form an effective treatment schedule against NASH. Till date, several plant extracts, polyherbal formulations, and phytochemicals have been evaluated for their possible therapeutic potential in preventing onset and progression of NASH in experimental models, but clinical studies using the same are sparse. Herbal extracts with antioxidants, antidiabetic, and antihyperlipidemic properties have been shown to ameliorate symptoms of NASH. This review article is a meticulous compilation of our current knowledge on the role of natural products in alleviating NASH and possible lacunae in research that needs to be addressed.

scholarly journals The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3219 ◽  
Author(s):  
Balbina García-Reyes ◽  
Anna-Laura Kretz ◽  
Jan-Philipp Ruff ◽  
Silvia von Karstedt ◽  
Andreas Hillenbrand ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Ductal Adenocarcinoma ◽  
Transcriptional Elongation ◽  
Cyclin Dependent Kinases ◽  
Dismal Prognosis ◽  
The Family ◽  
Cycle Regulation

The family of cyclin-dependent kinases (CDKs) has critical functions in cell cycle regulation and controlling of transcriptional elongation. Moreover, dysregulated CDKs have been linked to cancer initiation and progression. Pharmacological CDK inhibition has recently emerged as a novel and promising approach in cancer therapy. This idea is of particular interest to combat pancreatic ductal adenocarcinoma (PDAC), a cancer entity with a dismal prognosis which is owed mainly to PDAC’s resistance to conventional therapies. Here, we review the current knowledge of CDK biology, its role in cancer and the therapeutic potential to target CDKs as a novel treatment strategy for PDAC.

scholarly journals Pharmacological Rationale for Targeting IL-17 in Asthma

2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Current Knowledge ◽  
Experimental Models ◽  
Airflow Limitation ◽  
Interleukin 17 ◽  
Asthma Phenotype ◽  
T Helper 2 ◽  
Bronchial Biopsies

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.

scholarly journals The complex functions of microRNA-150 in allergy, autoimmunity and immune tolerance

2021 ◽  
Vol 5 (4) ◽  
pp. 195-221
Author(s):  
Katarzyna Nazimek ◽  
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Signaling Cascades ◽  
Cell Functions ◽  
Regulatory Circuits ◽  
Complex Functions ◽  
Genetic Level

<abstract> <p>At present, special efforts are being made to develop the strategies allowing for activation of long-lasting antigen-specific immune tolerance in therapy of allergic and autoimmune diseases. Some of these therapeutic approaches are aimed at modulating cell functions at genetic level by using miRNA-based and miRNA-targeting treatments. Simultaneously, the crucial role of extracellular vesicles as natural miRNA conveyors is highlighted for induction of antigen-specific immune tolerance, especially that they appear to be easily manipulatable for therapeutic applications. Among other immune-related miRNAs, miR-150 is getting special attention as it is differently expressed by immune cells at various stages of their maturation and differentiation. In addition, miR-150 is involved in different signaling cascades orchestrating humoral and cell-mediated mechanisms of both innate and adaptive immune responses. Therefore, miR-150 is considered a master regulator of immunity in mammals. Currently, physiological miR-150-dependent regulatory circuits and causes of their malfunctioning that underlie the pathogenesis of allergic and autoimmune disorders are being unraveled. Thus, present review summarizes the current knowledge of the role of miR-150 in the pathogenesis and complications of these diseases. Furthermore, the involvement of miR-150 in regulation of immune responses to allergens and self-antigens and in induction of antigen-specific immune tolerance is discussed with the special emphasis on the therapeutic potential of this miRNA.</p> </abstract>

scholarly journals The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1887 ◽  
Author(s):  
Francesco Bonollo ◽  
George N. Thalmann ◽  
Marianna Kruithof-de Julio ◽  
Sofia Karkampouna
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapy Resistance ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Progression ◽  
Normal Prostate ◽  
Prostate Tumorigenesis

Tumors strongly depend on their surrounding tumor microenvironment (TME) for growth and progression, since stromal elements are required to generate the optimal conditions for cancer cell proliferation, invasion, and possibly metastasis. Prostate cancer (PCa), though easily curable during primary stages, represents a clinical challenge in advanced stages because of the acquisition of resistance to anti-cancer treatments, especially androgen-deprivation therapies (ADT), which possibly lead to uncurable metastases such as those affecting the bone. An increasing number of studies is giving evidence that prostate TME components, especially cancer-associated fibroblasts (CAFs), which are the most abundant cell type, play a causal role in PCa since the very early disease stages, influencing therapy resistance and metastatic progression. This is highlighted by the prognostic value of the analysis of stromal markers, which may predict disease recurrence and metastasis. However, further investigations on the molecular mechanisms of tumor–stroma interactions are still needed to develop novel therapeutic approaches targeting stromal components. In this review, we report the current knowledge of the characteristics and functions of the stroma in prostate tumorigenesis, including relevant discussion of normal prostate homeostasis, chronic inflammatory conditions, pre-neoplastic lesions, and primary and metastatic tumors. Specifically, we focus on the role of CAFs, to point out their prognostic and therapeutic potential in PCa.

scholarly journals Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone

2021 ◽  
Vol 12 ◽  
Author(s):  
Shashank Kumar ◽  
Kumari Sunita Prajapati ◽  
Mohd Shuaib ◽  
Prem Prakash Kushwaha ◽  
Hardeep Singh Tuli ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Therapeutic Potential ◽  
Experimental Models ◽  
Xenograft Models ◽  
Inhibitory Potential ◽  
Pharmacological Potential

In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells. In vivo anticancer potential of kurarinone has been extensively studied in lungs (non-small and small) using experimental xenograft models. In in vitro anticancer studies, kurarinone showed IC50 in the range of 2–62 µM while in vivo efficacy was studied in the range of 20–500 mg/kg body weight of the experimental organism. The phytochemical showed higher selectivity toward cancer cells in comparison to respective normal cells. kurarinone inhibits cell cycle progression in G2/M and Sub-G1 phase in a cancer-specific context. It induces apoptosis in cancer cells by modulating molecular players involved in apoptosis/anti-apoptotic processes such as NF-κB, caspase 3/8/9/12, Bcl2, Bcl-XL, etc. The phytochemical inhibits metastasis in cancer cells by modulating the protein expression of Vimentin, N-cadherin, E-cadherin, MMP2, MMP3, and MMP9. It produces a cytostatic effect by modulating p21, p27, Cyclin D1, and Cyclin A proteins in cancer cells. Kurarinone possesses stress-mediated anticancer activity and modulates STAT3 and Akt pathways. Besides, the literature showed that kurarinone possesses anti-inflammatory, anti-drug resistance, anti-microbial (fungal, yeast, bacteria, and Coronavirus), channel and transporter modulation, neuroprotection, and estrogenic activities as well as tyrosinase/diacylglycerol acyltransferase/glucosidase/aldose reductase/human carboxylesterases 2 inhibitory potential. Kurarinone also showed therapeutic potential in the clinical study. Further, we also discussed the isolation, bioavailability, metabolism, and toxicity of Kurarinone in experimental models.

The Therapeutic Potential of MAPK/ERK Inhibitors in the Treatment of Colorectal Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Mehran Pashirzad ◽  
Reihaneh Khorasanian ◽  
Maryam Mahmoudi Fard ◽  
Mohammad-Hassan Arjmand ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Erk Signaling ◽  
Clinical Settings ◽  
Cancer Cell Proliferation ◽  
Resistance Mutations ◽  
Clinical Value

: The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer.

scholarly journals Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Adaze Bijou Enogieru ◽  
William Haylett ◽  
Donavon Charles Hiss ◽  
Soraya Bardien ◽  
Okobi Eko Ekpo
Keyword(s):  
Therapeutic Potential ◽  
Current Knowledge ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Experimental Models ◽  
Mitogen Activated Protein Kinase ◽  
Antioxidant Enzyme Activities ◽  
Beneficial Effects ◽  
Wide Range ◽  
Mitogen Activated Protein

A wide range of neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and prion diseases, share common mechanisms such as neuronal loss, apoptosis, mitochondrial dysfunction, oxidative stress, and inflammation. Intervention strategies using plant-derived bioactive compounds have been offered as a form of treatment for these debilitating conditions, as there are currently no remedies to prevent, reverse, or halt the progression of neuronal loss. Rutin, a glycoside of the flavonoid quercetin, is found in many plants and fruits, especially buckwheat, apricots, cherries, grapes, grapefruit, plums, and oranges. Pharmacological studies have reported the beneficial effects of rutin in many disease conditions, and its therapeutic potential in several models of NDs has created considerable excitement. Here, we have summarized the current knowledge on the neuroprotective mechanisms of rutin in various experimental models of NDs. The mechanisms of action reviewed in this article include reduction of proinflammatory cytokines, improved antioxidant enzyme activities, activation of the mitogen-activated protein kinase cascade, downregulation of mRNA expression of PD-linked and proapoptotic genes, upregulation of the ion transport and antiapoptotic genes, and restoration of the activities of mitochondrial complex enzymes. Taken together, these findings suggest that rutin may be a promising neuroprotective compound for the treatment of NDs.

Therapeutic Potential of miR-494 in Thrombosis and Other Diseases: A Review

2016 ◽  
Vol 69 (10) ◽  
pp. 1078 ◽  
Author(s):  
Jasmine Tay ◽  
Jim Tiao ◽  
Quintin Hughes ◽  
Grace Gilmore ◽  
Ross Baker
Keyword(s):  
Nucleic Acids ◽  
Contraceptive Use ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Protein S ◽  
Oral Contraceptive Use ◽  
S Deficiency ◽  
Functional Nucleic Acids

Functional nucleic acids, such as microRNAs (miRNAs), have been implicated in the pathophysiology of many diseases. The miRNA expression profiles of various cancers including haematological malignancies are well defined, but the role of miRNAs in haemostasis and the regulation of coagulation is poorly understood. We identified that miR-494 is oestrogen responsive and directly targets the anticoagulant protein, Protein S, as a mechanism for acquiring Protein S deficiency under high oestrogenic conditions such as during pregnancy and oral contraceptive use. Furthermore, previous studies have also characterised miR-494 to be involved in many biological processes. This paper reviews the current knowledge in the role of miRNAs in regulating haemostatic proteins and the known biological functions of miR-494, highlighting miR-494 as an emerging therapeutic target, with an overview of the strategy we have employed in identifying functional nucleic acids such as miRNAs that target haemostatic factors and the therapeutic potential of miR-494-directed therapy for the treatment of thrombotic disorders.

scholarly journals Does Gut-Microbiome Interaction Protect against Obesity and Obesity-Associated Metabolic Disorders?

2020 ◽  
Vol 9 (1) ◽  
pp. 18
Author(s):  
Agnieszka Zawada ◽  
Anna Maria Rychter ◽  
Alicja Ewa Ratajczak ◽  
Agata Lisiecka-Masian ◽  
Agnieszka Dobrowolska ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Intestinal Microbiota ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Microbiota Composition ◽  
Obesity Prevalence ◽  
Factors Affecting ◽  
Prevention And Treatment ◽  
Qualitative Changes

More research has recently focused on the role of the gut microbiota in the development or course of numerous diseases, including non-communicable diseases. As obesity remains prevalent, the question arises as to what microbial changes are associated with increased obesity prevalence and what kind of prevention and treatment approaches it could provide. Moreover, the influence of the gut-brain axis on obesity is also crucial, since it can affect metabolism and food intake. The quantitative and qualitative changes in the microbiota composition are called dysbiosis; however, in view of the current knowledge, it is difficult to conclude which microbial imbalances are adverse or beneficial. Increased numbers of pathological microorganisms were observed among patients with obesity and comorbidities associated with it, such as diabetes, cardiovascular disease, and insulin resistance. Our review provides current knowledge regarding changes in the intestinal microbiota associated with obesity and obesity-associated comorbidities. Nevertheless, given that dietary patterns and nutrients are two of the factors affecting the intestinal microbiota, we also discuss the role of different dietary approaches, vitamins, and minerals in the shaping of the intestinal microbiota.

scholarly journals NUPR1: A Critical Regulator of the Antioxidant System

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3670
Author(s):  
Can Huang ◽  
Patricia Santofimia-Castaño ◽  
Juan Iovanna
Keyword(s):  
Oxidative Stress ◽  
Antioxidant System ◽  
Mitochondrial Function ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Redox Homeostasis ◽  
Antioxidant Genes ◽  
Intrinsically Disordered ◽  
And Oxidative Stress

Nuclear protein 1 (NUPR1) is a small intrinsically disordered protein (IDP) activated in response to various types of cellular stress, including endoplasmic reticulum (ER) stress and oxidative stress. Reactive oxygen species (ROS) are mainly produced during mitochondrial oxidative metabolism, and directly impact redox homeostasis and oxidative stress. Ferroptosis is a ROS-dependent programmed cell death driven by an iron-mediated redox reaction. Substantial evidence supports a maintenance role of the stress-inducible protein NUPR1 on cancer cell metabolism that confers chemotherapeutic resistance by upregulating mitochondrial function-associated genes and various antioxidant genes in cancer cells. NUPR1, identified as an antagonist of ferroptosis, plays an important role in redox reactions. This review summarizes the current knowledge on the mechanism behind the observed impact of NUPR1 on mitochondrial function, energy metabolism, iron metabolism, and the antioxidant system. The therapeutic potential of genetic or pharmacological inhibition of NUPR1 in cancer is also discussed. Understanding the role of NUPR1 in the antioxidant system and the mechanisms behind its regulation of ferroptosis may promote the development of more efficacious strategies for cancer therapy.

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