Costunolide—A Bioactive Sesquiterpene Lactone with Diverse Therapeutic Potential

Sesquiterpene lactones constitute a major class of bioactive natural products. One of the naturally occurring sesquiterpene lactones is costunolide, which has been extensively investigated for a wide range of biological activities. Multiple lines of preclinical studies have reported that the compound possesses antioxidative, anti-inflammatory, antiallergic, bone remodeling, neuroprotective, hair growth promoting, anticancer, and antidiabetic properties. Many of these bioactivities are supported by mechanistic details, such as the modulation of various intracellular signaling pathways involved in precipitating tissue inflammation, tumor growth and progression, bone loss, and neurodegeneration. The key molecular targets of costunolide include, but are not limited to, intracellular kinases, such as mitogen-activated protein kinases, Akt kinase, telomerase, cyclins and cyclin-dependent kinases, and redox-regulated transcription factors, such as nuclear factor-kappaB, signal transducer and activator of transcription, activator protein-1. The compound also diminished the production and/expression of proinflammatory mediators, such as cyclooxygenase-2, inducible nitric oxide synthase, nitric oxide, prostaglandins, and cytokines. This review provides an overview of the therapeutic potential of costunolide in the management of various diseases and their underlying mechanisms.

Download Full-text

Isoform-Selective PI3K Inhibitors for Various Diseases

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200106141717 ◽

2020 ◽

Vol 20 (12) ◽

pp. 1074-1092 ◽

Cited By ~ 4

Author(s):

Rammohan R.Y. Bheemanaboina

Keyword(s):

Intracellular Signaling ◽

Kinase Inhibitors ◽

Therapeutic Potential ◽

Type I ◽

Selective Inhibitors ◽

Pi3k Inhibitors ◽

Wide Range ◽

Lipid Kinases ◽

Isoform Selectivity

Phosphoinositide 3-kinases (PI3Ks) are a family of ubiquitously distributed lipid kinases that control a wide variety of intracellular signaling pathways. Over the years, PI3K has emerged as an attractive target for the development of novel pharmaceuticals to treat cancer and various other diseases. In the last five years, four of the PI3K inhibitors viz. Idelalisib, Copanlisib, Duvelisib, and Alpelisib were approved by the FDA for the treatment of different types of cancer and several other PI3K inhibitors are currently under active clinical development. So far clinical candidates are non-selective kinase inhibitors with various off-target liabilities due to cross-reactivities. Hence, there is a need for the discovery of isoform-selective inhibitors with improved efficacy and fewer side-effects. The development of isoform-selective inhibitors is essential to reveal the unique functions of each isoform and its corresponding therapeutic potential. Although the clinical effect and relative benefit of pan and isoformselective inhibition will ultimately be determined, with the development of drug resistance and the demand for next-generation inhibitors, it will continue to be of great significance to understand the potential mechanism of isoform-selectivity. Because of the important role of type I PI3K family members in various pathophysiological processes, isoform-selective PI3K inhibitors may ultimately have considerable efficacy in a wide range of human diseases. This review summarizes the progress of isoformselective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.

Download Full-text

Advances in Studies on the Pharmacological Activities of Fucoxanthin

Marine Drugs ◽

10.3390/md18120634 ◽

2020 ◽

Vol 18 (12) ◽

pp. 634

Author(s):

Han Xiao ◽

Jiarui Zhao ◽

Chang Fang ◽

Qi Cao ◽

Maochen Xing ◽

...

Keyword(s):

Biological Activities ◽

Intestinal Flora ◽

Small Molecular Weight ◽

Pharmacological Activities ◽

Beneficial Effects ◽

Wide Range ◽

Cell Components ◽

Underlying Mechanisms ◽

Organ Fibrosis ◽

Active Can

Fucoxanthin is a natural carotenoid derived mostly from many species of marine brown algae. It is characterized by small molecular weight, is chemically active, can be easily oxidized, and has diverse biological activities, thus protecting cell components from ROS. Fucoxanthin inhibits the proliferation of a variety of cancer cells, promotes weight loss, acts as an antioxidant and anti-inflammatory agent, interacts with the intestinal flora to protect intestinal health, prevents organ fibrosis, and exerts a multitude of other beneficial effects. Thus, fucoxanthin has a wide range of applications and broad prospects. This review focuses primarily on the latest progress in research on its pharmacological activity and underlying mechanisms.

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

Genome editing for blood disorders: state of the art and recent advances

Emerging Topics in Life Sciences ◽

10.1042/etls20180147 ◽

2019 ◽

Vol 3 (3) ◽

pp. 289-299 ◽

Cited By ~ 2

Author(s):

Marianna Romito ◽

Rajeev Rai ◽

Adrian J. Thrasher ◽

Alessia Cavazza

Keyword(s):

Gene Editing ◽

Therapeutic Potential ◽

State Of The Art ◽

Clinical Success ◽

Zinc Finger Nucleases ◽

Transcription Activator ◽

Blood Disorders ◽

Flexible Tool ◽

Wide Range ◽

Made In

Abstract In recent years, tremendous advances have been made in the use of gene editing to precisely engineer the genome. This technology relies on the activity of a wide range of nuclease platforms — such as zinc-finger nucleases, transcription activator-like effector nucleases, and the CRISPR–Cas system — that can cleave and repair specific DNA regions, providing a unique and flexible tool to study gene function and correct disease-causing mutations. Preclinical studies using gene editing to tackle genetic and infectious diseases have highlighted the therapeutic potential of this technology. This review summarizes the progresses made towards the development of gene editing tools for the treatment of haematological disorders and the hurdles that need to be overcome to achieve clinical success.

Download Full-text

Methanol Extract ofArtemisia apiaceaHance Attenuates the Expression of Inflammatory Mediators via NF-κB Inactivation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/494681 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 9

Author(s):

Ji Choul Ryu ◽

Sang Mi Park ◽

Min Hwangbo ◽

Sung Hui Byun ◽

Sae Kwang Ku ◽

...

Keyword(s):

Nitric Oxide ◽

Therapeutic Potential ◽

Interleukin 1 ◽

Dependent Manner ◽

Nuclear Factor ◽

Paw Edema ◽

Concentration Dependent Manner ◽

Proinflammatory Mediators ◽

Inducible Nitric Oxide

Artemisia apiaceaHance is one of the most widely used herbs for the treatment of malaria, jaundice, and dyspeptic complaint in oriental medicine. This study investigated the effects of methanol extracts ofA. apiaceaHance (MEAH) on the induction of inducible nitric oxide synthase (iNOS) and proinflammatory mediators by lipopolysaccharide (LPS) in Raw264.7 macrophage cells and also evaluated thein vivoeffect of MEAH on carrageenan-induced paw edema in rats. MEAH treatment in Raw264.7 cells significantly decreased LPS-inducible nitric oxide production and the expression of iNOS in a concentration-dependent manner, while MEAH (up to 100 μg/mL) had no cytotoxic activity. Results from immunoblot analyses and ELISA revealed that MEAH significantly inhibited the expression of cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in LPS-activated cells. As a plausible molecular mechanism, increased degradation and phosphorylation of inhibitory-κBαand nuclear factor-κB accumulation in the nucleus by LPS were partly blocked by MEAH treatment. Finally, MEAH treatment decreased the carrageenan-induced formation of paw edema and infiltration of inflammatory cells in rats. These results demonstrate that MEAH has an anti-inflammatory therapeutic potential that may result from the inhibition of nuclear factor-κB activation, subsequently decreasing the expression of proinflammatory mediators.

Download Full-text

Traditional Applications, Phytochemistry, and Pharmacological Activities of Eupatorium lindleyanum DC.: A Comprehensive Review

Frontiers in Pharmacology ◽

10.3389/fphar.2020.577124 ◽

2020 ◽

Vol 8 ◽

Author(s):

Xueyi Wang ◽

Shangying Ma ◽

Feifan Lai ◽

Yiqi Wang ◽

Chenghua Lou

Keyword(s):

Biological Activities ◽

Sesquiterpene Lactones ◽

Research Work ◽

Preclinical Research ◽

Pharmacological Activities ◽

Bioactive Substances ◽

Traditional Use ◽

Clinical Safety ◽

Traditional Chinese Herbal Medicine ◽

Underlying Mechanisms

Eupatorium lindleyanum DC. (EL) has a long history of traditional use in China to cure coughs, chronic bronchitis, lobar pneumonia, and hypertension. Because of this extensive use of EL in traditional medicine, this present review gives a systematic overview of the conventional applications, phytochemistry, and pharmacological effects of the herb. Literature was systematically searched using the scientific databases ScienceDirect, SciFinder, CNKI, Wiley, Baidu Scholar, SpringerLink, PubMed, Web of Science, and other professional websites. Information was also gathered from books on traditional Chinese herbal medicine, the Chinese Pharmacopoeia and Chinese Materia Medica. To date, many preparations of EL have been widely used clinically to treat various diseases of the respiratory system. More than 100 compounds have been isolated from the herb, including triterpenes, sesquiterpenes, sesquiterpene lactones, flavonoids, acyclic diterpenoids, sterols, and so on. Among them, terpenoids are considered to be the most important bioactive substances in EL. The pharmacological functions of EL, including anti-asthmatic, anti-tussive, anti-inflammatory, anti-hyperlipidemic, anti-hypertensive, anti-virus, and anti-tumor activities, have been widely investigated. However, most of the studies are preclinical research. Further studies are required to examine the underlying mechanisms of action. Traditionally, EL is used for treating many diseases, especially respiratory diseases. Unfortunately, up to now, modern studies have not yet well elucidated the conventional usage of EL. Most importantly, its biological activities and the corresponding constituents are still unclear. Moreover, studies on the pharmacokinetics and toxicity of EL are few, so data on the clinical safety of EL are lacking. Taken together, research work on EL is quite preliminary. More in-depth studies of phytochemistry, pharmacological activities, pharmacokinetics, and toxicity of the herb are needed. This review aims to provide valuable information on EL to guide future investigations and applications.

Download Full-text

The Complexity of Omega-3 Fatty Acid Modulation of Signaling Pathways Related to Pancreatic Cancer

Current Medicinal Chemistry ◽

10.2174/0929867324666170616111225 ◽

2018 ◽

Vol 25 (22) ◽

pp. 2608-2623 ◽

Cited By ~ 5

Author(s):

Carolina Torres ◽

Andrew M. Diaz ◽

Daniel R. Principe ◽

Paul J. Grippo

Keyword(s):

Pancreatic Cancer ◽

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Signaling Pathways ◽

Intracellular Signaling ◽

Biological Activities ◽

The United States ◽

Major Public Health Problem ◽

Wide Range ◽

Membrane Structure And Function

Cancer is a major public health problem worldwide and is the second leading cause of death in the United States. Although cancer death rate has dropped by 23% since 1991, there are certain types of cancer for which death rates are still increasing, such as pancreatic cancer. There is an urgent need to find new therapies that could help improve this dreadful outcome. In this regard, the role of nutrition in health and disease has attracted much attention. Several dietary components are involved in metabolic, physiologic and cell signaling affecting tumor growth and progression. Although lipids, and more specifically polyunsaturated fatty acids, have been traditionally studied due to their health effects in cardiovascular disease, it is now clear that they can impact an extensive array of cellular processes that influence a wide range of diseases such as type II diabetes, inflammatory disorders and cancer. These biological activities may be grouped as regulation of: (1) membrane structure and function, (2) intracellular signaling pathways, (3) transcription factor activity, (4) gene expression, and (5) production of bioactive lipid mediators. The aim of this review is to assimilate the current state of knowledge about these potential mechanism(s) of action and signaling pathways modulated by polyunsaturated fatty acids in pancreatic cancer.

Download Full-text

A Panoramic Review of Benzimidazole Derivatives and Their Potential Biological Activity

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557522666220104150051 ◽

2022 ◽

Vol 22 ◽

Author(s):

Hiram Hernández-López ◽

Christian Jairo Tejada-Rodríguez ◽

Socorro Leyva-Ramos

Keyword(s):

Biological Activity ◽

Hydrophobic Interactions ◽

Therapeutic Potential ◽

Biological Activities ◽

Benzimidazole Derivatives ◽

Drug Candidate ◽

Hydrogen Bond Donor ◽

Wide Range ◽

Donor Acceptor ◽

Potent Drug

Abstract: The therapeutic potential of the benzimidazole nucleus dates back to 1944, being and important heterocycle system due to its presence in a wide range of bioactive compounds such as antiviral, anticancer, antibacterial, and so on, where optimization of substituents in this class of pharmacophore has resulted in many drugs. Its extensive biological activity is due to its physicochemical properties like hydrogen bond donor-acceptor capability,  stacking interactions, coordination bonds with metals as ligands and hydrophobic interactions; properties that allow them to easily bind with a series of biomolecules, including enzymes and nucleic acids, causing a growing interest in these types of molecules. This review aims to present an overview to leading benzimidazole derivatives, as well as to show the importance of the nature and type of substituents at the N1, C2, and C5(6) positions, when they are biologically evaluated, which can lead to obtaining potent drug candidate with significant range of biological activities.

Download Full-text

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

Toxins ◽

10.3390/toxins10020069 ◽

2018 ◽

Vol 10 (2) ◽

pp. 69 ◽

Cited By ~ 2

Author(s):

Carolina Nicolau ◽

Alyson Prorock ◽

Yongde Bao ◽

Ana Neves-Ferreira ◽

Richard Valente ◽

...

Keyword(s):

Therapeutic Potential ◽

Biological Activities ◽

Rna Extraction ◽

Breast Adenocarcinoma ◽

South American ◽

Snake Venoms ◽

Bothrops Jararaca ◽

Drug Classes ◽

Wide Range ◽

Activity Screening

Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.

Download Full-text

Dendropanax Morbiferus and Other Species from the Genus Dendropanax: Therapeutic Potential of Its Traditional Uses, Phytochemistry, and Pharmacology

Antioxidants ◽

10.3390/antiox9100962 ◽

2020 ◽

Vol 9 (10) ◽

pp. 962

Author(s):

Rengasamy Balakrishnan ◽

Duk-Yeon Cho ◽

In Su-Kim ◽

Dong-Kug Choi

Keyword(s):

Therapeutic Potential ◽

Biological Activities ◽

Safety Evaluation ◽

Biological Properties ◽

Comprehensive Analysis ◽

Flowering Plant ◽

High Concentration ◽

Medicinal Uses ◽

Wide Range ◽

Bioactive Ingredients

The Dendropanax genus is a kind of flowering plant in the family of Araliaceae that encompasses approximately 91 to 95 species. Several Dendropanax species are used as traditional medicinal plants, extensively used Korea and South America and other parts of the world. Almost every part of the plant, including the leaves, bark, roots, and stems, can be used as traditional medicine for the prevention and management of a broad spectrum of health disorders. This paper sought to summarizes the ethnopharmacological benefits, biological activities, and phytochemical investigations of plants from the genus Dendropanax, and perhaps to subsequently elucidate potential new perspectives for future pharmacological research to consider. Modern scientific literature suggests that plants of the Dendropanax genus, together with active compounds isolated from it, possess a wide range of therapeutic and pharmacological applications, including antifungal, anti-complement, antioxidant, antibacterial, insect antifeedant, cytotoxic, anti-inflammatory, neuroprotective, anti-diabetic, anti-cancer, and anti-hypouricemic properties. The botanical descriptions of approximately six to 10 species are provided by different scientific web sources. However, only six species, namely, D. morbiferus, D. gonatopodus, D. dentiger, D. capillaris, D. chevalieri, and D. arboreus, were included in the present investigation to undergo phytochemical evaluation, due to the unavailability of data for the remaining species. Among these plant species, a high concentration of variable bioactive ingredients was identified. In particular, D. morbifera is a traditional medicinal plant used for the multiple treatment purposes and management of several human diseases or health conditions. Previous experimental evidence supports that the D. morbifera species could be used to treat various inflammatory disorders, diarrhea, diabetes, cancer, and some microbial infections. It has recently been reported, by our group and other researchers, that D. morbifera possesses a neuroprotective and memory-enhancing agent. A total of 259 compounds have been identified among six species, with 78 sourced from five of these species reported to be bioactive. However, there is no up-to-date information concerning the D. morbifera, its different biological properties, or its prospective benefits in the enhancement of human health. In the present study, we set out to conduct a comprehensive analysis of the botany, traditional medicinal history, and medicinal resources of species of the Dendropanax genus. In addition, we explore several phytochemical constituents identified in different species of the Dendropanax genus and their biological properties. Finally, we offer comprehensive analysis findings of the phytochemistry, medicinal uses, pharmacological actions, and a toxicity and safety evaluation of the D. morbifera species and its main bioactive ingredients for future consideration.

Download Full-text