scholarly journals Potential of natural products in osteosarcoma treatment: Focus on molecular mechanisms

2021 ◽  
Vol 144 ◽  
pp. 112257
Author(s):  
Mohammad Tobeiha ◽  
Ali Rajabi ◽  
Arash Raisi ◽  
Mahshad Mohajeri ◽  
Soheil Mohammadi Yazdi ◽  
...  
Keyword(s):  
Natural Products ◽  
Molecular Mechanisms ◽  
Treatment Focus

Impact of Natural Dietary Agents on Multiple Myeloma Prevention and Treatment: Molecular Insights and Potential for Clinical Translation

2020 ◽  
Vol 27 (2) ◽  
pp. 187-215 ◽  
Author(s):  
Lavinia Raimondi ◽  
Angela De Luca ◽  
Gianluca Giavaresi ◽  
Agnese Barone ◽  
Pierosandro Tagliaferri ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Multiple Myeloma ◽  
Natural Products ◽  
Bone Disease ◽  
Molecular Mechanisms ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
Signal Transduction Pathways ◽  
Pharmacologically Active ◽  
Dietary Agents

: Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed to shed light on the effects of natural products on tumor growth and survival, disclosing the most relevant signal transduction pathways targeted by such compounds. Overall, anti-inflammatory, anti-oxidant and cytotoxic effects of dietary agents on tumor cells are supported either by results from epidemiological or animal studies and even by clinical trials. : Multiple myeloma is a hematologic malignancy characterized by abnormal proliferation of bone marrow plasma cells and subsequent hypercalcemia, renal dysfunction, anemia, or bone disease, which remains incurable despite novel emerging therapeutic strategies. Notably, increasing evidence supports the capability of dietary natural compounds to antagonize multiple myeloma growth in preclinical models of the disease, underscoring their potential as candidate anti-cancer agents. : In this review, we aim at summarizing findings on the anti-tumor activity of dietary natural products, focusing on their molecular mechanisms, which include inhibition of oncogenic signal transduction pathways and/or epigenetic modulating effects, along with their potential clinical applications against multiple myeloma and its related bone disease.

scholarly journals Molecular basis for two stereoselective Diels-Alderases that produce decalin skeletons

2021 ◽  
Author(s):  
Keisuke Fujiyama ◽  
Naoki Kato ◽  
Suyong Re ◽  
Kiyomi Kinugasa ◽  
Kohei Watanabe ◽  
...  
Keyword(s):  
Natural Products ◽  
Crystal Structures ◽  
Molecular Mechanism ◽  
Density Functional ◽  
Molecular Mechanisms ◽  
Site Directed Mutagenesis ◽  
Bioactive Molecules ◽  
Docking Simulations ◽  
Primary And Secondary Metabolites ◽  
Binding Models

SummaryMolecular chirality, discovered by Louis Pasteur in the middle of the 19th century1, is found in most primary and secondary metabolites. Particularly, the so-called natural products are rich in chiral centres2. The stereochemistry of natural products is strictly recognized in living organisms, and is thus closely related to their biological functions. The Diels–Alder (DA) reaction, which forms a six-membered ring with up to four chiral centres, is a fundamental practical reaction for C–C bond formation in synthetic chemistry3. Nature has also adopted this reaction to elaborate the complex structures of natural products using enzymes derived from various progenitor proteins4-7. Although enzymes catalysing the DA reaction, Diels–Alderases (DAases), have attracted increasing attention, little is known about the molecular mechanism by which they control the stereochemistry and perform catalysis. Here, we solved the X-ray crystal structures of a pair of decalin synthases, Fsa2 and Phm7, that catalyse intramolecular DA reactions to form enantiomeric decalin scaffolds during biosynthesis of the HIV-1 integrase inhibitor equisetin and its stereochemical opposite, phomasetin8,9. Based on the crystal structures, docking simulations followed by all-atom molecular dynamics simulations provided dynamic binding models demonstrating the folding of linear polyenoyl tetramic acid substrates in the binding pocket of these enzymes, explaining the stereoselectivity in the construction of decalin scaffolds. Site-directed mutagenesis studies verified the binding models and, in combination with density functional theory calculations, clarified how hydrophilic amino acid residues in the Phm7 pocket regulate and catalyse the stereoselective DA reaction. This study highlights the distinct molecular mechanisms of the enzymatic DA reaction and its stereoselectivity experimentally and computationally. We anticipate that clarified molecular mechanism herein provides not only the basic understanding how these important enzymes work but also the guiding principle to create artificial enzymes that produce designer bioactive molecules.

scholarly journals Apoptotic or Antiproliferative Activity of Natural Products against Keratinocytes for the Treatment of Psoriasis

2019 ◽  
Vol 20 (10) ◽  
pp. 2558 ◽  
Author(s):  
Tse-Hung Huang ◽  
Chwan-Fwu Lin ◽  
Ahmed Alalaiwe ◽  
Shih-Chun Yang ◽  
Jia-You Fang
Keyword(s):  
Natural Products ◽  
Molecular Mechanisms ◽  
Structural Diversity ◽  
Product Management ◽  
Synergistic Activity ◽  
Herbal Products ◽  
Keratinocyte Proliferation ◽  
Psoriasis Therapy

Natural products or herbs can be used as an effective therapy for treating psoriasis, an autoimmune skin disease that involves keratinocyte overproliferation. It has been demonstrated that phytomedicine, which is used for psoriasis patients, provides some advantages, including natural sources, a lower risk of adverse effects, and the avoidance of dissatisfaction with conventional therapy. The herbal products’ structural diversity and multiple mechanisms of action have enabled the synergistic activity to mitigate psoriasis. In recent years, the concept of using natural products as antiproliferative agents in psoriasis treatment has attracted increasing attention in basic and clinical investigations. This review highlights the development of an apoptotic or antiproliferatic strategy for natural-product management in the treatment of psoriasis. We systematically introduce the concepts and molecular mechanisms of keratinocyte-proliferation inhibition by crude extracts or natural compounds that were isolated from natural resources, especially plants. Most of these studies focus on evaluation through an in vitro keratinocyte model and an in vivo psoriasis-like animal model. Topical delivery is the major route for the in vivo or clinical administration of these natural products. The potential use of antiproliferative phytomedicine on hyperproliferative keratinocytes suggests a way forward for generating advances in the field of psoriasis therapy.

scholarly journals Natural Products, Traditional Uses and Pharmacological Activities of the Genus Biebersteinia (Biebersteiniaceae)

Plants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 595 ◽  
Author(s):  
Benyin Zhang ◽  
Xiaona Jin ◽  
Hengxia Yin ◽  
Dejun Zhang ◽  
Huakun Zhou ◽  
...  
Keyword(s):  
Natural Products ◽  
Molecular Mechanisms ◽  
Chemical Properties ◽  
Pharmacological Properties ◽  
Pharmacological Activities ◽  
Drug Discovery And Development ◽  
Chemical Structures ◽  
Traditional Uses ◽  
Novel Drugs ◽  
Major Chemical

Medicinal plants have been known as a rich source of natural products (NPs). Due to their diverse chemical structures and remarkable pharmacological activities, NPs are regarded as important repertoires for drug discovery and development. Biebersteinia plant species belong to the Biebersteiniaceae family, and have been used in folk medicines in China and Iran for ages. However, the chemical properties, bioactivities and modes of action of the NPs produced by medicinal Biebersteinia species are poorly understood despite the fact that there are only four known Biebersteinia species worldwide. Here, we reviewed the chemical classifications and diversity of the various NPs found in the four known Biebersteinia species. We found that the major chemical categories in these plants include flavonoids, alkaloids, phenylpropanoids, terpenoids, essential oils and fatty acids. We also discussed the anti-inflammatory, analgesic, antibacterial, antioxidant, antihypertensive and hypoglycemic effects of the four Biebersteinia species. We believe that the present review will facilitate the exploration of traditional uses and pharmacological properties of Biebersteinia species, extraction of the NPs and elucidation of their molecular mechanisms, as well as the development of novel drugs based on the reported properties and mode-of-action.

scholarly journals Sensitization of tumor cells to chemotherapy by natural products: A systematic review of preclinical data and molecular mechanisms

Fitoterapia ◽  
2018 ◽  
Vol 129 ◽  
pp. 383-400 ◽  
Author(s):  
Raimundo Gonçalves de Oliveira Júnior ◽  
Alves Ferraz Christiane Adrielly ◽  
Jackson Roberto Guedes da Silva Almeida ◽  
Raphaël Grougnet ◽  
Valérie Thiéry ◽  
...  
Keyword(s):  
Systematic Review ◽  
Natural Products ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Preclinical Data

Therapeutic Advances in Myeloproliferative Neoplasms: The Role of New-Small Molecule Inhibitors

2012 ◽  
pp. 406-410 ◽  
Author(s):  
Srdan Verstovsek
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Myeloproliferative Neoplasms ◽  
Janus Kinase ◽  
Treatment Focus ◽  
Rational Combination ◽  
Short And Long Term ◽  
Jak2 Inhibitors

Overview: The discovery that a somatic point mutation (JAK2V617F) in the Janus kinase 2 ( JAK2) is highly prevalent in patients with myeloproliferative neoplasms (MPNs) has been a crucial breakthrough in our understanding of the underlying molecular mechanisms of these diseases. Therefore, preclinical and clinical research in recent years has focused intensely on the development of new therapies targeted to JAK2. These efforts culminated in recent approval of ruxolitinib as the first official therapy for patients with intermediate- or high-risk myelofibrosis (MF). Therapy with JAK2 inhibitors substantially improves quality of life and reduces organomegaly in MF with or without JAKV617F mutation. Recent results suggest that patients with advanced MF may live longer when receiving therapy with ruxolitinib. However, JAK2 inhibitors do not eliminate the disease and new medications are needed to expand on the benefits seen with JAK2 inhibitors. Although many agents are still in the early stages of development, the wealth of publications and presentations has continued to support our growing understanding of the pathophysiology of MF as well as the potential short- and long-term outcomes of these new and diverse approaches to treatment. Focus of ongoing efforts is particularly on the improvements in anemia and fibrosis, as well as on rational combination trials of JAK2 inhibitors and other potentially active agents. Therapeutic potential and limitations of JAK2 inhibitors and other novel medications in clinical studies are reviewed.

scholarly journals Microglia Specific Drug Targeting Using Natural Products for the Regulation of Redox Imbalance in Neurodegeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Shashank Kumar Maurya ◽  
Neetu Bhattacharya ◽  
Suman Mishra ◽  
Amit Bhattacharya ◽  
Pratibha Banerjee ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Neuroprotective Effect ◽  
Inhibitory Effect ◽  
Dual Function ◽  
Redox Imbalance ◽  
The Brain

Microglia, a type of innate immune cell of the brain, regulates neurogenesis, immunological surveillance, redox imbalance, cognitive and behavioral changes under normal and pathological conditions like Alzheimer’s, Parkinson’s, Multiple sclerosis and traumatic brain injury. Microglia produces a wide variety of cytokines to maintain homeostasis. It also participates in synaptic pruning and regulation of neurons overproduction by phagocytosis of neural precursor cells. The phenotypes of microglia are regulated by the local microenvironment of neurons and astrocytes via interaction with both soluble and membrane-bound mediators. In case of neuron degeneration as observed in acute or chronic neurodegenerative diseases, microglia gets released from the inhibitory effect of neurons and astrocytes, showing activated phenotype either of its dual function. Microglia shows neuroprotective effect by secreting growths factors to heal neurons and clears cell debris through phagocytosis in case of a moderate stimulus. But the same microglia starts releasing pro-inflammatory cytokines like TNF-α, IFN-γ, reactive oxygen species (ROS), and nitric oxide (NO), increasing neuroinflammation and redox imbalance in the brain under chronic signals. Therefore, pharmacological targeting of microglia would be a promising strategy in the regulation of neuroinflammation, redox imbalance and oxidative stress in neurodegenerative diseases. Some studies present potentials of natural products like curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane to suppress activation of microglia. These natural products have also been proposed as effective therapeutics to regulate the progression of neurodegenerative diseases. The present review article intends to explain the molecular mechanisms and functions of microglia and molecular dynamics of microglia specific genes and proteins like Iba1 and Tmem119 in neurodegeneration. The possible interventions by curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane on microglia specific protein Iba1 suggest possibility of natural products mediated regulation of microglia phenotypes and its functions to control redox imbalance and neuroinflammation in management of Alzheimer’s, Parkinson’s and Multiple Sclerosis for microglia-mediated therapeutics.

scholarly journals Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Xie ◽  
Yi Chen ◽  
Huidan Tan ◽  
Bo Liu ◽  
Ling-Li Zheng ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Therapy ◽  
Signaling Pathways ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Therapeutic Benefits ◽  
Small Molecule Drugs

Natural products are well-characterized to have pharmacological or biological activities that can be of therapeutic benefits for cancer therapy, which also provide an important source of inspiration for discovery of potential novel small-molecule drugs. In the past three decades, accumulating evidence has revealed that natural products can modulate a series of key autophagic signaling pathways and display therapeutic effects in different types of human cancers. In this review, we focus on summarizing some representative natural active compounds, mainly including curcumin, resveratrol, paclitaxel, Bufalin, and Ursolic acid that may ultimately trigger cancer cell death through the regulation of some key autophagic signaling pathways, such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, AMPK, ULK1, Beclin-1, Atg5 and p53. Taken together, these inspiring findings would shed light on exploiting more natural compounds as candidate small-molecule drugs, by targeting the crucial pathways of autophagy for the future cancer therapy.

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