scholarly journals Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases

2021 ◽  
Vol 22 (22) ◽  
pp. 12162
Author(s):  
Manzar Alam ◽  
Sabeeha Ali ◽  
Sarfraz Ahmed ◽  
Abdelbaset Mohamed Elasbali ◽  
Mohd Adnan ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Ursolic Acid ◽  
Water Solubility ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Drug ◽  
Protective Agent ◽  
Cancer Proliferation ◽  
Pentacyclic Triterpenoid ◽  
Anti Inflammatory

Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat multiple diseases, including cancer, diabetic neuropathy, and inflammatory diseases. UA inhibits cancer proliferation, metastasis, angiogenesis, and induced cell death, scavenging free radicals and triggering numerous anti- and pro-apoptotic proteins. The biochemistry of UA has been examined broadly based on the literature, with alterations frequently having been prepared on positions C-3 (hydroxyl), C12–C13 (double bonds), and C-28 (carboxylic acid), leading to several UA derivatives with increased potency, bioavailability and water solubility. UA could be used as a protective agent to counter neural dysfunction via anti-oxidant and anti-inflammatory effects. It is a potential therapeutic drug implicated in the treatment of cancer and diabetic complications diseases provide novel machinery to the anti-inflammatory properties of UA. The pharmacological efficiency of UA is exhibited by the therapeutic theory of one-drug → several targets → one/multiple diseases. Hence, UA shows promising therapeutic potential for cancer and diabetic neuropathy diseases. This review aims to discuss mechanistic insights into promising beneficial effects of UA. We further explained the pharmacological aspects, clinical trials, and potential limitations of UA for the management of cancer and diabetic neuropathy diseases.

MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium

2016 ◽  
Vol 44 (06) ◽  
pp. 1111-1125 ◽  
Author(s):  
Muhammad Jahangir Hossen ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho
Keyword(s):  
Mouse Model ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Elevated Serum ◽  
Human Monocyte ◽  
Serum Levels ◽  
Mitogen Activated Protein Kinase ◽  
Xanthium Strumarium ◽  
U937 Cells ◽  
Anti Inflammatory

Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.

Advances in Anti-inflammatory Activity, Mechanism and Therapeutic Application of Ursolic Acid

2021 ◽  
Vol 21 ◽  
Author(s):  
Mingzhu Luan ◽  
Huiyun Wang ◽  
Jiazhen Wang ◽  
Xiaofan Zhang ◽  
Fenglan Zhao ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Inflammatory Activity ◽  
Inflammatory Factors ◽  
Inflammatory Stimuli ◽  
Bowel Diseases ◽  
Anti Inflammatory

: In vivo and in vitro studies reveal that ursolic acid (UA) is able to counteract endogenous and exogenous inflammatory stimuli, and has favorable anti-inflammatory effects. The anti-inflammatory mechanisms mainly include decreasing the release of histamine in mast cells, suppressing the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of nitric oxide and reactive oxygen species, blocking the activation of signal pathway, down-regulating the expression of inflammatory factors, and inhibiting the activities of elastase and complement. These mechanisms can open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle inflammatory diseases such as arthritis, atherosclerosis, neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications are reviewed in this paper.

scholarly journals Considerable Improvement of Ursolic Acid Water Solubility by Its Encapsulation in Dendrimer Nanoparticles: Design, Synthesis and Physicochemical Characterization

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2196 ◽  
Author(s):  
Silvana Alfei ◽  
Anna Maria Schito ◽  
Guendalina Zuccari
Keyword(s):  
Ursolic Acid ◽  
Water Solubility ◽  
Drug Loading ◽  
Physicochemical Characterization ◽  
Systemic Toxicity ◽  
Water Soluble ◽  
Design Synthesis ◽  
Pentacyclic Triterpenoid

Ursolic acid (UA) is a pentacyclic triterpenoid found in many medicinal plants and aromas endowed with numerous in vitro pharmacological activities, including antibacterial effects. Unfortunately, UA is poorly administered in vivo, due to its water insolubility, low bioavailability, and residual systemic toxicity, thus making urgent the development of water-soluble UA formulations. Dendrimers are nonpareil macromolecules possessing highly controlled size, shape, and architecture. In dendrimers with cationic surface, the contemporary presence of inner cavities and of hydrophilic peripheral functions, allows to encapsulate hydrophobic non-water-soluble drugs as UA, to enhance their water-solubility and stability, and to promote their protracted release, thus decreasing their systemic toxicity. In this paper, aiming at developing a new UA-based antibacterial agent administrable in vivo, we reported the physical entrapment of UA in a biodegradable not cytotoxic cationic dendrimer (G4K). UA-loaded dendrimer nanoparticles (UA-G4K) were obtained, which showed a drug loading (DL%) much higher than those previously reported, a protracted release profile governed by diffusion mechanisms, and no cytotoxicity. Also, UA-G4K was characterized by principal components analysis (PCA)-processed FTIR spectroscopy, by NMR and elemental analyses, and by dynamic light scattering experiments (DLS). The water solubility of UA-G4K was found to be 1868-fold times higher than that of pristine UA, thus making its clinical application feasible.

Development and Evaluation of Ursolic Acid Co-Delivered Tamoxifen Loaded Dammar Gum Nanoparticles to Combat Cancer

2019 ◽  
Vol 11 (11) ◽  
pp. 1115-1124
Author(s):  
Neeraj Sethi ◽  
Prashant Bhardwaj ◽  
Sandeep Kumar ◽  
Neeraj Dilbaghi
Keyword(s):  
Ursolic Acid ◽  
Growth Regulation ◽  
Plant Secondary Metabolites ◽  
Cancer Proliferation ◽  
Pentacyclic Triterpenoid ◽  
Transmission Electron ◽  
Hela Cell Lines ◽  
Anti Cancer ◽  
Anti Oxidant

Therapeutic approaches used to manage cancer, are often associated with drug tolerance or multidrug resistance. The anticancer activity exhibited by plant secondary metabolites can be effectively enhanced by formulating them at nanometric scale. Ursolic acid (UA) is a pentacyclic triterpenoid that reduces cancer proliferation by interfering cell growth regulation. Tamoxifen (TAM) is an adjuvant molecule employed for hormonal therapy of cancer especially breast cancer. To improve the bioavailability and synergism, UA and TAM loaded Dammar gum nanoparticles (UTDNPs) were prepared in current study by employing oil in oil (O/O) emulsion solvent evaporation method. Zeta potential value of UTDNPs was found to be +23 mV demonstrating relative stability of nanoformulation. The percentage encapsulation efficiency value was found to be 72.5% for UA and 76.6% for TAM. The UTDNPs posses particle size in the range of 45–55 nm as revealed by transmission electron microscopy. The UTDNPs showed sustained release and their anti-oxidant and anti-cancer potential was much more pronounced than free UA and TAM particles alone. The in vitro studies demonstrated that UA and TAM encapsulated in dammar gum inhibited growth of A-549, MCF-7, and Hela cell lines more effectively than UA and TAM alone which proved their robust anticancer potential.

scholarly journals Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 147 ◽  
Author(s):  
Abigail L Clutterbuck ◽  
David Allaway ◽  
Pat Harris ◽  
Ali Mobasheri
Keyword(s):  
Articular Cartilage ◽  
Matrix Metalloproteinase ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Primary Cultures ◽  
Cartilage Explants ◽  
Prostaglandin E ◽  
Primary Chondrocytes ◽  
Chondrocyte Death ◽  
Anti Inflammatory

Objective: Curcumin (diferuloylmethane) is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA). The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β)-stimulated inflammation and catabolism in an explant model of cartilage inflammation.Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2) and matrix metalloproteinase (MMP)-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG) release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB) assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days.Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001) after 24 hours. After 48 hours and five days, curcumin (≥25μM) significantly increased cell death (p<0.001 both time points). In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM) significantly reduced IL-1β-stimulated PG (p<0.05) and PGE2 release (p<0.001) from explants, whilst curcumin (≥12μM) significantly reduced MMP-3 release (p<0.01).Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

scholarly journals Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System

2020 ◽  
Vol 21 (14) ◽  
pp. 4850 ◽  
Author(s):  
Cristiane F. Villarreal ◽  
Dourivaldo S. Santos ◽  
Pedro S. S. Lauria ◽  
Kelly B. Gama ◽  
Renan F. Espírito-Santo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Diabetic Neuropathy ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Immune Homeostasis ◽  
No Production ◽  
Painful Diabetic Neuropathy ◽  
Antioxidant Genes ◽  
Anti Inflammatory

Diabetic neuropathy is a frequent complication of diabetes. Symptoms include neuropathic pain and sensory alterations—no effective treatments are currently available. This work characterized the therapeutic effect of bergenin in a mouse (C57/BL6) model of streptozotocin-induced painful diabetic neuropathy. Nociceptive thresholds were assessed by the von Frey test. Cytokines, antioxidant genes, and oxidative stress markers were measured in nervous tissues by ELISA, RT-qPCR, and biochemical analyses. Single (3.125–25 mg/kg) or multiple (25 mg/kg; twice a day for 14 days) treatments with bergenin reduced the behavioral signs of diabetic neuropathy in mice. Bergenin reduced both nitric oxide (NO) production in vitro and malondialdehyde (MDA)/nitrite amounts in vivo. These antioxidant properties can be attributed to the modulation of gene expression by the downregulation of inducible nitric oxide synthase (iNOS) and upregulation of glutathione peroxidase and Nrf2 in the nervous system. Bergenin also modulated the pro- and anti-inflammatory cytokines production in neuropathic mice. The long-lasting antinociceptive effect induced by bergenin in neuropathic mice, was associated with a shift of the cytokine balance toward anti-inflammatory predominance and upregulation of antioxidant pathways, favoring the reestablishment of redox and immune homeostasis in the nervous system. These results point to the therapeutic potential of bergenin in the treatment of painful diabetic neuropathy.

scholarly journals Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 624 ◽  
Author(s):  
Nuna Araújo ◽  
Carla S. B. Viegas ◽  
Eva Zubía ◽  
Joana Magalhães ◽  
Acácio Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protective Factor ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Cartilage Explants ◽  
Protective Agent ◽  
Human Cartilage ◽  
Effective Prevention ◽  
Anti Inflammatory

Osteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga Cystoseira usneoides, has demonstrated anti-inflammatory activity. Here, we investigated the YP anti-osteoarthritic potential, by using a novel OA preclinical drug development pipeline designed to evaluate the anti-inflammatory and anti-mineralizing activities of potential OA-protective compounds. The workflow was based on in vitro primary cell cultures followed by human cartilage explants assays and a new OA co-culture model, combining cartilage explants with synoviocytes under interleukin-1β (IL-1β) or hydroxyapatite (HAP) stimulation. A combination of gene expression analysis and measurement of inflammatory mediators showed that the proposed model mimicked early disease stages, while YP counteracted inflammatory responses by downregulation of COX-2 and IL-6, improved cartilage homeostasis by downregulation of MMP3 and the chondrocytes hypertrophic differentiation factors Col10 and Runx2. Importantly, YP downregulated NF-κB gene expression and decreased phosphorylated IkBα/total IkBα ratio in chondrocytes. These results indicate the co-culture as a relevant pre-clinical OA model, and strongly suggest YP as a cartilage protective factor by inhibiting inflammatory, mineralizing, catabolic and differentiation processes during OA development, through inhibition of NF-κB signaling pathways, with high therapeutic potential.

scholarly journals A vimentin-targeting oral compound with host-directed antiviral and anti-inflammatory actions addresses multiple features of COVID-19 and related diseases

2021 ◽  
Author(s):  
Zhizhen Li ◽  
Jianping Wu ◽  
Ji Zhou ◽  
Baoshi Yuan ◽  
Jiqiao Chen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Cellular Protein ◽  
New Drugs ◽  
Lung Damage ◽  
Therapeutic Drug ◽  
Endosomal Trafficking ◽  
Toxic Agent ◽  
Anti Inflammatory

ABSTRACTDamage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overreactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small molecule compound, in treating COVID-19 through its host-directed antiviral and anti-inflammatory actions. We found that by altering the physical properties of vimentin filaments, ALD-491 affected general cellular processes as well as specific cellular functions relevant to SARS-CoV-2 infection. Specifically, ALD-R491 reduced endocytosis, endosomal trafficking, and exosomal release, thus impeding the entry and egress of the virus; increased the microcidal capacity of macrophages, thus facilitating the pathogen clearance; and enhanced the activity of regulatory T cells, therefore suppressing the overreactive immune responses. In cultured cells, ALD-R491 potently inhibited the SARS-CoV-2 spike protein and human ACE2-mediated pseudoviral infection. In aged mice with ongoing, productive SARS-CoV-2 infection, ALD-R491 reduced disease symptoms as well as lung damage. In rats, ALD-R491 also reduced bleomycin-induced lung injury and fibrosis. Our results indicate a unique mechanism and significant therapeutic potential for ALD-R491 against COVID-19. We anticipate that ALD-R491, an oral, fast-acting, and non-toxic agent targeting the cellular protein with multipart actions, will be convenient, safe, and broadly effective, regardless of viral mutations, for patients with early- or late-stage disease, post-COVID complications and other related diseases.IMPORTANCEWith the Delta variant currently fueling a resurgence of new infections in the fully-vaccinated population, developing an effective therapeutic drug is especially critical and urgent in fighting COVID-19. In contrast to the many efforts to repurpose existing drugs or address only one aspect of COVID-19, we are developing a novel agent with first-in-class mechanism-of-actions that address both the viral infection and the overactive immune system in the pathogenesis of the disease. Unlike virus-directed therapeutics that may lose efficacy due to viral mutations and immunosuppressants that require ideal timing to be effective, this agent, with its unique host-directed antiviral and anti-inflammatory actions, can work against all variants of the virus, be effective during all stages of the disease, and even resolve post-disease damage and complications. A further development of the compound will provide an important tool in the fight against COVID-19, its complications, as well as future outbreaks of new viruses.

scholarly journals Harnessing Pivotal Advances for Production and Structural Derivation of the Promising Molecule Ursolic Acid

2021 ◽  
Author(s):  
Hao-ran Liu ◽  
Nadeem Ahmad ◽  
Bo Lv ◽  
Chun Li
Keyword(s):  
Ursolic Acid ◽  
Large Scale ◽  
Structural Modification ◽  
Therapeutic Potential ◽  
Scale Production ◽  
Pharmacological Activities ◽  
Significant Safety ◽  
Pentacyclic Triterpenoid ◽  
Large Scale Production ◽  
Vast Range

Ursolic acid (UA) is a ursane-type pentacyclic triterpenoid compound, naturally produced in plants via specialized metabolism and exhibits vast range of remarkable physiological activities and pharmacological manifestations. Owing to significant safety and efficacy in different medical conditions, UA may serve as a backbone to produce its derivatives with novel therapeutic functions. This review systematically provides an overview of the pharmacological activities, acquisition methods and structural modification methods of UA. In addition, we focused on the synthetic modifications of UA to yield its valuable derivatives with enhanced therapeutic potential. Furthermore, harnessing the essential advances for green synthesis of UA and its derivatives by advent of metabolic engineering and synthetic biology are highlighted. In combination with the advantages of UA biosynthesis and transformation strategy, large-scale production and applications of UA is a promising platform for further exploration.

scholarly journals Observing the Anti-oxidant and Anti-inflammatory Effect of Nigella Sativa Combined With Silybum Marianum Extracts on the Acute Peritonitis Mouse Model

2021 ◽  
Vol 24 (3) ◽  
pp. 372-385
Author(s):  
Maryam Bahrami ◽  
◽  
Ali Ghazavi ◽  
Ali Ganji ◽  
Ghasem Mosayebi ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Nigella Sativa ◽  
Control Group ◽  
Silybum Marianum ◽  
Acute Peritonitis ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Background and Aim: In addition to free radicals such as Nitric Oxide (NO), inflammation is one of the most important pathophysiological causes of peritonitis. Over thousands of years, Nigella Sativa (NS) and Silybum Marianum (SM) are two plants known for their anti-oxidant and anti-inflammatory properties. However, the effect of its compound is unclear. Thus, in this study, we evaluated the anti-inflammatory effect of NS and SM extracts and their combination on inflammatory diseases like thioglycollate peritoneal. Methods & Materials: Alcoholic extracts of SM and NS were obtained by the soxhlet method. Male Balb/C mice were divided into 5 groups and gavage orally for 14 days with SM, NS, the mixture of extracts of these two, DMSO 30% as the control group, and dexamethasone as the positive control group. The safety profile and acute toxicity in mice were assessed. On day 10, acute peritonitis was induced by thioglycollate 3%. Finally, the total anti-oxidant power and NO concentration were measured by FRAP and Griess method, respectively, in the serum of treated mice. Ethical Considerations: All experimental process was performed following the guidelines according to the Animal Ethics Committee of Arak University of Medical Sciences (IR.ARAKMU.REC.1397.359). Results: Acute toxicity test showed no significant changes in weight and physical appearance of the mice. However, the extract and their mixture decreased NO level significantly (P=0.000) in serum. Also, the mixture significantly increased total anti-oxidant power (P=0.015). Conclusion: Results showed that the SM and NS extract mixture demonstrated anti-inflammatory activity, inhibiting inflammatory mediators such as NO and increasing anti-oxidant power, thus supporting its therapeutic potential in slowing down inflammatory processes in inflammation disorders.

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