Reactive oxygen species

Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases

Structural diversity and bioactivities of natural benzophenones.

In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19.

Non-communicable diseases (NCDs) such as cancer, diabetes, and chronic respiratory and cardiovascular diseases continue to be threatening and deadly to human kind. Resistance to and side effects of known drugs for treatment further increase the threat, while at the same time leaving scientists to search for alternative sources from nature, especially from plants. Pentacyclic triterpenoids (PT) from medicinal plants have been identified as one class of secondary metabolites that could play a critical role in the treatment and management of several NCDs. One of such PT is ursolic acid (UA, 3 β-hydroxy-urs-12-en-28-oic acid), which possesses important biological effects, including anti-inflammatory, anticancer, antidiabetic, antioxidant and antibacterial effects, but its bioavailability and solubility limits its clinical application. Mimusops caffra, Ilex paraguarieni, and Glechoma hederacea, have been reported as major sources of UA. The chemistry of UA has been studied extensively based on the literature, with modifications mostly having been made at positions C-3 (hydroxyl), C12-C13 (double bonds) and C-28 (carboxylic acid), leading to several UA derivatives (esters, amides, oxadiazole quinolone, etc.) with enhanced potency, bioavailability and water solubility. This article comprehensively reviews the information that has become available over the last decade with respect to the sources, chemistry, biological potency and clinical trials of UA and its derivatives as potential therapeutic agents, with a focus on addressing NCDs.

Ursolic Acid and Its Derivatives as Bioactive Agents

2-Methoxy-1,4-naphthoquinone (MNQ) induces apoptosis of A549 lung adenocarcinoma cells via oxidation-triggered JNK and p38 MAPK signaling pathways

Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs) are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX) enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS). The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in various in vivo and in vitro experimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB)/COX-2 expression, upstream protein kinase signaling, and phospholipase A2 enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli.

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Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

The pathogenesis of skin inflammatory diseases such as atopic dermatitis, acne, psoriasis, and skin cancers generally involve the generation of oxidative stress and chronic inflammation. Exposure of the skin to external aggressors such as ultraviolet (UV) radiation and xenobiotics induces the generation of reactive oxygen species (ROS) which subsequently activates immune responses and causes immunological aberrations. Hence, antioxidant and anti-inflammatory agents were considered to be potential compounds to treat skin inflammatory diseases. A prime example of such compounds is xanthone (xanthene-9-one), a class of natural compounds that possess a wide range of biological activities including antioxidant, anti-inflammatory, antimicrobial, cytotoxic, and chemotherapeutic effects. Many studies reported various mechanisms of action by xanthones for the treatment of skin inflammatory diseases. These mechanisms of action commonly involve the modulation of various pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNF-α), as well as anti-inflammatory cytokines such as IL-10. Other mechanisms of action include the regulation of NF-κB and MAPK signaling pathways, besides immune cell recruitment via modulation of chemokines, activation, and infiltration. Moreover, disease-specific activity contributed by xanthones, such as antibacterial action against Propionibacterium acnes and Staphylococcus epidermidis for acne treatment, and numerous cytotoxic mechanisms involving pro-apoptotic and anti-metastatic effects for skin cancer treatment have been extensively elucidated. Furthermore, xanthones have been reported to modulate pathways responsible for mediating oxidative stress and inflammation such as PPAR, nuclear factor erythroid 2-related factor and prostaglandin cascades. These pathways were also implicated in skin inflammatory diseases. Xanthones including the prenylated α-mangostin (2) and γ-mangostin (3), glucosylated mangiferin (4) and the caged xanthone gambogic acid (8) are potential lead compounds to be further developed into pharmaceutical agents for the treatment of skin inflammatory diseases. Future studies on the structure-activity relationships, molecular mechanisms, and applications of xanthones for the treatment of skin inflammatory diseases are thus highly recommended.

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Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application.

Background The extensive usage of zinc oxide nanoparticles (ZnO NPs) in industrial and consumer products raises the risk of releasing their residues into the aquatic environment. The presence of ZnO NPs in the aquatic environment could potentially cause cytotoxic effects on aquatic organisms. Thus, investigating the cytotoxic effects of ZnO NPs on microalgae, which form the base for the food web of aquatic biota, is essential to gain information regarding the ecotoxicological effects of metallic oxide nanoparticles in the aquatic ecosystem. Therefore, the present study has investigated in detail the assorted cytotoxic effects of ZnO NPs on S. platensis using various concentrations of ZnO NPs (10-200 mg/L) from 6 to 96 h to explore the dose- and time-dependent cytotoxic effects. Methods The cytotoxic effects were all assessed through quantification of loss in cell viability, reduction in biomass and decrease in photosynthetic pigments such as chlorophyll-a, carotenoids and phycocyanin. The surface interactions of nanoparticles and the subsequent morphological alterations on algal cells were examined by optical and scanning electron microscopy (SEM). The intracellular alterations of algal cells were studied using transmission electron microscopy. Furthermore, Fourier transformed infrared (FTIR) spectrum was obtained to investigate the involvement of algal surface biomolecules in surface binding of ZnO NPs on algal cells. Results The treatment of ZnO NPs on S. platensis exhibited a typical concentration- and time-dependent cytotoxicity. Results showed a significant (p < 0.05) cytotoxicity from 24 h onwards for all tested concentrations of ZnO NPs. The maximum cytotoxicity on algal cells was achieved at 96 h of exposure to ZnO NPs. In comparison with control, the algal cells that interacted with 200 mg/L of ZnO NPs for 96 h showed 87.3 ± 1% loss in cell viability, 76.1 ± 1.7% reduction in algal biomass, 92.5 ± 2.2%, 76.2 ± 2.2% and 74.1 ± 3.4% decrease in chlorophyll-a, carotenoids and phycocyanin contents respectively. Our study confirmed the cytotoxicity of ZnO NPs through the algal growth inhibition with 72 h EC10 and EC50 values of 1.29 and 31.56 mg/L, respectively. The microscopic examinations of the algal cells that interacted with ZnO NPs showed severe cell membrane and intracellular damage. The SEM EDX spectrum of ZnO NPs treated algal biomass evidenced the surface accumulation of zinc in the biomass. Finally, the FTIR spectrum confirmed the involvement of amino, hydroxyl and carboxylic groups of algal cell wall in the surface interaction of ZnO NPs on the algal cells. Discussion The results showed that the treatment of ZnO NPs on S. platensis triggered substantial cytotoxicity and caused cell death. Hence, S. platensis could be potentially used as a bioindicator for testing toxicity of ZnO NPs in aquatic environment.

Cytotoxic effects of zinc oxide nanoparticles on cyanobacterium Spirulina (Arthrospira) platensis.

Six anthraquinones (nordamnacanthal, alizarin-1-methyl ether, rubiadin, soranjidiol, lucidin-ω-methyl ether and morindone) isolated from the cell suspension culture of Morinda elliptica were assayed for antitumor promoting and antioxidant activities. All compounds exhibited strong antitumor promoting activity at the concentration of 2.0 µg/ml when assayed using the inhibition test of Epstein Barr Virus (EBV) activation on Raji cells. At the concentration of 0.4 µg/ml, only nordamnacanthal exhibited strong antitumor promoting activity with the inhibition rate and the cell viability of 75.0% and 75.8%, respectively, which was stronger than the reference compounds genistein and quercetin. In antioxidant assay using ferric thiocyanate (FTC) method, nordamnacanthal and morindone showed stronger antioxidant activity than α-tocopherol. However when the com- pounds were assayed for scavenging activity of the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals, only morindone was considered to be active as free radical scavenger with fifty percent inhibition concentration (IC 50 ) of 40.6 µg/ml.

Yang Mooi Lim

Papers

2-Methoxy-1,4-naphthoquinone (MNQ) induces apoptosis of A549 lung adenocarcinoma cells via oxidation-triggered JNK and p38 MAPK signaling pathways

Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application.

Cytotoxic effects of zinc oxide nanoparticles on cyanobacterium Spirulina (Arthrospira) platensis.

Antitumor promoting and actioxidant activities of anthraquinones isolated from the cell suspension culture of Morinda elliptica