Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects

We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6–37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.

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Anti-Inflammatory Effects of Formononetin 7-O-phosphate, a Novel Biorenovation Product, on LPS-Stimulated RAW 264.7 Macrophage Cells

Molecules ◽

10.3390/molecules24213910 ◽

2019 ◽

Vol 24 (21) ◽

pp. 3910 ◽

Cited By ~ 2

Author(s):

Min-Seon Kim ◽

Jin-Soo Park ◽

You Chul Chung ◽

Sungchan Jang ◽

Chang-Gu Hyun ◽

...

Keyword(s):

Biological Properties ◽

In Vitro Assays ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Dependent Manner ◽

Macrophage Cells ◽

Anti Inflammatory ◽

Reduced Toxicity

Biorenovation is a microbial enzyme-catalyzed structural modification of organic compounds with the potential benefits of reduced toxicity and improved biological properties relative to their precursor compounds. In this study, we synthesized a novel compound verified as formononetin 7-O-phosphate (FMP) from formononetin (FM) using microbial biotransformation. We further compared the anti-inflammatory properties of FMP to FM in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. We observed that cell viabilities and inhibitory effects on LPS-induced nitric oxide (NO) production were greater in FMP-treated RAW 264.7 cells than in their FM-treated counterparts. In addition, FMP treatment suppressed the production of proinflammatory cytokines such as prostaglandin-E2 (PGE2), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner and concomitantly decreased the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). We also found that FMP exerted its anti-inflammatory effects through the downregulation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa B (NF-κB) signaling pathways. In conclusion, we generated a novel anti-inflammatory compound using biorenovation and demonstrated its efficacy in cell-based in vitro assays.

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ANTI-INFLAMMATORY ACTIVITY OF TINOCRISPOSIDE BY INHIBITING NITRIC OXIDE PRODUCTION IN LIPOPOLYSACCHARIDES-STIMULATED RAW 264.7 CELLS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i4.23739 ◽

2018 ◽

Vol 11 (4) ◽

pp. 149 ◽

Cited By ~ 1

Author(s):

Adek Zamrud Adnan ◽

Muhammad Taher ◽

Tika Afriani ◽

Annisa Fauzana ◽

Dewi Imelda Roesma ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Diseases ◽

Positive Control ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Dependent Manner ◽

Anti Inflammatory

Objective: The aim of this study was to investigate in vitro anti-inflammatory activity of tinocrisposide using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophage cells. Tinocrisposide is a furano diterpene glycoside that was isolated in our previous study from Tinospora crispa.Methods: Anti-inflammatory effect was quantified spectrometrically using Griess method by measuring nitric oxide (NO) production after the addition of Griess reagent.Results: The sample concentrations of 1, 5, 25, 50, and 100 μM and 100 μM of dexamethasone (positive control) have been tested against the LPS-stimulated RAW 264.7 cells, and the results showed NO level production of 39.23, 34.00, 28.9, 20.25, 16.3, and 13.68 μM, respectively, and the inhibition level of 22.67, 33.00, 43.03, 60.10, 68.00, and 73%, respectively.Conclusions: From the study, it could be concluded that tinocrisposide was able to inhibit the formation of NO in the LPS-stimulated RAW 264.7 cells in concentration activity-dependent manner, with half-maximal inhibition concentration 46.92 μM. It can be developed as anti-inflammatory candidate drug because NO is a reactive nitrogen species which is produced by NO synthase. The production of NO has been established as a mediator in inflammatory diseases.

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Effects of Sibseonsan as an Anti-Inflammatory, Anti-Wrinkle, and Skin Whitening Treatment

Journal of Acupuncture Research ◽

10.13045/jar.2020.00024 ◽

2020 ◽

Vol 37 (2) ◽

pp. 88-93

Author(s):

Na Young Jo

Keyword(s):

Treatment Group ◽

Cell Line ◽

Radical Scavenging ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Tnf Α ◽

Anti Inflammatory

Background: The purpose of this study was to investigate whether Sibseonsan (SSS) is an effective anti-inflammatory, anti-wrinkling, and whitening agent.Methods: To determine whether SSS had an anti-inflammatory effect, a murine macrophage cell line was used (RAW 264.7) and production of DPPH, NO, TNF-α, and PGE2 were measured. To ascertain potential anti-wrinkle effects of SSS in these cells, collagenase and elastase production were measured. To verify whether SSS had a whitening effect, tyrosinase activity and DOPA staining were performed using a melanoma cell line (B16/F10).Results: There was no significant reduction in survival of SSS-treated RAW 264.7 cells, up to 400 μg/mL. Free radical scavenging (23.96 ± 1.85%) was observed in RAW 264.7 cells treated with SSS at a concentration of 400 μg/mL. The SSS treatment group (400 μg/mL) significantly inhibited NO production compared with the LPS stimulated treatment group. The SSS treatment of macrophage cells appeared to reduce production of TNF-α in a concentration dependent manner. There was a significant reduction in the concentration of PGE2 by about 25% in the SSS treatment (400 μg/mL) group (p = 0.05). Compared with the control, the production of collagenase and elastase in B16/F10 cells treated with SSS (400 μg/mL) was greater by 26.37% and 45.71%, respectively. The SSS treatment (400 μg/mL) group showed a significant reduction by about 17% in tyrosinase production in B16/F10 cells. The SSS treatment group showed little change in DOPA staining. Conclusion: SSS extract may be useful for the treatment and prevention of inflammatory diseases and may have anti-wrinkle and whitening effects. These results may support the use of SSS in clinical practice.

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Anti-Inflammatory Effects of 6-Methylcoumarin in LPS-Stimulated RAW 264.7 Macrophages via Regulation of MAPK and NF-κB Signaling Pathways

Molecules ◽

10.3390/molecules26175351 ◽

2021 ◽

Vol 26 (17) ◽

pp. 5351

Author(s):

Jin-Kyu Kang ◽

You-Chul Chung ◽

Chang-Gu Hyun

Keyword(s):

Nitric Oxide ◽

Inflammatory Cytokines ◽

Mitogen Activated Protein Kinase ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Persistent inflammatory reactions promote mucosal damage and cause dysfunction, such as pain, swelling, seizures, and fever. Therefore, in this study, in order to explore the anti-inflammatory effect of 6-methylcoumarin (6-MC) and suggest its availability, macrophages were stimulated with lipopolysaccharide (LPS) to conduct an in vitro experiment. The effects of 6-MC on the production and levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α) and inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) in LPS-stimulated RAW 264.7 cells were examined. The results showed that 6-MC reduced the levels of NO and PGE2 without being cytotoxic. In addition, it was demonstrated that the increase in the expression of pro-inflammatory cytokines caused by LPS stimulation, was decreased in a concentration-dependent manner with 6-MC treatment. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which increased with LPS treatment, were decreased by 6-MC treatment. Mechanistic studies revealed that 6-MC reduced the phosphorylation of the mitogen-activated protein kinase (MAPK) family and IκBα in the MAPK and nuclear factor-kappa B (NF-κB) pathways, respectively. These results suggest that 6-MC is a potential therapeutic agent for inflammatory diseases that inhibits inflammation via the MAPK and NF-κB pathways.

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Anti-inflammatory Constituents from Caulis Trachelospermi

Planta Medica ◽

10.1055/a-1712-8209 ◽

2021 ◽

Author(s):

Hongzhi Song ◽

Jinni Tan ◽

Ruijing Ma ◽

Edward J Kennelly ◽

Qingang Tan

Keyword(s):

Chemical Constituents ◽

Preliminary Investigation ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Spectrometric Data ◽

Phytochemical Investigation ◽

Anti Inflammatory

AbstractCaulis Trachelospermi, the stems with leaves of Trachelospermum jasminoides, is a well-known herbal drug of the Apocynaceae family recorded in the Chinese pharmacopeia and used for the treatment of inflammation-related diseases by ethnic minorities of China. The mechanism of anti-inflammatory activity and responsible constituents of T. jasminoides have not been well elucidated in previous studies. Preliminary investigation showed that both the water and the ethyl ester extracts of T. jasminoides exhibited potent inhibitory activity on nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated murine macrophages. Phytochemical investigation on these extracts afforded 23 compounds, including three new compounds (1 –3) identified on the basis of spectroscopic and mass spectrometric data. Anti-inflammatory bioassay showed that compounds 17, 18, 22, and 23 inhibited significantly the production of NO in a concentration-dependent manner. Further studies indicated that compound 23 inhibited significantly TNF-α and IL-6 produced by LPS-stimulated RAW 264.7 cells with good selectivity, as well as protein expression of iNOS in RAW 264.7 cells. These chemical constituents may contribute to the anti-inflammatory potential of T. jasminoides.

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New 12,23-Epoxydammarane Type Saponins Obtained from Panax notoginseng Leaves and Their Anti-Inflammatory Activity

Molecules ◽

10.3390/molecules25173784 ◽

2020 ◽

Vol 25 (17) ◽

pp. 3784

Author(s):

Jingya Ruan ◽

Ying Zhang ◽

Wei Zhao ◽

Fan Sun ◽

Lifeng Han ◽

...

Keyword(s):

Nitric Oxide ◽

Panax Notoginseng ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Necrosis Factor Alpha ◽

Anti Inflammatory

Two new 12,23-epoxydammarane-type saponins, notoginsenosides NL-I (1) and NL-J (2), were isolated and identified from Panax notoginseng leaves through the combination of various chromatographies and extensive spectroscopic methods, as well as chemical reactions. Among them, notoginsenoside NL-J (2) had a new skeleton. Furthermore, the lipopolysaccharide (LPS)-induced RAW 264.7 macrophage model was used to identify the in vitro anti-inflammatory activity and mechanisms of compounds 1 and 2. Both of them exerted strong inhibition on nitric oxide (NO) productions in a concentration-dependent manner at 1, 10, and 25 μM. Moreover, these two compounds significantly decreased the secretion of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB/p65), and nitric-oxide synthase (iNOS) in LPS-activated RAW 264.7 cells.

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Antioxidant and Anti-Inflammatory Activities of Safflower (Carthamus tinctorius L.) Honey Extract

Foods ◽

10.3390/foods9081039 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1039

Author(s):

Li-Ping Sun ◽

Feng-Feng Shi ◽

Wen-Wen Zhang ◽

Zhi-Hao Zhang ◽

Kai Wang

Keyword(s):

Chemical Composition ◽

Biological Activities ◽

Carthamus Tinctorius ◽

Raw 264.7 Cells ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Unique Type ◽

Antioxidant Genes ◽

Anti Inflammatory

Safflower honey is a unique type of monofloral honey collected from the nectar of Carthamus tinctorius L. in the Apis mellifera colonies of northwestern China. Scant information is available regarding its chemical composition and biological activities. Here, for the first time, we investigated this honey’s chemical composition and evaluated its in vitro antioxidant and anti-inflammatory activities. Basic physicochemical parameters of the safflower honey samples in comparison to established quality standards suggested that safflower honeys presented a good level of quality. The in vitro antioxidant tests showed that extract from Carthamus tinctorius L. honey (ECH) effectively scavenged DPPH and ABTS+ free radicals. In lipopolysaccharides (LPS) activated murine macrophages inflammatory model, ECH treatment to the cells inhibited the release of nitric oxide and down-regulated the expressions of inflammatory-relating genes (iNOS, IL-1β, TNF-α and MCP-1). The expressions of the antioxidant genes TXNRD, HO-1, and NQO-1, were significantly boosted in a concentration-dependent manner. ECH decreased the phosphorylation of IκBα and inhibited the nuclear entry of the NF-κB-p65 protein, in LPS-stimulated Raw 264.7 cells, accompany with the increased expressions of Nrf-2 and HO-1, suggesting that ECH achieved the anti-inflammatory effects by inhibiting NF-κB signal transduction and boosting the antioxidant system via activating Nrf-2/HO-1 signaling. These results, taken together, indicated that safflower honey has great potential into developing as a high-quality agriproduct.

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Cordyceps militaris Fungus Extracts-Mediated Nanoemulsion for Improvement Antioxidant, Antimicrobial, and Anti-Inflammatory Activities

Molecules ◽

10.3390/molecules25235733 ◽

2020 ◽

Vol 25 (23) ◽

pp. 5733

Author(s):

Esrat Jahan Rupa ◽

Jin Feng Li ◽

Muhammad Huzaifa Arif ◽

Han Yaxi ◽

Aditi Mitra Puja ◽

...

Keyword(s):

Zeta Potential ◽

Tween 80 ◽

In Vitro Cytotoxicity ◽

Cordyceps Militaris ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Anti Inflammatory

This study aimed to produce and optimize a Cordyceps militaris-based oil-in-water (O/W) nanoemulsion (NE) encapsulated in sea buckthorn oil (SBT) using an ultrasonication process. Herein, a nonionic surfactant (Tween 80) and chitosan cosurfactant were used as emulsifying agents. The Cordyceps nanoemulsion (COR-NE) was characterized using Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and field-emission transmission electron microscope (FE-TEM). The DLS analyses revealed that the NE droplets were 87.0 ± 2.1 nm in diameter, with a PDI value of 0.089 ± 0.023, and zeta potential of −26.20 ± 2. The small size, low PDI, and stable zeta potential highlighted the excellent stability of the NE. The NE was tested for stability under different temperature (4 °C, 25 °C, and 60 °C) and storage conditions for 3 months where 4 °C did not affect the stability. Finally, in vitro cytotoxicity and anti-inflammatory activity were assessed. The results suggested that the NE was not toxic to RAW 264.7 or HaCaT (human keratinocyte) cell lines at up to 100 µL/mL. Anti-inflammatory activity in liposaccharides (LPS)-induced RAW 264.7 cells was evident at 50 µg/mL and showed inhibition of NO production and downregulation of pro-inflammatory gene expression. Further, the NE exhibited good antioxidant (2.96 ± 0.10 mg/mL) activity and inhibited E. coli and S. aureus bacterial growth. Overall, the COR-NE had greater efficacy than the free extract and added significant value for future biomedical and cosmetics applications.

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In vitro and in vivo anti-inflammatory activities of a sterol-enriched fraction from freshwater green alga, Spirogyra sp.

Fisheries and Aquatic Sciences ◽

10.1186/s41240-020-00172-9 ◽

2020 ◽

Vol 23 (1) ◽

Author(s):

Lei Wang ◽

You-Jin Jeon ◽

Jae-Il Kim

Keyword(s):

Nitric Oxide ◽

Green Alga ◽

Raw 264.7 Cells ◽

Ros Generation ◽

Prostaglandin E ◽

No Production ◽

Raw 264.7 ◽

Anti Inflammatory

Abstract Background Inflammation plays a crucial role in the pathogenesis of many diseases such as arthritis and atherosclerosis. In the present study, we evaluated anti-inflammatory activity of sterol-rich fraction prepared from Spirogyra sp., a freshwater green alga, in an effort to find bioactive extracts derived from natural sources. Methods The sterol content of ethanol extract of Spirogyra sp. (SPE) was enriched by fractionation with hexane (SPEH), resulting 6.7 times higher than SPE. Using this fraction, the in vitro and in vivo anti-inflammatory activities were evaluated in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells and zebrafish. Results SPEH effectively and dose-dependently decreased the production of nitric oxide (NO) and prostaglandin E2 (PGE2). SPEH suppressed the production of pro-inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β through downregulating nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW 264.7 cells without cytotoxicity. The in vivo test results indicated that SPEH significantly and dose-dependently reduced reactive oxygen species (ROS) generation, cell death, and NO production in LPS-stimulated zebrafish. Conclusions These results demonstrate that SPEH possesses strong in vitro and in vivo anti-inflammatory activities and has the potential to be used as healthcare or pharmaceutical material for the treatment of inflammatory diseases.

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IN VITRO ANTI-INFLAMMATORY ACTIVITY OF THE COMPONENTS OF AMOMUM TSAO-KO IN MURINE MACROPHAGE RAW 264.7 CELLS

African Journal of Traditional Complementary and Alternative Medicines ◽

10.21010/ajtcamv15i2.4 ◽

2018 ◽

Vol 15 (2) ◽

pp. 26

Author(s):

Chun Whan Choi ◽

Ju Young Shin ◽

Changon Seo ◽

Seong Su Hong ◽

Eun-Kyung Ahn ◽

...

Keyword(s):

Nitric Oxide ◽

Benzoic Acid ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Dependent Manner ◽

Murine Macrophage ◽

Etoh Extract ◽

Anti Inflammatory

Background: Plants still remain the prime source of drugs for the treatment of inflammation and can provide leads for the development of novel anti-inflammatory agents. Material and methods: An in vitro bioassay guide revealed that the 80% ethanol (EtOH) extract of the whole plant, Amomum tsao-ko (Zingiberaceae), displayed anti-inflammatory activity after assessing its effects on murine macrophage RAW 264.7 cells. Result: Phytochemical study of the 80% EtOH extract of Amomum tsao-ko led to the isolation of eight compounds: 4-hydroxy-3-methoxy-benzoic acid (1), meso-hannokinol (2), (+)-hannokinol (3), coumaric acid (4), 4-hydroxy-benzoic acid (5), (+)-epicatechin (6), (-)-catechin (7), and myrciaphenone A (8). The results indicated that two of the isolated components, (+)-epicatechin (6) and (-)-catechin (7), inhibited the production of nitric oxide (NO) significantly in lipopolysaccharide treated RAW 264.7 cells. Conclusion: LPS-induced interleukin tumor necrosis factor-alpha (TNF-), IL-1β and IL-10 production was also decreased in a dose-dependent manner. In addition, western blot analysis revealed that (+)-epicatechin (6) and (-)-catechin (7) reduced the expression of inducible nitric oxide synthase and inhibited nuclear localization of nuclear factor kappa-B (NF-κB).

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