scholarly journals Cudratricusxanthone A Inhibits Lipid Accumulation and Expression of Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes

2021 ◽  
Vol 22 (2) ◽  
pp. 505
Author(s):  
Hyo-Shin Kwon ◽  
Gil-Saeng Jeong ◽  
Byeong-Churl Jang

Cudratricusxanthone A (CTXA) is a natural bioactive compound extracted from the roots of Cudrania tricuspidata Bureau and has been shown to possess anti-inflammatory, anti-proliferative, and hepatoprotective activities. However, at present, anti-adipogenic and anti-inflammatory effects of CTXA on adipocytes remain unclear. In this study, we investigated the effects of CTXA on lipid accumulation and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, two known inflammatory enzymes, in 3T3-L1 preadipocytes. Strikingly, CTXA at 10 µM markedly inhibited lipid accumulation and reduced triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. On mechanistic levels, CTXA at 10 µM suppressed not only expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A, but also phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during 3T3-L1 preadipocyte differentiation. In addition, CTXA at 10 µM up-regulated phosphorylation levels of cAMP-activated protein kinase (AMPK) while down-regulating expression and phosphorylation levels of acetyl-CoA carboxylase (ACC) during 3T3-L1 preadipocyte differentiation. Moreover, CTXA at 10 µM greatly attenuated tumor necrosis factor (TNF)-α-induced expression of iNOS, but not COX-2, in 3T3-L1 preadipocytes. These results collectively demonstrate that CTXA has strong anti-adipogenic and anti-inflammatory effects on 3T3-L1 cells through control of the expression and phosphorylation levels of C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, STAT-3/5, AMPK, and iNOS.

2021 ◽  
Author(s):  
Anuradha Kalita ◽  
MANAS DAS ◽  
Bhabajyoti Das ◽  
Momita Rani Baro

Abstract Garcinia is a tropical plant that has been traditionally used in medicinal folklore for its potential antioxidant, antibacterial, anti-hyperlipidemic, anti-diabetic, hepatoprotective, etc. In this study, Garcinia herbal extract (GHE) and one of its important phytocompound (garcinol) were evaluated for their inhibitory action against important inflammatory markers inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. iNOS and COX-2 plays an major role in the process of inflammation and inhibition of these molecules will help to alleviate the inflammatory process. The cells were pre-treated with two doses of Garcinia (230µg/ml and 115µg/ml); garcinol (12µM and 6µM) followed by stimulation with 1µg/ml of LPS for 24h. The results of the study demonstrated that GHE and garcinol plays an important role in suppressing LPS- induced relative mRNA expression of iNOS, COX-2 and subsequent reduction in the levels of nitric oxide and prostaglandin E 2 . Molecular docking analysis of garcinol and hydroxycitric acid, the major active components of GHE with iNOS and COX-2 proteins showed potent interaction with low binding energies. This study suggests that GHE (containing high percentage of HCA) and garcinol may possess anti-inflammatory activity thus providing a possibility for drug designing as iNOS and COX-2 inhibitors.


2020 ◽  
Vol 44 (7-8) ◽  
pp. 381-387
Author(s):  
Mohammad Nur-e-Alam ◽  
Sarfaraz Ahmed ◽  
Muhammad Yousaf ◽  
Shabana I Khan ◽  
Ramzi A Mothana ◽  
...  

Scoparia dulcis L. is one of the edible widely distributed Scropholariaceae species in Asia, Africa and America. It is used in the treatment of respiratory and inflammatory diseases, diabetes, hypertension, cancer, hepatitis and tuberculosis. A phytochemical investigation on S. dulcis led to the isolation of two new acyclic diterpenes Acetic acid 6-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-4,8-dimethyl-undeca-4,8-dienyl ester (1) and Acetic acid 8-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-6,10-dimethyl-undeca-5,9-dienyl ester (2) in addition to eight known compounds (3–10), namely scopadulciol (3), 4- epi-scopadulcic acid B (4), dulcidiol (5), scopadulcic acid B (6), hymenoxin (7), glutinol (8), eupatilin (9) and 5-demethylnobiletin (10). The structures elucidation was performed using spectroscopic means, including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrum spectrometric analysis. Furthermore, the isolated compounds were investigated for their anti-inflammatory activity through the determination of inhibition of nuclear factor-kappa B activity in human chondrosarcoma (SW1353) cells, the inhibition of inducible nitric oxide synthase mouse macrophages (RAW264.7) and the decrease in cellular oxidative stress in HepG2 cells. Moreover, the cytotoxic activity was investigated against four cancer and two kidney cell lines. Among the isolates, 3, 5 and 10 showed anti-inflammatory activity in terms of inhibiting nuclear factor-kappa B and inducible nitric oxide synthase. Compounds 3–5 were the most cytotoxic towards cancer cell lines (IC50: 3.8 µM to 42.3 µM) followed by 10 (IC50: 30.9- > 64.4 µM). Cytotoxicity of compounds 3–5 was comparable to the activity of doxorubicin.


Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1405 ◽  
Author(s):  
Thanh-Hao Huynh ◽  
Lee-Shing Fang ◽  
Yu-Hsin Chen ◽  
Bo-Rong Peng ◽  
You-Ying Chen ◽  
...  

Five 8,17-epoxybriaranes, including three new compounds—briarenols I–K (1–3), along with two known analogues, briaexcavatolide P (4) and briaexcavatin P (5), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1–3 were elucidated by spectroscopic methods, including 1D and 2D NMR studies and (+)-HRESIMS. Briarane 4 exerted inhibition effects on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) release from RAW 264.7.


2006 ◽  
Vol 291 (3) ◽  
pp. F567-F577 ◽  
Author(s):  
Li-Mei Chen ◽  
Cindy Wang ◽  
Mengqian Chen ◽  
Matthew R. Marcello ◽  
Julie Chao ◽  
...  

Prostasin is a glycosylphosphatidylinositol-anchored serine protease, with epithelial sodium channel activation and tumor invasion suppression activities. We identified the bladder as an expression site of prostasin. In the mouse, prostasin mRNA expression was detected by reverse transcription and real-time polymerase chain reaction in the bladder, and the prostasin protein was localized by immunohistochemistry in the urothelial cells. In mice injected intraperitoneally with bacterial lipopolysaccharide (LPS), bladder prostasin mRNA expression was downregulated, whereas the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interferon-γ (IFN-γ), TNF-α, IL-1β, and IL-6 was upregulated. Viral promoter-driven expression of the human prostasin homolog in the bladder of transgenic mice attenuated the LPS induction of iNOS but did not abolish the induction. LPS induction of COX-2, TNF-α, IL-1β, and IL-6 expression, however, was not reduced by prostasin transgene expression. Liposome-mediated delivery of prostasin-expressing plasmid into mouse bladder produced similar attenuation effects on LPS-induced iNOS expression, while not affecting COX-2 or cytokine induction. Mice receiving plasmid expressing a catalytic mutant prostasin did not manifest the iNOS induction attenuation phenotype. We propose a proteolytic mechanism for prostasin to intercept cytokine signaling during LPS-induced bladder inflammation.


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