scholarly journals Antinociceptive Activities and the Mechanisms of Anti-Inflammation of Asiatic Acid in Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Shyh-Shyun Huang ◽  
Chuan-Sung Chiu ◽  
Hsien-Jung Chen ◽  
Wen-Chi Hou ◽  
Ming-Jyh Sheu ◽  
...  

Asiatic acid (AA), a pentacyclic triterpene compound in the medicinal plantCentella asiatica, was evaluated for antinociceptive and anti-inflammatory effects. Treatment of male ICR mice with AA significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, AA decreased the paw edema at the 4th and 5th h afterλ-carrageenan (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue. AA decreased the nitric oxide (NO), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) levels on serum level at the 5th h after Carr injection. Western blotting revealed that AA decreased Carr-induced inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and nuclear factor-κB (NF-κB) expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with AA also diminished neutrophil infiltration into sites of inflammation as did indomethacin (Indo). The anti-inflammatory mechanisms of AA might be related to the decrease in the level of MDA, iNOS, COX-2, and NF-κB in the edema paw via increasing the activities of CAT, SOD, and GPx in the liver.

2019 ◽  
Vol 47 (07) ◽  
pp. 1571-1588
Author(s):  
Hwa-Jeong Lee ◽  
Jung Up Park ◽  
Rui Hong Guo ◽  
Bok Yun Kang ◽  
In-Kyu Park ◽  
...  

Canavalia gladiata, known as sword bean, has been used as a Chinese traditional medicine for anti-inflammatory effects. However, the action mechanisms of sword bean have not yet been clearly defined. In the present study, the whole parts of a ripened sword bean (RSB) and the green sword bean (GSB) containing bean pod were extracted with ethanol by reflux extraction. The two crude extracts (RSBE and GSBE) from RSB and GSB were validated by a liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis of gallic acid as a reference chemical. The anti-inflammatory effects of two sword bean extracts were extensively investigated using LPS-stimulated macrophage cells. First, RSBE and GSBE significantly inhibited the production of pro-inflammatory mediators, such as tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-6 (IL-6), prostaglandinE2 (PGE2), and nitric oxide (NO) in LPS-induced RAW264.7 cells. RSBE and GSBE showed no cytotoxicity to RAW264.7 cells and mouse peritoneal macrophage cells. In addition, the overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) induced by LPS in RAW264.7 cells was significantly decreased by RSBE and GSBE. Western blotting and immunostaining analysis showed that RSBE and GSBE inhibited the nuclear translocation of NF-[Formula: see text]B subunits, which correlated with the inhibitory effects on inhibitor kappa B (I[Formula: see text]B) degradation. In dextran sulfated sodium (DSS)-induced colitis mice model, RSBE restored body weight, colon length, and the levels of pro-inflammatory cytokines, such as TNF-[Formula: see text], IL-6, interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interferon-[Formula: see text] (IFN-[Formula: see text]). In addition, RSBE significantly suppressed the expression of COX-2, iNOS, and NF-[Formula: see text]B.


2014 ◽  
Vol 9 (7) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Min Hye Yang ◽  
Zulfiqar Ali ◽  
Ikhlas A. Khan ◽  
Shabana I. Khan

This study was aimed at the evaluation of the anti-inflammatory activity of twelve compounds isolated from the methanolic extract of fruits of Terminalia chebula. The activity was determined in terms of their ability to inhibit inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Two gallotannins [chebulinic acid (1) and 2,3,6-tri- O-galloyl-β-D-glucose (2)] and two triterpenoids [arjunic acid (3) and arjunolic acid (4)] efficiently reduced nitric oxide (NO) production with IC50 values of 53.4, 55.2, 48.8, and 38.0 μM, respectively. The protein expressions of iNOS and COX-2 were decreased in macrophages by treatment with compounds 1–4 (54–69% and 33–37%, respectively) at 50 μM. This is the first report of anti-inflammatory property of 1–4 mediated by inhibition of iNOS and COX-2 activities at the cellular level.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Dan-Dan Zhang ◽  
Hong Zhang ◽  
Yuan-zhi Lao ◽  
Rong Wu ◽  
Jin-wen Xu ◽  
...  

GarciniaLinn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNγ-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of NO and PGE2 during inflammation progress. Additionally, TIE also suppressed the expression of inflammatory cytokines IL-6, IL-12, and TNF-α. TIE-led suppression in iNOS, COX-2, and cytokines production were probably the consequence of TIE’s capability to block ERK and p38MAPK signaling pathway. Moreover, TIE blocked activation of nuclear factor-kappa B (NF-κB) as well as NF-κB regulation of miR155 expression. Our study suggests that TIE may represent as a potential therapeutic agent for the treatment of inflammatory diseases.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Chanyong Yun ◽  
Youngchul Jung ◽  
Wonjoo Chun ◽  
Beodeul Yang ◽  
Junghyun Ryu ◽  
...  

The leaves ofArtemisia argyiLev. et Vant. andA. princepsPamp. are well known medicinal herbs used to treat patients in China, Japan, and Korea with skin problems such as eczema and itching, as well as abdominal pain and dysmenorrhoea. We investigated the anti-inflammatory effects ofArtemisialeaf extract (ALE) using CD mice and Raw 264.7 cells. The effects of ALE on histopathological changes and cytokine production in ear tissues were assessed in mice with CD induced by 1-fluoro-2,4-dinitrobenzene (DNFB). Moreover, the anti-inflammatory effects on production levels of prostaglandin E2(PGE2) and nitric oxide (NO) and expression levels of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were investigated in Raw 264.7 cells. Topical application of ALE effectively prevented ear swelling induced by repeated DNFB application. ALE prevented epidermal hyperplasia and infiltration of immune cells and lowered the production of interferon- (IFN-) gamma (γ), tumour necrosis factor- (TNF-) alpha (α), and interleukin- (IL-) 6 in inflamed tissues. In addition, ALE inhibited expression of COX-2 and iNOS and production of NO and PGE2in Raw 264.7 cells. These results indicate thatArtemisialeaf can be used as a therapeutic agent for inflammatory skin diseases and that its anti-inflammatory effects are closely related to the inhibition of inflammatory mediator release from macrophages and inflammatory cytokine production in inflamed tissues.


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.


Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4089
Author(s):  
Seung-Hwa Baek ◽  
Tamina Park ◽  
Myung-Gyun Kang ◽  
Daeui Park

We evaluated the anti-inflammatory effects of SNAH in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by performing nitric oxide (NO) assays, cytokine enzyme-linked immunosorbent assays, Western blotting, and real-time reverse transcription-polymerase chain reaction analysis. SNAH inhibited the production of NO (nitric oxide), reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6. Additionally, 100 μM SNAH significantly inhibited total NO and ROS inhibitory activity by 93% (p < 0.001) and 34% (p < 0.05), respectively. Protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) stimulated by LPS were also decreased by SNAH. Moreover, SNAH significantly (p < 0.001) downregulated the TNF-α, IL-6, and iNOS mRNA expression upon LPS stimulation. In addition, 3–100 µM SNAH was not cytotoxic. Docking simulations and enzyme inhibitory assays with COX-2 revealed binding scores of −6.4 kcal/mol (IC50 = 47.8 μM) with SNAH compared to −11.1 kcal/mol (IC50 = 0.45 μM) with celecoxib, a known selective COX-2 inhibitor. Our results demonstrate that SNAH exerts anti-inflammatory effects via suppression of ROS and NO by COX-2 inhibition. Thus, SNAH may be useful as a pharmacological agent for treating inflammation-related diseases.


2014 ◽  
Vol 42 (06) ◽  
pp. 1485-1506 ◽  
Author(s):  
Shyh-Shyun Huang ◽  
Jeng-Shyan Deng ◽  
Jaung-Geng Lin ◽  
Chao-Ying Lee ◽  
Guan-Jhong Huang

In this study, we have investigated the anti-inflammatory effects of trilinolein (TL) using a lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) and carrageenan (Carr)-induced mouse paw edema model. When RAW264.7 macrophages were treated with different concentrations of TL together with LPS, a significant concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1 (IL-1β), and IL-6 production was detected. Western blotting revealed that TL blocked the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), IκBα, and mitogen-activated protein kinases (MAPKs). In the anti-inflammatory test, TL decreased the paw edema at the 5th h after λ-Carr administration in paw edema. We also demonstrated TL significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th h after Carr injection. TL decreased the NO and TNF-α levels on the serum level at the 5th h after Carr injection. Western blotting revealed that TL decreased Carr-induced iNOS and COX-2 expressions at the 5th h in the edema paw. The anti-inflammatory mechanisms of TL might be related to the decrease in the level of iNOS, COX-2, IκBα, and MAPK pathway through the suppression of TNF-α, IL-1β, and IL-6.


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.


Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 470
Author(s):  
Kyong Kim ◽  
Eun-Young Park ◽  
Dong-Jae Baek ◽  
Chul-Young Kim ◽  
Yoon-Sin Oh

This study was conducted to evaluate the fractions isolated from Allomyrina dichotoma larva extract (ADLE) that exhibited anti-apoptotic and anti-inflammatory effects. A total of 13 fractions were eluted from ADLE by centrifugal chromatography (CPC), and the polar AF-13 fraction was selected, which exerted a relatively protective effect against fat-induced toxicity in INS-1 cells. AF-13 treatment of palmitate-treated INS-1 cells decreased the expression level of apoptosis-related proteins and DNA fragmentation. AF-13 also significantly inhibited the production of nitric oxide and reactive oxygen species and the triglyceride content induced by palmitate, and the effect was found to be similar to that with ADLE treatment. Palmitate upregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) through the activation of NF-κB p65; however, this effect was significantly attenuated by AF-13 treatment. In conclusion, AF-13 is one of the major components of ADLE responsible for anti-apoptotic and anti-inflammatory activities.


Author(s):  
IDA MUSFIROH ◽  
HANIFAHZIN KHATAMI ◽  
SANDRA MEGANTARA ◽  
MUCHTARIDI MUCHTARIDI

Objective: The aim of this study was to determine the stability interaction of asiatic acid derivatives (AA) complex with inducible nitric oxide synthase (iNOS) enzyme as an anti-inflammatory using Molecular Dynamic (MD) simulation. Methods: The methods were consisting of validation of molecular docking, molecular docking to calculate binding affinity within the complex between the compounds and iNOS enzyme by using MMGBSA (Molecular Mechanics/Generalized Born Surface Area), and MD system preparation, MD production as well as MD analysis using AMBER18. Results: The result of validation and molecular docking were AA5 has the most negative Gibbs energy that is -9.17 kcal/mol, which has better binding affinity than other derivatives than other derivatives. The molecular dynamics simulation of the modified structure of asiatic acid showed that binding energy value and RMSD of AA5, AA6 and AA9 have a lower value compared to arginine as a substrate of iNOS enzyme. Molecular Dynamics that have been occurred to the best three compounds chosen shown good result in terms of stability after 100 ns length simulation. And the lowest binding affinity has been achieved by a compound called AA5. Out of all ligands that have been simulated shown that their binding affinity was lower than AA5 that reached-44.6753 kcal/mol. Conclusion: This studies conclude that AA5 considerably more potential as a selective inhibitor of iNOS enzyme as an anti-inflammatory.


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