scholarly journals Stauntonia hexaphylla leaf extract (YRA-1909) suppresses inflammation by modulating Akt/NF-κB signaling in lipopolysaccharide-activated peritoneal macrophages and rodent models of inflammation

Author(s):  
Jaeyong Kim ◽  
Gyuok Lee ◽  
Huwon Kang ◽  
Ji-Seok Yoo ◽  
Yongnam Lee ◽  
...  

Background: Inflammation is emerging as a key contributor to many vascular diseases and furthermore plays a major role in autoimmune diseases, arthritis, allergic reactions, and cancer. Lipopolysaccharide (LPS), which is a component constituting the outer membrane of Gram-negative bacteria, is commonly used for an inflammatory stimuli to mimic inflammatory diseases. Nuclear factor-kappa B (NF-κB) is a transcription factor and regulates gene expression particularly related to the inflammatory process. Stauntonia hexaphylla (Lardizabalaceae) is widely used as a traditional herbal medicine for rheumatism and osteoporosis and as an analgesic, sedative, and diuretic in Korea, Japan, and China. Objective: The purpose of this study was to investigate the anti-inflammatory activity of YRA-1909, the leaf aqueous extract of Stauntonia hexaphylla using LPS-activated rat peritoneal macrophages and rodent inflammation models. Results: YRA-1909 inhibited the LPS-induced nitric oxide (NO) and proinflammatory cytokine production in rat peritoneal macrophages without causing cytotoxicity and reduced inducible NO synthase and prostaglandin E2 levels without affecting the cyclooxygenase-2 expression. YRA-1909 also prevented the LPS-stimulated Akt and NF-κB phosphorylation and reduced the carrageenan-induced hind paw edema, xylene-induced ear edema, acetic acid-induced vascular permeation, and cotton pellet-induced granuloma formation in a dose-dependent manner in mice and rats. Conclusions: S. hexaphylla leaf extract YRA-1909 had anti-inflammatory activity in vitro and in vivo that involves modulation of Akt/NF-κB signaling. Thus, YRA-1909 is safe and effective for the treatment of inflammation.

Author(s):  
Mingzhu Luan ◽  
Huiyun Wang ◽  
Jiazhen Wang ◽  
Xiaofan Zhang ◽  
Fenglan Zhao ◽  
...  

: 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.


Author(s):  
Adek Zamrud Adnan ◽  
Muhammad Taher ◽  
Tika Afriani ◽  
Annisa Fauzana ◽  
Dewi Imelda Roesma ◽  
...  

 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.


Author(s):  
Ali Sandi Dwi Cahyo ◽  
Sri Oktavia ◽  
Ifora Ifora

Inflammatory diseases have affected a large proportion of the population worldwide, and inflammation is a major risk factor for several dangerous disease pathologies. The increasing incidence and impact of inflammatory diseases have prompted research into pharmacological strategies to deal with them. Chromolaena odorata is traditionally used as an anti-inflammatory, antipyretic, antioxidant, analgesic, and as a wound-healing agent. Therefore, this review aimed to obtain a comprehensive review of the anti-inflammatory activity of Chromolaena odorata. This review provides evidence in the literature for the anti-inflammatory and analgesic activity of Chromolaena odorata, from 2010 to 2021. Three bibliographic databases were used as primary sources of information (PubMed, ScienceDirect, and Google Scholar). The keywords in this research were "Anti-inflammatory", "Analgesic" and "Chromolaena odorata". A total of 7 studies were included in this review according to the required criteria, 3 of which were in vitro studies and 4 in vivo studies.Pharmacological studies reported that Chromolaena odorata was proven to have anti-inflammatory activity by inhibiting NO, NF-κβ, p38 MAPK, IL-1β, TNF-α, suppressed leukocyte cell migration, reduced of edema and Chromolaena odorata also was shown analgesic activity through significantly reduced stomach writhing and reduction pain sensation in rats. This review explains the potential importance of Chromolaena odorata as a natural anti-inflammatory and analgesic.


2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Shi Hyoung Kim ◽  
Jae Gwang Park ◽  
Jongsung Lee ◽  
Woo Seok Yang ◽  
Gye Won Park ◽  
...  

Even though a lot of reports have suggested the anti-inflammatory activity of kaempferol (KF) in macrophages, little is known about its exact anti-inflammatory mode of action and its immunopharmacological target molecules. In this study, we explored anti-inflammatory activity of KF in LPS-treated macrophages. In particular, molecular targets for KF action were identified by using biochemical and molecular biological analyses. KF suppressed the release of nitric oxide (NO) and prostaglandin E2(PGE2), downregulated the cellular adhesion of U937 cells to fibronectin (FN), neutralized the generation of radicals, and diminished mRNA expression levels of inflammatory genes encoding inducible NO synthase (iNOS), TNF-α, and cyclooxygenase- (COX-) 2 in lipopolysaccharide- (LPS-) and sodium nitroprusside- (SNP-) treated RAW264.7 cells and peritoneal macrophages. KF reduced NF-κB (p65 and p50) and AP-1 (c-Jun and c-Fos) levels in the nucleus and their transcriptional activity. Interestingly, it was found that Src, Syk, IRAK1, and IRAK4 responsible for NF-κB and AP-1 activation were identified as the direct molecular targets of KF by kinase enzyme assays and by measuring their phosphorylation patterns. KF was revealed to havein vitroandin vivoanti-inflammatory activity by the direct suppression of Src, Syk, IRAK1, and IRAK4, involved in the activation of NF-κB and AP-1.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Wei Gong ◽  
Yingru Zheng ◽  
Fan Chao ◽  
Yuan Li ◽  
Zhizhen Xu ◽  
...  

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence(Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box.


Author(s):  
Mohammad Mustakim Billah ◽  
Abir Huzaifa ◽  
M. Abdul Kader Khan ◽  
Nusrat Jahan Vabna ◽  
Kashfia Nawrin ◽  
...  

Background: Crotalaria verrucosa is a traditional plant frequently prescribed by the tribes for its medicinal value against inflammation. The present study was designed to investigate the scientific basis for medicinal value in inflammation by in vivo and in vitro analysis.Methods: Anti-inflammatory activity of the plant’s leaf was evaluated by two in vivo methods - carrageenan induced rat paw edema and xylene induced mice ear edema. Moreover, in vitro analysis was performed through heat induced hemolysis and heat induced protein denaturation methods.Results: The inflammation produced by carrageenan and xylene were effectively suppressed by the aqueous leaf extract of C. verrucosa (CVAQ) at 600 mg/kg body weight which was comparable to the standards. In heat induced hemolysis test the extract was able to inhibit the lysis up to 70% at 500 µg/ml whereas in heat induced protein denaturation test it reduces the percentage till 69% at the same concentration.Conclusions: The findings suggested that CVAQ possess moderate to high anti-inflammatory activity when applied in low to high concentrated doses. However, the study can only conclude from this basic evaluation that the extract needs to be further investigated for identifying the potential compound which contributed to such medicinal value of the plant.


2021 ◽  
Author(s):  
Ravindra Jagannath Waghole ◽  
Ashwini Vivek Misar ◽  
Neha Shashikant Kulkarni ◽  
Feroz Khan ◽  
Dattatraya Gopal Naik ◽  
...  

Abstract The severity and perseverance of the inflammation have been demonstrated in many health conditions. The limitations of existing medications, propose the need for newer alternative anti-inflammatory medications. In our earlier studies, we demonstrated the topical anti-inflammatory potential of crude ethanolic extract of Tetrastigma sulcatum leaves and its fractions. In the present study, we further explored anti-inflammatory activity of T. sulcatum extract, fractions, pure compound and its derivatives using in vitro and in vivo bioassay techniques. We attempted to isolate a pure compound from leaf extract and was identified as Friedelan-3β-ol (CI) and its derivatives Friedelinol acetate (C II) and Friedelinol methyl ether (C III) were synthesized. Treatment with crude extract and its fractions demonstrated a significant reduction in the mRNA expression levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and nitric oxide (NO) production in LPS-stimulated inflammation in RAW 264.7 cells. Likewise, compounds CI, CII and CIII showed a similar pattern of significant inhibition of proinflammatory cytokines and NO production. In vivo study in Carrageenan induced paw-inflammatory mice model demonstrated reduced paw oedema and proinflammatory cytokines levels in a dose-dependent manner upon treatment of extract, its fractions, pure compound (CI), and their derivatives (CII and CIII.). The docking study showed all the compounds (CI, CII and CIII) share common residues with Dexamethasone. TNF- α exhibited the most interacting residues with the compounds. The present study confirmed the T. sulcatum ’s anti-inflammatory activity, suggesting Friedelan-3β-ol as an active component in a crude extract.


Author(s):  
Vineela Satuluri ◽  
Vidyadhara Suryadevara ◽  
Vijetha Pendyala ◽  
Narasimhareddy M.

Thrombotic disorders like myocardial and cerebral infarction are fatal blood clotting related diseases. Synthetic therapeutics used in such disorders has serious adverse effects, so there is a need to investigate some more safe natural thrombolytic agents. Present study is a preliminary work towards such endeavors. During this study analysis of thrombolytic activity and anti-inflammatory activity of Thespesia populnea leaf extract using a simple and quick in vitro clot lysis assay was performed. Various concentrations of leaf extract i.e. 200μg/ml; 400μg/ml and 600μg/ml were tested at various time intervals including; 24, 48 and 72 hours duration of incubation at 37°C for observing maximum clot lysis. The result findings indicated that concentrations of leaf extract enhanced the percentage of clot lysis in dose dependent manner along with the incubation time factor. However; streptokinase SK a reference standard and water were used as a positive and negative control showed clot lysis maximum 96.35% and 35.22% in 72 hours of incubation respectively. Alcohol extract of whole plant of Thespesia populnea (Family: Malvaceae) was assessed for its anti-inflammatory activity by in vitro methods. In vitro anti-inflammatory activity was evaluated using albumin denaturation assay at different concentrations. Diclofenac sodium was used as standard drug. The results showed that Thespesia populnea alcohol extract at a concentration range of 400-1600μl significantly protects from protein denaturation.


2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Han Gyung Kim ◽  
Subin Choi ◽  
Jongsung Lee ◽  
Yo Han Hong ◽  
Deok Jeong ◽  
...  

Celtis choseniana is the traditional plant used at Korea as a herbal medicine to ameliorate inflammatory responses. Although Celtis choseniana has been traditionally used as a herbal medicine at Korea, no systemic research has been conducted on its anti-inflammatory activity. Therefore, the present study explored an anti-inflammatory effect and its underlying molecular mechanism using Celtis choseniana methanol extract (Cc-ME) in macrophage-mediated inflammatory responses. In vitro anti-inflammatory activity of Cc-ME was evaluated using RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS), pam3CSK4 (Pam3), or poly(I:C). In vivo anti-inflammatory activity of Cc-ME was investigated using acute inflammatory disease mouse models, such as LPS-induced peritonitis and HCl/EtOH-induced gastritis. The molecular mechanism of Cc-ME-mediated anti-inflammatory activity was examined by Western blot analysis and immunoprecipitation using whole cell and nuclear fraction prepared from the LPS-stimulated RAW264.7 cells and HEK293 cells. Cc-ME inhibited NO production and mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and tumor necrosis factor-alpha (TNF-α) in the RAW264.7 cells and peritoneal macrophages induced by LPS, pam3, or poly(I:C) without cytotoxicity. High-performance liquid chromatography (HPLC) analysis showed that Cc-ME contained anti-inflammatory flavonoids quercetin, luteolin, and kaempferol. Among those, the content of luteolin, which showed an inhibitory effect on NO production, was highest. Cc-ME suppressed the NF-κB signaling pathway by targeting Src and interrupting molecular interactions between Src and p85, its downstream kinase. Moreover, Cc-ME ameliorated the morphological finding of peritonitis and gastritis in the mouse disease models. Therefore, these results suggest that Cc-ME exerted in vitro and in vivo anti-inflammatory activity in LPS-stimulated macrophages and mouse models of acute inflammatory diseases. This anti-inflammatory activity of Cc-ME was dominantly mediated by targeting Src in NF-κB signaling pathway during macrophage-mediated inflammatory responses.


2020 ◽  
Vol 1 (2) ◽  
pp. 46-53
Author(s):  
Lusi Agus Setiani ◽  
Zaldi Rusli

Inflammation is the immune system's main response to infection and irritation. African leaf (Gymnanthemum amygdalinum) is one of the medicinal plants that can be used as anti-inflammatory because of the presence of flavonoid compounds. Flavonoid compounds have an anti-inflammatory effect that can regulate arachidonic acid metabo-lism by inhibiting cyclooxygenase (COX) and lipooksigenase activi-ties. This study aims to obtain scientific information and the potential of African leaf extract as an anti-inflammatory in vitro and in vivo test. In this study, in vitro and in vivo anti-inflammatory activity tests were carried out. The in vitro anti-inflammatory activity was evaluated by the ability of African leaf extracts to prevent protein denaturation and in vivo anti-inflammatory activity by observing the reduction of edema in the soles of rats induced by carrageenan by giving three lev-els of doses of African leaf extract. The results showed that the African leaf extract at a concentration of 8273.91 mg L-1 was able to inhibit 50% denatured protein (IC50), while in the in vivo test African leaf had the potential as an anti-inflammatory with the most effective percent-age of inhibition at a dose of 200 mg kg-1 which is 85.20%. African leaf have the potential of approximately 2 times greater than the positive control of diclofenac sodium which is 45.70%.


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