scholarly journals The Roles of Betulinic Acid on Circulating Concentrations of Creatine Kinase and Immunomodulation in Mice Infected With Chloroquine-Susceptible and Resistant Strains of Plasmodium Berghei

Author(s):  
Oludele John Olanlokun ◽  
Praise Oghenegare Okoro ◽  
Olufunso Olabode Olorunsogo

Abstract Complete malarial therapy depends largely on the immunological and inflammatory response of the host to the invading potentials of malarial parasite. In this study, we evaluated the roles of betulinic acid on immunological response, anti-inflammatory potentials and concentrations of creatine kinase in mice infected with chloroquine susceptible (NK 65) and resistant (ANKA) strains of Plasmodium berghei. Serum Interlukins 1β and 6 (IL-1 β, IL-6), tumour necrosis factor alpha (TNFα), immunoglobulins G and M (IgG and IgM), C-reactive protein (CRP) and creatine kinas (CK). Furthermore, liver marker enzymes; aspartate, alanine aminotransferases (AST and ALT, respectively) and gamma glutammyl transferase (GGT) were determined. The results showed that betulinic acid dose dependently decreased IL-1 β, IL-6, TNFα and CRP relative to the infected control. The IgG and IgM levels significantly increased in both models while CK decreased insignificantly in both models. Serum AST, ALT and GGT significantly decreased compared to the infected control. These results showed that betulinic acid has anti-inflammatory, immunomodulatory and mitigating effects on malarial infection in mice. Furthermore, the down-regulatory effect of betulinic acid on CK is indicative of decrease in muscle injury which is a major pathological concern in malarial infection and treatment.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Soo-Min Ha ◽  
Ji-Hyeon Kim ◽  
Jong-Won Kim ◽  
Do-Yeon Kim ◽  
Min-Seong Ha

Korean mistletoe has anti-inflammatory and antioxidant functions and may be a useful training supplement. We investigated the effect of Korean mistletoe extract (KME) on inflammatory markers after high-intensity exercise by 20 university male rowers (KME group vs. CON group) consuming 110 mL KME/dose (2 times a day over 8 weeks). Blood samples were collected for measurement of serum cytokine levels at baseline, immediately after exercise, and following 30 minutes of recovery. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were used as markers for inflammation. After supplementation, IL-6 and TNF-α levels were significantly lowered in the KME group than in the CON group at baseline, immediately after exercise, and following 30 minutes of recovery. KME can reduce high-strength exercise-induced increases in the levels of serum inflammatory cytokines in active individuals and improve anti-inflammatory functions.


2021 ◽  
Vol 22 (14) ◽  
pp. 7482
Author(s):  
Hwan Lee ◽  
Zhiming Liu ◽  
Chi-Su Yoon ◽  
Linsha Dong ◽  
Wonmin Ko ◽  
...  

Aging is associated with immune disregulation and oxidative stress which lead to inflammation and neurodegenerative diseases. We have tried to identify the anti-neuroinflammatory and anti-inflammatory components of Coreopsis lanceolata L. The dried flowers of C. lanceolata were extracted with 70% EtOH, and the obtained extract was divided into CH2Cl2, EtOAc, n-BuOH, and H2O fractions. The CH2Cl2 fraction was separated using silica gel and C-18 column chromatography to yield phenylheptatriyne (1), 2′-hydroxy-3,4,4′-trimethoxychalcone (2), and 4′,7-dimethoxyflavanone (3). Additionally, the EtOAc fraction was subjected to silica gel, C-18, and Sephadex LH-20 column chromatography to yield 8-methoxybutin (4) and leptosidin (5). All the compounds isolated from C. lanceolata inhibited the production of nitric oxide (NO) in LPS-induced BV2 and RAW264.7 cells. In addition, phenylheptatriyne and 4′,7-dimethoxyflavanone reduced the secretion of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6. Among them, phenylheptatriyne was significantly downregulated in the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequently, phenylheptatriyne also effectively inhibited nuclear factor-kappa B (NF-κB) activation in LPS-stimulated BV2 and RAW264.7 cells. Based on these results, the anti-neuroinflammatory effect of phenylheptatriyne isolated from C. lanceolata was confirmed, which may exert a therapeutic effect in treatment of neuroinflammation-related diseases.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 956
Author(s):  
Yonelian Yuyun ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Wiwat Supasena ◽  
Piyapan Suwattananuruk ◽  
Kemika Praengam ◽  
...  

Curcumin (CUR) has been used as adjuvant therapy for therapeutic application in the treatment of psoriasis through several mechanisms of action. Due to the poor oral bioavailability of CUR, several approaches have been developed to overcome the limitations of CUR, including the prodrug strategy. In this study, CUR was esterified with mycophenolic acid (MPA) as a novel conjugate prodrug. The MPA-CUR conjugate was structurally elucidated using FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Bioavailable fractions (BFs) across Caco-2 cells of CUR, MPA, and MPA-CUR were collected for further biological activity evaluation representing an in vitro cellular transport model for oral administration. The antipsoriatic effect of the BFs was determined using antiproliferation and anti-inflammation assays against hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced human keratinocytes (HaCaT). The BF of MPA-CUR provided better antiproliferation than that of CUR (p < 0.001). The enhanced hyperproliferation suppression of the BF of MPA-CUR resulted from the reduction of several inflammatory cytokines, including IL-6, IL-8, and IL-1β. The molecular mechanisms of anti-inflammatory activity were mediated by an attenuated signaling cascade of MAPKs protein, i.e., p38, ERK, and JNK. Our results present evidence for the MPA-CUR conjugate as a promising therapeutic agent for treating psoriasis by antiproliferative and anti-inflammatory actions.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 143 ◽  
Author(s):  
Jingnan Zhao

Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 was released from AuNCs, intracellularly when HA was hydrolyzed by hyaluronidase. HA-AuNCs/T/P show a much higher intracellular uptake than AuNCs/T/P, and exhibit a much higher efficacy on the suppression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) than free TPCA-1, suggesting great improvement to the anti-inflammatory efficacy of TPCA-1 through the application of AuNCs. HA-AuNCs/T/P can also reduce the production of reactive oxygen species in inflammatory cells. This study suggests that HA-AuNCs/T/P may be potential agents for anti-inflammatory treatment, and are worthy of further investigation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Jayasingha Arachchige Chathuranga C Jayasingha ◽  
Yung Hyun Choi ◽  
Rajapaksha Gedara Prasad Tharanga Jayasooriya ◽  
Chang-Hee Kang ◽  
...  

AbstractFisetin is a naturally occurring flavonoid that possesses several pharmacological benefits including anti-inflammatory activity. However, its precise anti-inflammatory mechanism is not clear. In the present study, we found that fisetin significantly inhibited the expression of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Additionally, fisetin attenuated LPS-induced mortality and abnormalities in zebrafish larvae and normalized the heart rate. Fisetin decreased the recruitment of macrophages and neutrophils to the LPS-microinjected inflammatory site in zebrafish larvae, concomitant with a significant downregulation of proinflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase-2a (COX-2a), IL-6, and TNF-α. Fisetin inhibited the nuclear localization of nuclear factor-kappa B (NF-κB), which reduced the expression of pro-inflammatory genes. Further, fisetin inactivated glycogen synthase kinase 3β (GSK-3β) via phosphorylation at Ser9, and inhibited the degradation of β-catenin, which consequently promoted the localization of β-catenin into the nucleus. The pharmacological inhibition of β-catenin with FH535 reversed the fisetin-induced anti-inflammatory activity and restored NF-κB activity, which indicated that fisetin-mediated activation of β-catenin results in the inhibition of LPS-induced NF-κB activity. In LPS-microinjected zebrafish larvae, FH535 promoted the migration of macrophages to the yolk sac and decreased resident neutrophil counts in the posterior blood island and induced high expression of iNOS and COX-2a, which was accompanied by the inhibition of fisetin-induced anti-inflammatory activity. Altogether, the current study confirmed that the dietary flavonoid, fisetin, inhibited LPS-induced inflammation and endotoxic shock through crosstalk between GSK-3β/β-catenin and the NF-κB signaling pathways.


2011 ◽  
Vol 39 (05) ◽  
pp. 943-956 ◽  
Author(s):  
Jen-Chieh Tsai ◽  
Wen-Huang Peng ◽  
Tai-Hui Chiu ◽  
Shang-Chih Lai ◽  
Chao-Ying Lee

The aims of this study intended to investigate the anti-inflammatory activity of the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) in the edema paw tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. The betulinic acid content in SDE was detected by high performance liquid chromatography (HPLC). In the anti-inflammatory model, the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40 mg/kg) reduced the paw edema at 3, 4 and 5 h after λ-carrageenan administration. Moreover, SDE and betulinic acid affected the levels of COX-2, NO, TNF-α and IL1-β in the λ-carrageenan-induced edema paws. The activities of SOD, GPx and GRd in the liver tissue were increased and the MDA levels in the edema paws were decreased. It is suggested that SDE and betulinic acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms appear to be related to the reduction of the levels of COX-2, NO, TNF-α and IL1-β in inflamed tissues, as well as the inhibition of MDA level via increasing the activities of SOD, GPx and GRd. The analytical result showed that the content of betulinic acid in SDE was 6.25 mg/g extract.


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 967
Author(s):  
Micaely Cristina dos Santos Tenório ◽  
Nayara Gomes Graciliano ◽  
Fabiana Andréa Moura ◽  
Alane Cabral Menezes de Oliveira ◽  
Marília Oliveira Fonseca Goulart

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.


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