scholarly journals Si Miao San Attenuates Inflammation and Oxidative Stress in Rats with CIA via the Modulation of the Nrf2/ARE/PTEN Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Pan Shen ◽  
Yao Huang ◽  
Xin Ba ◽  
Weiji Lin ◽  
Kai Qin ◽  
...  

Objective. Si Miao San (SMS) is a traditional Chinese formula used in China to treat rheumatic diseases. To date, its mechanism in rheumatoid arthritis (RA) treatment is uncertain. Our study aims to assess the antiarthritic effects of SMS in experimental arthritic rats. Materials and Methods. SMS (8.63, 4.31, and 2.16 g/kg/day) was orally administered after the first immunization from day 14 to day 53. The effects of SMS on rats with collagen-induced arthritis (CIA) were evaluated by arthritis score and histological assessment. The levels of cytokines and anti-CII antibodies in rat serum were measured by ELISAs. The expression of oxidative stress parameters was detected by biochemical assay kits. The levels of Nrf2, HO-1, NQO1, and PTEN were determined by western blotting. Results. Medium- and high-dose SMS treatment significantly decreased arthritis scores and alleviated ankle joint histopathology in the rats with CIA. It inhibited the production of IL-6, TNF-α, COX-2, and PGE2 in rat serum. SMS also suppressed the expression of anti-CII antibodies IgG1 and IgG2a. Moreover, SMS significantly suppressed the levels of MDA and MPO in the synovial tissues while increasing the levels of SOD and CAT in the rats with CIA. The levels of Nrf2, HO-1, NQO1, and PTEN were upregulated by SMS in rat synovial tissues. Conclusions. This study demonstrated that SMS effectively alleviated the disease progression of CIA by decreasing the levels of proinflammatory cytokines and reducing oxidative stress damage, as indicated by IL-6, TNF-α, COX-2, and PGE2 levels; inhibiting the overproduction of MDA and MPO; and enhancing antioxidant enzymes by upregulating the Nrf2/ARE/PTEN signalling pathway.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noha H. Habashy ◽  
Ahmad S. Kodous ◽  
Marwa M. Abu-Serie

AbstractCarbon tetrachloride (CCl4) is an abundant environmental pollutant that can generate free radicals and induce oxidative stress in different human and animal organs like the kidney, lung, brain, and spleen, causing toxicity. The present study evaluated the alleviative mechanism of the isolated polyphenolic fraction from seedless (pulp and skin) black Vitis vinifera (VVPF) on systemic oxidative and necroinflammatory stress in CCl4-intoxicated rats. Here, we found that the administration of VVPF to CCl4-intoxicated rats for ten days was obviously ameliorated the CCl4-induced systemic elevation in ROS, NO and TBARS levels, as well as MPO activity. Also, it upregulated the cellular activities of the enzymatic (SOD, and GPx) and non-enzymatic (TAC and GSH) antioxidants. Furthermore, the gene expression of the ROS-related necroinflammatory mediators (NF-κB, iNOS, COX-2, and TNF-α) in the kidney, brain, and spleen, as well as IL-1β, and IL-8 in the lung were greatly restored. The histopathological studies confirmed these biochemical results and showed a noticeable enhancing effect in the architecture of the studied organs after VVPF intake. Thus, this study indicated that VVPF had an alleviative effect on CCl4-induced necroinflammation and oxidative stress in rat kidney, lung, brain, and spleen via controlling the ROS/NF-κB pathway.


2020 ◽  
Vol 19 (7) ◽  
pp. 1429-1433
Author(s):  
Jihong Shu ◽  
Zhenjiao Fang ◽  
Xinjun Xiong

Purpose: To investigate the effect of penehyclidine hydrochloride (PHC) on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α), and oxidative stress levels in lung tissues of acute lung injury (ALI) neonatal rats.Methods: 40 male Sprague-Dawley (SD) rats were assigned to model, low-dose PHC, high-dose PHC, and control groups (n = 10). Levels of IL-6, TNF-α and HIF-1α were evaluated by enzyme-linked immunosorbent assay (ELISA). Pulmonary lesions were determined histologically using H&E staining.Results: The lung tissue levels of IL-6, TNF-α and HIF-1α were significantly higher in model rats than in control rats, and significantly lower in PHC-treated rats than in model group, with decrease in levels as PHC dose increased (p < 0.05). The lung tissue activity of MPO and level of MDA in model rats were significantly higher than those in control rats, but significantly lower in the lung tissues of the two PHC groups than in the model group; decrease in levels occurred as PHC dose increased (p < 0.05).Conclusion: PHC decreases the lung and serum levels of IL-6, TNF-α and HIF-1α in a rat model of ALI, and mitigates pulmonary oxidative stress and lung tissue damage. Thus, penehyclidine hydrochloride may be useful to mitigate ALI-induced damage in patients. However, further studies and clinical trials are required to ascertain this Keywords: Penehyclidine hydrochloride, Alveolar septum, Acute lung injury, Inflammatory cells, IL-6, TNF-α, HIF-1α, Oxidative stress


Author(s):  
Rukiye Nalan Tiftik ◽  
Meryem Temiz-Reşitoğlu ◽  
Demet Sinem Güden ◽  
Gülsen Bayrak ◽  
İsmail Ün ◽  
...  

It has been clearly indicated that osteoarthritis (OA) is an inflammatory and degenerative disease that could be promoted by Rho-kinase (ROCK); however, little is known about the role of ROCK/inhibitor κB alpha (IκB-α)/nuclear factor-κB (NF-κB) p65 pathway activation in interleukin-1β (IL-1β) induced inflammatory response and oxidative stress in primary human chondrocytes. To test this hypothesis, we focused on determining ROCK-II, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), p22phox, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subtype 4 (NOX4) protein expression, ROCK-II activity, NADPH oxidase levels, and total antioxidant capacity (TAC) in the presence and absence of ROCK-inhibitor fasudil. IL-1β (2 ng·mL–1, 24 h) increased the expression of ROCK-II, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, TNF-α, COX-2, and p22phox proteins, and decreased the expression of IκB-α, and the NOX4 protein level did not alter. ROCK activity and NADPH oxidase levels were increased, whereas the TAC was decreased by IL-1β. Fasudil (10−5–10−7 M) reversed all these changes induced by IL-1β. These results demonstrate that ROCK/IκB-α/NF-κB p65 pathway activation contributes to the IL-1β-induced inflammatory response and oxidative stress, and thus, ROCK inhibition might be a beneficial treatment option for OA patients mainly based on its anti-inflammatory and antioxidant effects.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4492
Author(s):  
Azim Ullah Shamsul Islam ◽  
Björn Hellman ◽  
Fred Nyberg ◽  
Naheed Amir ◽  
Richard L. Jayaraj ◽  
...  

Physiological Glucocorticoids are important regulators of the immune system. Pharmacological GCs are in widespread use to treat inflammatory diseases. Adrenalectomy (ADX) has been shown to exacerbate renal injury through inflammation and oxidative stress that results in renal impairment due to depletion of GCs. In this study, the effect of myrcene to attenuate renal inflammation and oxidative stress was evaluated in the adrenalectomized rat model. Rats were adrenalectomized bilaterally or the adrenals were not removed after surgery (sham). Myrcene (50 mg/kg body weight, orally) was administered post ADX. Myrcene treatment resulted in significant downregulation of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) compared to untreated ADX rats. In addition, myrcene resulted in significant downregulation of immunomodulatory factors (IFNγ and NF-κB) and anti-inflammatory markers (IL-4 and IL-10) in treated ADX compared to untreated ADX. Myrcene significantly increased the antioxidant molecules (CAT, GSH, and SOD) and decreased MDA levels in treated ADX compared to untreated. Moreover, myrcene treatment reduced the expression of COX-2, iNOS, KIM-1, and kidney functional molecules (UREA, LDH, total protein, and creatinine) in ADX treated compared to ADX untreated. These results suggest that myrcene could be further developed as a therapeutic drug for treatment of kidney inflammation and injury.


2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.


2016 ◽  
Vol 32 (2) ◽  
pp. 519-528 ◽  
Author(s):  
Lara M. Gomes ◽  
Milena Carvalho-Silva ◽  
Letícia J. Teixeira ◽  
Joyce Rebelo ◽  
Isabella T. Mota ◽  
...  

2021 ◽  
Vol 406 ◽  
pp. 113226
Author(s):  
Talita Tuon ◽  
Sandra S. Meirelles ◽  
Airam B. de Moura ◽  
Thayse Rosa ◽  
Laura A. Borba ◽  
...  

Author(s):  
Basiru Olaitan Ajiboye ◽  
Babatunji Emmanuel Oyinloye ◽  
Jennifer Chidera Awurum ◽  
Sunday Amos Onikanni ◽  
Adedotun Adefolalu ◽  
...  

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.


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