scholarly journals Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinhe Li ◽  
Yinshuang Ye ◽  
Wenwen Zhou ◽  
Qilin Shi ◽  
Lin Wang ◽  
...  

Arthritis is the most common cause to lead to chronic pain. Botulinum toxin type A (BoNT/A) has been widely used to treat chronic pain. In our previous study, we confirmed the anti-inflammatory and antinociceptive effects of BoNT/A in the Complete Freund’s Adjuvant (CFA)-induced arthritis model, but the underlying anti-inflammatory mechanism was not fully elucidated. The purpose of this study was to investigate the anti-inflammatory effects and mechanisms of BoNT/A on arthritis using transcriptomic analysis. The BoNT/A was injected into the rat ankle joint on day 21 after CFA injection. The von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. Five days after BoNT/A treatment, gene expression profiling in dorsal root ganglion (DRG) was performed using RNA sequencing (RNA-seq). The differentially expressed genes (DEGs) were analyzed by various tools. The mechanical allodynia and thermal hyperalgesia were significantly reversed after BoNT/A injection. RNA-seq revealed 97 DEGs between the CFA group and Sham group; these DEGs were enriched inflammatory response, IL-17 signaling pathway, etc. There are 71 DEGs between the CFA+BoNT/A group and the CFA group; these DEGs related to response to peptide, PI3K-Akt signaling pathway, ECM–receptor interactions, etc. Three key genes were significantly decreased after CFA-induced arthritis pain, while BoNT/A increased the expression of these genes. The identification of S100A9, S100A8, and MMP8 genes can provide new therapeutic targets for arthritis pain and affect the signaling pathway to play an anti-inflammatory role after the treatment of BoNT/A.

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Srinivasa Reddy Jitta ◽  
Prasanthi Daram ◽  
Karthik Gourishetti ◽  
C. S. Misra ◽  
Picheswara Rao Polu ◽  
...  

Terminalia tomentosa bark belongs to the family Combretaceae. The plant bark is astringent and useful in the treatment of ulcers, vata, fractures, hemorrhages, bronchitis, and diarrhea. Phytochemical investigation of T. tomentosa bark confirms the presence of flavonoids, polyphenols, and tannins. The plant has not been investigated for its anti-inflammatory and antiarthritic activity. The present study was undertaken to explore its possible anti-inflammatory and antiarthritic activity. Anti-inflammatory activity of alcoholic and aqueous extracts of the bark was assessed by in vivo methods. In vivo antiarthritic potential of the extracts was evaluated by Complete Freund’s Adjuvant (CFA) induced arthritis in Wistar rats. Our findings showed that the alcoholic and aqueous extracts exhibited anti-inflammatory activity at 500 mg/kg oral dose in carrageenan-induced hind paw edema and carrageenan-induced air pouch inflammation models. We also found alcoholic as well as aqueous extracts of the bark restored the altered blood and serum parameters caused by the Complete Freund’s Adjuvant-induced arthritis in Wistar rats. This study shows that the T. tomentosa bark extracts possess anti-inflammatory activity and have pronounced effects on adjuvant arthritis also. Future studies are necessary to provide deeper insight into the exact mechanism of the action of anti-inflammatory and antiarthritic activity of T. tomentosa.


2017 ◽  
Vol 127 (1) ◽  
pp. 147-163 ◽  
Author(s):  
Zhiqiang Pan ◽  
Zhou-Ya Xue ◽  
Guo-Fang Li ◽  
Meng-Lan Sun ◽  
Ming Zhang ◽  
...  

Abstract Background Ten-eleven translocation methylcytosine dioxygenase converts 5-methylcytosine in DNA to 5-hydroxymethylcytosine, which plays an important role in gene transcription. Although 5-hydroxymethylcytosine is enriched in mammalian neurons, its regulatory function in nociceptive information processing is unknown. Methods The global levels of 5-hydroxymethylcytosine and ten-eleven translocation methylcytosine dioxygenase were measured in spinal cords in mice treated with complete Freund’s adjuvant. Immunoblotting, immunohistochemistry, and behavioral tests were used to explore the downstream ten-eleven translocation methylcytosine dioxygenase-dependent signaling pathway. Results Complete Freund’s adjuvant-induced nociception increased the mean levels (± SD) of spinal 5-hydroxymethylcytosine (178 ± 34 vs. 100 ± 21; P = 0.0019), ten-eleven translocation methylcytosine dioxygenase-1 (0.52 ± 0.11 vs. 0.36 ± 0.064; P = 0.0088), and ten-eleven translocation methylcytosine dioxygenase-3 (0.61 ± 0.13 vs. 0.39 ± 0.08; P = 0.0083) compared with levels in control mice (n = 6/group). The knockdown of ten-eleven translocation methylcytosine dioxygenase-1 or ten-eleven translocation methylcytosine dioxygenase-3 alleviated thermal hyperalgesia and mechanical allodynia, whereas overexpression cytosinethem in naïve mice (n = 6/group). Down-regulation of spinal ten-eleven translocation methylcytosine dioxygenase-1 and ten-eleven translocation methylcytosine dioxygenase-3 also reversed the increases in Fos expression (123 ± 26 vs. 294 ± 6; P = 0.0031; and 140 ± 21 vs. 294 ± 60; P = 0.0043, respectively; n = 6/group), 5-hydroxymethylcytosine levels in the Stat3 promoter (75 ± 16.1 vs. 156 ± 28.9; P = 0.0043; and 91 ± 19.1 vs. 156 ± 28.9; P = 0.0066, respectively; n = 5/group), and consequent Stat3 expression (93 ± 19.6 vs. 137 ± 27.5; P = 0.035; and 72 ± 15.2 vs. 137 ± 27.5; P = 0.0028, respectively; n = 5/group) in complete Freund’s adjuvant-treated mice. Conclusions This study reveals a novel epigenetic mechanism for ten-eleven translocation methylcytosine dioxygenase-1 and ten-eleven translocation methylcytosine dioxygenase-3 in the modulation of spinal nociceptive information via targeting of Stat3.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yuwen Tang ◽  
Zhiyou Peng ◽  
Shoujun Tao ◽  
Jianliang Sun ◽  
Wenyuan Wang ◽  
...  

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, it remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in inflammatory pain mediated by Cdk5 in the inflammatory pain model induced by complete Freund’s adjuvant (CFA). Our results showed that the coexpression of Cdk5/VGLUT2 in small- and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.


1995 ◽  
Vol 23 (03n04) ◽  
pp. 273-278 ◽  
Author(s):  
Hwa-Woei Chih ◽  
Chun-Ching Lin ◽  
Kung-Sheng Tang

"Ham-Hong-Chho" is a folk medicine in Taiwan, derived from the entire plants of Bidens pilosa L. var. minor (Blume) Sherff (Compositae), B. pilosa L. and B. chilensis DC. The anti-inflammatory effect of aqueous extracts of the three plants against paw edema induced by carrageenan and chronic arthritis induced by complete Freund's adjuvant were determined in rats. The results indicated that paw edema induced by carrageenan was significantly decreased by treatment with aqueous extracts (150 or 300 mg/kg) of all three plants ( p < 0.05) and that the effect of Bidens pilosa var. minor was the most potent. However, only extracts (500 mg/kg) of B. pilosa L. var. minor and B.pilosa L. significantly decreased the paw edema induced by complete Freund's adjuvant ( p < 0.05).


2017 ◽  
Vol 3 (2) ◽  
pp. 191-198
Author(s):  
Reza Setiawan Sudirman ◽  
Usmar Usmar ◽  
Abdul Rahim ◽  
Muh. Akbar Bahar

A research about anti-inflammatory effect of Beluntas leaves extract on CFA (Complete Freund’s Adjuvant) induced inflammatory model has been conducted. The objective of this research was to determine the effect of Beluntas leaves extract in alleviating CFA-induced paw edema in mice (Mus musculus). The number of mice used was 15 and was divided into 5 groups. Group I was treated with NaCMC. Group II, III, and IV were given suspension of Beluntas leaves extract 100 mg/Kg, 300 mg/Kg, and 500 mg/Kg BW, respectively. Group V was a positive control treated with suspension of diclofenac sodium 0.1 ml/10 g orally. The determination of anti-inflammatory potency was based on the average time needed to ameliorate the edema volume. The shortest  time period of edema reduction was produced by diclofenac sodium (within 9.33 days), then followed by Beluntas leaves extract with the concentration of 300 mg/Kg (within 12 days), 500 mg/Kg (within 14.33 days), and 100 mg/Kg (within 17.67 days), consecutively. These results are significantly different compared to negative control group which did not reduce the edema volume during 18 days of observation. In conclusion, ethanol extract of Beluntas leaves has an effective anti-inflamatory effect.


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