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Tanshinone IIA Downregulates HMGB1 and TLR4 Expression in a Spinal Nerve Ligation Model of Neuropathic Pain.

Ma YQ, Chen YR, Leng YF, Wu ZW - Evid Based Complement Alternat Med (2014)

Bottom Line: Both the mechanical and heat pain thresholds were significantly decreased.After Tan IIA treatment, HMGB1, and TLR4 mRNA and protein levels, the expression of TNF-α and IF-1β was reduced significantly.These results indicate that Tanshinone IIA inhibited SNL-induced neuropathic pain via multiple effects, and targeting the HMGB1-TLR4 pathway could serve as the basis of new antinociceptive agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu 730000, China.

ABSTRACT
Fifty-four Sprague-Dawley rats weighing 200~240 g were randomly divided into sham-operated group (sham group), vehicle-treated SNL group (model group), and Tan IIA-treated SNL group (Tan IIA group). Tan IIA was administered intraperitoneally to rats in the Tan IIA-treated group at a dose of 30 mg/kg daily for 14 days after SNL surgery. Paw withdrawal mechanical thresholds (PWTs) and paw withdrawal thermal latencies (PWLs) were measured. High-mobility group box 1 (HMGB1) and Toll-like Receptor 4 (TLR4) mRNA and protein expression in the spinal cord were measured. Tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-10 (IL-10) in the spinal cord were measured, too. Both the mechanical and heat pain thresholds were significantly decreased. After Tan IIA treatment, HMGB1, and TLR4 mRNA and protein levels, the expression of TNF-α and IF-1β was reduced significantly. In conclusion, Tanshinone IIA reversed SNL-induced thermal hyperalgesia and mechanical allodynia and downregulated HMGB1 and TLR4 levels and inhibited the HMGB1-TLR4 pathway. Tanshinone IIA inhibited TNF-α and IL-1β expression but not IF-10 expression in the spinal cords of SNL rats. These results indicate that Tanshinone IIA inhibited SNL-induced neuropathic pain via multiple effects, and targeting the HMGB1-TLR4 pathway could serve as the basis of new antinociceptive agents.

No MeSH data available.


Related in: MedlinePlus

The expression of TNF-α, IF-1β, and IF-10 in spinal cords of SNL rats on the different postoperative days. (a) TNF-α was upregulated in the spinal cord of SNL rats (aP < 0.05 versus sham group). After Tan IIA treatment, TNF-α expression reduced significantly (bP < 0.05 versus model group). (b) IF-1β was upregulated in the spinal cord of SNL rats (aP <0.05 versus sham group). After Tan IIA treatment, TNF-α expression reduced significantly (bP < 0.05 versus model group). (c) IF-10 was downregulated in the spinal cord of SNL rats (aP < 0.05 versus sham group). After Tan IIA treatment, TNF-α expression increased significantly (bP < 0.05 versus model group). Data are shown as the mean ± S.D. SNL: spinal nerve ligation. TNF-α: tumor necrosis factor alpha. IF-1β: interleukin-1 beta. IF-10: interleukin-10. S.D standard deviation.
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fig4: The expression of TNF-α, IF-1β, and IF-10 in spinal cords of SNL rats on the different postoperative days. (a) TNF-α was upregulated in the spinal cord of SNL rats (aP < 0.05 versus sham group). After Tan IIA treatment, TNF-α expression reduced significantly (bP < 0.05 versus model group). (b) IF-1β was upregulated in the spinal cord of SNL rats (aP <0.05 versus sham group). After Tan IIA treatment, TNF-α expression reduced significantly (bP < 0.05 versus model group). (c) IF-10 was downregulated in the spinal cord of SNL rats (aP < 0.05 versus sham group). After Tan IIA treatment, TNF-α expression increased significantly (bP < 0.05 versus model group). Data are shown as the mean ± S.D. SNL: spinal nerve ligation. TNF-α: tumor necrosis factor alpha. IF-1β: interleukin-1 beta. IF-10: interleukin-10. S.D standard deviation.

Mentions: SNL significantly increased TNF-α and IL-1β expression at 3, 7, and 14 days after SNL (P < 0.05, compared with sham group). In addition, there was significant downregulation of TNF-α and IL-1β in the Tan IIA administration group that was subjected to SNL (P < 0.05, compared with SNL). TNF-α and IL-1β were upregulated, whereas IL-10 was downregulated in the spinal cord of the SNL rats. IL-10 increased after Tan IIA administration (P < 0.05). The results indicated that intraperitoneal Tan IIA significantly attenuated IL-1β and TNF-α expression and enhanced IL-10 expression in the spinal cord of SNL rats (Figure 4).


Tanshinone IIA Downregulates HMGB1 and TLR4 Expression in a Spinal Nerve Ligation Model of Neuropathic Pain.

Ma YQ, Chen YR, Leng YF, Wu ZW - Evid Based Complement Alternat Med (2014)

The expression of TNF-α, IF-1β, and IF-10 in spinal cords of SNL rats on the different postoperative days. (a) TNF-α was upregulated in the spinal cord of SNL rats (aP < 0.05 versus sham group). After Tan IIA treatment, TNF-α expression reduced significantly (bP < 0.05 versus model group). (b) IF-1β was upregulated in the spinal cord of SNL rats (aP <0.05 versus sham group). After Tan IIA treatment, TNF-α expression reduced significantly (bP < 0.05 versus model group). (c) IF-10 was downregulated in the spinal cord of SNL rats (aP < 0.05 versus sham group). After Tan IIA treatment, TNF-α expression increased significantly (bP < 0.05 versus model group). Data are shown as the mean ± S.D. SNL: spinal nerve ligation. TNF-α: tumor necrosis factor alpha. IF-1β: interleukin-1 beta. IF-10: interleukin-10. S.D standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: The expression of TNF-α, IF-1β, and IF-10 in spinal cords of SNL rats on the different postoperative days. (a) TNF-α was upregulated in the spinal cord of SNL rats (aP < 0.05 versus sham group). After Tan IIA treatment, TNF-α expression reduced significantly (bP < 0.05 versus model group). (b) IF-1β was upregulated in the spinal cord of SNL rats (aP <0.05 versus sham group). After Tan IIA treatment, TNF-α expression reduced significantly (bP < 0.05 versus model group). (c) IF-10 was downregulated in the spinal cord of SNL rats (aP < 0.05 versus sham group). After Tan IIA treatment, TNF-α expression increased significantly (bP < 0.05 versus model group). Data are shown as the mean ± S.D. SNL: spinal nerve ligation. TNF-α: tumor necrosis factor alpha. IF-1β: interleukin-1 beta. IF-10: interleukin-10. S.D standard deviation.
Mentions: SNL significantly increased TNF-α and IL-1β expression at 3, 7, and 14 days after SNL (P < 0.05, compared with sham group). In addition, there was significant downregulation of TNF-α and IL-1β in the Tan IIA administration group that was subjected to SNL (P < 0.05, compared with SNL). TNF-α and IL-1β were upregulated, whereas IL-10 was downregulated in the spinal cord of the SNL rats. IL-10 increased after Tan IIA administration (P < 0.05). The results indicated that intraperitoneal Tan IIA significantly attenuated IL-1β and TNF-α expression and enhanced IL-10 expression in the spinal cord of SNL rats (Figure 4).

Bottom Line: Both the mechanical and heat pain thresholds were significantly decreased.After Tan IIA treatment, HMGB1, and TLR4 mRNA and protein levels, the expression of TNF-α and IF-1β was reduced significantly.These results indicate that Tanshinone IIA inhibited SNL-induced neuropathic pain via multiple effects, and targeting the HMGB1-TLR4 pathway could serve as the basis of new antinociceptive agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu 730000, China.

ABSTRACT
Fifty-four Sprague-Dawley rats weighing 200~240 g were randomly divided into sham-operated group (sham group), vehicle-treated SNL group (model group), and Tan IIA-treated SNL group (Tan IIA group). Tan IIA was administered intraperitoneally to rats in the Tan IIA-treated group at a dose of 30 mg/kg daily for 14 days after SNL surgery. Paw withdrawal mechanical thresholds (PWTs) and paw withdrawal thermal latencies (PWLs) were measured. High-mobility group box 1 (HMGB1) and Toll-like Receptor 4 (TLR4) mRNA and protein expression in the spinal cord were measured. Tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-10 (IL-10) in the spinal cord were measured, too. Both the mechanical and heat pain thresholds were significantly decreased. After Tan IIA treatment, HMGB1, and TLR4 mRNA and protein levels, the expression of TNF-α and IF-1β was reduced significantly. In conclusion, Tanshinone IIA reversed SNL-induced thermal hyperalgesia and mechanical allodynia and downregulated HMGB1 and TLR4 levels and inhibited the HMGB1-TLR4 pathway. Tanshinone IIA inhibited TNF-α and IL-1β expression but not IF-10 expression in the spinal cords of SNL rats. These results indicate that Tanshinone IIA inhibited SNL-induced neuropathic pain via multiple effects, and targeting the HMGB1-TLR4 pathway could serve as the basis of new antinociceptive agents.

No MeSH data available.


Related in: MedlinePlus