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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

(a) Transcript measured by quantitative real-time PCR showed significant differences in the TLR4 gene level on the different postoperative days (aP < 0.05 versus sham group, bP < 0.05 versus model group). (b) The TLR4 measurement by western blotting showed that the TLR4 (94 kDa) protein was at a low level in the sham group; the TLR4 protein began to increase at 3 days after SNL surgery and remained at a high level during the experiment (aP < 0.05 versus sham group); after Tan IIA treatment, the TLR4 protein reduced significantly (bP < 0.05 versus model group). (c) Summary data of western blot showed significant differences in the TLR4 protein level on different postoperative days (aP < 0.05 versus sham group, bP < 0.05 versus model group). Data are shown as the mean ± S.D. SNL: spinal nerve ligation. TLR4: Toll-Like Receptor 4. Blank: sham group. Drug: Tan IIA group. S.D: standard deviation.
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fig3: (a) Transcript measured by quantitative real-time PCR showed significant differences in the TLR4 gene level on the different postoperative days (aP < 0.05 versus sham group, bP < 0.05 versus model group). (b) The TLR4 measurement by western blotting showed that the TLR4 (94 kDa) protein was at a low level in the sham group; the TLR4 protein began to increase at 3 days after SNL surgery and remained at a high level during the experiment (aP < 0.05 versus sham group); after Tan IIA treatment, the TLR4 protein reduced significantly (bP < 0.05 versus model group). (c) Summary data of western blot showed significant differences in the TLR4 protein level on different postoperative days (aP < 0.05 versus sham group, bP < 0.05 versus model group). Data are shown as the mean ± S.D. SNL: spinal nerve ligation. TLR4: Toll-Like Receptor 4. Blank: sham group. Drug: Tan IIA group. S.D: standard deviation.

Mentions: The expression of the HMGB1 and TLR4 genes in the spinal cord in the SNL group was lower on the postoperative 3rd, 7th, and 14th days (P < 0.05 versus sham group). The HMGB1 and TLR4 gene levels in the spinal cord in the Tan IIA group were higher on the postoperative 3rd, 7th, and 14th days (P < 0.05 versus SNL group). Our results showed that the HMGB1 and TLR4 gene levels were significantly upregulated in the SNL rats. The HMGB1 and TLR4 gene levels decreased after Tan IIA treatment (Figures 2 and 3).


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)

(a) Transcript measured by quantitative real-time PCR showed significant differences in the TLR4 gene level on the different postoperative days (aP < 0.05 versus sham group, bP < 0.05 versus model group). (b) The TLR4 measurement by western blotting showed that the TLR4 (94 kDa) protein was at a low level in the sham group; the TLR4 protein began to increase at 3 days after SNL surgery and remained at a high level during the experiment (aP < 0.05 versus sham group); after Tan IIA treatment, the TLR4 protein reduced significantly (bP < 0.05 versus model group). (c) Summary data of western blot showed significant differences in the TLR4 protein level on different postoperative days (aP < 0.05 versus sham group, bP < 0.05 versus model group). Data are shown as the mean ± S.D. SNL: spinal nerve ligation. TLR4: Toll-Like Receptor 4. Blank: sham group. Drug: Tan IIA group. S.D: standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: (a) Transcript measured by quantitative real-time PCR showed significant differences in the TLR4 gene level on the different postoperative days (aP < 0.05 versus sham group, bP < 0.05 versus model group). (b) The TLR4 measurement by western blotting showed that the TLR4 (94 kDa) protein was at a low level in the sham group; the TLR4 protein began to increase at 3 days after SNL surgery and remained at a high level during the experiment (aP < 0.05 versus sham group); after Tan IIA treatment, the TLR4 protein reduced significantly (bP < 0.05 versus model group). (c) Summary data of western blot showed significant differences in the TLR4 protein level on different postoperative days (aP < 0.05 versus sham group, bP < 0.05 versus model group). Data are shown as the mean ± S.D. SNL: spinal nerve ligation. TLR4: Toll-Like Receptor 4. Blank: sham group. Drug: Tan IIA group. S.D: standard deviation.
Mentions: The expression of the HMGB1 and TLR4 genes in the spinal cord in the SNL group was lower on the postoperative 3rd, 7th, and 14th days (P < 0.05 versus sham group). The HMGB1 and TLR4 gene levels in the spinal cord in the Tan IIA group were higher on the postoperative 3rd, 7th, and 14th days (P < 0.05 versus SNL group). Our results showed that the HMGB1 and TLR4 gene levels were significantly upregulated in the SNL rats. The HMGB1 and TLR4 gene levels decreased after Tan IIA treatment (Figures 2 and 3).

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