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. 2021 May 4;12:606682. doi: 10.3389/fphar.2021.606682

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Copyright © 2021 Li, Ren, Wang, Ma, Chen, Xie, Li, Li and Wang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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(A) Inflammatory cells involved in ischemic brain injury include inherent immune cells in the brain and circulating immune cells infiltrating into the CNS. Borneol attenuates the neuronal damage caused by inflammation via reducing the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6, and down-regulating the expression of COX-2 and 5-LOX, etc. (B) The forest plots: the borneol group vs. the control group on IL-1β levels. According to different detection methods, four studies were divided into two subgroups, subgroup 1 heterogeneity (n_T/n_C = 58/58, SMD −0.94, 95% CI: −1.34 to −0.54, p < 0.00001, heterogeneity χ ² = 8.96, df = 5, I ² = 44%) and overall heterogeneity (n_T/n_C = 62/62, SMD −0.98, 95% CI: −1.38 to −0.59, p < 0.00001, heterogeneity χ ² = 14, df = 6, I ² = 57%), suggesting that borneol can reduce the levels of IL-1β levels compared with the control group. (C) The forest plots: the borneol group vs. the control group on TNF-α levels. Meta-analysis of six studies showed that animals in the borneol group had statistically significant lower TNF-α levels than the control group (n_T/n_C = 75/75, SMD −1.71, 95% CI: −2.11 to −1.31, p < 0.00001, heterogeneity χ ² = 8.31, df = 8, I ² = 4%). (D) The forest plots: the borneol group vs. the control group on expression of COX-2. The expression levels of COX-2 were determined by ELISA and Western bolt analysis in subgroup 1 and subgroup 2, respectively. The results showed that the expression levels of COX-2 in the tested animals was significant decreased after administration of borneol with total heterogeneity (n_T/n_C = 48/47, SMD −1.63, 95% CI: −2.13 to −1.13, p < 0.00001, heterogeneity χ ² = 7.07, df = 4, I ² = 43%). (E) The forest plots: the borneol group vs. the control group on expression of 5-LOX. Meta-analysis of two studies with six comparisons showed that animals in the borneol group had significant lower 5-LOX levels than the control group (n_T/n_C = 65/64, MD −0.86, 95% CI: −0.99 ∼ −0.73, p < 0.00001, heterogeneity χ² = 40.91, df = 5, I ² = 88%). The source of heterogeneity was not found by eliminating the literature one by one. (F) The forest plots: the borneol group vs. the control group on IL-6 levels. Meta-analysis of two studies with five comparisons showed that animals in the borneol group had lower IL-6 levels than the control group with substantial heterogeneity (n_T/n_C = 48/48, MD −28.82, 95% CI: −33.99 to −23.64, p < 0.00001, heterogeneity χ ² = 86.18, df = 4, I ² = 95%).