Berberine promotes nerve regeneration through IGFR‑mediated JNK‑AKT signal pathway - PubMed (original) (raw)

Berberine promotes nerve regeneration through IGFR‑mediated JNK‑AKT signal pathway

Hai-Na Zhang et al. Mol Med Rep. 2018 Dec.

Abstract

Berberine presents therapeutic ability for various central nervous system disorders, including Alzheimer's disease and cerebral ischemia. The present study investigated the role of berberine in nerve regeneration and analyzed the potential mechanism mediated by berberine in hippocampal pyramidal neurons. Reverse transcription‑quantitative poylmerase chain reaction, western blot, TUNEL assay and immunofluorescence were used to analyze the therapeutic effects of berberine on nerve regeneration. Berberine treatment increased growth and viability of hippocampal pyramidal neurons. Berberine treatment inhibited apoptosis of hippocampal pyramidal neurons and increased apoptosis regulator Bcl‑2 and Bcl‑w expression. Neuroinflammation of tumor necrosis factor α, interleukin (IL)1β, IL6 levels and autophagy‑related proteins microtubule‑associated proteins 1A/1B light chain 3B, autophagy related 16 like 1 and autophagy related 7 were downregulated by berberine treatment in hippocampal pyramidal neurons. Notably, study has found that berberine increased insulin-like growth factor receptor (IGFR) and decreased c‑Jun N‑terminal kinase (JNK) and protein kinase B (AKT) expression in hippocampal pyramidal neurons. IGFR antagonist abolished berberine‑increased growth of hippocampal pyramidal neurons. In conclusion, these results indicate that berberine can promote nerve regeneration through IGFR‑mediated JNK‑AKT signal pathway.

Keywords: berberine; nerve regeneration; IGFR; JNK; AKT.

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Figures

Figure 1.

Figure 1.

Effects of berberine on growth and viability of hippocampal pyramidal neurons. (A) Hippocampal pyramidal neurons growth was measured by crystal violet staining analysis. Magnification, ×400. Scale bar, 100 µm. (B) Viability of hippocampal pyramidal neurons was increased determined by MTT assay. *P<0.05 and **P<0.01 vs. control.

Figure 2.

Figure 2.

Effects of berberine on apoptosis of hippocampal pyramidal neurons. (A) Apoptosis of hippocampal pyramidal neurons was determined by TUNEL assay. (B) Anti-apoptosis protein Bcl-2 and Bcl-w expression levels in hippocampal pyramidal neurons between berberine and PBs group was determined by western blot. **P<0.01 vs. control.

Figure 3.

Figure 3.

Effects of berberine on neuroinflammation in hippocampal pyramidal neurons. (A) Expression of TNFα, IL1β and IL6 protein level in hippocampal pyramidal neurons between berberine and PBs group was determined by western blot. (B) Expression of LC3B, ATG16L and ATG7 in hippocampal pyramidal neurons between berberine and PBs group was determined by western blot. (C) Expression of CNPase positive oligodendrocyte expressing ATG5 in hippocampal pyramidal neurons between berberine and PBs group was determined by immunofluorescence staining. **P<0.01 vs. control.

Figure 4.

Figure 4.

Berberine regulates nerve regeneration through IGFR-mediated JNK-AKT signal pathway. (A) Expression of IGFR, JNK and AKT in hippocampal pyramidal neurons between berberine and PBs group was determined by western blot. (B) Expression of IGFR and increased JNK and AKT in IGFRAG-treated hippocampal pyramidal neurons determined by western blot. **P<0.01 vs. control. (C) Growth of hippocampal pyramidal neurons after treatment with IGFRAG measured by crystal violet staining analysis. *P<0.05 vs. IGFRAG, **P<0.01 vs. control or berberine. IGFR, insulin-like growth factor receptor; IGFRAG, IGFR antagonist.

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