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Tác dụng bảo vệ thần kinh của curcumin đối với các rối loạn nhận thức và vận động do viêm não tự miễn nghiệm ở chuột: cái nhìn sâu sắc về vai trò của con đường AMPK/SIRT1
Inflammopharmacology - 2023
Tóm tắt
Bệnh đa xơ cứng (MS) là một bệnh lý thần kinh thoái hóa mãn tính không thể chữa khỏi, trong đó sự tự miễn, stress oxy hóa và viêm thần kinh hợp tác dẫn đến sự phá hủy vỏ myelin. Thú vị thay, curcumin, một polyphenol tự nhiên, đã cho thấy tác dụng bảo vệ thần kinh trong nhiều bệnh thoái hóa thần kinh, bao gồm cả MS. Tuy nhiên, ảnh hưởng của curcumin đối với sự suy giảm nhận thức do MS vẫn còn mờ mịt. Do đó, chúng tôi đã gây ra viêm não tự miễn nghiệm (EAE) ở chuột bằng cách sử dụng huyết thanh tủy sống (SCH) và chất kích thích Freund hoàn chỉnh, điều này cuối cùng mô phỏng tình trạng của MS. Nghiên cứu này không chỉ nhằm đánh giá hiệu quả của curcumin chống lại sự suy giảm nhận thức và vận động do EAE gây ra, mà còn khám phá một cơ chế hành động mới, qua đó curcumin phát huy tác dụng có lợi trong bệnh MS. Hiệu quả của curcumin (200 mg/kg/ngày) được đánh giá qua các thử nghiệm hành vi, kiểm tra mô bệnh học và các xét nghiệm sinh hóa. Tóm lại, curcumin đã cải thiện các rối loạn nhận thức và vận động do EAE gây ra, như được chứng minh qua các thử nghiệm hành vi và kiểm tra mô bệnh học ở vùng hải mã. Thú vị là, curcumin đã kích hoạt trục protein kinase được kích hoạt bởi adenosine monophosphate/silent mating type information regulation 2 homolog 1 (AMPK/SIRT1), kích thích con đường protein liên kết yếu tố phản ứng cyclic AMP/nhân tố dinh dưỡng thần kinh có nguồn gốc từ não/protein myelin cơ bản (CREB/BDNF/MBP), từ đó ngăn chặn quá trình mất myelin ở thể chằng. Hơn nữa, sự kích hoạt AMPK/SIRT1 đã làm tăng yếu tố hạt erythroid 2 liên quan (Nrf2), một chất chống oxy hóa mạnh mẽ, cải thiện stress oxy hóa do EAE gây ra. Thêm vào đó, curcumin đã loại bỏ tình trạng viêm thần kinh do EAE bằng cách ức chế trục Janus kinase 2 /các yếu tố truyền tín hiệu và hoạt hóa phiên mã 3 (JAK2/STAT3), qua nhiều con đường khác nhau, bao gồm cả sự kích hoạt AMPK/SIRT1. Sự ức chế JAK2/STAT3 đã chặn quá trình tổng hợp cytokine viêm. Tóm lại, tác dụng bảo vệ thần kinh của curcumin trong EAE được kiểm soát, ít nhất là một phần, bởi sự kích hoạt AMPK/SIRT1, cuối cùng làm giảm thiểu sự mất myelin neuron, stress oxy hóa và viêm thần kinh do EAE gây ra. Hình minh họa đồ họa của những con đường phân tử khả thi liên quan đến việc quản lý EAE nhờ curcumin. Curcumin kích hoạt AMPK/SIRT1, và điều này lần lượt kích hoạt nhiều con đường khác làm giảm thiểu sự thoái hóa thần kinh, stress oxy hóa và viêm thần kinh. Hơn nữa, curcumin đã vượt qua được con đường viêm JAK2/STAT3/NF-kβ.
Từ khóa
#đa xơ cứng #curcumin #bảo vệ thần kinh #viêm não tự miễn nghiệm #AMPK/SIRT1Tài liệu tham khảo
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