2. Academic Validation
  3. Deoxyshikonin inhibited rotavirus replication by regulating autophagy and oxidative stress through Sirt1/FoxO1/Rab7 axis

Deoxyshikonin inhibited rotavirus replication by regulating autophagy and oxidative stress through Sirt1/FoxO1/Rab7 axis

  • Microb Pathog. 2023 Mar 10;106065. doi: 10.1016/j.micpath.2023.106065.
Haohai Huang 1,  Dan Liao 2,  Bin He 3,  Rong Pu 4,  Yejia Cui 4,  Guanghui Zhou 5
Affiliations

Affiliations

  • 1 Medical and Pharmacy Research Laboratory, SSL Central Hospital of Dongguan, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China; Department of Clinical Pharmacy, SSL Central Hospital of Dongguan, Dongguan Third People's Hospital, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China. Electronic address: haohaihuangmpr@21cn.com.
  • 2 Medical and Pharmacy Research Laboratory, SSL Central Hospital of Dongguan, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China; Department of Gynaecology, SSL Central Hospital of Dongguan, Dongguan Third People's Hospital, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.
  • 3 Medical and Pharmacy Research Laboratory, SSL Central Hospital of Dongguan, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.
  • 4 Department of Laboratory, SSL Central Hospital of Dongguan, Dongguan Third People's Hospital, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.
  • 5 Department of TCM Rehabilitation, SSL Central Hospital of Dongguan, Dongguan Third People's Hospital, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.
PMID: 36907361 DOI: 10.1016/j.micpath.2023.106065
Abstract

Background: Rotavirus (RV) is a double-stranded RNA virus. RV prevention and treatment remain a major public health problem due to the lack of clinically specific drugs. Deoxyshikonin is a natural compound isolated from the root of Lithospermum erythrorhizon and one of the shikonin derivatives which owns remarkable therapeutic effects on multiple diseases. The purpose of this research was to inquire Deoxyshikonin's role and mechanism in RV Infection.

Methods: Deoxyshikonin's function in RV was estimated using Cell Counting Kit-8 analysis, cytopathic effect inhibition assay, virus titer determination, quantitative Real-Time PCR, Enzyme linked-immunosorbent assay, Western blot, immunofluorescence, and glutathione levels detection. Also, Deoxyshikonin's mechanism in RV was appraised with Western blot, virus titer determination, and glutathione levels detection. Moreover, Deoxyshikonin's function in RV in vivo was determined using animal models, and diarrhea score analysis.

Results: Deoxyshikonin owned anti-RV activity and repressed RV replication in Caco-2 cells. Furthermore, Deoxyshikonin reduced Autophagy and oxidative stress caused by RV. Mechanistically, Deoxyshikonin induced low protein levels of SIRT1, ac-Foxo1, Rab7, VP6, low levels of RV titers, low Autophagy and oxidative stress. SIRT1 overexpression abolished the effects of Deoxyshikonin on RV-treated Caco-2 cells. Meanwhile, in vivo research affirmed that Deoxyshikonin also possessed anti-RV function, and this was reflected in increased survival rate, body weight, GSH levels, and decreased diarrhea score, RV virus antigen, LC-3II/LC3-I.

Conclusion: Deoxyshikonin reduced RV replication through mediating Autophagy and oxidative stress via SIRT1/FoxO1/Rab7 pathway.

Keywords

Autophagy; Deoxyshikonin; Oxidative stress; Rotavirus; Sirt1/FoxO1/Rab7.

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