Therapeutic Effect of Tanshinone IIA on Liver Fibrosis and the Possible Mechanism: A Preclinical Meta-Analysis

Background Liver fibrosis is a serious human health problem, and there is a need for specific antifibrosis drugs in the clinic. Tanshinone IIA has recently been reported to have a role in the treatment of liver fibrosis. However, the evidence supporting its antifibrotic effect is not sufficient, and the underlying mechanism is not clear. We thus performed this meta-analysis of animal research to assess the therapeutic effect of tanshinone IIA on liver fibrosis and analyzed the possible associated mechanism to provide a reference for further clinical drug preparation and clinical research. Methods We collect related articles from the databases PubMed, Web of Science, Embase, Wanfang, VIP, and CNKI. The quality of the included studies was evaluated according to the SYRCLE risk of bias tool for animal studies. Data were analyzed using RavMan 5.3 and Stata 12.0 software. Results A total of 404 articles were retrieved from the databases. After screening, 11 articles were included in the analysis. The included studies' methodological quality was generally low, and an obvious publication bias was found. The results showed that tanshinone IIA significantly improved liver function in experimental animals and reduced the level of liver fibrosis by reducing inflammation and inhibiting immunity, antiapoptotic processes, and HSC activation. Conclusion Tanshinone IIA can effectively improve liver fibrosis and liver function in animal models and is worthy of future higher quality animal studies and clinical drug trials.


Rationale
3 Describe the rationale for the review in the context of what is already known.

2-4
Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

2-5 METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.
18 Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

5-6
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

6-7
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

6-7
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

7
Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. 7 Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

Section/topic # Checklist item Reported on page #
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

8
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection
17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

8-9
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

9-10
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

10
Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

11-14
Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.

11-14
Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15).

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

17-18
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

18
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research. The search strategy in WOS: TS=(tanshinone or tanshinone II A or tanshinone IIA) and TS=(Liver