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Meta-Analysis
. 2024 Sep 27;25(1):65.
doi: 10.1186/s40360-024-00793-z.

Effectiveness of DL-3-n-butylphthalide in the treatment of poststroke cognitive impairment and its associated predictive cytokines: a systematic review and meta-analysis

Zhen Wang #  1   2 , Jiahui Wang #  3 , Jiajia Yun #  1 , Jun Song  2 , Qi Chen  4 , Deqiang Wang  5 , Chao Ren  6   7
Affiliations
Meta-Analysis

Effectiveness of DL-3-n-butylphthalide in the treatment of poststroke cognitive impairment and its associated predictive cytokines: a systematic review and meta-analysis

Zhen Wang et al. BMC Pharmacol Toxicol. .

Abstract

Background: The efficacy of DL-3-n-butylphthalide (NBP) in the treatment of post-stroke cognitive impairment (PSCI) has been reported previously. However, the course of treatment that shows curative effect and cytokines predictive of the efficacy of NBP in the treatment of PSCI have not been systematically evaluated. This study aimed to assess the efficacy, course of treatment, and cytokines that can predict the effectiveness of NBP in treating poststroke cognitive impairment PSCI.

Methods: This study has been registered with PROSPERO (registration number CRD42024518768). Randomized controlled trial (RCT) data dated by November 12, 2023 were retrieved from the PubMed, Embase, Cochrane Library, Web of Science, Wanfang, CNKI, CSTJ, and SinoMed databases using medical subject terms combined with free words. The updated Cochrane RoB-I Risk of Bias tool was utilized for literature quality evaluation. Statistical analysis were carried out using Review Manager 5.4.1 software.

Results: Thirty-eight original studies involving 5417 PSCI patients were analyzed. The results showed that NBP had a beneficial impact on cognitive function in PSCI patients when used alone or in combination therapy, as assessed by the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale. The effect sizes were significant for both monotherapy and combination therapy. Subgroup analyses based on treatment cycle indicated that NBP enhanced cognitive function in PSCI patients from 1 week after intervention: MMSE (SMD = 0.43, 95% CI [0.28, 0.58], P < 0.001), MoCA (SMD = 0.44, 95% CI [0.27, 0.61], P < 0.001). There was a cumulative enhancement in cognitive function within 6 months after NBP treatment based on the MoCA scores (SMD = 0.61, 95% CI [0.30, 0.91], P < 0.001). Furthermore, decreased levels of the cytokines Hs-CRP, TNF-α, IL-6, IL-8, Hcy, NSE, MDA, MMP-9, and Cys-C (SMD = -2.28, 95% CI [-2.97, 1.58], P < 0.001) and increased levels of BDNF, VEGF, and TIMP-1 (SMD = 2.80, 95% CI [1.66, 3.94], P < 0.001) were also predictive of treatment efficacy.

Conclusion: NBP plays a beneficial role in improving cognitive function in PSCI patients, and their prognoses could be predicted by serum cytokine levels. However, high-quality, multicenter, multisample, and RCTs are still needed to confirm the clinical validity of NBP due to its low methodological quality.

Keywords: Cognitive function; MMSE; MoCA; Potential mechanisms; Randomized controlled trial.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart for data screen and filter
Fig. 2
Fig. 2
Meta-analysis of cognitive assessment scale for NBP as monotherapy. a MMSE, b MoCA
Fig. 3
Fig. 3
Meta-analysis of cognitive assessment scale for NBP as combination therapy. a MMSE, b MoCA
Fig. 4
Fig. 4
Meta analysis of different treatment courses of NBP for cognitive assessment scale. a MMSE, b MoCA
Fig. 5
Fig. 5
Meta analysis of serum factors before and after treatment. a Inflammatory factors, b Nutrient factors and enzymes, c Other serum factors
Fig. 6
Fig. 6
Diagram of the mechanism of NBP treatment for PSCI
See this image and copyright information in PMC

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