A comprehensive search across multiple databases was performed up to 31 July 2023, including EMBASE, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang database, and Chinese Biological Medical Database (CBM).

Two reviewers (Longhua Wang and Xinning Yao) independently screened all citations using Mesh terms and free terms retrieval methods. The searching strategies for PubMed were comprehensively outlined in Table 2.

Two researchers, Longhua Wang and Xinning Yao, individually utilized Endnote X9.1 to select the studies. They carefully examined the title, abstract, and full text of each study based on predefined criteria for inclusion and exclusion. In case of any disagreement between the two researchers, a third researcher named Xia Ding acted as an arbitrator.

Subsequently, Longhua Wang and Ping Li independently extracted relevant information from selected studies including literature title, first author, sample size, publication year, diagnostic criteria, interventions, duration of treatment, indicators for evaluating outcomes, findings, duration of follow-up and adverse events. Any discrepancies were resolved by a final decision made by Fenglei Wang.

The risk of bias was independently assessed by two researchers (Longhua Wang and Ping Li) using the Cochrane risk of bias tool. The evaluation encompassed seven aspects, namely the generation of random sequences, concealment of allocation, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. A low, high, or unclear risk assessment was assigned for each item. In case of the researchers, a final decision was reached through discussion.

The analysis of data was conducted utilizing RevMan 5.4.1 software. For dichotomous data, relative risks (RR) with corresponding 95% confidence intervals (CI) were used; for continuous data standardized mean difference (SMD) with corresponding 95% CI were examined. Heterogeneity was assessed using χ ² test and inconsistency index statistic (I ²). If substantial heterogeneity was present (I ² > 50% or p < 0.05), a random effects model was applied to compute the pooled RR; Conversely, in the absence of significant heterogeneity, a fixed effects model was utilized instead. Sensitivity analysis examined potential sources of heterogeneity and assessed result robustness. Statistically significance for pooled results was when p < 0.05. In addition, funnel plots were utilized to assess publication bias.

The search strategy identified a total of 633 studies from databases, including 5 in PubMed, 11 in Embase, 2 in the Cochrane Library, 163 in CNKI, 193 in Wanfang, 102 in VIP, and 157 in CBM. Among these studies, there were duplicates (n = 343), irrelevant studies excluded based on title and abstract screening (n = 200), non-RCTs (n = 12), incomplete date (n = 3), and studies not meeting inclusion criteria (n = 52). Ultimately, a total of 23 RCTs conducted exclusively in China met the inclusion criteria for this meta-analysis (Figure 1).

Of 2,101 patients with FD: experiment groups included 1,081 cases while control groups had 1,020 cases. XSLJZD or modified XSLJZD was administered solely to the experiment groups whereas Western medicine, placebo, or Chinese patent drugs were used as controls. Detailed characteristics of the included studies can be found in Supplementary Table S1.

Methodological quality displayed in Table 3. Figures 2, 3 describe assessment of risk bias.

The total clinical effectiveness rate was described in twenty-one studies (Wang et al., 2008; Fan, 2010; Yang et al., 2010; Zhou, 2010; Liang, 2011; He, 2012; Lu and Hong, 2012; Cai et al., 2014; Liao, 2014; Chen, 2015; Cheng and Zhu, 2015; Wang and Yang, 2016; Zhou et al., 2016; Sun, 2017; Xu et al., 2017; Zeng and Tang, 2017; Zhou et al., 2018; Feng, 2020; Wang, 2020; Jiang, 2022; Li et al., 2022). XSLJZD demonstrated a significantly higher clinical effectiveness rate compared to the control group (RR 1.27; 95% CI 1.21, 1.33; p < 0.00001), with low heterogeneity observed (p = 0.68, I ² = 0%) (Figure 4).

The potential publication bias of the twenty-one studies (Wang et al., 2008; Fan, 2010; Yang et al., 2010; Zhou, 2010; Liang, 2011; He, 2012; Lu and Hong, 2012; Cai et al., 2014; Liao, 2014; Chen, 2015; Cheng and Zhu, 2015; Wang and Yang, 2016; Zhou et al., 2016; Sun, 2017; Xu et al., 2017; Zeng and Tang, 2017; Zhou et al., 2018; Feng, 2020; Wang, 2020; Jiang, 2022; Li et al., 2022) were evaluated using a funnel plot analysis (Figure 6). According to the results obtained from the analysis of the funnel plot in this research, no significant evidence of potential publication bias was observed.

FD is a highly prevalent digestive disorder with an intricate pathophysiology that hampers effective treatment strategies (Ford et al., 2020). Consequently, there is a pressing need to explore novel complementary and alternative therapies for FD. Furthermore, no comprehensive systematic review or meta-analysis on the efficacy of XSLJZD for FD has been published in English literature. Notably, XSLJZD has gained widespread usage in China as a therapeutic approach for FD. In this review, we performed a meta-analysis aiming to evaluate the efficacy of XSLJZD in managing FD symptoms. Our findings revealed that: 1) XSLJZD exhibited significantly superior clinical efficacy compared to the control group; 2) XSLJZD demonstrated notable improvements in gastric emptying rate and symptom scores.

According to the pharmacology of herbal medicine, Dolomiaea costus (Falc.) Kasana and A.K.Pandey has been reported to enhance gastrointestinal motility, protect gastric mucosa, and exhibit anti-ulcer and anti-inflammatory effects (Zheng et al., 2022). Wurfbainia villosa (Lour.) Škorničk. and A.D.Poulsen has demonstrated significant potential in promoting gastric emptying, enhancing gastrointestinal peristalsis for gastroprotection, and exerting anti-ulcer properties (Lu et al., 2016). Panax ginseng C.A.Mey is known for its ability to invigorate vital energy and benefit the spleen and lung. Total ginsenosides have shown promising results in improving gastrointestinal motility in rats with FD by modulating gastrointestinal hormone levels and alleviating motility disorders (Lin et al., 2020). Poria cocos (Schw.) Wolf can enhance the reparative capacity of gastrointestinal mucosa by modulating immune and gastrointestinal functions (Zuo et al., 2023). Atractylodes macrocephala Koidz exerts gastroprotective effects through bidirectional regulation of gastrointestinal motility and modulation of intestinal microecology (Zhang W. X. et al., 2022). Pinellia ternata (Thunb.) Makino significantly promotes gastrointestinal motility and regulates gastric acid secretion to safeguard gastric mucosa integrity (Li et al., 2021). Citrus reticulata Blanco can effectively improve digestion and alleviate symptoms of indigestion (Xu et al., 2022).

Numerous researchers have reported the effectiveness of XSLJZD for treating FD, which aligns with our findings. XSLJZD demonstrated a significant improvement in gastrointestinal motility with the restoration of mitochondrial quality control system by inhibiting PINK1/Parkin-mediated mitophagy and division (Zhang J. et al., 2022). Additionally, XSLJZD was found to downregulate TRPV1 and 5-HT expression levels in the duodenum of rats with FD, thereby alleviating gastric hypersensitivity, which may contribute to its therapeutic mechanisms for FD (Zhao et al., 2019). Through network pharmacology analysis and experimental validation (Zhao et al., 2023b), it was observed that XSLJZD effectively reduced p-ERK, p-P38MARK, as well as downstream p-NF-κBp65 levels to modulate low-grade duodenal inflammation and ameliorate FD symptoms. Importantly, recent understanding of FD pathophysiology suggests that low-grade duodenal inflammation plays a central role (Miwa et al., 2019).

This review has several limitations. First of all, the included studies exhibited low quality, potentially introducing a high-risk bias across all enrolled studies. Secondly, most studies lacked published protocols or sufficient information to assess the risk of bias adequately. The inclusion of all studies did not adhere to double-blinding protocols, specifically due to the inherent differences in external characteristics between herbal decoctions and Western medicine. Therefore, it is imperative to meticulously plan and implement a rigorous blinding protocol, such as employing a double-placebo method, while providing detailed descriptions of the methodology. Furthermore, all included studies were exclusively conducted in China. It is great need to enhance international collaboration in order to conduct multi-regional and multi-ethnic clinical studies that can validate the clinical efficacy of XSLJZD. Moreover, no follow-up assessments were conducted to determine the long-term effectiveness of XSLJZD. To precisely determine the clinical efficacy of XSLJZD for FD, further investigations with extended treatment and follow-up periods are warranted. The present review ultimately revealed a lack of description regarding quality control and chemical profile in all the studies included, thereby resulting in contentious conclusions. The future clinical trials on botanical drug extracts should provide comprehensive information regarding the composition, extraction process, and drug extraction ratio of the study material.

This review not only assessed the total clinical effectiveness rate, but also evaluated the enhancement in gastric emptying rate and symptom score, distinguishing it from previous studies (Zeng et al., 2013; He et al., 2018). The studies included in our analysis were limited to those that provided comprehensive details on the administration information and components of herbal prescriptions for the purpose of enhancing clarity. In addition, the scope of our search encompasses not only Chinese databases but also international databases, significantly expanding the time range for our investigation. Finally, we conducted subgroup and sensitivity analyses to assess result reliability and identify sources of heterogeneity. However, the limitation we face was the absence of Jadad rating in the literature compared with previous studies.

Compared to conventional Western medicine, XSLJZD demonstrated significant efficacy and a lower incidence of adverse events. Therefore, XSLJZD may serve as an effective complementary and alternative therapy for FD. Considering the suboptimal quality of the included studies, it is imperative to conduct robust large-scale RCTs in order to validate our findings. To enhance the evidential support for the efficacy of XSLJZD in patients with FD, well-designed RCTs should be undertaken, encompassing diverse outcome measures pertaining to dyspeptic symptoms. In addition, In order to enhance the robustness and reproducibility of findings, future studies on botanical drugs should provide detailed descriptions regarding their origin, composition, extraction process of metabolites, and drug ratios. Moreover, the efficacy of XSLJZD should be evaluated in the future studies with a long-term follow-up period.