Clinical efficacy of Xifeng Huashi and its effect on mental status in patients with diarrheal irritable bowel

Abstract

BACKGROUND

Diarrheal irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder characterized by abdominal pain accompanied by recurrent diarrhea that significantly impacts the quality of life and mental health of patients.

AIM

To investigate the clinical efficacy of Xifeng Huashi and its effects on the mental status of patients diagnosed with IBS-D.

METHODS

Data from 128 patients with IBS-D treated at the Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine between June 2023 and May 2024 were divided into control and research groups, with 64 patients in each group. The control group received conventional treatment with Western medicine alone, whereas the research group was prescribed Xifeng Huashi. Differences in specific indices between the two groups were observed and compared using relevant assessment tools.

RESULTS

The research group showed a higher total effective rate (92.19% vs 76.56%; P = 0.027) and lower traditional Chinese medicine symptom score (5.07 ± 3.11 vs 7.38 ± 3.68; P < 0.001) than the control group. Post-treatment, the research group exhibited significantly lower levels of pro-inflammatory cytokines (tumor necrosis factor-α: 18.80 ± 4.02 ng/L vs 21.09 ± 4.10 ng/L, P = 0.002; interleukin-6:14.84 ± 4.06 ng/L vs 19.80 ± 4.42 ng/L, P < 0.001) and higher levels of the anti-inflammatory cytokine interleukin-10 (48.53 ± 5.02 ng/L vs 46.06 ± 4.94 ng/L, P = 0.006). Moreover, markers of intestinal mucosal barrier function (diamine oxidase: 6.53 ± 2.35 ng/mL vs 7.66 ± 2.40 ng/mL, P = 0.008; D-lactate: 0.18 ± 0.04 mmol/L vs 0.20 ± 0.06 mmol/L, P = 0.004; lipopolysaccharides: 44.77 ± 8.16 pg/mL vs 48.20 ± 8.15 pg/mL, P = 0.019) were significantly improved in the research group. In addition, Self-rating Anxiety Scale (37.33 ± 5.73 vs 39.59 ± 6.36; P = 0.036) and Self-rating Depression Scale scores (34.77 ± 6.71 vs 38.06 ± 6.52; P = 0.006) were lower in the research group. The recurrence rate was significantly lower in the research group than in the control group (18.64% vs 40.82%, P = 0.001).

CONCLUSION

Xifeng Huashi is effective for the treatment of IBS-D and manifests advantages in improving clinical symptoms and mental status, as well as reducing the short-term relapse rate.

Key Words: Xifeng Huashi prescription; Irritable bowel syndrome; Clinical efficacy; Intestinal mucosal barrier; Mental status

Core Tip: Diarrheal irritable bowel syndrome (IBS-D) significantly affects the quality of life and psychological health of patients. This study investigated the clinical efficacy of Xifeng Huashi and its effects on the mental status of patients with IBS-D. Xifeng Huashi is effective for the treatment of IBS-D and manifests advantages in improving clinical symptoms and mental status, as well as reducing the short-term relapse rate.

INTRODUCTION

Irritable bowel syndrome (IBS) is a widespread functional gastrointestinal disorder that affects approximately 4%-10% of individuals worldwide[1-3]. Diarrheal IBS (IBS-D), a prevalent subtype of IBS, is characterized by recurrent abdominal pain associated with defecation and a marked increase in loose or watery stool[4]. The pathogenesis of IBS-D is complex and stems from the interaction of multiple factors, including abnormal intestinal motility, visceral hypersensitivity, gut microbiota dysbiosis, brain–gut axis dysfunction, and psychological influences[5-9]. IBS-D seriously affects the quality of life, work productivity, and mental health of those affected[10,11]. Psychological distress exacerbates gastrointestinal symptoms, whereas persistent bowel symptoms worsen mental health, creating a vicious cycle. The current mainstream management strategies for IBS-D include dietary interventions, pharmacotherapy, and psychological therapies. Although these approaches can provide symptomatic relief for some patients, limitations persist, including variable efficacy, potential side effects of long-term medication use, poor patient adherence to restrictive diets, and limited access to psychological interventions[12-15].

Traditional Chinese medicine (TCM) has unique advantages and a rich clinical history regarding IBS-D treatment. According to TCM, IBS-D is mostly caused by emotional disorders, poor diet, and physical weakness, which lead to liver depression, spleen deficiency, spleen and stomach weakness, and intestinal conduction disorders, triggering intestinal dysfunction[16-18]. As a clinical TCM formula, prescription of Xifeng Huashi is a subtle approach that focuses on IBS-D pathogenesis, with the main treatment targeted at calming the liver, extinguishing wind, strengthening the spleen, and resolving dampness. The formula consists of white peony, hook vine, Scutellaria baicalensis (an antifungal), Septoria, and Glycyrrhiza glabra, which are combined to regulate the liver and spleen, resolve dampness, and improve intestinal function, thus alleviating diarrhea and abdominal pain symptoms[19]. Although preliminary evidence supports the benefits of TCM in patients with IBS-D, clinical studies evaluating its gastrointestinal and psychological effects are limited[20,21]. Therefore, this study aimed to investigate the clinical efficacy of Xifeng Huashi in patients diagnosed with IBS-D, focusing on improvements in intestinal function and mental status, with the aim of providing better clinical evidence to support the treatment of IBS-D with TCM.

MATERIALS AND METHODS

Patients

Data from 128 patients with IBS-D admitted to the outpatient clinic of Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine between June 2023 and May 2024 were included in this study. Based on the order of consultation, 128 patients were randomly divided into two groups: Research (n = 64) and control (n = 64). The control group received conventional treatment with Western medicine alone, whereas the research group was prescribed Xifeng Huashi. The study protocol was approved by the local medical ethics committee. Informed about the study details, all participating patients and their families provided voluntary consent by signing an informed consent form. A biostatistician conducted a statistical review of this study.

Diagnostic criteria

Western medicine refers to the Rome IV diagnostic criteria for IBS in functional gastrointestinal disorders, with symptoms present for ≥ 6 months at the time of presentation and the patient’s fecal characteristics consistent with a diarrheal pattern[22]. The diagnostic criteria for TCM were based on the Expert Consensus Opinion on Chinese Medicine Diagnosis and Treatment of Irritable Bowel Syndrome (2017), which met the diagnostic criteria for IBS-D Liver Depression and Spleen Deficiency. Primary symptoms include irritability and abdominal pain, which decrease after diarrhea. The three secondary symptoms were distension and fullness in both hypochondrial regions, tiredness, fatigue, and anorexia. This syndrome is defined as the presence of two major symptoms and at least one minor symptom.

Inclusion and exclusion criteria

The inclusion criteria were as follows: (1) Fulfilment of the Western medical diagnostic criteria for IBS-D (Rome IV criteria); (2) Fulfilment of the Chinese Medicine Diagnostic Criteria for Liver Depression and Spleen Deficiency; (3) Age 18-65 years; (4) Voluntary participation in the study; and (5) Provision of written informed consent.

The exclusion criteria were as follows: (1) Abdominal pain and diarrhea caused by infectious diarrhea, inflammatory bowel disease, parasitic infections, colorectal tumors, malabsorption syndrome, lactose intolerance, and other systemic diseases; (2) Severe circulatory, respiratory, hematopoietic, and endocrine diseases or malignant tumors; (3) Primary illnesses such as hepatic, renal, endocrine, cardiovascular, and hematopoietic diseases; (4) Lactation or pregnancy; (5) Allergic body, or allergic to many drugs and foods, or known hypersensitivity to the drugs and ingredients used in this study; anxiety disorders, depression, and other serious mental illnesses; (6) Use of drugs used for the treatment of IBS-D in the previous 2 weeks, or participation in other clinical trials in the previous month; and (7) Other factors that the investigators considered to be inappropriate for enrollment.

Treatment

Control group: The control group received conventional Western medicine only. According to the symptoms, the following were prescribed: Compound Lactobacillus acidophilus tablets (specification: 0.5 g × 24 tablets), 2 tablets each time, 3 times per day, and pivoxyl bromide tablets (specification, 50 mg × 15 tablets), 1 tablet each time, 3 times per day.

Research group: The research group was prescribed Xifeng Huashi, consisting of white peony (15 g), hook vine (10 g), Tribulus terrestris (15 g), Atractylodes macrocephala (10 g), Mucuna pruriens (6 g), Rhizoma coptidis (3 g), ginger (3 g), Scutellaria baicalensis (6 g), Pericarpium citri reticulatae (6 g), Fenpeng (6 g), Fructus septentrionalis (15 g), pomegranate peel (10 g), and Glycyrrhiza glabra (6 g). The medication was administered twice daily with water.

Both groups continued to use the medicine for eight weeks to observe its therapeutic effect(s). During the medication period, patients were advised to maintain a light diet and avoid allergenic foods to facilitate easy flatulence and avoid spicy, greasy, and other similar foods.

Observation indicators

Overall clinical efficacy: Overall efficacy was determined using the nimodipine method and calculated as follows: Efficacy index (%) = [(pre-treatment score - post-treatment score)/pre-treatment score] × 100%. Ineffective: No significant improvement in symptoms and signs, or even aggravation and reduction of symptoms by < 30%. Effective: Improvement in signs and symptoms by 30%, and symptom score reduction by < 70%. Significant effect: Significant improvement in symptoms and signs: 70%; reduction in symptoms: < 95%. Clinical recovery: Disappearance or basic disappearance of main signs and symptoms, and efficacy index ≥ 95%.

TCM symptom score (evaluation of 5 symptoms): Main symptoms include abdominal pain decreased from diarrhea, irritability, and no symptoms to severe symptoms in the order of 0, 2, 4, and 6 points, respectively. Secondary symptoms include distension and fullness in both hypochondrial regions, tiredness, fatigue, and anorexia of 0, 1, 2, and 3 points, from symptomless to severe symptoms; the more severe the symptoms, the higher the score.

Serum testing: Fasting venous blood samples were obtained from patients on the day of the initial consultation and at the end of treatment. Serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), lipopolysaccharides (LPS), diamine oxidase (DAO), and D-lactic acid were measured using a commercially available colorimetric ELISA kit (Wuhan Huamei Bioengineering Co., Wuhan, China).

Psychological status: The Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were used[23,24]. Both the SAS and SDS consist of 20 items, each rated on a 1-4 scale. The standard cutoff score for the SAS was 50 points. A standard score < 50 indicates no anxiety, while ≥ 50 suggests the presence of anxiety symptoms, with higher scores indicating more severe anxiety. The standard cutoff score for the SDS was 53. A standard score < 53 indicates no depression, while ≥ 53 suggests the presence of depressive symptoms, with higher scores indicating more severe depression.

Recurrence: A follow-up assessment was performed 2 months post-treatment to evaluate and compare the recurrence rates between the two groups.

Statistical analysis

Statistical analyses and data visualization were performed using Prism version 8.0 (GraphPad Inc., San Diego, CA, United States). Continuous variables are expressed as mean ± SD, while categorical variables are expressed as n (%). Comparisons between groups for continuous variables were performed using the t-test, and the χ² test was used for categorical variables. Fisher’s exact test was applied in instances in which the expected frequency fell to < 5. Differences were considered statistically significant at P < 0.05.

RESULTS

General data

General clinical data, such as age, sex, body mass index, education level, disease duration, history of herbal medicine use, smoking history, drinking history, mean visual analog scale score, mean weekly stool frequency, and mean weekly Bristol score, were not significantly different between the study and control groups (P > 0.05; Table 1).

Table 1 Comparison of the general data of the two groups of patients.

Characteristic	Research group (n = 64)	Control group (n = 64)	P value
Age (years)	43.45 ± 12.58	41.97 ± 11.71	0.400
Sex			0.246
Men	48 (75.00)	42 (65.63)
Female	16 (25.00)	22 (34.37)
BMI, kg/m2	23.16 ± 2.33	22.86 ± 2.62	0.573
Educational level			0.648
Primary school	28 (43.75)	21 (32.81)
Junior high school	16 (25.00)	19 (29.69)
Secondary and high school	12 (18.75)	15 (23.44)
College, bachelor's degree and above	8 (12.50)	9 (14.06)
Duration of disease (years)	4.56 ± 2.48	4.12 ± 2.19	0.195
History of using herbal medicine	14 (21.88)	18 (28.13)	0.414
Smoking history	22 (34.38)	19 (29.69)	0.570
Drinking history	26 (40.63)	24 (37.50)	0.717
Mean VAS score (cm)
Global IBS-D symptoms	6.86 ± 1.48	7.16 ± 1.36	0.146
Abdominal pain	5.52 ± 1.53	5.34 ± 1.47	0.407
Bloating	5.24 ± 1.32	5.06 ± 1.38	0.358
Urgency	5.88 ± 1.28	6.06 ± 1.40	0.354
Tiredness	4.14 ± 1.45	4.38 ± 1.52	0.265
Mean weekly stool frequency	16.26 ± 3.43	15.52 ± 3.51	0.142
Mean weekly Bristol score	6.03 ± 0.82	6.09 ± 0.77	0.657

Data were showed as n (%) or mean ± SD. BMI: Body mass index; VAS: Visual analog scale; IBS-D: Diarrheal irritable bowel syndrome.

Clinical effectiveness

After treatment, the distribution of the outcomes in the research group was as follows: Recovery, n = 21 (32.81%); remarkable effect, n = 20 (31.25%); effective treatment, n = 18 (28.13%); and invalidity, n = 5 (7.81%). The distribution of outcomes in the control group was as follows: Recovery, n = 14 (21.87%); marked improvement, n = 16 (25.00%); partial efficacy, n = 19 (29.69%); and ineffectiveness, n = 15 (23.44%). A significantly superior overall efficacy was achieved in the research group (92.19%) compared to the control group (76.56%; P = 0.015; Table 2).

Table 2 Comparison of overall efficacy between two groups of patients, n (%).

Classification	Recover	Remarkable effect	Efficiently	Not valid	Total effective number
Research group (n = 64)	21 (32.81)	20 (31.25)	18 (28.13)	5 (7.81)	59 (92.19)
Control group (n = 64)	14 (21.87)	16 (25.00)	19 (29.69)	15 (23.44)	49 (76.56)
χ2					5.926
P value					0.015

TCM syndrome points

Before treatment, no significant differences were found between the 2 groups in terms of individual TCM symptom scores and total scores (13.52 ± 3.39 vs 13.75 ± 3.46; P > 0.05). After treatment, both groups exhibited a significant decrease in individual symptom scores and total scores, and the mean total score in the research group (5.07 ± 3.11 vs 7.38 ± 3.68) was significantly lower than that in the control group (P < 0.001; Table 3).

Table 3 The two patient groups were compared regarding their traditional Chinese medicine syndrome points (mean ± SD).

Classification treatment		Research group (n = 64)	Control group (n = 64)	t value	P value
Abdominal pain decreases after diarrhea	Before	3.12 ± 1.36	3.04 ± 1.21	0.431	0.668
	After	1.06 ± 0.78	1.61 ± 0.67	5.241	< 0.001
Irritable	Before	3.38 ± 1.64	3.44 ± 1.53	0.262	0.794
	After	1.36 ± 1.19	1.87 ± 1.02	3.188	0.002
Distension and fullness of both hypochondria regions	Before	2.32 ± 1.03	2.51 ± 1.12	1.223	0.223
	After	0.81 ± 0.72	1.27 ± 0.87	3.991	< 0.001
Anorexia	Before	2.63 ± 0.94	2.52 ± 1.08	0.753	0.453
	After	0.97 ± 0.39	1.32 ± 0.37	6.38	< 0.001
Tiredness and fatigue	Before	2.17 ± 0.88	2.24 ± 0.95	0.53	0.597
	After	0.89 ± 0.67	1.18 ± 0.73	2.868	0.005
Total points	Before	13.52 ± 3.39	13.75 ± 3.46	0.465	0.643
	After	5.07 ± 3.11	7.38 ± 3.68	4.698	< 0.001

Inflammatory factors and intestinal mucosal barrier function

Before the intervention, no statistically significant differences (P > 0.05) were observed in the baseline levels of inflammatory factors (TNF-α, IL-6, and IL-10) between the two groups. After intervention, the levels of TNF-α (18.80 ± 4.02 ng/L vs 21.09 ± 4.10 ng/L, P = 0.002; IL-6 (14.84 ± 4.06 ng/L vs 19.80 ± 4.42 ng/L; P < 0.001) levels were significantly lower and IL-10 (48.53 ± 5.02 ng/L vs 46.06 ± 4.94 ng/L; P = 0.006) levels were significantly higher in the research group than those in the control group. In addition, before treatment, no statistically significant differences were found between the two groups in the indicators of intestinal mucosal barrier function, including DAO, D-lactate, and LPS levels (P > 0.05). After treatment, the levels of DAO (6.53 ± 2.35 ng/mL vs 7.66 ± 2.40 ng/mL; P = 0.008), D-lactate (0.18 ± 0.04 mmol/L vs 0.20 ± 0.06 mmol/L; P = 0.004), and LPS (44.77 ± 8.16 pg/mL vs 48.20 ± 8.15 pg/mL; P = 0.019) in the research group were significantly lower than those in the control group (Figure 1).

Figure 1 Inflammatory factors and indicators of intestinal mucosal barrier function. A-C: Inflammatory factor levels: Tumor necrosis factor-α levels before and after treatment (A); Interleukin-6 levels before and after treatment (B); and interleukin-10 levels before and after treatment (C); D-F: Indicators of intestinal mucosal barrier function: Diamine oxidase levels before and after treatment (D); D-lactate levels before and after treatment (E); Lipopolysaccharides levels before and after treatment (F). ^aP < 0.05; ^bP < 0.01; ^cP < 0.001. NS: Not significant; TNF-α: Tumor necrosis factor-α; IL-6: Interleukin-6; IL-10: Interleukin-10; DAO: Diamine oxidase; LPS: Lipopolysaccharides.

Psychological condition

Before the intervention, the 2 groups exhibited comparable baseline levels for both SAS (45.16 ± 8.07 vs 46.17 ± 7.69) and SDS (43.77 ± 7.32 vs 44.17 ± 6.61) scores, with no statistically significant differences (P > 0.05). After intervention, SAS and SDS scores of the 2 groups were significantly decreased, and the SAS (37.33 ± 5.73 vs 39.59 ± 6.36; P = 0.036) and SDS scores (34.77 ± 6.71 vs 38.06 ± 6.52; P = 0.006) were significantly lower in the research group than in the control group (Figure 2).

Figure 2 Psychological state score. A: Self-rating anxiety scale scores before and after treatment; B: Self-rating depression scale scores before and after treatment. ^aP < 0.05; ^bP < 0.01. NS: Not significant; SAS: Self-rating anxiety scale; SDS: Self-rating depression scale.<br/>

Relapse rate

Patients who received effective treatment in both groups were followed up for 2 months after the end of the treatment course. The recurrence rate in the research group was 18.64% (11/59), which was significantly lower than that of the control group [40.82% (20/49)], and the difference was statistically significant (P = 0.011; Table 4).

Table 4 Recurrence rates compared between the two patient groups, n (%).

Classification	Effective number	Number of non-relapses	Number of relapses
Research group (n = 64)	59 (92.19)	48 (81.36)	11 (18.64)
Control group (n = 64)	49 (76.56)	29 (59.18)	20 (40.82)
χ2			6.430
P value			0.011

DISCUSSION

The results of the present study demonstrated that the treatment of IBS-D with Xifeng Huashi resulted in significantly better outcomes than conventional Western medicine in improving clinical symptoms, regulating intestinal inflammation and barrier function, relieving unfavorable psychological status, and reducing recurrence rates. The results demonstrated that the total effective rate in the Xifeng Huashi prescription group (92.19%) was significantly higher than that in the conventional Western medicine group (76.56%), and the improvement in the TCM symptom score was significantly better (P < 0.05). Western drugs relieve symptoms mainly by regulating the intestinal flora and relieving intestinal smooth muscle spasms; however, their impact on disease pathogenesis is relatively limited[25,26]. In contrast, the Xifeng Huashi prescription is based on TCM theories in which Paeonia lactiflora and Crocus sativus synergistically play a role in soothing the liver and extinguishing wind, whereas Atractylodes macrocephalus and Tribulus terrestris synergistically play a role in strengthening the spleen to expel dampness. White ginger grass and licorice remove heat and toxins and harmonize the effects of other herbs[27-29]. This multi-target, all-encompassing approach to regulation may be the key to the remarkable clinical efficacy of Xifeng Huashi. Patients with IBS-D often exhibit increased intestinal mucosal permeability, leading to bacterial translocation and immune activation[30,31]. Modern pharmacological studies have shown that Paeoniflorin can alleviate visceral hypersensitivity by modulating intestinal 5-hydroxytryptamine [5-HT (i.e., serotonin)] signaling, baicalin inhibits the TLR4/NF-κB pathway to reduce intestinal inflammation, and Atractylodis macrocephalae polysaccharide enhances intestinal tight junction protein expression and repairs the intestinal mucosal barrier[27,28,32]. TNF-α and IL-6 are key pro-inflammatory cytokines that are often significantly elevated in patients with IBS-D, participating in the pathological processes of intestinal mucosal inflammation and visceral hypersensitivity. IL-10, on the other hand, possesses anti-inflammatory and immunomodulatory effects, and elevated levels help suppress excessive inflammatory responses and promote tissue repair. The results of this study indicate that compared with the control group, patients in the Xifeng Huashi treatment group exhibited significantly reduced levels of the pro-inflammatory factors TNF-α and IL-6 in serum, while levels of the anti-inflammatory factor IL-10 were significantly elevated. This suggests that Xifeng Huashi may improve the clinical symptoms of IBS-D by regulating the inflammatory balance and alleviating intestinal inflammatory states. LPS is a component of the cell wall of gram-negative bacteria, and elevated levels indicate impaired intestinal barrier function and bacterial translocation. DAO and D-lactic acid are key biomarkers reflecting the integrity and permeability of the intestinal mucosa. The research findings indicated that post-treatment serum levels of LPS, DAO, and D-lactic acid were significantly lower in the research group than in the control group. Improvements in these indicators suggest that Xifeng Huashi reduces endotoxin entry into the bloodstream and systemic inflammatory responses by repairing the intestinal mucosal barrier and lowering intestinal permeability. This aligns with its clinical efficacy in alleviating diarrhea and abdominal pain.

Anxiety and depression comorbidities are common in patients with IBS-D[33,34]. In this study, we found that Xifeng Huashi significantly reduced the SAS and SDS scores of patients with IBS-D, and its effect was more pronounced than that of conventional Western medicine. According to TCM, the liver is the main regulator of excretion, and emotional upset results in liver qi stagnation, which multiplies the spleen and causes diarrhea. This formula improves the mental state of patients by soothing the liver and regulating qi. In addition, from the perspective of modern mechanisms, the inflammatory factors IL-6 and TNF-α can cross the blood-brain barrier and affect central neurotransmitters, such as 5-HT and gamma aminobutyric acid (i.e., gamma-aminobutyric acid). In the present study, this formula significantly reduced IL-6/TNF-α and elevated the anti-inflammatory factor IL-10, suggesting that it may treat both body and mind by suppressing the positive feedback loop of “intestinal inflammation - brain-gut axis disorder”.

After 2 months of treatment, the recurrence rate in the research group (18.64%) was significantly lower than that in the control group (40.82%; P = 0.011), suggesting that Xifeng Huashi may have lasting efficacy. Although Western drug treatment can relieve smooth muscle spasms in the short term, it does not fundamentally regulate the intestinal microecology and neuroimmune network. Huanglian, Scutellaria baicalensis, and Septoria inhibit the proliferation of pathogenic bacteria and promote colonization by probiotics, whereas Chenpi and Muxiang regulate intestinal motility rhythms and reduce recurrent episodes of diarrhea. In addition, improvements in psychological state may reduce recurrence by reducing the stress response[35]. These results highlight the long-term value of TCM in chronic disease management.

Limitations to the current first-line treatments for IBS-D are that antispasmodic drugs exert side effects on the central nervous system and that rifaximin may induce drug resistance with long-term use[36]. As a natural compound preparation, the multi-component and multi-target mode of action of Xifeng Huashi is consistent with the multifactorial pathogenesis of IBS-D. It is noteworthy that Xifeng Huashi improved physical symptoms while simultaneously regulating psychological status.

Limitations

This study provides a multidimensional, evidence-based rationale for the treatment of IBS-D using Xifeng Huashi. However, this study has some limitations. The relatively small sample size and relatively short study period did not allow further confirmation of the efficacy and safety of Xifeng Huashi prescription; therefore, a larger, multicenter, long-term follow-up study is needed. The specific mechanism of action of Xifeng Huashi in IBS-D requires further exploration at the molecular and cellular levels. Future studies should use advanced techniques, such as gene chip analysis and proteomics, to elucidate the exact mechanisms(s). In addition, this study mainly focused on the improvement of mental status in patients with IBS-D; however, the relationship between mental status and gut microbiota merits further in-depth study. Future studies should explore the bidirectional regulatory mechanisms between Xifeng Huashi prescriptions, gut microbiota, and mental status.

CONCLUSION

Xifeng Huashi is effective in the treatment of IBS-D and has advantages in improving clinical symptoms and mental status and reducing the short-term relapse rate. Its multi-target mechanism involves regulating inflammation, restoring intestinal barrier integrity, and modulating the gut-brain axis, highlighting its potential as a comprehensive treatment approach for IBS-D. However, further mechanistic studies and optimization of therapeutic regimens are required.