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Abstract

The study aimed to evaluate the impact of combining silibinin capsules with Jiangzhi Paizhuo Decoction (JZPZ) versus silibinin capsules alone in patients with MAFLD. The research was carried out at the Xi'an Hospital of Traditional Chinese Medicine using a case-control design following to STROBE guideline. Eligible participants meeting the inclusion criteria were randomly allocated into two groups. The participants in control group and intervention group were assigned to receive oral administration of 70 mg (3 times daily) silibinin capsules or 70 mg silibinin capsules (3 times daily) plus colon dialysis with 150 ml JZPZ decoction for 8 weeks. The primary outcome and secondary outcome on the effects of JZPZ decoction in MAFLD were detected. We found that liver function significantly improved in both groups after treatment (p < 0.05) compared with the baseline. Importantly, JZPZ decoction was associated with significant decrease in hepatic steatosis (CAP changes: −18.91 ± 11.50 vs −26.86 ± 16.62, P = 0.0305). The JZPZ decoction reduced significantly the TCM syndromes score compared to control (−5.74 ± 0.95 versus −7.17 ± 1.23, P < 0.0001). Meanwhile, the weight and BMI in JZPZ group increased significantly more than control group (P = 0.0003, P < 0.0001). In conclusion, the JZPZ decoction combined with silibinin capsules in the treatment of MAFLD patients with liver depression and heat syndrome has more advantages in decreasing hepatic steatosis and TCM syndromes scores. It is worthy of clinical recommendation.

Keywords

Metabolic associated fatty liver disease (MAFLD)traditional Chinese medicine (TCM)Jiangzhi Paizhuo decoction (JZPZ)hepatic steatosis liver stiffness

Highlight

Liver function significantly improved in both groups after treatment.

The JZPZ decoction significantly decreased hepatic steatosis.

Changes of TCM syndromes score were more remarkable in JZPZ decoction treatment.

Introduction

Nonalcoholic fatty liver disease (NAFLD), characterized by an abnormal buildup of fat in liver and associated with metabolic dysfunction, affects a worldwide 30% of the population and is increasing.¹ In 2020, experts have reached consensus that metabolic associated fatty liver disease (MAFLD) was suggested as a more appropriate overarching term than NAFLD, which does not reflect current knowledge.² The MAFLD has become the most important cause of chronic liver disease and contributes to an increased liver-related mortality and morbidity. This will have an important impact on public health, however, there is still no approved drug therapy. As a greater understanding of the causes and progression of metabolic liver diseases has emerged, researchers have started to re-evaluate natural products as potential therapies for liver diseases. Natural products can serve as a vast platform that may provide a good alternative with comparable safety but lower costs.³

In China, Silybum marianum, a member of the asteraceae family, is a traditional Chinese medicine (TCM) herb with a 2200-year history. Silybum marianum fruits contain a mixture of flavonolignans collectively known as silymarin, in which silybin (also named silibinin) is the main component accounting for 50%–70%.⁴ According to reports, silymarin has been shown to possess various pharmacological properties, such as reducing blood lipid levels, acting as an antioxidant, preventing the onset of diabetes, exhibiting anti-inflammatory effects, inhibiting the growth of certain tumors, providing neuroprotection, and regulating the immune system.^5–8 Additionally, silybin has a hepatoprotective effect by reducing the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), and TG (triglyceride) in the NAFLD mice model, and also lowering the levels of high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C).⁹ The use of silibinin capsules, which is a silybin-phospholipid complex containing silybin as its main active component, has been established as an effective treatment option for various liver diseases, such as MAFLD or hepatic steatosis.^10,11

However, many MAFLD patients have excessive intestinal gas production such as constipation, bloating or diarrhea. Therefore, colon dialysis with Chinese herbs was administered to the comprehensive treatment for MAFLD patients by gut-targeted interventions in our hospital. Jiangzhi Paizhuo Decoction (JZPZ) is a traditional Chinese medicine based on “Sangming Heji (SMHJ)”,¹² developed by Dr Yang Zhen who was dubbed by government as the “master of TCM”. The SMHJ is an empirical formula for treating MAFLD under the guidance of TCM theory, which has been applied in the treatment of liver disease for more than 60 years. It can enhance the functions of clearing liver heat, promote bowel movements, and eliminate dampness. As a representative formula for treating MAFLD liver depression and heat pattern in the national key specialty of liver disease, it has been applied in clinical practice for more than 10 years with significant therapeutic effects.¹³ Generally, colon cleansing refers to colonic irrigation or hydrotherapy, a process where the large intestine is flushed out with a water-based liquid to remove waste. However, there has been a lack of evidence-based research on the therapeutic effects of JZPZ Decoction.

It is well known that MAFLD can be assessed by measuring the extent of fat deposition in the liver, assessing the possible presence of metabolic and cardiovascular risk factors and complications, evaluating the degree of liver inflammation and damage, and examining for the presence of other underlying liver conditions.¹⁴ Additionally, the degree of liver fibrosis can also be evaluated to determine the overall severity of the condition. To obtain a better understanding the therapeutic effects of JZPZ decoction, the present study aimed to observe changes in metabolomics, TCM symptom scores, BMI index, biochemical indicators, as well as imaging results in MAFLD patients with liver depression and heat syndrome.

Methods

Subjects

The present study was conducted in the Xi'an Hospital of Traditional Chinese Medicine with a case–control design according to STROBE guideline. The participants in this study were recruited through random sampling from December 2021 to November 2022. They were diagnosed as MAFLD patients (18-65 years old) referring to “Guiding Principles for Clinical Research of new TCM drugs” promulgated by the Ministry of Health in 2002, the classification criteria in the textbooks of “ TCM Internal Medicine “ and “ TCM Diagnosis”, as well as “Diagnosis and Treatment Guidelines for Non-Alcoholic Fatty Liver Disease”.

The inclusion criteria for this study: (1) No use of antibiotics within the past two months. (2) No excessive alcohol consumption or overeating in the past two weeks. (3) Serum aspartate aminotransferase (AST) ≤ 2 times the upper limit of normal, alanine aminotransferase (ALT) ≤ 2 times the upper limit of normal, and total bilirubin (TBIL) ≤ 2 times the upper limit of normal. (4) Absence of other liver disorders, malignancies, cardiovascular, respiratory and kidney disorders, no history of weight loss or bariatric surgery in recent years. Exclusion criteria: pregnancy or breastfeeding; patients who have already used other drugs for the treatment of MAFLD; Long-term history of alcohol consumption, usually exceeding 5 years, with an equivalent amount of ethanol in men of 40 g/day and in women of 20 g/day; or a recent history of heavy alcohol consumption within 2 weeks with an equivalent amount of ethanol >80 g/day.

Trial Design

Eligible participants who met inclusion criteria were randomly divided into two groups. The participants in control group were assigned to receive oral administration of 70 mg (3 times daily) silibinin capsules with one capsule containing 35 mg silybin (H20040299, Tasly, Tianjin, China) for 8 weeks. The participants in intervention group were assigned to receive oral administration of 70 mg silibinin capsules (3 times daily, H20040299, Tasly, Tianjin, China) plus colon dialysis with 150 ml JZPZ decoction (0.375 g/mL, once a week, Xi'an Hospital of Traditional Chinese Medicine, Xi’an, China) for 8 weeks.

The JZPZ prescriptions was composed of Bupleurum chinense (Chinese thorowax root), Scutellaria baicalensis Georgi (baical skullcap root), the leaves of Morus alba L. (mulberry leave), Flos Chrysanthemi (chrysanthemum flower), Catsia tora Linn (sickle senna seed) and so on. These combined mixture of herbs (total 150 g, serves 1) were soaked for about 30 min in cold water and boiled twice. For the first time, added 1800 mL water, brought to boil over big fire, then simmered over medium-low fire for about 2 h and poured the decoction immediately. For the second time, added 1500 mL water, brought to boil over big fire, then simmered over medium-low fire for about 1.5 h and poured the decoction immediately. Finally, mixed the decoction from the first and second time and concentrated into 400 mL (0.375 g/mL).

Outcomes

In the present study, the effects of JZPZ decoction on liver function tests were the primary outcome. Secondary outcome measures were blood lipid, blood sugar, liver stiffness and fatty changes, and TCM syndrome score. All biochemical tests were precisely assessed in the same laboratory.

Demographic Features, Liver and Renal Function Tests

Weight and height were measured by standard procedures for all patients at the baseline and the end of trail (after 8 weeks). Body mass index (BMI) was calculated as weight (kilograms) divided by the square of height (meters). After 12 h fasting, serum concentration of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), and γ-glutamyl transferase (GGT) were assessed using enzymatic methods at baseline and after 8 weeks of the intervention in all patients. In addition, the concentration of uric acid (UA) was assessed in the morning at baseline and after 8 weeks of the intervention in all patients.

Lipid Profile and Fasting Blood Glucose

After 12 h fasting, serum concentration of triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), cholesterol (CHOL) as well as glucose (GLU) and insulin (INS) in the morning were assessed using an auto analyzer (Hitachi 7170, Hitachi, Tokyo, Japan) at baseline and after 8 weeks of the intervention in all patients.

Hepatic Fibrosis and Steatosis

At the began and the end of study, hepatic fibrosis and steatosis were evaluated using Fibroscan^®. FibroScan is a special ultrasound technology that measures liver stiffness (hardness) and fatty changes in liver. Controlled attenuation parameter（CAP）score was measured in decibels per meter (db/m), suggesting how much of the liver was affected by fat buildup. A score below 238 db/m means the amount of fatty change in liver is not higher than normal. CAP < 238 dB/m denoted no hepatic steatosis, 238 ≤ CAP ≤ 259 dB/m denoted mild, 259 < CAP ≤ 291 dB/m denoted moderate, and CAP > 291 dB/m denoted severe hepatic steatosis.¹⁵ The liver stiffness result was measured in kilopascals (kPa, E). Normal results were usually between 2 and 7 kPa. When the result was higher than the normal range, liver disease maybe happened. This assay was performed by the same operator in our hospital.

TCM Syndrome Scales

Moreover, clinical syndrome of TCM in all participants was evaluated using a questionnaire (Table 1). Severities ranged from no symptoms to continuous lasting are divided into 6 classes (1 to 6 points score), and the higher score means the higher severe symptoms. This questionnaire was all self-rating scale completed by the patients themselves, and the investigators provided the necessary guidance and instructions to the patients. The TCM syndromes index = [(A_{the total TCM syndromes scores before treatment}-B_{the total TCM syndromes scores after treatment}) / A_{the total TCM syndromes scores before treatment}] × 100%. Clinical control is defined as ≥ 95% decrease in the TCM syndromes score; obvious improvement as ≥ 70% and < 95% decrease; “effective” as ≥ 30% and < 70% decrease, and ineffective as < 30% decrease.

Table 1.

Traditional Chinese Medicine Syndrome Questionnaire.

Primary syndrome	Score grading
Primary syndrome	0	2	4	6
Pain in the chest and rib-side	NO	Mild pain	Moderate pain	Severe pain, become unbearable
Secondary syndrome	Score grading
Secondary syndrome	0	1	2	3
Dry eyes	NO	Dry eyes without blurry vision	Dry eyes with blurry vision	Dry eyes with blurry vision and conjunctival congestion
Bitter taste and dry mouth	NO	Bitter taste only in the morning	Frequent bitter taste	Frequent bitter taste becomes more severe
Emotional symptoms	NO	Irritability, cannot interfere with daily life	Irritability, interfere with daily life	Irritability, easily angered, seriously interfere with daily life
Abdominal distention and fullness	NO	Now and then	Last for less than 6 h every day	Last for over 6 h every day
Dizziness, tinnitus	NO	Occasionally	Intermittently	Often
Yellow urine	NO	Yellow, alleviates after drinking water	Yellow, have not alleviates after drinking water	Dark urine, have not alleviates after drinking water

Statistical Analyses

Graphpad prism 6.0 for windows software (GraphPad Software, San Diego, California USA) was used for data analysis. Data are exhibited as mean ± standard deviation (SD). The normality of distribution of variables was assessed by Kolmogorov-Smirnov and Shapiro-Wilk tests. T test or non-parametric test will be used for quantitative data, while chi-square test will be used for qualitative data. If distribution of data was normal, paired t test (before treatment vs after treatment in the same group) or student t test (control vs intervention group) were used to compare variables within and between groups, respectively. But if not, Wilcoxon and Mann-Whitney U tests was used. Moreover, the participants with BMI have been stratified in data analysis according to the healthy weight range (BMI ≤ 23.9 kg/m²), overweight (23.9 < BMI < 28 kg/m²), and obesity (BMI ≥ 28 kg/m²) to control the impact of obesity as the confounding factor. T-test was used. Statistically significance was presented as p value < 0.05.

Results

Baseline Characteristics of Patients in Both Groups

In this study, 112 participants were enrolled. In the control group, three patients who did not receive treatment and medication on time, lost to follow-up; two patients underwent surgery during the treatment period, and then their treatments were terminated; two patients were found to have incomplete data and input errors during the analysis. Therefore, total 43 patients were finally included in the control group. After colon dialysis, 3 people were unwilling to continue treatment, and one patient could not come to the hospital on time due to work reasons and epidemic reasons; the other 3 patients lost to follow-up. One person's data was incomplete during the analysis. Finally, total 42 patients were included in JZPZ group. Additionally, the included or excluded reasons of participants are shown in Figure 1. Finally, 85 patients completed the study in specified period. No participants reported any adverse effects, suggesting JZPZ decoction was safe. Baseline characteristics of participants are shown in Table 2. There were not any significant differences between two groups in age, sex, demographic features, liver and renal function indices, blood lipid and sugar level, as well as hepatic fibrosis and steatosis before the intervention (Table 2).

Figure 1.

The flow chart of the study.

Table 2.

Clinical and Biochemical Features in Subjects at Baseline in Patients with MAFLD.

Variables	Control (n = 43, mean ± SD)	JZPZ Treatment (n = 42, mean ± SD)	P value
Age (year)	44.70 ± 14.22	45.02 ± 14.31	0.9703
Sex (male, n,(%))	28(64.12%)	27(64.29%)	0.9361
Weight (kg)	81.88 ± 17.12	81.18 ± 18.10	0.8540
BMI (kg/m²)	27.79 ± 4.04	27.95 ± 4.03	0.8617
TB (μmol/L)	18.72 ± 7.80	18.67 ± 7.42	0.9599
ALT (U/L)	78.02 ± 54.09	77.63 ± 72.99	0.5018
AST (U/L)	46.78 ± 29.68	45.93 ± 24.64	0.8354
GGT (U/L)	66.42 ± 49.94	81.14 ± 80.35	0.7150
CHOL (mmol/L)	5.18 ± 0.898	5.02 ± 0.96	0.4271
UA (μmol/L)	429.1 ± 92.88	425.6 ± 95.13	0.8633
GLU (mmol/L)	5.86 ± 0.98	6.07 ± 1.79	0.7512
TG (mmol/L)	2.56 ± 1.54	2.41 ± 0.99	0.7512
HDL-C (mmol/L)	1.28 ± 0.26	1.34 ± 0.68	0.9425
LDL-C (mmol/L)	2.77 ± 0.69	2.63 ± 0.73	0.3596
INS (mmol/L)	14.11 ± 5.52	13.80 ± 6.11	0.5387
CAP (db/m)	297.7 ± 52.05	287.2 ± 47.99	0.1875
E (kPa)	8.81 ± 4.30	8.06 ± 4.25	0.3430
score	9.47 ± 1.47	9.88 ± 1.69	0.2249

MAFLD, metabolic associated fatty liver disease; BMI, body mass index; ALT, aminotransferase; AST, aspartate aminotransferase; TB, total bilirubin; GGT, γ-glutamyl transferase; UA, uric acid; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; CHOL, cholesterol; GLU, glucose; INS, insulin; E, elasticity; CAP, controlled attenuation parameters.

In addition, there were any systematic differences related to the outcome or exposures between those who completed the study and those who were lost to follow-up in Figure 1. Patients who were lost to follow up were younger than those who completed the study. Clinical outcome and TCM syndrome scales were better in those who were lost to follow-up than those who completed the study. Baseline characteristics of participants who were lost to follow-up are shown in Supplementary Table 1.

Comparison of Changes Before and After Treatment Between two Groups of Patients

As shown in Table 3, there were significant decrease in the weight and BMI within both groups (P < 0.0001); the weight and BMI in JZPZ group increased significantly more than control group (P = 0.0003, P < 0.0001). There was significant decrease in the liver and renal function within both groups (P < 0.0001), however, there was no significant difference between changes in two groups (P > 0.05). Similarly, significant decrease in the blood lipid and sugar level within both groups (P < 0.0001) but no significant difference between changes in two groups (P > 0.05), except for CHOL changes between two groups (P = 0.0185).

Table 3.

Clinical Characteristic Changes After 8 Weeks of Intervention in Patients with MAFLD.

Variables	Baseline (mean ± SD)	After 8 weeks (mean ± SD)	P^a	Changes (mean ± SD)	P^b
Weight (kg)
Control	81.88 ± 17.12	78.97 ± 15.53	<0.0001	−2.91 ± 2.73	0.0003
JZPZ Treatment	81.18 ± 18.10	76.41 ± 16.38	<0.0001	−6.57 ± 6.20
BMI (kg/m²)
Control	27.79 ± 4.04	26.83 ± 3.65	<0.0001	−0.96 ± 0.88	<0.0001
JZPZ Treatment	27.95 ± 4.03	25.68 ± 3.41	<0.0001	−2.27 ± 2.17
TB (μmol/L)
Control	18.72 ± 7.80	14.75 ± 4.99	<0.0001	3.97 ± 5.90	0.1017
JZPZ Treatment	18.67 ± 7.42	13.64 ± 4.92	<0.0001	−5.03 ± 4.15
ALT (U/L)
Control	78.02 ± 54.09	46.07 ± 27.97	<0.0001	−31.95 ± 34.00	0.4743
JZPZ Treatment	77.63 ± 72.99	33.56 ± 22.06	<0.0001	−44.07 ± 54.18
AST (U/L)
Control	46.78 ± 29.68	31.91 ± 17.36	<0.0001	−14.87 ± 17.33	0.1193
JZPZ Treatment	45.93 ± 24.64	24.74 ± 9.20	<0.0001	−21.19 ± 19.79
GGT (U/L)
Control	66.42 ± 49.94	48.77 ± 32.71	<0.0001	−17.65 ± 21.64	0.1995
JZPZ Treatment	81.14 ± 80.35	43.14 ± 28.62	<0.0001	−38.00 ± 58.62
CHOL (mmol/L)
Control	5.18 ± 0.898	4.85 ± 0.72	0.0002	−0.33 ± 0.52	0.0185
JZPZ Treatment	5.02 ± 0.96	4.30 ± 0.77	<0.0001	−0.72 ± 0.72
UA (μmol/L)
Control	429.1 ± 92.88	393.1 ± 95.91	<0.0001	−36.00 ± 40.04	0.4609
JZPZ Treatment	425.6 ± 95.13	379.2 ± 78.54	<0.0001	−46.38 ± 53.22
GLU (mmol/L)
Control	5.86 ± 0.98	5.56 ± 0.60	0.0046	−0.30 ± 0.66	0.1996
JZPZ Treatment	6.07 ± 1.79	5.31 ± 0.56	<0.0001	−0.76 ± 1.75
TG (mmol/L)
Control	2.56 ± 1.54	2.10 ± 1.19	<0.0001	−0.45 ± 0.63	0.6507
JZPZ Treatment	2.41 ± 0.99	1.89 ± 0.73	<0.0001	−0.52 ± 0.58
HDL-C (mmol/L)
Control	1.28 ± 0.26	1.373 ± 0.32	0.0073	0.09 ± 0.21	0.1026
JZPZ Treatment	1.34 ± 0.68	1.52 ± 0.52	<0.0001	0.18 ± 0.34
LDL-C (mmol/L)
Control	2.77 ± 0.69	2.52 ± 0.65	0.0031	−0.25 ± 0.59	0.1094
JZPZ Treatment	2.63 ± 0.73	2.16 ± 0.61	<0.0001	−0.47 ± 0.44
INS (mmol/L)
Control	14.11 ± 5.52	12.32 ± 3.96	<0.0001	−1.78 ± 2.23	0.3634
JZPZ Treatment	13.80 ± 6.11	10.30 ± 2.30	<0.0001	−3.50 ± 4.51
CAP (db/m)
Control	297.7 ± 52.05	278.8 ± 47.21	<0.0001	−18.91 ± 11.50	0.0305
JZPZ Treatment	287.2 ± 47.99	260.4 ± 44.45	<0.0001	−26.86 ± 16.62
E (kPa)
Control	8.81 ± 4.30	8.05 ± 3.41	<0.0001	−0.76 ± 1.50	0.8660
JZPZ Treatment	8.06 ± 4.25	7.08 ± 3.19	<0.0001	−0.98 ± 1.22
score
Control	9.47 ± 1.47	3.72 ± 0.91	<0.0001	−5.74 ± 0.95	<0.0001
JZPZ Treatment	9.88 ± 1.69	2.71 ± 0.74	<0.0001	−7.17 ± 1.23

P values indicate comparison within groups.

P values indicate comparison between the changes of each variable between two groups.

The JZPZ decoction was associated with significant decrease in hepatic steatosis (CAP changes: −18.91 ± 11.50 vs −26.86 ± 16.62, P = 0.0305). Moreover, JZPZ decoction reduced significantly the TCM syndromes score compared to control (−5.74 ± 0.95 versus −7.17 ± 1.23, P < 0.0001). In the control group, there was only 60% decrease in the TCM syndromes score (effective). However, 72.6% decrease in the TCM syndromes score was found in JZPZ treatment group (obvious improvement).

Besides, To control the impact of obesity as the confounding factor, the participants with BMI have been stratified in data analysis according to the healthy weight range (BMI ≤ 23.9 kg/m²), overweight (23.9 < BMI < 28 kg/m²), and obesity (BMI ≥ 28 kg/m²). In the three different BMI sub-group, there was a statistically negative association between the control and treatment groups (Table 4, all P > 0.05). Therefore, no difference in BMI between the control and treatment groups in each BMI range indicated that BMI was not confounding factor.

Table 4.

the Results of Stratified Analysis Based on BMI.

BMI (kg/m²)	Control (mean ± SD)	JZPZ Treatment (mean ± SD)	P value
≤23.9	21.75 ± 1.60	21.90 ± 1.30	0.853
23.9 < BMI < 28	26.26 ± 1.23	25.78 ± 0.85	0.281
≥28	30.90 ± 2.80	30.70 ± 2.63	0.806

Discussion

A total of 112 patients were recruited in the present study, and 85 MAFLD patients who met the inclusion and exclusion criteria. Finally, there were 42 and 43 patients in the JZPZ group and control group, respectively. After 8 weeks of treatment and 2 years of follow-up time, BMI, the liver and renal function, GLU, TG, CAP and TCM syndromes score in both of JZPZ and control group were significantly decreased when compared with baseline. Moreover, this further study found that some indexes in JZPZ group were significantly better than that of the control group. In particular, the changes of CAP, CHOL, body weight, BMI, and TCM symptom score in the JZPZ group significantly reduced than that of the control group.

The liver function tests are basic tools in the assessment of liver disease. The increase in ALT and AST levels may mean liver damage, liver disease or muscle damage. The NAFLD therapy is associated with improvements in serum ALT levels and weight loss, and that decreases of ALT values into the normal range (to ≤40 U/L and by 30% of baseline) are usually associated with histological improvement in disease activity (steatosis, inflammation, cell injury).¹⁶ As previously reported, in the NAFLD mice model, silibinin capsules have reduced the levels of ALT, AST, TB, HDL-C and LDL-C,⁹ and also markedly decreases HFD-induced hepatic TG accumulation.¹⁰ In the present study, the similar results were found in the MAFLD patients after treatment with SC and JZPZ decoction. For instance, ALT level was 33.56 ± 22.06 U/L after 8-weeks treatment with silibinin capsules plus JZPZ decoction, but ALT level was 77.63 ± 72.99 U/L before treatment (Table 3). In the previous research, the TG accumulation in hepatocytes was the main pathological feature of NAFLD, resulting in steatosis.¹⁷ The content of TG ranged from 2.41 ± 0.99 mmol/L to 1.89 ± 0.73 mmol/L (changes = -0.52 ± 0.58, P < 0.0001) in the trial. However, there was no significant different on TG changes between the control and JZPZ group (P = 0.6507). As the previous study reported, High-CHOL diet was a risk factor of NAFLD development. High-CHOL can spontaneously and sequentially induced fatty liver, steatohepatitis, fibrosis and NAFLD. Furthermore, NAFLD–HCC formation could be completely prevented through anti-CHOL treatment.¹⁸ Therefore, JZPZ decoction combined with silibinin capsules or used silibinin capsules alone can has a hepatoprotective effect in MAFLD patients by improving liver function and reducing blood lipid.

However, we found that the changes of CAP, CHOL, body weight, BMI, and TCM symptom score significantly reduced after JZPZ decoction combined with silibinin capsules treatment than that of only silibinin capsules treatment. Most studies found an association between NAFLD and risk factors such as older age, male sex, higher BMI, diabetes and dyslipidemia.¹⁹ As we known, hepatic CHOL contents also were related to hepatic steatosis.²⁰ Meanwhile, CAP score was a measurement of fatty change in our liver,²¹ and CAP has shown repeatable performance for the detection and semi-quantification of steatosis in several biopsy-controlled clinical studies.²² The meta-analysis also indicated that CAP could be used to identify NAFLD populations, although the cut-off values used for diagnosis may vary with BMI, and so on. therefore, the treatment of JZPZ decoction combined with silibinin capsules in NAFLD patients with liver depression and heat syndrome has more advantages in decreasing hepatic steatosis compared to silibinin capsules alone.

Additionally, there were some limitations in this study. First, the study populations were from a single center based on Chinese population, and the followed-up time was relatively short. The prospective study would be designed in the next step. Larger sample and multicenter long-term follow-up data are needed to support our conclusions in the future. Second, the mechanism of the treatment of MAFLD with JZPZ decoction has not yet been clarified. Previous studies have reported that the development of MAFLD is closely related to the imbalance of gut microbiota.²³ So, we suppose JZPZ decoction is also used to treat MAFLD by regulating intestinal flora, which needs more time to be explored in the further study.

The colon dialysis with JZPZ decoction might act directly on the gut circulation due to deliver the drugs directly to site of action. It avoided the first-pass effect of the liver, improved patient outcomes, and also had good patient compliance. More appropriate therapeutic options would be provided for MAFLD patients who are intolerant to oral administration.

Conclusion

These results confirmed that the therapeutic effects of JZPZ decoction is beneficial in MAFLD patients with liver depression and heat syndrome. JZPZ decoction combined with silibinin capsules in the treatment of MAFLD patients with liver depression and heat syndrome has more advantages in decreasing hepatic steatosis and TCM syndromes score than using silibinin capsules alone.

Supplemental Material

sj-docx-1-npx-10.1177_1934578X241274900 - Supplemental material for Jiangzhi Paizhuo Decoction Combined with Silibinin Capsules Improve the Outcomes of Metabolic Associated Fatty Liver Disease

Supplemental material, sj-docx-1-npx-10.1177_1934578X241274900 for Jiangzhi Paizhuo Decoction Combined with Silibinin Capsules Improve the Outcomes of Metabolic Associated Fatty Liver Disease by Jianmei Hao, Yuanjing Xie, Zhiping Yang, Jianwei Dou, Minghua Mao and Xiaofang Li in Natural Product Communications

Footnotes

Acknowledgements

The authors acknowledge the support from Xi'an Hospital of Traditional Chinese Medicine, and the department of clinical laboratory in our hospital, as well as the nurses in the Department of Hepatology for cooperation.

Author Contributions

HJ was responsible for the study design and manuscript writing. XY did the data collection and data analysis, YZ did the data cleaning and analysis. DJ participated in the study design and manuscript revision. MM and LX participated in the sample collection. All authors contributed to the article and approved the submitted version.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical Approval

The study protocol was approved by the Ethics Committee of Xi'an Hospital of Traditional Chinese Medicine (LLSCPJ2021028、LLSCYJ2021005), Shaanxi Province, China.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Shaanxi Provincial Administration of Traditional Chinese Medicine (grant numbers 2021-GJ-LC005), Xi ‘an Innovation Ability Strong base plan - Medical research project (grant numbers 2021JH-03-0303).

Statement of Human and Animal Rights

All procedures in this study were conducted in accordance with the Ethics Committee of Xi'an Hospital of Traditional Chinese Medicine (LLSCPJ2021028、LLSCYJ2021005)approved protocols. This study does not contain any studies with animal subjects.

Statement of Informed Consent

Informed consent was obtained from each subject who was included in the study.

ORCID iD

Jianmei Hao

Supplemental Material

Supplemental material for this article is available online.

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