Retrospective Study Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2024; 30(45): 4791-4800
Published online Dec 7, 2024. doi: 10.3748/wjg.v30.i45.4791
Effect of Dendrobium nobile powder combined with conventional therapy on mild to moderate fatty liver
Xi Le, Yin Zhang, Mei Yang, Juan Deng, Hong-Min Zhang, Department of Endocrinology, People’s Hospital of Chongqing Liang Jiang New Area, Chongqing 400000, China
Jie Li, The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400000, China
Hao Wang, Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400000, China
Jin-Lin Wu, Department of Endocrinology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400000, China
ORCID number: Xi Le (0000-0001-9684-0167); Hong-Min Zhang (0009-0007-9292-409X).
Co-first authors: Xi Le and Yin Zhang.
Co-corresponding authors: Juan Deng and Hong-Min Zhang.
Author contributions: Le X and Zhang Y designed the research and wrote the first manuscript; Le X, Zhang Y, Yang M, Li J, Wang H, Wu JL, Deng J and Zhang HM contributed to conceiving the research and analyzing data; Le X and Zhang Y conducted the analysis and provided guidance for the research; All authors reviewed and approved the final manuscript.
Supported by the Chongqing Science and Health Joint Medical Research Project, No. 2022MSXM133; and the First Batch of Key Disciplines on Public Health in Chongqing, Natural Science Foundation of Chongqing, No. CSTB2022NSCQ-MSX1522.
Institutional review board statement: This study was approved by the Ethic Committee of People’s Hospital of Chongqing Liang Jiang New Area, No. 2022-11.
Informed consent statement: Due to the retrospective and de-identified nature of this study, written informed consent was waived.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong-Min Zhang, MMed, Attending Doctor, Department of Endocrinology, People’s Hospital of Chongqing Liang Jiang New Area, No. 199 Renxing Road, Renhe Street, Chongqing 400000, China. zhanghongmin0501@163.com
Received: September 6, 2024
Revised: October 23, 2024
Accepted: October 28, 2024
Published online: December 7, 2024
Processing time: 68 Days and 2.6 Hours

Abstract
BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol. Recently, traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver, among which Dendrobium nobile Lindl. powder has been affirmed by many doctors and patients to be effective. However, there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.

AIM

To survey the effect of combining Dendrobium nobile Lindl. powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.

METHODS

Eighty patients with mild to moderate NAFLD participated in this retrospective study, classified into two groups: The observation group (n = 40) and the control group (n = 40). In November 2020 and November 2022, the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area. The control group received standard treatment, while the observation group received Dendrobium nobile Lindl. powder based on the control group. The study compared differences in traditional Chinese medicine clinical syndrome scores, liver fibrosis treatment, liver function indicators, lipid levels, and serum inflammatory factor levels before and after treatment, and we calculated the incidence of adverse reactions for both groups.

RESULTS

The total effective rate was 97.50% in the observation group and 72.5% in the control group. After 8 weeks of treatment, the main and secondary symptom scores remarkably decreased, especially in the observation group (P < 0.05), and there was a significant reduction in the serum levels of hyaluronic acid (HA), laminin (LN), human rocollagen III (PC III), and collagen type IV (CIV). The levels of HA, LN, PC III, and CIV were significantly lower in the observation group (P < 0.05). After 8 weeks, both groups indicated remarkable improvements in liver function and blood lipid levels, with the observation group having even lower levels (P < 0.05). Serum levels of interleukin-1β, tumor necrosis factor-α, and interleukin-8 also dropped significantly. The observation group had a lower rate of adverse reactions (5.00%) compared to the control group (22.50%).

CONCLUSION

Adding Dendrobium nobile Lindl. powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease. It also enhances hepatic function and lipid profile, ameliorates liver fibrosis indices, and lowers the risk of side effects. Consequently, this therapeutic protocol shows promise for clinical implementation and dissemination.

Key Words: Dendrobium nobile Lindl. powder; Nonalcoholic fatty liver disease; Combination treatment; Mild to moderate fatty liver; Liver function; Lipid metabolism disorder

Core Tip: Nonalcoholic fatty liver disease (NAFLD) can progress to hepatitis, liver fibrosis, and eventually liver cancer, threatening patients’ health and well-being. Dendrobium nobile Lindl. is one of the classical and valuable traditional Chinese medicines in China, but its combined effect routine treatment on liver function and lipid metabolism in mild to moderate NAFLD has not been reported. Thus, this study aims to investigate its therapeutic effect and safety.



INTRODUCTION

Nonalcoholic fatty liver disease (NAFLD) is defined as having at least 5% fat in the liver without excessive alcohol consumption[1]. Globally, NAFLD affects about 25% of the population[2]. Over the past decade, the incidence of in China has grown rapidly, peaking at 22.2%, and is projected to rise to an alarming 314.58 million cases by 2030[3,4]. Without effective treatment, NAFLD can progress to hepatitis, liver fibrosis, and eventually liver cancer, posing serious health risks[5]. Despite extensive research and investment by pharmaceutical companies in the field of NAFLD, no specific drugs for NAFLD have been approved, mainly due to the complexity of the disease[6,7].

The “two-hit” hypothesis explains NAFLD development, where the first hit is insulin resistance and fat buildup in the liver, resulting in hepatic steatosis and heightened liver vulnerability. Steatosis occurs due to an imbalance between lipid synthesis and metabolism. Recent evidence suggests that 60%-70% of the fat in NAFLD patients originates from lipolysis in adipose tissue, with a smaller fraction from diet and de novo lipogenesis. High-fat diets promote insulin resistance and fat tissue growth, impairing the insulin sensitivity of hypertrophic adipose tissue, limiting its capacity to store lipids. Consequently, lipolysis intensifies, releasing copious amounts of free fatty acids (FFAs) into the systemic circulation, leading to lipid deposition in the liver, pancreas, and skeletal muscle, resulting in systemic lipo-toxicity[8]. Among them, lipids accumulate in the liver, which can directly induce NAFLD, while a large amount of FFA is enriched in the liver, creating a lipotoxic environment and inducing the “second blow” of the liver. This leads to hepatic mitochondrial dysfunction, manifested by mitochondrial enlargement, reduction in round cristae, and accumulation of typical dense mitochondrial granules[9]. This, in turn, triggers the activation of pro-apoptotic signaling pathways within the B cell leukemia/Lymphoma-2 family, leading to liver cell death[10]. In addition, the liver lipotoxic environment can induce liver inflammation and oxidative stress[11], and activate mitogen-activated protein kinase and other classical inflammatory signal pathways that release inflammatory factors like interleukin (IL)-6 and IL-1β, worsening fat buildup[12,13] and liver damage. Since adipose tissue is the central node of systemic metabolism, to treat NAFLD, it is crucial to improve adipose tissue health, reduce mitochondrial damage, and prevent liver cell death and inflammation.

There is no record of nonalcoholic fatty liver in Chinese medical classics. NAFLD should belong to the category of hypochondriac pain, liver stagnation, phlegm turbidity, accumulation, phlegm swelling, and fat qi in traditional Chinese medicine (TCM) theory[3]. In TCM, the etiology and pathogenesis of NAFLD are multifactorial and involve several interrelated mechanisms. Poor diet (high in fat and sugar), stress, and lifestyle factors such as prolonged immobility, irregular work-rest schedules, and sleep deprivation contribute to liver depression, spleen deficiency, and kidney deficiency, which impair the transport functions of qi, blood, and body fluids, leading to the accumulation of phlegm and blood stasis in the liver, ultimately resulting in NAFLD. During the early stages of NAFLD, it is often characterized by spleen deficiency or excessive dampness, whereas liver depression and phlegm stasis continue throughout the disease course. In advanced stages, kidney deficiency may also develop due to the prolonged disease duration. TCM represents a valuable source of natural bioactive compounds to manage NAFLD. The diverse and complex chemical composition of TCM aligns well with the complex causes of NAFLD, making TCM a promising therapy in addressing the complex and interconnected pathological pathways underlying NAFLD.

Dendrobium nobile Lindl. is one of the classical and valuable TCMs in China. Dendrobium nobile polysaccharide is one of the main effective pharmacological components of Dendrobium nobile Lindl.[14], which has anti-tumor, immune-bossting, antioxidant, and anti-inflammatory effects. At present, the effect of Dendrobium nobile Lindl. powder combined with routine treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD has not been reported, and its therapeutic effect and safety need to be further verified. Therefore, in-depth research is essential.

MATERIALS AND METHODS
General information

Eighty patients with mild to moderate NAFLD were included in this retrospective study, classified into two groups: the observation group (n = 40) and the control group (n = 40). In November 2020 and November 2022, the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area. The control group received standard treatment, and the observation group received Dendrobium powder based on the control group. The control group had 40 participants (23 men and 17 women), and the observation group also had 40 participants (25 men and 15 women). There were no significant difference in the general characteristics of the two groups (Table 1) (P > 0.05).

Table 1 The general information, n (%)/mean ± SD.
Characteristic
Observation group (n = 40)
Control group (n = 40)
χ2/t value
P value
Gender0.2080.648
Male25 (62.50)23 (57.50)
Female15 (37.50)17 (42.50)
Age (years)41.87 ± 5.4942.15 ± 5.820.2210.825
Weight (kg)70.98 ± 5.3771.32 ± 5.140.2890.773
Disease course (years)4.72 ± 0.514.57 ± 0.621.1820.241
Education level0.2810.964
Elementary and junior high school7 (17.50)8 (20.00)
Senior high school13 (32.50)11 (27.5)
Technical secondary school10 (25.00)11 (27.5)
Junior college10 (25.00)10 (25.00)

Inclusion criteria were as follows: (1) All patients were diagnosed with mild to moderate NAFLD upon hospital admission based on liver ultrasound characteristics[15]. Mild fatty liver is characterized by a normal liver shape and size, fine light spots covering two-thirds of the liver parenchyma in the near field, slightly enhanced echo, slightly attenuated echo in one-third of the liver parenchyma in the far field, and clear display of the diaphragm band. In moderate fatty liver, the liver maintains a normal or slightly increased shape and size, with fine light spots present in 1/2 of the liver parenchyma in the near field, enhanced echo, thinner light spots in 1/2 of the liver parenchyma in the far field, and an unclear diaphragmatic band. Severe fatty liver is characterized by a full liver shape, increased volume, dull leaf margins, obvious fine light spots covering the liver parenchyma in the near field, obvious echo enhancement, obvious echo attenuation in the liver parenchyma in the far field, obvious reduction in the tubular results in the liver, thinned and illegible, and an unclear diaphragm light band; (2) All patients were treated for the first time; and (3) Patients with altered liver function and increased serum lipid levels met the criteria for dyslipidemia, which refers to the presence of inherited or acquired abnormalities in lipid metabolism, leading to altered levels and distribution of lipids and their metabolic products in the blood and other tissues and organs[16-18].

Exclusion criteria for this study included the following: (1) Patients with a documented history of drug allergy; (2) Patients with advanced liver cirrhosis; (3) Patients with abnormal renal function; (4) Patients with poor treatment compliance; (5) Patients who have received other treatments within 4 weeks prior to enrollment, and (6) Patients with cognitive impairment or mental disorders. Sample size calculation: With bilateral α set to 0.05 and β set to 0.20, the therapeutic effect (total effective rate) was used as the effect index. An average dropout rate of 10% was considered when calculating the sample size of 36 cases per group. Therefore, each group would include approximately 40 patients, resulting in a total of 80 patients (Figure 1).

Figure 1
Figure 1 Subjects screening enrollment chart.
Methods

The control group received routine western medicine and a low-fat diet, along with liver-protecting and enzyme-lowering treatment. They took polyene phosphatidylcholine capsules (456 mg) orally three times a day and bicyclol (25 mg) three times daily. The observation group received the same treatment as the control group, plus Dendrobium nobile Lindl. powder at a dosage of one bag per administration, three times a day, brewed for half an hour after a meal. Both groups continued this treatment for 8 weeks.

Observation index

Observation index including: (1) Evaluation of clinical curative effect. Clinical cure refers to the control of symptoms, restoration of liver function and blood lipid levels, disappearance of fatty liver, and normalization of liver size by B-ultrasound. Effective treatment means control of symptoms and remarkable improvement in liver function, blood lipid levels, and ultrasound index. Partially effective treatment refers to improvement in clinical symptoms, liver function, blood lipid levels, and ultrasound index. Ineffectiveness is defined as no improvement or worsening of symptoms and no remarkable improvement or aggravation of liver function, blood lipid levels, and ultrasound index. Clinical efficacy was evaluated after 8 weeks of treatment, and the total effective rate = (clinical cured cases + extremely effective cases + effective cases)/total cases × 100%; (2) The improvement of TCM total symptom score before and after treatment was compared. The TCM symptom score standard was jointly established by the members participating in this study and evaluated before and 8 weeks after treatment. Fatigue: Occasional fatigue that goes away on its own (2 points); Fatigue that occurs repeatedly and can be temporarily alleviated by rest (4 points); Persistent and severe fatigue (6 points). Lessened appetite: Reduced food intake by less than 25% (2 points); Reduced food intake by 25%-50% (4 points); Reduced food intake by more than 50% (6 points). Hypochondriac pain: Mild, occasional pain that eases on its own (1 point); Repeated hypochondriac pain (2 points); Persistent hypochondriac pain (3 points). Loose stools: Thin stools, occurring less than 3 times per week and with normal frequency (1 point); Thin stools, occurring 3-5 times per week (2 points); Thin stools, occurring more than 7 times per week (3 points); (3) The index of liver fibrosis. A baseline evaluation was conducted before and 8 weeks after treatment to detect indicators of hepatic fibrosis. A fasting venous blood sample of 5 mL was collected and centrifuged at 3000 r/minute (with a centrifugal radius of 10 cm) for 10 minutes. After separating the serum, levels of serum hyaluronic acid (HA), laminin (LN), human rocollagen III (PC III), and collagen type IV (CIV) were examined by competitive radioimmunoassay. The kits used in this study were provided by the Biotechnology Center of Shanghai Naval Medical Research Institute, and all procedures were carried out in strict accordance with the instructions provided with the kits; (4) Liver function and blood lipid level: Before and 8 weeks after treatment, a fasting venous blood sample of 5 mL was collected from each participant. The sample was centrifuged at 3000 rpm for 10 minutes using a centrifuge with a radius of 10 cm to separate the serum. Glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), total cholesterol (TC), and triglyceride (TG) levels were measured using an automatic biochemical analyzer (Beckman Coulter Biotechnology, Model AU5800) in accordance with the manufacturer’s instructions; (5) The level of serum inflammatory factors. Before and after the treatment, every participant provided a fasting venous blood sample of 5 mL. After collection, the blood was centrifuged at 3000 rpm for 10 minutes in a centrifuge with a radius of 10 cm. The serum levels of tumor necrosis factor-α (TNF-α), IL-1β, and IL-8 were determined using enzyme-linked immunosorbent assays; and (6) Incidence of adverse reactions: The incidence of adverse reactions such as nausea and vomiting, rash, dizziness, and headache during treatment was analyzed and compared using statistical methods. The total incidence of adverse reactions = the sum of all kinds of adverse reactions/the total number of cases × 100%. Nausea is the feeling of discomfort in the stomach that may lead to vomiting. Vomiting is the forceful expulsion of stomach contents through the mouth. Rash refers to various manifestations of skin damage and inflammation. Dizziness is a sensation of lightheadedness, unsteadiness, or disorientation often accompanied by visual disturbance, nausea, or vomiting. Headache refers to pain located between the eyebrow arch and the upper neck (Figure 2).

Figure 2
Figure 2 Technology roadmap. HA: Hyaluronic acid; LN: Laminin; PC III: Human rocollagen III; CIV: Collagen type IV; ALT: Glutamic pyruvic transaminase; AST: Glutamic oxaloacetic transaminase; TC: Total cholesterol; TG: Triglyceride; TNF: Tumor necrosis factor; IL: Interleukin.
Statistical analysis

The data were analyzed and processed by statistical product and service solutions 21.0 statistical software. We used the one-sample Kolmogorov-Smirnov test to examine the normality of continuous variables. A (mean ± SD) symbol is used to indicate measurements with a normal distribution or approximate normal distribution. Comparing the two groups was done using Student’s t tests. Count data were presented as n (%) and analyzed with the χ2 test. P < 0.05 indicates statistically significant differences.

RESULTS
Comparison of therapeutic effects

In the observation group, 25 cases were cured, 8 were extremely successful, 6 were successful, and 1 was unsuccessful, resulting in a total successful rate of 97.50%. In the control group, 18 cases were cured, 7 were extremely successful, 4 were successful, and 11 were unsuccessful, resulting in a total successful rate of 72.5% (P < 0.05). All results are shown in Table 2.

Table 2 The therapeutic effects, n (%).
Group
n
Heal
Remarkable effect
Effective
Invalid
Total efficiency (%)
Observation group4025 (62.50)8 (20.00)6 (15.00)1 (2.50)39 (97.50)
Control group4018 (45.00)7 (17.50)4 (10.00)11 (27.50)29 (72.50)
χ2/t value9.804
P value0.002
TCM syndrome scores before and after treatment

No significant differences were found in the scores of primary and secondary symptoms before treatment (P > 0.05). After 8 weeks of treatment, both primary and secondary symptom scores significantly decreased, with the observation group showing notably lower scores (P < 0.05). All results are presented in Table 3.

Table 3 Traditional Chinese medicine syndrome scores before and after treatment (n = 40, points, mean ± SD).
Group
Main symptoms
Secondary symptoms
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Observation group9.46 ± 1.381.82 ± 0.2915.16 ± 1.391.23 ± 0.231
Control group9.33 ± 1.273.76 ± 0.6625.22 ± 1.422.87 ± 0.712
t value0.43817.0200.19113.898
P value0.662< 0.0001a0.849< 0.0001a
The liver fibrosis before and after treatment

Before treatment, there were no significant differences in the levels of HA, PC III, and CIV (P > 0.05). After 8 weeks of treatment, levels of HA, LN, PC III, and CIV significantly decreased. Furthermore, the observation group demonstrated remarkably lower levels of HA, LN, PC III, and CIV (P < 0.05). All results are shown in Table 4.

Table 4 The liver fibrosis before and after treatment (n = 40, ng/mL, mean ± SD).
Group
Hyaluronic acid
Laminin
PC III
Type IV collagen
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Observation group118.29 ± 20.4168.82 ± 12.361113.86 ± 26.6390.58 ± 9.781110.02 ± 18.8184.35 ± 9.91175.36 ± 13.1860.45 ± 8.481
Control group117.87 ± 20.33108.56 ± 18.812112.91 ± 25.48101.17 ± 25.652109.87 ± 17.7595.52 ± 13.36275.58 ± 14.0471.56 ± 11.512
t value0.09211.1670.1632.4400.0444.2470.0724.915
P value0.927< 0.0001a0.8710.0170.971< 0.0001a0.943< 0.0001a
Comparison of liver function and blood lipid levels before and after treatment

There was no significant difference between ALT, AST, TC, and TG levels before treatment (P > 0.05). After 8 weeks of treatment, both groups showed significant improvements in liver function and blood lipid levels compared to before treatment. Moreover, the observation group demonstrated remarkably lower levels of liver function and blood lipid parameters after treatment (P < 0.05). All results are presented in Table 5.

Table 5 The liver function and blood lipid levels before and after treatment (n = 40, mean ± SD).
Group
ALT (U/L)
AST (U/L)
TC (mmol/L)
TG (mmol/L)
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Observation group78.74 ± 7.7153.35 ± 5.54165.25 ± 8.8334.03 ± 4.0116.09 ± 1.354.03 ± 1.0812.11 ± 0.431.34 ± 0.251
Control group77.78 ± 8.0560.48 ± 6.25264.98 ± 8.9150.82 ± 6.4326.02 ± 1.265.78 ± 1.2222.15 ± 0.291.89 ± 0.342
t value0.5455.3990.13614.0130.2406.7930.4888.243
P value0.588< 0.0001a0.892< 0.0001a0.811< 0.0001a0.627< 0.0001a
Serum inflammatory factors before and after treatment

No statistical differences were found between serum levels of IL-1β, TNF-α and IL-8 before treatment (P > 0.05). After 8 weeks of treatment, serum levels of IL-1β, TNF-α, and IL-8 significantly decreased, with a particularly noticeable reduction in the observation group, where levels were considerably lower (P < 0.05). All results are shown in Table 6.

Table 6 Serum inflammatory factors before and after treatment in patients in group 5 (n = 40, mean ± SD).
GroupTNF-α (ng/L)
IL-1β (pg/mL)
IL-8 (μg/L)
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Before treatment
After 8 weeks of treatment
Observation group12.05 ± 2.289.03 ± 2.08159.87 ± 5.1644.13 ± 4.65128.71 ± 5.2419.06 ± 3.361
Control group12.47 ± 2.1911.58 ± 2.06258.86 ± 6.3155.26 ± 5.09227.98 ± 5.5423.68 ± 4.462
t value0.8405.5090.78410.2100.6055.233
P value0.403< 0.0001a0.436< 0.0001a0.547< 0.0001a
Comparison of incidence of adverse reactions

The observation group had a 5.00% incidence of adverse reactions, while the control group had a 22.50% incidence (P < 0.05). All results are shown in Table 7.

Table 7 Comparison of adverse reactions, n (%).
Group
n
Nausea and vomiting
Skin rash
Dizziness and headache
Total incidence rate (%)
Observation group400 (0.00)1 (2.50)1 (2.50)2 (5.00)
Control group403 (7.50) 4 (10.00)2 (5.00)9 (22.50)
χ2 value5.165
P value0.023
DISCUSSION

NAFLD has become a significant global health issue, and making the search for effective prevention and treatment strategies a key area of interdisciplinary investigation. In individuals with NAFLD, excessive eating and a genetic predisposition are important contributors, while a history of prolonged alcohol consumption is not involved[19]. Bicyclol, a biphenyl derivative, shows promise in treating hepatocyte injury induced by multiple factors, especially in reducing ALT levels. Polyene phosphatidylcholine serves as a cell membrane stabilizer and aids in hepatocyte repair. Although it is effective for abnormal liver function resulting from drug-induced hepatitis and viral hepatitis, its long-term efficacy remains suboptimal in NAFLD patients[20].

In TCM, NAFLD is categorized as “liver stagnation”, and improper diet is considered a major cause. Long-term overeating and a preference for fatty and sweet foods can lead to the accumulation of damp heat in the body. This can harm the spleen and the stomach, which are important for postnatal health. Spleen weakness can exacerbate endogenous dampness, further affecting the production of qi and blood. The retention of dampness can disrupt the spleen and stomach’s ability to transport and transform nutrients, creating a harmful cycle. Dendrobium nobile is a kind of Chinese herbal medicine known for its antioxidant properties and ability to regulate sugar and lipid metabolism[21]. It can inhibit the overexpression of nuclear factor-κB in vascular endothelial cells by reducing the microglia activation, which helps control inflammation and enhances repair of vascular endothelial cells[22]. Over the last few years, more scholars have focused on the pharmacology of polysaccharides from Dendrobium nobile Lindl. These polysaccharides can improve the antioxidant capacity of aging mice, inhibit the increase of malondialdehyde in serum, and increase the activity of antioxidant factors superoxide dismutase and glutathione peroxidase[23]. In addition, Dendrobium nobile polysaccharides have been noted for their anticancer and anti-inflammatory effects[24-26]. Some scholars used Dendrobium nobile polysaccharides when treating hyperlipidemic Wistar rats. The results show that Dendrobium nobile polysaccharides can remarkably lower serum TC and TG levels[27]. Therefore, this study combined Dendrobium nobile Lindl. powder with standard treatment. The observation group had an effective rate of 97.50%, while the control group had an effective rate of 72.50%. After 8 weeks of treatment, both main and secondary symptoms significantly decreased, with the observation group showing significantly lower scores. This demonstrates that the addition of Dendrobium nobile Lindl. powder to conventional treatment can have a synergistic effect, leading to a notable improvement in therapeutic outcomes and greater alleviation of clinical symptoms in patients.

Hepatic fibrosis is the liver’s ongoing response to chronic injury. Its primary pathological characteristic is the excessive accumulation of extracellular matrix (ECM) in the liver, without the formation of pseudo-lobules and regenerative nodules. ECM is primarily composed of HA, LN, PC III, CIV, and other components. Therefore, alterations in these indicators are sensitive and non-invasive markers for reflecting liver fibrosis progression. Moreover, the combined use of these indicators can provide an accurate evaluation of hepatic fibrosis[9]. After 8 weeks of treatment, levels of HA, LN, PC III, and CIV significantly decreased, with the observation group showing particularly notable reductions. ALT and total bilirubin are crucial parameters to assess liver function. ALT is predominantly found in the liver, myocardium, and skeletal muscle, serving as a specific marker for liver damage, with elevated levels typically indicating acute liver injury. AST, conversely, is mainly present in the mitochondria of the liver, heart, and kidneys, and an increase in AST levels usually corresponds to chronic injury of the liver[28].

This study showed a remarkable decrease in liver function and blood lipid levels following 8 weeks of treatment. The observation group demonstrated a greater decrease in liver function and blood lipid levels before and after treatment. This proves that Dendrobium nobile polysaccharides can regulate the liver function of patients with mild to moderate fatty liver. Some animal studies have pointed out that during liver function injury, toll-like receptor (TLR) signal pathway and heme oxygenase (HO-1) signal pathway are involved in the process of inflammatory response[29]. Among them, TLRs are pattern recognition receptors that are highly conserved through evolution, with 12 important members of TLR family, the most studied being TLR4. TLR4 signal pathway mainly mediates the responses of IL-6 and TNF-α during liver injury. In inflammation, HO family proteins and TLR family proteins interact, contributing to the onset and progression of the disease. HO family proteins are an important stress response proteins in the body, which is also a starting enzyme and rate-limiting enzyme, which can effectively catalyze the process of heme degradation. Following the onset of NAFLD, the body experiences hypoxia and endotoxin stimulation, leading to an increase in the secretion of HO-1. This elevation in HO-1 secretion can reduce tissue inflammation, thereby protecting hepatocytes[30]. In this study, the results indicated that after 8 weeks of treatment, serum levels of IL-1β, TNF-α, and IL-8 significantly decreased, with lower levels in the observation group. This suggests that Dendrobium nobile can inhibit the expression of ILs, TNF, and cell adhesion molecules; inhibit the binding of exogenous ligands to TLR4; and reduce the inflammatory reaction. In this study, the observation group had lower levels of inflammatory factors after treatment, which may be because the application of Dendrobium nobile Lindl. powder can promote the increase of HO-1 secretion, reducing tissue inflammation. Moreover, the observation group experienced a 5.00% incidence of adverse reactions, while the control group had a 22.50% incidence. This suggests that combining Dendrobium nobile Lindl. powder with routine treatment for NAFLD patients did not increase the incidence of adverse reactions and was safe. This may be attributed to the gentle nature of Dendrobium nobile powder, which is well-tolerated by patients.

This study has some limitations. The nature of the retrospective analysis prevented randomization of the two patient groups, thereby compromising their similarity. Also, due to this being a retrospective study, the data collected from the medical records was limited. In addition, we did not investigate the underlying mechanisms of how Dendrobium nobile Lindl. powder affects liver function and lipid metabolism, which might help explain the observed clinical outcomes. Therefore, a well-designed, randomized, controlled trial with prospective data collection and sample size calculation is needed to confirm our findings.

CONCLUSION

In conclusion, combining Dendrobium nobile Lindl. powder with routine therapy can effectively improve clinical symptoms, liver function, and blood lipid profile in NAFLD patients. Furthermore, it regulates inflammatory markers and improves liver fibrosis without causing adverse reactions. Thus, this treatment regimen holds promise for widespread adoption. A small sample size, lack of regional diversity, and lack of feedback, however, are some of the study’s limitations. Future research should include large, multi-center studies across different regions to obtain more accurate evidence for better clinical management of NAFLD.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country of origin: China

Peer-review report’s classification

Scientific Quality: Grade B, Grade B

Novelty: Grade B, Grade B

Creativity or Innovation: Grade C, Grade C

Scientific Significance: Grade C, Grade C

P-Reviewer: Iso H; Suzuki S S-Editor: Fan M L-Editor: A P-Editor: Yu HG

References
1.  Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397:2212-2224.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 461]  [Cited by in F6Publishing: 1244]  [Article Influence: 414.7]  [Reference Citation Analysis (33)]
2.  Henry L, Paik J, Younossi ZM. Review article: the epidemiologic burden of non-alcoholic fatty liver disease across the world. Aliment Pharmacol Ther. 2022;56:942-956.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 91]  [Article Influence: 45.5]  [Reference Citation Analysis (0)]
3.  Younossi ZM. Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol. 2019;70:531-544.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 943]  [Cited by in F6Publishing: 1277]  [Article Influence: 255.4]  [Reference Citation Analysis (0)]
4.  Tilg H, Adolph TE, Dudek M, Knolle P. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity. Nat Metab. 2021;3:1596-1607.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 134]  [Cited by in F6Publishing: 185]  [Article Influence: 61.7]  [Reference Citation Analysis (0)]
5.  Cai J, Zhang XJ, Li H. Progress and challenges in the prevention and control of nonalcoholic fatty liver disease. Med Res Rev. 2019;39:328-348.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 104]  [Article Influence: 17.3]  [Reference Citation Analysis (0)]
6.  Chao HW, Chao SW, Lin H, Ku HC, Cheng CF. Homeostasis of Glucose and Lipid in Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2019;20.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 56]  [Cited by in F6Publishing: 101]  [Article Influence: 20.2]  [Reference Citation Analysis (0)]
7.  Safari Z, Gérard P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci. 2019;76:1541-1558.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 317]  [Cited by in F6Publishing: 299]  [Article Influence: 59.8]  [Reference Citation Analysis (0)]
8.  Targher G, Tilg H, Byrne CD. Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach. Lancet Gastroenterol Hepatol. 2021;6:578-588.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 99]  [Cited by in F6Publishing: 234]  [Article Influence: 78.0]  [Reference Citation Analysis (0)]
9.  Shaunak M, Byrne CD, Davis N, Afolabi P, Faust SN, Davies JH. Non-alcoholic fatty liver disease and childhood obesity. Arch Dis Child. 2021;106:3-8.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 37]  [Article Influence: 12.3]  [Reference Citation Analysis (0)]
10.  Ahadi M, Molooghi K, Masoudifar N, Namdar AB, Vossoughinia H, Farzanehfar M. A review of non-alcoholic fatty liver disease in non-obese and lean individuals. J Gastroenterol Hepatol. 2021;36:1497-1507.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 45]  [Article Influence: 15.0]  [Reference Citation Analysis (0)]
11.  Cataldo I, Sarcognato S, Sacchi D, Cacciatore M, Baciorri F, Mangia A, Cazzagon N, Guido M. Pathology of non-alcoholic fatty liver disease. Pathologica. 2021;113:194-202.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 8]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
12.  Juanola O, Martínez-López S, Francés R, Gómez-Hurtado I. Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors. Int J Environ Res Public Health. 2021;18.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 21]  [Cited by in F6Publishing: 128]  [Article Influence: 42.7]  [Reference Citation Analysis (0)]
13.  Lee CH, Lui DT, Lam KS. Non-alcoholic fatty liver disease and type 2 diabetes: An update. J Diabetes Investig. 2022;13:930-940.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 35]  [Article Influence: 17.5]  [Reference Citation Analysis (0)]
14.  Farzanegi P, Dana A, Ebrahimpoor Z, Asadi M, Azarbayjani MA. Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation. Eur J Sport Sci. 2019;19:994-1003.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 93]  [Cited by in F6Publishing: 215]  [Article Influence: 43.0]  [Reference Citation Analysis (0)]
15.  Abenavoli L, Spagnuolo R, Scarlata GGM, Scarpellini E, Boccuto L, Luzza F. Ultrasound Prevalence and Clinical Features of Nonalcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Diseases: A Real-Life Cross-Sectional Study. Medicina (Kaunas). 2023;59.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 8]  [Reference Citation Analysis (0)]
16.  Martin A, Lang S, Goeser T, Demir M, Steffen HM, Kasper P. Management of Dyslipidemia in Patients with Non-Alcoholic Fatty Liver Disease. Curr Atheroscler Rep. 2022;24:533-546.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 13]  [Article Influence: 6.5]  [Reference Citation Analysis (0)]
17.  Cohen DE, Fisher EA. Lipoprotein metabolism, dyslipidemia, and nonalcoholic fatty liver disease. Semin Liver Dis. 2013;33:380-388.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 91]  [Cited by in F6Publishing: 97]  [Article Influence: 8.8]  [Reference Citation Analysis (0)]
18.  Kaya E, Yilmaz Y. Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver. J Clin Transl Hepatol. 2022;10:329-338.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 68]  [Cited by in F6Publishing: 62]  [Article Influence: 31.0]  [Reference Citation Analysis (0)]
19.  Mandala A, Janssen RC, Palle S, Short KR, Friedman JE. Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms. Nutrients. 2020;12.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 29]  [Article Influence: 7.3]  [Reference Citation Analysis (0)]
20.  Campos-Murguía A, Ruiz-Margáin A, González-Regueiro JA, Macías-Rodríguez RU. Clinical assessment and management of liver fibrosis in non-alcoholic fatty liver disease. World J Gastroenterol. 2020;26:5919-5943.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 26]  [Cited by in F6Publishing: 29]  [Article Influence: 7.3]  [Reference Citation Analysis (3)]
21.  Li M, Trapika IGSC, Tang SYS, Cho JL, Qi Y, Li CG, Li Y, Yao M, Yang D, Liu B, Li R, Yang P, Ma G, Ren P, Huang X, Xie D, Chen S, Li M, Yang L, Leng P, Huang Y, Li GQ. Mechanisms and Active Compounds Polysaccharides and Bibenzyls of Medicinal Dendrobiums for Diabetes Management. Front Nutr. 2021;8:811870.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 7]  [Article Influence: 3.5]  [Reference Citation Analysis (0)]
22.  Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W, Kassir R, Singhal R, Mahawar K, Ramnarain D. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord. 2022;22:63.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 271]  [Article Influence: 135.5]  [Reference Citation Analysis (0)]
23.  Xu L, Zeng X, Liu Y, Wu Z, Zheng X, Zhang X. Inhibitory effect of Dendrobium officinale polysaccharide on oxidative damage of glial cells in aging mice by regulating gut microbiota. Int J Biol Macromol. 2023;247:125787.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 10]  [Reference Citation Analysis (0)]
24.  Wu W, Lin Y, Farag MA, Li Z, Shao P. Dendrobium as a new natural source of bioactive for the prevention and treatment of digestive tract diseases: A comprehensive review with future perspectives. Phytomedicine. 2023;114:154784.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 5]  [Reference Citation Analysis (0)]
25.  Paternostro R, Trauner M. Current treatment of non-alcoholic fatty liver disease. J Intern Med. 2022;292:190-204.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 97]  [Cited by in F6Publishing: 80]  [Article Influence: 40.0]  [Reference Citation Analysis (0)]
26.  Hao Y, Lao S, Liu H, Chen X, Ye G, Wang Z, Liao W. Isolation and characterization of a nephroprotective polysaccharide from Dendrobium chrysotoxum Lindl against LPS-induced acute kidney injury mice. Int J Biol Macromol. 2023;253:126614.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
27.  Fan C, Sun X, Wang X, Yu H. Therapeutic potential of the chemical composition of Dendrobium nobile Lindl. Front Pharmacol. 2023;14:1163830.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 7]  [Reference Citation Analysis (0)]
28.  Polyzos SA, Kechagias S, Tsochatzis EA. Review article: non-alcoholic fatty liver disease and cardiovascular diseases: associations and treatment considerations. Aliment Pharmacol Ther. 2021;54:1013-1025.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 27]  [Cited by in F6Publishing: 47]  [Article Influence: 15.7]  [Reference Citation Analysis (0)]
29.  Buyco DG, Martin J, Jeon S, Hooks R, Lin C, Carr R. Experimental models of metabolic and alcoholic fatty liver disease. World J Gastroenterol. 2021;27:1-18.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 10]  [Cited by in F6Publishing: 17]  [Article Influence: 5.7]  [Reference Citation Analysis (1)]
30.  Gottlieb A, Canbay A. Why Bile Acids Are So Important in Non-Alcoholic Fatty Liver Disease (NAFLD) Progression. Cells. 2019;8.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 47]  [Cited by in F6Publishing: 87]  [Article Influence: 17.4]  [Reference Citation Analysis (0)]