Effects of Zhenren Yangzang Decoction Combined with Modified Shenling Baizhu Powder on Immune Function and Intestinal Microecology of Diarrhea Patients with Deficiency and Cold Syndrome

Zhang Ran (張 然)

Department of Spleen and Gastroenterology, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000, China

ABSTRACT OBJECTIVE: To observe the effects of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder on the immune function and intestinal microecology of diarrhea patients with deficiency and cold syndrome.METHODS: A total of 60 diarrhea patients with deficiency and cold syndrome were randomly divided into observation group and control group, with 30 cases in each group. The control group was treated with conventional western medicine.The observation group was given the treatment of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder on the basis of the same treatment for 4 weeks. The clinical symptoms, fecal flora and immunoglobulin content of the 2 groups were observed and the clinical efficacy was evaluated. RESULTS: After treatment, the symptoms scores of fecal diarrhea, aversion to cold, cold limbs, loss of appetite, cold and painful waist and knee, abdominal fullness, abdominal distension and abdominal pain, and intestinal bacilli contents were significantly decreased (P ＜ 0.05). The contents of lactobacillus, bifidus bacilli, IgG, IgM and IgA were significantly increased (P ＜ 0.05), and the improvement of the above indexes in the observation group was significantly better than that in the control group (P ＜ 0.05). The total effective rate after treatment in the observation group was 93.3%, which was significantly higher than 73.3% of the control group(P ＜ 0.05). CONCLUSION: The treatment of diarrhea patients with deficiency and cold syndrome with Zhenren Yangzang Decoction and modified Shenling Baizhu Powder can effectively improve the intestinal micro-ecological environment,improve the immune function of patients and promote the rapid recovery of patients.

KEYWORDS: Diarrhea; Deficiency and cold syndrome; Zhenren Yangzang Decoction combined with Modified Shenling Baizhu Powder; Immune function; Intestinal micro-ecology

Diarrhea is one of the common diseases of the gastrointestinal system of the internal medicine. The clinical manifestation is that the number of defecations is obviously increased, and the faeces are thin or even water-like[1]. The disease has a long course, and the disease is difficult to heal. It is easy to cause imbalance of nutrients, lack of trace elements, water and electrolyte imbalance, immune function reduction, and even multiple infectious diseases, which seriously affect the health and quality of life of patients[2]. At present, western medicine treatment of diarrhea is mainly based on symptomatic treatment, such as stopping diarrhea, adjustment of intestinal flora, correction of water and electrolyte disorders, etc., but the treatment efficacy is not good. In addition to the high rate of clinical recurrence, and serious drug side effects after drug withdrawal, some patients show a lack of sensitivity due to long course of disease[3].Traditional Chinese Medicine treatment of diarrhea has unique advantages and rich experience. It can be treated according to the specific clinical characteristics of patients based on syndrome differentiation. It cannot only quickly improve the clinical symptoms of patients,but also effectively prevent the disease from continuing to develop. It has overall regulation, treatment of both the symptoms and the root causes. From January 2015 to February 2016, the author used Zhenren Yangzhong Decoction combined with modified Shenling Baizhu Powder to treat 30 diarrhea patients with deficiency and cold syndrome, and the curative effect was good. The case report was as follows:

CLINICAL DATA

General information

A total of 60 patients with diarrhea admitted to our hospital during the above period were selected. The diagnostic criteria for western medicine referred to the provisions of Practical Internal Medicine[4]for chronic diarrhea: the frequency of stools is significantly increased than usual, and the stool characteristics are loose and sticky,and water like, etc. The diagnosis of Chinese medicine and the classification of syndrome types are all based on the Guidelines for Clinical Research of New Drugs of Traditional Chinese Medicine[5]. The spleen and stomach deficiency type and the kidney yang deficiency type are characterized by fecal diarrhea, loose stools, and abdominal distension. The waist and knees are sore, the limbs are cold, the appetite is weak, and the umbilical abdomen is cold and so on. The tongue is pale, the fur is white, and the pulse is fine. The patients were 18 to 70 years old who had a course of over 2 months. They had not been treated with other methods for nearly 1 week. The patients volunteered to participate in the study and signed an informed consent form. Patients with inflammatory bowel disease, diarrhea caused by cholera, dysentery and other infectious factors,malignant tumors, systemic diseases, etc., combined with severe cardiovascular and cerebrovascular system, liver and kidney system, endocrine system and hematopoietic system were excluded. Those who were pregnant or breast-feeding were accompanied by severe mental illness or a lower level of clinical treatment. They were randomly divided into 2 groups: 30 patients in the observation group, 13 males and 17 females; aged 20-69 (41.8±5.6)years old, duration of disease ranged from 3 months to 10 years (5.1±0.7) years. There were 30 patients in the control group, 12 males and 18 females; the age ranged from 21 to 68 (40.2±5.5) years old; the course of disease ranged from 5 months to 11 years (5.3±0.8) years. There were no significant differences in gender, age, and duration of disease between the two groups (P ＞ 0.05).

Treatment methods

The control group was given montmorillonite powder(SFDA approval number: H20093601, Sichuan Weiao Pharmaceutical Co., Ltd., specification: 3 g) 3 g/time,3 times/day, taken with warm water; metronidazole tablets(SFDA approval number: H53021408, Yunnan Dianchi Pharmaceutical Co., Ltd., specification: 0.2 g) 0.2 g/time,2times/day orally, for 4 weeks continuous treatment. On the basis of the above treatment, the observation group was given the treatment of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder.The prescriptions were: Poria 30 g, Semen Coicis 30, Rhizoma Dioscoreae 20 g, Radix Ginseng 15 g,Semen Dolichoris Album 15 g, Radix Paeoniae Alba 15 g, Rhizoma Atractylodis Macrocephalae 15 g, Radix Angelicae Sinensis 10 g, Pericarpium Papaveris 10 g,Radix Aucklandiae 10 g, Fructus Chebulae 10 g, Fructus Amomi Villosi 10 g, Semen Nelumbinis 10 g, Radix Glycyrrhizae 10 g, Cortex Cinnamomi 6 g. Modification:abdominal cold pain, preference for warmth and pressing,add Radix Aconiti Lateralis Preparata 10 g, Rhizoma Zingiberis 10 g; limb cold and back soreness, add Herba Epimedii 30 g, Fructus Psoraleae 15 g, Rhizoma Curculigins 15 g; severe dampness, add Rhizoma Cimicifugae 10 g,Herba Pogostemonis 10 g and Radix Saposhnikoviae 10 g.The above herbs were decocted in water, 1 dose/d, taken 2 times in the morning and evening with warm water, 4 weeks as a course of treatment, a total of 1 course of treatment.

Observation indicators

Clinical efficacy

According to the Criteria for Diagnosis and Efficacy Evaluation of TCM Syndrome[6], clinical cured: daily stool frequency, stool volume and stool traits returned to normal after treatment, clinical symptoms and signs such as abdominal pain and body weakness disappeared,and laboratory indicators for diarrhea returned to normal;markedly effective: after treatment, daily stool frequency is 2-3 times, the stool trait was close to be formed, or diarrhea once a day. The clinical symptoms and signs such as abdominal pain and body weakness were obviously improved, and the laboratory tests for diarrhea were significantly improved. Effective: the number of times and stool characteristics of patients were improved,and clinical symptoms and signs such as abdominal pain and physical weakness were alleviated, and laboratory tests for diarrhea were improved. Invalid: clinical symptoms, signs and laboratory test related to diarrhea after treatment were no improvements. Cured, markedly effective, improved were considered as totally effective.

Clinical symptoms

Before and after treatment, the 2 groups of stool diarrhea, aversion to cold and cold limbs, loss of appetite,cold and knee pain, abdominal fullness and abdominal distension and abdominal pain were scored. The higher the score was, the more serious the symptoms were.

Fecal microflora

The middle and end of the stool was taken out before and after treatment, and the contents of Enterobacter,Enterococcus, Lactobacillus and Bifidobacteria were analyzed by bacterial culture experiments.

Immunoglobulin contents

Peripheral venous blood was taken before and after treatment, and IgG, IgM and IgA levels were detected by immunoturbidimetric assay.

Statistical methods

Statistical analysis was performed using SSPS 19.0 statistical software. Measurement data were expressed as mean ± standard deviation, and t-test was used for comparison. The chi-square test was used to compare the count data. P ＜ 0.05 indicates that the difference was statistically significant.

RESULTS

Comparison of the therapeutic effects of the 2 groups

After treatment, the total effective rate of the observation group was 93.3%, which was significantly higher than that of the control group (73.3%) (P ＜ 0.05). See Table 1.

Comparison of clinical symptoms and signs before and after treatment in the 2 groups

Before treatment, there were no significant differences in the scores of fecal diarrhea, aversion to cold and cold limbs, loss of appetite, cold pain in waist and knee, abdominal fullness and abdominal distension and abdominal pain (P ＞ 0.05). After treatment, the scores of 2 groups were significantly decreased (P ＜ 0.05), and the scores of the above indicators in the observation group were significantly lower than the control group after treatment (P ＜ 0.05). See Table 2.

Comparison of 4 bacterial groups in feces before and after treatment

There was no significant difference in the content of Enterobacter, Enterococcus, Lactobacillus and Bifidobacteria between the 2 groups before treatment (P ＞ 0.05). After treatment, the contents of Enterobacteriaceae in the 2 groups were significantly decreased (P ＜ 0.05), and the contents of Enterococcus, Lactobacillus and Bifidobacteria were significantly increased (P ＜ 0.05). The improvement of the above indicators was more obvious in the observation group than the control group (P ＜ 0.05). See Table 3.

Comparison of immunoglobulin content before and after treatment in the 2 groups

Before treatment, there was no significant difference in the levels of IgG, IgM and IgA between the 2 groups (P ＞ 0.05). After treatment, the levels of IgG, IgM and IgA in the two groups were significantly increased (P ＜ 0.05), and the immunoglobulin content in the observation group was significantly higher than that in the control group (P ＜ 0.05). See Table 4.

DISCUSSION

In recent years, with the acceleration of socialrhythm and changes in people's dietary and lifestyles, the clinical incidence of diarrhea has shown a rapid increase.Although the disease does not endanger life, the condition is lingering, easy to recurrent, causing greater adverse effects on the patient's body and mind[7]. Modern medical research has found that there is a relationship between the intestinal flora and the host, which is characterized by mutual dependence and mutual restraint, and the two maintain the micro-ecological balance of the intestinal tract[8]. Under normal conditions, the host is the provider of nutrients and living environment of the intestinal flora.In turn, the intestinal flora provides the host with synthetic nutrients and activated immune system and biological antagonism. If the balance between the intestinal flora and the host is broken, the intestinal flora will undergo abnormal changes in quantity, composition and location,which may eventually lead to pathological changes in the body[9]. In addition, the function of the immune system is closely related to human health. The pathological study of most diseases can involve the immune system, and clinical studies have confirmed that the immune system has a very important influence on the living environment of the intestinal flora[10]. IgG is a human serum immunoglobulin and the most persistent and important antibody in the primary immune system response.It dominates most of the antibacterial and antiviral antibodies in the body and plays a major role in the body's anti-infection. The role of IgM is mainly in serum, which is a high-performance anti-biological antibody, and it has a very strong bacteriolysis, bactericidal and phagocytosis,which is the main force of the body's early defense; IgA is roughly divided into serotype and secretory, in which secretory IgA is a major component of the intestinal mucosal defense system, and can effectively combat some pathogenic microorganisms and viruses, and plays an important role in the activation of mucosal immunity and the maintenance of the intestinal environment[11]. At present, Western medicine mainly provides symptomatic treatment for clinical symptoms of patients, but it can only cure its "manifestations", but cannot cure its "root causes",with a high clinical recurrence rate after treatment.

Table 1. Comparison of the therapeutic effects of the 2 groups

Table 2. Comparison of clinical symptoms and signs before and after treatment in the 2 groups

Table 3. Comparison of 4 bacterial groups in feces before and after treatment (, Log10 nCFU/g)

Table 3. Comparison of 4 bacterial groups in feces before and after treatment (, Log10 nCFU/g)

Notes: ①Compared with before treatment, P ＜ 0.05. ②Compared with control group, P ＜ 0.05.

treatment After treatment Before treatment After treatment Before treatment After treatment Before treatment After treatment Observation group 8.91±0.91 7.03±0.81①② 6.23±0.74 8.02±0.91①② 6.94±0.76 8.76±0.92①② 7.37±0.84 9.59±1.03①②Control group 8.95±0.93 7.81±0.88① 6.26±0.76 7.31±0.84① 7.03±0.75 7.93±0.84① 7.41±0.82 8.13±0.92①Group Enterobacter Enterococcus Lactobacillus Bifidobacteria Before

Table 4. Comparison of immunoglobulin content before and after treatment in the 2 groups (, Log10 nCFU/g)

Table 4. Comparison of immunoglobulin content before and after treatment in the 2 groups (, Log10 nCFU/g)

Notes: ①Compared with before treatment, P ＜ 0.05. ②Compared with control group, P ＜ 0.05.

Chinese medicine classifies diarrhea as "abdominal pain", "diarrhea" and "abdominal pain". It is considered that "the diarrhea is based on the spleen and stomach"and "no dampness no diarrhea". It can be seen that spleen deficiency and dampness are the key causes of the disease.And it is believed that the spleen deficiency is the basic pathogenesis. Long-term illness could damage spleen yang, and severe cases can damage the kidney yang.Therefore the spleen and kidney deficiency is commonly seen in clinical practice. The treatment of deficiency cold diarrhea should be both considering spleen and kidney.In this study, Zhenren Yangzang Decoction combined with Modified Shenling Baizhu Powder was the basic prescription, and the treatment was effective with modification. Among them, Zhenren Yangzang Decoction is from Prescriptions of the Bureau of Taiping People's Welfare Pharmacy Volume 6 Treatment of Diarrhea:"Adult and children with spleen and stomach weakness,... red and white diarrhea, or with blood, like a fish brain,tenesmus, umbilical and abdominal pain in day and night,... all kinds of medicines are not effective, and they are all used for treatment." This formula consists of Radix Ginseng, Radix Angelicae Sinensis, Cortex Cinnamomi,Pericarpium Papaveris, Radix Paeoniae Alba, Radix Aucklandiae, Fructus Chebulae, of which Radix Ginseng could invigorate the spleen and benefit kidney, and benefit qi for relieving depletion. Radix Angelicae Sinensis has the function of regulating meridians and relieving pain. Cortex Cinnamomi has the function of promoting blood circulation, dispelling cold and relieving pain.Pericarpium Papaveris has the function of relieving diarrhea with astringing, astringing the lung and relieving pain. Radix Paeoniae Alba has the function of relaxing the middle and relieving pain; Radix Aucklandiae has the functions of activating qi, relieving pain, regulating qi and strengthening the spleen; Fructus Chebulae could astringe the intestine and stop diarrhea. Modified Shenling Baizhu Powder is from Prescriptions of the Bureau of Taiping People's Welfare Pharmacy, which consists of Radix Ginseng, Rhizoma Atractylodis Macrocephalae, Poria,Semen Coicis, Rhizoma Dioscoreae, Semen Dolichoris Album, Radix Glycyrrhizae, Fructus Amomi Villosi and Semen Nelumbinis. In the formula, Rhizoma Atractylodis Macrocephalae has the power of strengthening the spleen and replenishing qi. Poria has the power to tonify the middle and strengthen the spleen; Semen Coicis has the function of removing dampness and wind, clearing heat and relieving pain; Rhizoma Dioscoreae has the power of tonifying the middle and replenishing qi. Semen Dolichoris Album has the function of strengthening spleen and resolving dampness. Radix Glycyrrhizae has the effects of tonifying the middle and replenishing qi, relaxing the middle and relieving pain. Fructus Amomi Villosi has the power of warming the spleen and stopping diarrhea. Semen Nelumbinis has the power of strengthening the spleen and kidney. The abovementioned various herbs are compatible with each other,and treating both manifestations and root causes with functions of strengthening spleen and tonifying kidney,stopping diarrhea and percolating dampness. Modern pharmacological studies have shown that Radix Ginseng has the effects of correcting gastrointestinal dysfunction,fighting gastric mucosal damage and improving immunity; Radix Angelicae Sinensis has the effects of enhancing immune function[12]; Cortex Cinnamomi has obvious antibacterial and antifungal infection effects[13];Pericarpium Papaveris contains codeine and morphine and other ingredients, which can effectively increase the tension of the gastrointestinal sphincter, reduce the secretion of digestive juice, and can effectively delay the intention. Radix Paeoniae Alba has obvious effects of analgesic, anti-inflammatory, immune regulation and improving blood rheology[14]. Radix Aucklandiae decoction has the effects of regulating gastrointestinal motility, promoting intestinal propulsion and gastric emptying, and can significantly inhibit intestinal diarrhea induced by senna and castor oil in mice. Fructus Chebulae has obvious antidiarrheal effect on mouse diarrhea, and its decoction has a good inhibitory effect on various bacteria such as Staphylococcus aureus,Pseudomonas aeruginosa and Shigella dysenteriae[15].Rhizoma Atractylodis Macrocephalae has strong effects of strengthening spleen and stomach and enhancing body resistance. Poria can effectively inhibit a variety of acute and chronic inflammation, and can significantly enhance the body's immune function[16]; Semen Coicis contains coixol, which has mild warm and antiinflammatory analgesic effect. Rhizoma Dioscoreae has the effects of regulating gastrointestinal function.Semen Dolichoris Album has obvious inhibitory effects on dysentery bacillus. Radix Glycyrrhizae has obvious anti-inflammatory and anti-viral effects; Fructus Amomi Villosi extract has obvious anti-inflammatory and analgesic effects and can be effective in inhibiting tomato leaf induced diarrhea in mice[17].

The results of this study showed that the total effective rate of the observation group was significantly higher than that of the control group, and the improvement of clinical symptoms, Enterobacter, Lactobacillus,Bifidobacterium, IgG, IgM and IgA in the observation group was significantly better than that of the control group. It is suggested that the treatment of deficiency cold type diarrhea with Zhenren Yangzang Decoction and modified Shenling Baizhu Powder can effectively improve the intestinal micro-ecological environment of patients, improve the immune function of patients, and promote the rapid recovery of patients. The curative effect is exact and worthy of clinical application.