Clinical experiences---Effect of the detoxifying and myogenic herb enema in treating 19 patients with ulcerative colitis

Gaochang

Sulfasalazine and corticosteroids have been the mainstays of treatment for ulcerative colitis (UC), but therapy has been hampered by symptoms of dose-related intolerance to sulfasalazine in one third to one half of patients, and fever, rash, or other manifestations of drug allergy in a lesser proportion of patients. Similarly, steroids therapies were complicated with one litany of short and long term side-effect, while neither sulfasalazine nor the steroids have been able (alone or in combination) to control the disease in more than two thirds to three quarters of patients over the short or long term. Recent advances such as 5-aminosalicylic acid (50-ASA) and new steroid preparations have improved our ability to treat UC, but side effect such as local irritation, occasional diarrhea, skin rashes, or hair loss were reported in some cases.

Recently, some researches demonstrate that some of traditional Chinese drugs, such as Pollen Typhae, Halloysitum Rubrum, Rhizoma Smilacis Glabrae, Indigo Pulverata Levis et al, have gastroenteric mucosal protective and are used clinically to treat gastritis, peptic ulcer and chronic diarrhea. Under the guidance of the traditional Chinese medicine theory of detoxifying and myogenic method, the authors observed the clinical effect of the Chinese herb retention enema on UC.

Methods:

Clinical Data

Referring to the standard proposed by relevant national conference, patients were diagnosed by air contrast barium enema, colonscopy., biopsy, and bacteriological examinations. Results of the examinations showed the pathogenic bacteria were isolated in none of the cases, nor were there amebae. The tested group includes 19 cases, among whom 10 were males and 9 females, aged 21-71 years, with the course of disease as 2 months to 20 years, 4.5 years in average. There were 10 proctitis, 6 with left-sided colitis, and 3 with total colitis. 4 cases among 19 patients had received oral treatment of sulfasalazine or corticosteroids in 2 months to 2 years. The patients were excluded who received any medication including experimental drugs, narcotics, sulfasalazine, steroid, non-steroidal anti-inflammatory or narcotic antagonists for 6 months before the study, or who had severe UC. In addition, 32 healthy subjects were selected as the control group. Among them were 16 males and 16 females, aged 20-43, averaging 37.4 years.

Observation of Disease Activity

Ulcerative colitis activity index (UCAI) was grade by Collawn index which include clinical, sigmoidoscopic, and histologic criteria at the beginning and end of the treatment as previously described in detail by Collawn. Clinical and laboratory evaluation were performed at screening a days 1, 14, 28, 42. Assessments were made by a pathologist and endoscopic investigator without access to clinical or drug history. Patients were instructed to contact the investigator if they had any questions or adverse reactions. They were questioned at each visit regarding possible adverse reaction as well as compliance with the drug regimen.

Method of Treatment

The enema was composed of 5 traditional Chinese drugs including Halloysitum Rubrum 20g, Rhizoma Bletillae 20g, Rhizoma Smilacis Glabrae 30g, Indigo Pulverata Levis 10g, and Pollen Typhae 20g. The mixture had 400- 600ml of water added to it and boiled for 10- 20 min to form a thin paste and then was filtered. Before bed-time 200-350 ml filtrate was used as retention enema. All of the 19 patients received enema once a day for 4-8 weeks. During the treatment, other drugs were suspended.

Measurements of Acute-Phase Response Protein

The contents of serum haptoglobin (HP), fibronectin(FN), α₁-acid glycoprotein (α₁-AG), α₁-antitrypasin (α₁-AT) were tested by radical immune diffusion (RID). The RID kits were supplied by Shanghai Institute of Biology.

Evaluation of Therapeutic Efficacy

Clinically cured: All symptoms subsided, colonfiberscopy showed that congestion and edema of colonic mucosa vanished and ulcers were healed. No recurrence was observed in a follow-up of half a year. Effective: Clinical symptoms subsided, stool examination essentially normal, and congestion, edema and ulceration of colonic mucosa were improved. Ineffect: There was no subjective or objective improvement after the treatment.

Statistical Analysis

The effect of treatment on symptoms scales, endoscopy scores, and biopsy grading were assessed by t and rank test. To study the correlation between the UCAI and contents of serum acute-phase response protein, the Spearman’s correlation coefficient was adopted.

Results of Treatment

According to the criteria for evaluation of the therapeutic efficacy, 12 cases were clinically cured, 6 cases markedly effective, and 1 case ineffective. The average period of the treatment course was 43 days. The 12 clinically cured cases were followed up for 8 months to 2 years after treatment, and 2 cases were recurrent, both with symptoms of a minor degree.

All adverse symptoms recorded by patients in their diary were considered. Symptoms were in no case attributed to the treatment, and in no case were the same symptoms described by two or more patients. Serial laboratory results usually were normal.

DISCUSSION

The etiology of UC is still unclear, but in recent years, it is associated with a defect in the intestinal mucosal barrier and function abnormality. Human colonic mucus contains a complex mixture of low molecular weight glycoproteins which play an important role as a nonimmunological defence system. They maintain the integrity of the mucosa and act as a barrier against harmful agents in the gut lumen. In UC there is a selective reduction human colonic mucin glycoprotein IV—a defect that persists during remission. In active UC, there is increased transport of luminal contents, including bacteria or their cell wall products across the mucosa. Among the potent bacterial inflammatory products are lipopolysaccharide (LPS), endotoxins, peptidoglycan polysaccharide complexes (PG-PS), and F-met-leu-phe (FMLP). This alteration in mucin reflects an underlying structural mucosal defect in susceptible people and results easily in a series of mucus inflammation. According to the traditional Chinese medicine theory of detoxifying and myogenic method, myogenic drugs are used for local treating of UC in our study. Our research showed traditional Chinese retention enema has certain effect on UC.

α₁-AG , α₁-AT, Haptoglobin and FN have the functions of immune regulation and stimulating cell production. Furthermore, the functions of these proteins are closely associated with cell differentiation, healing of injuries and inflammatory process, etc. Some researches demonstrate that serum protein values tended to reflect the degree of activity of the UC^(4-6). This study also observed that serum levels of haptoglobin, α₁-AG , α₁-AT were higher and FN was significantly lower than in the normal control. Till the end of the treatment, the symptoms of all of the patients decreased in some degree, and the gross appearance in the colonfiberscope improved. The UCAI of patients and HP, α₁-AG, α₁-AT were significantly decreased and FN was obviously raised. It was found in a few patients that their serum levels of α₁-AG, HP were higher than those in the normal control and the gross appearance of endoscopy showed the mucositis was often severe. These patients with higher HP and α₁-AG were apt to have recurrence, which indicates there was a correlation between the serum level of α₁-AG, HP and UC activity.

The Chinese drug Indigo Pulverata Levis mainly consists of Indigo and Indirubin and has immunosuppressive effect. Bletilla mannan is an active constituent of Rhizoma Bletillae, a medicinal herb which has long been known to have beneficial effect on peptic ulcer in traditional Chinese medicine and was recently round to demonstrate the mechanism on peptic ulcer. This maybe increased the synthesis or releasing of endogenous prostaglandin levels. When swallowed, it forms an adherent, protective complex with proteinaceous material over the ulcer itself, preventing acid, pepsin and bile salts from aggravating the lesion. Halloysitum Rubrum also forms an adherent protective complex over the gastrointestinal mucosal surface itself, preventing absorption of materials such as bacterial products, etc. from aggravating the mucosal ulcer. The water extract of Pollen Typhae has marked inhibition on ADP or arachidonic acid (eicosanoid)- induced platelet aggregation in vivo or in vitro, and the inflammatory reaction in UC is characterized by activation arachidonic acid with increased release of chemical mediations. The exact mechanism of detoxifying and myogenic herb enema are not known to us. A long term controlled double-blind research is needed, which may lead to a new therapeutic approach in UC.