Alternative Medicine in Inflammatory Bowel Disease

Alternative Medicine in Inflammatory Bowel Disease

Alternative Medicine in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease including ulcerative colitis (UC) and Crohn’s disease (CD). Approximately 1.4 million Americans are affected by IBD, and the peak onset age is 15 to 30 years old [1]. IBD patients present with persistent diarrhea with blood and mucous in stool lasting weeks to months, and experience recurrent flares and remissions.

The pathogenesis of IBD is still unclear and may result from an overactive and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual.  It involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. The latest studies showed that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the aberrant immune response has been considered to play an important role in the etiology of IBD [2,3].

Simply, when the immune system tries to fight off bacterium, an abnormal immune response causes the immune system to attack our own cells in the digestive tract which called autoimmune response. Several molecular signaling pathways have been found in regulating innate and adaptive immune responses in IBD including nucleotide oligomerization domain 2 (NOD2), autophagy gene ATG16L1 and interleukin 23-type 17 helper T-cell (IL23-Th17) pathway [2].

Except for gastrointestinal symptoms such as lack of appetite, diarrhea, abdominal pain and cramping, blood and mucus in stool, painful or difficult bowel movements patients may also have symptoms that do not appear to be related to the digestive system like fever , fatigue, unintended weight loss, arthritis, inflammation of eyes, skin disorder and liver disease. Diagnosis and differentiation of IBD relies on endoscopy and tissue biopsy. Ulcerative colitis is characterized by continuous, symmetric inflammation commonly in the rectum, and inflammation limits to mucosa and submucosa only. Crohn’s disease has discontinuous, asymmetric inflammation in any region of the intestine with the characteristic cobblestone appearance under endoscopy, and the inflammation is often transmural.

Current treatment for IBD includes anti-inflammatory, Immunosuppressives, antibiotics, probiotics biologics and surgical intervention [3]. As disease significantly impact quality of life of affected patients in school, work, social activity, an individually, integrative and multidisciplinary care is needed to improve quality of life of IBD patients.

Epidemiology shows that patients with IBD are among the highest users of complementary and alternative medicines (CAM). The reasons include: 1) there is no cure for IBD; 2) this is a chronic, relapsing, inflammatory disorder; 3) it is difficult to predict and control the frequency and severity of disease exacerbation; 4) many patients are inadequate response to conventional therapy aforementioned; and 5) patients are suffer from severe side effects. Currently available CAM in the treatment of IBD include herbal medicine, acupuncture and mind-body intervention.

Andrographis paniculata


Andrographis paniculata extract is a pure herbal agent that is currently in the process of approval as a botanical drug by the FDA. It has been traditionally used to treat infections in traditional Chinese medicine. Research data revealed that paniculata extract inhibits NF-kB, TNF-1a, IL-1b signaling. Clinical trials found that it significantly increases response rate, improves clinical symptom severity and endoscopic and histological signs [4]. Another clinical study showed paniculata extract was as potent as mesalamine in the treatment of mild-to-moderate UC [5].

Cannabis


Cannabis inhibits GI tract motility and secretion which reduce inflammation-associated hypermotility in IBD. Cannabis is also a potent analgesic mainly affecting neuropathic and inflammatory pain. Experiments data show that cannabinoid modulates immune system by suppressing cell-mediated immunity and Th1 cytokine production, enhancing adaptive immunity and Th2 cytokine production, inhibiting TNF-a secretion and LPS-induced macrophage activation [6-10]. Clinical trials shows cannabis reduces Crohn’s disease activity and improves symptom control and quality of life [11]. Finally, side effects such as addiction, memory deficit and motor vehicle accidents must be considered as well.

Curcumin


Curcumin has been used for centuries in traditional Chinese medicine to treat inflammatory diseases and has been extensively investigated for its anti-inflammatory, antitumor effects. In vitro and in vivo animal studies showed that curcumin inhibits NF-kappa B-TNF-a signaling pathway, reduces chemokine expression and neutrophil migration through mucosal barrier [12, 13].  Two Randomized controlled add-on clinical trials demonstrated in ulcerative colitis patients that curcumin was superior to placebo in maintaining clinical remission, improving both clinical and endoscopic manifestation in ulcerative colitis patients [14, 15]. Topical curcumin enema confirmed better outcomes in clinical response, clinical remission and endoscopic findings [16].

Germinated barley foodstuff


As the imbalance of the microbiome homeostasis is believed to play a role in the pathogenesis of IBD, antibiotics were prescribed in severe ulcerative colitis and are often used in Crohn’s disease involving the colon. Germinated barley foodstuff (GBF) is a prebiotic product derived from fractions of germinated barley. Animal studies show that GBF reduces IL-6, STAT3, NF-kB activity, increases cecal butyrate levels, and ameliorates chemically induced colonic mucosa damage, which is comparable to antibiotics (vancomycin, metronidazole) [17-19]. Clinical studies demonstrated that GBF significantly reduced serum IL-6 and IL-8 levels, relapse rate, steroid usage, and improved patient’s symptoms and endoscopic disease scores [20-22].

Tripterygium wilfordii


Tripterygium wilfordii is a Chinese medicinal herb with immunomodulatory and anti-inflammatory activities. Preclinical studies reveals that tripterygium extract inhibits inflammatory cytokines, adhesion molecules release. Clinical trials showed that tripterygium extract significantly reduces cytokine TNF-a, IL-1b level and improves symptoms patients with Crohn’s disease [23, 24]. Another two clinical studies found that tripterygium prevented the postoperative recurrence of Crohn’s disease at least as potent as mesalazine [25, 26].

Compound Chinese herbal medicine


Chinese herbal medicine is usually used combinationally instead of single herb in clinical application. Several TCM formulae have successfully passed animal studies and were in clinical trials on IBD patients. FAHF-2 formula (base on Chinese herbal formula (Wu Mei Wan 乌梅丸) contains 9 Chinese medicinal herbs and has been approved by FDA as a botanical product in the treatment of patients with food allergies. A recent animal studies from Columbia University showed that FAHF-2 inhibited both innate and adaptive immune proinflammatory cytokine responses in Crohn’s disease by blocking NF-kB activation, suggesting that FAHF-2 has potential as a novel treatment of Crohn disease. [27]. Several clinical trials from different groups showed that formula Xilei-san reduces relapse rate, improves clinical symptoms, endoscopic and histologic scores in ulcerative colitis compared with placebo [28, 29]. Formula Kui jie qing (KJQ) as an enema approach was studied in patients with active ulcerative colitis. Compared with conventional drugs Kui jie qing (KJQ) showed a 95% effectiveness rate compared 62% for conventional drugs [30].

Acupuncture


Acupuncture is an integral part of traditional Chinese medicine and has been extensively investigated in its application in the treatment of various diseases. Recently two clinical studies were conducted to investigate the efficacy of acupuncture on Crohn’s disease and ulcerative colitis. Results showed that acupuncture significant decreased in colitis activity index (in Ulcerative colitis) and improved general well-being and quality of life in patients with Crohn disease. No serious adverse events were observed [31, 32].

Mind-body intervention


Clinical studies have been conducted to investigate the effect of lifestyle modification on patients with ulcerative colitis. Results showed significant improvement in psychological disorder and, quality of life [33, 34]. Mindfulness intervention were found to have significant effects on quality of life and stress in IBD patients [35]. A stress management program including 6 x 3 h of training in planning skills, communication skills and autogenic training was shown to remarkably improve symptoms and stress in IBD patients. Same results were found in a study of relaxation training [36].

References


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