Aloe Vera (Xanthorrhoeaceae) is a stemless, drought-resisting succulent plant of the lily family. It is indigenous to hot countries and has been shown to have anti-inflammatory and antioxidant properties. Aloe vera gel is the mucilaginous aqueous extract of the leaf pulp of Aloe barbadensis and can act as a barrier such as in colitis. Aloe vera contains an abundance of phytochemical substances such as mannans and anthraquinone. Its immunomodulating activity is thought to work through the induction of maturation of dendritic cells and in vitro inhibition of prostaglandin E2 and IL-8. Topical administration of aloe gel is considered safe but if taken orally has been found to cause abdominal cramps, diarrhea, and dehydration. This has also been linked to thyroid dysfunction, acute hepatitis, and perioperative bleeding.

Aloe vera gel has been used in the treatment of mild-to-moderate ulcerative colitis. A randomized double-blind controlled trial from the United Kingdom showed that aloe vera gel, when administered to patients with moderately active ulcerative colitis for 4 weeks, was superior to placebo. The primary outcome measures were clinical remission (Simple Clinical Colitis Activity Index < 2), sigmoidoscopic remission (Baron score < 1), and histological remission (Saverymuttu score < 1). Aloe vera gel taken for 4 weeks appeared to be safe, produced a clinical response (p < 0.05), reduction in median SSCAI (p<0.01), and reduction in histological disease activity (p < 0.03) in comparison to placebo. [22].

Wheat grass has shown significant benefit as single or adjuvant treatment for active distal ulcerative colitis. In a randomized, double-blind, multicenter study from Israel, 23 patients with active distal UC were given either daily wheat grass juice or placebo for 4 weeks. Patients were found to have clinical improvement (reduction in rectal bleeding, abdominal pain, physical global assessment score) in 10/11 patients on wheat grass (91%) vs. 5/12 on placebo (42%). Gross improvement was also seen on sigmoidoscopy in 78% or 7/9 patients on wheat grass vs. 30% or 3/10 on placebo [23].

Andrographis paniculata (Acanthaceae) is a bitter-tasting annual plant in Asia. This has been marketed in China as Kan Jang, Kold Kare, KalmCold, and Paractin. Andrographis has been found to have antibacterial, antioxidant, anti-inflammatory, anticancer, and immune-stimulating properties. Its active constituents are diterpenoid lactones known as andrographolides. Its anti-inflammatory activity works by inhibiting nitric oxide production, cyclooxygenase-2 expression, and TNF-alpha, IL-1b, and NF-kB. Side effects include headache, fatigue, hypersensitivity, lymphadenopathy, nausea, diarrhea, altered taste, transaminitis, and acute kidney injury. Andrographis extract may inhibit 1A2, 2C9, and 3A4 and induce CYP1A1. These two properties can affect the intracellular concentration of drugs metabolized by these enzymes.

Andrographis has been found to be an efficacious alternative to mesalamine in the treatment of active UC. A randomized double-blind multicenter 8-week parallel-group study showed that Andrographis paniculata (HMPL-004) was as effective as mesalamine (response 76% vs. 82%; remission 21% vs. 16%) in the treatment of mild-to-moderate ulcerative colitis, but there was no difference in endoscopic remission rates at 8 weeks between the two groups, 28% vs. 24% [24]. This was followed up by a larger randomized, double-blind controlled trial in 224 adults with mild-to-moderate ulcerative colitis. HMPL-004 given at a higher dose (1800 mg daily) was associated with a greater clinical response than placebo (60% vs. 40%; P = 0.018) although remission rates at 8 weeks were not different between both groups, 38% vs. 34%; P = 0.101 [25].

Jian Pi Ling (JPL) tablet and Yukui tang tablets are herbal therapies that have been studied in China in the treatment for ulcerative colitis [26, 27, 28, 29]. In a randomized controlled trial, 153 patients with UC were randomly assigned to three groups: group I, Jian Pi Ling (JPL) tablet with retention enema of Radix Sophorae Flavescentis and Flos Sophora decoction; group II, sulfasalazine and retention enema of dexamethasone; and group III, placebo and retention enema of decoction. Remission rates at 3 months in group 1 were significantly higher (53%) than those in the other two groups (28 and 19%, respectively) [26, 27]. Another study evaluated 118 patients with active UC who were treated with oral Yukui tang tablets and herbal decoction enemas, in addition to oral prednisolone 15 mg daily, neomycin, and vitamin B for 40 days. Eighty-six control patients who received only low-dose prednisolone, neomycin, and vitamin B were used for comparison. The remission rates and response rates were 33 and 51%, respectively, in the active group, compared with 17 and 43%, in the control group [26, 27].

Primrose oil has been used in the treatment of ulcerative colitis. In a placebo-controlled study, 43 patients with stable ulcerative colitis were randomized to receive MaxEPA (Oenothera biennis) (n = 16), super evening primrose oil (n = 19), or olive oil as placebo (n = 8) for 6 months, in addition to their normal treatment. Evening primrose oil significantly improved stool consistency, and the difference was maintained even after treatment was discontinued. There was no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance, or histology in the three treatment groups [30].

Curcumin is the active yellow pigment of the spice turmeric. It is an herb belonging to the ginger family native to India and Southeast Asia. Curcumin is commonly used in Indian traditional cuisine and medicine. It has been found to have anti-inflammatory, antioxidant, and antitumor effects. Curcumin is thought to cause the suppression of the nuclear factor kappa-light chain enhancer of activated B cells (NF-KB). Furthermore, curcumin activity includes suppression of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF α), two main cytokines that play important roles in the regulation of inflammatory responses. Side effects include dyspepsia, diarrhea, distension, GERD, gassiness, nausea, and vomiting. It also has been found to interact with anticoagulants, hypoglycemic medications, and iron and can increase sulfasalazine levels. Thus, this must be discontinued at least 2 weeks prior to any surgery.

Curcumin has been used in the treatment of both ulcerative colitis and Crohn’s disease. A 2012 Cochrane review found curcumin is safe and an effective therapy for maintenance of remission in quiescent UC when given as adjunctive therapy along with mesalamine or sulfasalazine. A multicenter randomized double-blind Japanese study evaluated 89 patients who were randomized to receive either curcumin (1 g twice daily) or placebo, in addition to sulfasalazine or mesalamine, for 6 months. Relapse rate was significantly lower in the curcumin group, 4.7% compared to placebo 20.5%, p = 0.04 [31]. This was reinforced by a multicenter double-blind randomized control trial, which evaluated 50 patients with active mild-moderate UC on 5-ASA, who did not respond to 2 weeks of max 5-ASA oral and topical therapy. Patients were randomly assigned to curcumin 3 g/d (n = 26) or placebo (n = 24) × 4 weeks. Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. three patients (12.5%) in the placebo group (P < 0.001). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with 0 of 16 patients evaluated in the placebo group p = 0.04 [32]. Curcumin has been also evaluated in Crohn’s disease. A pilot study of five patients demonstrated that 360 mg of curcumin TID could cause a mean reduction in CDAI of 55 points, ESR reduction of 10 mm/hr, and CRP reduction of 0.1 mg/dl [33]. A pediatric tolerability study was performed in 11 patients with mild UC or CD. Three patients had a decrease in their PUCAI or PCDAI scores and none had a relapse or worsening of symptoms [34].

Boswellia has been used in the treatment of ulcerative colitis and Crohn’s disease. Two studies had compared the efficacy of herbal therapy to mesalamine. In the first study, 30 patients with chronic active UC were randomized to gum resin of Boswellia serrata (900 mg daily in three doses; n = 20) or sulfasalazine (3 g daily in three doses; n = 10) for 6 weeks. Fourteen of 20 patients treated with Boswellia gum resin and 4 of 10 treated with sulfasalazine achieved remission. Eighteen of 20 patients treated with Boswellia gum resin and 6 of 10 patients on sulfasalazine showed an improvement in one of more of the parameters including stool properties, histopathology, and scanning electron microscopy [35].