Inhibitory effects of SKI3246, the rhizome extract of Atractylodes japonica, on visceral hypersensitivity in experimental irritable bowel syndrome rat models

Abstract

We evaluated the effect of SKI3246, the 50% ethanol extract of the rhizome of Atractylodes japonica, on visceral hypersensitivity, which is a major characteristic feature of IBS. We used various rat models of visceral hypersensitivity to assess the visceral pain responses to colorectal distension (CRD) in comparison with conventional IBS treatments. Oral administration of SKI3246 dose-dependently and significantly attenuated the abdominal withdrawal reflex (AWR) score in a model of acetic acid-induced visceral hypersensitivity. We also found that it reduced the number of abdominal contractions in response to CRD in a model of 2,4,6-trinitrobenzenesulfonic acid-induced visceral hypersensitivity, which was comparable to ramosetron or alosetron. Furthermore, treatment with SKI3246 also increased the pain threshold and abolished the elevated AWR scores to CRD in a rat model of neonatal maternal separation. We presumed that the modulation of the NK2 receptor is involved in the inhibitory activity of SKI3246 on the basis that it significantly inhibited the contraction of the distal colonic muscle induced by neurokinin A, the NK2 receptor agonist. The present results indicate that SKI3246 has the potential to be an effective therapeutic agent for IBS, especially insofar as it can relieve visceral hypersensitivity.

The Effects of an Extract ofAtractylodes JaponicaRhizome, SKI3246 on Gastrointestinal Motility in Guinea Pigs

“…In preliminary animal experiments, an extract of A. japonica rhizome (SKI3246) significantly reduced visceral pain in visceral hypersensitivity rats model using trinitrobenzene sulfonic acid (TNBS) or acetic acid. 1 The treatment also ameliorated castor oil-induced diarrhea in mice (unpublished data). These findings suggest that SKI3246 may potentially provide some relief for irritable bowel syndrome (IBS), especially when diarrhea is a principal component.…”

“…Although the pharmacological action of SKI3246 is not completely defined, this complex preparation has been shown its action through the neurokinin (NK) receptor antagonism, especially NK2 receptor. 1 Meanwhile, it has been known that MO displays proinflammatory activity mainly via inducing plasma extravasation, which is principally due to the release of substance P and to NK1 receptor activation. [7][8][9][10] These differences in mechanism between the 2 agents may explain in part the lack of GI motility response to SKI3246 in the MO-induced model in this study.…”

Sesquiterpenoids Isolated from the Rhizomes of Genus Atractylodes

“…(1S,4S,5R,7R,10R)‐11,14‐Dihydroxy‐guai‐3‐one‐11‐ O ‐β‐D‐glucopyranoside ( 80 ), [62] (1S,4S,5S,7R,10R)‐10,11,14‐trihydroxy‐guai‐3‐one‐11‐ O ‐β‐D‐glucopyranoside ( 82 ), [62] atractyloside A ( 84 ), [62] 10‐epi‐atractyloside A ( 85 ), [62] atractyloside B ( 87 ), [62] and (1S,5R,7R,10R)‐seco‐atractylolactone‐11‐ O ‐β‐D‐glucopyranoside ( 96 ), [62] have been isolated from the rhizome of A. japonica . Atractyloside A ( 84 ), [27] (4R,5R)‐atractylmacrene A ( 98 ), [32] (4S,5S)‐Atractylmacrene A ( 99 ), [32] (1R,4R,5R)‐atractylmacrene B ( 100 ), [32] and (1S,4S,5S)‐atractylmacrene B ( 101 ) [32] guai‐10(14)‐en‐11‐ol ( 102 ), [31] have been isolated from the rhizome of A. macrocephala .…”

“…A. macrocephala [26,28,30,32–35,38,42–44,47–49,51–54,58,59] A. japonica [18,20,21,60–62] A. chinensis [16,67] A. lancea [11,64,66] A. ovata [68–71] …”

“Ninjinto” (Ginseng Decoction), a Traditional Japanese Herbal Medicine, Improves Gastrointestinal Symptoms and Immune Competence in Patients with Chronic Intestinal Failure

“…The other important crude drug in NJT is Atractylodes japonica . It has been reported that SKI3246 of the rhizome of Atractylodes japonica is potentially effective in treating visceral hypersensitivity in experimental rat model of irritable bowel syndrome [ 12 ]. According to the Kampo diagnosis, NJT improves interior cold, a pathological state characterized by the preponderance of yin cold or a decline in yang qi in the interior, thus tonifying the digestive system.…”