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. 2022 Apr 27:14:149-165.
doi: 10.2147/JEP.S345599. eCollection 2022.

Investigation of HPLF-111624 in Modified Experimental Models of Ulcerative Proctitis and Anal Fissure in Rats

Mallappa Onkaramurthy  1 , Mohammed Mukhram Azeemuddin  1 , Mirza Rizwan Baig  2 , Pavan Heggadadevanakote Kendaganna  2 , Mohamed Rafiq  1 , Uddagiri Venkanna Babu  3
Affiliations

Investigation of HPLF-111624 in Modified Experimental Models of Ulcerative Proctitis and Anal Fissure in Rats

Mallappa Onkaramurthy et al. J Exp Pharmacol. .

Abstract

Background: Although ulcerative proctitis (UP) and anal fissure (AF) are common anorectal diseases, there are no appropriate experimental models to screen the drugs intended for these conditions. In this context, existing experimental models mimicking these diseases were modified and the polyherbal formulation, HPLF-111624 was evaluated in these models.

Objective: To establish animal model for UP and AF and to evaluate polyherbal formulation, HPLF-111624 in these disease models.

Methods: An experimental model of UP was selected based on the modification of the ulcerative colitis model using different concentrations of acetic acid. The concentration used for induction were 2.5%, 5% and 10% v/v and different weights used to induce AF were 25 g, 50 g and 100 g, which were selected based on the severity of inflammation, fecal score, gross pathology, and histopathological evaluation. Furthermore, these animal models were used to evaluate the efficacy of HPLF-111624, a polyherbal formulation known to be beneficial in anal diseases.

Results: Acetic acid at 5% produced typical pathological changes that resembled UP, with a significant increase in the fecal score, gross lesion, and histopathological changes. Similarly, among the three weights, physical injury with a 100 g weight produced significant changes in the histopathological score in the model of AF. Intervention with HPLF-111624 at doses of 250 and 500 mg/kg b.wt., showed a reduction in the inflammatory cytokines and a significant improvement in the histopathological findings in both the conditions.

Conclusion: The results showed that the modified experimental models for UP and AF resemble the human pathological conditions and are simple, versatile and may be used for screening drugs intended for these conditions. Intervention with HPLF-111624 was found to be effective in improving the pathological state of UP and AF.

Keywords: anal fissure; anorectal disorders; histopathological evaluation; inflammation; polyherbal formulation; ulcerative proctitis.

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Conflict of interest statement

The authors are employees of Himalaya Wellness Company, Bengaluru, Karnataka, India. The authors declare no other conflicts of interest in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
A line graph showing the different groups fecal consistency score or fecal score induced with different concentrations of acetic acid (AA) in the ulcerative proctitis model development.
Figure 2
Figure 2
Representative gross morphology rectum pictures and the impact of rectal damage induced by different concentrations of acetic acid in the ulcerative proctitis model.
Figure 3
Figure 3
Representative photomicrographs of histopathological changes in the rectal tissues induced with different concentrations of acetic acid in ulcerative proctitis model.
Figure 4
Figure 4
Representative gross morphological rectum pictures of different groups with clear slit/ fissure formation by physical injury technique using different weights suspended on electro nickel–plated wire in anal fissure model development.
Figure 5
Figure 5
Representative photomicrographs of histopathological changes in the rectal tissue caused by the induction of anal fissure using different weights in anal fissure model.
Figure 6
Figure 6
A line graph showing the effect of HPLF-111624 on the fecal score in acetic acid-induced ulcerative proctitis.
Figure 7
Figure 7
Representative gross morphology rectum picture showed the protective effect of HPLF-111624 in acetic acid-induced ulcerative proctitis animals.
Figure 8
Figure 8
Representative photomicrographs showed the effect of HPLF-111624 on the histopathological changes of rectum tissues in acetic acid-induced ulcerative proctitis.
Figure 9
Figure 9
Representative gross morphology rectum pictures showed the effect of HPLF-111624 on the anal fissure.
Figure 10
Figure 10
Representative photomicrographs showed the effect of HPLF-111624 treatment on the histopathological changes of the rectal tissue in the anal fissure.
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