Onkaramurthy Mallappa, Azeemuddin Mohammed Mukhram, Baig Mirza Rizwan, Kendaganna Pavan Heggadadevanakote, Rafiq Mohamed, Babu Uddagiri Venkanna
Discovery Sciences Group, Research and Development Center, Himalaya Wellness Company, Bengaluru, Karnataka, India.
Microbiology and Toxicology Department, Research and Development Center, Himalaya Wellness Company, Bengaluru, Karnataka, India.
J Exp Pharmacol. 2022 Apr 27;14:149-165. doi: 10.2147/JEP.S345599. eCollection 2022.
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.
To establish animal model for UP and AF and to evaluate polyherbal formulation, HPLF-111624 in these disease models.
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.
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.
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.
尽管溃疡性直肠炎（UP）和肛裂（AF）是常见的肛肠疾病，但尚无合适的实验模型来筛选针对这些病症的药物。在此背景下，对现有的模拟这些疾病的实验模型进行了改良，并在这些模型中对多草药配方HPLF - 111624进行了评估。
建立UP和AF的动物模型，并在这些疾病模型中评估多草药配方HPLF - 111624。
基于对溃疡性结肠炎模型的改良，使用不同浓度的乙酸选择了UP的实验模型。诱导所用的浓度为2.5%、5%和10%（v/v），用于诱导AF的不同重量为25 g、50 g和100 g，这些是根据炎症严重程度、粪便评分、大体病理学和组织病理学评估选择的。此外，这些动物模型用于评估HPLF - 111624的疗效，HPLF - 111624是一种已知对肛门疾病有益的多草药配方。
5%的乙酸产生了类似于UP的典型病理变化，粪便评分、大体病变和组织病理学变化显著增加。同样，在这三种重量中，100 g重量的物理损伤在AF模型中导致组织病理学评分出现显著变化。以250和500 mg/kg体重的剂量用HPLF - 111624进行干预，在两种病症中均显示炎症细胞因子减少，组织病理学结果有显著改善。
结果表明，改良后的UP和AF实验模型类似于人类病理状况，简单、通用，可用于筛选针对这些病症的药物。发现用HPLF - 111624进行干预可有效改善UP和AF的病理状态。
