Exploring Molecular Mechanisms of Aloe barbadmsis Miller on Diphenoxylate-Induced Constipation in Mice

Abstract

Aloe barbadensis Miller (Aloe) known as a common succulent perennial herb had been traditionally used in constipation for more than 1,000 years. Aloe contained anthraquinones and other active compounds which had laxative effect and could modulate constipation. However, the therapeutic effects and mechanisms of aloe in constipation were still unclear. To explore the therapeutic effects and mechanisms of aloe in treating constipation, we employed network pharmacology, molecular docking, and mice experiments in this study. Our network pharmacology indicated that beta-carotene, sitosterol, campest-5-en-3beta-ol, CLR, arachidonic acid, aloe-emodin, quercetin, and barbaloin were the main active ingredients of aloe in treating constipation. Besides, the MAPK signaling pathway was the principal pathway utilized by aloe in treating constipation. Molecular docking results revealed that beta-carotene and sitosterol were acting as interference factors in attenuating inflammation by binding to an accessory protein of ERK, JNK, AKT, and NF-κB p65. Otherwise, in vivo experiments, we used diphenoxylate-induced constipation mice model to explore the therapeutic effects and mechanisms of aloe. Results showed that aloe modulated the constipation mice by reducing the discharge time of first melena, improving the fecal conditions, increasing the gastric intestinal charcoal transit ratio, and improving the intestinal secretion in small intestine. Besides, aloe played an important regulation in promoting intestinal motility sufficiency and the levels of neurotransmitters balance with 5-HT, SP, and VIP on constipation mice. Moreover, aloe significantly inhibited the mRNA and proteins expressions of ERK, JNK, AKT and NF-κB p65 in colon. Our study proved that aloe could reverse diphenoxylate-induced changes relating to the intestinal motility, intestinal moisture, and inhibition of the MAPK (ERK, JNK)/AKT/NF-κB p65 inflammatory pathway. Our study provided experimental evidences of the laxative effect of aloe, which was beneficial to the further research and development of aloe.

Review of Medicinal Plants Traditionally Used to Treat Diarrhea by the People in the Amhara Region of Ethiopia

“…The antidiarrheal activity of the chemical components of Aloe spp. includes polysaccharides, glycoproteins, and anthraquinones, exhibits anti-inflammatory effects [ 122 ], modulates intestinal motility [ 123 ], possesses antimicrobial activity [ 124 ], protects the intestinal mucosa [ 125 ], and regulates ion transport [ 126 ].…”

The Potential Application of Aloe Barbadensis Mill. as Chinese Medicine for Constipation: Mini-Review

“…Moreover, the intervention resulted in increased SP and decreased VIP content in mice serum, promoting the contraction of intestinal smooth muscle and enhancing intestinal propulsion. 34 Beck et al conducted a study that demonstrated the inhibitory effect of nitric oxide (NO) on gastrointestinal motility by reducing intracellular calcium levels and relaxing smooth muscle cells through stimulation of intracellular soluble guanylyl cyclase (sGC). 35 Meanwhile, Izzo et al showed that Aloe barbadensis Mill.…”

Evaluation of Semen Quality, Seminal Biochemical Traits, and Histological Features of Aloe Vera Extract Administrated to Rabbit Bucks

“…The clear gel inside the leaf is extracted and used as an excellent treatment for various skin wounds and burns, and other skin problems, as it helps speeds up the healing rate, reduces the risk of infection, and improves the quality of skin texture (Hekmatpou et al, 2019). It can also be used as a treatment for chronic constipation, low appetite, and recurring digestive problems (Tang et al, 2022). Vitamins, enzymes, minerals, carbohydrates, lignin, saponins, salicylic acids, and amino acids are among 75 potentially active constituents in Aloe vera (Atherton, 1998).…”