Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats

Abstract

Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF.

Imidazole alkaloids inhibit the pro-inflammatory mechanisms of human neutrophil and exhibit anti-inflammatory propertiesin vivo

“…This mechanical test has an advantage over chemical tests, such as acetic acid‐induced writhing and the formalin tests, since it mimics clinical conditions associated with cutaneous hyperalgesia, such as neuropathic pain and osteoarthritis . Our data also suggest that EPI and EPIIS diminish the accumulation of neutrophils in the paw, as measured by the activity of the MPO enzyme in the tissue, corroborating previous studies have shown that these alkaloids inhibit the migration of cells to the inflammatory focus . This may be due to the blockade of the activation of neutrophils, as reported in the in vitro experiments because ROS generated by neutrophils can amplify their own recruitment and increase the severity of the inflammatory response by activation of transcription factors sensitive to changes in redox conditions, such as NF‐kB, which can control the expression of inflammatory cytokines and chemokines, thus favouring the recruitment of immune cells.…”

“…[45][46][47] Our data also suggest that EPI and EPIIS diminish the accumulation of neutrophils in the paw, as measured by the activity of the MPO enzyme in the tissue, corroborating previous studies have shown that these alkaloids inhibit the migration of cells to the inflammatory focus. [13][14][15] This may be due to the blockade of the activation of neutrophils, as reported in the in vitro experiments because ROS generated by neutrophils can amplify their own recruitment and increase the severity of the inflammatory response by activation of transcription factors sensitive to changes in redox conditions, such as NF-kB, which can control the expression of inflammatory cytokines and chemokines, thus favouring the recruitment of immune cells. However, we cannot exclude the possibility that EPI and EPIIS might also act directly on the neutrophils migration or exerting other anti-inflammatory mechanisms.…”

“…The antinociceptive effect of EPI seems to be partially mediated by the activation of the opioid receptors, while the anti‐inflammatory effect occurred by the reduction in the paw oedema and decrease in leucocyte migration, and TNF‐α and IL‐1β levels in the peritoneal cavity . Additionally, EPI showed gastroprotective effects against naproxen‐induced gastric damage and intestinal inflammation . Thus, it might be an alternative to NSAIDs.…”

“…[13] Additionally, EPI showed gastroprotective effects against naproxen-induced gastric damage and intestinal inflammation. [14,15] Thus, it might be an alternative to NSAIDs. On the other hand, there are very few studies exploring EPIIS.…”

Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties

“…mansoni [ 17 , 19 , 20 – 21 ]. Other biological functions have been described, including anti-inflammatory, anti-contraceptive [ 22 ], and gastro-protective effects [ 23 ]. The pharmacological action of epiisopilosine (EPIIS) and isopilosine (ISOP) against S .…”