Changrui enema inhibits inflammation-induced angiogenesis in acute radiation proctitis by regulating NF-κB and VEGF

Abstract

Purpose Changrui enema, a traditional Chinese medicine prescription, is used as a supplementary treatment for acute radiation proctitis (ARP). Herein we explored the inhibition effects of Changrui enema on NF-κB and VEGF in ARP mice. Methods A total of 120 C57BL/6 mice were divided randomly into normal mice group, ARP mice group, western medicine enema group (dexamethasone combined with gentamicin), and Changrui enema group. ARP mice were established by pelvic local irradiation. The expression of IL-1β, NF-κB, VEGF, AQP1, AQP3, p-ERK1/2 and p-JNK was determined by immunohistochemistry or western blot. Results The study firstly found that Changrui enema alleviated ARP mice. The expression of IL-1β, NF-κB, VEGF, AQP1 and p-ERK1/2 was increased in ARP mice, and was reserved by Changrui enema. However, the expression of AQP3 and p-JNK was decreased in ARP mice, and was up-regulated by Changrui enema. Conclusions Changrui enema is an effective treatment with fewer side effects for ARP. The mechanism of Changrui enema may be related to the inhibition of inflammation-induced angiogenesis. Changrui enema inhibits IL-1β and NF-κB expression as well as VEGF expression. Interestingly, AQP1 promotes angiogenesis, while AQP3 inhibits inflammation. Changrui enema probably inhibits AQP1 expression by down-regulating p-ERK1/2, and improves AQP3 expression by up-regulating p-JNK.

Novel mechanisms underlying inhibition of inflammation-induced angiogenesis by dexamethasone and gentamicin via PI3K/AKT/NF-κB/VEGF pathways in acute radiation proctitis

“…Spleen is the largest lymphoid organ 62 and modulates the immune system by producing lymphocytes, immunoglobulin and complement, etc. Our previous study found that DXM + GM enema reduced spleen weight and promoted lymphocyte apoptosis by increasing Bax and suppressing Bcl-2 5 . We propose that apoptosis induction of DXM + GM may be an organ-specific effect.…”

“…As everyone knows, VEGF is one of the most key cytokines in promoting angiogenesis 24 . Studies 5,21 have demonstrated that the high expression of VEGF is related to angiogenesis in ARP. Here, we put forward a hypothesis that "inflammation-induced angiogenesis" exists in pathogenesis of ARP.…”

“…Our previous study showed that DXM and GM combination enema could alleviate the symptoms of ARP mice 5 . Inflammation and angiogenesis are thought to play key roles in ARP.…”

“…Our previous study has found that the commonly accepted treatment for patients with radiation proctitis in China is dexamethasone (DXM) combined with gentamicin (GM) 20 . But in some extent, the combination of DXM and GM results in decrease in immunity of ARP mice 5 .…”

“…Radiation proctitis is traditionally divided into acute radiation proctitis (ARP) and chronic radiation proctitis (CRP), which are up to 50-75% and 5%, respectively 3 . The mechanism of radiation proctitis is not completely clarified but several signaling pathways have been suggested as part of the pathogenesis of this disease, including inflammatory response 4 , angiogenesis [5][6][7] , immune system 4 , cell adhesion 8 , and extracellular matrix remodeling 9 . It is characterized by abdominal pain, mucous bloody diarrhea, as well as anal spasm and tenesmus 3 , even intestinal obstruction or perforation.…”