Protective Effects ofTotal Glucosides of Paeonyon N-nitrosodiethylamine-induced Hepatocellular Carcinoma in Rats via Down-regulation of Regulatory B Cells

Abstract

Total glucoside of paeony (TGP), extracted from the root of Paeonia Lactiflora, has been known to show anti-inflammatory, anti-oxidative, hepato-protective and immuno-regulatory activities. The aim of this present study was to determine the anti-tumor effect of TGP against N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) in rats, and to find the related mechanisms. Rat HCC model was established by intragastrically administrating with DEN (8 mg/kg). We found the number of tumor nodules and the index of liver and spleen were increased in the model group compared with the normal group, and was significantly decreased by TGP. Additionally, TGP obviously improved the hepatic pathological lesions induced by DEN, and decreased the elevated levels of serum alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST), alkaline phosphatase (ALP) and alpha fetoprotein (AFP) by DEN. Moreover, TGP decreased the level of B cell-activating factor (BAFF) and the proportion of IL-10-producing regulatory B cells (Bregs), and the decrease of BAFF by TGP is positively correlated to the decrease of IL-10-producing Bregs by TGP. These results suggest that TGP had a good therapeutic action on DEN-induced HCC rats, which might be due to its down-regulation of Bregs through reducing the level of BAFF.

Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer

“…94 Other mediators, such as total glucosides of paeony and Lipoxin A4, also exerted an antitumor effect by inhibiting Bregs. 95,96 These molecules attenuated the expansion of Bregs by inactivating Stat3 and/or ERK, leading to a reduction in IL-10 or TGF-β, which further decreases Breg-induced Treg generation. 94,96 In addition, the inactivation of the 5-lipoxygenase/leukotriene/PPARα pathways in Bregs, for example, using MK886 is sufficient to abrogate cancer escape and metastasis through the loss of Tregs and the release of effector CD8 + T cells in lung metastasis.…”

Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer

“…Mechanistically, MEK inhibition might reduce Bregs through the interruption of chronic BCR signaling, thus impairing the upregulation of specific suppressive surface molecules. Regarding HCC, total glucoside of paeony (TGP), which is extracted from the root of Paeonia Lactiflora, decreased the proportion of B10 cells in the spleens of experimental rats, which at least partially contributed to the anti tumor effect of TGP on rat HCC (97). In addition, lipoxin A4 (LXA4) is an arachidonic acid-derived anti-inflammatory lipid mediator that possesses anti-tumor potential through modulating tumor-immune microenvironments.…”

A Pharmacological Review of Bioactive Constituents ofPaeonia lactifloraPallas andPaeonia veitchiiLynch

“…The concentration of these compounds varies, depending on the sample and extraction method; however, paeoniflorin is always the primary compound. Other major TGP constituents include paeonin, albiflorin and benzoylpaeoniflorin, whilst minor constituents include paeoniflorigenone, paeonianiin E, paeonidanin A, paeonidanin B and paeonidanin C (He and Dai, 2011;Song et al, 2015). Individually, these monoterpene glycosides display inhibitory effects on nitric oxide (NO) production, reduce inflammatory response and prevent NO hyperfunction such as tissue damage.…”