Immunoadhesive regulation using multiphytoadaptogene for spontaneous hepatocarcinomas prevention
Authors: Bocharov E. V. , Bocharova O. A. , Karpova R. V. , Kucheryanu V. G. , Kazeev I. V. , Inozemceva E. S. , Soloviev Y. N. , Shprakh Z. S. 
Published: November 2018

The purposeof this investigation was to evaluate the efficacy of correcting the LFA-1 and Mac-1 leukocyte integrins expression on peripheral blood cells as well as IL-6 and IL-10 serum levels using liquid form multiphytoadaptogene preventive application for hepatocarcinomas incidence suppression and life-span increase of CBA inbreed mice.

Materials and methods.The study was carried out on 439 males of inbred CBA mouse strain (subline CBA/LacY). The experimental mice received 10 % liquid form multiphytoadaptogene complex (MPAC) solution in drinking water during the first month of life including the final time period of liver differentiation (preventive administration). MPAC is the standardized herbal formula composed of 40 plant extracts components including adaptogenes Panax ginseng, Eleutherococcus senticosus, Rhodiola rosea, as well as compounds with phenolic structure (flavonoids, triterpene glycosides, etc). Anti-mutagenic, anti-oxidant, immunomodifying activities of MPAC were demonstrated. The CD11a and CD11b antigens expressions on peripheral blood cells were analyzed by indirect immunofluorescence reaction, serum cytokines IL-6 and IL-10 concentrations were determined by enzyme-linked immunosorbent assay as well as the liver tissue morphology were analyzed at the age of 4, 8, 22 months. Tumor incidence and volumes were evaluated at the age of 8 and 22 months. Motor activity and physical status (body weight, coat state) were estimated in the ontogenesis. The average life-span and survival median was analyzed by the Kaplan–Meier method. Statistical analysis was performed with the program STATISTICA 6.0.

Results.Inhibited expression of LFA-1 and Mac-1 leukocyte integrins on peripheral blood cells as well as elevated IL-6 and IL-10 serum levels, high incidence of liver tumors (100 % of mice-males), their high number and big sizes in the late period of postnatal ontogenesis in CBA high-cancer inbrede mice, also as life-span not reaching two years was demonstrated. At the same time plural tumor-infiltrating limphocytes were not found. Short-term MPAC preventive administration (during the first month of mouse life occupying the final differentiation period of liver tissue genetically predisposal to hepatoms incidence) revealed the long-term heterotypic adhesion molecules leukocyte integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) up-regulated expression, providing the contact interactions of immune effectors and cancer cells. The events shown is able to enhance the anti-tumor activity of immune reactions including spontaneous hepatocarcinomas lymphocytes infiltration and destruction of tumor tissue. As a result, the hereditary tumors incidence, their number and sizes were reduced as well as life-span and life quality of animals were improved.

Conclusion.Up-regulated leukocyte integrins expression on peripheral blood cells, reduced IL-6 and IL-10 serum levels accompanied by tumors lymphocyte infiltration and destruction using MPAC preventive administration is essential for tumor incidence down-regulation. The herbal formula with multiple components is capable to controle anti-tumor immune reactions, as well as the life-span and life quality of high-cancer animals. Hence, the regulation of adhesion violations involved in tumor incidence can be cancer preventive.