Study Of Hepatoprotective And Anti-inflammatory Effects Of Long Dan Xie Gan Decoction And Their Mechanisms

Long Dan Xie Gan decoction (LDXGD), a formula in Yi Fang Ji Jie (Collection of Prescriptions with Notes), is well known for its effect in draining excessive fire from the liver and gallbladder, and purging damp heat from San Jiao. It is composed of Longdancao (Radix Gentinae), Huangqin (Radix Scutellariae Baicalensis), Zhizi (Semen Garfeniae Jasminoidis), Zexie (Rhizoma Alismatis Orientalitis), Mutong (Caulis Akebiae), Danggui (Radix Angelicae Sinensisi), Shengdihuang (Radix Rhemanniae Glutinosae), Chaihu (Radix Bupleurii) and shenggancao (Radix Glycyrrhizae Uralensis). It has been reported that the different herbs composing this formula have many therapeutic effects such as antimicrobial, anti-inflammatory, antipyretic, cholagogic, hepatoprotective, hypotensor, diuretic and blood-fat-lowering effects. Other studies in laboratory animals showed that LDXGD can increase immune organ relative weight and macrophage phagocytic function, and induce lymphoid cell transformation and that its therapeutic effects may be related to this immuno-stimulating effects.The present study was conducted to further study the effect of this formula on the immune system, investigate its hepatoprotective effect and observe whether or not it has any side-effect under experiment conditions.In the first part, biochemical parameters reflecting liver (ALT, AST, ALB, TP, UA) and renal function(UA, CRE), and muscle tissue integrity(CK) were monitored three times in 4 weeks, time during which three different doses of LDXGD were administered to different groups of mice. The results show that there is no significant difference in the serum level of the monitored parameters between the animals treated with LDXGD and the control animals. This suggests that, under experiment conditions, LDXGD has no side effect on liver and renal function, and muscle tissue integrity.In the second part, the hepatoprotective effect of LDXGD was studied in mice with CCl₄-induced hepatitis. The results show that LDXGD significantly decreases the level of serum ALT and LDH in the treated animals; it also reduces CCl₄-induced damages in liver tissue. This confirms similar results reported in other studies and indicates that LDXGD has hepatoprotective effect.In the third part, the effect of LDXGD on the immune system was investigated by observing the effect of the administration during 20 days of three different doses (0.5～20 g/Kg/day) of the formula on T lymphocytes subpopulation dynamic changes, immune organs relative weight and intestinal mucosal IgA level. The results show that a dose of 0.5 g/Kg/day has the best effect on T cell subpopulation dynamic changes in that it can both increase the CD4⁺ T cell percentage and decrease CD8⁺ T cell percentage, and thus increase CD4⁺/CD8⁺ ratio; administration of both 0.5 g/Kg/day and 2 g/Kg/day doses during 20 days significantly increases spleen index; the three doses no-significantly decrease the intestinal IgA level with a negative correlation between the dose administered and the decrease in IgA level. These results suggest that LDXGD has a potentiating effect on the systemic immunity by inducing the multiplication and differentiation of lymphocytes. As for its observed effect on the intestinal IgA level, it may be due to its possible inhibiting effect on mucosal immunity after a long-time of oral administration. To better elucidate the effect of LDXGD on the mucosal immunity, further studies should be carried out to study its effect on the mucosa-associated lymphoid tissues both at tissular and molecular levels.