Short-term oral administration of ginseng extract induces type-1 cytokine production.

Ginseng radix (Panax ginseng C.A. Meyer) is a popular herbal medicine used as a major ingredient in tonic recipes in eastern Asian countries. In our study, male BALB/c mice were treated orally with various doses of ginseng root extract for 5 consecutive days. The extract reduced the serum level of IgG but elevated the level of IgA. Under in vitro condition, the lipopolysaccharide-stimulated spleen cells from the ginseng-treated mice also showed a significant decrease in IgG production but an increase in IgA production. The serum level and production of IgM was unaffected. The interleukin-2, interferon-gamma (Th1-type cytokines), and interleukin-10 (Tr1-type cytokine) production by Con A-stimulated spleen cells from the ginseng-treated mice showed an upregulation relative to the control group. However, the production of interleukin-4 (Th2-type cytokine) showed no significant change. The activity of natural killer cells was increased in the ginseng group, but the percentages of T-lymphocytes (CD3(+)) and CD4(+)8(-), CD4(-)8(+) subset were reduced. Thus, short-term oral administration of ginseng extract appears to enhance Th1-type cytokine production.

Long-term oral administration of ginseng extract modulates humoral immune response and spleen cell functions.

Ginseng radix (Panax ginseng C.A. Meyer) is a popular herbal medicine in Oriental countries. We investigated the effect of long-term oral administration of ginseng extract on the antigen-specific antibody response. Male BALB/c mice were treated orally for 30 consecutive days with 2 g/kg of a 50% ethanol extract of ginseng root. Mice treated with ginseng and immunized with ovalbumin (OVA), resulting in an eight-fold increase in titers of anti-OVA immunoglobulin (Ig)G in the serum compared to the group receiving OVA immunization without ginseng treatment; the level of IgG was also significantly elevated in the mice treated with ginseng and immunized with OVA. Mice treated with ginseng without OVA immunization exhibited significantly reduced IgG and IgA production by spleen cells. However, IgG production was not affected in mice treated with ginseng and OVA immunization in spleen cells. Interleukin (IL)-2, interferon (IFN)-gamma and IL-4 secretion by spleen cells from either ginseng-treated mice or OVA-immunized mice were down-regulated compared to that in the control group; while the production of IL-10 was unchanged. The percentage of CD8+ cells was significantly reduced in spleen cells from ginseng-treated, OVA-immunized mice. Thus, long-term oral administration of ginseng extract appears to potentiate humoral immune response but suppress spleen cell functions.

Intraperitoneal injection of ginseng extract enhances both immunoglobulin and cytokine production in mice.

Ginseng is one of the most widely used Chinese herbal medicines. In this report, the relatively short-term effect of ginseng extract on the immunoglobulin production and cytokine production was studied. The ginseng extract was prepared by boiling the ground ginseng root in 50% ethanol. The specific pathogen-free mice were intraperitoneally (i.p.) injected with various doses of ginseng extract for 3 consecutive days. The results indicated that the serum levels of immunoglobulin (Ig)M, IgG and IgA were significantly elevated after the mice were i.p. injected with 4 g/kg/day of ginseng extract. Under in vitro condition, the lipopolysaccharide (LPS)-stimulated spleen cells showed a dose-dependent increase in secretion of IgM, IgG and IgA. However, at a higher dosage (4 g/kg/day), the amount of IgA secretion began to decline. The serum level of interleukin (IL)-2, interferon (IFN)-gamma[T-helper (Th) 1-type cytokines] and IL-4 and IL-10 (Th2-type cytokines) were significantly elevated after the mice were i.p. injected with 2 g/kg/day or higher doses of ginseng extract. The amount of cytokine secretion by concanavalin A (Con A)-stimulated spleen cells was also significantly enhanced after the mice were i.p. injected with 0.4 g/kg/day or higher dose of ginseng extracted. To further confirm the results from enzyme-linked immunosorbent assay (ELISA), the spleen cells were cultured for 36 hours in the presence of 1 microgram/ml of Con A. Total mRNA was isolated and assayed for mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR). The results revealed that expression of IL-2 and IFN-gamma mRNA were dose-dependently enhanced by the ethanol extract of ginseng. The levels of IL-4 and IL-10 mRNA expression were also elevated in the spleen cells of ginseng-treated mice in comparison with that of the control group. In addition, we observed that the concentrations of IgG1, IgG2a and IgG2b in culture supernatants of spleen cells were dose-dependently increased by in vivo treatment of ginseng extract, suggesting that both Th1- and Th2-type cytokines were involved in IgG production. Our observation in this study demonstrated that the Chinese herbal drug ginseng was able to regulate antibody production by augmenting Th1- (IL-2, IFN-gamma) and Th2-type (IL-4, IL-10) cytokine production.

Identification and characterization of LDL receptor gene mutations in hyperlipidemic Chinese.

DNA screening for LDL receptor mutations was performed in 170 unrelated hyperlipidemic Chinese patients and two clinically diagnosed familial hypercholesterolemia patients. Two deletions (Del e3-5 and Del e6-8), eight point mutations (W-18X, D69N, R94H, E207K, C308Y, I402T, A410T, and A696G), and two polymorphisms (A370T and I602V) were identified. Of these mutations, C308Y and Del e6-8 were found in homozygosity, and D69N and C308Y were seen in unrelated patients. The effects of mutations on LDL receptor function were characterized in COS-7 cells. The LDL receptor level and activity were close to those of wild type in A696G transfected cells. A novel intermediate protein and reduction of LDL receptor activity were seen in D69N transfected cells. For R94H, E207K, C308Y, I402T, and A410T mutations, only approximately 20-64% of normal receptor activities were seen. Conversely, Del e3-5 and Del e6-8 lead to defective proteins with approximately 0-13% activity. Most of the mutant receptors were localized intracellularly, with a staining pattern resembling that of the endoplasmic reticulum and Golgi apparatus (D69N, R94H, E207K, C308Y, and I402T) or endosome/lysosome (A410T and Del e6-8). Molecular analysis of the LDL receptor gene will clearly identify the cause of the patient's hyperlipidemia and allow appropriate early treatment as well as antenatal and family studies.

A Chinese herbal medicine, fu-ling, regulates interleukin-10 production by murine spleen cells.

Fu-ling is one of the most widely used Chinese herbal medicines. In this study, we investigated the regulatory effect of fu-ling on interleukin-10 (IL-10) production in vivo. Mice were i.p. administered 0.1 mg to 1.0 mg fu-ling per gram body weight daily for three days. The spleen cells were isolated and assayed for both IL-10 and immunoglobulin (Ig) production. Results indicated that the mice treated with fu-ling had significantly increased spleen cell ability to secrete IL-10. Spleen cells isolated from the mice injected with either 0.1 mg or 1.0 mg fu-ling per gram body weight also showed an increase in IL-10 mRNA expression. As IL-10 is a potent differentiation factor of B-lymphocytes, the possible effect of fu-ling on Ig production was also studied. Results indicated that fu-ling significantly induced an increase in IgG and IgA secretion by spleen cells but showed no effect on IgM secretion. Thus, fu-ling may affect the function of B-lymphocytes via stimulating IL-10 production.