What Is the Benefit of Epimedium Extract?

Epimedium, also known as “herbs of the immortals”. It is a traditional Chinese medicine that tonifies the kidneys and strengthens the yang, strengthens the muscles and bones, and dispels rheumatism. In recent years, Epimedium has been used to treat coronary heart disease, hypertension, chronic bronchitis, polio, neurasthenia, and sexual neurasthenia, with certain efficacy. Pharmacological studies of traditional Chinese medicine have shown that Epimedium has sex hormone-like effects; anti-catecholamine effects, as well as blood pressure lowering, blood lipid lowering, blood sugar lowering, antibacterial and other effects. 2,3. A large number of studies have shown that in the pathological state of “yang deficiency”, the immune function of the body is in a low state, and Epimedium has a good effect of tonifying the kidney and strengthening yang. From this perspective, many domestic scholars have studied the effects of Epimedium and its extracts on the immune function of humans and animals. A large number of experimental studies have shown that Epimedium and its extracts have a significant enhancing and regulating effect on the immune function of the body. This paper intends to summarize the current research status in this area.

1 Effect on immune organs

Ding Yan et al. studied the immunopharmacological effects of Epimedium polysaccharides on the thymus. 4 They found that Epimedium polysaccharides (10-50 mg/kg) injected subcutaneously can cause the thymus of mice to shrink, and at the same time, they found that the number of thymus L-cells and L3-cells decreased, and the response to PHA was weakened, indicating a decrease in mature and more mature T cells in the thymus. On the other hand, thymus ³HTdR incorporation increased, and interleukin-2 (IL-2) synthesis increased, indicating robust thymus cell proliferation. In addition, studies have shown that after injection of Epimedium polysaccharide, there is no sign of cell necrosis or tissue structure damage in the thymus of mice. 5 Therefore, It is believed that the immunological pharmacological effect of Icaris polysaccharide on the thymus is mainly to promote the release of mature cells from the thymus (the effect of promoting the release of thymocytes is more obvious than that of promoting the proliferation of thymocytes), and its effect of thymus shrinkage is not the result of immunosuppression, but one of the mechanisms of enhancing the body's cellular immune function.

Wang Tianran et al. found that 15–60 mg/kg·d of icariin continuously injected for 7 days can significantly enlarge the spleen and increase the number of nucleated cells in the spleen, indicating that icariin can promote the proliferation of antigen-activated lymphocytes, but has no significant effect on the thymus.

2. Effects on immune cells

2.1 Effects on macrophages

Macrophages (M) are important immune cells with multiple functions, and can play an important regulatory role in immune function by processing antigens and releasing soluble factors. Wang Tianran et al. used 25 mg/kg and 50 mg/kg of Icaris flavonoids to continuously administer mice, which increased the phagocytosis rate of peritoneal MØ by 52% and 99%, and the phagocytosis index by 69% and 191%. This shows that Icaris total flavonoids can significantly improve the phagocytic function of MØ. Luo Bao et al. (8) started with the in vitro effect of hydrocortisone and observed the protective effect of the tonifying-qi and yang-promoting formula. They found that Icaris, whether in compound or single herb form, has a certain enhancing effect on the functional state of M receptors. This enhancing effect is not significant under normal conditions of the body, but becomes apparent under the in vitro action of immunosuppressants. The experimental results show that one of the mechanisms by which the traditional Chinese medicine Epimedium sagittatum affects the body's immune function may be through influencing certain immune functions of Fc receptors mediated by M, thereby adjusting and improving the body's immune status.

2.2 Effect on T cells

T cells are divided into many subgroups according to their function, such as T helper cells (TH), T suppressor cells (Ts), cytotoxic T cells (Tc), etc., and the body's cellular immune function is mainly accomplished by these types of cells. A study of the effects of a decoction of Epimedium brevicornum on peripheral blood lymphocytes in vitro in normal people showed that Epimedium brevicornum increased the rate of active Ea (Ea) but not the total Ea (Et), suggesting that the mode of action of Epimedium brevicornum in enhancing cellular immunity may be similar to that of thymosin. It was also found that the water decoction of Epimedium brevicornum at high concentrations also inhibited the Ea and Et rates (while also detecting and excluding the cytotoxic effect of Epimedium brevicornum on lymphocytes), exhibiting a concentration-dependent bidirectional effect. However, the water decoction of Epimedium brevicornum at high and low concentrations had different degrees of effect on reducing the percentage of ANAE+ lymphocytes, The high concentration group is particularly significant. 9'Hor- witz found that ANAE activity is lost during lymphocyte transformation. 10Cheng Qingzhu et al. found that the water decoction of Epimedium brevicornum promotes lymphocyte transformation in rats with chronic renal insufficiency model of 7/8 nephrectomy. (1) This seems to suggest that the inhibition of ANAE activity in lymphocytes by Epimedium brevicornum is somehow related to the promotion of lymphocyte transformation.

Yang Guizhen, Wang Tianran, et al. (12,7) found that Icaris total flavonoids can significantly enhance lymphocyte transformation in ConA-stimulated immune-suppressed mice, and promote the continuous dynamic changes in T lymphocyte transformation stimulated by ConA in immune-suppressed mice, which is highly statistically significant (P<0.01) compared with the control group. Ding Yan et al. showed that (133 Epimedium polysaccharide has a promoting effect on ³HTdR incorporation in mouse thymocytes, indicating that Epimedium polysaccharide can promote T cell proliferation, and the effect in vivo occurs rapidly, with an effect 12 hours after administration. It is believed that Epimedium polysaccharide has a mitogenic-like effect on mouse lymphocytes.

Recently, many scholars believe that the immune function promoted or inhibited by drugs may be related to regulatory T cells, especially suppressor T cells (Ts). Ts cells play a very important role in the immune regulatory loop, and many immune disorders are related to the dysfunction of Ts cells. Studying the effect of drugs on immune regulatory cells, especially Ts cells, is of great significance for regulating the body's immune function and thus preventing and treating diseases.

Wang Tianran et al. induced Ts cell activity by intraperitoneal super-dose immunization (SOI) with SRBC 4 × 10⁹/mouse in normal donor mice. The spleen cells of this donor mouse were then injected intravenously at 4 × 10⁷/mouse into a normal recipient mouse of the same species, and the recipient mouse was also immunized intraperitoneally with SRBC 4 × 10⁸/mouse at the same time. Five days after immunization, the antibody production level of the recipient mouse's spleen cells was measured (the drug was injected into the donor mouse).

The results showed that Icaris polysaccharide (50 mg/kg·d×7SC) can promote the production of SOI-induced Ts cells and inhibit antibody production in the recipient mouse, thereby significantly reducing the antibody production level of the recipient mouse compared to the SOI control group (P<0.001). In contrast to Icaris polysaccharide, icariside has a weakening effect on Ts cell production, resulting in a significantly higher antibody production level in the receptor mouse than in the SOI control group (P<0.001). The opposite regulatory effects of Icariin and Icariin on Ts cell activity suggest that the traditional Chinese medicine Epimedium has a bidirectional regulatory effect on the body's immune function. Further research on the regulatory effect of Epimedium on T cell subsets is of great practical significance for the development and application of Epimedium in the prevention and treatment of immune disorders.

2.3 Effect on B cells

B lymphocytes differentiate into plasma cells to secrete immunoglobulins and are responsible for humoral immunity. Geng Pai-li et al. found that Icaris flavonoids can restore the low antibody-forming cell function of “yang deficiency” mice to normal through spectrophotometric (QHS) measurement of erythrocyte hemolysis mediated by spleen cells in “yang deficiency” animals. Blood coagulation antibody titer (HT) measurement showed that Icaris total flavonoids have a significant effect on the antibody titer of “yang deficiency” animals, and it was found that Icaris total flavonoids can counteract the immunosuppressive effect of corticosteroids. Another experiment found that when the dose of Icaris total flavonoids was increased to 100 mg/kg·d, the effect of promoting antibody production was not significant. This suggests a bidirectional regulatory effect of Icaris total flavonoids.

Icaris polysaccharide can increase the incorporation of ³H-TdR into splenocytes in nude mice, indicating that it has a stimulating effect on the proliferation of B cells. 13) Experimental studies by Wang Tianran et al. have shown that icaris polysaccharide can increase the circulating hemolytic antibody levels in mice immunized with SRBC, and that the antibody levels increase even more with increasing doses of icaris polysaccharide. This indicates that Icaris polysaccharide can promote the production of specific antibodies, and this effect is significantly positively correlated with the dose. One month after sensitizing the Icaris polysaccharide group and the control group with SRBC, the antibody levels in the treated group were still higher than those in the control group and lasted longer, thus demonstrating that Icaris polysaccharide can enhance the function of “immune memory”. This effect is strongest at 10 mg/kg·d; increasing the dose no longer has a enhancing effect.

It is worth noting that although both epimedium polysaccharides and epimedium flavonoids can enhance humoral immune function, their mechanisms of action are not exactly the same. Icaris polysaccharides increase the number of antibody-producing cells in the spleen and promote the production of antibodies by each plasma cell by influencing antibody-producing cells in the spleen. The total flavonoids work by influencing the inhibitory components in the immune regulatory loop (total flavonoids can weaken the function of Ts cells). Although the number of antibody-producing cells in the spleen increases, it does not promote the production of antibodies by each plasma cell. This shows that the two have different characteristics.

Studies on the role of icariin in promoting antibody production have found that 6mg/kg·d icariin can increase the level of hemolysin in SR-BC immune mice, with 15mg/kg achieving the maximum effect, which is highly statistically significant (P<0.001) compared to the control group.      Icariin 20mg/kg·d for 7 consecutive days increased the number of antibody-producing cells in the spleens of SRBC-immunized mice, but had no significant effect on the diameter of the empty spots. Icariside 15 ~30mg/kg·d    Starting from the day after a single injection of cyclophosphamide (50mg/kg) in mice, continuous administration for 4d increased the level of antibody production in the spleen by 2 and 2.4 times (P<0.001) compared to mice given cyclophosphamide alone. This indicates that Epimedium not only enhances the humoral immune function of mice, but also counteracts the immunosuppressive effect of cyclophosphamide.

3 Effect on immune factors

In the immune response process, the interaction of immune cells is not only through direct contact between cells, but also through the soluble factors released during the interaction of immune cells. Interleukin (IL) is an important type of immune factor secreted mainly by TH cells and M . Research by Cheng Qingzhu et al. shows that (12) in rats with a chronic renal insufficiency model (renal 7/8 resection), stimulation of mononuclear macrophages in the abdominal cavity with LPS increases IL-1 production (P<0.05), while stimulation of splenic lymphocytes with PHA reduces the response and the level of IL-2 produced (P<0.01). After treatment with Epimedium extract, these changes were improved, and there was a statistically significant difference compared to the group that was not given Epimedium (P<0.05). IL-1 has functions such as activating TH cells, but it also has pyrogenic and pro-inflammatory effects. Therefore, IL-1 may be of great significance in the pathological evolution of 7/8 nephrectomy. The main function of IL-2 is to maintain the growth of T cells in vitro and activate a variety of immune cells. 18 A study of the effect of IL-2 on normal human peripheral blood mononuclear cells found that 19 the effect of Icaris polysaccharide on human IL-2 activity was significantly dose-dependent.

Lower concentrations (100 μg/ml and 1000 μg/ml) can increase IL-2 activity, while higher concentrations (2500 μg/ml and 5000 μg/ml) have the opposite effect of inhibiting IL-2 activity. It has been experimentally proven that the inhibitory effect of high concentrations on IL-2 is not the cytotoxic effect of the drug itself. The mechanism of this two-way regulatory effect of epimedium polysaccharide remains to be explored. Preliminary observations from direct drug induction experiments indicate that epimedium polysaccharide cannot directly induce IL-2 production, but rather promotes PHA-induced T cell production of IL-2, which may change the reactivity of T cells to PHA.

Chen Xiangmei et al. showed that (20, Epimedium extract can also significantly increase the expression of interleukin 2 receptors (IL-2R) on peripheral blood lymphocytes in normal people, patients with glomerulonephritis, and patients with chronic renal insufficiency. The difference is highly statistically significant (P<0.01) compared with the normal control group. IL-2R is present on various immune cells such as TH and NK cells and other immune cells. IL-2 must bind to the IL-2R on the cell to exert its biological effect. This study provides a direction for studying the regulatory effect of traditional Chinese medicine on immune function from the perspective of receptor expression.

Ding Yan et al. reported that (132) 100 mg/kg of Epimedium polysaccharide has an inducers effect on interferon (IFN). Preliminary experimental results show that Epimedium polysaccharide is likely to induce Y-interferon (Y-IFN), and its induction effect is 1/3 of POIYI:C. However, given its advantages of being abundant in medicinal sources, easy to extract, low in price, and non-toxic, it is an effective and novel in vivo interferon inducer.

The aforementioned studies by various scholars have proven that the effects of Epimedium and its extracts on immune function definitely act on multiple levels and in multiple links, but the molecular basis of the mechanism of action is not yet fully understood. The following aspects may become the focus of future research: (1) The effect on important biological molecules related to the body. Yang Guizhen et al. conducted a very meaningful discussion in this regard. Starting from the effect of changes in the cGMP/cAMP ratio on the activation of immunologically active cells, it was observed that Icaris flavonoids can increase cGMP and decrease cAMP in immunosuppressed mice, thereby increasing the cGMP/cAMP ratio, which in turn promotes increased DNA synthesis and cell proliferation, to enhance the immune function of immune-suppressed mice. (12) This line of research has given us some good ideas. (2) Attention should be paid to the study of the effects on the activity of enzymes and receptors closely related to immune function. (3) The mechanism of action of certain immune cells, such as MØ, NK cells, and T cell subsets, should be studied in depth. (4) It is important to consider the immunomodulatory effects of Epimedium and its extracts in the neuroendocrine-immune regulatory network, paying attention to the combination of the microscopic and macroscopic, and the combination of analysis and synthesis. (5) Strengthen research on the immunomodulatory effects of pathological models, because one of the characteristics of the therapeutic and regulatory effects of traditional Chinese medicine on the body is that it often does not have a significant effect on the normal body; it only exerts its effect under pathological conditions. In short, the immunopharmacological studies conducted on Epimedium and its extracts have shown that they may become promising drugs for enhancing the immune function and immune regulation of the body, and play a role in the treatment of immunodeficiency and immune dysfunction.

References

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