3 Effects of Pei's Shengxue Granules on Cellular Immunity

3 Effects of Pei's Shengxue Granules on Cellular Immunity

The presence of tumors not only suppresses the body's cellular immune function but also impairs humoral immunity, and the use of chemotherapeutic agents can exacerbate this immunosuppression. Therefore, enhancing the immune function of cancer patients, especially preventing and treating the severe immunosuppression that occurs after chemotherapy, has become a major focus of anti-tumor treatment. The body's anti-tumor response is primarily mediated by cellular immunity, which plays a dominant role in eliminating tumors. Particularly in anti-tumor immunity, cellular immunity takes the lead, with T cells and NK cells being the mainstay of cellular immunity and the core force behind the body's anti-tumor defense. The proliferation rate of T lymphocytes is an important immune factor that reflects the body's overall immune capacity. NK cells are a non-specific component of cellular immunity, primarily responsible for immune surveillance and anti-tumor actions. Their anti-tumor effect relies on both non-specific and specific immunity pathways: they can not only inhibit and kill tumor cells but also do so without requiring antigen stimulation, without relying on antibodies or complement, and without MHC restrictions. Compared with specific immunity, their response is faster, their effect is more immediate, and their action is more pronounced. They can also enhance the anti-tumor effects of other cells by producing IL-2, interferon, and other cytokines, playing an important role in the body's immune response. Therefore, the cytotoxic activity of NK cells can effectively reflect the body's immune function [38].

Animal experiments have demonstrated that T-cell-mediated immunity plays a crucial role in rejecting tumors caused by toxins, physical factors, chemical factors, and other carcinogenic influences, as well as in the rejection of allogeneic tumors by normal mice [39]. It has now been confirmed that T-cell-mediated cellular immunity is essential for killing tumor cells and controlling tumor growth, with CD3 representing total T lymphocytes. Based on differences in the TCRVβCD molecule, T cells are divided into two subgroups, expressing CD4 and CD8 molecules respectively, and maintaining a stable balance between the two ensures the body's normal immune response [40]. The ratio of CD4 to CD8 in lymphocytes is a sensitive indicator of immune dysfunction; when immune function is suppressed, CD4 decreases, CD8 increases, and the CD4/CD8 ratio declines. Both CD4 and CD8 can recognize tumor cells, and in many tumors, CD8 can directly kill tumor cells through cytolysis, making it a key effector cell in anti-tumor immunity. CD4+, on the other hand, recognizes tumor cells through various cytokines and enzymes, such as IL-2, IFN-γ, TNF-β, perforin, cytolysins, serine proteases, and telomerase, dissolving target cells. Its anti-tumor effect mainly comes from activating monocytes, macrophages, and NK cells through the release of these cytokines, with monocytes, macrophages, and NK cells acting as mediators. However, in rare cases, CD4+ also plays a supporting role in activating CD8+, providing a second signal for activation through the IL-2 it secretes. Thus, it is evident that T-cell-mediated cellular immunity is a Cytokines are small-molecule proteins secreted by activated immune cells and certain stromal cells. Cytokines themselves form a complex network, playing an important immunoregulatory role in the initiation, propagation, and regulation of immune responses. Many traditional Chinese medicines can promote cytokine secretion. Interleukin (IL) originally referred to cytokines produced by white blood cells that also act among white blood cells; although it was later discovered that interleukins can be produced by other cells and can also act on other cells, this name is still widely used. Currently, 18 types of interleukins have been reported. Interleukin-2 (IL-2) plays a key role in the body's cytokine network, promoting various immune-active cells and serving as an important regulatory factor in the immunity against malignant tumors. IL-2 was discovered in 1976 and was once called T-cell growth factor because of its ability to stimulate T-cell growth [41].

IL-2 is primarily a polypeptide cytokine produced by activated helper T cells, which upregulates the functions of T cells, B cells, NK cells, and macrophages. The biological activity of IL-2 mainly arises through its effects on various target cells, resulting in immune enhancement and immune regulation. Its main biological effects on tumor cells include:

1. Induction of CTL (cytotoxic T lymphocyte) activity. After IL-2 binds to its receptor, it can induce clonal proliferation of activated T cells, thereby enhancing the cytotoxic activity of CTLs against tumor cells.
2. Induction of NK cell activity. It promotes the proliferation and activation of NK cells, increasing their ability to kill tumor cells. NK cells activated by IL-2 are known as lymphokine-activated killer cells (LAK). LAK exhibits broad-spectrum antitumor activity; Rosenberg first discovered in 1982 that lymphocytes from the spleens of tumor-bearing mice and the peripheral blood of cancer patients, after being stimulated and cultured with IL-2, could recognize and kill their own tumor cells.
3. Induction of cytokine secretion. IL-2 can induce peripheral blood mononuclear cells to secrete TNF-α, which kills tumor cells.
4. Promotion of the proliferation and differentiation of activated B cells, as well as enhancement of the tumor-killing effect of macrophages M(Φ), and the IFN-γ and other lymphokines secreted by IL-2-activated NK cells can further enhance the antitumor activities of M(Φ) and NK cells.

Studies have shown that cancer patients exhibit decreased cellular immune function, and the production of IL-2 and IFN-γ, which regulate immune-related cytokines, is also correspondingly reduced. It is now believed that the reduced production of IL-2 and IFN-γ may be the reason why cancer patients cannot induce the natural antitumor activity of NK cells and macrophages [42].

An experiment investigated the effect of Pei’s Shengxue Granules combined with 5-Fu on serum IL-2 levels in tumor-bearing mice. The results showed that the 5-Fu group had significantly lower IL-2 levels, whereas the Pei’s Shengxue Granules plus 5-Fu combination group significantly increased IL-2 levels in tumor-bearing mice, suggesting that Pei’s Shengxue Granules can enhance the body's immune function by acting on IL-2. IL-2 promotes the proliferation and activation of NK cells, enhancing the tumor-killing effect of tumor-bearing mice; therefore, increasing IL-2 levels can indirectly boost the activity of NK cells and macrophages, strengthening the body's immune function. This synergizes with the effects of Pei’s Shengxue Granules in enhancing NK cells and macrophages through other mechanisms, making the granules' ability to enhance immunity even more pronounced.

5 Synergistic Effects of Pei’s Shengxue Granules: Enhancing Efficacy While Reducing Toxicity

The occurrence and development of tumors is a multifactorial, multistage process; accordingly, tumor treatment is also a multi-target, multi-step process. In addition to mechanisms such as enhancing the body's immune function, increasing cytotoxic effects, inducing tumor cell differentiation and apoptosis, reversing tumor drug resistance, and influencing the expression of oncogenes and tumor suppressor genes, traditional Chinese medicine for cancer treatment also involves altering the chemical composition of tumor cells, affecting their metabolism, regulating signal transduction, changing telomerase activity, inhibiting angiogenesis, and exerting anti-mutagenic effects, thereby achieving antitumor effects. Chemotherapy can inhibit tumor growth and improve clinical symptoms during cancer treatment, but it often disrupts the body's immune balance, reducing patients' quality of life. How to increase tumor sensitivity to chemotherapy drugs while reducing their adverse reactions has become an increasingly important and worthy topic of discussion in the field of cancer treatment. Enhancing efficacy refers to increasing tumor sensitivity to chemotherapy drugs and improving therapeutic outcomes during treatment, while reducing toxicity means alleviating patients' adverse reactions during chemotherapy—objectively, this involves using experimental techniques to measure the impact of chemotherapy drugs on experimental indicators. However, the enhancement and reduction of toxicity in chemotherapy should not be viewed in isolation; rather, they should be organically combined to complement each other. On the one hand, reducing toxicity helps enhance efficacy: by boosting patients' immunity and strengthening their immune killing capacity during detoxification, it facilitates the destruction of cancer cells. On the other hand, enhancing efficacy helps reduce toxicity: by indirectly lowering the required dose of chemotherapy, it can mitigate or even prevent adverse reactions. This demonstrates that the immune function of cancer patients is not only closely related to the occurrence and development of tumors, but also serves as an important reference for assessing treatment outcomes and predicting disease prognosis [43–49].

This experiment found that after administering 5-Fu to tumor-bearing mice, both T-lymphocyte proliferation activity and serum IL-2 secretion decreased; however, after combining 5-Fu with Pei’s Shengxue Granules, both parameters increased, indicating that Pei’s Shengxue Granules can counteract the immunosuppression caused by the chemotherapy drug 5-Fu, promote recovery of the body's immune function, and thus enhance its antitumor effects. These results not only support the claim that Pei’s Shengxue Granules have both detoxifying and efficacy-enhancing effects in cancer treatment, but also directly demonstrate an increased tumor suppression rate, objectively confirming the granules' efficacy-enhancing role in cancer therapy and further illustrating that their efficacy-enhancing and detoxifying effects are mutually reinforcing.

Research on Pei Zhengxue’s series of prescriptions

Conclusion

First, Pei’s Shengxue Granules can increase the inhibitory effect of the chemotherapy drug 5-fluorouracil (5-Fu) on the growth of H22 liver cancer xenografts, with a synergistic effect when the two are used together.

Second, Pei’s Shengxue Granules can increase the spleen index and thymus index of H22 tumor-bearing mice after 5-Fu chemotherapy.

Third, Pei’s Shengxue Granules can significantly increase the levels of T-lymphocyte subsets CD3 and CD4, as well as the CD4/CD8 ratio, in the peripheral blood of H22 tumor-bearing mice after 5-Fu chemotherapy, while decreasing the level of CD8.

Fourth, Pei’s Shengxue Granules can significantly increase the serum IL-2 levels of H22 tumor-bearing mice after 5-Fu chemotherapy.

In summary, Pei’s Shengxue Granules have a certain regulatory effect on the immune function of H22 tumor-bearing mice after 5-Fu chemotherapy. From a macro perspective, the granules’ antitumor effect in these mice is achieved through overall tonifying and consolidating actions that improve abnormal immunosuppressive states; microscopically, flow cytometry reveals that Pei’s Shengxue Granules can regulate the cellular immune function of tumor-bearing mice, thereby enhancing their own immune capabilities to achieve efficacy-enhancing and detoxifying effects, improving the survival quality of the mice, and yielding favorable therapeutic evaluations.

Reflections and Prospects

5-Fluorouracil (5-Fu) is a commonly used anticancer drug belonging to the pyrimidine class of antimetabolites, widely employed in chemotherapy for various gastrointestinal tumors. Due to its strong toxic side effects, particularly its damage to the immune system and gastrointestinal function, its high-dose use is limited [4]. T lymphocytes constitute the main cell population of the body's immune system; IL-2, as a cytokine, is an active substance produced by activated T cells and plays an important role in immune and inflammatory responses. It can induce T cells to kill other cells, but does not directly kill tumor cells; its antitumor mechanism lies in stimulating and activating effector cells, thereby indirectly exerting antitumor effects. Pei’s Shengxue Granules, as a purely traditional Chinese medicine preparation, are composed entirely of tonifying and consolidating herbs. Since Professor Pei Zhengxue formulated this prescription, it has been widely used in clinical practice for over 40 years, proving that Pei’s Shengxue Granules are not only highly effective against leukemia but also show significant clinical efficacy against malignant tumors, especially those associated with weakened immune function caused by radiotherapy and chemotherapy. Recent animal experiments have preliminarily confirmed that its effects are consistent with the clinical efficacy observed in practice.

The basis for this research stems from Professor Pei Zhengxue’s more than forty years of clinical experience, fully embodying the idea that clinical experience guides experimental research and avoiding blind experimentation. In future studies, we will make full use of new achievements in modern science and technology to conduct in-depth research on the material basis and related mechanisms by which Pei’s Shengxue Granules regulate immune function to achieve efficacy-enhancing and detoxifying effects, explore Professor Pei’s academic thought on integrating traditional Chinese and Western medicine as well as his clinical diagnostic approaches and treatment methods, so that this granule can receive more objective and microscopic explanations.

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Appendix 1 Flow Cytometry Detection of T-Lymphocyte Subset Levels

The T-cell subset levels in the model group are shown in Figures 1-1 and 1-2:

(F1 AND CD3 FL1 LOG FL2 LOG)
C 59.4% 10^4 18.5% 0.5%
MTSA 10^4
50 120 10
10^2 10^3 10^4 10^5
C 0.4% 76.7%
10^2 10^3 10^4 10^5
FL1 LOG

Figures 1-1 and 1-2

The T-cell subset levels in the 5-Fu group are shown in Figures 2-1 and 2-2:

(F1 AND CD3 FL1 LOG FL2 LOG)
C 54.6% 10^4 22.5% 20.3%
MTSA 10^4
50 120 10
10^2 10^3 10^4 10^5
C 30.9% 46 76.3%
10^2 10^3 10^4 10^5
FL1 LOG

Figures 2-1 and 2-2

The T-cell subset levels in the low-dose Pei’s Shengxue Granules + 5-Fu group are shown in Figures 3-1 and 3-2:

(F1 AND CD3 FL1 LOG FL2 LOG)
C 69.0% 10^4 17.1% 20.2%
MTSA 10^4
50 120 10
10^2 10^3 10^4 10^5
C 32.1% 48 80.6%
10^2 10^3 10^4 10^5
FL1 LOG

Figures 3-1 and 3-2

The T-cell subset levels in the medium-dose Pei’s Shengxue Granules + 5-Fu group are shown in Figures 4-1 and 4-2:

(F4 LOG LIN)(F1 AND 34I: F1 LOG FL2 LOG)
C 71.8% 10^4 15.3% 20.2%
MTSA 50 120 0
10^2 10^3 10^4 10^5
C 31.3% 48 83.2%
10^2 10^3 10^4 10^5
FL1 LOG

Figures 4-1 and 4-2

The T-cell subset levels in the high-dose Pei’s Shengxue Granules + 5-Fu group are shown in Figures 5-1 and 5-2:

(F1 AND CD4B FL1 LOG FL2 LOG)
C 85.6% 10^4 12.4% 20.1%
MTSA 50 120 10
10^2 10^3 10^4 10^5
C 31.5% 86.0%
10^2 10^3 10^4 10^5
FL1 LOG

Figures 5-1 and 5-2

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The Effect of Pei’s Blood-Boosting Granules on VEGF Expression in H₂₂ Tumor Tissue and Serum IL-12 Levels in Mice

Liang Xi