Discussion

Discussion

Pei's Shengxue Granules are mainly composed of Liuwei Dihuang Decoction combined with Shengmai Powder, plus Taizishen, Beishashen, Ludangshen, and other ingredients, all of which belong to the category of tonifying and consolidating formulas. The formula heavily uses Taizishen, Ludangshen, and Beishashen to strengthen the spleen, while Liuwei Dihuang Decoction is used to tonify the kidneys, fully embodying the traditional Chinese medicine principle of "tonifying the righteous qi and consolidating the root."

In terms of pathogenesis, traditional Chinese medicine regards "deficiency of righteous qi" as the fundamental cause of disease. As stated in the "Discussion on Acupuncture Techniques for Treating Epidemic Diseases" in the "Plain Questions": "When righteous qi resides within, evil cannot invade," and in the "Discussion on Feverish Illnesses": "Wherever evil gathers, qi must be deficient." In treatment, the principle of tonifying the righteous qi and consolidating the root has been proposed. The body's "righteous qi," also known as "true qi," is described in the "Spiritual Pivot: On Puncturing True Evil and Genuine Qi" as "the qi received from heaven, which combines with the qi from food to fill the body." True qi encompasses both innate and acquired aspects. Throughout history, physicians have attributed the innate aspect to the two kidneys, calling it "yuan qi" (original qi), and the acquired aspect to the spleen and stomach, calling it "zhong qi" (middle qi). The spleen governs middle qi, while the kidneys govern yuan qi; therefore, in the principle of "tonifying the righteous qi and consolidating the root," strengthening the spleen and tonifying the kidneys are the two most important components. Experimental studies have demonstrated that the "spleen" and "kidneys" in traditional Chinese medicine play significant roles in the immune system, endocrine system, metabolic system, autonomic nervous system, and gastrointestinal–pancreatic endocrine system, among others. Strengthening the spleen and tonifying the kidneys can improve the function of these systems. The concept of "tonifying the righteous qi and consolidating the root," which aims to enhance and mobilize the body's resistance to disease, shares considerable common ground with modern immunology. In general, what traditional Chinese medicine refers to as "righteous qi" represents the body's intrinsic ability to resist disease, which is equivalent to the physiological functions of the human immune system. The immune system comprises non-specific immunity and specific immunity. Traditional Chinese medicine's "zhong qi" and "wei qi" bear similarities to modern non-specific immunity, while "yuan qi" is akin to specific immunity. Specific and non-specific immunity mutually reinforce each other to achieve the body's immune response, just as zhong qi and yuan qi work together to form the body's righteous qi. Therefore, "tonifying the righteous qi and consolidating the root" can enhance the body's immune function [2].

With the advancement of immunology and molecular biology, research has confirmed that the occurrence and development of malignant tumors are closely related to a decline in the body's immune function. Currently, the primary treatments for malignant tumors include radiotherapy, chemotherapy, and surgery. Chemotherapy is one of the main modalities in comprehensive cancer treatment; however, because chemotherapeutic agents lack absolute selectivity between normal cells and tumor cells, they not only kill tumor cells but also cause some degree of damage to normal tissues and cells. Consequently, reducing the cytotoxicity caused by chemotherapy and the resulting suppression of immune function remains a major challenge in clinical oncology. Moreover, even when local tumors are completely eradicated through surgery, radiotherapy, or chemotherapy, patients often do not benefit significantly due to severe impairment of their immune function, leading to distant metastasis and a decline in quality of life, as well as shortened survival. The role of immune function in tumor initiation, progression, metastasis, reversal, and regression is increasingly recognized. The immunomodulatory and anti-cancer effects of traditional Chinese medicine have thus garnered growing attention [22–34].

Professor Pei Zhengxue, a renowned expert in integrated traditional Chinese and Western medicine and a mentor, drawing on his more than forty years of clinical experience, believes that deficiency of righteous qi is the fundamental cause of malignant tumor development; tonifying the righteous qi and consolidating the root is the basic principle for treating malignant tumors, with "strengthening the spleen and tonifying the kidneys" as its essence. Based on this principle, he formulated the "Lanzhou Formula," which, after more than forty years of continuous refinement and reorganization, eventually evolved into "Pei's Shengxue Granules." Pei's Shengxue Granules are developed according to the sophisticated theory of syndrome differentiation and treatment in traditional Chinese medicine, with Liuwei Dihuang Decoction and Shengmai Powder as the core formulas. As classic prescriptions for tonifying the righteous qi in traditional Chinese medicine, they possess the effect of tonifying the righteous qi and consolidating the root. Their composition mainly includes Liuwei Dihuang Decoction, Shengmai Powder, Beishashen, Ludangshen, Taizishen, Guizhi, Jujube, Wuweizi, Zhigancao, and Baishao. Previous studies have extensively investigated this formulation, and animal experiments have demonstrated that Pei's Shengxue Granules can significantly increase the levels of hemoglobin, white blood cells, and platelets in the peripheral blood of aplastic anemia model mice (established by whole-body irradiation with a 3.0 Gy linear accelerator), thereby markedly restoring the hematopoietic function of the bone marrow in these mice. Immunohistochemical analysis of CD4 and CD8 T-cell counts in the spleen shows that Pei's Shengxue Granules can increase CD4 T-cell counts while decreasing CD8 counts, raising the CD4/CD8 ratio and thus enhancing the immune function of aplastic anemia model mice. At the same time, these granules can enhance the phagocytic function of peritoneal macrophages; pathological tissue sections of the spleen reveal that Pei's Shengxue Granules can alleviate pathological changes in the spleen of aplastic anemia model mice, reduce the rate of lymphocyte apoptosis, promote the recovery of germinal centers, expand the area of the white pulp, thin the capsule, and restore dilated sinusoids to near-normal conditions [10, 11]. Furthermore, Pei's Shengxue Granules exhibit a significant inhibitory effect on H22 tumor-bearing mice. Enhancing immune function is a key mechanism underlying the anti-tumor action of Pei's Shengxue Granules. By increasing the weight of the thymus and spleen—immune organs—in tumor-bearing mice, Pei's Shengxue Granules enhance the non-specific immune function of these animals. They also promote the proliferation of splenic lymphocytes stimulated by ConA, thereby strengthening the cellular immune function of tumor-bearing mice and improving their anti-tumor efficacy. Additionally, Pei's Shengxue Granules can stimulate the secretion of IL-2 and the expression of IFN-γ mRNA in tumor-bearing mice, suggesting that these granules regulate the body's immune function by influencing cytokines [12, 13]. Pei's Shengxue Granules can also modulate the body's dysregulated immune state; by enhancing the cellular immune function of tumor-bearing mice, they can mitigate delayed-type hypersensitivity reactions. Quantitative analysis further reveals that Pei's Shengxue Granules can significantly inhibit mutant p53 and increase the protein expression of Caspase-3, thereby suppressing tumor formation. Moreover, by inhibiting NF-κB expression, they affect gene transcription, blocking the transition of tumor cells from G1 phase to S phase, thus inhibiting DNA synthesis and replication in tumor cells, suppressing tumor growth and proliferation, prolonging survival, improving quality of life, slowing down tumor growth, consistent with the therapeutic effects achieved by Pei's Shengxue Granules in clinical practice over many years [13, 14].

Although colleagues have made great efforts in researching and developing Pei's Shengxue Granules, there is still insufficient microscopic exploration regarding the enhancement of efficacy and reduction of toxicity for this clinically proven, highly effective formula. In light of this, we established a tumor-bearing mouse model and observed the combined effect of Pei's Shengxue Granules and 5-Fu in combating H22 tumors. We found that the combination significantly elevates serum IL-2 levels in tumor-bearing mice, indicating that this formula has the effect of enhancing efficacy while reducing toxicity.

Research on Pei Zhengxue's Series of Formulas and Medicines

The tumor-suppressing rate of the group receiving Pei's Shengxue Granules combined with 5-Fu was significantly higher than that of the 5-Fu-only group, suggesting that Pei's Shengxue Granules have a certain synergistic effect in enhancing the anti-tumor growth activity of 5-Fu, and that the two drugs exert an additive effect when used together. Analysis of the impact of Pei's Shengxue Granules on organ indices in tumor-bearing mice reveals that these granules significantly increase the thymus index and spleen index of such mice, implying that they enhance the non-specific immune function of tumor-bearing mice. This experiment, using flow cytometry, found that in the low-, medium-, and high-dose groups of Pei's Shengxue Granules combined with 5-Fu, CD3 and CD4 levels were higher than in the 5-Fu-only group, while CD8 levels were lower; moreover, the CD4/CD8 ratio increased significantly in the medium-dose group. Using radioimmunoassay to measure the effect of Pei's Shengxue Granules at different doses combined with 5-Fu on serum IL-2 levels in tumor-bearing mice, we discovered that the medium-dose group had significantly higher serum IL-2 levels than the 5-Fu-only group, demonstrating that Pei's Shengxue Granules counteract the post-chemotherapy immune suppression caused by 5-Fu, thereby achieving a detoxifying effect. This study aims to explore the targeted mechanisms of Pei's Shengxue Granules in combating tumors, providing scientific, microscopic, objective evidence for promoting their application in the treatment of malignant tumors, as well as offering a scientific basis for traditional Chinese medicine and integrated traditional Chinese and Western medicine in cancer treatment.