2.4 Effect on NO Levels in Tumor-Bearing H₂₂ Mice

2.4 Effect on NO Levels in Tumor-Bearing H₂₂ Mice

The amounts of NO produced in the low-, medium-, and high-dose Pei's Shengxue Granules groups were 52.3, 57.0, and 58.0, respectively. Both the Pei's Shengxue Granules group and the Zhenqi Fuzheng Granules group showed significant differences compared with the model group (p<0.01), indicating that the low-, medium-, and high-dose Pei's Shengxue Granules groups can increase NO secretion. See Table 3:

Table 3: Effect of Pei's Shengxue Granules on NO Levels in Tumor-Bearing H₂₂ Mice (x̄±s, n=10)

Note: Compared with the model group, p<0.01

Effect of Pei's Shengxue Granules on NO Levels in Tumor-Bearing H22 Mice

Effect of Pei's Shengxue Granules on NO levels in tumor-bearing H22 mice (x±S, n=10)

Note: Compared with the model group, *p<0.01

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2.5 Effect on IL-1 in Tumor-Bearing H22 Mice

The amounts of IL-1 produced in the low-, medium-, and high-dose Pei's Shengxue Granules groups were 168.3, 183.7, and 244.8, respectively. The high-dose Pei's Shengxue Granules group and the Zhenqi Fuzheng Granules group showed significant differences compared with the model group (p<0.05), indicating that the low-, medium-, and high-dose Pei's Shengxue Granules groups can increase IL-1 levels. See Table 4:

Table 4: Effect of Pei's Shengxue Granules on IL-1 in Tumor-Bearing H22 Mice (x±S, n=10)

Note: Compared with the model group, *p<0.05

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2.6 Effect on IFN-γ in Tumor-Bearing H22 Mice

The medium-dose Pei's Shengxue Granules group showed significant differences compared with the model group (p<0.05), and the high-dose Pei's Shengxue Granules group showed even more significant differences compared with the model group (p<0.01). See Table 5:

Table 5: Effect of Pei's Shengxue Granules on IFN-γ in Tumor-Bearing H22 Mice (x±S, n=10)

Note: Compared with the model group, **p<0.01, *p<0.05

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2.7 Effect on DTH in Tumor-Bearing H22 Mice

The medium- and high-dose groups of Pei’s Shengxue Granules, as well as the Zhenqi Fuzheng Granules group, all showed significant differences compared with the model group (p<0.01). See Table 6:

Table 6: Effects of Pei’s Shengxue Granules on DTH in H22 Tumor-Bearing Mice (x±S, n=10)

Note: Compared with the model group, *p<0.01

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Discussion

Pei’s Shengxue Granules is one of the proven prescriptions developed by Professor Pei Zhengxue, a nationally renowned expert in integrated traditional Chinese and Western medicine, drawing on over forty years of clinical experience. It is a pure herbal granular preparation with the effects of warming the kidneys, strengthening the spleen, replenishing qi, and nourishing blood, designed to combat tumors and enhance the body’s immune function. To date, this formula has been used to treat tens of thousands of patients both within and outside the province, and its clinical efficacy has been recognized by clinicians and patients alike. It has been employed in cancer treatment for more than thirty years, achieving remarkable results in the treatment of esophageal cancer, gastric cancer, leukemia, myelodysplastic syndromes, and various deficiency-related diseases.

According to the “Inner Canon,” “Where evil gathers, qi must be deficient,” and “When righteous qi resides within, evil cannot invade.” These are the fundamental views of traditional Chinese medicine regarding the relationship between righteousness and evil. The ebb and flow of righteousness and evil constitute the progression of disease. As the ancients said, “When evil qi is strong, the condition is real; when righteous qi is depleted, the condition is虚.” This indicates that the nature of a disease—whether it is real or虚—is entirely determined by the balance between righteousness and evil. In the Ming Dynasty, the renowned physician Chen Shigong proposed in his “Orthodox Surgery” that “accumulation arises from deficiency of righteous qi; only when righteous qi is deficient can accumulation form.” He directly applied the principle from the “Plain Questions”—that “disease arises from deficiency of righteous qi”—to the pathogenesis of tumors, arguing that only when righteous qi is insufficient can evil qi invade the body, leading to dysfunction of the zang-fu organs and imbalance of qi, blood, yin, and yang, ultimately resulting in tumor formation. Meanwhile, modern immunology in Western medicine also incorporates the concept of “righteous qi” from traditional Chinese medicine. Therefore, the TCM understanding of malignant tumors is not simply a case of being purely real or purely虚; rather, it is fundamentally rooted in deficiency, with excess serving as the manifestation. The progression or regression of the disease thus depends on the dynamic interplay between righteousness and evil. Since tumors can only develop when righteous qi is deficient, and since deficiency of the spleen and kidneys plays a central role in the pathogenesis, reinforcing righteous qi and consolidating the root cause has become the basic approach to treating cancer. Professor Pei’s prescription for reinforcing righteous qi in the treatment of malignant tumors consists of Liuwei Dihuang Tang combined with Shengmai San, supplemented with Taizishen, Beishashen, Dangshen, and other herbs, integrating warming the kidneys, strengthening the spleen, replenishing qi, and nourishing blood into a single formula, with the overarching principle of reinforcing righteous qi and consolidating the root cause. Numerous studies have demonstrated that several classic herbal formulas known for their ability to nourish yin and yang, replenish qi and blood, tonify the liver and kidneys, and strengthen the spleen—such as Liuwei Dihuang Tang, Jinkui Shenqi Tang, and Shengmai San—can regulate the body’s dysregulated immune function and even reverse the suppression of bone marrow and thymus cell proliferation caused by cyclophosphamide, restoring cellular proliferative activity to normal levels or even increasing it.

This study experimentally confirms that Pei’s Shengxue Granules adjusts the body’s dysregulated immune state through multiple mechanisms, thereby enhancing immune function and improving overall health. In selecting research indicators, the role of macrophages in anti-tumor immunity is not only as antigen-presenting APCs but also as effector cells that lyse tumor cells. Activated macrophages, upon binding to tumor cells, utilize lysosomal enzymes...

Research on Pei Zhengxue’s series of prescriptions

and directly kill tumor cells; they process and present antigens, and through the secretion of IL-1, IL-12, and other cytokines, activate T cells to generate specific anti-tumor cellular immune responses; macrophages possess Fc receptors on their surface, which mediate ADCC effects against tumor cells via specific antibodies; activated macrophages also secrete TNF, nitric oxide (NO), and other cytotoxic factors to indirectly kill tumor cells [10].

IL-1 is an important cytokine that directly influences both humoral and cellular immunity. IL-1 promotes T-cell activation as well as B-cell growth and differentiation, stimulates the proliferation of multipotent hematopoietic stem cells in the bone marrow, enhances NK-cell cytotoxicity, prompts monocytes and macrophages to produce IL-6 and TNF, and through monocytes and macrophages induces IL-8-mediated chemotaxis of neutrophils. Interferon (IFN-γ) is another crucial anti-tumor cytokine that inhibits tumor cell proliferation, strengthens monocytes/macrophages and promotes their Fc receptor expression, and further enhances their phagocytic and ADCC activities against tumor cells. IFN-γ can also activate NK cells to kill tumor cells. Moreover, it synergizes with other cytokines to amplify its anti-tumor effects. T cells produce IFN-γ and colony-stimulating factors (CSF), among others, which induce the expression of IL-2 receptors on T cells. Therefore, IL-2 and IFN-γ are indispensable cytokines for inducing CTL proliferation and differentiation, playing a synergistic role in the body’s immune surveillance and tumor immunity. Increased secretion of IL-2 and IFN-γ may be a key factor in enhancing CTL cytotoxic effects, further demonstrating that TAP primarily suppresses tumor growth by activating T-cell functions, including Th regulation and CTL killing [11].

Nitric oxide (NO) is a cytotoxic factor that broadly affects the body’s immune function by regulating the synthesis and secretion of various immune-active mediators. NO is an important effector molecule in the killing of tumor cells by activated macrophages, and it works in both complementary and synergistic ways with TNF-α. NO causes DNA damage in tumor cells, thereby inhibiting their proliferation [12].

The results of this study show that Pei’s Shengxue Granules can regulate the body’s dysregulated immune state, leading to increased levels of cytokines such as IL-1, IFN-γ, and NO in tumor-bearing mice; it also enhances the phagocytic function of peritoneal macrophages and increases delayed-type hypersensitivity reactions in these mice. Pei’s Shengxue Granules exhibits a clear inhibitory effect on tumors in H22 tumor-bearing mice. Enhancing immune function is a key mechanism underlying the anti-tumor effects of Pei’s Shengxue Granules.

Conclusion