Keywords:方药研究, 实验研究, 配方资产, 转化沟通, 1 实验材料
Section Index
1 Pei's Blood-Boosting Granules Inhibit Tumor Growth
In this experiment, it was observed that tumor weights in all treatment groups were lower than those in the model group, with statistically significant differences (P<0.05); PG low, medium, and high
Research on Pei Zhengxue’s series of formulas
The combined dose of PG with 5-Fu resulted in lower tumor weights compared to the 5-Fu group alone, with the medium-dose group showing a statistically significant difference relative to the 5-Fu group (P<0.05). The tumor inhibition rates for the PG low-, medium-, and high-dose groups combined with 5-Fu, as well as the 5-Fu group alone, were 51.17%, 61.07%, 56.03%, and 47.93%, respectively. These results indicate that Pei's Blood-Boosting Granules can enhance the anti-tumor efficacy of 5-Fu.
In recent years, colleagues have also demonstrated through animal experiments that Pei's Blood-Boosting Granules can inhibit NF-κB expression, affect gene transcription, and block the progression of tumor cells from G1 phase to S phase, thereby suppressing DNA synthesis and replication, reducing cell proliferation. Moreover, Pei's Blood-Boosting Granules can promote or induce apoptosis in tumor cells, increasing the apoptosis rate [9]. Some researchers have further explored the molecular mechanisms underlying Pei's Blood-Boosting Granules' inhibitory effects on H22 tumors in mice, finding that the formulation can significantly suppress mutant P53 and upregulate Caspase-3 protein expression, suggesting that the drug may induce tumor cell apoptosis and inhibit tumorigenesis by downregulating mutant P53 and upregulating Caspase-3 protein expression [10].
2 Pei's Blood-Boosting Granules Promote Bone Marrow Hematopoiesis
The toxic side effects of 5-Fu on the hematopoietic system manifest as reductions in individual or total blood cell counts in peripheral blood and decreased bone marrow proliferation. This experiment revealed that, compared with the normal group and the model group, the 5-Fu group exhibited significant decreases in white blood cells, red blood cells, hemoglobin, and platelet counts (P<0.05). However, in the Pei's Blood-Boosting Granules groups combined with 5-Fu at various doses, white blood cell counts increased markedly, with statistically significant differences compared to the 5-Fu group (P<0.05). Similarly, platelet counts in the high- and medium-dose Pei's Blood-Boosting Granules groups combined with 5-Fu rose significantly, again showing statistically significant differences relative to the 5-Fu group (P<0.05). No significant increases in red blood cells or hemoglobin were observed in this experiment; the Pei's Blood-Boosting Granules groups combined with 5-Fu showed no statistically significant differences in red blood cell count or hemoglobin levels compared to the 5-Fu group (P>0.05), possibly because the regeneration period for RBCs and HGB is about four months, whereas the duration of this experiment was relatively short, making it difficult for changes in bone marrow function to be reflected in peripheral blood counts within such a brief timeframe. Furthermore, DNA content in bone marrow cells was higher in all Pei's Blood-Boosting Granules groups combined with 5-Fu than in the 5-Fu group alone, with the high- and medium-dose groups showing statistically significant differences (P<0.05). These findings clearly demonstrate that Pei's Blood-Boosting Granules can promote bone marrow hematopoiesis and alleviate chemotherapy-induced bone marrow suppression.
3 Pei's Blood-Boosting Granules Regulate Immune Function
TNF (tumor necrosis factor) is a cytokine involved in the body's immune response that can cause hemorrhage and necrosis. Produced by monocytes/macrophages, it exhibits specific cytotoxic activity against various tumor cells and is currently considered the most potent anti-tumor cytokine discovered [29]. TNF-α originates from activated monocytes and exerts its biological activity by binding to receptors on target cell membranes, displaying diverse anti-tumor effects such as activating lymphokines, promoting apoptosis and necrosis, and simultaneously upregulating ICAM-1 (intercellular adhesion molecule) to activate LAK cells, thereby exerting a series of immune functions [30]. In vitro experiments show that TNF-α can inhibit the proliferation of certain tumor cells and directly kill them, yet it does not affect the growth or metabolic functions of normal human cells [31].
TNF-α selectively causes tumor cells to lyse and promotes the proliferation of fibroblasts and lymphocytes. Its anti-tumor mechanisms include: ① TNF-α has a direct lytic effect on tumors in vitro and can induce tumor necrosis in vivo. ② By affecting blood vessels in the tumor region, it can lead to hemorrhagic necrosis of malignant tumors. Specifically, it alters the structure of vascular endothelial cells, causing rearrangement of actin microfilaments and loss of tight junctions between cells, thereby inhibiting endothelial cell growth and directly damaging endothelial cells. Damage to endothelial cells results in massive leakage of plasma proteins and fluids into tissues, leading to capillary leakage and subsequently hemorrhagic necrosis of tumor tissue. ③ It enhances the activity of the monocyte-macrophage system at inflammatory sites, thereby boosting their cytotoxic capabilities, an effect achieved by promoting the cytotoxic action of NK cells [32]. TNF-α can also effectively stimulate T-cell differentiation and proliferation, promote IL-2 production, induce inflammatory responses, and enhance the expression of IL-2 receptors, epidermal growth factor receptors, and major histocompatibility complex class II antigens, playing an important role in host defense responses.
In this experiment, radioimmunoassay was used to measure the concentration of TNF-α in the peripheral blood of tumor-bearing mice. It was found that the serum TNF-α concentration in the 5-Fu group decreased significantly compared with the model group (P<0.05), whereas the serum TNF-α concentrations in all Pei's Blood-Boosting Granules groups combined with 5-Fu increased to varying degrees, with the medium-dose group showing a statistically significant difference relative to the 5-Fu group (P<0.05). These results indicate that Pei's Blood-Boosting Granules can promote TNF-α secretion, thereby regulating the body's immune function and anti-tumor effects.
IFN-γ, also known as type II interferon, is primarily secreted by activated T cells and natural killer cells. It is the most important Th1-type cytokine and occupies a central position in cellular immunity, exerting its effects by regulating the expression of hundreds of different genes. IFN-γ can inhibit tumor cell proliferation, promote antibody production by B cells, induce cytotoxic effects in NK cells and cytolytic T cells (CTL), synergize with IL-2 to enhance the activation of lymphokines by LAK cells, upregulate the expression of major histocompatibility complex class I molecules on tumor cells to facilitate the formation of antigen-specific CTLs and increase sensitivity to cytotoxic cells [33][34]. IFN-γ possesses antiviral activity and can also enhance the body's non-specific immune function, thus playing a regulatory role in immunity and anti-tumor effects. It serves as a potential activator of mononuclear phagocytes, directly inducing enzyme synthesis and fully activating macrophages to eliminate ingested microorganisms; however, only activated macrophages are capable of killing tumor cells. It promotes CTL maturation, stimulates B cells to secrete antibodies, and activates neutrophils and NK cells. IFN-γ can inhibit tumor cell synthesis, slow down the progression of various phases of cell proliferation, and reduce the speed of cell division. It also has broad regulatory functions, such as regulating and controlling cell replication, proliferation, and immune system functions, playing a role in pathological conditions like malignant tumors, immune diseases, vascular proliferative diseases, and fibrotic diseases.
In this experiment, ELISA was used to measure the concentration of IFN-γ in the serum of tumor-bearing mice. The results showed that the serum IFN-γ concentration in the 5-Fu group decreased significantly compared with the model group (P<0.05), whereas the serum IFN-γ concentrations in all Pei's Blood-Boosting Granules groups combined with 5-Fu increased to varying degrees, with the high- and medium-dose groups showing statistically significant differences relative to the 5-Fu group (P<0.05). These findings demonstrate that Pei's Blood-Boosting Granules can counteract the immunosuppression caused by the chemotherapy drug 5-Fu, regulate the body's immune function, and thus exhibit a detoxifying and efficacy-enhancing effect on chemotherapy.
Conclusion
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