2 Reflections and Prospects

2 Reflections and Prospects

Pei’s Soft Liver and Anti-Bloating Pill integrates the principles of reinforcing vital energy and consolidating the root, promoting qi circulation and activating blood to remove stasis, softening the liver and dispersing nodules, and clearing heat and detoxifying—all in one formulation. It is a purely herbal preparation primarily focused on reinforcing vital energy and consolidating the root. Since Professor Pei Zhengxue first formulated this prescription, it has been widely used in clinical practice for more than forty years. Practice has proven that Pei’s Soft Liver and Anti-Bloating Pill is highly effective not only for primary liver cancer but also for esophageal and gastric cancers, particularly showing remarkable clinical efficacy in addressing immune dysfunction caused by radiotherapy and chemotherapy. Recent animal experiments have preliminarily confirmed that its effects are consistent with those observed in clinical applications.

This study was inspired by 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 research, we will make full use of new advances in modern science and technology to delve deeper into the material basis and related mechanisms by which Pei’s Soft Liver and Anti-Bloating Pill regulates immune function, and explore Professor Pei’s ideas and methods of integrating traditional Chinese medicine with Western medicine in the prevention and treatment of tumors, so that his clinical formulas can be further elucidated at a microscopic level.

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[26] Liu Xiaolan, Chen Jiaxu, Liu Yan et al. Study on the induction of HL60 cell apoptosis by demethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldemethyldem...... Objective: Through observing the effect of Peishiruanganxiaopi pills (PRGXP) on the vascular endothelial growth factor (VEGF) and P53 (P53) in H22 tumor bearing mice, we aim to explore the basic mechanism of PRGXP's effect on primary carcinoma of the liver, in order to support for its clinical use.

Methods: Firstly, through the subcutaneous inoculation of mice right anterior axillary and mice were injected H22 tumor cells, then they were divided into 6 groups: the normal group, model group, the PRGXP high-dose group, PRGXP medium-dose group, PRGXP low-dose group and compound cantharis capsule group. After ten days that they were fed, all mice were killed. Those tumors, thymuses and spleens were peeled off and weighted. The antitumor rate, the thymus index (TI) and the spleen index (SI) were calculated. The expression of VEGF and p53 protein in the tumor tissue was studied by immunohistochemistry, and we analyzed the statistics.

Results:

1. The inhibition rate of the tumor was higher in PRGXP groups than that in model group especially when it was remarkably higher in medium dose group. The average tumor in high dose group is (0.926±0.237)g and in medium dose group is (0.776±0.122)g and in lower dose group is (0.935±0.227)g (p<0.05);
2. The TI and SI were increased in PRGXP groups. In medium, the TI was (53.2±15.6)mg/10g which was significantly increased (p<0.05), and rose by 31.4% respectively. The SI in high-dose group, medium-dose group and low-dose group were (55.2±15.9)mg/10g, (65.0±10.1)mg/10g, (58.9±14.5)mg/10g, (70.53±18.96)mg/10g, and rose by 23.2%, 45.1%, 34.5%, (p<0.05);
3. The concentration of VEGF in PRGXP groups was lower than that in model group, significantly in those groups (p<0.05), they were 0.3±0.008, 0.287±0.014, 0.298±0.007;
4. The concentration of p53 in PRGXP groups was lower than that in model group, significantly in those groups (p<0.05), they were 0.266±0.005, 0.260±0.007, 0.263±0.008.

Conclusion: PRGXP plays the role of antitumor through increasing the thymus index and the spleen index in H22 tumor-bearing mice and inhibiting the formation of VEGF and P53.

Keywords: Peishiruanganxiaopi pill; H22 (transplanted liver cancer); vascular endothelial growth factor; P53

Foreword

Liver cancer is a common malignant gastrointestinal tumor in clinical practice and is listed as one of the top ten malignancies by the World Health Organization. Its incidence has been increasing year by year worldwide, currently exceeding 626,000 cases per year, ranking fifth among malignant tumors; deaths are close to 228

Research on Pei Zhengxue’s series of prescriptions

600,000 per year, ranking third among cancer-related deaths. China is a high-incidence area for liver cancer, accounting for about 55% of global cases, and second in cancer-related mortality, making it a major killer seriously threatening human health. Therefore, in the “Outline of China’s Cancer Prevention and Control Plan,” liver cancer is listed as a key disease for cancer prevention and control in China [2].

The pathogenesis of liver cancer is still not fully understood, but modern research suggests it is related to the activation of oncogenes and the inactivation of tumor suppressor genes. P53 is the most extensively and deeply studied tumor suppressor gene to date, closely associated with cell proliferation, differentiation, apoptosis, invasion, and metastasis. P53 is divided into two types: wild-type P53 (wt-P53) and mutant P53 (mt-P53). wt-P53 is considered the most important tumor suppressor gene in the development of liver cancer, with its main biological functions being regulation of the cell cycle, induction of apoptosis, maintenance of normal genomic and cellular function, preservation of organismal stability, and suppression of tumorigenesis—hence it is known as the guardian of the genome. When subjected to internal and external carcinogenic factors, wt-P53 mutates and transforms into mt-P53. mt-P53 exhibits characteristics of an oncogene: not only does it lose its tumor-suppressive function, but it also promotes the formation of a tumor angiogenesis phenotype, induces the expression of vascular endothelial growth factor (VEGF), and facilitates tumor growth, invasion, and metastasis.

Liver cancer is a typical multi-vascular tumor whose growth requires extensive new blood vessel support—on one hand, to obtain abundant nutrients from the host, and on the other, to export large numbers of malignant cells back to the host, thereby driving continuous tumor growth and metastasis. Thus, angiogenesis plays a crucial role in tumor initiation and progression. VEGF, as the primary pro-angiogenic factor produced by malignant tumor cells, holds an irreplaceable position in the occurrence, invasion, and metastasis of liver cancer.

There are many treatment options for liver cancer, including surgery, interventional therapy, radiotherapy, systemic chemotherapy, local treatment, biological therapy, and immunotherapy. Although these approaches have achieved certain therapeutic effects, they remain less than ideal. Traditional Chinese medicine, with its advantages of high efficacy, low toxicity, multiple pathways, multi-target action, and significant reversal of multidrug resistance, is increasingly attracting worldwide attention. In recent years, with the rapid development of molecular biology and medical immunology, research on liver cancer using traditional Chinese medicine has become ever deeper and more microscopic, reaching the molecular level.

Pei’s Soft Liver and Anti-Bloating Pills are an effective prescription for preventing and treating liver cancer created by Professor Pei Zhengxue, a renowned expert in integrated Chinese and Western medicine in China, based on over forty years of clinical experience. The formula consists of Astragalus, Salvia miltiorrhiza, Curcuma wenyujin, Laminaria japonica, Ziziphus jujuba spines, Hedyotis diffusa, and Scutellaria barbata, among others, collectively exerting the effects of strengthening the spleen and replenishing qi, activating blood circulation and removing blood stasis, softening hard masses and dispersing nodules, and clearing heat and detoxifying. This approach both reinforces the body’s righteous qi while eliminating pathogenic factors, removes evil without harming righteousness, and treats both root and branch simultaneously. After decades of clinical verification, Pei’s Soft Liver and Anti-Bloating Pills have demonstrated satisfactory efficacy in alleviating adverse reactions from radiotherapy and chemotherapy, prolonging survival time, and improving quality of life.

This experiment uses animal models to observe the effects of Pei’s Soft Liver and Anti-Bloating Pills on the H22 liver cancer mouse model, calculating the tumor inhibition rate, thymus index, and spleen index. Immunohistochemical methods are employed to examine the expression levels of VEGF and p53 proteins in the tumor tissues of H22 liver cancer mice, exploring the anti-tumor mechanisms of Pei’s Soft Liver and Anti-Bloating Pills and providing a theoretical basis for their widespread clinical application.

Rationale for the Study