1 Theoretical Basis for Using Pei's Soft Liver and Anti-bloating Pills in Treating PLC

1 Theoretical Basis for Using Pei's Soft Liver and Anti-bloating Pills in Treating PLC

Based on clinical symptoms such as hepatomegaly, ascites, jaundice, loss of appetite, and bleeding tendency, PLC corresponds to categories in TCM like liver accumulation, abdominal distension, jaundice, zhengjia, and jiju. Clinical manifestations are complex and variable, and there is no unified standard for syndrome differentiation and treatment. Si Fuchun et al.[1] conducted a study on 339 articles related to TCM diagnosis and treatment of PLC indexed in the China Journal Database from June 1979 to June 2010. The results showed that PLC presents 33 different syndromes, among which liver-kidney yin deficiency, liver-gallbladder damp-heat, qi stagnation and blood stasis, and liver depression and spleen deficiency are common syndromes, accounting for 50.92% of all syndromes; 10 syndrome elements were summarized, with solid syndrome elements accounting for 62.57%; the affected organs are mainly the liver and spleen, accounting for 48.56% and 34.20% respectively. Since the primary site of the disease is the liver, drugs that enter the liver meridian account for 20.3% of all treatments. Looking at clinical symptoms—abdominal pain, abdominal distension, diarrhea, poor appetite, nausea, vomiting, emaciation, weakness, etc.—they all fall under the category of spleen deficiency in TCM. Li Yan's "Introduction to Medicine" states: "The best way to treat zhengjia is to regulate qi and break blood, eliminate food and clear phlegm, weaken the majority and stop—it should not be aggressively attacked, as this will harm the original qi. It is better to support the spleen and stomach qi and let it self-correct." Therefore, the spleen and stomach are fundamental for protecting yang qi and supporting the body's vital energy, making them a key focus in treating PLC. Drugs that enter the spleen meridian account for 17.1%. The top three types of drugs used in treating liver cancer are tonifying drugs, clearing heat drugs, and activating blood circulation and removing blood stasis drugs, totaling 59.43%. Among these, tonifying drugs are used most frequently, accounting for 27.18%, mainly including qi-tonifying and yin-nourishing medicines as well as blood-tonifying drugs. Mr. Pei believes that PLC is a case of inherent deficiency with external excess—the tumor is a local manifestation of a systemic disease, reflecting overall deficiency with localized excess. Therefore, treatment should focus on strengthening the body to eliminate accumulation, while eliminating accumulation to consolidate the foundation. Inherent deficiency may include spleen deficiency, liver-kidney yin deficiency, and liver-spleen dual deficiency. "Where evil gathers, qi must be deficient," so the occurrence and development of tumors largely depend on which force—righteous qi or pathogenic qi—is dominant. Thus, when treating PLC, tonifying drugs must be used.

1.1 Composition of Pei's Soft Liver and Anti-bloating Pills

This formula consists of pure herbal preparations including astragalus, salvia miltiorrhiza, curcuma, zedoary, panax notoginseng, leech, melia azedarach, processed myrrh, hedyotis diffusa, hemiphragmium, coix seed, prunella vulgaris, bupleurum, citrus aurantium, and others. Its main functions are to strengthen the body and consolidate the foundation, break down accumulation and eliminate tumors, activate blood circulation and remove blood stasis, soften hard masses and disperse nodules, clear heat and drain fire, promote diuresis and reduce swelling, and regulate qi to relieve pain.

Formula Explanation: TCM believes that "accumulation arises from deficiency of righteous qi; only when righteous qi is deficient does accumulation form." Mr. Pei advocates tonifying to treat the root cause, with astragalus tonifying qi and strengthening the spleen, and salvia miltiorrhiza nourishing blood. These two herbs together replenish qi and blood, primarily strengthening the body and consolidating the foundation. The "Treasury of Health" records: "If you nurture the righteous qi, the accumulation will naturally dissipate, making true qi strong and stomach qi robust, thus eliminating accumulation automatically." Therefore, using astragalus and salvia miltiorrhiza to strengthen the body and consolidate the foundation helps break down accumulation and eliminate tumors. Once accumulation has formed, it needs to be broken down and eliminated, and curcuma, zedoary, and other ingredients serve as powerful agents for breaking down accumulation and eliminating tumors. The "Pharmacopoeia" mentions: "Zedoary has a pungent and potent flavor, specifically targeting blood within qi, mainly breaking down accumulation and hard masses, eliminating accumulated phlegm and nodules, resolving blood stasis and menstrual disorders, and alleviating pain. Its effects are quite similar to those of curcuma, but should not be taken in excess." For zhengjia accumulation, there is also blood stasis, so panax notoginseng and leech are used to activate blood circulation and remove blood stasis as complementary treatments; blood stasis inevitably involves qi stagnation, because qi is the commander of blood, and blood is the mother of qi—when qi flows, blood flows, and when qi stagnates, blood stasis occurs. Qi stagnation and blood stasis lead to blockage of qi and blood flow, causing pain; chuanliangzi and processed myrrh help regulate qi and relieve pain, serving as complementary treatments as well; zhengjia accumulation often leads to internal heat, so white snake tongue grass, hemiphragmium, and prunella vulgaris are used to clear heat and drain fire as complementary treatments; coix seed not only softens hard masses and disperses nodules

Research on Pei Zhengxue's series of prescriptions

but also promotes diuresis and reduces dampness, which is beneficial for zhengjia accumulation blocking the triple burner and causing water-dampness to overflow—coix seed can penetrate and drain moisture, serving as a complementary treatment as well. The liver is naturally inclined to release and diffuse, so any zhengjia accumulation anywhere needs the liver's release and diffusion to be dispersed—bupleurum, citrus aurantium, white peony, and licorice can take on this important task and act as conduits.

1.2 Single Herb Research

Astragalus (Radix Astragali), the root of leguminous herbaceous plants such as Mongolian astragalus and membranous astragalus[17], first recorded in the "Shennong's Classic of Materia Medica," with taste: sweet, warm. Meridians: lung and spleen. Functions: expelling toxins and draining pus, tonifying qi and reinforcing the exterior, promoting diuresis and reducing swelling. Used as medicinal material as early as 2,000 years ago, with pharmacological effects including enhancing immunity, anti-aging, liver protection, stress resistance, blood pressure reduction, diuresis, and broad-spectrum antibacterial action[18]. Xiao Shunhan et al.[19] found that astragalus polysaccharides can increase interleukin levels in mouse serum.

Salvia miltiorrhiza (Salvia miltiorrhiza), a labiate plant, with taste: bitter; slightly cold nature. Meridians: heart and liver. Functions: activating blood circulation and removing blood stasis; cooling blood and eliminating abscesses. Main indications: dysmenorrhea in women; amenorrhea; postpartum blood stasis and abdominal pain; zhengjia accumulation; heat invading the blood; poor sleep; boils and carbuncles, etc. Pharmacological effects include cardiovascular protection, liver protection, antibacterial, lipid-lowering effects. Multiple studies have shown that salvianolic acid in salvia miltiorrhiza can kill tumor cells[20].

Curcuma (Common Buried Rubber), a black curcuma plant, with taste: bitter, neutral nature. Effects: breaking blood and regulating qi, relieving pain and eliminating accumulation. Main indications: zhengjia accumulation, qi stagnation and blood stasis, pain under the ribs, etc. Li Juan et al.[21] used rats with liver fibrosis as a model, administering curcuma and zedoary via gavage, and found that curcuma and zedoary could inhibit the formation of liver fibrosis. Several experimental studies have shown that curcuma has significant anti-tumor effects[22–24].

Zedoary, first recorded in the "Lei Gong's Treatise on Processing Medicinal Herbs," with taste: spicy and bitter; warm nature. Meridians: liver and spleen. Effects: eliminating accumulation and relieving pain; regulating qi and breaking blood. Main indications: blood-stasis-related pain, food stagnation, abdominal distension, blood stasis causing menstrual disorders, dysmenorrhea, zhengjia and lump formation, injuries from falls and blows. Zedoary's pharmacological effects include anti-tumor action, alleviation of chemotherapy side effects, enhancement of immune protection, antibacterial and anti-inflammatory effects, liver protection, and anti-thrombotic effects. Zedoary oil is the main active ingredient of zedoary, and clinical research shows[25–26] that compound zedoary oil can be used as a new hepatic arterial embolization agent for treating PLC, with remarkable efficacy. Meanwhile, experimental studies confirm[27] that elemene contained in zedoary can inhibit and kill various tumor cells safely and effectively, while greatly protecting and enhancing the body's immune and hematopoietic functions[28].

Frankincense (Frankincense), with taste: warm, slightly bitter, with effects of activating blood circulation and removing blood stasis, reducing swelling and relieving pain. Myrrh (Myrrh), with taste: neutral, bitter; with effects of activating blood circulation and relieving pain, reducing swelling and promoting tissue regeneration. Frankincense and myrrh are often used together; the "Compendium of Materia Medica" mentions: "Frankincense activates blood, myrrh disperses blood, both can relieve pain, reduce swelling, and promote tissue regeneration, so the two are often used in combination." Pharmacological studies of both show analgesic, anti-inflammatory, antibacterial, antioxidant, lipid-lowering, and anti-tumor effects[29]. Xiao Juan et al.[30] found that the volatile oil component of frankincense can inhibit the proliferation of the liver cancer cell line SMMC-7721 and upregulate the Bax/Bcl-2 expression ratio in mitochondria, thereby inducing apoptosis of SMMC-7721 cells.

Citrus aurantium (Szechwan Chinaberry Fruit), with taste: bitter and cold. Meridians: liver, bladder, and small intestine. Functions: soothing the liver and clearing heat, regulating qi and relieving pain, killing insects. Main indications: pain in the epigastrium, flanks, and hernias, as well as tinea capitis. Pharmacological studies have shown anti-cancer, antiviral, analgesic, anti-inflammatory, and insect-repelling effects. Its main component, limonin, has anti-tumor effects. Liu Xiaoling et al.[31–32] found that limonin induces apoptosis of K562 cells through the mitochondrial pathway.

Bupleurum refers to the dried roots of either Bupleurum chinense DC. or Bupleurum scorzonerifolium Willd., a umbelliferous plant[33], with taste: bitter, slightly pungent, slightly cold, entering the liver and gallbladder meridians. It has functions of releasing exterior and interior, reducing fever, and soothing the liver and relieving depression. Bupleurum contains triterpenoid saponins, volatile oils, polysaccharides, flavonoids, and other components[34]. Bupleurum can inhibit the growth of human liver cancer cells and combat human hepatocellular carcinoma[35], and its extract has an inhibition rate of 87.21% against the S-180 solid tumor in mice[36].

2 Analysis of Clinical Study Results