New application of ginseng-guben oral liquid in preventing and treating radiation-induced lung injury

Abstract

The present invention belongs to the field of medicine, and relates to a new use of ginseng guben oral liquid, and specifically to a new use of ginseng guben oral liquid for preventing and treating radiation lung injury. Ginseng guben oral liquid can significantly reduce the levels of IL-6 and TGF-β1 in radiation lung injury model rats, reduce the lung coefficient, and compared with the model group, ginseng guben oral liquid can significantly increase the weight of radiation model rats, improve the mental state, and has a significant therapeutic effect on radiation lung injury.

Description

Technical Field

[0001] The present invention belongs to the field of medicine and relates to a new medicinal use of ginseng guben oral liquid, and specifically relates to a new medicinal use of ginseng guben oral liquid for preventing and treating radiation-induced lung injury. Background Art

[0002] Radiation therapy is a primary treatment for cancer. According to statistics, approximately 50% of cancer patients in the United States choose and receive radiotherapy. Radiation-induced lung injury (RLI) is a major complication of radiotherapy for thoracic malignancies. RLI refers to non-infectious lung inflammation caused by radiation doses exceeding the threshold for biological effects in lung tissue. Early manifestations include radiation pneumonitis, and later manifestations include radiation-induced pulmonary fibrosis (RFF). Radiation pneumonitis is characterized by cough, dyspnea, fever, and chest pain. Diagnosis is primarily based on imaging changes, symptoms, medical history, and serological changes. Ionizing radiation damages alveolar and vascular endothelial cells, leading to pulmonary congestion and elevated expression of multiple inflammatory factors. The timeline between RLI and RPF ranges from weeks to six months. RLI limits the irradiation dose to the tumor target, reduces local tumor control, compromises the efficacy of local radiotherapy, and significantly impacts patients' quality of life. Currently, Western medical treatments primarily rely on glucocorticoids and anti-inflammatory therapies. Research is underway for stem cell therapy, chemotherapy, and physical interventions, which have yet to be clinically applied.

[0003] Traditional Chinese Medicine (TCM) understands radiation pneumonitis from the perspectives of "fire-heat toxic evil" and "dryness evil," based on the characteristics of radiation that deplete Qi and damage body fluids and develop overdue. The pathogenesis is generally based on the fact that fire-heat or dryness evil damages blood vessels, depletes Qi and Yin, and leads to the accumulation of fire and heat. The main pathological factors are heat toxicity, Yin deficiency, and blood stasis. Qi and Yin deficiency is the most common syndrome, followed by heat toxicity invading the lungs and phlegm and blood stasis. Treatment focuses on nourishing Yin, activating blood circulation, and clearing away heat and detoxifying. Ginseng Guben Oral Liquid, an over-the-counter Chinese patent medicine, nourishes Yin and replenishes Qi, strengthening the body and nourishing the vital energy. It is used for symptoms such as Yin deficiency and weak Qi, asthenic cough, palpitations and shortness of breath, bone steaming and hot flashes, low back pain and tinnitus, nocturnal emission, night sweats, and dry stools. Summary of the Invention

[0004] In view of the universality of tumor radiotherapy and radiation-induced lung injury, the present invention provides a new medicinal use of Ginseng Guben Oral Liquid for preventing and treating radiation-induced lung injury.

[0005] The object of the present invention is achieved through the following technical solutions:

[0006] A rat model of radiation-induced lung injury was established. By administering Ginseng Guben Oral Liquid, the differences in various indicators between the Ginseng Guben Oral Liquid group and the non-administered model group were observed to investigate the preventive and therapeutic effects of Ginseng Guben Oral Liquid on radiation-induced lung injury. The specific results were as follows:

[0007] (1) Ginseng Guben oral liquid can improve the general condition of rats with radiation-induced lung injury, as shown by: improving the mental state of rats with radiation-induced lung injury, reducing the phenomenon of hair loss and hair dryness in rats with radiation-induced lung injury; increasing the weight of rats with radiation-induced lung injury, and playing a comprehensive conditioning role in rats with radiation-induced lung injury.

[0008] (2) Protect the lung structure of rats with radiation-induced lung injury, reduce inflammatory damage, and prevent the process of fibrosis.

[0009] (3) Reduced the serum IL-6 factor level in rats with radiation-induced lung injury. Specifically, the expression level of serum IL-6 factor in the model group after radiation exposure was significantly higher than that in the normal group, and the increase was more obvious at the 5th week than at the 3rd week. The expression levels at both time points were significantly different from those in the normal group (P<0.05). There were significant differences between the ginseng-guben oral liquid group and the normal group and the model group (P<0.05).

[0010] (4) Reduce the lung index of rats with radiation-induced lung injury and prevent and treat radiation-induced pulmonary fibrosis. Specifically, compared with the normal group, the lung index of the model group was significantly increased, and the difference was statistically significant (P<0.05), and the value at week 5 was greater than that at week 3; the lung index of the ginseng-solidifying oral liquid group was significantly lower than that of the model group, and the difference was statistically significant (P<0.05). There was no significant difference in the lung index between the ginseng-solidifying oral liquid group and the normal group.

[0011] (5) Reduced TGF-β1 protein expression, specifically manifested as follows: no expression or a small amount of positive brown-yellow product was observed in the lung tissue sections of the normal group; at week 3-5, the expression of TGF-β1 protein in the above-mentioned parts of the model group rats increased significantly, and the difference was statistically significant compared with the normal group (P<0.05); the expression of TGF-β1 protein in the lung tissue of the rats in the Ginseng Guben Oral Liquid group was higher than that in the normal group and lower than that in the model group. The differences were statistically significant at week 3 and week 5 compared with the model group (P<0.05), and the difference was statistically significant at week 3 compared with the normal group (P<0.05).

[0012] The ginseng strengthening oral liquid is prepared from ginseng, rehmannia root, prepared rehmannia root, cornus officinalis, yam, peony bark, oriental water plantain, tuckahoe, asparagus cochinchinensis and ophiopogon japonicus.

[0013] The one-time pre-administration of the ginseng-tonifying oral liquid can improve and treat lung damage caused by radiotherapy.

[0014] Multiple pre-administrations of the ginseng-boosting oral solution can improve and treat lung damage caused by radiotherapy.

[0015] The application of the ginseng-tonifying oral liquid in drugs for reducing IL-6 and TGF-β1.

[0016] The dosage of the ginseng strengthening oral liquid is 0.1-100 ml / kg.

[0017] A pharmaceutical composition is prepared from ginseng-tonifying oral liquid and other drugs for treating lung injury.

[0018] The invention discloses a use of ginseng-guben oral liquid in preparing a drug for preventing and treating radiation-induced lung injury, wherein the radiation-induced lung injury is lung injury caused by tumor radiotherapy.

[0019] The above-mentioned radiation-induced lung injury is radiation pneumonitis or radiation-induced pulmonary fibrosis.

[0020] The ginseng-tonifying oral liquid provided by the present invention has the following advantages in preventing and treating radiation-induced lung injury:

[0021] (1) Exact efficacy and comprehensive effects

[0022] Ginseng Guben oral liquid can significantly reduce the levels of IL-6 and TGF-β1 in rats with radiation-induced lung injury, reduce the lung coefficient, and has a significant therapeutic effect on radiation-induced lung injury.

[0023] (2) Comprehensive conditioning helps restore the patient's overall function

[0024] As an over-the-counter Chinese patent medicine, Ginseng Guben Oral Liquid has the effects of nourishing yin and qi, strengthening the foundation and replenishing the vital energy. While eliminating the inflammatory damage and fibrosis process of radiation-induced lung injury, it can comprehensively regulate the patient's body and is beneficial to the recovery of the disease. Specific embodiments

[0025] The following further illustrates the content of the present invention through specific examples, but it should be understood that the examples of the present invention do not limit the present invention in any way.

[0026] Animal Pharmacological Efficacy Example: Therapeutic Effect of Ginseng Guben Oral Liquid on Radiation Lung Injury Model Rats

[0027] 1. Animal Grouping and Modeling

[0028] Sixty male SD rats were randomly divided into three groups (n=20): a normal group, a model group, and a ginseng-guben oral liquid group. The other two groups, except the normal group, received a single whole-thoracic irradiation with a total dose of 20 Gy (6 mV, X-ray, 300 cGy / min) using a linear accelerator. The specific operation is as follows: rats are injected intraperitoneally with 4% chloral hydrate (0.9 ml / kg). After they fall asleep under general anesthesia, they are placed flat on the irradiation table in a prone position and fixed. Lead blocks are placed around them. The height of the lead blocks is the same as that of the rats in the prone position. The irradiation field is adjusted to the chest and back of the rats, from the line connecting the midpoints of the two armpits of the forelimbs to the xiphoid process. The source-target distance is 100 cm. Six rats are placed side by side on the treatment bed at the same time. A 1.5 cm thick equivalent film is covered on the top of the lead blocks and fits the back of the rats. During the irradiation, the condition of the rats is monitored by the monitoring screen. The irradiation is completed as soon as possible before the rats wake up. The accelerator room is disinfected with ultraviolet light before irradiation. After the irradiation, the rats wake up naturally and are returned to the animal room. They are transferred to an independent animal room together with the normal group and raised as usual.

[0029] 2. Dosage and administration cycle

[0030] On the second day of irradiation, the Ginseng Guben Oral Liquid group was given 2 ml / kg of Ginseng Guben Oral Liquid by gavage, while the normal and model groups were given an equal volume of normal saline by gavage. The administration was continued for 5 weeks.

[0031] 3. Detection indicators

[0032] 3.1 General observation of animals and body weight determination

[0033] 3.2 Changes in the appearance of lung tissue in rats in each group

[0034] 3.3 Expression of IL-6 in lung tissue of rats in each group

[0035] At the 3rd and 5th weeks of drug administration, 10 rats were randomly selected from each group and anesthetized with 10% chloral hydrate intraperitoneally. 5 mL of blood was collected from the abdominal aorta and the rats were rotated at 3000 r·min. －1 After centrifugation for 10 min, the IL-6 content in rat serum was determined by ELISA.

[0036] 3.4 Rats in each group

[0037] 3.4 Lung Index Determination

[0038] The anesthetized rats in 3.3 were dissected and the lung tissues were weighed. The lung coefficient of each group of rats was calculated according to the formula: lung coefficient = lung wet weight (mg) / body weight (g) * 100%;

[0039] 3.5 TGF-β1 immunohistochemistry detection

[0040] The lung tissue weighed in 3.4 was routinely fixed and slides were treated to prevent detachment. Positive results were determined according to the standards provided in the company's instructions. TGF-β1 was localized in the cytoplasm, with clear brown-yellow staining considered positive and no staining considered negative. Expression was determined by the extent and intensity of staining. Ten high-power fields were randomly selected from the upper, lower, left, right, and central sections of each slide. All sections were reviewed by an experienced pathologist, and semi-quantitative analysis of the stained sections was performed using a double-blind method. Staining results were categorized into five categories based on the number of positive cells: less than 5% (grade 0) (negative); ≥5%-25% (grade I) (focal positivity); >25%-50% (grade II) (diffuse weak positivity); >50%-75% (grade III) (diffuse moderate positivity); and >75% (grade IV) (diffuse strong positivity). The degree of immunohistochemical staining was positively correlated with the intensity of TGF-β1 expression.

[0041] 4. Statistical methods

[0042] Experimental data were expressed as mean ± standard deviation (X ± S). SPSS statistical software was used to test the normal distribution and homogeneity of variance of each group. Independent sample t-test or nonparametric test was used. P < 0.05 was considered to be significantly different.

[0043] 5. Test results

[0044] 5.1 General observation and weight measurement of animals

[0045] With the exception of the normal group, the other two groups of rats began to exhibit mental abnormalities, including hair loss and dry, dull hair, at the end of the first week of irradiation. Compared to the normal group, both irradiated groups were more easily startled, agitated, and prone to hurting others. The model group showed significantly lower mental status than the ginseng-strengthening oral liquid group. Regarding the extent of hair loss, by the fourth week after irradiation, the model group began to experience exposed back skin, even with skin ulcers and exudation. In the ginseng-strengthening oral liquid group, sparse hair was observed in the irradiated areas, but hair loss was milder, with no noticeable skin exposure or ulcers.

[0046] In addition, the rats in each group were weighed and found that after irradiation, the rats in the model group were significantly thinner than those in the normal group, and the difference was statistically significant (P<0.05); the rats in the ginseng-solidifying oral liquid group did not show obvious weight loss compared with the model group, and the weight of the rats increased significantly from the 3rd week to the 5th week, and the weight difference was statistically significant compared with the model group (P<0.05). The weight measurement results of each group are shown in Table 1.

[0047] Table 1 Body weight of rats in each group at week 3 and week 5 ( n=10)

[0048] Group Number of animals Week 3 Week 5 Normal group 10 289.23±20.08 328.12±16.19 Model Group 10 <![CDATA[202.36±17.07 # ]]> <![CDATA[213.34±19.38 # ]]> Ginseng Guben Oral Liquid Group 10 <![CDATA[278.26±19.37 ﹩ ]]> <![CDATA[301.29±20.22 ﹩ ]]>

[0049] Compared with the normal group,# P < 0.05;

[0050] Compared with the model group, ﹩ P<0.05.

[0051] The above results show that Ginseng Guben Oral Liquid can improve the mental depression of irradiated rats, comprehensively regulate the body functions of irradiated rats, and significantly increase the weight of irradiated rats.

[0052] 5.2 Changes in the appearance of lung tissue in rats in each group

[0053] At the 3rd and 5th weeks in the normal group, the lung tissue structure was clear, the bronchial epithelial cells were normal without desquamation or necrosis, the bronchial muscle layer was not thickened, the alveolar wall was thin, there was no exudation or inflammatory cell infiltration in the alveolar cavity, and there was no abnormality in the interstitial blood vessels.

[0054] At week 3 in the model group, bronchial epithelial cells showed mild degeneration, with no shedding or necrosis. The bronchial muscle layer showed mild thickening, the alveolar wall was slightly widened, a large number of inflammatory cells infiltrated in the interstitium, the vascular wall muscle layer was thickened, and the surrounding area was obviously edema. At week 5, bronchial epithelial cells showed mild degeneration, with local shedding and necrosis. The degree of thickening of the bronchial muscle layer and the degree of widening of the alveolar wall increased. Alveolar structure collapsed and fused, the alveolar structure disappeared, extensive fibrous foci formed, a large amount of exudation in the alveolar cavity, inflammatory cell infiltration, lymphoid follicle formation, vascular wall muscle layer hypertrophy, local thinning of the vascular wall, and the passage and outflow of red blood cells and inflammatory cells. Vascular dilation and congestion were also observed.

[0055] In the Ginseng Guben Oral Liquid group, at week 3, there was no obvious degeneration of bronchial epithelial cells, slightly widened alveolar septa, a small amount of inflammatory cell infiltration, intact alveolar structure, and no edema of alveolar septa. At week 5, the appearance of lung tissue was similar to that at week 3, with no progressive worsening.

[0056] The above results show that the ginseng-guben oral liquid provided by the present invention has a significant therapeutic effect on radiation-induced lung injury caused by tumor radiation, can effectively prevent the transformation of early radiation pneumonitis to radiation-induced pulmonary fibrosis, and has a significant preventive and therapeutic effect on radiation pneumonitis and radiation-induced pulmonary fibrosis.

[0057] 5.3 Expression of IL-6 in lung tissue of rats in each group

[0058] The expression levels of serum IL-6 factor in rats of each group are shown in Table 2. It can be seen from the table that the expression level of serum IL-6 factor in the model group after radiation exposure was significantly higher than that in the normal group, and the increase was more obvious at the 5th week than at the 3rd week. The expression levels at the two time points were significantly different from those in the normal group (P<0.05); there were significant differences between the ginseng Guben oral liquid group and the normal group and the model group (P<0.05).

[0059] Table 2 Comparison of serum IL-6 expression levels in rats of each group (pg·mg －1 , n=10)

[0060]

[0061] Compared with the normal group, # P < 0.05;

[0062] Compared with the model group, ﹩ P<0.05.

[0063] 5.4 Determination of lung index

[0064] The results of lung index determination of rats in each group are shown in Table 3. As can be seen from the table, compared with the normal group, the lung index of rats in the model group was significantly increased, the difference was statistically significant (P < 0.05), and the value at week 5 was greater than that at week 3; the lung index of the Ginseng Guben Oral Liquid group was significantly lower than that of the model group, the difference was statistically significant (P < 0.05), and there was no significant difference in the lung index between the Ginseng Guben Oral Liquid group and the normal group.

[0065] Table 3 Lung index results of rats in each group (( n=10))

[0066] Group Week 3 Week 5 Normal group 5.34±0.67 5.31±0.79 Model Group <![CDATA[9.17±0.87 # ]]> <![CDATA[10.03±1.02 # ]]> Ginseng Guben Oral Liquid Group <![CDATA[6.68±1.04 ﹩ ]]> <![CDATA[6.01±0.96 ﹩ ]]>

[0067] Compared with the normal group, # P < 0.05;

[0068] Compared with the model group, ﹩ P<0.05.

[0069] The lung index is one of the indicators reflecting the degree of pulmonary fibrosis. Its level is closely related to lung weight and body weight. The increase in lung weight is the main reason for the increase in lung coefficient. Ginseng Guben oral liquid can significantly reduce the lung index of radioactive rats, indicating that it has a significant therapeutic effect on radiation-induced pulmonary fibrosis.

[0070] 5.5 Light microscopic observation of lung TGF-β1 immunohistochemical staining

[0071] Positive expression of TGF-β1 protein was primarily observed in the cytoplasm of peribronchiolar epithelial cells, followed by lymphocytes, macrophages, and alveolar epithelial cells. No expression or a small amount of positive brownish-yellow product was observed in lung tissue sections of the normal group. However, TGF-β1 protein expression in the aforementioned areas was significantly increased in the model group rats between weeks 3 and 5, with a statistically significant difference compared with the normal group (P < 0.05). TGF-β1 protein expression in the lung tissue of rats in the Renshen Guben oral liquid group was higher than that in the normal group and lower than that in the model group. The differences were statistically significant at weeks 3 and 5 compared with the model group (P < 0.05), and at week 3 compared with the normal group (P < 0.05). Specific results are shown in Table 4.

[0072] Table 4 Comparison of TGF-β1 protein expression in the lungs of rats in each group (( n=10))

[0073] Group Week 3 Week 5 Normal group 0.11±0.04 0.10±0.06 Model Group <![CDATA[0.43±0.05 # ]]> <![CDATA[0.46±0.08 # ]]> Ginseng Guben Oral Liquid Group <![CDATA[0.22±0.07 #﹩ ]]> <![CDATA[0.13±0.09 ﹩ ]]>

[0074] Compared with the normal group, # P < 0.05;

[0075] Compared with the model group, ﹩ P<0.05.

[0076] Cytokines are involved in the occurrence and development of radiation-induced lung injury. The continuous release of cytokines promotes the infiltration and aggregation of inflammatory cells, leading to the occurrence of early acute radiation pneumonitis and late pulmonary fibrosis. TGF-β1 plays a key role in the above pathological changes. Ginseng Guben oral liquid can significantly reduce the expression of lung TGF-β1 protein and has a significant therapeutic effect on radiation pneumonitis and radiation pulmonary fibrosis.

Claims

1. Use of ginseng guben oral liquid in preparing a drug for treating radiation lung injury, characterized in that: The ginseng strengthening oral liquid is prepared from ginseng, rehmannia root, prepared rehmannia root, cornus officinalis, yam, peony bark, oriental water plantain, tuckahoe, asparagus cochinchinensis and ophiopogon japonicus.

2. The use according to claim 1, characterized in that The radiation lung injury is lung injury caused by tumor radiotherapy.

3. The use according to claim 2, characterized in that The radiation lung injury is radiation pneumonitis.

4. The use according to claim 2, characterized in that The radiation-induced lung injury is radiation-induced pulmonary fibrosis.

5. The use according to claim 1, characterized in that The application of the ginseng-tonifying oral liquid in drugs for reducing IL-6 and TGF-β1.

6. Use of ginseng-guben oral liquid in the preparation of drugs for preventing radiation-induced pulmonary fibrosis.

7. The use according to claim 1 or 6, characterized in that The dosage of the ginseng tonic oral liquid is 0.1-100 ml / kg.

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