Use of gentisic acid and pharmaceutically acceptable salts thereof for the preparation of a medicament for the treatment of pulmonary fibrosis
By using a pharmaceutical composition prepared from gentianic acid and its pharmaceutically acceptable salts, extracellular matrix deposition and hydroxyproline expression are inhibited, thus solving the problems of high cost and insignificant efficacy in the treatment of pulmonary fibrosis and achieving effective treatment of pulmonary fibrosis.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NANJING UNIV OF TRADITIONAL CHINESE MEDICINE
- Filing Date
- 2026-04-03
- Publication Date
- 2026-05-29
AI Technical Summary
Existing treatments for pulmonary fibrosis are expensive and have limited efficacy. Furthermore, insufficient transplant donors or immune rejection restrict their widespread application, and there is a lack of effective drug interventions.
A pharmaceutical composition for treating pulmonary fibrosis was prepared using gentic acid and its pharmaceutically acceptable salts as active ingredients, which alleviates lung damage by inhibiting extracellular matrix deposition and reducing hydroxyproline expression.
It significantly reduces the degree of pulmonary fibrosis, improves survival rate, stabilizes alveolar structure, reduces cell nucleus aggregation, and lowers the lung coefficient, demonstrating significant efficacy.
Smart Images
Figure CN122097328A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical technology, and more specifically to the use of gentian acid and its pharmaceutical compositions in the preparation of drugs for treating pulmonary fibrosis. Background Technology
[0002] Pulmonary fibrosis (PF) is a chronic, progressive, and fatal lung disease, representing the end stage of many diseases, and its pathogenesis remains unclear. PF severely impairs respiratory function, manifesting as dry cough and progressive dyspnea (a feeling of insufficient air), with respiratory function continuously deteriorating as the disease progresses and lung damage worsens. The incidence and mortality rates of idiopathic pulmonary fibrosis are increasing annually, with an average survival of only 2.8 years after diagnosis, a mortality rate higher than most cancers, leading to its being termed a "tumor-like disease." Patients with pneumonia may also develop pulmonary fibrosis after recovery. Current treatments for PF primarily include pirfenidone, nintedanib, oxygen therapy, invasive / non-invasive mechanical ventilation, and lung transplantation. However, these methods are costly, have limited efficacy, and their widespread application is restricted by insufficient transplant donors, immune rejection, and poor patient compliance. Therefore, actively exploring the pathogenesis of pulmonary fibrosis and developing new interventional drugs is crucial.
[0003] Gentisic acid (GA) has the following structural formula:
[0004]
[0005] It is a metabolite of aspirin and a natural product derived from the roots of the Gentiana genus. It is a phenolic acid with anti-inflammatory, neuroprotective, and antioxidant activities. Most current reports limit its effects to cardiovascular and mental illnesses; no reports have been found on its role in inhibiting extracellular deposition and thus exerting anti-pulmonary fibrosis effects. Summary of the Invention
[0006] The purpose of this invention is to provide new pharmaceutical uses of gentic acid and its pharmaceutically acceptable salts, namely, the use of gentic acid and its pharmaceutically acceptable salts in the preparation of medicaments for the treatment of pulmonary fibrosis.
[0007] Another object of the present invention is to provide the use of a pharmaceutical composition in the preparation of a medicament for treating pulmonary fibrosis, said pharmaceutical composition comprising gentianic acid and its pharmaceutically acceptable salts or pharmaceutically acceptable excipients.
[0008] Beneficial effects
[0009] Through extensive experimental screening, this invention has discovered a novel mechanism of action and efficacy of gentic acid. Experimental results show that gentic acid effectively inhibits lung damage caused by extracellular matrix deposition in lung tissue. These results also indicate that this compound can be applied to the preparation of drugs for pulmonary fibrosis. Attached Figure Description
[0010] Figure 1 Gentianic acid (GA) can significantly reduce the degree of pulmonary fibrosis in mice.
[0011] Figure 2 Gentianic acid (GA) can significantly reduce the lung coefficient in mice.
[0012] Figure 3 Gentianic acid (GA) significantly improved the survival rate of mice.
[0013] Figure 4 Gentian acid (GA) can inhibit extracellular matrix deposition, stabilize alveolar structure, and reduce cell nucleus aggregation.
[0014] Figure 5 Gentian acid (GA) can inhibit the expression level of hydroxyproline. Detailed Implementation
[0015] The present invention will be further described below with reference to specific embodiments, but these embodiments should not be construed as limiting the present invention.
[0016] Example 1: Gentianic acid reduces the degree of bleomycin-induced pulmonary fibrosis in mice.
[0017] This invention utilizes MicroCT to detect the protective effect of gentianic acid (GA) on lung tissue in a bleomycin (BLM)-induced pulmonary fibrosis model mouse. Experimental results show that treatment with gentianic acid significantly reduces the degree of pulmonary fibrosis and improves the survival rate of mice.
[0018] 1. Experimental Principle
[0019] This experiment induced a pulmonary fibrosis model in mice by intraoral instillation of bleomycin solution, followed by treatment with gentianic acid. The effect of gentianic acid on the degree of bleomycin-induced pulmonary fibrosis in mice was assessed by quantifying the volume of normal lung tissue and lung coefficient using CT scans and 3D reconstruction of the mouse lungs. Survival curves were plotted based on mouse mortality to evaluate mouse survival rates.
[0020] 2. Experimental Materials and Methods
[0021] Male C57BL / 6J mice aged 6-8 weeks were purchased from Jiangsu Huachuang Xinno. After one week of acclimatization, they were anesthetized using an inhalation anesthesia machine with isoflurane inhalation, and bleomycin solution (5 mg / kg, administration volume: 0.35 mL / kg) was administered via oral-tracheal infusion to establish a pulmonary fibrosis model. Eight days later, small animal CT scans were used to assess the success of the model. Mice were then divided into a blank control group (normal mice), a model group, a low-dose gentianic acid group (50 mg / kg), and a high-dose gentianic acid group (100 mg / kg) based on the degree of pulmonary fibrosis. Gentianic acid was administered by gavage for 20 days. Small animal CT imaging experiments were performed before modeling, on days 8 and 18 after modeling, and one day before sacrifice to observe the degree of pulmonary fibrosis. After sacrifice, lung tissue was collected and weighed. The lung coefficient was obtained by multiplying the ratio of lung wet weight (g) to body weight (kg) by 100%. The number of mice that died in each group from bleomycin modeling to sacrifice was recorded, and survival curves were plotted.
[0022] 3. Experimental Results
[0023] like Figure 1 As shown, gentianic acid significantly reduced the degree of pulmonary fibrosis in mice. Twenty days after administration, the volume of normal lung tissue in the treated group was significantly larger than that in the model group. Figure 2 The results showed that gentianic acid significantly reduced the lung coefficient in bleomycin-induced model mice. Figure 3 As shown, gentic acid significantly improved the survival rate of mice. * p<0.05, ** p<0.01, *** p<0.001 indicates a difference between the gentian acid treatment group and the blank control group. Statistical analysis was performed using the t-test.
[0024] Example 2: Gentianic acid inhibits bleomycin-induced extracellular matrix deposition and hydroxyproline levels in mouse lung tissue.
[0025] This invention investigated the inhibitory effect of gentianic acid on extracellular matrix deposition in mouse lung tissue samples using HE, Masson, and Sirius red staining experiments, and detected hydroxyproline levels using a hydroxyproline kit. The experimental results showed that gentianic acid significantly inhibited extracellular matrix deposition and hydroxyproline expression levels.
[0026] 1. Experimental Principle
[0027] This experiment induced a pulmonary fibrosis model in mice by intraoral instillation of bleomycin solution, followed by treatment with gentianic acid. Finally, lung tissue was collected from the mice, and the extracellular matrix deposition was detected by Masson, HE, and Sirius red staining experiments after tissue sectioning. The hydroxyproline level was detected by a hydroxyproline kit to evaluate the effect of gentianic acid on the degree of bleomycin-induced pulmonary fibrosis in mice.
[0028] 2. Experimental Materials and Methods
[0029] Hydroxyproline assay kits were purchased from Boxbio, and Masson, HE, and Sirius red reagents for histochemical staining were purchased from Solarbio. Male C57BL / 6J mice aged 6-8 weeks were purchased from Jiangsu Huachuang Xinno. After one week of acclimatization, mice were anesthetized using an inhalation anesthesia machine with isoflurane inhalation, and bleomycin solution (5 mg / kg, administration volume: 0.35 mL / kg) was administered via oral-tracheal infusion to establish a pulmonary fibrosis model. Eight days later, small animal CT scans were used to assess the success of the model. Mice were then divided into a blank control group (normal mice), a model group, a low-dose gentianic acid group (50 mg / kg), and a high-dose gentianic acid group (100 mg / kg) based on the degree of pulmonary fibrosis. Lung tissue samples were collected 20 days after intraperitoneal injection of gentianic acid, and paraffin sections were prepared to obtain mouse lung tissue sections.
[0030] 3. Experimental Results
[0031] The results are as follows Figure 4 As shown, gentic acid can inhibit extracellular matrix deposition, stabilize lung tissue structure, and reduce cell nucleus aggregation. Figure 5 As shown, gentianic acid can reduce hydroxyproline secretion. This indicates that gentianic acid has a significant concentration-dependent inhibitory effect on extracellular matrix deposition and hydroxyproline levels. * p<0.05, ** p<0.01, *** p<0.001 indicates a difference between the gentian acid treatment group and the blank control group. Statistical analysis was performed using the t-test.
[0032] The above embodiments are merely exemplary embodiments of the present invention and are not intended to limit the present invention. The scope of protection of the present invention is defined by the claims. Those skilled in the art can make various modifications or equivalent substitutions to the present invention within its spirit and scope of protection, and such modifications or equivalent substitutions should also be considered to fall within the scope of protection of the present invention.
Claims
1. The use of gentic acid and its pharmaceutically acceptable salts in the preparation of drugs for the treatment of pulmonary fibrosis.
2. According to claim 1, gentianic acid and its pharmaceutically acceptable salts inhibit lung damage caused by extracellular matrix deposition in lung tissue.
3. Use of a pharmaceutical composition in the preparation of a medicament for treating pulmonary fibrosis, said pharmaceutical composition comprising gentianic acid and pharmaceutically acceptable excipients.
4. The application according to claim 3, characterized in that, Pharmaceutically acceptable salts of gentianic acid are inorganic or organic salts of gentianic acid.