Application of p-CA in relieving renal fibrosis
By using p-CA to inhibit M2 macrophage infiltration, a pharmaceutical composition was prepared to alleviate renal fibrosis, and the problem of lack of non-invasive diagnostic and therapeutic methods in the prior art was solved, and significant improvements in renal morphology and function were achieved.
Patent Information
- Application Number
- CN202510506319.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-22
- Publication Date
- 2025-07-11
AI Technical Summary
There is a lack of effective non-invasive diagnosis and specific treatment methods in the prior art to prevent and treat renal fibrosis, and the formation mechanism of renal fibrosis has not been fully understood, and the existing treatment methods do not significantly improve patients' prognosis.
P-CA (p-hydroxycinnamic acid) is used to relieve renal fibrosis by inhibiting the infiltration of M2 macrophages, and is prepared into a pharmaceutical composition and introduced into the body through injection, oral or gastrointestinal devices. The carrier includes a diluent, a lyser, etc., and the preferred dosage is 100-150 mg/kg/day.
In the UUO model, the renal morphology and function were significantly improved, the serum creatinine, urea nitrogen and uric acid levels were reduced, renal fibrosis was reduced, and the renal histological integrity was not affected.
Smart Images
Figure CN120284938A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of drugs, and particularly to the application of p-CA in alleviating renal fibrosis. Background Art
[0002] Renal fibrosis is a pathophysiological change, which is a progressive process in which the function of the kidney changes from healthy to damaged, then to damaged, and finally to loss of function. Due to various pathogenic factors such as trauma, infection, inflammation, blood circulation disorders, and immune responses, the intrinsic cells of the kidney are damaged. In the later stage, a large amount of collagen deposition and accumulation occur, causing the renal parenchyma to gradually harden, form scars, and eventually the kidney completely loses its organ function. The process of fibrosis and sclerosis of the intrinsic cells in the kidney is also the process of renal fibrosis. Renal fibrosis is characterized by the abnormal deposition of extracellular matrix (ECM).
[0003] In recent years, with the continuous in-depth research, although important progress has been made in our understanding of the pathogenesis and potential therapeutic targets of renal fibrosis, clinically, renal fibrosis is still mainly prevented and treated by controlling the risk factors that exacerbate the deterioration of renal function, and the prognosis of patients has not been significantly improved. Therefore, how to effectively prevent and treat renal fibrosis remains an important problem in the field of CKD research. Existing studies have shown that renal fibrosis is the result of abnormal repair after kidney damage, and its mechanism has not been fully clarified yet. Currently, it is considered that the molecular mechanism of renal fibrosis formation is mainly related to the following aspects: kidney injury initiates an inflammatory response, and a large number of various inflammatory cells infiltrate; a large amount of fibrosis-related factors are released, such as cytokines, growth factors, and chemokines, etc., leading to the amplification of the injury process; the imbalance between the synthesis and degradation of ECM, and excessive accumulation of ECM in the renal interstitium; the phenotypic mesenchymal transformation of renal intrinsic cells (mesangial cells, podocytes, tubular cells, endothelial cells, fibroblasts, pericytes, etc.), and the reduction of the number of intrinsic cells; renal microvascular lesions leading to tissue ischemia and hypoxia. Intervening in these aspects is of great significance for the prevention and treatment of renal fibrosis. However, at present, a non-invasive diagnostic method for renal fibrosis has not been established, and specific treatment means are almost absent.
[0004] p-CA is p-coumaric acid, that is, p-hydroxycinnamic acid, which is 3-(4-hydroxyphenyl)-2-acrylic acid. This product has varying degrees of inhibitory effects on Staphylococcus aureus, Shigella dysenteriae, Escherichia coli, and Pseudomonas aeruginosa; animal experiments have proved that this product also has a lipid-lowering effect. How to successfully develop drugs for alleviating renal fibrosis has important scientific and clinical significance. Summary of the Invention
[0005] The object of the present invention is to provide a new pharmaceutical use of p-CA.
[0006] In order to achieve the above object, the present invention is realized by the following technical solutions: Application of p-CA in alleviating renal fibrosis. p-CA alleviates renal fibrosis by inhibiting the infiltration of M2 macrophages.
[0007] A pharmaceutical composition comprising p-CA and a conventional pharmaceutical carrier.
[0008] Preferably, the pharmaceutical composition is introduced into the body by injection, oral administration or a gastric gavage device; or is introduced into the body after being mixed or encapsulated with other substances.
[0009] Preferably, the body includes any one of muscle, intradermal, subcutaneous, intravenous, mucosal tissue, and stomach.
[0010] Preferably, the carrier includes one or more of a diluent, a solvent, a filler, a binder, a wetting agent, a disintegrant, an absorption enhancer, a surfactant, an adsorption carrier, and a lubricant.
[0011] Preferably, the solvent includes a 0.5% carboxymethyl cellulose solution.
[0012] Preferably, when the pharmaceutical composition is introduced into the body by a gastric gavage device, the dosage of p-CA is 100 - 150 mg / kg / day.
[0013] The beneficial effects of the present invention are as follows: The present invention established a mouse renal interstitial fibrosis model by unilateral ureteral obstruction (UUO model) to study the effect of p-CA on renal fibrosis, its efficacy, toxicity and safety. When introduced into the body by a gastric gavage device, at dosages of 100 mg / kg / day and 150 mg / kg / day, the renal morphology and function after UUO were significantly improved after 14 days, manifested as a decrease in serum creatinine, urea nitrogen and uric acid levels. The treatment did not affect the histological integrity of major organs such as the heart, liver, spleen, and right kidney, effectively reducing renal fibrosis and having no toxicity. Description of the Drawings
[0014] Figure 1 It is a diagram of the change state of the kidney after the dosage of p-CA is 0 mg / kg / day; Figure 2 It is a diagram of the change state of the kidney after the dosage of p-CA is 50 mg / kg / day; Figure 3 It is a diagram of the change state of the kidney after the dosage of p-CA is 100 mg / kg / day; Figure 4 It is a diagram of the change state of the kidney after the dosage of p-CA is 150 mg / kg / day; Figure 5 It is a diagram of the renal function indexes after the dosage of p-CA is 100 mg / kg / day; Figure 6 It is a diagram of the renal function indexes after the dosage of p-CA is 150 mg / kg / day. DETAILED DESCRIPTION
[0015] The technical solution of the present invention is further described below in conjunction with the accompanying drawings: Male C57BL / 6J mice (6-8 weeks old) were purchased from Hangzhou Ziyuan Experimental Animal Technology Co., Ltd. (Hangzhou, China). The mice were randomly divided into four groups (n = 10 per group) and anesthetized under sterile conditions. The mice were placed in the supine position. Then p-CA was dissolved in 0.5% carboxymethylcellulose (CMC) solution. To determine the effective dose, four groups of mice were given different doses (0, 50, 100 and 150 mg / kg / day) by oral gavage for 14 consecutive days. The mice were killed on the 14th day, and kidney tissues were collected for metabolomics and histological analysis. The experimental results showed that with the increase of p-CA dose, kidney swelling gradually decreased, especially at 100 and 150 mg / kg / day ( Figures 1 to 4 as shown).
[0016] Renal function indicators showed that p-CA reduced renal fibrosis in a dose-dependent manner, with 100 mg / kg / day being the optimal dose. At this dose, renal function of UUO mice was significantly improved, while further increasing to 150 mg / kg / day did not bring additional benefits (e.g. Figure 5 and Figure 6 Treatment with 100 mg / kg / day of p-CA significantly improved renal morphology and function after UUO, as indicated by the decrease in serum creatinine, urea nitrogen, and uric acid levels.
[0017] p-Coumaric acid has a wide range of pharmacological effects in various renal diseases and fibrosis models, including free radical scavenging, lipid peroxidation inhibition, DNA oxidative damage inhibition, anti-inflammatory, and immunomodulatory effects. p-CA alleviates renal fibrosis by reducing the number of macrophages and inhibiting M2 macrophage polarization. p-CA has a renal protective effect in UUO-induced renal fibrosis by significantly reducing the number of macrophages and inhibiting M2 polarization.
[0018] It should be noted that the above is only a specific embodiment of the present invention. Obviously, the present invention is not limited to the above embodiment, and there are many variations. In short, all variations that can be directly derived or associated with the content disclosed by ordinary technicians in this field should be considered as the protection scope of the present invention.
Claims
1. Application of p-CA in alleviating renal fibrosis, wherein p-CA alleviates renal fibrosis by inhibiting infiltration of M2 macrophages.
2. A pharmaceutical composition, characterized in that: Comprising p-CA as claimed in claim 1 and a conventional pharmaceutical carrier.
3. The pharmaceutical composition according to claim 2, characterized in that, The pharmaceutical composition is introduced into the body by injection, oral administration or via a gavage device; or is introduced into the body after being mixed or encapsulated with other substances.
4. The pharmaceutical composition according to claim 3, characterized in that, The body includes any one of muscle, intradermal, subcutaneous, intravenous, mucosal tissue, and stomach.
5. The pharmaceutical composition according to claim 4, wherein The carrier includes one or more of a diluent, a solubilizer, a filler, a binder, a wetting agent, a disintegrant, an absorption enhancer, a surfactant, an adsorption carrier, and a lubricant.
6. The pharmaceutical composition according to claim 5, wherein The solubilizer includes a carboxymethyl cellulose solution with a concentration of 0.5%.
7. The pharmaceutical composition according to claim 2, wherein When the pharmaceutical composition is introduced into the body via a gavage device, the dosage of p-CA is 100 - 150 mg / kg / day.