CN103520181B - The application of Phyllanthoid A in preparation treatment and preventing renal fibrosis medicine - Google Patents

Abstract

The present invention provides Phyllanthoid? The application of A in the preparation of drugs for the treatment or prevention of renal fibrosis belongs to the technical field of new uses of drugs and is disclosed for the first time. Since the skeleton type is a brand-new skeleton type and has strong inhibitory activity against renal fibrosis, it has outstanding substance Features, and at the same time, it is obviously a significant progress in the prevention and treatment of renal fibrosis.

Description

Application of Phyllanthoid A in the preparation of medicines for treating and preventing renal fibrosis

technical field

The present invention relates to a new application of compound Phyllanthoid A, in particular to the application of Phyllanthoid A in the preparation of medicines for treating and preventing renal fibrosis.

Background technique

Renal fibrosis (including renal interstitial fibrosis and glomerular sclerosis) is the main pathological basis of the final stage of renal damage caused by various reasons. Proliferation and activation of stromal cells are related to the imbalance of vasoactive substances, cytokines and extracellular matrix transformation. Renal interstitial fibrosis is almost a common path for all primary or secondary renal diseases to progress to end-stage renal failure.

The compound Phyllanthoid A involved in the present invention is a new compound published in 2013 (Jian-QiangZhao, et al., Two New Highly Oxygenated and Rearranged Limonoids from Phyllanthuscochinchinensis. Organic Letters, 2013, 15 (10) 2414-2417.), this compound has a new skeleton type, and the current use is only Inhibiting the proliferation of breast cancer cells (Jian-QiangZhao, et al., Two New Highly Oxygenated and Rearranged Limonoids from Phyllanthus scchinchinensis. Organic Letters, 2013, 15 (10) 2414-2417.), the use of Phyllanthoid A involved in the present invention in the preparation of drugs for the treatment and prevention of renal fibrosis is disclosed for the first time.

Contents of the invention

The purpose of the present invention is to provide the application of Phyllanthoid A in the preparation of medicines for treating and preventing renal fibrosis according to the current situation that no report has found that it has the activity of treating and preventing renal fibrosis in the existing Phyllanthoid A research.

The structure of the compound PhyllanthoidA is shown in formula (I):

The use of Phyllanthoid A involved in the present invention in the preparation of drugs for the treatment or prevention of renal fibrosis is disclosed for the first time. Since the skeleton type belongs to a new skeleton type, and it has strong inhibitory activity against renal fibrosis, it has outstanding substantive features. It is also used for The prevention and treatment of renal fibrosis clearly has significant progress.

detailed description

For the preparation method of the compound Phyllanthoid A involved in the present invention, please refer to the literature (Jian-QiangZhao, et al., Two New Highly Oxygenated and Rearranged Limonoids from Phyllanthus scchinchinensis. Organic Letters, 2013, 15 (10) 2414-2417.)

The present invention will be described in further detail below through examples, but the protection scope of the present invention is not limited by any specific examples, but is defined by the claims.

Embodiment 1: the preparation of the compound PhyllanthoidA tablet involved in the present invention:

Take 5 grams of compound Phyllanthoid A and add 195 grams of dextrin, mix well, and make 1000 tablets by conventional tableting.

Embodiment 2: the preparation of compound PhyllanthoidA capsules involved in the present invention:

Get 5 grams of compound Phyllanthoid A, add 195 grams of starch, mix well, and pack into capsules to make 1000 capsules.

The following pharmacodynamic experiments will further illustrate its drug activity.

Test Example 1: Effect of Phyllanthoid A on renal interstitial fibrosis in rats with unilateral ureteral ligation

1.1 Materials

Benazepril was produced by Beijing Novartis Pharmaceutical Co., Ltd.; hydroxyproline (HYP) kit was purchased from Nanjing Jiancheng Biological Company; fibronectin (FN) kit was purchased from Shanghai Institute of Biological Products.

Experimental animals: ordinary Wistar rats, male, weighing 150-200 g, from the Experimental Animal Center of Nanjing Medical University.

1.2 Test methods and results

90 rats were randomly divided into 9 groups, namely sham operation group, model group, benazepril intragastric administration 10mg/kg group, PhyllanthoidA intravenous injection 2.5mg/kg group, PhyllanthoidA intravenous injection 5mg/kg group, PhyllanthoidA intravenous injection 25mg group /kg group, PhyllanthoidA 5mg/kg group, PhyllanthoidA 10mg/kg group, PhyllanthoidA 50mg/kg group, the animals were fed for 1 week, and each rat was anesthetized by intraperitoneal injection of 10% chloral hydrate 3.0mL/kg , fixed the rat in the right lateral position on the operating table, disinfected the operating area with iodine wine and 75% alcohol after shearing, made a left abdominal incision, cut the skin, muscle and abdominal wall layer by layer, exposed and separated the left side Ureter, in the sham operation group, only the abdominal cavity was cut and the left ureter was freed, but not ligated and cut off. Rats in other groups were ligated twice with 4-0 silk thread. The last ligation point was at the level of the lower pole of the left kidney, and then the two The ureter was cut off at the ligation point, and sutured layer by layer. On the 10th day after the operation, the animals in each group were anesthetized with 10% chloral hydrate, and the animals in each group were sacrificed. The left kidney was collected after repeated lavage with normal saline, and the kidney tissue was fixed with 4% paraformaldehyde buffer. Cut out an appropriate amount of kidney tissue, and measure hydroxyproline according to the determination instructions of the hydroxyproline kit.

Routine pathological examination ①Visual observation: The kidneys in the sham-operated group were bright red, smooth, with a glossy capsule and no adhesions. The kidneys in the other groups were enlarged, pale in color, and showed a granular shape, similar to the large white kidney of a human body, with a small number of renal capsule adhesions. ②Light microscopic examination: the results of nephrons in the sham operation group were clear, and there was no expansion of glomerulus or infiltration of inflammatory cells. In the model control group, a large area of renal tubular necrosis, renal interstitial fibroblast proliferation, renal tubular dilation, a large number of brown-yellow light-shielding substances or necrotic and exfoliated epithelial cells, a decrease in the number of glomeruli, and some glomerular fibrosis and Bowman's The cyst wall adheres, and the cyst cavity disappears. The lesions in each drug administration group were similar to those in the model control group, but all had different degrees of morphological improvement, especially in the Phyllanthoid A high-dose intragastric administration groups, which were significantly different from the model control group.

Table 1 Effect of Phyllanthoid A on renal interstitial fibrosis in rats with unilateral ureteral ligation

*p<0.05, **p<0.01, compared with model group

T test was performed on FN and HYP in each group. The results are shown in Table 1, the PhyllanthoidA intravenous injection 5mg/kg group, the PhyllanthoidA intravenous injection 25mg/kg group, the PhyllanthoidA 10mg/kg intragastric administration group, and the PhyllanthoidA 50mg/kg intragastric administration group reduced FN and HYPP levels (compared with the model control group, P< 0.05 or 0.01).

Conclusion: Phyllanthoid A can significantly reduce the increase of FN and HYPP levels in renal interstitial fibrosis, inhibit renal interstitial fibrosis, and can be used to prepare anti-renal fibrosis drugs.

Claims (1)

1. The application of 1.PhyllanthoidA in preparation treatment and preventing renal fibrosis medicine, described compound PhyllanthoidA structure is as shown in formula I: