CN-122005577-A - Application of lupeol in preparation of medicine for preventing or treating kidney injury caused by cisplatin

Abstract

The invention belongs to the technical field of biology, and particularly relates to application of lupeol in preparing a medicament for preventing or treating kidney injury caused by cisplatin. The invention discovers that the natural compound lupeol has potential protection effect on kidney injury caused by cisplatin for the first time, and in vivo and in vitro models prove that the lupeol obviously reduces kidney dysfunction, tissue pathological injury and increase of kidney injury markers caused by cisplatin, inhibits apoptosis and promotes proliferation of tubular cells. Transcriptome sequencing results show that lupeol enhances cell survival and proliferation by activating the PI3K/Akt signaling pathway, and simultaneously regulates Nrf2 pathway against oxidative stress, inhibits nuclear translocation of nfkb and reduces pro-inflammatory cytokines, inhibiting inflammatory response. The results indicate that lupeol may be an option for alleviating cisplatin nephrotoxicity.

Inventors

• HE DAWEI
• LEI LI
• WANG ZHAOYING

Assignees

• 重庆医科大学附属儿童医院

Dates

Publication Date

20260512

Application Date

20260413

Claims (10)

1. 1. Use of lupeol in the manufacture of a medicament for the prevention or treatment of kidney injury.
2. 2. The use of claim 1, wherein the kidney injury is cisplatin-induced kidney injury.
3. 3. The use according to claim 2, wherein the lupeol is administered by intraperitoneal injection, subcutaneous injection or oral administration.
4. 4. The use according to claim 3, wherein, administration of lupeol the mode of administration is selected from oral administration.
5. 5. The use of claim 1, wherein the medicament further comprises a pharmaceutically acceptable carrier.
6. 6. The use of claim 5, wherein the pharmaceutically acceptable carrier comprises at least one of a diluent, a binder, a surfactant, a lubricant, a filler, and a disintegrant.
7. 7. The use according to claim 1, wherein the pharmaceutical dosage forms include granules, powders, tablets, capsules, syrups, suppositories, injections and elixirs.
8. 8. A pharmaceutical composition, characterized in that, the pharmaceutical composition comprises cisplatin and lupeol.
9. 9. A medicine is characterized in that, the pharmaceutical product comprising the pharmaceutical composition of claim 8.
10. 10. The pharmaceutical product of claim 9, further comprising a pharmaceutically acceptable carrier.

Description

Application of lupeol in preparation of medicine for preventing or treating kidney injury caused by cisplatin Technical Field The invention belongs to the technical field of biology, and particularly relates to application of lupeol in preparing a medicament for preventing or treating kidney injury caused by cisplatin. Background Acute Kidney Injury (AKI) is a clinical syndrome characterized by a sudden decrease in renal function, manifested by a sudden decrease in Glomerular Filtration Rate (GFR), accumulation of nitrogen products, and a decrease in urine volume. Acute kidney injury can be caused by a variety of pathological conditions including severe infections and hypovolemia (40% -60%), urinary tract obstruction (15% -25%), or kidney toxic injury (20% -40%) caused by non-steroidal anti-inflammatory drugs, nephrotoxic antibiotics or chemotherapeutics, etc. Worldwide, the incidence of AKI has a significant trend, and mortality rates are high, with about 13300000 new cases occurring annually, resulting in about 170000 deaths (about 21.6% for adults, about 23.9% for children, up to 33.7% for children, and about 13.8% for hospitalized patients). In the Intensive Care Unit (ICU), AKI occurs in up to 50% of patients, with up to 8% of cases progressing to Chronic Kidney Disease (CKD), which results in excessive medical resource consumption and a huge socioeconomic burden. Cisplatin is used as a first-line platinum antitumor drug and is widely used for treating solid tumors such as bladder cancer, lung cancer, ovarian cancer, head and neck tumor and the like. In vivo, cisplatin is metabolized primarily in the liver and kidneys, with over 90% of cisplatin excreted through the kidneys, so nephrotoxicity is one of the most common adverse effects of cisplatin. Currently, about 20% -30% of cancer patients receiving cisplatin treatment annually worldwide experience acute kidney injury, about 50 ten thousand of which are forced to adjust treatment regimens, with about 17% of patients progressing to chronic kidney disease, significantly increasing the risk of patient mortality. According to recent researches on the action mechanism of cisplatin nephrotoxicity, cisplatin mediates acute kidney injury mainly through local accumulation, disturbing DNA injury and repair, oxidative stress, activating programmed cell death, activating inflammatory cascade reaction, endoplasmic reticulum stress, mitochondrial injury and the like. Disclosure of Invention In view of the above, the present invention provides the use of lupeol in the preparation of a medicament for preventing or treating kidney damage caused by cisplatin, to solve the above-mentioned problems. In order to realize the scheme, the technical scheme of the invention is as follows: the invention provides application of lupeol in preparing medicines for preventing or treating kidney injury. Optionally, the kidney injury is a kidney injury caused by cisplatin. Alternatively, the lupeol is administered by intraperitoneal injection, subcutaneous injection, or oral administration. Alternatively, the process may be carried out in a single-stage, administration of lupeol the mode of administration is selected from oral administration. Optionally, the medicament further comprises a pharmaceutically acceptable carrier. Optionally, the pharmaceutically acceptable carrier includes at least one of a diluent, a binder, a surfactant, a lubricant, a filler, and a disintegrant. Alternatively, dosage forms of the medicament include granules, powders, tablets, capsules, syrups, suppositories, injections and elixirs. The invention also provides a pharmaceutical composition comprising cisplatin and lupeol. The invention also provides a pharmaceutical product comprising a pharmaceutical composition as described above. Optionally, the pharmaceutical product further comprises a pharmaceutically acceptable carrier. The invention has the following beneficial effects that the natural compound lupeol has potential protection effect on kidney injury caused by cisplatin for the first time, and in vivo and in vitro models prove that the lupeol obviously reduces kidney dysfunction, tissue pathological injury and increase of kidney injury markers caused by cisplatin, inhibits apoptosis and promotes proliferation of renal tubular cells. Transcriptome sequencing results show that lupeol enhances cell survival and proliferation by activating the PI3K/Akt signaling pathway, and simultaneously regulates Nrf2 pathway against oxidative stress, inhibits nuclear translocation of nfkb and reduces pro-inflammatory cytokines, inhibiting inflammatory response. The results indicate that lupeol may be an option for alleviating cisplatin nephrotoxicity. Drawings FIG. 1 shows results of an experiment relating to acute kidney injury in mice induced by lupeol reduction, wherein A is a Weight change curve of mice, B is a kidney function evaluation result of each group of mice, C is a kidney H & E staining and PAS staini