CN-122011161-A - Peptide YIYT with osteoporosis relieving and antioxidant activities, and preparation method and application thereof

Abstract

The invention discloses a peptide YIYT with osteoporosis relieving and antioxidant activities, and a preparation method and application thereof, and belongs to the technical field of biological medicines. The amino acid sequence of the lactoferrin hydrophobic peptide YIYT is tyrosine-isoleucine-tyrosine-threonine (Tyr-Ile-Tyr-Thr, YIYT). Experiments prove that YIYT can obviously promote proliferation, differentiation and mineralization of osteoblasts, accelerate the cell cycle process, inhibit the activity of the osteoclasts, reduce the bone resorption level and restore the bone metabolism balance. In an animal model, YIYT can effectively improve the bone density of an ovariectomized mouse, improve the microstructure related to the bone, and has the double effects of promoting bone formation and inhibiting bone resorption. The lactoferrin hydrophobic peptide YIYT provided by the invention is safe in source and definite in action mechanism, and provides a new candidate substance and application direction for developing a novel anti-osteoporosis drug.

Inventors

• WANG CONG
• CHANG ZHIHUI
• CHENG SHUZHEN
• MA XIAOYU
• WU CHAO
• XU XIANBING
• DU RONGYAO

Assignees

• 大连工业大学

Dates

Publication Date

20260512

Application Date

20260130

Claims (10)

1. 1. The application of lactoferrin hydrophobic peptide YIYT in preparing anti-osteoporosis medicine is characterized in that the amino acid sequence of lactoferrin hydrophobic peptide YIYT is Tyr-Ile-Tyr-Thr.
2. 2. The use according to claim 1, wherein the medicament further comprises a pharmaceutically acceptable carrier, diluent or excipient.
3. 3. The use according to claim 1, wherein the carrier comprises microcapsules, microspheres, nanoparticles and/or liposomes.
4. 4. The use according to claim 1, wherein the medicament is administered by one or more of oral administration, intraperitoneal injection, subcutaneous injection or intramuscular injection.
5. 5. The use according to claim 1, wherein the pharmaceutical is in the form of one of a tablet, a capsule, a granule, an oral liquid, an injection or a gel.
6. 6. The use according to claim 1, wherein the medicament is administered at a dose of 5-20 mg/kg.
7. 7. Application of lactoferrin hydrophobic peptide YIYT in preparing health care products for improving bone mineral density.
8. 8. Use of lactoferrin hydrophobic peptide YIYT in the preparation of a product that contributes to antioxidant properties.
9. 9. The use according to claim 8, wherein the product comprises a daily chemical or health product.
10. 10. The use according to claim 9, wherein the daily chemical product comprises a skin care product or a cosmetic product.

Description

Peptide YIYT with osteoporosis relieving and antioxidant activities, and preparation method and application thereof Technical Field The invention relates to the technical field of biological medicines, in particular to a peptide YIYT with osteoporosis relieving and antioxidant activities, a preparation method and application thereof. Background Osteoporosis is a metabolic bone disease characterized by reduced bone mass and deterioration of bone tissue microstructure, and its central pathological mechanism is imbalance between bone formation and bone resorption. The existing anti-osteoporosis medicines commonly used clinically have obvious limitations that anti-absorption medicines such as bisphosphonates can only inhibit bone loss, can not promote new bone formation, and can possibly cause adverse reactions such as atypical femur fracture, jaw necrosis and the like after long-term use, and synthetic medicines such as teriparatide have certain treatment effects on vertebral body fracture, but have black frame warning of increased bone and meat tumor risks. Therefore, the development of a novel drug which is safe and effective and can simultaneously regulate the balance of bone formation and bone resorption has important clinical demands and social values. Lactoferrin is an 80kDa iron-binding glycoprotein contained in mammalian milk, and its enzymatic products have significant osteogenic potential. The prior researches find that the crude enzymolysis product of the lactoferrin can promote osteoblast proliferation through ERK phosphorylation and increase the bone trabecular volume of an ovariectomized rat, but the related researches mostly treat the lactoferrin peptide as a single whole, and do not pay attention to key peptides which are effective in treating osteoporosis in the lactoferrin peptide. Disclosure of Invention [ Problem ] The invention aims to provide an application of lactoferrin hydrophobic peptide YIYT in preparation of anti-osteoporosis drugs, the peptide has definite osteogenesis activity and bone resorption inhibition effect, is safe in source and clear in action mechanism, and can solve the limitations of the existing anti-osteoporosis drugs. [ Technical solution ] The invention provides a novel active peptide YIYT which has unique sequence, is proved by in vitro and in vivo experiments to be capable of efficiently relieving osteoporosis so as to play a role in bone formation, and simultaneously, the peptide segment has strong free radical scavenging capability and reducing power and can effectively relieve oxidative stress injury. The synergistic effect of the two activities provides a better solution for preventing and relieving osteoporosis and complications thereof. A lactoferrin hydrophobic peptide YIYT, the amino acid sequence of which is tyrosine-isoleucine-tyrosine-threonine (Tyr-Ile-Tyr-Thr, YIYT). The peptide fragment is derived from enzymolysis products of lactoferrin, is obtained by simulating gastrointestinal tract digestion (pepsin-trypsin hydrolysis, pH 2.5-7.0) and C18 chromatographic separation, and belongs to active peptide fragments in hydrophobic components (LF-HD) of lactoferrin. The invention provides an application of lactoferrin hydrophobic peptide YIYT in preparing anti-osteoporosis drugs, and the key action mechanism is as follows: 1. Promote osteoblast function, obviously raise proliferation activity of osteoblast (MC 3T3-E1 Subclone 14), accelerate cell cycle conversion from G0/G1 stage to S stage and G2/M stage, up-regulate mRNA and protein expression of osteogenic related markers (ALP, BMP-2, RUNX-2 and COL-I, OCN, OPN, BSP, SP 7), raise differentiation and mineralization capacity of osteoblast, and increase number and area of mineralized nodules. 2. Activating key signal channels, namely cooperatively activating Wnt/beta-catenin and BMP/Smad signal channels, up-regulating the expression of core regulatory molecules such as beta-catenin, smad1/5/8 and the like, starting an osteogenesis program and promoting the synthesis and maturation of bone matrix. 3. Inhibiting bone resorption, reducing RANKL level in serum of ovariectomized mice, increasing OPG level, down regulating RANKL/OPG ratio, reducing TRAP positive osteoclast number, inhibiting osteoclast activity, and relieving bone resorption injury. 4. Improving bone tissue morphology, remarkably improving bone density (BMD) of an osteoporosis model animal, increasing bone volume fraction (Bv/Tv), bone trabecular number (Tb.N) and bone trabecular thickness (Tb.Th), reducing bone trabecular spacing (Tb.Sp), and recovering bone tissue microstructure integrity. In one embodiment, the anti-osteoporosis medicine of the invention takes YIYT as an active ingredient, and can be prepared into various dosage forms according to clinical requirements, including but not limited to tablets, capsules, granules, oral liquid, injection, gel and the like. In one embodiment, the medicament may further comprise pharmaceutically acc