CN116139121A - Small molecular compound for promoting cartilage regeneration - Google Patents
Small molecular compound for promoting cartilage regeneration Download PDFInfo
- Publication number
- CN116139121A CN116139121A CN202211008832.9A CN202211008832A CN116139121A CN 116139121 A CN116139121 A CN 116139121A CN 202211008832 A CN202211008832 A CN 202211008832A CN 116139121 A CN116139121 A CN 116139121A
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- China
- Prior art keywords
- cartilage
- repair
- royal jelly
- jelly acid
- promoting
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
The invention discloses an effect of royal jelly acid in promoting cartilage regeneration and repair, protecting cartilage function and treating osteoarthritis through targeting ASPH, and relates to the field of biological medicine. According to the invention, the OA model of the mice is treated by lavage feeding and joint cavity injection of the royal jelly acid, and the direct curative effect of the royal jelly acid on the OA is systematically evaluated from multiple aspects of cartilage anabolism, cartilage cell survival, aging and the like, and the ASPH is verified to be an action target of the royal jelly acid in promoting cartilage regeneration and repair and maintaining normal functions of cartilage. The royal jelly acid disclosed by the invention can promote proliferation of chondrocytes, promote anabolism of cartilage, reduce catabolism, repair cartilage tissues and protect cartilage homeostasis, thereby promoting cartilage regeneration and repair, maintaining normal functions of cartilage and improving osteoarthritis.
Description
Technical Field
The invention belongs to the technical field of biological medicine, and develops a novel small molecule drug for promoting cartilage regeneration and protecting normal functions of cartilage: royal Jelly Acid (RJA) or 10-hydroxy-2-decenoic Acid (10-HDA); the molecular formula: C10H18O3; molecular weight: 186.25; the molecular structure is shown in figure 1.
Royal jelly acid belongs to human endogenous metabolite, is fatty acid component of Lac Regis Apis, and has effects of promoting neuron growth and protecting, and reducing anxiety-like phenotype. The research shows that the royal jelly acid has the effect of promoting cartilage regeneration and repair, and can be used as a medicament for treating osteoarthritis and a nutritional preparation for maintaining normal functions of cartilage. The novel function of the royal jelly acid is protected by the invention.
Background
Unbalance of articular cartilage injury and degeneration, and chondrocyte metabolism caused by factors such as age, strain, wound, obesity, inflammation, metabolic disorder, heredity, etc. is a primary factor for inducing Osteoarthritis (OA), and is also a major pathological change of osteoarticular diseases. OA is the most common arthritis, which is a degenerative joint disease mainly manifested by joint pain due to joint fibrosis, chapping and loss caused by various factors, and is a result of aging of the human body, weakening of the natural regulation mechanism of the body, and imbalance. Along with the acceleration of the aging process in China, the incidence of OA is gradually increased, and the OA becomes a great problem affecting the life quality of the aged, so that great economic burden is caused to patients, families and society. Studies have shown that OA can lead to long-term disability in people over 50 years of age, with a final mortality rate of up to 53%. OA is therefore a major public health challenge that will be faced in the next decades.
The pathological research results of OA show that the articular cartilage injury is the most important pathological change, and is mainly represented by degradation of articular cartilage, apoptosis of chondrocytes, progressive degradation of extracellular matrix (extracellular matrix, ECM) and the like, and other pathological features also include overgrowth of bones (such as formation of osteophytes and thickening of subchondral bones), synovial hyperplasia and the like. Therefore, how to repair the damage of the articular cartilage and promote the regeneration of the cartilage is an important point and a difficult point of the current OA treatment. Studies prove that cartilage has little self-repairing ability after being damaged due to the avascular and neural specificity, and progressive tissue loss and dysfunction can be caused along with the damage and degeneration of the cartilage, so that degenerative osteoarthropathy is caused; therefore, cartilage damage and regenerative repair have been the scientific problems of great concern in the current research field.
Disclosure of Invention
In order to solve the problems in the background art, the invention provides a small molecular compound for treating osteoarthritis and maintaining the bioactivity function of cartilage, namely 10-Hydroxy-2-decenoic acid (10-HDA). The selected animal model was a mouse osteoarthritis DMM (medial meniscal destabilization) model, and the selected representative cells were human chondrocyte cell line C28I2. Through researches, the 10-HDA can obviously promote the growth and proliferation of chondrocytes and cartilage anabolism (figures 2,3 and 4) and has the function of regulating the expression of genes related to the proliferation of the chondrocytes and the cartilage anabolism (figures 4,5 and 6); secondly, the cartilage degradation caused by OA is obviously delayed in a mouse DMM model, and symptoms such as cartilage degradation and pain related to OA are relieved (figures 7 and 8), which shows that 10-HDA has potential delay effect on OA in vitro and in vivo. Furthermore, we have found and validated for the first time that the action target of royal jelly acid in eukaryotic cells is aspartic acid beta-hydroxylase (ASPH), ASPH was isolated as a new target for 10-HDA to regulate chondrocytes, and the regulation of chondrocytes by 10-HDA was dependent on ASPH. Therefore, the 10-HDA can be used as a small molecule targeting drug for regulating and controlling the regeneration and proliferation of chondrocytes, anabolism of cartilage and relieving OA pain, and provides a new targeting therapeutic strategy for clinical osteoarthritis and cartilage protection.
Drawings
For a clearer description of the present invention, the drawings that are required to be used will be briefly described.
FIG. 1 shows a simplified structure of royal jelly acid.
FIG. 2 is the effect of varying concentrations of royal jelly acid on chondrocyte viability.
FIG. 3 is the effect of varying concentrations of royal jelly acid on chondrocyte viability upon treatment with inflammatory factor IL-1. Beta.
FIG. 4 shows the effect of varying concentrations of royal jelly acid on the chondrocyte proliferation marker genes PCNA, cyclinB1 and CyclinD1 upon treatment with inflammatory factor IL-1. Beta.
FIG. 5 shows the effect of varying concentrations of royal jelly acid on the chondrocyte metabolic marker genes Col2, aggrecan and MMP13 upon treatment with inflammatory factor IL-1. Beta.
FIG. 6 shows the effect of varying concentrations of royal jelly acid on the cartilage tissue metabolism marker genes Col2, aggrecan, COMP and MMP13 upon treatment with inflammatory factor IL-1. Beta.
Fig. 7 is a graph showing the results of safranin fast green staining of joint tissues, OARSI score, cartilage thickness and chondrocyte quantification analysis of joint cartilage after 6 weeks of injection of royal jelly acid into joint cavities of mice.
Fig. 8 is an analysis of the pain sensitivity of Von frey filaments detection mice 6 weeks after injection of royal jelly acid into the joint cavities of mice.
Claims (4)
1. Use of novel small molecule medicine Lac Regis Apis acid in promoting cartilage regeneration, protecting cartilage function, and treating degenerative diseases such as osteoarthritis is provided.
2. Use according to claim 1, characterized in that: the proliferation and anabolism of chondrocytes are regulated by orally feeding or injecting small molecular medicines with cartilage regeneration and repair and anti-inflammatory effects into joint cavities.
3. The invention belongs to the field of medical and health, and can be directly applied to the clinical and basic medical fields such as cartilage repair, bone surgery or wound repair.
4. The use of the small molecule drug of claim 1 for preparing drugs for protecting cartilage function, treating osteoarthritis and other related diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211008832.9A CN116139121A (en) | 2022-08-22 | 2022-08-22 | Small molecular compound for promoting cartilage regeneration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211008832.9A CN116139121A (en) | 2022-08-22 | 2022-08-22 | Small molecular compound for promoting cartilage regeneration |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116139121A true CN116139121A (en) | 2023-05-23 |
Family
ID=86349462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211008832.9A Pending CN116139121A (en) | 2022-08-22 | 2022-08-22 | Small molecular compound for promoting cartilage regeneration |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116139121A (en) |
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2022
- 2022-08-22 CN CN202211008832.9A patent/CN116139121A/en active Pending
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