CN113633645B

CN113633645B - Application of diosgenin in preparation of medicine for relieving neuralgia caused by oxaliplatin

Info

Publication number: CN113633645B
Application number: CN202111024483.5A
Authority: CN
Inventors: 高文远; 满淑丽; 刘轩硕
Original assignee: Tianjin University
Current assignee: Tianjin University
Priority date: 2021-09-02
Filing date: 2021-09-02
Publication date: 2024-08-20
Anticipated expiration: 2041-09-02
Also published as: CN113633645A

Abstract

The invention discloses application of diosgenin in preparing a medicine for relieving neuralgia caused by oxaliplatin, and experiments prove that the diosgenin can improve mechanical and cold stimulation allodynia caused by oxaliplatin.

Description

Application of diosgenin in preparation of medicine for relieving neuralgia caused by oxaliplatin

Technical Field

The invention belongs to the field of medicines, and particularly relates to application of diosgenin in preparation of a medicine for relieving neuralgia caused by oxaliplatin.

Background

Diosgenin (Diospgenin) is a hydrolysis product of dioscin, and widely exists in plants such as yam, lily, caryophyllus and the like, and traditional Chinese medicine considers that the yam has the effects of eliminating phlegm, promoting digestion and diuresis, relaxing tendons and activating blood and the like. Modern pharmacological studies have shown that diosgenin has a number of pharmacological effects, is used for treating cancer, hyperlipidemia, inflammation and infection, and has low toxic and side effects, so that the application is relatively wide. In recent years, a great deal of research reports that diosgenin can be used for preventing and treating nervous system diseases, including Alzheimer's disease, neuroinflammation, spinal cord injury, neuropathic pain caused by diabetes and the like.

Oxaliplatin (Oxaliplatin) is a third generation platinum-based anticancer drug, and is a first-line therapeutic drug for colorectal cancer, liver cancer and other cancers. However, in up to 90% of cases, irreversible peripheral neuropathy (chemotherapy induced peripheral neuropathy, CIPN) occurs during or after oxaliplatin treatment, severely limiting its clinical use in tumor chemotherapy, mainly manifested as paresthesia, allodynia, hyperalgesia, cold-stimulus allergy, gunshot or electrocution etc. However, the mechanism of neuropathic pain caused by oxaliplatin is not clear, and there is currently no effective therapeutic agent in clinic, and a need for a drug to alleviate it is urgent.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides the application of diosgenin in preparing a medicine for relieving neuralgia caused by oxaliplatin.

The technical scheme of the invention is summarized as follows:

Use of diosgenin in preparing medicine for relieving neuralgia caused by oxaliplatin is provided.

The invention has the advantages that:

The source of the diosgenin is wide, the diosgenin is widely applied to plants such as yam, lily, caryophyllus and the like, and the toxic and side effects are low. Experiments prove that the diosgenin can obviously relieve neuralgia caused by oxaliplatin.

Drawings

Figure 1 is a graph showing the mechanical pain threshold of mice as a function of time of administration.

Figure 2 is a graph showing the changes in cold allodynia in mice following dosing.

Detailed Description

Diosgenin has molecular formula of C ₂₇H₄₂O₃, molecular weight of 414.63, white crystal powder, and is soluble in organic solvents such as methanol, ethanol, and DMSO. CAS number: 512-04-9, the structural formula is shown as formula I:

The invention is further illustrated by the following examples.

Experimental method

1.1 Model building and dosing modes

Male C57BL/6 mice of 6 weeks of age were randomly divided into normal, model and diosgenin groups (8 per group), all mice were free to drink water at ambient temperature (20.+ -. 2). Model group and diosgenin group were continuously intraperitoneally injected with oxaliplatin (3.0 mg/kg in 5% dextrose injection) 1 time per day for 5 days, at rest for 5 days, and the administration was repeated again for 5 days, reaching a total cumulative amount of oxaliplatin of 30mg/kg in total 10 injections. The pain index change of the normal group was monitored by injecting an equal dose of 5% glucose injection. Compared with the normal group, the two groups of mechanical pain threshold values of oxaliplatin injection are obviously reduced (see the zero point of figure 1), the cold allodynia phenomenon is obvious (see the zero point of figure 2), and the establishment of the neuralgia model caused by the oxaliplatin is proved to be successful. After successful molding, the administration of the stomach infusion was started, and the diosgenin group was administered with diosgenin (30 mg/kg, infused once every other day for 21 days (suspension prepared with physiological saline) in total, while normal group and model group mice were infused with an equal amount of physiological saline.

1.2 Measurement of mechanical pain threshold by a fiber yarn pain measuring instrument (Von Frey)

When the measurement is carried out, the mice are placed in an organic glass lattice with a grid at the bottom, after 20min of adaptation, a series of von Frey filaments are used for stimulating the skin in the middle of the soles of the feet of the mice according to the up and down method introduced by Dixon, and the foot contraction reaction is observed. The absence of a response is indicated as negative response "O", and the presence of a response (footstrike or licking) is indicated as positive response "X". If the first filament stimulus does not respond, then a first level of force is imparted to the filament stimulus; if the reaction exists, the filament with one-step smaller force is used for stimulation, and the analogy is repeated, 5 times of measurement are started from the reaction, a series of sequences combined by 'O' or 'X' are obtained, and the mechanical pain threshold value is calculated by inputting the sequences and the force of the last filament into a formula and is used as the mechanical pain threshold value, as shown in figure 1.

1.3 Cold allodynia assessment

The paw penetration test was used to evaluate cold allodynia, and a reduced penetration time indicated cold allodynia. The mice were habituated to testing (to adapt them to equipment or manual constraints) three days before the evaluation was performed. In the experiment, the ipsilateral hind paws of the mice were immersed in a water bath maintained at 15.0.+ -. 0.2 ℃ until signs of paw withdrawal or struggle were observed, which is the paw withdrawal latency (cut-off time 15 s), and each mouse was repeatedly tested twice to average, see figure 2.

And II, experimental results are shown in fig. 1 and 2.

Third conclusion

The results show that: diosgenin can significantly improve pain threshold lowering and cold allodynia caused by oxaliplatin, so that the diosgenin can be used for relieving neuralgia caused by oxaliplatin.

Claims

1. Use of diosgenin in preparing medicine for relieving neuralgia caused by oxaliplatin is provided.