Application of notoginsenoside R1 in preparation of medicine for treating chemotherapy-induced peripheral neuropathy

Abstract

The invention belongs to the field of medicines, and discloses application of notoginsenoside R1 (NgR1) in preparation of a medicine for treating chemotherapy-induced peripheral neuropathy. The NgR1 can significantly increase the mechanical pain threshold of chemotherapy pain, reduce inflammatory cell infiltration in dorsal root ganglions and expression of inflammatory factors such as IL-6, TNF-alpha and IL-1beta, also can significantly improve microcirculation disturbance, reduce expression of CGRP and c-fos in spinal cords, reduce expression of Cleved caspase 3 (a marker of cell apoptosis) in the dorsal root ganglions, and significantly improve chemotherapy pain. Therefore, the chemotherapy-induced peripheral neuropathy is relieved in a multi-target manner. The NgR1 treats the CIPN through three ways of relieving inflammatory response, improving microcirculation disturbance and inhibiting neuronal apoptosis, the safe and effective treatment purpose is achieved, and a new strategy is provided for clinical treatment of the CIPN.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and specifically relates to the application of notoginseng saponin R1 in preparing a medicine for treating chemotherapy-induced peripheral neuropathy. Background Art

[0002] Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting adverse reaction induced by chemotherapy drugs in clinical practice. Its clinical symptoms include numbness, hypoesthesia, paresthesia and pain in the extremities, which are distributed in a "glove-sock" pattern. The incidence rate exceeds 70%, which seriously delays the chemotherapy process of cancer patients and affects the quality of life of patients. Existing pathological mechanisms show that chemotherapy drugs promote the production of reactive oxygen species (ROS), destroy the mitochondrial electron transport chain, and directly affect the production of ATP in neurons by changing the activity of voltage-gated, ligand-gated ion channels and transient receptor potential channels, which participates in the occurrence and development of CIPN. However, current research has not clarified the pathogenesis of CIPN, and there is a lack of clinical treatment methods. According to a survey by the American Society of Clinical Oncology, there is no officially recommended drug for the prevention of CIPN in clinical practice, and the only recommendation is to suspend or delay chemotherapy. Therefore, it is an urgent clinical need to explore the treatment of CIPN.

[0003] Panax notoginseng is the dried root and rhizome of Panax notoginseng, a plant of the genus Panax, in the Araliaceae family. Its flowers and leaves can be used as medicine. It has been used in my country for more than 400 years and is one of the important traditional Chinese medicines. In the Chinese Pharmacopoeia, its official name is "Sanqi", and it has other names such as Shanqi, Xueshen, and Jinbuhuan. According to traditional Chinese medicine, Panax notoginseng tastes sweet and slightly bitter, is warm in nature, and enters the liver, stomach, heart and other meridians. It has the effects of dispersing blood stasis, stopping bleeding, reducing swelling and relieving pain. It is mainly used to treat blood stasis caused by falls, bleeding from trauma, pain caused by carbuncle, postpartum blood fainting, and retained lochia.

[0004] Notoginsenoside R1 (NgR1) is a unique component of Panax notoginseng. Whether NgR1 has a therapeutic effect on CIPN has not been studied yet. Summary of the invention

[0005] In order to solve the above problems, the purpose of the present invention is to provide a Chinese medicine monomer Notoginsenoside R1 (NgR1) for use in the preparation of a preparation for treating chemotherapy-induced peripheral neuropathy. The Chinese medicine monomer NgR1 has a good effect in treating CIPN, and is a natural active ingredient, safe and has no toxic side effects.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] Application of notoginseng saponin R1 (NgR1) in the preparation of drugs for treating chemotherapy-induced peripheral neuropathy.

[0008] Preferably, the application is the application of notoginsenoside R1 in the preparation of a drug for treating chemotherapy-induced peripheral neuropathy by exerting at least one of the following effects:

[0009] Inhibit the expression of inflammatory factors in dorsal root ganglia of chemotherapy-induced peripheral neuropathy;

[0010] Improve microcirculation disorders;

[0011] Reduced expression of CGRP and c-fos in the spinal cord;

[0012] Reduced inflammatory cell infiltration and expression of Cleaved caspase 3 (a marker of apoptosis).

[0013] The present invention provides application of NgR1 in preparing a medicine for improving the mechanical pain threshold of chemotherapy-induced peripheral neuropathy.

[0014] The present invention provides application of NgR1 in preparing medicine for reducing the expression of inflammatory factors in chemotherapy-induced peripheral neuropathy.

[0015] The present invention provides application of NgR1 in preparing a medicine for improving microcirculation disorder of chemotherapy-induced peripheral neuropathy.

[0016] The present invention provides application of NgR1 in preparing medicine for reducing the expression of CGRP and c-fos in chemotherapy-induced peripheral neuropathy.

[0017] The present invention provides application of NgR1 in preparing medicine for reducing inflammatory cell infiltration and cleaved caspase 3 expression.

[0018] The present invention has no special requirements on the dosage form of the drug, and conventional pharmaceutically acceptable excipients in the art are used with NgR1 to prepare a pharmaceutically acceptable dosage form; or NgR1 can be used directly as a therapeutic drug without adding excipients.

[0019] Based on the mouse dose conversion, the dose of NgR1 for patients with chemotherapy-induced peripheral neuropathy is 1.375-5.5 mg / kg.

[0020] Specifically, the doses of NgR1 were 1.375, 2.75 and 5.5 mg / kg.

[0021] The present invention has no special requirements on the source of NgR1, and can use common commercial products in the field. NgR1 is a natural compound product with low toxicity, wide application, simple preparation, safety and effectiveness.

[0022] The Chinese medicine monomer NgR1 can significantly increase the mechanical pain threshold of chemotherapy-induced pain, reduce the expression of inflammatory factors such as IL-6, TNF-α and IL-1β in dorsal root ganglia (DRG), and significantly improve microcirculatory disorders, reduce the expression of CGRP and c-fos in the spinal cord, and reduce cell apoptosis, thereby alleviating chemotherapy-induced peripheral neuropathy through multiple targets. NgR1 treats CIPN by reducing inflammatory response, improving microcirculatory disorders and inhibiting neuronal apoptosis, achieving safe and effective treatment goals, and providing a new strategy for the clinical treatment of CIPN. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The results of the mechanical pain threshold of the plantar part and the inflammatory factors in the DRG of mice in each treatment group are shown in Figure 2; A is the pain threshold of the plantar part of mice in each treatment group; B is the IL-6 protein level in the DRG of mice in each treatment group; C is the TNF-α protein level in the DRG of mice in each treatment group; D is the IL-1β protein level in the DRG of mice in each treatment group; Figure 1 In A, ***p<0.001, indicating a significant difference compared with the control group. ## p<0.01, ### p<0.001, indicating a significant difference compared with the oxaliplatin group; Figure 1 In B, ***p<0.001, indicating a significant difference.

[0024] Figure 2 The results of intestinal microcirculation detection of mice in each treatment group; A is the laser Doppler blood flow map, and B is the statistical diagram of the laser Doppler blood flow map; ***p<0.001, indicating significant difference.

[0025] Figure 3 The effects of each treatment group on the expression of CGRP and c-fos in the spinal cord of mice; A is the immunofluorescence image of CGRP in the spinal cord of each treatment group; B is the statistical graph of the expression of CGRP in the spinal cord of each treatment group; C is the immunofluorescence image of c-fos in the spinal cord of each treatment group; D is the statistical graph of the expression of c-fos in the spinal cord of each treatment group; *p<0.05, ***p<0.001, indicating significant differences.

[0026] Figure 4 The effects of each treatment group on the tissue morphology of mouse DRG and the expression of Cleaved caspase 3; wherein, A is the HE staining result of mouse DRG tissue in each treatment group; B is the effect of each treatment group on the expression of Cleaved caspase3 in mouse DRG tissue. DETAILED DESCRIPTION

[0027] The application of NgR1 in the CIPN mouse model can not only eliminate neuroinflammation, but also alleviate microcirculation disorders, effectively alleviating CIPN from multiple aspects and angles, providing a new and effective treatment for chemotherapy-induced peripheral neuropathy, a clinical problem that needs to be solved urgently, and for the vast number of patients suffering from neuralgia.

[0028] The present invention provides the use of NgR1 in the preparation of a drug for treating chemotherapy-induced peripheral neuropathy. The Chinese medicine monomer NgR1 can significantly increase the mechanical pain threshold of chemotherapy-induced CIPN model mice, improve the microcirculatory disorder of CIPN model mice, inhibit the inflammatory cell infiltration and inflammatory response of CIPN mice, and reduce the expression of CGRP, c-fos and Cleaved caspase3 (a marker of cell apoptosis), and has a significant effect on the treatment of CIPN.

[0029] The present invention provides the use of NgR1 in the preparation of a drug for increasing the mechanical pain threshold of chemotherapy-induced peripheral neuropathy. The traditional Chinese medicine monomer NgR1 can significantly increase the mechanical pain threshold of chemotherapy-induced peripheral neuropathy, relieve the nerve pain of CIPN, and has a significant effect on the treatment of CIPN.

[0030] The present invention provides the use of NgR1 in the preparation of a drug for inhibiting the expression of inflammatory factors in the DRG part of chemotherapy-induced peripheral neuropathy. The traditional Chinese medicine monomer NgR1 can significantly reduce the accumulation of inflammatory factors IL-6, TNF-α and IL-1β in the DRG part, and has a significant effect on the treatment of CIPN.

[0031] The present invention provides the use of NgR1 in preparing a drug for improving microcirculatory disorders. The Chinese medicine monomer NgR1 can significantly improve the circulatory disorders of CIPN induced by chemotherapy and has a significant effect on the treatment of CIPN.

[0032] The present invention provides the use of NgR1 in preparing a drug for reducing the expression of CGRP and c-fos in the spinal cord of mice. The Chinese medicine monomer NgR1 can significantly reduce the expression of CGRP and c-fos, and has a significant effect on the treatment of CIPN.

[0033] The present invention provides the use of NgR1 in preparing a drug for reducing inflammatory cell infiltration and expression of Cleaved caspase 3. The Chinese medicine monomer NgR1 can significantly reduce and inhibit inflammatory cell infiltration and reduce the expression of Cleaved caspase 3, and has a significant effect on the treatment of CIPN.

[0034] In order to further illustrate the technical solution of the present invention, the Chinese medicine monomer for treating chemotherapy-induced peripheral neuropathy and its application provided by the present invention are described in detail below in combination with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0035] NgR1 was purchased from TargetMol Chemicals Inc. with a purity of 100% and no special requirements for particle size and diameter.

[0036] Example 1

[0037] Dissolve 12.5 mg of NgR1 powder in 10 mL of sterile water, vortex and mix thoroughly to obtain a NgR1 solution with a concentration of 1.25 mg / mL.

[0038] Example 2

[0039] Dissolve 25 mg of NgR1 powder in 10 mL of sterile water, vortex and mix thoroughly to obtain a 2.5 mg / mL NgR1 solution.

[0040] Example 3

[0041] Dissolve 50 mg of NgR1 powder in 10 mL of sterile water, vortex and mix thoroughly to obtain a 5 mg / mL NgR1 solution.

[0042] Example 4

[0043] Evaluation of the effect of the traditional Chinese medicine monomer Notoginseng saponin R1 (NgR1) in the treatment of CIPN

[0044] Experimental protocol:

[0045] 1 Experimental animals: Male C57BL / 6J mice, SPF grade, 6-8 weeks old, provided by Zhejiang Weitong Lihua Experimental Animal Technology Co., Ltd. Tongxiang Branch, and raised in the Experimental Animal Center of Nanjing Medical University. C57BL / 6J mice were used for animal experiments. All experimental animals were kept in an independent environment with 12h light and dark alternation, free access to water and food, and the temperature of the breeding environment was maintained at 22±2℃. The experiment was carried out after 1 week of adaptation. All experimental operations followed the regulations of the Ethics Committee of the International Association for the Study of Pain.

[0046] 2 Experimental methods:

[0047] (1) Grouping: SPF-grade healthy adult male C57BL / 6J mice (24-26 g) were selected and randomly divided into five groups (n=6), namely, a control group (Con group), an oxaliplatin group (L-OHP group), three oxaliplatin + NgR1 groups (L-OHP + NgR1 groups, i.e., treatment groups), and an NgR1 group.

[0048] Control group: 0.1mL / 10g sterile water, gavage; L-OHP group: oxaliplatin (dosage: 3mg / kg / day), mice were intraperitoneally injected with oxaliplatin solution prepared with sterile water for 5 consecutive days to establish a CIPN model; 3 treatment groups: NgR1 (dosage: 12.5, 25 and 50mg / kg / day, corresponding to the NgR1 solution of Examples 1, 2 and 3, respectively), continuous administration for 7 days, for the first 5 days, mice were gavage 20 minutes before oxaliplatin administration, and only NgR1 was gavaged for the next 2 days; NgR1 group: the NgR1 solution of Example 2 was administered, and NgR1 (dosage: 25mg / kg / day) was gavaged for 7 consecutive days. The mechanical pain threshold of mice was measured every day, and intestinal Doppler blood flow measurement was performed on the 7th day of modeling to examine microcirculatory disorders. On the 7th day of modeling, DRG tissues and spinal cord tissues of mice were collected for immunofluorescence experiments, HE staining experiments and ELISA experiments to examine the expression of CGRP, c-fos and Cleavedcaspase 3 and the infiltration of inflammatory cells.

[0049] (2) Determination of mechanical withdrawal reflex threshold: using von Frey hair test [1] The mechanical pain threshold of mice was measured. The pain-testing fiber was composed of 20 nylon Von Frey Hairs (0.008-300g of stimulation force), which was mainly used to evaluate the tactile pain sensation of the skin. The stimulation force of Von Frey Hairs was positively correlated with its thickness.

[0050] Specific measurement method: Determine the pain threshold of the right sole of the mouse. During the measurement, the mouse was placed in a transparent acrylic compartment to familiarize itself with the environment for 20 minutes. The bottom of the transparent compartment was a wire mesh. After the mouse's exploratory behavior stopped and all four limbs were in contact with the wire mesh, the test was performed. First, thin Von Frey Hairs were selected to vertically stimulate the skin of the mouse's sole until the Von Frey Hairs were bent. If the mouse showed a retraction reflex, the mouse's retraction, licking, and other actions were considered a positive reaction, indicating that the stimulation force at this time was the mechanical pain threshold of the mouse's sole. Each measurement was performed at an interval of 3 minutes, and the average value of 3 measurements was taken. The test results are shown in Figure 1 A. If the mouse does not show positive reactions such as paw retraction and licking, it is necessary to replace it with coarser Von Frey Hairs for stimulation until the mouse shows a positive reaction when the Von Frey Hairs are bent, and the mechanical pain threshold of the mouse is recorded.

[0051] Figure 1 A is the effect of each treatment group on the pain threshold of the mouse plantar. Figure 1The results of A show that the Chinese medicine monomer NgR1 (12.5mg / kg, 25mg / kg and 50mg / kg) can significantly increase the mechanical pain threshold of mice. The effect of NgR1 on relieving CIPN pain in mice is dose-dependent, especially the therapeutic effects of 25mg / kg and 50mg / kg are the most obvious. Subsequent experiments all selected 25mg / kg as the dosage of NgR1. In 2017, a study showed that the CIPN model was established using oxaliplatin, and duloxetine (10, 30 and 60mg / kg) was used for treatment. The results showed that 10mg / kg of duloxetine could not relieve CIPN pain in mice, 30mg / kg and 60mg / kg of duloxetine could partially relieve CIPN pain in mice, but the efficacy of 30mg / kg was poor, and 60mg / kg of duloxetine could only relieve 40% of CIPN pain in mice, but it would cause adverse reactions such as drowsiness in mice. [2] The Chinese medicine monomer NgR1 can significantly alleviate CIPN pain in mice, and the therapeutic dose has no adverse reactions.

[0052] (3) ELISA method to detect inflammatory factor levels

[0053] On the 7th day of modeling, DRG tissues of mice in the control group, L-OHP group, treatment group (NgR1 dosage 25 mg / kg / day), and NgR1 group (NgR1 dosage 25 mg / kg / day) were extracted, and the protein levels of IL-6, TNF-α, and IL-1β in the DRG tissues of mice were detected according to the instructions of ELISA reagent (R&D Biosystems).

[0054] Figure 1 B is the IL-6 protein level in DRG of mice in each treatment group. Figure 1 C is the TNF-α protein level in DRG of mice in each treatment group, Figure 1 D is the IL-1β protein level in DRG of mice in each treatment group. Figure 1 As shown in Figures B-D, NgR1 can significantly reduce the expression levels of inflammatory factors IL-6, TNF-α and IL-1β in the DRG of CIPN mice, reduce the inflammatory response in the DRG area, and significantly alleviate CIPN.

[0055] (4) Doppler blood flow measurement: The mice in the control group, L-OHP group, treatment group (NgR1 administration dose 25 mg / kg / day), and NgR1 group (NgR1 administration dose 25 mg / kg / day) were placed in the induction box of the small animal anesthesia machine, and the mice were anesthetized by adjusting the appropriate isoflurane gas concentration. After anesthesia, the mice were placed under the lens of the moorFLPI2 Doppler speckle blood flow meter, and the mouth and nose of the mice were placed in the anesthesia maintenance catheter to maintain anesthesia. A small incision of about 1 cm was made in the abdomen of the mouse, and part of the colon was removed with forceps and placed in the center of the lens of the moorFLPI2 Doppler speckle blood flow meter. The blood flow was continuously detected for 10 seconds. The mice could not move during the process. After the shooting was completed, the intestinal blood flow values ​​of the mice were counted and analyzed.

[0056] Figure 2 The effects of each treatment group on the intestinal microcirculation of mice, among which, Figure 2 In A, under the same contrast, the darker the red, the richer the blood flow, and the darker the blue, the more microcirculatory disorders and blood flow obstruction. Compared with the control group, the intestinal microcirculatory blood flow of the L-OHP group mice (i.e., CIPN model mice) was significantly reduced, and the microcirculatory disorders were serious. The intestinal blood flow of the mice in the NgR1 treatment group was significantly improved, which had an obvious therapeutic effect.

[0057] (5) Immunofluorescence detection of CGRP and c-fos protein expression levels

[0058] A. Frozen section fixation: Samples were collected on the 7th day of modeling. On the same day, mice in the control group (Con group), L-OHP group, treatment group (L-OHP+NgR1 group, NgR1 dose 25 mg / kg / day), and NgR1 group (NgR1 dose 25 mg / kg / day) were perfused. Use a large-range syringe to draw 20 mL of saline in advance, connect the three-way valve and the syringe needle, open the mouse chest, and gently insert the syringe needle tip into the mouse apex. It should not be too deep. At the same time, cut off the liver to allow blood to flow out, and start pushing in saline. After the end, change the syringe to draw 20 mL of 4% paraformaldehyde, change the direction of the corresponding three-way valve, and push in paraformaldehyde for fixation. Then take the mouse spinal cord and DRG and place them in paraformaldehyde. After 24 hours, transfer them to 40% sucrose solution for dehydration. After dehydration for one week (tissue sank to the bottom of the EP tube), OTC glue was used for embedding, and spinal cord and DRG tissue sections were sliced ​​using a freezing microtome with a thickness of 15 μm. DRG sections were adhered to adhesive slides and dried in a 37°C oven for two hours.

[0059] B. Blocking and antibody incubation: Take out the slides to be subjected to immunofluorescence, rinse three times in 1×PBS on a shaker at a speed of 60-70rpm, 10min each time. Other slides are stored in a -20℃ refrigerator. After rinsing with PBS three times, use filter paper to dry the slides, taking care to avoid touching the spinal cord and DRG tissues, then use an immunohistochemistry pen to draw circles on the corresponding parts of the spinal cord and DRG tissues, drop 10% donkey serum into the circle, and block at room temperature for two hours. After two hours, discard the 10% donkey serum, prepare the blocking and penetration solution, add 3‰-5‰ Triton to the 10% donkey serum, vortex mix on a shaker, drop it back into the circle of the histochemistry pen, and block and penetrate overnight in a 4℃ refrigerator. Rinse with PBS the next day, rinse three times on a shaker at a speed of 60-70rpm, 10min each time. After rinsing with PBS three times, wipe the slide dry with filter paper, be careful not to touch the DRG tissue, then use the immunohistochemistry pen to re-circle the corresponding parts of the spinal cord and DRG tissue, drop the primary antibody (dilute according to the dilution ratio of the antibody manual), and incubate overnight in a 4°C refrigerator. Rinse with PBS on the third day, rinse three times on a shaker, with a speed of 60-70rpm, 10min each time. After rinsing with PBS three times, wipe the slide dry with filter paper, be careful not to touch the DRG tissue, then use the immunohistochemistry pen to re-circle the corresponding parts of the spinal cord and DRG tissue, drop the secondary antibody (prepare the corresponding species-derived fluorescent antibody according to the primary antibody manual), and incubate at room temperature for two hours away from light.

[0060] C. Sealing: After two hours, discard the secondary antibody and rinse with PBS. Rinse three times on a shaker at 60-70 rpm for 10 minutes each time. After three PBS rinses, wipe the slide dry with filter paper, being careful not to touch the spinal cord and DRG tissue, and seal the slide with 50% glycerol prepared with PBS. Keep it away from light throughout the process.

[0061] D. Photography and data analysis: After sealing, immunofluorescence analysis was performed under a confocal microscope. ImageJ software was used to scan the grayscale of each group of data images, and Graphpad was used for data statistics and analysis.

[0062] Figure 3 The results of the detection of CGRP and c-fos in the spinal cord of mice in each treatment group are shown in Table 1. Figure 3 A and C are the expression levels of CGRP in the spinal cord of mice in each treatment group. Figure 3 B and D are the expression levels of c-fos in the spinal cord of mice in each treatment group. Compared with the control group, the expression levels of CGRP and c-fos in the spinal cord of mice in the L-OHP group (i.e., CIPN model mice) were significantly increased, and NgR1 could significantly reduce the expression levels of CGRP and c-fos in the spinal cord of mice, significantly alleviating CIPN.

[0063] HE staining: Mouse DRG tissue was stained with hematoxylin and eosin (HE). DRG tissue was fixed in 4% paraformaldehyde, embedded in paraffin, cross-sectioned, and dewaxed. After 10 minutes of hematoxylin staining, it was differentiated with 1% hydrochloric acid ethanol and then stained with weak alkaline blueing solution. It was gradually dehydrated with 80%, 95% and anhydrous ethanol, and finally the tissue sample was sealed with neutral resin for microscopic examination, image acquisition and analysis.

[0064] Figure 4 The tissue morphology of DRG and the expression of Cleaved caspase 3 in mice in each treatment group are shown in Figure 2. Figure 4 A is the detection result of DRG tissue morphology of mice in each treatment group, and B is the detection result of Cleaved caspase 3 expression in DRG tissue of mice in each treatment group. HE staining results showed that compared with the control group, there were a large number of inflammatory cells infiltrating in the DRG tissue of mice in the L-OHP group (i.e., CIPN model mice), and NgR1 could significantly reduce the inflammatory cells in the DRG tissue of mice. Immunofluorescence results showed that compared with the control group, the expression of Cleaved caspase 3 in the DRG tissue of CIPN model mice was significantly increased, indicating a large number of cell apoptosis. NgR1 could significantly reduce the expression of Cleaved caspase 3 in the DRG tissue of CIPN model mice, inhibit cell apoptosis, and treat CIPN.

[0065] In summary, the traditional Chinese medicine monomer NgR1 can significantly increase the mechanical pain threshold of oxaliplatin-induced CIPN model mice, reduce inflammatory cell infiltration and inflammatory response, and improve microcirculation disorders in CIPN model mice, and has a very significant therapeutic effect on CIPN.

[0066] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

[0067] References:

[0068] [1]Yang X,Jia RM,Hu F,Fan W,Lin TT,Zhang XT,Xu CJ,Ruan SR,Jiang CY,LiY,Pan CL,Yang Y,Hu L,Qi Chen,Wen-Tao Liu.Promoting AMPK / SR-A1-mediatedclearance ofHMGB1 attenuates chemotherapy-induced peripheral neuropathy.CellCommun Signal.2023;21(1),99.DOI:10.1186 / s12964-023-01100-9.PMID:37143083。

[0069] [2]Kim W,Chung Y,Choi S,Min BI,Kim SK.Duloxetine ProtectsagainstOxaliplatin-Induced Neuropathic Pain and Spinal NeuronHyperexcitability in Rodents.Int J MolSci.2017 Dec 5;18(12):2626.doi:10.3390 / ijms18122626.PMID:29206213。

Claims

1. Application of notoginseng saponin R1 in the preparation of drugs for treating chemotherapy-induced peripheral neuropathy.

2. The use according to claim 1, characterized in that: The application is the application of notoginseng saponin R1 in the preparation of a drug for treating chemotherapy-induced peripheral neuropathy by exerting at least one of the following effects: Inhibit the expression of inflammatory factors in dorsal root ganglia of chemotherapy-induced peripheral neuropathy; Improve microcirculation disorders; Reduced expression of CGRP and c-fos in the spinal cord; Reduced inflammatory cell infiltration and cleaved caspase 3 expression.

3. Application of notoginseng saponin R1 in the preparation of drugs for increasing the mechanical pain threshold of chemotherapy-induced peripheral neuropathy.

4. Application of notoginseng saponin R1 in the preparation of drugs for inhibiting the expression of inflammatory factors in dorsal root ganglia of chemotherapy-induced peripheral neuropathy.

5. Application of notoginseng saponin R1 in the preparation of drugs for improving microcirculation disorders.

6. Application of notoginseng saponin R1 in the preparation of drugs for reducing the expression of CGRP and c-fos.

7. Application of Panax notoginseng saponin R1 in the preparation of drugs for reducing inflammatory cell infiltration and cleaved caspase 3 expression.

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