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CN-122005661-A - Application of peony-derived exosome-like nano vesicles in preparation of medicines for treating inflammatory bowel disease

CN122005661ACN 122005661 ACN122005661 ACN 122005661ACN-122005661-A

Abstract

The invention discloses an application of peony-derived exosome-like nano vesicles in preparation of medicines for treating inflammatory bowel diseases, which is characterized in that peony roots are taken as raw materials, exosome-like nano vesicles are extracted through a high-speed centrifugation method, POELNs morphology and size are confirmed through electron microscopy and particle size detection, and miRNA sequencing and non-targeted metabolic analysis action mechanisms are detected through a mouse in-vivo colonitis model and an in-vitro cell inflammation model. The method has the advantages of easily available raw materials, simple preparation, mild condition and high production safety.

Inventors

  • LIU ZHIFANG
  • WANG JIANGHUI
  • WANG QI
  • LI JIAN
  • HAN CHENJING

Assignees

  • 山东省农业科学院

Dates

Publication Date
20260512
Application Date
20260211

Claims (10)

  1. 1. An application of peony-derived exosome-like nano vesicle (POELNs) in preparing a medicament for treating inflammatory bowel disease.
  2. 2. The use of claim 1, wherein said peony-derived exosome-like nanovesicles are prepared by a process comprising the steps of: a) Squeezing peony root and collecting juice; b) Subjecting the juice to a first centrifugation and collecting a first supernatant; c) Subjecting the first supernatant to a second centrifugation process, and collecting a second supernatant; d) Subjecting the second supernatant to a third centrifugation, and collecting a third supernatant; e) Subjecting the third supernatant to ultracentrifugation, and collecting the precipitate; f) Washing the precipitate with PBS buffer to obtain the peony-derived exosome-like nanovesicles.
  3. 3. The use according to claim 2, wherein the first centrifugal treatment has a centrifugal force of 1000g for 10 minutes, the second centrifugal treatment has a centrifugal force of 3000g for 20 minutes, the third centrifugal treatment has a centrifugal force of 10000g for 40 minutes, and the ultracentrifugation treatment has a centrifugal force of 100000g for 90 minutes.
  4. 4. The use according to claim 1, wherein said peony-derived exosome-like nanovesicles have an average particle size of 50 nm to 300 nm, preferably 104.6 nm to 210.3 nm, more preferably an average diameter of 115.7 nm.
  5. 5. Use according to claim 1, wherein the Zeta potential of the peony-derived exosome-like nanovesicles is negative, preferably-29.0 mV.
  6. 6. The use of claim 1, wherein the therapeutic effect of the peony-derived exosome-like nanovesicles is achieved at least in part by modulating the expression profile of mirnas in the intestinal tissue of the receptor, wherein the modulated mirnas are associated with modulation of NF- κb signaling pathway, T-cell receptor signaling pathway.
  7. 7. The use of claim 1, wherein said peony-derived exosome-like nanocapsules comprise one or more lipid components selected from the group consisting of glycerophosphorylcholine, glycerophosphoinositol, fatty acids, glycosphingolipids, and combinations thereof.
  8. 8. Use according to claim 1, wherein the medicament is formulated as an oral formulation, preferably as a granule, capsule, soft capsule, oral liquid formulation, injection or transdermal formulation.
  9. 9. A pharmaceutical composition comprising a therapeutically effective amount of the peony-derived exosome-like nanovesicle of any one of claims 1-7, and a pharmaceutically acceptable carrier.
  10. 10. The pharmaceutical composition of claim 9, formulated for oral administration for the treatment of inflammatory bowel disease.

Description

Application of peony-derived exosome-like nano vesicles in preparation of medicines for treating inflammatory bowel disease Technical Field The invention relates to an application of peony-derived exosome-like nano vesicles (POELNs) in preparation of a medicament for treating inflammatory bowel disease. Background The disclosure of this background section is only intended to increase some understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art. Ulcerative colitis (ulcerative colitis, UC) is a typical Inflammatory Bowel Disease (IBD), affecting millions of people who are full-ball, placing a heavy burden on the healthcare system. Clinical manifestations of UC include diarrhea, rectal bleeding, abdominal pain, and weight loss. In the case of UC, the persistent and diffuse inflammatory process is never confined to the colonic mucosa, and in turn extends from the rectum towards the proximal colon. The etiology of UC is complex, involving interactions of genetic variations of various diseases, increases in pro-inflammatory cytokines, disruption of intestinal barrier function, environmental cues, and the like. Existing therapies such as aminosalicylates, corticosteroids, etc. have more or less side effects and they do not alleviate symptoms in patients with UC over a long period of time. Thus, new therapies are urgently needed to overcome these drawbacks. In recent years, exosome nanotherapeutics aimed at colonitis tissues and colon tumors have been widely used. The exosomes are extracellular vesicles secreted by eukaryotic cells and have a diameter of 30-150 nm, and play an important role in regulating intercellular communication and affecting the progress of various diseases. The exosomes of natural origin contain abundant bio-functional molecules and have good biosafety and large-scale production potential. Studies have shown that plants act on mammalian cells (especially intestinal macrophages and stem cells) via exosome-like nanoparticles, and that exosomes of different types of plants have different biological effects. Exosome-like nanoparticles, such as grape, grapefruit, citrus-derived, have the effect of targeting intestinal cells and can play a role in protecting mice from sodium dextran sulfate-induced colitis. Studies have shown that hydrophobic curcumin can be delivered into colon tumors and normal colon tissues by plant exosomes, which can be used as carriers for cell-processing oncogenic miRNAs. Peony (Paeonia ostii T. Hong et J.X. Zhang) belongs to Paeonia genus of Paeoniaceae family, commonly called Paeonia ostii, root bark is used as a medicine, and peony bark, also called Paeonia suffruticosa bark, is a common blood-cooling and stasis-removing Chinese medicine. Dan Pi is slightly cold in nature and bitter and pungent in flavor. It enters heart, liver and kidney meridians. Modern researches have shown that cortex moutan has antibacterial, antiinflammatory, antiallergic, antitumor, hemostatic, blood stasis dispelling, heat and toxic materials clearing away, tranquilizing, analgesic, spasmolytic, and other activities, and can promote phagocytic function of monocytes, enhance specific immunity, and increase weight of immune organs. The effect and mechanism of peony on inflammatory bowel disease are not known. In a similar case to the present invention, zhao et al found that blueberry-derived exosome-like nanoparticles (BELNs) can alleviate rotenone-induced oxidative stress in HepG2 cells and C57BL/6 mouse models, thereby effectively alleviating non-alcoholic fatty liver disease (Zhao et al, 2021). Liu et al reported that oral turmeric (turmeric) exosomes were effective in repairing damaged intestinal barriers, modulating intestinal microbiota, remodelling macrophage phenotype, and together showed powerful anti-inflammatory effects (Liu et al, 2022). The exosome-like nano particles derived from citrus have pharmacological actions such as anti-tumor, anti-oxidation, anti-inflammatory and the like, can also be used as a drug delivery carrier, and have wide application prospects in disease treatment (Han Fei, 2024). Current treatments for UC are divided into surgery and medicine, the latter involving a variety of pharmacological agents, such as aminosalicylic acid (ASA) derivatives, glucocorticoids, immunosuppressants, and biotherapeutic agents. Although these treatments can alleviate symptoms in patients with UC, they are often limited by resistance and adverse reactions, thus preventing complete control of the disease. In addition, the plant exosome nanoparticles are quite different, the biological functions are quite different, and the nanoparticles which can effectively relieve symptoms of UC patients and are hopefully popularized as edible plant-derived nanoparticles are not easy to seek. Disclosure of Invention Although the