Novel polymethoxyflavone compounds for skeletal muscle modulation, methods and uses thereof

A technology of polymethoxyflavonoids and compounds, which can be used in pharmaceutical formulations, drug combinations, muscular system diseases, etc., can solve the problem of low regeneration potential of myoblasts, and achieve the effect of promoting muscle regeneration.

Inactive Publication Date: 2021-07-23
SOC DES PROD NESTLE SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Previous experimental therapies that have included myoblast transplantation have not been entirely successful because the more committed and differentiated myoblasts have a lower regenerative potential compared to muscle stem cells

Method used

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  • Novel polymethoxyflavone compounds for skeletal muscle modulation, methods and uses thereof
  • Novel polymethoxyflavone compounds for skeletal muscle modulation, methods and uses thereof
  • Novel polymethoxyflavone compounds for skeletal muscle modulation, methods and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0297] Example 1: Selection of compounds that modulate muscle stem cells

[0298] Selection of human skeletal muscle myoblasts

[0299] The inventors developed a high content screen to test compounds on primary human adult muscle cells in vitro. Human skeletal muscle myoblasts (HSMM) were purchased from Lonza ( https: / / bioscience.lonza.com ). These cells were isolated from normal donor upper arm or leg muscle tissue and used after a second passage. Several donors were tested to ensure cell viability and purity before selecting the final donors who were a 36-year-old Caucasian female (Donor 8) and a 20-year-old Caucasian female (Donor 4).

[0300] Muscle Stem Cell Commitment Assay

[0301] The primary screening assay was based on the detection of high levels of two important myogenic regulators (Pax7 and MyoD) by immunofluorescence. Pax7 and MyoD are major markers of stemness and commitment of muscle stem cells and can be used to monitor muscle stem ce...

Embodiment 2

[0304] Example 2: In Vivo Muscle Regeneration Using Thistaxanthin or Turmericol

[0305] To recapitulate the physiological process of muscle regeneration in adult skeletal muscle in response to injury or disease, we injected cardiotoxin intramuscularly into mouse hindlimb muscles. One week before the induction of muscle damage, the mice were given gavage compound of the present invention; 100 mg / kg body weight of thisraxanthin or turmericol and water were used as controls. Mice were handled once a day until the end of the experiment. To assess the efficiency of muscle regeneration, previously injured muscles were harvested 5 days after injury and cryosections were prepared. Several myogenic markers are then measured. Cryosections were stained with specific antibodies against Pax7, myogenin, laminin, and embryonic myosin heavy chain (eMHC) expression and counterstained with Hoechst33342 to visualize nuclei.

[0306] Figure 5 demonstrates that thisxanthin and turmericol are...

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Abstract

The present invention relates to novel polymethoxyflavone compounds for improving skeletal muscle plasticity regeneration to maintain or increase muscle function and / or muscle mass by modulating muscle stem cells. For example, the present invention is useful for subjects to promote muscle repair and / or subjects suffering from precachexia, cachexia, sarcopenia, myopathy, dystrophy and / or recovery after muscle injury or surgery.

Description

technical field [0001] The present invention relates to novel polymethoxylated flavone compounds for improving skeletal muscle plasticity by regulating muscle stem cells to maintain or increase muscle function and / or muscle mass. For example, the invention may be used in individuals who want to promote muscle repair and / or in individuals suffering from precachexia, cachexia, sarcopenia, myopathy, malnutrition, and / or recovery from muscle injury or surgery. Background technique [0002] Skeletal muscle regeneration is an important mechanism for repairing and maintaining muscle mass and function throughout the lifespan. Skeletal muscle regeneration primarily requires the involvement of myogenic progenitor cells, called muscle stem cells or satellite cells. [0003] Nonproliferative quiescent satellite cells adjacent to resting skeletal muscle can be identified by their variable location between the sarcolemma and basal lamina, high nuclear to cytoplasmic volume ratio, few org...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/353A61P21/06A61P21/00A61P43/00
CPCA61K31/353A61P21/00A61P21/06A61P43/00A61K31/352
Inventor J·米肖J·费奇P·斯图尔萨茨S·卡拉兹D·M·巴伦Y·拉蒂诺B·布林
Owner SOC DES PROD NESTLE SA
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