Solving a long standing puzzle as to how Astragalus membranaceus functions as a pain reliever: Mechanistic insights into how Astragalus membranaceus-derived compound Astragaloside  functions as a pain medication: Astragaloside, derived from Astragalus membranaceus or its oil,  increases the expression of PD-L1, TRPV1, and CGPR, decreases the expression of Cox-2, attenuates acutes and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene, 12/July/2019, 11.39 pm

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Introduction:What they say:

A recent study from Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, US shows that “PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.” This study was published, in the 22 May 2017 issue of Nature Neuroscience (one of the best journals in Neurobiology with an impact factor of 16.724+), by Prof Ru-Rong Ji, Chen G and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, the Director-cum-chief Scientist of GBMD, reports that:  Solving a long standing puzzle as to how Astragalus membranaceus functions as a pain reliever: Mechanistic insights into how Astragalus membranaceus-derived compound Astragaloside  functions as a pain medication: Astragaloside, derived from Astragalus membranaceus or its oil,  increases the expression of PD-L1, TRPV1, and CGPR, decreases the expression of Cox-2, attenuates acutes and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene


What is known?

It has recently been shown that blocking PD-1 with antibodies one could make tumors shrink. This work, relating to Cancer immunotherapy, has been chosen as Science’s breakthrough of the year. However, the work published recently, which is described below, may highlight the caveat in such an approach, as blocking PD-L1 may promote spontaneous pain and allodynia in cancer-bearing mice.

Prof. Ji has shown recently that: (1) Programmed cell death ligand-1 (PD-L1), produced by melanoma and normal neural tissues, inhibits acute and chronic pain; (2) injection of PD-L1 alleviates pain, and thereby functions as an analgesic agent; (3) Neutralization of PD-L1 or Block of PD1 promotes mechanical allodynia (hypersensitivity to pain); (4) PD1 null mice suffer from thermal and mechanical hypersensitivity; (5) PD-L1 promotes phosphorylation of SHP-1 and inhibits Sodium channels via PD-1 activation; and (6) PD-L1 inhibits nociceptive neuron excitability in dorsal root ganglion and thereby functions as a neuromodulator, suggesting that increasing the expression or the level of PD-L1/PD1 may alleviate pain and thermal and mechanical hypersensitivity.


From research findings to therapeutic opportunity:

Astragalus membranaceus is used in India, and in other asian countries, in ayurvedic medicine, for centuries; however, the mechanistic basis of its therapeutic effect, in the treatment of pain, remains largely obscure for centuries. This study provides, for the first time, mechanistic insights into how commonly used Astragalus membranaceus and its constituents, such as Astragaloside, may attenuate pain and trauma.

A therapeutic mix encompassing Astragaloside, by increasing the expression of its target genes, it increases PD-L1 and decreases Cox-2 (Cyclooxygenase-2) , TRPV1 (transient receptor potential vanilloid 1) and CGPR (Calcitonin gene-related peptide)  levels(fig. 1). Thereby, it: (a) inhibits acute and chronic pain and trauma; (b) alleviates thermal and mechanical hypersensitivity; (c) activates signal transduction cascade downstream of PD-1 receptor; (c) phosphorylates SHP-1; (d) inhibits sodium channels and nociceptive neuron excitability (Fig 2-4).

Figure 1.Mechanistic insights into how Astragalus membranaceus-derived compound Astragaloside inhibits acute and chronic pain.  A pharmaceutical mixture encompassing Astragaloside enhances PD-L1, while decreasing Cox-2 & TRPV1 levels. Thereby, it suppresses thermal and mechanical hypersensitivity, phosphorylates SHP-1, inhibits activation of sodium channels, alleviates nociceptive neuron excitability, and attenuates acute and chronic pain.

Figure 2. Astragalus membranaceus-derived Astragaloside functions as an analgesic medication through induction of PD-L1, and down regulation of Cox-2.

Figure 4. Astragaloside, derived from Astragalus membranaceus, attenuates acute and chronic pain and trauma through down regulation of Cox-2, and up regulation of PD-L1.

Figure 4. While pharmacological activation of PD-L1 has been shown to attenuate acute and chronic pain, this study suggests that topical application of Astragaloside essential oil or turmeric-derived compound curcumin attenuates acute and chronic pain and trauma, through down regulation of Cox-2, and up regulation of PD-L1.

Thus, a pharmacological mixture encompassing Astragaloside  or its analogs, either alone or in combination with other drugs, can be used to treat acute and chronic pain and trauma.

Given: (1) the mechanistic basis as to how Astragaloside (fig.1) may aid in attenuating or decreasing or alleviating short- and long-term pain and trauma; and (2) that Astragalus membranaceus-derived compound Astragaloside is largely side-effect free, unlike most of analgesics available in the market, which ‘re experimentally proven to be liver toxic, in larger doses, physicians/orthopedicians/pain therapists may consider either prescribing Astragaloside to the needy patients or put this interesting observation into a clinical trial.

Together, this study, for the first time,  paves, not only a way to identify new analgesic drugs from Astragalus membranaceus, but also suggests as to how Astragalus oil-based massage therapy may function as an adjuvant therapy, for patients suffering from short- and long-term pain and trauma (Figure 2-4).


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $1, 500#

Undisclosed mechanistic information: How does Astragaloside  increase the expression of PD-L1?

# Research cooperation


References:

Citation: Boominathan, L., Solving a long standing puzzle as to how Astragalus membranaceus functions as a pain reliever: Mechanistic insights into how Astragalus membranaceus-derived compound Astragaloside  functions as a pain medication: Astragaloside, derived from Astragalus membranaceus or its oil,  increases the expression of PD-L1, TRPV1, and CGPR, decreases the expression of Cox-2, attenuates acutes and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene, 12/July/2019, 11.38 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Web: http://genomediscovery.org or http://newbioideas.com

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