Oridonin

Some research that appeared on our radar recently: “Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 – NEK7 mediated inflammasome activation” (March 23, 2021).

Link to the paper:

https://www.sciencedirect.com/science/article/pii/S1567576921002125

Excerpt:

Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.

What does that mean?

Here is an extremely loose – but simple – explanation of what this means:

inflammation is involved in noise-induced hearing loss (NIHL)
we aren’t sure how, exactly
but it seems that… sometimes… inflammation can go way too far
which might actually make things worse, or interfere with healing
this could be what happens in the ear after acoustic trauma
we aren’t sure about that either
but according to this theory…
maybe a drug that keeps the inflammation process from going way too far…
… might also help with the healing process and prevent further damage
(by making sure inflammation does not get carried away)
this might apply in the context of noise-induced hearing loss
Oridonin, anakinra are two drugs worth studying for this
but we aren’t sure… yet

Now, for those of you who prefer the nitty gritty details… diving deep into the science… and the technical side of things…

Here is some further reading about Oridonin – “a covalent NLRP3 inhibitor with strong anti-inflammasome activity” – from Nature:

https://www.nature.com/articles/s41467-018-04947-6

From that paper:

Oridonin (Ori) is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens and has anti-inflammatory activity, but the target of Ori remains unknown. NLRP3 is a central component of NLRP3 inflammasome and has been involved in a wide variety of chronic inflammation-driven human diseases.

Hmmm…

(I wonder if it has anything to do with osteoclasts…)

That’s all for now.

CATEGORY:
Research

SCREENSHOT:
Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 - NEK7 mediated inflammasome activation

TITLE:
Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 – NEK7 mediated inflammasome activation

CONTENT:
Int Immunopharmacol. 2021 Mar 23;95:107576. doi: 10.1016/j.intimp.2021.107576. Online ahead of print.

ABSTRACT

Inflammation is involved in noise-induced hearing loss (NIHL), but the mechanism is still unknown. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which triggers the inflammatory cascade, has been implicated in several inflammatory diseases in response to oxidative stress. However, whether the NLRP3 inflammasome is a key factor for permanent NIHL is still unknown. In this study, quantitative real-time polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assays (ELISAs) demonstrated that the expression levels of activated caspase-1, interleukin (IL)-1β, IL-18, and NLRP3 were significantly increased in the cochleae of mice exposed to broadband noise (120 dB) for 4 h, compared with the control group. These results indicate that the activation of inflammasomes in the cochleae of mice during the pathological process of NIHL as well as NLRP3, a sensor protein of reactive oxygen species (ROS), may be key factors for inflammasome assembly and subsequent inflammation in cochleae. Moreover, many recent studies have revealed that NEK7 is an important component and regulator of NLRP3 inflammasomes by interacting with NLRP3 directly and that these interactions can be interrupted by oridonin. Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.

PMID:33770730 | DOI:10.1016/j.intimp.2021.107576

SOURCE:
International immunopharmacology

PUBLISHER:

PMID:
pubmed:33770730

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33770730

DOI:
10.1016/j.intimp.2021.107576

DATE – PUBLISHED:
Fri, 26 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-23T12:47:43Z

DATE – ADDED:
03/27/21 10:05AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33770730/

LINK – DOI:
https://doi.org/10.1016/j.intimp.2021.107576

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1567576921002125?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-27T14:05:04+00:00, https://www.hearinglosstreatmentreport.com.