Metabolic features of the cell danger response

[lansbergen]

Good question. That makes me wonder if shutting off the cell danger response could have negative effects for some of us.

Go walk on the highway and hope no car will hit you.

 

[adreno]

I don't think anyone wants to shut off the response, just turn it down a notch.

 

[wastwater]

Using a motorway analogy,the signs would be flashing cancer ahead the cars would have crawled to a halt and then as so often on a motorway there would be no signs of an accident ie cancer

 

[Tabitha]

Using a motorway analogy,the signs would be flashing cancer ahead the cars would have crawled to a halt and then as so often on a motorway there would be no signs of an accident ie cancer

So you're saying the cell danger response causes our body to not notice and kill off cancer cells, or are you saying it wouldn't signal it to us (if you're starting to get cancer)? Sorry, my brain fog's really bad.

 

[wastwater]

I don't really know what I'm on about,but that never stopped me before so I shall continue with ideas,erm let's say there are 10 steps to cancer and cancer keeps getting to step 2,maybe this is what would trigger systemic shutdown,cell danger response
Could the immune system mistake viral replication for cancer?

 

[Tabitha]

tetramethylpyrazine looks interesting.

Someone should buy some and experiment with it. It's been used on rats.

@wastwater Interesting.

 

[BruceInOz]

Does anyone have a feel for how novel Naviaux's Cell Danger Response theory is? Is it just an incremental idea building on lots of well established knowledge or is it really revolutionary? With such a long list of conditions implicated it looks to me like a case of extraordinary claims requiring extraordinary evidence. Is that evidence mostly already in the bag?

 

[wastwater]

I'm genetically missing parts of tumour suppression pathways so when a known cancer virus like EBV comes along its not surprising something goes wrong,I wonder what happens then some kind of emergency step involving cytokines that are toxic to mitochondria?
I always look to interleukin2 as that's mentioned in oslers web and can understand how that could cause a depressive state and effect the thyroid.
Putting back the anti cancer antiviral pathway would be the answer,easier said than done,does ampligen do that.
And does rituximab lighten the EBV load
What took the pathway away to begin with,in my case I was born like that.

 

[pattismith]

Here is a paper that lists some natural antagonists of P2X:

• emodin, an anthraquinone obtained from rhubarb
• An herbal product used in Chinese medicine called ligustrazine
  (tetramethylpyrazine), an alkaloid derived from Ligusticum wallichii
• bisflavonoids from the methanolic extract fractions of Rheedia logifolia

EDIT: Pharmaceutical antagonists listed here and in here.

really interesting!

@Hip @ljimbo423

Tetramethylpyrazine is a P2X3 antagonist that alleviate pain and can act both in Dorsal Root Ganglia and brain (microglia)
It could be an interesting drug for us!



J Inflamm (Lond). 2017
Tetramethylpyrazine attenuates periorbital allodynia and neuroinflammation in a model of traumatic brain injury.
Wang Z1, Wang Q2, Wang C1, Xu X3, Yu H2.

Abstract

BACKGROUND:

Traumatic brain injury (TBI) is a public health issue. As the major complaint in 51% of TBI patients, chronic pain is an important aspect in TBI treatment. Tetramethylpyrazine (TMP) is an important compound in Ligustrazine, an analgesic drug in traditional Chinese medicine, but its potential in relieving pain symptom in TBI has not been tested. We established a TBI mouse model with controlled cortical impact (CCI), and measured periorbital hypersensitivity with von Frey monofilaments. We examined activated microglia and astrocytes and the levels of substance P (SP) and inducible isoform of nitric oxide synthase (iNOS) with immunohistochemistry, measured mRNA and protein levels of proinflammatory cytokines with qPCR and enzyme-linked immunosorbent assay, respectively. Western blot was employed to detect molecules in NF-κB signaling pathway.

RESULTS:

TMP significantly attenuated periorbital hypersensitivity in TBI mice. Within 3 days after CCI, TMP attenuated activation of microglia and astrocytes, levels of SP, iNOS, and CGRP in trigeminal pathway, and levels of proinflammatory cytokines (including IL-6, TNF-α, IL-12). In isolated microglia, TMP attenuated the effects of lipopolysaccharide on the phosphorylation of cytoplasmic IKKα/β and IKB-α, and levels of nucleic p65.

CONCLUSION:

TMP reversed periorbital hypersensitivity by limiting neuroinflammation at the primary stage of TBI, and could be a promising drug for pain treatment in TBI.

 

[Hip]

Tetramethylpyrazine is a P2X3 antagonist that alleviate pain and can act both in Dorsal Root Ganglia and brain (microglia)
It could be an interesting drug for us!

Looks like tetramethylpyrazine (also called ligustrazine) is the main active component of the Chinese herb Ligusticum wallichii (also called Ligusticum chuanxiong, Sichuan lovage root, and Huan Xiong).


A summary of the medicinal benefits of this herb is given here:

Spoiler: Tetramethylpyrazine from Ligusticum wallichii

Ligusticum wallichii (Chuan Xiong)

The root of Ligusticum wallichii is the part used for medicine. Dosage: dried crude herb 3–9 g day/adult patient. Nontoxic; LD50 is 65.9±31.3 g/kg. Alkaloids Ligusticum wallichii (TMP) is the main active principle [44,117]. It also contains ferulic acid [44]. Ligusticum wallichii protects endothelial cells against reperfusion injury, improves the microcirculation [118], promotes blood flow and removes blood stasis [44] as well as prevents proliferation of vascular smooth muscle cells [46,119]. Ligusticum and TMP have been used in treatment of ischemic stroke and angina pectoris in China since the 1960s. TMP has been used to work in three ways: as antithrombotic agent, antagonist of vasoconstriction, and anti-inflammatory compound.

TMP reduces the infarct volume via scavenging free radicals and prohibiting neutrophil migration [75]. It releases the vascular resistance to abolish coronary vasoconstriction and increase blood circulation by reducing plasma endothelin-1 (ET-1) levels during and after acute ischemia [120,121] and by inhibiting platelet aggregation and decreasing the synthesis of ET-1 and TXA2 in endothelia [44,122,123]. Inhibiting ET-1 production from endothelia [122] lowers the vascular resistance and increases CBF [44,120,121,124].

TMP has antithrombotic effects [110] by inhibiting platelet activity in humans [111,120,125]. In addition, TMP is an inflammatory inhibitor [75], antioxidant [126], and calcium antagonist [127]. TMP readily crosses the BBB and is evenly distributed throughout the intact rat brain in 20 minutes after oral administration [55,56]. LD50 of TMP is 239 mg/kg i.v. [44]. In addition, ferulic acid also inhibits inflammation after ischemia [128].


Source: here.

 

[frozenborderline]

Looks like tetramethylpyrazine (also called ligustrazine) is the main active component of the Chinese herb Ligusticum wallichii (also called Ligusticum chuanxiong, Sichuan lovage root, and Huan Xiong).


A summary of the medicinal benefits of this herb is given here:

Spoiler: Tetramethylpyrazine from Ligusticum wallichii

Ligusticum wallichii (Chuan Xiong)

The root of Ligusticum wallichii is the part used for medicine. Dosage: dried crude herb 3–9 g day/adult patient. Nontoxic; LD50 is 65.9±31.3 g/kg. Alkaloids Ligusticum wallichii (TMP) is the main active principle [44,117]. It also contains ferulic acid [44]. Ligusticum wallichii protects endothelial cells against reperfusion injury, improves the microcirculation [118], promotes blood flow and removes blood stasis [44] as well as prevents proliferation of vascular smooth muscle cells [46,119]. Ligusticum and TMP have been used in treatment of ischemic stroke and angina pectoris in China since the 1960s. TMP has been used to work in three ways: as antithrombotic agent, antagonist of vasoconstriction, and anti-inflammatory compound.

TMP reduces the infarct volume via scavenging free radicals and prohibiting neutrophil migration [75]. It releases the vascular resistance to abolish coronary vasoconstriction and increase blood circulation by reducing plasma endothelin-1 (ET-1) levels during and after acute ischemia [120,121] and by inhibiting platelet aggregation and decreasing the synthesis of ET-1 and TXA2 in endothelia [44,122,123]. Inhibiting ET-1 production from endothelia [122] lowers the vascular resistance and increases CBF [44,120,121,124].

TMP has antithrombotic effects [110] by inhibiting platelet activity in humans [111,120,125]. In addition, TMP is an inflammatory inhibitor [75], antioxidant [126], and calcium antagonist [127]. TMP readily crosses the BBB and is evenly distributed throughout the intact rat brain in 20 minutes after oral administration [55,56]. LD50 of TMP is 239 mg/kg i.v. [44]. In addition, ferulic acid also inhibits inflammation after ischemia [128].


Source: here.

A lot of powerful substances in tcm herbs Not sure about acupuncture and their overall epistemology but I’m impressed by the herbs. Considering getting a materia medica. In TCM there’s something called gu syndrome that seems like a superstition but when one looks closer may be addressing chronic infectious and inflammatory multisystem illness. I’m still skeptical about alternative medicine overall but it seems like they have some folk epistemology making metaphors around real things that they treated

 

[Hip]

@debored13, I bought some Ligusticum wallichii just recently, just to see if its anti-inflammatory effect on the brain's blood vessels might be of benefit. Unfortunately I got some mental health symptom side effects from just one dose of the herb, so I've put my test of it on hold for moment.

 

[pattismith]

Looks like tetramethylpyrazine (also called ligustrazine) is the main active component of the Chinese herb Ligusticum wallichii (also called Ligusticum chuanxiong, Sichuan lovage root, and Huan Xiong).


A summary of the medicinal benefits of this herb is given here:

Spoiler: Tetramethylpyrazine from Ligusticum wallichii

Ligusticum wallichii (Chuan Xiong)

The root of Ligusticum wallichii is the part used for medicine. Dosage: dried crude herb 3–9 g day/adult patient. Nontoxic; LD50 is 65.9±31.3 g/kg. Alkaloids Ligusticum wallichii (TMP) is the main active principle [44,117]. It also contains ferulic acid [44]. Ligusticum wallichii protects endothelial cells against reperfusion injury, improves the microcirculation [118], promotes blood flow and removes blood stasis [44] as well as prevents proliferation of vascular smooth muscle cells [46,119]. Ligusticum and TMP have been used in treatment of ischemic stroke and angina pectoris in China since the 1960s. TMP has been used to work in three ways: as antithrombotic agent, antagonist of vasoconstriction, and anti-inflammatory compound.

TMP reduces the infarct volume via scavenging free radicals and prohibiting neutrophil migration [75]. It releases the vascular resistance to abolish coronary vasoconstriction and increase blood circulation by reducing plasma endothelin-1 (ET-1) levels during and after acute ischemia [120,121] and by inhibiting platelet aggregation and decreasing the synthesis of ET-1 and TXA2 in endothelia [44,122,123]. Inhibiting ET-1 production from endothelia [122] lowers the vascular resistance and increases CBF [44,120,121,124].

TMP has antithrombotic effects [110] by inhibiting platelet activity in humans [111,120,125]. In addition, TMP is an inflammatory inhibitor [75], antioxidant [126], and calcium antagonist [127]. TMP readily crosses the BBB and is evenly distributed throughout the intact rat brain in 20 minutes after oral administration [55,56]. LD50 of TMP is 239 mg/kg i.v. [44]. In addition, ferulic acid also inhibits inflammation after ischemia [128].


Source: here.

new study for tetramethylpyrazine


Tetramethylpyrazine ameliorates isoflurane‑induced cognitive dysfunction by inhibiting neuroinflammation via miR‑150 in rats