Editing Berberine

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[[Special:MyLanguage/Information on nutritional supplements people with ALS have been taking|Information on nutritional supplements people with ALS have been taking]]

* [https://en.wikipedia.org/wiki/Berberine Wikipedia page]

* [http://examine.com/supplements/Berberine/ Examine.com] summarizes berberine:
:* alkaloid extracted from various plants used in Traditional Chinese Medicine.
:* supplemented for its '''anti-inflammatory''' and '''anti-diabetic''' effects. 
:* can also '''improve intestinal health''' and '''lower cholesterol'''. 
:* able to '''reduce glucose production in the liver'''.   
:* 1500mg, taken in three doses of 500mg each, is equally effective as taking 1500mg of metformin or 4mg glibenclamide, two pharmaceuticals for treating type II diabetes. (human and animal research evidence). Effectiveness was measured by how well the drugs reduced biomarkers of type II diabetes.
:* may also synergize with anti-depressant medication and may help with body fat loss. Both of these benefits need additional evidence before berberine can be recommended specifically for these reasons.
:* main mechanism is partly responsible for its anti-diabetic and anti-inflammatory effects. 
:* able to activate an enzyme AMPK while inhibiting Protein-Tyrosine Phosphatase 1B (PTP1B).

According to Wikipedia, the half-life ''in vivo'' seems to be 3-4 hours, thus suggesting administration three times a day if steady levels are to be achieved.


== Effect of berberine on ALS ==

In rat cerebral cortex, berberine inhibits synaptosomal glutamate release.{{#pmid:23840629|Lin2013}} By downregulating several proinflammatory pathways{{#pmid:19208854|Jeong2009}} it presumably reduces the neuroinflammatory component of ALS.

Berberine activates AMPK apparently by inhibiting mitochondria{{#pmid:19208854|Jeong2009}}, resulting into increased glycolysis. ''Note: progression seems to correlate with AMPK activation in SOD1 ALS but with AMPK inactivation in TDP-43 ALS{{#pmid:24595038|Perera2014}} .''

In a study{{#pmid:21086546|Campisi2011}} on rat astrocyte primary cultures, berberine and the alkaloid extract of B. aetnensis roots were able to restore the oxidative status modified by glutamate and the levels of TG2 to control values. Consequently berberine or the alkaloid extract of B. aetnensis roots are able to ameliorate the excessive production of glutamate, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration.  

Berberine is a PPAR gamma inhibitor{{#pmid:18520050|Zhou2008}}. ''Note: the significance of this for ALS needs further elaboration.'' It may be helpful against leaky gut, which is hypothetized to be a part of ALS pathology [source needed].


==Cautions and risks==

On the negative side, berberine has been found to '''impair muscle metabolism''' by two mechanisms. It impairs mitochondrial function stimulating the expression of [http://www.pnas.org/content/98/25/14440.full atrogin-1] without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulates protein degradation but also suppresses protein synthesis, causing muscle atrophy.{{#pmid:20522589|Wang2010}} It has also been found{{#pmid:20393601|Sarna2010}} to restore SOD1 activity inhibited by lipopolysaccharides.


== Discussion threads on the ALSTDI forum ==

* [http://www.alstdi.org/forum/yaf_postst48627_berberine.aspx Berberine]

* [http://www.alstdi.org/forum/default.aspx?g=posts&t=46945 Berberine Suppresses Pro-Inflammatory Responses]:
:''In adipose tissue of obese db/db mice, BBR treatment significantly down-regulated the expression of pro-inflammatory genes such as TNFalpha, IL-1beta, IL-6, MCP-1, iNOS and COX2. Consistently, BBR inhibited LPS-induced expression of pro-inflammatory genes including IL-1beta, IL-6, iNOS, MCP-1, COX 2, and MMP9 in peritoneal macrophages and RAW 264.7 cells. Upon various pro-inflammatory signals including LPS, free fatty acids, and hydrogen peroxide, BBR suppressed the phosphorylation of MAPKs such as p38, ERK, and JNK, and the level of reactive oxygen species in macrophages.''{{#pmid:17971514|Yin2008}}

* [http://www.alstdi.org/forum/yaf_postst54133_ampk-activation-status-in-different-types-of-als.aspx AMPK activation status in different types of ALS]:
:''While AMPK activation in motor neurons correlates with progression in mutant SOD1-mediated disease, AMPK inactivation mediated by PP2A is associated with mutant TDP-43-linked ALS.''

* [http://www.alstdi.org/forum/yaf_postst50860_interesting--leaks-and-neuro-diseases.aspx Interesting - leaks in neuro diseases]
:''According to a 2010 study, berberine ameliorated damage to the tight junctions of intestinal epithelial cells induced by pro-inflammatory cytokines (in vitro). Berberine may thus serve as a targeted therapeutic agent for restoring barrier function in intestinal disease states.[16]''


== Regulated pathways ==


== Where to get it ==

* [http://www.amazon.co.uk/Swanson-Berberine-400mg-60-Capsules/dp/B006MRK8LG Amazon.co.uk (400 mg capsules)]


== References ==

[[Category:Supplement data pages]]
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-<!--T:1-->
 [[Special:MyLanguage/Information on nutritional supplements people with ALS have been taking|Information on nutritional supplements people with ALS have been taking]]
-<!--T:2-->
 * [https://en.wikipedia.org/wiki/Berberine Wikipedia page]
-<!--T:3-->
 * [http://examine.com/supplements/Berberine/ Examine.com] summarizes berberine:
 :* alkaloid extracted from various plants used in Traditional Chinese Medicine.
@@ Line 18: / Line 15: @@
 :* able to activate an enzyme AMPK while inhibiting Protein-Tyrosine Phosphatase 1B (PTP1B).
-<!--T:4-->
 According to Wikipedia, the half-life ''in vivo'' seems to be 3-4 hours, thus suggesting administration three times a day if steady levels are to be achieved.
-== Effect of berberine on ALS == <!--T:5-->
+== Effect of berberine on ALS ==
-<!--T:6-->
 In rat cerebral cortex, berberine inhibits synaptosomal glutamate release.{{#pmid:23840629|Lin2013}} By downregulating several proinflammatory pathways{{#pmid:19208854|Jeong2009}} it presumably reduces the neuroinflammatory component of ALS.
-<!--T:7-->
 Berberine activates AMPK apparently by inhibiting mitochondria{{#pmid:19208854|Jeong2009}}, resulting into increased glycolysis. ''Note: progression seems to correlate with AMPK activation in SOD1 ALS but with AMPK inactivation in TDP-43 ALS{{#pmid:24595038|Perera2014}} .''
-<!--T:8-->
 In a study{{#pmid:21086546|Campisi2011}} on rat astrocyte primary cultures, berberine and the alkaloid extract of B. aetnensis roots were able to restore the oxidative status modified by glutamate and the levels of TG2 to control values. Consequently berberine or the alkaloid extract of B. aetnensis roots are able to ameliorate the excessive production of glutamate, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration.
-<!--T:9-->
 Berberine is a PPAR gamma inhibitor{{#pmid:18520050|Zhou2008}}. ''Note: the significance of this for ALS needs further elaboration.'' It may be helpful against leaky gut, which is hypothetized to be a part of ALS pathology [source needed].
-"BACKGROUND:
-In the central nervous system regions of the sporadic and familial FTLD and ALS patients, TDP-43 has been identified as the major component of UBIs inclusions which is abnormally hyperphosphorylated, ubiquitinated, and cleaved into C-terminal fragments to form detergent-insoluble aggregates. So far, the effective drugs for FTLD and ALS neurodegenerative diseases are yet to be developed. Autophagy has been demonstrated as the major metabolism route of the pathological TDP-43 inclusions, hence activation of autophagy is a potential therapeutic strategy for TDP-43 pathogenesis in FTLD and ALS. '''Berberine, a traditional herbal medicine, is an inhibitor of mTOR signal and an activator for autophagy'''. Berberine has been implicated in several kinds of diseases, including the neuronal-related pathogenesis, such as Parkinson's, Huntington's and Alzheimer's diseases. However, the therapeutic effect of berberine on FTLD or ALS pathology has never been investigated.
-RESULTS:
-Here we studied the molecular mechanism of berberine in cell culture model with TDP-43 proteinopathies, and found that berberine is able to reverse the processing of insoluble TDP-43 aggregates formation through deregulation of mTOR/p70S6K signal and activation of autophagic degradation pathway. And inhibition of autophagy by specific autophagosome inhibitor, 3-MA, reverses the effect of berberine on reducing the accumulation of insoluble TDP-43 and aggregates formation. These results gave us the notion that '''inhibition of autophagy by 3-MA reverses the effect of berberine on TDP-43 pathogenesis, and activation of mTOR-regulated autophagy plays an important role in berberine-mediated therapeutic effect on TDP-43 proteinopathies.'''
-CONCLUSION:
-We supported an important notion that the traditional herb '''berberine is a potential alternative therapy for TDP-43-related neuropathology. Here we demonstrated that berberine is able to reverse the processing of insoluble TDP-43 aggregates formation through deregulation of mTOR/p70S6K signal and activation of autophagic degradation pathway. mTOR-autophagy signals plays an important role in berberine-mediated autophagic clearance of TDP-43 aggregates. Exploring the detailed mechanism of berberine on TDP-43 proteinopathy provides a better understanding for the therapeutic development in FTLD and ALS.'''"{{#pmid:27769241|Chang2016}}
-==Cautions and risks== <!--T:10-->
+==Cautions and risks==
-<!--T:11-->
 On the negative side, berberine has been found to '''impair muscle metabolism''' by two mechanisms. It impairs mitochondrial function stimulating the expression of [http://www.pnas.org/content/98/25/14440.full atrogin-1] without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulates protein degradation but also suppresses protein synthesis, causing muscle atrophy.{{#pmid:20522589|Wang2010}} It has also been found{{#pmid:20393601|Sarna2010}} to restore SOD1 activity inhibited by lipopolysaccharides.
-== Regulated pathways == <!--T:17-->
+== Discussion threads on the ALSTDI forum ==
-== Where to get it == <!--T:18-->
+* [http://www.alstdi.org/forum/yaf_postst48627_berberine.aspx Berberine]
+* [http://www.alstdi.org/forum/default.aspx?g=posts&t=46945 Berberine Suppresses Pro-Inflammatory Responses]:
+:''In adipose tissue of obese db/db mice, BBR treatment significantly down-regulated the expression of pro-inflammatory genes such as TNFalpha, IL-1beta, IL-6, MCP-1, iNOS and COX2. Consistently, BBR inhibited LPS-induced expression of pro-inflammatory genes including IL-1beta, IL-6, iNOS, MCP-1, COX 2, and MMP9 in peritoneal macrophages and RAW 264.7 cells. Upon various pro-inflammatory signals including LPS, free fatty acids, and hydrogen peroxide, BBR suppressed the phosphorylation of MAPKs such as p38, ERK, and JNK, and the level of reactive oxygen species in macrophages.''{{#pmid:17971514|Yin2008}}
+* [http://www.alstdi.org/forum/yaf_postst54133_ampk-activation-status-in-different-types-of-als.aspx AMPK activation status in different types of ALS]:
+:''While AMPK activation in motor neurons correlates with progression in mutant SOD1-mediated disease, AMPK inactivation mediated by PP2A is associated with mutant TDP-43-linked ALS.''
+* [http://www.alstdi.org/forum/yaf_postst50860_interesting--leaks-and-neuro-diseases.aspx Interesting - leaks in neuro diseases]
+:''According to a 2010 study, berberine ameliorated damage to the tight junctions of intestinal epithelial cells induced by pro-inflammatory cytokines (in vitro). Berberine may thus serve as a targeted therapeutic agent for restoring barrier function in intestinal disease states.[16]''
+== Regulated pathways ==
+== Where to get it ==
-<!--T:19-->
 * [http://www.amazon.co.uk/Swanson-Berberine-400mg-60-Capsules/dp/B006MRK8LG Amazon.co.uk (400 mg capsules)]
-== References == <!--T:20-->
+== References ==
-<!--T:21-->
 [[Category:Supplement data pages]]
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