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The hair growth promoting effect of 4-O-methylhonokiol

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The hair growth promoting effect of 4-O-methylhonokiol Empty The hair growth promoting effect of 4-O-methylhonokiol

Post  CausticSymmetry Mon Sep 26, 2011 3:55 am

Eur J Dermatol. 2011 Sep 22. [Epub ahead of print]
The hair growth promoting effect of 4-O-methylhonokiol.
Kim SC, Kang JI, Kim MK, Boo HJ, Park DB, Lee YK, Kang JH, Yoo ES, Kim YH, Kang HK.
Source
Department of Pharmacology.

The Effect of 4-O-methylhonokiol, a main component from Magnolia officinalis, on TGF-beta1-induced cell cycle arrest in human keratinocyte cell line (HaCaT)
Sang-Cheol Kim, Department of pharmacology, Jeju National University school of Medicine, Korea
Jung-Il Kang, Department of pharmacology, Jeju National University school of Medicine, Korea
Jae-Hee Hyun, Department of pharmacology, Jeju National University school of Medicine, Korea
Hye-Jin Boo, Department of pharmacology, Jeju National University school of Medicine, Korea
Eun-Sook Yoo, Department of pharmacology, Jeju National University school of Medicine, Korea
Young Heui Kim, R&D Center, Bioland Ltd., Korea
Hee-Kyoung Kang, Korea

Transforming growth factor-beta (TGF-beta) signal pathway has an essential role in the induction of catagen phase in hair follicle cycle. 4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has various biological activates such as anti-inflammatory, neurite outgrowth activity, anti-acetylcholinesterase activity and hair growth promoting effect. However, the hair-growing mechanisms of 4-O-methylhonokiol on the TGF-beta signal pathway have not yet been elucidated. Thus, we examined the effect of 4-O-methylhonokiol on TGF-beta signal pathway in human keratinocyte HaCaT cells. When HaCaT cells were pretreated with 4-O-methylhonokiol, the TGF-beta1-induced p21 expression was decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3 and Smad4 and Sp1activation by TGF-beta1 . We observed that ERK activation by TGF-beta1 was significantly attenuated by treatment with 4-O-methylhonokiol. On the other hand, TGF-beta has been reported to increase reactive oxygen species (ROS) intracellular content in different cell types as well as the effects of TGF-beta on the cell growth arrest and apoptosis have been kwon to be mediated by oxidative stress. 4-O-methylhonokiol inhibited TGF-beta1-induced ROS production and suppressed mRNA expression of NOX4.These results indicate that 4-O-methylhonokiol could inhibit TGF-beta1-induced cell growth arrest through down regulation of Smad2/3, Smad4, and NOX4 in human keratinocyte HaCaT cell and that the hair-growing activity of 4-O-methylhonokiol might be at least related to its protective action on TGF-beta-induced apoptosis that is assumed to trigger catagen induction in hair cycle.

J Med Food. 2011 Jul-Aug;14(7-Cool:724-31. Epub 2011 Apr 18.
Anxiolytic-like effects of 4-O-methylhonokiol isolated from Magnolia officinalis through enhancement of GABAergic transmission and chloride influx.
Han H, Jung JK, Han SB, Nam SY, Oh KW, Hong JT.

College of Pharmacy, Chungbuk National University, Cheongju, Korea.

Abstract This study investigated the anxiolytic-like effects of 4-O-methylhonokiol, a neolignan compound of Magnolia officinalis, by using the experimental paradigms of anxiety and compared the results with those of a known anxiolytic, diazepam. A single treatment with 4-O-methylhonokiol (0.1, 0.2, and 0.5 mg/kg, p.o.) or treatment for 7 days (0.5 mg/kg in drinking water) increased the percentage of time spent in the open arms and the number of open arms entries in the elevated plus-maze test. However, the 4-O-methylhonokiol-increased percentage of time spent in the open arm was abolished by treatment with flumazenil, a benzodiazepine receptor antagonist (10 mg/kg). 4-O-Methylhonokiol also increased the number of head dips in the hole-board test, but decreased locomotor activity. Molecular experiments revealed that the α1-subunit of γ-aminobutyric acid (GABA) type A receptors was overexpressed in the cortex of brains of mice after treatment with 4-O-methylhonokiol for 7 days. In addition, 4-O-methylhonokiol also increased chloride influx in cultured cortical cells. It is concluded that 4-O-methylhonokiol may have anxiolytic-like effects and that these effects may be mediated by GABAergic transmission with the increase of Cl(-) channel opening.

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Post  Lucky13 Mon Sep 26, 2011 4:42 am

Topical or would this work through digestion? Its good for anxiety. Better than diazepam (vallium). 5 times better actually, without the side effects such as muscle relaxation.

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Post  imprisoned-radical Mon Sep 26, 2011 4:54 am


On the other hand, TGF-beta has been reported to increase reactive oxygen species (ROS) intracellular content in different cell types as well as the effects of TGF-beta on the cell growth arrest and apoptosis have been known to be mediated by oxidative stress.

This could be the mechanism by which tocotrienols promote hair growth. Counteracting the increase in oxidative stress induced by TGF-beta signaling.

For anyone who's interested, the dermal papilla is a cell-group at the base of the hair follicles. It's believed that the effects of DHT on hair follicles are mediated by the dermal papilla: DHT binds to androgen receptors in the dermal papilla cells, and the DHT-AR complex then binds to a hormone-receptive component of the DNA, resulting in alteration of protein synthesis. TGF-beta, DKK-1 are upregulated, whereas IGF-1 is downregulated. Also, there are activated leukocytes surrounding hair follicles and these are sources of pro-inflammatory cytokines like IL-1a, TNF-alpha which also contribute to hair loss.

Some more information about the chemical signaling pathways involved in AGA:


CHRONIC INFLAMMATION, HAIR LOSS, AND WHAT YOU CAN DO ABOUT IT

Chronic systemic inflammation has been found to at the root of many serious disorders, such as cardiovascular disease, asthma, arthritis, cancer, diabetes, depression and androgenetic alopecia. These “age related” disorders are accompanied by a pathological increase of inflammatory cytokines. Lowering pro-inflammatory cytokines, such as tumor necrosis factor –alpha, interleukin – 6, interleukin 1(B) and/or interleukin B4, could help prevent and treat many age related diseases. After several published studies, which showed that inflammation is present in androgenetic alopecia, MPB Research reported these important findings to readers, particularly stressing the need to address inflammation in any hair loss treatment approach, including our recommended protocol. Excessive levels of cytokines can be systemically and topically countered by an appropriate regimen of drugs, nutrients, dietary changes, and/or hormones. For example, fish oil has been shown to effectively lower these levels, as does DHEA, Nettle extract, GLA, and some antioxidants (vitamin E and N-acetyl cysteine). Meanwhile certain herbal extracts patented by Asian companies, Emu oil, copper peptides and ketoconazole can be used to topically partially inhibit cytokine formation. Following is an extensive analysis (in layman’s terms) that makes the connection between inflammation, and the “programmed cell death” of the hair follicle, a process known as “apoptosis”. It is partially based upon input from Waseda, a Japanese researcher who has been researching inflammation and androgenetic hair loss for many years. He has been able to initiate extensive hair regrowth after being a “slick bald” Norwood 5 for many years using an aggressive combination of therapies specifically designed to counter inflammation and an apoptosis factors.


TOWARDS A COMPREHENSIVE TREATMENT OF MPB

First we must recognize that hair loss is the consequence of hair cell apoptosis, or programmed cell death. Apoptosis is the final result of what is termed the caspase activation cascade. Essentially DHT, superoxide, and other free radicals damage the cell’s mitochondria, and the damaged mitochondria in turn vomits cytochrome C, which activates the caspase 9 cascade. TGF-beta and alpha activate caspase 9 around hair follicles. The activated caspase 9 propagates downstream into caspase 3. Activation of caspase 3 is thought to be a direct cause of cell apoptosis (programmed cell death) in general. What then causes a caspase activation cascade and how can one intervene in the context of hair loss?

Protein Kinase C (PKC) as an executor of apoptosis PKC isozymes are involved in the final execution of hair cell apoptosis in relation to caspase 3. What are good inhibitors of PKC? Cycloporin (dangerous), Grape Seed Extract, Resveratrol (as in red wine), Vitamin E, and N-Acetyl Cysteine. Topically, Grape Seed Extract (a patented treatment for hair loss), and Perilla Leaf Extract.

Tumor Necrosis Factor Alpha (TNF-a) as a promotor of PKC and hair cell apoptosis. TNF-a induces the PKC isozymes and causes cell death through this induction. This pathway is known to be a major cause of hair loss. TNF-a is a quick acting proinflammatory cytokine, and TNF-a is over secreted in cases of rapid hair loss. How can TNF-a be safely inhibited? Ginkgo Biloba Extract, Stinging Nettle Extract, Green Tea Extract, and essential fatty acids found in fish, Emu, Borage, and Perilla oils. Topically, Perilla leaf extract may be useful.

TGF-Family as the bridge between DHT and the activation of the caspase cascade. In recent studies researchers have found DHT promotes TGF, and TGF causes activation of the caspase cascade and thus, hair cell death, which clinically manifests as male and female pattern baldness. What inhibits TGH safely, as opposed to the dangerous anti-cancer compounds? Proteolytic Enzymes such as a bromelain, and the anti-oxidant Curcumin are TGF inhibitors. Shiseido, a Japanese cosmetic company found that Amacha, a sugar alternative found in the orient has TGF inhibition properties. Dr. Sawaya’s latest study about finasteride suggests that the best hair loss prevention would involve the blocking of caspase activation, especially caspase 3. Caspase 3 is the direct cause of programmed hair cell death (apoptosis) that originates “upstream”. The first triggers may be DHT damage or oxidative (free radical) stress on the mitochondria, TGF induction from DHT, TNF-A induction from allergic inflammation, or PKC upregulation by caspase activation. Here we can summarize the rationale behind the treatments of various pro-inflammatory mechanisms.

DHT inhibition- Finasteride, Saw Palmetto, Rivoflavin, Green Tea Extract, Copper, Peptides, and Topical Bayberry Extract.

PKC down regulation - Grape Seed Extract, Resveratrol, Vitamin E, Soy Isoflavones.

TNF-a down regulation- Curcumin, Ginkgo Biloba Extract, Stinging Nettle Extract, Green Tea Extract, Fish Oil, Borage Oil, Perilla Oil, and Topical Perilla leaf extract.

TGF down regulation- Curcumin, and topical Amacha.

Taking into account the inhibition of hair apoptosis factors, it is apparent that treatment can be taken to a new level. Again, Waseda himself is experiencing regrowth in all areas of his scalp after being a slick bald “Norwood 5” for many years.

I've seen these topics discussed on some of the non-BS threads on other hair loss forums like HLT, and I wonder if people just gave up on them due to lack of results.

I'd like to study these signaling molecules more carefully, and if we can come up with a topical that inhibits each of these pathways, I imagine we could see a lot of success in stopping hair loss.

imprisoned-radical

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Post  CausticSymmetry Mon Sep 26, 2011 6:48 am

There's been a lot of interesting research on honokiol lately. Currently many of the honokiol supplements are not concentrated enough, so I'm keeping an eye out for some better yielding products to come out. Right now, I think quercetin is one inexpensive way to ward of anxiety and corticotropin releasing hormone.


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My regimen
http://www.immortalhair.org/mpb-regimen

Now available for consultation (hair and/or health)
http://www.immortalhair.org/health-consultation
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Post  goten574 Mon Sep 26, 2011 2:16 pm

Thread on Quercetin and hair

Another
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