Nature-derived lignan compound VB-1 exerts hair growth-promoting effects by augmenting Wnt/β-catenin signaling in human dermal papilla cells.

PeerJ. 2018 May 8;6:e4737. doi: 10.7717/peerj.4737. eCollection 2018.
Nature-derived lignan compound VB-1 exerts hair growth-promoting effects by augmenting Wnt/β-catenin signaling in human dermal papilla cells.
Luo J1,2, Chen M1,2, Liu Y1,2, Xie H1, Yuan J3, Zhou Y4, Ding J4, Deng Z1,2,5, Li J1,2,5.

BACKGROUND:
Vitexin is a kind of lignan compound which has been shown to possess a variety of pharmacological effects, such as anti-inflammatory, anti-oxidative and anti-cancer activities. However the effect of vitexin on hair regeneration has not been elaborated.

METHODS:
The proliferation of human dermal papilla cells (hDPCs) was examined by cell counting and continuous cell culture after vitexin compound 1 (VB-1) was treated. The expression of lef1, wnt5a, bmp2, bmp4, alpl and vcan was examined by RT-PCR. The expression of dkk1, tgf-β1, active-β-Catenin, and AXIN2 was examined by RT-PCR or immunoblotting. Hair shaft growth was measured in the absence or presence of VB-1.

RESULTS:
We demonstrated that VB-1 significantly promotes the proliferation of hDPCs in a concentration-dependent manner within a certain concentration range. Among the hair growth-related genes investigated, dkk1 was clearly down-regulated in hDPCs treated with VB-1. The increased active β-Catenin and decreased AXIN2 protein levels suggest that VB-1 facilitates Wnt/β-catenin signaling in hDPCs in vitro. The expression of DP signature genes was also upregulated after VB-1 treatment. Our study further indicated that VB-1 promotes human hair follicle (HF) growth by HF organ culture assay.

DISCUSSION:
VB-1 may exert hair growth-promoting effects via augmenting Wnt/β-catenin signaling in hDPCs.

Full: https://peerj.com/articles/4737/

Is there anyway to obtain this is a topical?

What is the best source to take internally? And how much?

sizzlinghairs wrote:Is there anyway to obtain this is a topical?

What is the best source to take internally? And how much?

This research is interesting if we go way back to the mid 2000's. In those days, the latest research at that time was
secoisolariciresinol diglucoside (SDG) from flax seed hulls. You'll see how this relates from a separate, bur related paper.

That related paper below describes the precise dosages and extraction methods, which are exactly the same as the above paper, but for different purposes (cancer).

Interesting because SDG required metabolization in the intestines...whereas Vitexins does not.

Translational Relevance

The biological efficacy of classic lignans, e.g., secoisolariciresinol diglucoside in flaxseed, is primarily mediated by their metabolized bioactive mammalian lignans END and ENL. The antitumor effect of flaxseed lignan often depends on the actual amount of END and ENL, which can be affected by the activities of intestinal bacteria and the use of antibiotics.

We isolated a series of new lignan compounds, Vitexins, which belong to a new class of neolignan. In contrast to classic lignans, Vitexins are not metabolized to END and ENL, and thus, the antitumor efficacy may not require intestinal activation process. Although acting as phytoestrogens, classic lignans alternates steroid biosynthesis and metabolism, the exact mechanisms are poorly understood. Vitexins induce apoptosis by activation of caspases-3 and caspases-9, up-regulation of Bax, and down-regulation of Bcl-2, and have a potent and broad antitumor effect. Vitexins may prove to be a better lignan compounds for cancer intervention.

Lignans are a group of complex polyphenolic antioxidants found in plants. Lignans such as secoisolariciresinol (SDG) found high in flaxseed, have antitumor effect. Clinical studies suggest that lignans are one of the most promising classes of dietary agents for testing in cancer prevention (1–3). In particular, lignan may prevent hormone-dependent diseases such as breast cancer and prostate cancer. Several lignans have been extensively investigated in preclinical tumor xenograft models, prospective and case-control epidemiologic studies, and in some clinical trials (1–7). Many of the dietary plant lignans are converted by intestinal microbiota to mammalian metabolites of END and ENL (8–11). Mammalian lignans have been thought to be the major biologically active lignan, and suggested to be associated with low risk of cancer (4). Although there is no randomized clinical trial data that exist, indicating that lignan can reduce cancer growth, there are several biomarker-based neoadjuvant trials indicating that dietary intake of flaxseed lignan can inhibit tumor cell proliferation and induce apoptosis (2, 5). The ability to inhibit tumor growth kinetics in a neoadjuvant setting has previously been used as a measure of an agent's effectiveness in clinical circumstances (12–14). One neoadjuvant study, in a randomized double-blind placebo-controlled clinical trial, examined the effects of dietary flaxseed on tumor biological markers in postmenopausal patients with newly diagnosed breast cancer (5). In this study, patients were randomized to daily intake of either a 25-gram flaxseed-containing muffin or a control (placebo) muffin. Dietary supplement of flaxseed lignans for 39 days resulted in a significant reduction of proliferation index (Ki67 labeling index) by 34% and increase in apoptotic index by 31%. Very interestingly, HER2 expression in breast cancer was significantly reduced by 71% in the lignan treated group.

Based on the current understanding on lignan metabolism, the primary benefit of plant lignan consumption is to increase blood levels of mammalian lignan END and ENL. The mechanism of anticancer action of mammalian lignans is not yet fully understood, but there is intriguing evidence for ENL as a modulator of steroid hormone metabolism and signaling. ENL functions via several mechanisms to reduce estrogen levels. First, ENL inhibits the aromatase enzyme (15, 16). ENL and END inhibited the production of estrone and estradiol in MCF-7 breast cancer cells and reduced their proliferation (16). Second, ENL may also reduce estrogen levels by inhibiting its binding to its primary protein carrier sex hormone–binding globulin (17). This enables liver to more efficiently accelerate the natural metabolic clearance of estrogen. Third, among the three major estrogen hormones of estrone, estradiol, and estriol, estradiol (E2) is the most potent, and its levels are closely associated with high risk in breast cancer. ENL inhibits the enzyme 17-β hydroxysteroid dehydrogenases, which are responsible for the conversion of estrone into estradiol (4). Other mechanisms relevant to breast cancer development are alteration of growth factor action (18–22), but there is little evidence that these effects occur in vivo in human subjects. END has been shown to inhibit angiogenesis in animal models of hormone-dependent cancers (5). Consistent with the hypothesis that mammalian lignans behave like selective estrogen receptor modulators and alternate estrogen metabolism and signaling, a recent large prospective study indicate that higher dietary lignan intakes is associated with a reduced risk of hormone-dependent breast cancer (7). In this study, women who had the highest dietary intakes of total plant lignans have a statistically significant lower risk of postmenopausal breast cancer compared with women who had the lowest intakes. However, these inverse associations are limited to estogen receptor (ER) and progesterone receptor (PR)-positive breast cancers, for which such inverse associations between breast cancer risk and the intakes of mammalian lignans are also observed.

We reported here an isolation of a unique class of lignan compounds named as Vitexins from the seed of Chinese herb Vitex Negundo. Contrast to the classic lignans, Vitexins did not go through metabolic activation to generate mammalian lignans. Although Vitex Negundo has been traditionally used as a folk medicine for cough, asthma, rheumatism, and arthritis and shown to have anti-inflammatory activities (23–25), we found that Vitexins activate caspases, induce apoptosis, and have broad antitumor activity in cancer xenograft models.

Materials and Methods
Extraction and isolation
Air-dried seeds of Vitex Negundo (10 kg) were extracted with 40% ethanol (2 × 10 L) and subjected to separation on polyamide chromatography column (30-60 mesh, 10 × 120 cm). After eluting with ethanol-H2O (0%, 40%, 60% and 95%, 32 liters each), the strongest cytotoxicity against MCF-7 was found to be present in the 40% ethanol. The 40% ethanol elution was partitioned between EtOAc and H2O. The EtOAc layer was concentrated to form a mixture of lignan extracts, EVn-50 (81 grams). EVn-50 was first subjected to column chromatography over Sephadex LH-20 (5 × 70 cm) and eluted by increasing concentrations of methanol (between 0 and 60%) in water to give five fractions. Fraction D was crystallized from methanol to yield 6-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-3, 4-dihydro-2-naphthaldehyde (VB1).

That's very interesting, especially since flaxseed is so easy to consume.

I take ground flaxmeal by putting it in my smoothies.  I usually use two heaping tablespoons.

So this is definitely good for all hormones?  I keep wondering about the pro-estrogen effects of it (in men).  But I also read that it balances your hormones rather than increase or decrease them to unbalanced levels. So I'm kind of confused.

johndoe1225 wrote:That's very interesting, especially since flaxseed is so easy to consume.

I take ground flaxmeal by putting it in my smoothies.  I usually use two heaping tablespoons.

So this is definitely good for all hormones?  I keep wondering about the pro-estrogen effects of it (in men).  But I also read that it balances your hormones rather than increase or decrease them to unbalanced levels.  So I'm kind of confused.

Sorry, I did not intend this to be misunderstood. It has very little to do with flaxseeds. This was info closer to circa 2004.

This has to do with another type of seeds (Vitex Negundo).

So can you buy these seeds, crush them and make your own tincture with alcohol?

CausticSymmetry wrote:

johndoe1225 wrote:That's very interesting, especially since flaxseed is so easy to consume.

I take ground flaxmeal by putting it in my smoothies.  I usually use two heaping tablespoons.

So this is definitely good for all hormones?  I keep wondering about the pro-estrogen effects of it (in men).  But I also read that it balances your hormones rather than increase or decrease them to unbalanced levels.  So I'm kind of confused.

Sorry, I did not intend this to be misunderstood. It has very little to do with flaxseeds. This was info closer to circa 2004.

This has to do with another type of seeds (Vitex Negundo).

Oh I see, but even so, flaxseeds are all good, right?  I mean ground flaxmeal (just ground seeds).  I use Bob's redmill.  I just don't want to increase estrogen or anything like that. They are very tasty though and add a nice nutty taste to anything.

Been there done that with flaxseeds...talked about it for years on the forums...Am I still doing it? No.

Why?

It's all in the details I already posted. Flaxseeds have to convert to enterolactone via the intestines...that's not a given.

Nothing wrong with doing it though.

Someone found this:

https://amzn.to/2JGdoVy

CS,

This study seems to indicate that too much Vitexin causes damage to cells. I know the concentration added to the cell cultures was probably extremely high, but do you think there is a limit to how much Vitex Negundo we can consume internally before it would have a negative effect? I've been taking 1500mg a day.

Serge wrote:CS,

This study seems to indicate that too much Vitexin causes damage to cells. I know the concentration added to the cell cultures was probably extremely high, but do you think there is a limit to how much Vitex Negundo we can consume internally before it would have a negative effect?  I've been taking 1500mg a day.

Many people confuse toxicity with cytotoxicity (as in toxic to cancer cells).

Anyway I just looked at an acute toxicity study performed on mice. They used 2000 mg per Kilogram of body-weight (that's a lot). That's like a person who weights 100 pounds (or 45 Kg) to take 90,000 mg per day (it wound't kill even then).

CONCLUSION
In conclusion, this study provides the very valuable data on the acute and sub acute toxicity
profile of the combined extracts of Vitex leucoxylon, Vitex negundo and Vitex trifolia that should be very
useful for any future in vivo and clinical study of this plant medicine. Vitex leucoxylon, Vitex negundo and
Vitex trifolia was found to be less toxic when oral acute and sub acute toxicities in mice were performed.
ISSN: 0974-2115

www.jchps.com Journal of Chemical and Pharmaceutical Sciences
January – March 2014 58 JCPS Volume 7 Issue 1
Chronic toxicity, are necessary to further support the safe use of this herb. These results showed that the
use of extracts of Vitex leucoxylon, Vitex negundo and Vitex trifolia is safe and explained the extensive
utilization of the plant in traditional medicine.