TUMOR NECROSIS FACTOR ALPHA AND HAIR
LOSS
Tumor necrosis factor alpha (TNF-a) is a dangerous chemical messenger
(cytokine) that incites the immune system to attack healthy tissues
throughout the body. Elevated TNF-a causes a systemic inflammatory
cascade that results in arthritis, age related neurological problems,
vascular complications and the catabolic wasting effect seen in cancer.
Recent studies have conclusively shown that TNF-a plays a central role in the
genetically programmed death (apoptosis) of hair cells in MPB (androgenetic
alopecia). In fact, it is considered by several leading researchers to
be the most significant factor in hair cell death, even possibly more
significant than DHT.
There are currently a few TNF-a inhibitors on the market (e.g. Enbrel,
Remicade). These drugs are approved for use in the treatment of
rheumatoid arthritis and Crohn's disease. Scalp hair growth has been
occasionally observed as a side effect of using these compounds. Unfortunately these
drugs are very expensive and administered by injection and infusion only.
Surprisingly, the leaves of the common stinging nettle (Urtica dioica) have
been found to contain substances that affect cytokine levels in the
human body, particularly TNF-a. Nettle leaf extract has a long
tradition as a medical remedy in Germany for inflammatory conditions such a
rheumatoid arthritis and allergic rhinitis.
A study by Obertreis, Giller et al. (1996) showed that nettle leaf extract
inhibits the expression of several cytokines as well as the formation of
pro-inflammatory leukotrienes and prostaglandis, but its mode action has
remained unclear. It has now been discovered that the seemingly
insignificant herb reduces TNF-a levels by inhibiting a genetic transcription
factor known as a nuclear factor kappa beta (NF-kb), that controls the
expression of numerous enzymes and pro-inflammatory products including TNF-a
(Riehemann K e al., 1999).
In a study done in healthy volunteers (Obertries B, Ruttkowski T e al., 1996)
lipopolysaccaride was used to stimulate the secretion of pro-inflammatory
cytokines. When nettle leaf extract was given simultaneously, TNK-a
concentration was significantly reduced in a dose-dependent manner.
Already known as a hair growth promoter in Germany, this plant extract
deserves to be known also in this country as an antiaging and vitalizing
nutrient. The
most advanced extracts of stinging nettle are available in both the Natural
Prostate and Super Miraforte formulas in a sufficient dose to reduce levels
of this dangerous pro-inflammatory cytokine. Br J Dermatol 2000 Nov;143(5):1036-1039 GINKGO
AND TNF-a
In addition to its ability to protect against the age
related breakdown of microcapillary perfusion (microcirculation to the hair
follicles), Ginkgo Biloba Extract has also been shown to inhibit TNF-a,
making it a reasonable adjunctive agent in the prevention and treatment
of both androgenetic and age related hair loss.
High-dose proinflammatory cytokines induce apoptosis of hair bulb keratinocytes in vivo.
Ruckert R, Lindner G, Bulfone-Paus S, Paus R , Germany.
BACKGROUND: Hair loss following skin inflammation may in part be mediated by keratinocyte (KC) apoptosis. While the effects of different
cytokines or other apoptosis stimulating agents such as interferon (IFN)-gamma or tumour necrosis factor (TNF)-alpha on KC apoptosis in
vitro have been addressed in several studies, little is known about the effects of proinflammatory cytokines on KC apoptosis in vivo.
Objectives To study the effects of intradermally injected
TNF-alpha,
interleukin (IL)-1beta and IFN-gamma on KC apoptosis in the back skin
of C57BL/6 mice. METHODS: Apoptosis in epidermal and hair bulb KCs was
analysed by immunohistology using TUNEL staining. RESULTS: Injection
of TNF-alpha induced a significantly higher number of apoptotic cells
within the epidermis than vehicle; all three proinflammatory cytokines
together further increased their number. Intrafollicular hair bulb KCs
were much more susceptible to apoptosis induction by TNF-alpha or
IL-1beta; their injection significantly upregulated apoptosis after 6
h, which was further increased after 24 h. The combination of all
cytokines together accelerated intrafollicular apoptosis after 6 h by
doubling the number of apoptotic cells per hair bulb, compared with
the effects of TNF-alpha or IL-1beta alone. CONCLUSIONS: These data
suggest that programmed cell death of proliferating KCs in vivo can be
induced by proinflammatory cytokines.
Effects of Ginkgo biloba extract (EGb 761) and quercetin on
lipopolysaccharide-induced signaling pathways involved in the release of
tumor necrosis factor-alpha.
Wadsworth TL, McDonald TL, Koop DR.
Department of Physiology and Pharmacology, Oregon Health Sciences
University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098, USA.
Administration of bacterial lipopolysaccharide (LPS) to laboratory animals
and cultured macrophages induces tumor necrosis factor-alpha (TNF-alpha),
a pro-inflammatory cytokine. Pretreatment with Ginkgo biloba extract (EGb
761) inhibited the in vivo production of TNF-alpha (measured by ELISA)
after challenge with LPS. To begin to understand the mechanism of this
inhibition, we evaluated the in vitro effects of EGb 761 and its flavonoid
component, quercetin, on LPS-treated RAW 264.7 macrophages. Pretreatment
with EGb 761 or quercetin concentration-dependently inhibited TNF-alpha
release, as measured by the L929 fibroblast assay. Northern blotting demonstrated that quercetin inhibited LPS-induced TNF-alpha mRNA, but did
not alter its half-life. Activation of mitogen-activated protein kinases (MAPKs)
and the redox-sensitive transcription factors, nuclear factor-kappaB (NF-kappaB)
and activator protein 1 (AP-1), are key events in the signal transduction
pathways mediating TNF-alpha induction. Phosphorylation of extracellular
signal-related kinases 1 and 2 (ERK 1/2), p38 MAPK, and Jun N-terminal
kinase/stress-activated protein kinase (JNK/SAPK), members of the MAPK
family, was analyzed by western blotting. Our results suggest that
quercetin is unique in its ability to inhibit TNF-alpha transcription by
inhibiting the phosphorylation and activation of JNK/SAPK and, therefore,
suppressing AP-1-DNA binding [assessed by electrophoretic mobility shift
analysis (EMSA)]. Results from western analysis, EMSA, and transient
transfections suggest that EGb 761 diminishes LPS-induced NF-kappaB but
has no effect on LPS-induced TNF-alpha transcription. Both EGb 761 and
quercetin inhibited ERK1/2 phosphorylation and p38 MAPK activity, which
are important in the post-transcriptional regulation of TNF-alpha mRNA.