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Adenosine


Adenosine is a ribonucleoside comprised of adenine bound to ribose, with vasodilatory, antiarrhythmic and analgesic activities. A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.

Phosphorylated forms of adenosine play roles in cellular energy transfer, signal transduction and the synthesis of RNA.

An endogenous molecule that regulates tissue function via binding to and activating one of the four G-protein receptors, A1, A2A, A2B and A3

IS IT SAFE? ARE THERE SIDE EFFECTS?

Topical administration at the right percentage has reported no side effects, unless  the patient is allergic allergic to it.  Patients with heart conditions as arrhythmia or pacemakers should consult a physician before use of any skincare products or supplements.

EFFECTS ON HAIR LOSS

Since the first discovery of the practical effect of adenosine on the cardiac function, adenosine has been investigated in many studies, which have revealed that it is able to regulate all body organ systems sufficiently (18-21). In this regard, Lino et al. (20) demonstrated that adenosine could stimulate hair growth via up-regulating fibroblast growth factor 7 (FGF-7) in DPCs. Furthermore, Oura et al. (22) confirmed the role of adenosine in stimulation of hair growth and thickening of hair shafts in hair growth cycle anagen phase and stated that adenosine is useful for treating female pattern hair loss as well as androgenetic male alopecia. Another interesting finding by Hwang et al. (21) in 2012 showed the growth of DPCs and lengthening of the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles. minoxidil and adenosine have the same effect on recovery of hair loss in AGA and there is no superiority regarding treatment of AGA by adenosine. However, according to the patient satisfaction rate, adenosine is superior as the first-choice treatment for AGA due to faster prevention of hair loss and favorable appearance of newly grown hairs

STRUCTURE & SYNTHESIS

Adenosine synthesis and metabolic pathways inside and outside of a cell. Within the cell ATP and adenosine are continually recycled depending on energy requirements via a series of dephosphorylation and phosphorylation steps mediated by enzymes such as cytosolic 5′-nucleotidase (cyto-5′NT), adenosine kinase (AK), and AMP kinase (AMPK). Under physiological conditions the rate limiting enzyme is AK. Adenosine can also be generated from the hydrolysis of S-adenosyl-homocysteine (SAH). In response to high metabolic activity ATP and adenosine is extruded to the outside of the cell via facilitated diffusion and secondary active transport. Under such conditions there is further degradation of ATP to adenosine where it can activate adenosine receptors. Excess adenosine is irreversibly deamidated to inosine by the enzyme adenosine deaminase (ADA). Modified with permission from Blackburn (2003).

Adenosine receptor signaling. Adenosine mediates its action via four G-protein coupled receptors, A1, A2A, A2B, and A3 that are coupled primarily to the activation and inhibition of cAMP. There is also evidence to suggest that accumulated cAMP is linked to the modulation of ion-channel activity.

MECHANISMS OF ACTION

Adenosine upregulates the expression of vascular endothelial growth factor and fibroblast growth factor-7 in cultured dermal papilla cells. It has been shown that, in Japanese men, adenosine improves androgenetic alopecia due to the thickening of thin hair due to hair follicle miniaturization.significantly increased the anagen hair growth rate and the thick hair rate. No side-effects were encountered during the trial. Adenosine is useful for treating female pattern hair loss in women as well as androgenetic alopecia in men. 85% of patients responded to 3 mL of a lotion containing 0.75% adenosine after 12 months of treatment by stimulating adenosine receptor A2b in dermal papilla cells.14 On the other hand, reported inhibitory factor transforming growth factor (TGF)-β. adenosine promotes hair growth by modulating the expression of genes encoding growth factors such as FGF-7 and VEGF, or TGF-β in dermal papilla cells. adenosine improves hair loss in Japanese women by stimulating hair growth and by increasing thicker hairs. Adenosine also upregulates the production of fibroblast growth factor 7 (FGF-7)


1. Comparison of the efficacy of topical minoxidil 5% and adenosine 0.75% solutions on male androgenetic alopecia and measuring patient satisfaction rate.  Faghihi G1, Iraji F, Rajaee Harandi M, Nilforoushzadeh MA, Askari G. Acta Dermatovenerol Croat. 2013;21(3):155-9.
2. Topical adenosine increases the proportion of thick hair in Caucasian men with androgenetic alopecia.  Iwabuchi T1, Ideta R1, Ehama R1, Yamanishi H1, Iino M1, Nakazawa Y1, Kobayashi T2, Ohyama M3,Kishimoto J1. J Dermatol. 2016 May;43(5):567-70. doi: 10.1111/1346-8138.13159. Epub 2015 Oct 28.
3. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Hasko G, Linden J, Cronstein B, Pacher P.  Nat Rev Drug Discov 2008;7:759-70.
4. A2A receptors in inflammation and injury: lessons learned from transgenic animals. Hasko G, Pacher P. J Leukoc Biol 2008;83:447-55.
5. Adenosine stimulates fibroblast growth factor-7 gene expression via adenosine A2b receptor signaling in dermal papilla cells. Lino M, Ehama R, Nakazawa Y, Iwabuchi T, Ogo M, Tajima M, et al.  J Invest Dermatol 2007;127:1318-25.
6. Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles. Hwang KA, Hwang YL, Lee MH, Kim NR, Roh SS, Lee Y, et al.  Int J Mol Med 2012;29(2):195- 201.
7. Adenosine increases anagen hair growth and thick hairs in Japanese women with female pattern hair loss: a pilot, double-blind, randomized, placebo-controlled trial. Oura H, Lino M, Nakazawa Y, Tajima M, Ideta R Nakaya Y, et al.  J Dermatol 2008;35:763-7
8. An emerging role for adenosine and its receptors in bone homeostasis. Jack Ham1,2 and Bronwen A. J. Evans.  Endocrinol., 18 September 2012