Modulating testosterone pathway: a new strategy to tackle male skin aging?

Figures & data

Figure 1 Structure of honokiol, a hydroxybiphenyl compound.

Table 1 Final selection of putative molecules targeting testosterone pathways

Molecules	Structures	CAS	Targets	Sources
Honokiol		35354-74-6	Aromatase SHBG 5α-reductase	Magnolia spp. (L)
Phloretin		60-82-2	Aromatase SHBG	Helichrysum splendidum ([Thunb.] Less.)
(S)-3,5-Diiodothyronine		1041-01-6	Aromatase	Undaria pinnatifida (Harvey) Suringar

Abbreviations: CAS, Chemical Abstract Service index number; SHBG, sex hormone-binding globulin.

Figure 2 Honokiol (displayed in balls and sticks style) docked into the aromatase active site.

Notes: The backbone of the enzyme is represented as ribbons with red colors for helices, blue arrows for beta-sheets. Rose and yellow segments represent turns and loops, respectively. The heme with the ferric central atom (red sphere) is displays as capped sticks. The active site is modeled with a transparent surface; hydrophobic areas appear in brown, while hydrophilic and intermediate zones show blue and green colors, respectively. Carbon atoms are colored in white, nitrogen in blue, oxygen in red, and hydrogen in cyan.

Table 2 Inhibition of aromatase in vitro by honokiol and letrozole

Compound	Concentration	% inhibition aromatase
Honokiol	1 μM	0
	10 μM	13
	100 μM	88
Letrozole	10 nM	61

Table 3 Inhibition of 5α-reductase in vitro by honokiol and finasteride

Compound	Concentration	% inhibition 5α-reductase type 1	% inhibition 5α-reductase type 2
Honokiol	1 μM	1	NI
	10 μM	11	NI
	100 μM	64	NI
Finasteride	100 nM	11	55
	800 nM	48	89

Abbreviation: NI, no inhibition.

Figure 3A Antiwrinkle effect of a cream containing 1% of honokiol.

Note: Observations taken for two typical volunteers (number 9 to the left, and number 17 to the right) at start (day 0), halfway (day 28), and study end (day 56).

Figure 3B Antiwrinkle effect of a preparation containing 1% of honokiol, on the crow’s feet of two volunteers.

Note: Comparison between study start and end (day 0 and day 56).

Figure 4 Dermal redensifying effect of the 1% of honokiol preparation at day 0 and day 56.

Note: The redensifying effect of the dermis and the reformation of the extracellular matrix came close to statistical significance at P < 0.05 (P = 0.058).
Abbreviation: P, probability level.