© COPYRIGHT 2022 EDIZIONI MINERVA MEDICA or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher. This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove, © 2021 EDIZIONI MINERVA MEDICA Italian Journal of Dermatology and Venereology 2022 February;157(1):78-83 Online version at http://www.minervamedica.it DOI: 10.23736/S2784-8671.21.06915-7 ORIGINAL ARTICLE A new combination of molecules for the treatment of androgenetic alopecia and telogen effluvium: a double-blind randomized, monocentric, placebo-controlled study Alfredo ROSSI 1 *, Francesca MAGRI 1, Marco DI FRAIA 1, Gemma CARO 1, Maria C. FORTUNA 1, Marco PIACENTINI 2, Leonardo CELLENO 3 1Unitof Dermatology, Sapienza University, Rome, Italy; 2Eurofins Cosmetics & Personal Care, Rome, Italy; 3Sacred Heart Catholic University, Rome, Italy *Corresponding author: Alfredo Rossi, Unit of Dermatology, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy. E-mail: alfredo.rossi@uniroma1.it A B S TRA C T BACKGROUND: Androgenetic alopecia (AGA) is the most frequent form of alopecia. Telogen effluvium (TE) is a common form of diffuse hair loss mainly observed in women. The aim of our study was to evaluate the efficacy of a topical trichological treatment containing a new combination of molecules for the treatment of AGA and TE. METHODS: In-vitro tests were performed analyzing different combinations and concentrations of arginine, zinc and a third enzymatically neutral substance called AA on human follicles dermal papillae cells. These tests evaluated the capability of inhibiting the 5α-reductase (5-AR) enzyme and the 5-AR gene expression. We also performed an in-vivo study. Forty individuals affected by AGA and TE were divided into two groups. One group was administered a combination of zinc and arginine (lotion A), whilst the other placebo (lotion B). Therapy duration was 23 consecutive weeks. Follow-up examinations and pull tests occurred at baseline, after 6 weeks and at the end of the therapy. On 20 randomly selected patients we also performed noninvasive phototrichograms. RESULTS: In-vitro tests showed that the combination had a strong statistically significant inhibitory activity on 5-AR of dermal papillae cells. Number of hairs removed by pull-test significantly decreased at T0, T1 and T2 in patient treated with lotion A. We also observed an increase in the percentage of anagen hair and a decrease in telogen hairs. Concerning phototrichograms, all objective parameters evaluated showed better results in the lotion A group when compared with the placebo group. CONCLUSIONS: Based on our results, the combination of arginine and zinc tested in our study could represent a good therapeutic option for the treatment of AGA and TE and it might represent a valid alternative to finasteride. (Cite this article as: Rossi A, Magri F, Di Fraia M, Caro G, Fortuna MC, Piacentini M, et al. A new combination of molecules for the treatment of an- drogenetic alopecia and telogen effluvium: a double-blind randomized, monocentric, placebo-controlled study. Ital J Dermatol Venereol 2022;157:78- 83. DOI: 10.23736/S2784-8671.21.06915-7) Key words: Alopecia; Therapeutics; Arginine; Zinc. A ndrogenetic alopecia (AGA) is the most frequent form of non-scarring alopecia affecting up to 80% of male and 55% of female individuals during their life.1 er hand, the pathophysiology of female AGA is still not completely understood. Even though genetic and hormon- al factors are considered involved as in the more common It is characterized by a progressive miniaturization of hair male form, its link to androgen hormones is less direct follicles, especially involving the frontal and temporal than in females affected by complete androgen insensitiv- regions of the scalp and the vertex. In male AGA, hair ity syndrome.2, 3 thinning is caused by the activity of testosterone metabo- The main treatment options for male AGA are systemic lite dihydrotestosterone (DHT) on androgen-sensitive hair finasteride (1 mg per day) and topical (2% and 5%) mi- follicles of genetically predisposed subjects.1 On the oth- noxidil, which represent the only two products currently 78 Italian Journal of Dermatology and Venereology February 2022 © COPYRIGHT 2022 EDIZIONI MINERVA MEDICA or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher. This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove, NEW COMBINATION OF MOLECULES FOR AGA AND TE ROSSI approved by the American Food and Drug Administration Table I.—Different combination and concentration of molecules (FDA) and the European Medicines Agency (EMA). analyzed in the in-vitro test. Currently, minoxidil solution is the only FDA approved Molecules therapeutic option for female AGA. Testosterone 100 nM Arg 0.008% In addition, many other topical and systemic not-ap- Arg 0.04% proved therapeutic options are currently available for the ZnGl 0.008% management of AGA, including systemic dutasteride, top- ZnGl 0.04% ical finasteride, topical high and medium potent steroids, ZnGLArg 0.008% ZnGLArg oral minoxidil, topical cetirizine, platelet-rich plasma ArgAA 0.008% (PRP) therapy, mesotherapy, laser therapy. ArgAA 0.04% Finasteride inhibits the type-II 5α-reductase, which ZnGlAA 0.008% catalyzes the conversion of testosterone (T) to the more ZnGlAA 0.04% ZnGlArgAA 0.008% active form dihydrotestosterone (DHT).3 However, this ZnGlArgAA 0.04% molecule may be associated with several adverse events, Finasteride 10 nM mostly sexually related (0.7-5%),4, 5 such as decreased li- Arg: Arginine; ZnGl: zinc gluconate; AA: enzymatically neutral substance. bido, erectile disfunction, reduced spermatic volume; oth- er possible alterations are gynecomastia and depression. Telogen effluvium (TE) is a common form of diffuse molecules of inhibiting the 5-AR enzyme, and the 5-AR hair loss mainly observed in women. It occurs approxi- gene expression. mately three months after the exposition to several triggers, Eight *103 cells are seeded in 96-well plates and treated such as major surgery, infections, trauma, post-partum with the tested compounds plus 100 nM testosterone for hormonal alterations, dysthyroidism and iron deficiency.6 24 hours 20 ng/mL of BSA-DHT are coated ON at 4 °C in All these conditions alter the hair follicle cycle, inducing 100 uL of 50 mM sodium carbonate pH 9.0. After washing a large number of hairs in anagen phase to abruptly enter in PBS, the plate containing BSA-DHT is incubated with the telogen phase.7 As a consequence, TE is characterized 50 ul of cells supernatant plus 50 ul of primary antibody by shortening of the anagen phase and by the extension of anti-DHT conjugated with Biotin dissolved in PBS con- the telogen phase, with consequent reduction of the total taining 1% BSA. Two hours later, the plate is washed in hair volume.8 1X PBS 3 times, and incubated with 100 ul of streptavidin- The spontaneous remission of TE is frequent. Obvi- HRP 5 ug/mL in 1X PBS containing 1% BSA. The amount ously, therapeutic strategies are influenced by the eventual of DHT is measured by a colorimetric reaction using a 0.5 presence of underlying causes, which must be carefully mg/mL solution of OPD, 0.012%. The plate is incubated investigated. Topical steroids, topical minoxidil, oral iron, at room temperature up to color development and the ab- dietary and antioxidant supplementation are the most fre- sorbance at 490 nm is measured by a plate reader Victor3 quently prescribed therapies for TE. (PerkinElmer; Waltham, MA, USA). The aim of our double-blind randomized, monocentric, We also performed an in-vivo double-blind, randomized, placebo-controlled study was to evaluate the efficacy of a monocentric, placebo-controlled study on 26 individuals topical trichological treatment containing a new combina- affected by hair loss due to female and male AGA and 14 tion of molecules for the treatment of AGA and TE. affected by TE. All 26 patients with female and male AGA enrolled in our study presented a mild-to-moderate form of Materials and methods the disorder (II-IV stage of the Norwood-Hamilton Scale and I-II stage of the Ludwig Scale). All 14 patients with In this article we described the results of two studies: one TE had a mild-to-moderate form (I-III stage of the Savin in vitro and one in vivo. Scale). The individuals of our sample were randomly and In-vitro tests analyzing different combinations and equally divided into two groups. concentrations of arginine gluconate/ascorbate (ARG) One group was administered the active substance (lo- and zinc gluconate (ZNGL) and a third enzymatically tion A), whilst the other placebo (lotion B). Lotion A neutral substance called AA and finasteride 10 nM were contained a combination of ZNGL and ARG in associa- performed on human follicles dermal papillae cells (Table tion with AA (INCI: aqua, ascorbic acid, glycol, arginine, I). In-vitro tests evaluated the capability of the different gluconolactone, zinc gluconate, trans-anethole, ethylhex- Vol. 157 - No. 1 Italian Journal of Dermatology and Venereology 79 © COPYRIGHT 2022 EDIZIONI MINERVA MEDICA or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher. This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove, ROSSI NEW COMBINATION OF MOLECULES FOR AGA AND TE Table II.—Inclusion criteria of our sample. tions occurred at baseline (T0), after 6 weeks (T1) and at Inclusion criteria the end of the therapy (T2). At each visit, pull test was Both female and male gender; performed to evaluate the eventual decrease of telogen age 18 to 70 years; hairs with consequent increase of anagen hairs. In addi- Fitzpatrick skin type: I, II, III or IV; tion, systematic trichoscopic photographs were taken on persistent hair loss (telogen effluvium) for over a month, with no specific underlying diseases associated (anemia, dysthyroidism, three selected scalp regions with a video-dermoscope at hypoproteinemia, autoimmune or inflammatory disorders) or 50× magnification. On 20 randomly selected patients (10 Androgenetic Alopecia (AGA) (type II-IV of Hamilton-Norwood Scale from the lotion A group and 10 from the lotion B group), for male AGA; type I-II of Ludwig classification for female AGA); no other concomitant therapies. we also performed noninvasive phototrichograms with Trichoscan® HD (DermoScan GmbH; Regensburg, Ger- many), with the aim of monitoring the following param- ylglycerin, polysorbate 20, ellagic acid, phenoxyethanol, eters: vanillin butyl ether, menthol, octenidine HCl, sodium ben- • total number of hairs; zoate, parfum, sodium hyaluronate, magnesium stearate). • total hair density/cm2; Lotion B corresponded to a placebo solution containing • vellus hair density/cm2; mainly water and glycol. Inclusion criteria of the study are • terminal hair density/cm2. summarized in Table II. Investigators had to perform an objective assessment of Patients undergoing the topical treatment with lotion A products efficacy, based on pull test and trichoscopy. Fur- comprised 13 AGA and 7 TE individuals of both female thermore, a subjective assessment of the efficacy of prod- and male gender, whose age ranged between 29 and 72 ucts, as well as of their cosmetical qualities, was realized years old (median age: 51). with a satisfaction survey submitted to all 40 individuals Patients applying lotion B comprised 13 AGA and 7 TE at T1 and T2. female and male individuals, which were between 28 and Statistical analysis 69 years old (median age: 55). All 40 individuals were scrupulously informed on how Comparisons between treatments was performed using apply the examined products. 10 days before starting the Wilcoxon test and Student’s t-test. P value lower than 0.05 topical treatment with lotion A or B, patients were instruct- was considered statistically significant. ed to use a delicate shampoo for 2-3 times per week. Then, patients started the treatment, with an evening alternate- Results day topical application of the examined lotions (A or B) on the entire scalp (frontal/temporal/vertex region). Therapy In-vitro test studying the capability of inhibiting the 5-AR duration was 23 consecutive weeks. Follow-up examina- enzyme showed that the triple combination ZNGL-ARG- Figure 1.—5-alpha reductase enzymat- ic assay in dermal papilla. Testosterone 5-alpha reductase activity 100 nM was used as positive control. The values reported in the graphics are 120 the average of three different experi- ments, each of them performed in trip- 5-alpha reductase activity 100 licate. The bars marked with asterisks (% to control = 100) represent statistically significant values 80 (*P≤0.05; **P≤0.01; ***P≤0.0001). Arg: Arginine; ZnGl: zinc gluconate; 60 AA: enzymatically neutral substance. 40 20 0 Arg Arg ZnGl ZnGl ZnGLArg ZnGLArg ArgAA ArgAA ZnGIAA ZnGIAA ZnGIArgAA ZnGIArgAA Finasterid Untreated Control 0,008% 0,04% 0,008% 0,04% 0,008% 0,04% 0,008% 0,04% 0,008% 0,04% 0,008% 0,04% e 10 nM Testosteron 100nM 100,00 44,75 42,40 64,35 48,62 40,05 25,36 28,67 36,23 49,59 35,07 21,27 18,33 50,23 Untreated 20,36 80 Italian Journal of Dermatology and Venereology February 2022 © COPYRIGHT 2022 EDIZIONI MINERVA MEDICA or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher. This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove, NEW COMBINATION OF MOLECULES FOR AGA AND TE ROSSI AA had a strong statistically significant inhibitory activity in patients undergoing the treatment with lotion A after 6 on 5-AR of dermal papillae cells (Figure 1). Furthermore, (+15.59%) and 23 weeks (+29.91%), as opposed to pa- in-vitro 5-AR gene expression was evaluated. However, both tients applying lotion B (Table V). Concerning the density ZNGL and ARG showed a weak activity on reducing 5-AR of vellus hair, lotion B treatment did not induce significant gene expression. Thus, the examined substances have a changes, while lotion A treatment was associated with a mechanism of action similar to finasteride, causing the direct statistically significant progressive increase of this pa- inhibition of 5-AR with no influences on its gene expression. rameter after 6 (+7.37%) and 23 weeks (+25.19%) (Table Concerning the in-vivo study on our sample of 40 indi- VI). Moreover, the density of terminal hair presented a viduals, statistically significant decrease in removed hairs statistically significant increase after 6 (+12.03%) and 23 after pull test was evident after 6 and 23 weeks of therapy weeks (+48.20%) of lotion A treatment, while no signifi- with lotion A, compared to baseline. On the other hand, the cant variations were reported with lotion B (Table VII). In decrease was not significant in patients undergoing topical group A patients, anagen hairs removed after pull test were treatment with lotion B (Table III). significantly increased after 6 and 23 weeks (respectively Concerning the trichoscopic analysis, a remarkable im- provement of hair thickness and hair regrowth was evident after 6 and 23 weeks of treatment with lotion A, while no Table V.—Total hair density (number of total hairs/cm2) meas- ured by phototrichogram at T0, T1 (6 weeks) and T2 (23 weeks). evident changes in hair thickness and regrowth were ob- Lotions Time Average±SD Variation (%) served with lotion B, as also subjectively assessed by the Lotion A T0 185.97±21.36 investigators. T1 214.96±27.43 +15.59* Several parameters were measured with phototricho- T2 245.35±29.91 +29.91* grams. Firstly, a progressive statistically significant in- Lotion B T0 187.35±12.99 crease in total hair number was present after 6 (+15.83%) T1 188.85±14.91 +0.80 T2 187.75±14.57 +0.21 and 23 weeks (+52.52%) of therapy with lotion A, while Variation compared to T0 is expressed as percentage. no significant variations were observed after 6 and 23 *P value <0.05. SD: standard deviation. weeks of therapy with lotion B (Table IV). A statistically significant improvement of hair density was also observed Table VI.—Vellus hair density (number of vellus hairs/cm2) meas- Table III.—Number of total hairs removed after pull test at T0, T1 ured by phototrichogram at T0, T1 (6 weeks) and T2 (23 weeks). (6 weeks) and T2 (23 weeks). Lotions Time Average±SD Variation (%) Lotions Time Average±SD Variation (%) Lotion A T0 24.14±3.92 Lotion A T0 20.80±4.05 T1 25.92±4.15 +7.37* T1 16.45±3.17 -20.91* T2 30.22±6.57 +25.19* T2 14.35±3.12 -31.01* Lotion B T0 25.29±3.36 Lotion B T0 19.95±1.82 T1 25.65±3.26 +1.42 T1 19.70±2.49 -1.25 T2 25.67±3.76 +1.50 T2 19.25±2.77 -3.51 Variation compared to T0 is expressed as percentage. Variation compared to T0 is expressed as percentage. *P value <0.05. *P value <0.05. SD: standard deviation. SD: standard deviation. Table VII.—Terminal hair density (number of terminal hairs/ Table IV.—Number of total hairs measured by phototrichogram cm2) measured by phototrichogram at T0, T1 (6 weeks) and T2 at T0, T1 (6 weeks) and T2 (23 weeks). (23 weeks). Lotions Time Average±SD Variation (%) Lotions Time Average±SD Variation (%) Lotion A T0 106.15±13.62 Lotion A T0 119.47±12.41 T1 122.95±15.32 +15.83* T1 133.84±17.64 +12.03* T2 161.90±25.74 +52.52* T2 177.05±32.67 +48.20* Lotion B T0 104.70±12.51 Lotion B T0 120.21±13.47 T1 105.00±11.27 +0.29 T1 120.78±11.57 +0.47 T2 105.40±10.61 +0.67 T2 120.80±12.91 +0.49 Variation compared to T0 is expressed as percentage. Variation compared to T0 is expressed as percentage. *P value <0.05. *P value <0.05. SD: standard deviation. SD: standard deviation. Vol. 157 - No. 1 Italian Journal of Dermatology and Venereology 81 © COPYRIGHT 2022 EDIZIONI MINERVA MEDICA or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher. This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove, ROSSI NEW COMBINATION OF MOLECULES FOR AGA AND TE Table VIII.—Number of anagen hairs removed after pull test at Discussion T0, T1 (6 weeks) and T2 (23 weeks). Lotions Time Average±SD Variation (%) In this double-blind randomized, monocentric, placebo- Lotion A T0 56.35±4.94 controlled study we evaluated the efficacy of an alternative T1 59.32±6.21 +5.27* topical treatment for female and male AGA and TE. T2 68.88±7.83 +22.24* To date, therapeutic options for the management of hair Lotion B T0 57.66±5.60 loss conditions, such as AGA and TE, are partially limited T1 58.30±6.38 +1.11 and not definitive. T2 58.44±6.79 +1.35 Variation compared to T0 is expressed as percentage. Systemic finasteride is nowadays the most efficient *P value <0.05. product for the treatment of male AGA. It inhibits the SD: standard deviation. type-II 5α-reductase, which catalyzes the conversion of testosterone (T) to the more active form of dihydrotestos- terone (DHT), responsible of hair miniaturization.3 Table IX.—Number of telogen hairs removed after pull test at T0, However, finasteride may be associated with several ad- T1 (6 weeks) and T2 (23 weeks). verse events, such as decreased libido, erectile disfunction, Lotions Time Average±SD Variation (%) reduced spermatic volume, gynecomastia and depression. Lotion A T0 43.65±4.94 Even in the female population, systemic finasteride may T1 40.68±6.21 -6.80* T2 31.12±7.83 -28.71* cause sexual alterations, and its assumption is contraindi- Lotion B T0 42.34±5.60 cated during pregnancy because of the risk of feminization T1 41.70±6.38 -1.51 of the male fetus.3 T2 41.56±6.79 -1.84 In consideration of finasteride side effects, several sub- Variation compared to T0 is expressed as percentage. *P value <0.05. stances have been tested over the years with the aim of SD: standard deviation. finding alternative therapeutic options. In our study, the active substances tested were zinc glu- conate (ZNGL) and arginine gluconate/ascorbate (ARG), +5.27% and +22.24%) (Table VIII), while telogen hairs which resulted to be good alternative products inhibiting were statistically decreased after 6 (-6.80%) and 23 weeks the 5-AR enzyme. (-28.71%) (Table IX). No significant variations of anagen Zinc is an essential trace element, which must be sup- and telogen hair removed after pull test were registered in plied through diet. It is involved in several biological func- the placebo group. tions, such as DNA synthesis, hormone regulation, enzy- Objective assessment of products efficacy performed by matic reactions, gene expression and cell proliferation. investigators and subjective assessment made by patients In particular, zinc is involved as a structural element and were also evaluated. After 6 weeks of therapy with lotion regulatory factor and has a role in important functional ac- A, investigators observed a sufficient product efficacy in tivities within the hair follicle.9 40% of patients, a good efficacy in 40% of cases and a In fact, alopecia is a well-known sign of zinc deficien- great efficacy in 5% of individuals. Concerning lotion B, cy and zinc supplementation is associated with hair re- investigators indicated a poor efficacy in 80% of patients, growth.10 and a sufficient efficacy in 20% of individuals after 6 Arginine is a semi essential amino acid involved in nu- weeks. After 23 weeks of treatment with lotion A, investi- merous biological activities. In particular, arginine is the gators observed a sufficient product efficacy in 5% of pa- precursor for nitric oxide (NO) synthesis in animal cells. tients, a good efficacy in 60% of cases and a great efficacy In blood vessels, NO released by endothelial cells causes in 30% of individuals. Concerning lotion B, investigators smooth muscle relaxation and consequent vasodilation. indicated a poor efficacy in 60% of patients, a sufficient NO is an important molecule in trichology because of its efficacy in 15% and good efficacy in 25% of individuals role as vasodilator in the stimulation of hair growth. NO is after 23 weeks. also involved in opening potassium channels, the activity Patients assessment indicated a good efficacy of lotion mechanism of minoxidil.11, 12 A in 45% and 35% of cases after 6 and 23 weeks respec- To test the activity of ZNGL and ARG, in-vitro tests on tively. Concerning lotion B, a good efficacy was reported human follicles dermal papillae cells were performed. The only in 5% of cases after 6 weeks and in 25% of cases after aim of these tests was to evaluate the presence of a syner- 23 weeks. gic action between these two substances. 82 Italian Journal of Dermatology and Venereology February 2022 © COPYRIGHT 2022 EDIZIONI MINERVA MEDICA or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher. This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove, NEW COMBINATION OF MOLECULES FOR AGA AND TE ROSSI Firstly, an in-vitro test to study the capability of inhibit- Conclusions ing the 5-AR enzyme has been performed. ARG and ZNGL were tested: 1) individually; 2) together; and 3) together Based on our results, the combination of ARG and ZNGL combined with a third enzymatically neutral substance tested in our study could represent a good therapeutic op- called AA and turned out to be a strong “booster.” The test tion for the treatment of AGA and TE and it might repre- showed that the triple combination ZNGL-ARG-AA had sent a valid alternative to finasteride. the strongest statistically significant inhibitory activity on 5-AR of dermal papillae cells. Furthermore, 5-AR gene expression was evaluated. References However, both ZNGL and ARG showed a weak activity on 1. Piraccini BM, Alessandrini A. Androgenetic alopecia. G Ital Dermatol reducing 5-AR gene expression. Thus, the examined sub- Venereol 2014;149:15–24. stances have a mechanism of action similar to finasteride, 2. Cousen P, Messenger A. Female pattern hair loss in complete androgen insensitivity syndrome. Br J Dermatol 2010;162:1135–7. causing the direct inhibition of 5-AR with no influences on 3. Rossi A, Magri F, D’Arino A, et al. Efficacy of Topical Finasteride its gene expression. 0.5% vs 17α-Estradiol 0.05% in the Treatment of Postmenopausal Female In our in-vivo study on 40 individuals, after 23 weeks of Pattern Hair Loss: A Retrospective, Single-Blind Study of 119 Patients. Dermatol Pract Concept 2020;10:2020039. therapy with lotion A, great results were evident. The pull 4. Rossi A, Cantisani C, Scarnò M, Trucchia A, Fortuna MC, Calvieri S. Fin- test performed on patients under treatment with lotion A asteride, 1 mg daily administration on male androgenetic alopecia in different showed a statistically significant decrease in removed hair age groups: 10-year follow-up. Dermatol Ther (Heidelb) 2011;24:455–61. (-31.01%). Furthermore, lotion A was associated with hair 5. Sato A, Takeda A. Evaluation of efficacy and safety of finasteride 1 mg in 3177 Japanese men with androgenetic alopecia. J Dermatol 2012;39:27–32. regrowth and thickening, as observed trichoscopically by 6. Bennardo L, Del Duca E, Dastoli S, Schipani G, Scali E, Silvestri M, et the investigators. Moreover, lotion A was associated with al. Potential applications of topical oxygen therapy in dermatology. Der- a good cosmetic acceptability (for both patients and inves- matol Pract Concept 2018;8:272–6. tigators). 7. Hughes EC, Saleh D. Telogen effluvium. Treasure Island, FL: Stat- Pearls Publishing; 2020. Concerning phototrichograms, all objective parameters 8. Nistico S, Tamburi F, Bennardo L, Dastoli S, Schipani G, Caro G, et evaluated (total number of hairs; hair density/cm2; vellus al. Treatment of telogen effluvium using a dietary supplement containing hair density/cm2; terminal hair density/cm2; hair thickness) Boswellia serrata, Curcuma longa, and Vitis vinifera: results of an obser- vational study. Dermatol Ther (Heidelb) 2019;32:e12842. showed better results in the lotion A group when compared 9. Dhaher SA, Yacoub AA, Jacob AA. Estimation of Zinc and Iron Lev- with the placebo group. els in the Serum and Hair of Women with Androgenetic Alopecia: case- No side effects were reported in patients treated with control Study. Indian J Dermatol 2018;63:369–74. lotion A. 10. Almohanna HM, Ahmed AA, Tsatalis JP, Tosti A. The Role of Vitamins and Minerals in Hair Loss: A Review. Dermatol Ther (Heidelb) 2019;9:51–70. 11. Yazdani-Arazi SN, Ghanbarzadeh S, Adibkia K, Kouhsoltani M, Limitations of the study Hamishehkar H. Histological evaluation of follicular delivery of arginine via nanostructured lipid carriers: a novel potential approach for the treat- A study limitation is represented by the small sample size. ment of alopecia. Artif Cells Nanomed Biotechnol 2017;45:1379–87. 12. Vidal VP, Chaboissier MC, Lützkendorf S, Cotsarelis G, Mill P, Hui Further studies with larger sample are needed to confirm CC, et al. Sox9 is essential for outer root sheath differentiation and the our results. formation of the hair stem cell compartment. Curr Biol 2005;15:1340–51. Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Authors’ contributions.—Alfredo Rossi and Leonardo Celleno have given substantial contributions to manuscript conception and supervision, Francesca Magri, Marco Di Fraia, Gemma Caro and Maria Caterina Fortuna to in-vivo study and manuscript writing, Marco Piacentini to in-vitro experiments. All authors read and approved the final version of the manuscript. History.—Article first published online: April 21, 2021. - Manuscript accepted: January 18, 2021. - Manuscript revised: December 18, 2020. - Manuscript received: November 3, 2020. Vol. 157 - No. 1 Italian Journal of Dermatology and Venereology 83
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