Investigation of grape sap on wingless/integrated and β-catenin genes expression with histological factors on the hair follicle in rat

Mohammad Kazemi , Mohammad-Mohsen Taghavi, Ahmad Shabanizadeh, Zahra Taghipour, Ayat Kaeidi, Mahdi Shariati-Kohbanani


Background and purpose: Natural products are used to improve the damage caused by harmful reagents in various pathological situations. This study investigated the effect of grape sap as a natural product with antioxidant properties on follicle cell proliferation in bleomycin (as a chemotherapy agent with toxic effects on hair growth) treated rats skin.

Experimental approach: The bleomycin treated rats were administrated grape sap. Wingless/integrated (wnt) and β-catenin gene expression as follicle proliferative markers were evaluated using real-time polymerase chain reaction. Furthermore, histological factors and total antioxidant capacity were evaluated.

Findings / Results: The data showed that, grape sap increased the number of anagenic hair follicle in grape sap (100 mg/kg) group (P < 0.001), sebaceous glands (P < 0.001), blood vessel density (P < 0.001), and hair growth length (P < 0.001). Also, wnt and β-catenin gene expression was elevated. The data showed that wnt and β-catenin gene expression were elevated in grape sap treated animals versus bleomycin group (P < 0.01 and 0.001, respectively).

Conclusion and implications: Our finding showed that grape sap can be effective in increasing hair growth a gains bleomycin toxic effects on skin hair growth.


Antioxidant capacity; β-catenin; Grape sap, Hair follicle; wnt; Rat.

Full Text:



Mescher AL. Junqueira’s basic histology: text and atlas. 14th ed. New York; Mcgraw-hill Medical; 2013. pp. 193-208.

Hendriks FM, Brokken D, Oomens CW, Bader DL, Baaijens FP. The relative contributions of different skin layers to the mechanical behavior of human skin in vivo using suction experiments. Med Eng Phys. 2006;28(3):259-266.

DOI: 10.1016/j.medengphy.2005.07.001.

Shapiro J, Wiseman M, Lui H. Practical management of hair loss. Can Fam Physician. 2000;46(7):1469-1477.

Shah AA, Sinha AA. Oxidative stress and autoimmune skin disease. Eur J Dermatol. 2013;23(1):5-13.

DOI: 10.1684/ejd.2012.1884.

Ghobadi S, Dastan D, Soleimani M, Nili-Ahmadabadi A. Hepatoprotective potential and antioxidant activity of Allium tripedale in acetaminophen-induced oxidative damage. Res Pharm Sci. 2019;14(6):488-495.

DOI: 10.4103/1735-5362.272535.

Arck PC, Overall R, Spatz K, Liezman C, Handjiski B, Klapp BF, et al. Towards a ''free radical theory of graying'': melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. FASEB J. 2006;20(9):1567-1569.

DOI: 10.1096/fj.05-4039fje.

Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001;105(4):533-545.

DOI: 10.1016/s0092-8674(01)00336-1.

Sennett R, Rendl M. Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling. Seminars in cell & developmental biology. 2012;23(8):917-927.

DOI: 10.1016/j.semcdb.2012.08.011.

Enshell-Seijffers D, Lindon C, Kashiwagi M, Morgan BA. β-Catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. Dev Cell. 2010;18(4):633-642.

DOI: 10.1016/j.devcel.2010.01.016.

Jain PK, Das D, Singhai AK. Alternative herbal drugs used for treating hair disease. Asian J Pharm Clin Res. 2016;9(1):75-77.

Mecklenburg L, Tobin DJ, Müller-Röver S, Handjiski B, Wendt G, Peters EM, et al. Active hair growth (anagen) is associated with angiogenesis. J Investig Dermatol. 2000;114(5):909-916.

DOI: 10.1046/j.1523-1747.2000.00954.x.

Gizlenti S, Ekmekci TR. The changes in the hair cycle during gestation and the post-partum period. J Eur Acad Dermatol Venereol. 2014;28(7):878-881.

DOI: 10.1111/jdv.12188.

Hemmati AA, Foroozan M, Houshmand G, Moosavi ZB, Bahadoram M, Maram NS. The topical effect of grape seed extract 2% cream on surgery wound healing. Glob J Health Sci. 2014;7(3):52-58.

DOI: 10.5539/gjhs.v7n3p52.

Rishikaysh P, Dev K, Diaz D, Qureshi WMS, Filip S, Mokry J. Signaling involved in hair follicle morphogenesis and development. Int J Mol Sci. 2014;15(1):1647-1670.

DOI: 10.3390/ijms15011647.

Miller JR. The wnts. Genome Biol. 2001;3(1):reviews3001-1.

DOI: 10.1186/gb-2001-3-1-reviews3001.

Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149(6):1192-1205.

DOI: 10.1016/j.cell.2012.05.012.

MacDonald BT, Tamai K, He X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9-26.

DOI: 10.1016/j.devcel.2009.06.016.

Konczak I, Roulle P. Nutritional properties of commercially grown native Australian fruits: lipophilic antioxidants and minerals. Food Res Int. 2011;44(7):2339-2344.

DOI: 10.1016/j.foodres.2011.02.023.

Hofseth LJ, Wargovich MJ. Inflammation, cancer, and targets of ginseng. J Nutr. 2007;137(1 Suppl):183S-185S.

DOI: 10.1093/jn/137.1.183S.

Schieber A, Stintzing FC, Carle R. By-products of plant food processing as a source of functional compounds-recent developments. Trends Food Sci Technol. 2001;12(11):401-413. DOI: 10.1016/S0924-2244(02)00012-2.

Cheung DY, Kim JI, Park SH, Kim JK. Proanthocyanidin from grape seed extracts protects indomethacin-induced small intestinal mucosal injury. Gastroenterol Res Pract. 2014;2014:618068,1-8.

DOI: 10.1155/2014/618068.

Xia EQ, Deng GF, Guo YJ, Li HB. Biological activities of polyphenols from grapes. Int J Mol Sci. 2010;11(2):622-646.

DOI: 10.3390/ijms11020622.

Nicolescu MP, Nicolescu R. Ocular sevatherapy with the help of crying sap from grape vine. AMT. 2012;2(1):165-168.

Batchelor D. Hair and cancer chemotherapy: consequences and nursing care-a literature study. Eur J Cancer Care (Engl). 2001;10(3):147-163.

DOI: 10.1046/j.1365-2354.2001.00272.x.

Larki A, Hemmati AA, Arzi A, Borujerdnia MG, Esmaeilzadeh S, Karami MZ. Regulatory effect of caffeic acid phenethyl ester on type I collagen and interferon-gamma in bleomycin-induced pulmonary fibrosis in rat. Res Pharm Sci. 2013;8(4):243-252.

Trüeb RM. Systematic approach to hair loss in women. J Dtsch Dermatol Ges. 2010;8(4):284-297.

DOI: 10.1111/j.1610-0387.2010.07261.x.

Trost LB, Bergfeld WF, Calogeras E. The diagnosis and treatment of iron deficiency and its potential relationship to hair loss. J Am Acad Dermatol. 2006;54(5):824-844.

DOI: 10.1016/j.jaad.2005.11.1104.

Andl T, Reddy ST, Gaddapara T, Millar SE. WNT signals are required for the initiation of hair follicle development. Dev Cell. 2002;2(5):643-653.

DOI: 10.1016/s1534-5807(02)00167-3.

Baiomy AA. Protective role of grape seeds extract against cadmium toxicity in the lung of male wistar rats. J Cytol Histol. 2016;S5:1-8.

DOI: 10.4172/2157-7099.1000S5:004.

Zülli F, Belser E, Neuenschwander M, Muggli R. Antioxidants from grape seeds protect hair against reactive oxygen species. PCare. 2001;65-67.

Hajhashemi V, Vaseghi G, Pourfarzam M, Abdollahi A. Are antioxidants helpful for disease prevention? Res Pharm Sci. 2010;5(1):1-8.

Singha I, Das SK. Grapevine fruit extract protects against radiation-induced oxidative stress and apoptosis in human lymphocyte. Indian J Exp Biol. 2015;53(11):753-761.

Asha Devi S, Sagar Chandrasekar BK, Manjula KR, Ishii N. Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats. Exp Gerontol. 2011;46(11):958-964.

DOI: 10.1016/j.exger.2011.08.006.

Begum S, Gu LJ, Lee MR, Li Z, Li JJ, Hossain MJ, et al. In vivo hair growth-stimulating effect of medicinal plant extract on BALB/c nude mice. Pharm Biol. 2015;53(8):1098-1103.

DOI: 10.3109/13880209.2014.959614.

Soref CM, Fahl WE. A new strategy to prevent chemotherapy and radiotherapy-induced alopecia using topically applied vasoconstrictor. Int J Cancer. 2015;136(1):195-203.

DOI: 10.1002/ijc.28961.

Atit R, Sgaier SK, Mohamed OA, Taketo MM, Dufort D, Joyner AL, et al. β-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse. Dev Biol. 2006;296(1):164-176.

DOI: 10.1016/j.ydbio.2006.04.449.


  • There are currently no refbacks.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.