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Effectiveness of the combinational treatment of Laminaria japonica and Cistanche tubulosa extracts in hair growth


Since scalp hair loss has increased recently even in young people, seriously affecting individual’s quality of life, the hair growth-stimulating effects of Laminaria japonica extract (LJE) and Cistanche tubulosa extract (CTE) were investigated. After confirming anagen phase of follicles under shaving, male C57BL/6 mice were dermally applied with 3% Minoxidil or orally administered with the combinations of LJE and CTE for 21 days. Minoxidil promoted the hair regrowth and increased γ-glutamyl transpeptidase (γ-GTP) and alkaline phosphatase (ALP) activities. In addition, Minoxidil up-regulated epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) levels. Co-administration of LJE and CTE at 54 mg/kg LJE plus 162 mg/kg CTE exerted synergistic promoting effects on the hair regrowth, comparable to 3% Minoxidil. LJE preferentially enhanced ALP activity, while CTE increased both γ-GTP and ALP activities as well as EGF and VEGF expressions. In vivo air pouch inflammation model, carrageenan-induced vascular exudation and increased nitric oxide and prostaglandin E2 concentrations in the exudates were synergistically suppressed by co-administration of LJE and CTE. In addition, inflammatory cell infiltration was substantially inhibited by the combinational treatment. The results suggest that combinational oral treatment with LJE and CTE in appropriate doses and ratios prevent hair loss and improve alopecia, which might be in part mediated by their anti-inflammatory activities.


  1. 1.

    Kim JS, Kang BS, Park HJ, Kim DY, Hwang SY, Nam SY, Yun YW, Lee BJ. Promoting effect of herbal extracts mixtures on hair regrowth in C3H/HeJ mice. J Biomed Res 2009; 10(3): 99–108.

  2. 2.

    Paus R, Cotsarelis G. The biology of hair follicles. N Engl J Med 1999; 341(7): 491–497.

  3. 3.

    Cotsarelis G. The hair follicle: dying for attention. Am J Pathol 1997; 151(6): 1505–1509.

  4. 4.

    Cotsarelis G, Sun TT, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 1990; 61(7): 1329–1337.

  5. 5.

    Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y. Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 2001; 104(2): 233–245.

  6. 6.

    Burton JL, Marshall A. Hypertrichosis due to minoxidil. Br J Dermatol 1979; 101(5): 593–595.

  7. 7.

    Meisheri KD, Cipkus LA, Taylor CJ. Mechanism of action of minoxidil sulfate-induced vasodilation: a role for increased K+ permeability. J Pharmacol Exp Ther 1988; 245(3): 751–760.

  8. 8.

    Buhl AE, Waldon DJ, Baker CA, Johnson GA. Minoxidil sulfate is the active metabolite that stimulates hair follicles. J Invest Dermatol 1990; 95(5): 553–557.

  9. 9.

    Kaufman KD, Dawber RP. Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia. Expert Opin Investig Drugs 1999; 8(4): 403–415.

  10. 10.

    Feldman SC, Reynaldi S, Stortz CA, Cerezo AS, Damont EB. Antiviral properties of fucoidan fractions from Leathesia difformis. Phytomedicine 1999; 6(5): 335–340.

  11. 11.

    Wang J, Zhang Q, Zhang Z, Song H, Li P. Potential antioxidant and anticoagulant capacity of low molecular weight fucoidan fractions extracted from Laminaria japonica. Int J Biol Macromol 2010; 46(1): 6–12.

  12. 12.

    Bojakowski K, Abramczyk P, Bojakowska M, Zwoliñska A, Przybylski J, Gaciong Z. Fucoidan improves the renal blood flow in the early stage of renal ischemia/reperfusion injury in the rat. J Physiol Pharmacol 2001; 52(1): 137–143.

  13. 13.

    Li N, Zhang Q, Song J. Toxicological evaluation of fucoidan extracted from Laminaria japonica in Wistar rats. Food Chem Toxicol 2005; 43(3): 421–426.

  14. 14.

    Shimoda H, Tanaka J, Takahara Y, Takemoto K, Shan SJ, Su MH. The hypocholesterolemic effects of Cistanche tubulosa extract, a Chinese traditional crude medicine, in mice. Am J Chin Med 2009; 37(6): 1125–1138.

  15. 15.

    Yamada P, Iijima R, Han J, Shigemori H, Yokota S, Isoda H. Inhibitory effect of acteoside isolated from Cistanche tubulosa on chemical mediator release and inflammatory cytokine production by RBL-2H3 and KU812 cells. Planta Med 2010; 76(14): 1512–1518.

  16. 16.

    Kyung J, Kim D, Park D, Yang YH, Choi EK, Lee SP, Kim TS, Lee YB, Kim YB. Synergistic anti-inflammatory effects of Laminaria japonica fucoidan and Cistanche tubulosa extract. Lab Anim Res 2012; 28(2): 91–97.

  17. 17.

    Chee E, Fong KS, Al Jajeh I, Nassiri N, Rootman J. The association of lacrimal gland inflammation with alopecia areata. Orbit 2015; 34(1): 45–50.

  18. 18.

    Brzezinska-Wcislo L, Bergler-Czop B, Wcislo-Dziadecka D, Lis-Swiety A. New aspects of the treatment of alopecia areata. Postepy Dermatol Alergol 2014; 31(4): 262–265.

  19. 19.

    Hattori M, Ogawa H. Biochemical analysis of hair growth from the aspects of aging and enzyme activities. J Dermatol 1983; 10(1): 45–54.

  20. 20.

    Lee SH, Lee HJ, Baek IJ, Yon JM, Nam SY, Lee BJ, Yun YW, Kim YB, Hwang SY, Hong JT. Effect of DREAMMO® scalp lotion on hair growth promotion in an alopecia model of C57BL/6 mice. Lab Anim Res 2006; 22(1): 91–96.

  21. 21.

    Handjiski BK, Eichmüller S, Hofmann U, Czarnetzki BM, Paus R. Alkaline phosphatase activity and localization during the murine hair cycle. Br J Dermatol 1994; 131(3): 303–310.

  22. 22.

    Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L. VEGFreceptor signal transduction. Trends Biochem Sci 2003; 28(9): 488–494.

  23. 23.

    Shin S, Jeon JH, Park D, Jang JY, Joo SS, Hwang BY, Choe SY, Kim YB. Anti-inflammatory effects of an ethanol extract of Angelica gigas in a Carrageenan-air pouch inflammation model. Exp Anim 2009; 58(4): 431–436.

  24. 24.

    Kim D, Park D, Kyung J, Yang YH, Choi EK, Lee YB, Kim HK, Hwang BY, Kim YB. Anti-inflammatory effects of Houttuynia cordata supercritical extract in carrageenan-air pouch inflammation model. Lab Anim Res 2012; 28(2): 137–140.

  25. 25.

    Rebora A. Pathogenesis of androgenetic alopecia. J Am Acad Dermatol 2004; 50(5): 777–779.

  26. 26.

    Shirai A, Ikeda J, Kawashima S, Tamaoki T, Kamiya T. KF19418, a new compound for hair growth promotion in vitro and in vivo mouse models. J Dermatol Sci 2001; 25(3): 213–218.

  27. 27.

    Kawabe TT, Kubicek MF, Johnson GA, Buhl AE. Use of gammaglutamyl transpeptidase activity as a marker of hair cycle and anagen induction in mouse hair follicles. J Invest Dermatol 1994; 103(1): 122–126.

  28. 28.

    Hamada K, Suzuki K. Evaluation of biochemical indices as a hair cycle marker in C3H mice. Exp Anim 1996; 45(3): 251–256.

  29. 29.

    Park SJ, Lee KW, Lim DS, Lee S. The sulfated polysaccharide fucoidan stimulates osteogenic differentiation of human adiposederived stem cells. Stem Cells Dev 2012; 21(12): 2204–2211.

  30. 30.

    Danilenko DM, Ring BD, Pierce GF. Growth factors and cytokines in hair follicle development and cycling: recent insights from animal models and the potentials for clinical therapy. Mol Med Today 1996; 2(11): 460–467.

  31. 31.

    Ozeki M, Tabata Y. In vivo promoted growth of mice hair follicles by the controlled release of growth factors. Biomaterials 2003; 24(13): 2387–2394.

  32. 32.

    Fujie T, Katoh S, Oura H, Urano Y, Arase S. The chemotactic effect of a dermal papilla cell-derived factor on outer root sheath cells. J Dermatol Sci 2001; 25(3): 206–212.

  33. 33.

    Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev 2001; 81(1): 449–494.

  34. 34.

    Chapman RE, Hardy MH. Effects of intradermally injected and topically applied mouse epidermal growth factor on wool growth, skin and wool follicles of merino sheep. Aust J Biol Sci 1988; 41(2): 261–268.

  35. 35.

    Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995; 146(5): 1029–1039.

  36. 36.

    Ellis RA, Moretti G. Vascular patterns associated with categen hair follicles in the human scalp. Ann N Y Acad Sci 1959; 83: 448–457.

  37. 37.

    Stenn KS, Fernandez LA, Tirrell SJ. The angiogenic properties of the rat vibrissa hair follicle associate with the bulb. J Invest Dermatol 1988; 90(3): 409–411.

  38. 38.

    Yano K, Brown LF, Detmar M. Control of hair growth and follicle size by VEGF-mediated angiogenesis. J Clin Invest 2001; 107(4): 409–417.

  39. 39.

    Lachgar S, Charveron M, Ceruti I. Distribution of VEGF mRNA indifferent hair follicle stages by fluorescence in situ hybridization combined with confocal laser microscopy. In: Hair Research for the Next Millennium (Van Neste DJJ, ed), Elsevier, Amsterdam, 1996; pp 407–412.

  40. 40.

    Freyschmidt-Paul P, Sundberg JP, Happle R, McElwee KJ, Metz S, Boggess D, Hoffmann R. Successful treatment of alopecia areata-like hair loss with the contact sensitizer squaric acid dibutylester (SADBE) in C3H/HeJ mice. J Invest Dermatol 1999; 113(1): 61–68.

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Correspondence to Yun-Bae Kim.

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Shin, K., Kim, T., Kyung, J. et al. Effectiveness of the combinational treatment of Laminaria japonica and Cistanche tubulosa extracts in hair growth. Lab Anim Res 31, 24–32 (2015).

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  • Hair growth
  • inflammation
  • Laminaria japonica
  • Cistanche tubulosa
  • combinational treatment