In Vivo Phytotherapy in BALB/c Athymic Nude Mice: Hair Growth Promotion using Ficus religiosa L. and Morus alba L.

Jump To References Section

Authors

  • Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Pune, Maharashtra – 412115 ,IN
  • Symbiosis Centre for Research and Innovation, Symbiosis International (Deemed University), Pune, Maharashtra – 412115 ,IN
  • APT Research Foundation, Pune, Maharashtra – 411041 ,IN
  • APT Research Foundation, Pune, Maharashtra – 411041 ,IN
  • APT Research Foundation, Pune, Maharashtra – 411041 ,IN

DOI:

https://doi.org/10.18311/jnr/2021/26255

Keywords:

Anagen Phase, Ficus religiosa L., Hair Follicles, Morus alba L., Nude Mouse

Abstract

Ficus religiosa L. (FR) and Morus alba L. (ML) belonging to the family Moraceae have been tested as novel herbal agents for hair growth promotion and Hair Follicles (HFs) regeneration in BALB/c athymic nude mouse model. Current study tested different mixtures of 5% aqueous fractions: Test 1 (ML2+ML3+ML4+FR4), Test 2 (FR1+FR2+FR4), or Test 3 (ML2+ML3+ML4+FR1+FR2+FR4) from leaves of both plants including standard of care 2% minoxidil. Control mice were untreated. Animals were treated for 33 days by topical application on the back skin and changes in hair growth patterns were evaluated. Histology was performed to assess the HFs morphology, and modulation of hair cycle phases. Gene expression analysis was performed to understand potential mechanisms of action. All treatment groups had significantly higher anagen phase HFs compared with untreated control group based on histology analysis. Also, expressions of CD34, CD200R and Oct4 genes were upregulated in all treatment groups compared with untreated control. Present study demonstrated that a combinatorial therapy using either fractions of FR or FR and ML promoted hair growth and HFs regeneration through induction of anagen phase in conjunction with stem cells associated genes upregulation in BALB/c athymic nude mouse model of hair loss.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Downloads

Published

2021-02-26

How to Cite

Joshi, P. S., Patil, Y. B., Nagarkar, B., Paul, T. S., & Apte, K. G. (2021). In Vivo Phytotherapy in BALB/c Athymic Nude Mice: Hair Growth Promotion using <i>Ficus religiosa</i> L. and <i>Morus alba</i> L. Journal of Natural Remedies, 21(1), 51–60. https://doi.org/10.18311/jnr/2021/26255

Issue

Section

Research Articles
Received 2020-10-14
Accepted 2020-12-21
Published 2021-02-26

 

References

Porter RM. Mouse models for human hair loss disorders. J Anat. 2003; 202(1):125–31. https://doi. org/10.1046/j.1469-7580.2003.00140.x. PMid:12587927 PM Cid:PMC1571051

Schneider MR, Schmidt-Ullrich R, Paus R. The hair follicle as a dynamic miniorgan. Curr Biol. 2009; 19(3):R132–42. https://doi.org/10.1016/j.cub.20 08.12.005. PMid:19211055

Sundberg JP, Cordy WR, King LE, Jr. Alopecia areata in aging C3H/HeJ mice. J Invest Dermatol. 1994; 102(6):847–56. https://doi.org/10.1111/1523-1747.ep12382 416. PMid:8006447

McElwee KJ, Freyschmidt-Paul P, Sundberg JP, Hoffmann R. The pathogenesis of Alopecia areata in rodent models. J Investig Dermatol Symp Proc. 2003; 8(1):6–11. https:// doi.org/10.1046/j.1523-1747.2003.12164.x. PMid:12894987

Sundberg JP, McElwee K, Brehm MA, Su L, King LE, Jr. Animal models for Alopecia Areata: What and where? J Investig Dermatol Symp Proc. 2015; 17(2):23–6. https://doi.org/10.1038/jidsymp.2015.35. PMid:26551940 P MCid:PMC4722955

Muller-Rover S, Handjiski B, van der Veen C, et al. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol. 2001; 117(1):3–15. https://doi.org/10.1046/j.00 22-202x.2001.01377.x. PMid:11442744

Sun J, Silva KA, McElwee KJ, King LE, Jr., Sundberg JP. The C3H/HeJ mouse and DEBR rat models for alopecia areata: Review of preclinical drug screening approaches and results. Exp Dermatol. 2008; 17(10):793–805. https:// doi.org/10.1111/j.1600-0625.2008.00773.x. PMid:18798913 PMCid:PMC2778023

Flanagan SP. 'Nude', a new hairless gene with pleiotropic effects in the mouse. Genet Res. 1966; 8(3):295–309. https:// doi.org/10.1017/S0016672300010168. PMid:5980117

Wortis HH, Nehlsen S, Owen JJ. Abnormal development of the thymus in "nude" mice. J Exp Med. 1971; 134(3 Pt 1):681– 92. https://doi.org/10.1084/jem.134.3.681. PMid:15776569. PMCid:PMC2139084

Pantelouris EM. Athymic development in the mouse. Diffe rentiation. 1973; 1(6):437–50. https://doi.org/10.1111/j.143 2-0436.1973.tb00143.x. PMid:4547146

Kopf-Maier P, Mboneko VF, Merker HJ. Nude mice are not hairless. A morphological study. Acta Anat (Basel). 1990; 139(2):178–90. https://doi.org/10.1159/000146996. PMid:2288204

Mecklenburg L, Tychsen B, Paus R. Learning from nudity: lessons from the nude phenotype. Exp Dermatol.2005; 14(11):797–810. https://doi.org/10.1111/j.1600-0625.2005. 00362.x. PMid:16232301

Nakamura M, Sundberg JP, Paus R. Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: annotated tables. Exp Dermatol. 2001; 10(6):369–90. https://doi.org/10.1034/j.1600-0625.20 01.100601.x. PMid:11737257

Danilenko DM, Ring BD, Yanagihara D, et al. Keratinocyte growth factor is an important endogenous mediator of hair follicle growth, development, and differentiation. Normalization of the nu/nu follicular differentiation defect and amelioration of chemotherapy-induced alopecia. Am J Pathol. 1995; 147(1):145–54.

Sredni B, Gal R, Cohen IJ, et al. Hair growth induction by the Tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression. FASEB J. 2004; 18(2):400–2. https://doi. org/10.1096/fj.03-0552fje. PMid:14656992

Gafter-Gvili A, Sredni B, Gal R, Gafter U, Kalechman Y. Cyclosporin A-induced hair growth in mice is associated with inhibition of calcineurin-dependent activation of NFAT in follicular keratinocytes. Am J Physiol Cell Physiol. 2003; 284(6):C1593–1603. https://doi.org/10.1152/ ajpcell.00537.2002. PMid:12734112

Begum S, Lee MR, Gu LJ, Hossain J, Sung CK. Exogenous stimulation with Eclipta alba promotes hair matrix keratinocyte proliferation and downregulates TGF-beta1 expression in nude mice. Int J Mol Med. 2015; 35(2):496– 502. https://doi.org/10.3892/ijmm.2014.2022. PMid:25484 129

Bohr S, Patel SJ, Vasko R, et al. Highly upregulated Lhx2 in the Foxn1-/- nude mouse phenotype reflects a dysregulated and expanded epidermal stem cell niche. PLoS One. 2013; 8(5). https://doi.org/10.1371/journal.pone.006 4223. PMid:23696871 PMCid:PMC3656088

Purba TS, Haslam IS, Poblet E, et al. Human epithelial hair follicle stem cells and their progeny: Current state of knowledge, the widening gap in translational research and future challenges. Bioessays. May 2014; 36(5):513–25. https://doi.org/10.1002/bies.201300166. PMid:24665045

Inoue K, Aoi N, Sato T, et al. Differential expression of stem-cell-associated markers in human hair follicle epithelial cells. Lab Invest. 2009; 89(8):844–56. https://doi. org/10.1038/labinvest.2009.48. PMid:19506554

Ohyama M, Terunuma A, Tock CL, et al. Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest. 2006; 116(1):249–60. https://doi.org /10.1172/JCI26043. PMid:16395407 PMCid:PMC1323261

Elmaadawi IH, Mohamed BM, Ibrahim ZAS, et al. Stem cell therapy as a novel therapeutic intervention for resistant cases of alopecia areata and androgenetic alopecia. J Dermatolog Treat. 2018; 29(5):431–40. https://doi.org/10.1 080/09546634.2016.1227419. PMid:27553744

Li J, Jiang TX, Chuong CM. Many paths to alopecia via compromised regeneration of hair follicle stem cells. J Invest Dermatol. 2013; 133(6):1450–2. https://doi.org /10.1038/jid.2012.511. PMid:23673497. PMCid:PMC43786 44

Rosenblum MD, Olasz EB, Yancey KB, et al. Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance? J Invest Dermatol. 2004 Nov; 123(5):880–7. https://doi.org/10.1111/j.0022-202X.2004.23461.x. PMid:15482475

Chandrasekar SB, Bhanumathy M, Pawar AT, Soma sundaram T. Phytopharmacology of Ficus religiosa. Pharmacogn Rev. 2010; 4(8):195–9. https://doi.org/ 10.4103/0973-7847.70918.PMid:22228961. PMCid:PMC3 249921

Pawar PL, Nabar BM. Effect of plant extracts formulated in different ointment bases on MDR Strains. Indian J Pharm Sci. 2010; 72(3):397–401. https://doi.org/10.4103/0250-47 4X.70494 PMid:21188057. PMCid:PMC3003181

Bhangale JO, Acharya SR. Anti-parkinson activity of petroleum ether extract of Ficus religiosa (L.) Leaves. Adv Pharmacol Sci. 2016; 2016. https:// doi.org/10.1155/2016/9436106. PMid:26884755. PMCid: PMC4738991

Parameswari SA, Chetty CM, Chandrasekhar KB. Hepatoprotective activity of Ficus religiosa leaves against isoniazid+rifampicin and paracetamol induced hepatotoxicity. Pharmacognosy Res. Oct 2013; 5(4):271– 6. https://doi.org/10.4103/0974-8490.118828. PMid:2417 4821. PMCid:PMC3807992

Kapoor M, Jasani N, Acharya N, Acharya S, Kumar V. Phytopharmacological evaluation and anti-asthmatic activity of Ficus religiosa leaves. Asian Pac J Trop Med. 2011; 4(8):642–4. https://doi.org/10.1016/S1995-7645(11) 60163-6

Chan EW, Lye PY, Wong SK. Phytochemistry, pharmacology, and clinical trials of Morus alba. Chin J Nat Med. 2016; 14(1):17–30.

Li HX, Park JU, Su XD, et al. Identification of Anti-Melanogenesis Constituents from Morus alba L. Leaves. Molecules. 2018; 23(10). https://doi.org/10.3390/ molecules23102559. PMid:30297610. PMCid:PMC62228 40

Dhanotia R, Chauhan NS, Saraf DK, Dixit VK. Effect of Citrullus colocynthis Schrad fruits on testosteroneinduced alopecia. Nat Prod Res. 2011; 25(15):1432–43. https://doi.org/10.1080/14786410802632820. PMid:19764 005

Shahtalebi MA, Asghari GR, Rahmani F, Shafiee F, Jahanian- Najafabadi A. Formulation of herbal gel of antirrhinum majus extract and evaluation of its antipropionibacterium acne effects. Adv Biomed Res. 2018; 7:53. https://doi.org/10.4103/abr.abr_99_17. PMid:296579 38. PMCid:PMC5887696

Luna LG. Armed Forces Institute of Pathology (U.S.), Armed Forces Institute of Pathology (U.S.). Manual of histologic staining methods of the Armed Forces Institute of Pathology. 3d ed. New York,: Blakiston Division; 1968.

Lee J, Choi BI, Park SY, An SY, Han J, Kim JH. Fetal hematopoietic stem cells express MFG-E8 during mouse embryogenesis. Exp Mol Med. 2015; 47 pp. https://doi.org/10.1038/emm.2015.42. PMid:26206421. PMCid:PMC4525298

Cui W, Cuartas E, Ke J, et al. CD200 and its receptor, CD200R, modulate bone mass via the differentiation of osteoclasts. Proc Natl Acad Sci U S A. 2007; 104(36):14436– 41. https://doi.org/10.1073/pnas.0702811104. PMid:17726 108 PMCid:PMC1955461

Xiao L, Song Y, Huang W, et al. Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions. Reprod Biol Endocrinol. 2017; 15(1) :14. https://doi.org/10.1186/s12958-017-0234-9. PMid:282 53866. PMCid:PMC5335735

Militzer K. Hair growth pattern in nude mice. Cells Tissues Organs. 2001; 168(4):285–94. https://doi.org/10.1159/00004 7845. PMid:11275695

Toyoshima KE, Asakawa K, Ishibashi N, et al. Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches. Nat Commun. 2012 Apr 17; 3:784. https://doi.org/10.1038/ncomms1784. PMid:22510689. PMCid:PMC3337983

Paus R, Muller-Rover S, Van Der Veen C, et al. A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. J Invest Dermatol. 1999; 113(4):523–32. https://doi.org/10.1046/ j.1523-1747.1999.00740.x. PMid:10504436

Plikus MV, Chuong CM. Complex hair cycle domain patterns and regenerative hair waves in living rodents. J Invest Dermatol. May 2008; 128(5):1071–80. https://doi.org/10. 1038/sj.jid.5701180. PMid:18094733 PMCid:PMC2705329

Begum S, Gu LJ, Lee MR, et al. In vivo hair growthstimulating effect of medicinal plant extract on BALB/c nude mice. Pharm Biol. 2015; 53(8):1098–103. https://doi.or g/10.3109/13880209.2014.959614. PMid:25612775

Zhang NN, Park DK, Park HJ. Hair growth-promoting activity of hot water extract of Thuja orientalis. BMC Complement Altern Med. 2013; 13:9. https://doi.org/10. 1186/1472-6882-13-9. PMid:23305186. PMCid:PMC3637267

Kurooka H, Segre JA, Hirano Y, et al. Rescue of the hairless phenotype in nude mice by transgenic insertion of the wildtype Hfh11 genomic locus. Int Immunol. 1996 Jun; 8(6):961– 6. https://doi.org/10.1093/intimm/8.6.961. PMid:8671685

Garza LA, Yang CC, Zhao T, et al. Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. J Clin Invest. 2011 Feb 2011; 121(2):613– 22. https://doi.org/10.1172/JCI44478. PMid:21206086. PM Cid:PMC3026732

Begum S, Lee MR, Gu LJ, Hossain MJ, Kim HK, Sung CK. Comparative hair restorer efficacy of medicinal herb on nude (Foxn1nu) mice. Biomed Res Int. 2014; 2014. https://doi.org/10.1155/2014/319795. PMid:25478567. PMCid:PMC4247959