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Mechanism of action of herbs and their active constituents used in hair loss treatment The hair growth cycle consists of 4 stages known as the anagen (active growth phase; takes 2–7years), catagen (involuting or regressing phase; takes approx. 2weeks), telogen (short resting phase; takes approx. 4months) and exogen (shedding phase) . This cyclical growth of hair is regulated by diversity growth factors and cytokines. Increased expression of insulin-like growth factor-1 (IGF-1), fibroblast growth factor (FGF), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF) let maintain the anagen phase, while decreased expression of transforming growth factor beta (TGF-β) promotes hair apoptosis in catagen phase . Herbs and their active constituents used in order to promote hair growth showed different types of the mechanisms of action (Fig. 1). In general, mechanisms involving (1) IGF-1, (2) VEGF, (3) epidermal growth factor (EGF), (4) FGF-2, (5) endothelial nitric oxide synthase (eNOS), (6) Wnt/β-catenin signaling pathway, (7) prostaglandin E (PGE), (8) prostaglandin F (PGF) stimulate hair growth, whereas the mechanism engaging (1) 5α-reductase, (2) TGF-β, (3) FGF-5, (4) prostaglandin D2 (PGD2) inhibit hair growth.
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Intrinsic factors guiding oligodendrocyte and SC development Although both cells produce myelin to insulate and support axons, oligodendrocytes and SCs differ early in their genesis. Oligodendrocytes originate from neuroepithelial precursors, whereas SCs are derived from the neural crest. Furthermore, one oligodendrocyte can myelinate multiple axon segments, but one SC myelinates only a single axon segment (Figure 1, Figure 2). This is achieved through a process called radial sorting in which cytoplasmic processes from immature SCs extend into axon bundles and ‘select’ an axon segment . SC development is mediated by a host of transcription factors and signaling molecules, including Sox10, which persists throughout development and differentiation, activating other transcription factors . In pro-myelinating SCs, which have radially sorted p53 apoptosis and wrapped 1-1.5 turns around an axon, the G protein-coupled receptor (GPCR) GPR126/ADGRG6 elevates cAMP to promote expression of the transcription factor Oct6/Pou3f1 . Oct6 and Sox10, along with other factors, activate the master regulator of PNS myelination, Krox-20/Egr2, which is essential for expression of critical myelin genes, including Myelin basic protein (Mbp) . Proliferative and migratory oligodendrocyte precursor cells (OPCs) extend and retract numerous processes during development . Recent work has found that OPCs can migrate along blood vessels in a Wnt-dependent manner involving the receptor-ligand pair Cxcr4-Cxcl12, which are expressed on OPCs and endothelial cells, respectively . Oligodendrocyte differentiation requires some shared SC factors, including Sox10 and Yin yang 1 (Yy1), in addition to the oligodendrocyte specific regulators Olig1, Olig2, Nkx2.2  and Myelin regulatory factor, Myrf, which plays an analogous role to Krox-20 . Recent work in SCs and oligodendrocytes has identified novel roles for signaling molecules, including a suite of GPCRs, GPR17, GPR56 and GPR37 in the CNS [5, 6, 7, 8] and GPR44 and the zinc finger Zeb2 in the PNS [9, 10, 11]. While new myelin regulators remain to be uncovered, elucidating the function of known molecules and pathways is key to understanding myelination in development and repair.
Mechanical regulation of myelinating glia during development and differentiation A unique signaling mechanism in SCs occurs via the basal lamina (BL), and recent evidence points to the molecular mechanisms by which this structure mechanically regulates myelination. In SCs, GPR126 can interact with axonally-derived Prion protein (PrPc)  as well as two SC-derived components of the BL, collagen IV and Laminin-211 [13•, 14•]. Laminin-211 polymerization was proposed to activate GPR126 mechanically, initiating SC myelination (Figure 1) , and SCs respond to mechanical properties of the BL with intracellular molecules such as Focal adhesion kinase (FAK) . Recently, two Hippo pathway signaling molecules, YAP and TAZ (YAP/TAZ), have been implicated as mediators of mechanotransduction during SC development. YAP/TAZ respond to mechanical or chemical stimuli and translocate to the nucleus to regulate gene transcription. In vitro culture experiments found nuclear localized YAP/TAZ during SC spreading, plating on stiffer surfaces, plating on Laminin-211, and experimentally applied stretching (Figure 1). Analysis of mouse mutants demonstrated that YAP/TAZ signaling is required for radial sorting and myelination . YAP also has a role in modulating internode length during development and disease . In concert with TEAD transcription factors, nuclear YAP activates genes involved in the myelination program, including Krox-20/Egr2 and Myelin associated glycoprotein (MAG), Rab11, and Lamininϒ1. The polarity protein Crb3 inhibits YAP nuclear translocation and knock-down of Crb3 increases the length of SC myelin segments . Crb3 is therefore thought to modulate YAP activity to temper internode length. Interestingly, a dystrophic mouse model of peripheral neuropathy exhibited reduced nuclear YAP with shorter internodes, a phenotype that could be rescued by manual sciatic nerve elongation via femoral distraction to increase nuclear YAP . These data suggest that migration of SCs along axons and/or longitudinal nerve growth could activate YAP/TAZ signaling during development. Perhaps physical maturation of the BL and GPR126 activation is similarly linked to developmental YAP/TAZ signaling, as GPCRs are known upstream regulators of this pathway . Downstream of YAP/TAZ signaling, TEAD1 directly regulates Peripheral myelin protein 22 (Pmp22), mis-regulation of which causes Charcot-Marie-Tooth disease .