title: Apigenin induces dermal collagen synthesis via smad2/3 signaling pathway.
abstract: Decrease in fibroblast-produced collagen has been proven to be the pivotal cause of skin aging, but there is no satisfactory drug which directly increases dermal thickness and collage density. Here we found that a flavonoid natural product, apigenin, could significantly increase collagen synthesis. NIH/3T3 and primary human dermal fibroblasts (HDFs) were incubated with various concentrations of apigenin, with dimethyl sulfoxide (DMSO) serving as the negative control. Real-time reverse-transcription polymerase chain reaction (PCR), Western Blot, and Toluidine blue staining demonstrated that apigenin stimulated type-I and type-III collagen synthesis of fibroblasts on the mRNA and protein levels. Meanwhile, apigenin did not induce expression of alpha smooth muscle actin (α-SMA) in vitro and in vivo, a fibrotic marker in living tissues. Then the production of collagen was confirmed by Masson's trichrome stain, Picrosirius red stain and immunohistochemistry in mouse models. We also clarified that this compound induced collagen synthesis by activating smad2/3 signaling pathway. Taken together, without obvious influence on fibroblasts' apoptosis and viability, apigenin could promote the type-I and type-III collagen synthesis of dermal fibroblasts in vitro and in vivo, thus suggesting that apigenin may serve as a potential agent for esthetic and reconstructive skin rejuvenation.
authors.affiliation: Shanghai Jiao Tong University. zhangyifan82@126.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Cheng
authors.forename: B
authors.initials: B
authors.lastname: Yi
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Li
mesh_terms: D016475:3T3 Cells; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002648:Child; D003094:Collagen / Q000096:biosynthesis*; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D004396:Coloring Agents; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D034741:RNA, Small Interfering / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D015595:Skin Aging / Q000187:drug effects; D051899:Smad2 Protein / Q000187:drug effects* / Q000235:genetics; D051900:Smad3 Protein / Q000187:drug effects* / Q000235:genetics
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D004396:Coloring Agents; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D047310:Apigenin; D003094:Collagen