CN116870015A - 线粒体醌在干预和治疗雄激素性脱发中的应用 - Google Patents
线粒体醌在干预和治疗雄激素性脱发中的应用 Download PDFInfo
- Publication number
- CN116870015A CN116870015A CN202310860030.9A CN202310860030A CN116870015A CN 116870015 A CN116870015 A CN 116870015A CN 202310860030 A CN202310860030 A CN 202310860030A CN 116870015 A CN116870015 A CN 116870015A
- Authority
- CN
- China
- Prior art keywords
- mitochondrial
- quinone
- dht
- intervention
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 201000004384 Alopecia Diseases 0.000 title claims abstract description 50
- 230000002438 mitochondrial effect Effects 0.000 title claims abstract description 39
- 201000002996 androgenic alopecia Diseases 0.000 title claims abstract description 36
- 238000011282 treatment Methods 0.000 title claims abstract description 26
- 150000004053 quinones Chemical class 0.000 title description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims abstract description 70
- 206010068168 androgenetic alopecia Diseases 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 17
- 239000000126 substance Substances 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 11
- 235000013305 food Nutrition 0.000 claims description 9
- 239000002778 food additive Substances 0.000 claims description 9
- 235000013373 food additive Nutrition 0.000 claims description 9
- 230000009583 hair follicle growth Effects 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims 2
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 abstract description 38
- 210000003780 hair follicle Anatomy 0.000 abstract description 28
- 229960003473 androstanolone Drugs 0.000 abstract description 27
- 230000003660 hair regeneration Effects 0.000 abstract description 12
- 230000001737 promoting effect Effects 0.000 abstract description 10
- 230000002159 abnormal effect Effects 0.000 abstract description 9
- 231100000360 alopecia Toxicity 0.000 abstract description 8
- 230000002401 inhibitory effect Effects 0.000 abstract description 8
- 230000012010 growth Effects 0.000 abstract description 7
- 208000024963 hair loss Diseases 0.000 abstract description 6
- 230000003676 hair loss Effects 0.000 abstract description 6
- 230000009456 molecular mechanism Effects 0.000 abstract description 6
- 230000000638 stimulation Effects 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 241000699670 Mus sp. Species 0.000 description 28
- GVZFUVXPTPGOQT-UHFFFAOYSA-M mitoq Chemical compound CS([O-])(=O)=O.O=C1C(OC)=C(OC)C(=O)C(CCCCCCCCCC[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C GVZFUVXPTPGOQT-UHFFFAOYSA-M 0.000 description 23
- 210000004209 hair Anatomy 0.000 description 15
- 210000003491 skin Anatomy 0.000 description 14
- 238000010186 staining Methods 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 230000003698 anagen phase Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 235000003891 ferrous sulphate Nutrition 0.000 description 3
- 239000011790 ferrous sulphate Substances 0.000 description 3
- 210000000442 hair follicle cell Anatomy 0.000 description 3
- 230000003779 hair growth Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 3
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 230000002951 depilatory effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229960004199 dutasteride Drugs 0.000 description 2
- JWJOTENAMICLJG-QWBYCMEYSA-N dutasteride Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)N[C@@H]4CC3)C)CC[C@@]21C)NC1=CC(C(F)(F)F)=CC=C1C(F)(F)F JWJOTENAMICLJG-QWBYCMEYSA-N 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229960004039 finasteride Drugs 0.000 description 2
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 2
- 210000001061 forehead Anatomy 0.000 description 2
- 239000003163 gonadal steroid hormone Substances 0.000 description 2
- 230000031774 hair cycle Effects 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000003061 melanogenesis Effects 0.000 description 2
- 230000004089 microcirculation Effects 0.000 description 2
- 229960003632 minoxidil Drugs 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- 102100033875 3-oxo-5-alpha-steroid 4-dehydrogenase 2 Human genes 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101100298998 Caenorhabditis elegans pbs-3 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 206010019044 Hair growth abnormal Diseases 0.000 description 1
- 101000640851 Homo sapiens 3-oxo-5-alpha-steroid 4-dehydrogenase 2 Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241000490567 Pinctada Species 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 230000007488 abnormal function Effects 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960000978 cyproterone acetate Drugs 0.000 description 1
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000003752 improving hair Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002647 laser therapy Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000004065 mitochondrial dysfunction Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- -1 potassium ferricyanide acetate Chemical compound 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
本发明涉及医药技术领域,公开了一种线粒体醌在干预和治疗雄激素性脱发中的应用。本发明通过探讨线粒体醌在缓解DHT刺激下小鼠毛发脱落的应用及相关的分子机制,明确线粒体醌抑制双氢睾酮引起的小鼠毛囊生长异常、促进毛发再生方面的有效性,从而为干预或治疗脱发疾病尤其是雄激素性脱发的临床应用提供实验依据,给出了线粒体醌在干预和治疗雄激素性脱发中的应用,为有效防治雄激素性脱发提供了另一种安全高效的物质。
Description
技术领域
本发明涉及医药技术领域,尤其涉及线粒体醌在干预和治疗雄激素性脱发中的应用。
背景技术
雄激素性脱发(Androgenetic alopecia,AGA)又称脂溢性脱发或早秃,是一种发生于青春期或青春期后的毛发减少性疾病,也是最常见的进行性脱发的原因之一。在男性中,AGA主要表现为前额发际线后移、头顶部毛发进行性减少、变细,脱发区域逐渐增大;在女性中,则较少累积前额发际及颞部,而是头顶部毛发弥漫性减少、变细,发缝增宽。AGA主要病理表现为毛囊生长期缩短,进而导致毛囊微型化,富含色素、有髓质且粗而硬的终毛被无髓质且细软、色素淡化的毳毛所取代。研究显示,AGA发病机制涉及诸多因素,包括遗传易感性、雄激素代谢异常、基因改变、分子信号转导通路异常、毛囊区域微环境出现炎症反应等。
针对AGA的治疗药物与方法各有优势和局限,临床上一般采用口服药物与外用药物相联合的治疗方案。目前美国食品药品监督管理局(Food and Drug Administration,FDA)批准的药物包括非那雄胺和米诺地尔两种,分别针对男性型AGA和女性型AGA。男性口服药物还包括度他雄胺,同非那雄胺一样,主要通过抑制II型5α还原酶,抑制睾酮还原为二氢睾酮(DHT),改善毛囊微循环进而促进毛发生长;女性则主要可通过外用米诺地尔治疗,通过开放血管平滑肌和毛囊的钾通道,诱导微、小血管的舒张进而刺激毛囊周围的微循环;也可选择口服螺内酯和性激素(乙炔雌二醇及大剂量醋酸环丙孕酮)对抗雄激素。近年来,注射富血小板血浆、微针、低强度激光治疗、毛发移植、脂肪来源的干细胞成分提取物等作为新兴的治疗手段,可作为主流药物的辅助手段。
AGA患者体内的雄激素水平通常在正常范围内,因为除了在性腺和其他器官中的激素合成途径之外,性激素在毛囊中能够独立合成并发生相互作用进而影响基因的转录与表达。AGA伴有位于毛囊基部的雄激素敏感性毛囊周围细胞(DPCs)的衰老。高水平的DHT可能导致DPCs衰老或退化。
健康美丽的秀发能给人以美好的形象,让人在人际交往中更加自信,人们对于脱发的防治也越来越重视。在本领域,仍需寻找一种安全高效的药物,来有效防治雄激素性脱发。
发明内容
为了解决上述防治雄激素性脱发的技术问题,本发明提供了线粒体醌在干预和治疗雄激素性脱发中的应用。本发明通过探讨线粒体醌在缓解DHT刺激下小鼠毛发脱落的应用及相关的分子机制,明确线粒体醌抑制双氢睾酮引起的小鼠毛囊生长异常、促进毛发再生方面的有效性,从而为干预或治疗脱发疾病尤其是雄激素性脱发的临床应用提供实验依据,给出了线粒体醌在干预和治疗雄激素性脱发中的应用。
本发明的具体技术方案为:
一方面,本发明提供了线粒体醌在制备干预和/或治疗雄激素性脱发的产品中的应用。
线粒体醌,是一种存在于线粒体内的脂溶性物质,是一种人体内源性物质。现有技术中,线粒体醌作为一种线粒体靶向抗氧化剂被应用。本发明以小鼠皮肤中毛囊和毛囊部位细胞为研究对象,明确了线粒体醌在抵抗AGA模型小鼠的真皮乳头细胞线粒体功能异常及毛发生长周期异常方面的作用,基于此,给出了线粒体醌在干预和治疗雄激素性脱发中的应用,为有效防治雄激素性脱发提供了另一种安全高效的物质。
作为本发明上述技术方案的优选,所述产品为药品、日化用品、食品或食品添加剂。
作为本发明上述技术方案的优选,所述产品通过抵抗DHT引起的毛囊生长抑制来对雄激素性脱发进行干预和/或治疗。所述产品优选为抵抗DHT引起的毛囊生长抑制的药品、日化用品、食品、或食品添加剂。
本发明通过探讨线粒体醌在缓解DHT刺激下小鼠毛发脱落的应用及相关的分子机制,明确了线粒体醌在抑制双氢睾酮引起的小鼠毛囊生长异常的有效性,也证明了线粒体醌在促进毛发再生方面的可行性,为干预或治疗雄激素性脱发提供了依据,给出了线粒体醌通过抵抗DHT引起的毛囊生长抑制来对雄激素性脱发进行干预和/或治疗的可行性。
一方面,本发明提供了一种治疗雄激素性脱发的制品,所述制品的活性成分包括线粒体醌。
本发明以小鼠皮肤中毛囊和毛囊部位细胞为研究对象,明确了线粒体醌在抵抗AGA模型小鼠的真皮乳头细胞线粒体功能异常及毛发生长周期异常方面的作用,基于此,给出了线粒体醌在干预和治疗雄激素性脱发中的应用。
作为本发明上述技术方案的优选,所述制品的活性成分为线粒体醌。
本发明通过探讨线粒体醌在缓解DHT刺激下小鼠毛发脱落的应用及相关的分子机制,明确了线粒体醌在抑制双氢睾酮引起的小鼠毛囊生长异常的有效性,证明了线粒体醌在促进毛发再生方面的可行性,为干预或治疗雄激素性脱发提供了依据,给出了线粒体醌通过抵抗DHT引起的毛囊生长抑制来对雄激素性脱发进行干预和/或治疗的可行性。
作为本发明上述技术方案的优选,所述制品为药品、日化用品、食品、或食品添加剂。
作为本发明上述技术方案的优选,所述制品通过抵抗DHT引起的毛囊生长抑制来对雄激素性脱发进行干预和/或治疗。所述制品优选为抵抗DHT引起的毛囊生长抑制的药品、日化用品、食品、或食品添加剂。
与现有技术相比,本发明具有以下技术效果:
本发明通过探讨线粒体醌在缓解DHT刺激下小鼠毛发脱落的应用及相关的分子机制,明确线粒体醌在抑制双氢睾酮引起的小鼠毛囊生长异常、促进毛发再生方面的有效性,从而为干预或治疗脱发疾病尤其是雄激素性脱发的临床应用提供实验依据,给出了线粒体醌在干预和治疗雄激素性脱发中的应用,为有效防治雄激素性脱发提供了另一种安全高效的物质。
附图说明
图1为本发明实施例1中小鼠不同时期的毛发生长情况;
图2为本发明实施例3中处理19天后各组小鼠背部皮肤H&E染色情况;
图3为本发明实施例4中各组小鼠Ki67免疫荧光染色结果图;
图4为本发明实施例5中各组小鼠皮肤的黑色素染色观察结果图。
具体实施方式
下面结合实施例及附图对本发明作进一步的描述。本发明实施例中,线粒体醌简写为MitoQ。
本发明实施例相关材料的来源及处理如下:
①实验材料实验动物:清洁级6周龄雄性C57BL/6小鼠(购自浙江省医学科学院动物实验中心)。小鼠随机分组如下:未处理组(对照),DHT组,DHT+MitoQ组,每组4只,分笼饲养。
②饲养
浙江省医学科学院动物实验中心负责小鼠日常饲养。
③试剂
苏木素伊红染色试剂盒购自上海碧云天生物技术有限公司;DHT(美雄诺龙)购自上海麦克林生化科技有限公司;MitoQ购自西安瑞禧生物科技有限公司;二甲基亚砜(DMSO)购自Sigma-Aldrich公司;Anti-Ki67抗体购自Abcam[艾博抗(上海)贸易有限公司];荧光二抗购自南京艾思易生物科技有限公司;黑色素染色液(硫酸亚铁法)购自珠海贝索生物技术有限公司。
实施例1小鼠模型的建立
购买的小鼠适应性喂养7天后随机分组:对照组(仅剃毛),DHT组(颈背部涂抹DHT),DHT+MitoQ组(颈背部涂抹DHT,同时腹腔注射MitoQ),每组4只,共12只,分笼饲养。实验当日(记为Day 0)小鼠背部剃毛并涂抹脱毛膏脱毛,面积约为2cm×2cm,次日(记为Day1)起脱毛区域涂抹DHT溶解液200μl,处理组腹腔注射MitoQ溶解液200μl,每日1次,共19天。19天期间每天固定时间根据不同分组实施对应处理。第19天收集小鼠背部皮肤,进行后续指标检测。
第0、10、19天分别拍照,结果如图1所示。
实施例2蜡块制备及切片
取小鼠新鲜背部皮肤组织(1cm×1cm)用4%多聚甲醛固定,脱水后进行石蜡包埋。将蜡块切成厚度为4μm的切片后放进60℃烘箱内烤片,用于后续实验。
实施例3苏木素伊红(H&E)染色
将实施例2得到的切片置于二甲苯中浸泡15min,重复1次,将脱蜡后的切片逐级脱水放入苏木素水溶液中5min,流水冲洗15min,置于75%和90%乙醇中脱水各10min。取出置于0.5%乙醇-伊红染色液中2min,流水冲洗1min,染色后的切片经无水乙醇脱水。
切片置于二甲苯中透明3min,重复1次,中性树胶封片,显微镜拍照观察,结果如图2所示,其中,a为H&E染色观察结果图,b为毛囊数量统计图,c为皮肤厚度统计图。(**代表P<0.01,***代表P<0.001,ns代表无统计学差异)
实施例4免疫荧光观察
将实施例2得到的切片放入55℃恒温箱中30min,脱蜡并完成抗原修复后,用5%山羊血清孵育切片,置于湿盒内于37℃避光放置30min后加入1:200稀释后的Ki67兔抗(Abcam,Cambridge,UK),4℃孵育过夜。次日复温15min后,去除一抗并用PBS洗涤3次,每次5min。加入1:5000稀释后的橙色荧光鼠抗(ACE,南京,中国),室温下避光孵育1h后,去除二抗并用PBS洗涤3次,每次5min。加入DAPI工作液室温避光孵育10min后,用PBS液洗涤3次,每次5min。抗荧光萃灭剂封片后,荧光显微镜(IX70-141倒置显微镜,奥林巴斯,日本)观察,结果见图3。
实施例5黑色素染色
参照黑色素染色试剂盒(硫酸亚铁法)进行黑色素染色,具体步骤如下:
实施例2得到的切片放入55℃恒温箱中30min,脱蜡并完成抗原修复后,用蒸馏水洗1次,硫酸亚铁液处理1h,蒸馏水洗3次后滴加铁氰化钾醋酸液处理30min,冰醋酸液洗3s后甩干。Van Gieson液染色1min,去除染液后置于95%乙醇30sec,无水乙醇脱水后二甲苯透明并封片。
各组小鼠皮肤的黑色素染色观察结果图见图4。
数据分析
(1)对实施例1数据结果进行分析
图1为分别在药物处理0天、10天、19天对三组小鼠进行拍照观察背部毛发生长情况结果图。
由图1可知,在第10天可见对照组组和DHT+MitoQ组小鼠背部有毛发再生,而DHT组小鼠皮肤仍为粉红色且无毛发再生;第19天时对照组小鼠背部毛发几乎完全再生,DHT+MitoQ组毛发再生明显且皮肤变为灰黑色,DHT组小鼠皮肤无明显变化。由此表明,MitoQ具有促进毛发再生的作用。
(2)对实施例3数据结果进行分析
图2为第19天取三组小鼠皮肤做病理切片并进行H&E染色观察的结果图。
如图2a所示,DHT组毳毛比对照组和DHT+MitoQ组明显增加,而终毛数量比对照组和DHT+MitoQ组减少,且由可以观察到DHT+MitoQ组可恢复DHT导致的皮肤组织形态异常。如图2a及2b所示,在对照组和DHT+MitoQ组可见大量毛囊,与二者相比,DHT组毛囊数量极显著减少,且如图2a及2c所示,DHT组真皮层厚度较对照组和DHT+MitoQ组极显著变薄,因此说明DHT组小鼠背部毛发生长期延迟,而MitoQ可以促进毛发进入生长期。
由此可知,MitoQ具有增加毛囊和终毛数量的作用。
(3)对实施例4数据结果进行分析
图3为各组小鼠Ki67免疫荧光染色结果图。
如图3所示,对照组和DHT+MitoQ组可见毛囊部位细胞增殖明显,反之DHT组未显示明显增殖,DHT组小鼠背部毛发尚未进入生长期,由此可知,MitoQ的干预可以促进毛囊细胞增殖。
(4)对实施例5数据结果进行分析
图4为各组小鼠皮肤的黑色素染色观察结果图。
如图4所示,对照组和DHT+MitoQ组毛囊中均出现明显的黑色素分布,而DHT组毛囊中少见黑色素染色,表明MitoQ促进毛囊黑色素生成。
综上所述,线粒体醌具有促进毛发再生、增加毛囊和终毛数量、促进毛囊细胞增殖、促进毛囊黑色素生成的作用。进一步地,说明线粒体醌可以抑制双氢睾酮引起的小鼠毛囊生长异常,可以有效促进毛发再生,并证明了线粒体醌通过抵抗DHT引起的毛囊生长抑制来对雄激素性脱发进行干预和/或治疗的可行性。
上述实施例在动物实验水平上进一步探讨MitoQ在缓解DHT刺激下小鼠毛发脱落的应用及相关的分子机制。通过应用MitoQ腹腔注射,结合背部脱毛区域涂抹DHT溶液,明确MitoQ在抑制双氢睾酮引起的小鼠毛囊生长异常,促进毛发再生方面的有效性,从而为干预或治疗脱发疾病尤其是雄激素性脱发的临床应用提供实验依据,并为MitoQ作为药品、日化用品、食品或食品添加剂或其有效成分,用于干预和/或治疗雄激素性脱发提供了理论依据。
本发明中所用原料、设备,若无特别说明,均为本领域的常用原料、设备;本发明中所用方法,若无特别说明,均为本领域的常规方法。
以上所述,仅是本发明的较佳实施例,并非对本发明作任何限制,凡是根据本发明技术实质对以上实施例所作的任何简单修改、变更以及等效变换,均仍属于本发明技术方案的保护范围。
Claims (7)
1.线粒体醌在制备干预和/或治疗雄激素性脱发的产品中的应用。
2.如权利要求1所述的应用,其特征在于:所述产品为药品、日化用品、食品、或食品添加剂。
3.如权利要求2所述的应用,其特征在于:所述产品为抵抗DHT引起的毛囊生长抑制的药品、日化用品、食品、或食品添加剂。
4.一种治疗雄激素性脱发的制品,其特征在于:所述制品的活性成分包括线粒体醌。
5.根据权利要求4所述的一种治疗雄激素性脱发的制品,其特征在于:所述制品的活性成分为线粒体醌。
6.根据权利要求4所述的一种治疗雄激素性脱发的制品,其特征在于:所述制品为药品、日化用品、食品、或食品添加剂。
7.根据权利要求6所述的一种治疗雄激素性脱发的制品,其特征在于:所述制品为抵抗DHT引起的毛囊生长抑制的药品、日化用品、食品、或食品添加剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310860030.9A CN116870015A (zh) | 2023-07-13 | 2023-07-13 | 线粒体醌在干预和治疗雄激素性脱发中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310860030.9A CN116870015A (zh) | 2023-07-13 | 2023-07-13 | 线粒体醌在干预和治疗雄激素性脱发中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116870015A true CN116870015A (zh) | 2023-10-13 |
Family
ID=88260035
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310860030.9A Pending CN116870015A (zh) | 2023-07-13 | 2023-07-13 | 线粒体醌在干预和治疗雄激素性脱发中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116870015A (zh) |
-
2023
- 2023-07-13 CN CN202310860030.9A patent/CN116870015A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Semalty et al. | Hair growth and rejuvenation: an overview | |
US20100172865A1 (en) | Methods of enhancing hair growth | |
CN102159179A (zh) | 防止、治疗脱发或促进毛发生成的成分 | |
Inaba et al. | Androgenetic alopecia: modern concepts of pathogenesis and treatment | |
US9839606B2 (en) | Formulation for treatment of hairs | |
AU2015261537A1 (en) | Association of a tetrapeptide and a glyceryl ester for treating androgenic alopecia | |
US20110217260A1 (en) | Method of enhancing eyelash and eye brow hair growth | |
CN116870015A (zh) | 线粒体醌在干预和治疗雄激素性脱发中的应用 | |
Braun-Falco et al. | Diseases of the hair | |
CN113876955B (zh) | Pcsk9抑制剂在制备促进毛发生长产品中的应用 | |
EP3903807A1 (en) | Composition for treating hair loss or promoting hair growth comprising growth factor | |
US20230144955A1 (en) | Peptide for preventing or treating hair loss, and use thereof | |
KR20190136423A (ko) | 유데나필을 유효성분으로 포함하는 지방줄기세포의 발모 유도능 증진용 조성물 | |
Kim et al. | Gold thread implantation promotes hair growth in human and mice | |
Diba et al. | Diagnosis and management of female pattern hair loss | |
WO2013020719A2 (en) | New use of compositions to delay the onset of the catagen phase of the hair | |
Zaidi et al. | Hair disorders | |
KR101967338B1 (ko) | 센티페드그라스 추출물 또는 이의 분획물을 유효성분으로 함유하는 탈모 예방 또는 치료용 약학적 조성물 | |
EP3888625A1 (en) | Composition for scalp and hair | |
Trilisnawati et al. | Update treatment of male androgenetic alopecia | |
JP2021532150A (ja) | ヘアケアの分野において使用するためのレスペデザ・カピタータ抽出物 | |
Lee et al. | Hair growth effects of Laminaria japonica extract and growth factor mixture on a C57BL/6 mouse model | |
CN113058026B (zh) | Kisspeptin-234在促进毛发生长中的应用 | |
KR101355477B1 (ko) | 알파 하이드록시산을 유효성분으로 포함하는 모발성장 촉진용 조성물 | |
US20230023847A1 (en) | Composition for preventing hair loss and promoting hair regrowth |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |