Volume 3,Issue 1
环黄芪醇在皮肤领域的研究进展:从分子机制到递送技术
介绍了CA在皮肤抗衰老、屏障修复、抗炎及美白中的作用机制及其递送技术研究进展。在分子机制层面,CA通过激活端粒酶逆转录酶延缓细胞衰老,并调控Nrf2/ARE、MAPK/NF-κB等信号通路,增强皮肤抗氧化防御能力,抑制紫外线诱导的活性氧积累及基质金属蛋白酶表达,从而减少胶原降解。同时,CA有效提高UVB 损伤细胞中透明质酸水平和皮肤水合作用因子(filaggrin 和丝氨酸棕榈酰转移酶)的表达,改善皮肤弹性,维持皮肤健康。此外,CA通过调控TGF-β/Smad通路促进成纤维细胞增殖与Ⅰ /Ⅲ型胶原合成,协同PI3K/Akt/mTOR信号改善皮肤屏障功能,并通过抑制TLR4/NF-κB通路下调IL-6、TNF-α等促炎因子释放,在特应性皮炎及银屑病等炎症性皮肤病中展现治疗潜力。
[1]Chang YX, Ge AH, Donnapee S, et al The multi-targets integrated fingerprinting for screening anti-diabetic compounds from a Chinese medicine Jinqi Jiangtang Tablet [J]. Ethnopharmacol. 2015(4): 210-22.
[2]Guo Z, Lou Y, Kong M, et al. A Systematic Review of Phytochemistry, Pharmacology and Pharmacokinetics on Astragali
Radix: Implications for Astragali Radix as a Personalized Medicine[J].Int J Mol Sci. 2019(3): 1463.
[3] Fu J, Wang Z, Huang L,et al. Review of the botanical characteristics,phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi)[J]. Phytother Res. 2014(9): 1275-83.
[4] Guo K, He X, Lu D, et al. Cycloartane-type triterpenoids from Astragalus hoantchy French[J]. Nat Prod Res. 2017(2): 314-319.
[5]Zhou RN, Song YL, Ruan JQ, et al. Pharmacokinetic evidence on the contribution of intestinal bacterial conversion to beneficial effects
of astragaloside IV, a marker compound of astragali radix, in traditional oral use of the herb[J]. Drug Metab Pharmacokinet. 2012(6): 586-97.
[6]Zeng JK, Li YY, Wang TM, et al. Simultaneous quantification of multiple components in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Huangqi
decoction[J]. Biomed Chromatogr. 2018(5): e4178.
[7]Fathiazad F, Khosropanah MK, Movafeghi A. Cycloartane-type glycosides from the roots of Astragalus caspicus Bieb[J]. Nat Prod Res.2010(7): 1069-78.
[8]Feng LM, Lin XH, Huang FX, et al. Smith degradation, an efficient method for the preparation of cycloastragenol from astragaloside IV[J].Fitoterapia. 2014(6): 42-50.
[9]章诗迪. 环黄芪醇提取物的制备及其抗衰老活性研究[D].浙江:浙江工业大学, 2016.
[10]Li Y, Yang X, Li X, et al. Astragaloside IV and cycloastragenol promote liver regeneration through regulation of hepatic oxidative homeostasis and glucose/lipid metabolism[J]. Phytomedicine. 2024(12):
156165.
[11]Zhu LH, Liang YP, Yang L, et al. Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines[J]. Integr Med. 2024(7): 503-514.
[12]Fauce SR, Jamieson BD, Chin AC, et al. Telomerase-based pharmacologic enhancement of antiviral function of human CD8+ T lymphocytes[J]. Immunol. 2008(11): 7400-6.
[13]Wan Y, Xu L, Wang Y, et al. Preventive effects of astragaloside IV and its active sapogenin cycloastragenol on cardiac fibrosis of mice by inhibiting the NLRP3 inflammasome[J]. Eur Pharmacol. 2018(8): 545-554.
[14]Zhao Y, Li Q, Zhao W, et al. Astragaloside IV and cycloastragenol are equally effective in inhibition of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in the
endothelium[J]. Ethnopharmacol. 2015(7): 210-8.
[15]Chen T, Li Z, Li S, et al. Cycloastragenol suppresses M1 and promotes M2 polarization in LPS-stimulated BV-2 cells and ischemic stroke mice[J]. Int Immunopharmacol. 2022(12): 109290.
[16]Bagalagel A, Diri R, Noor A, et al. The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP-1α/miR-143 signalling[J]. Basic Clin Pharmacol Toxicol. 2022(11): 406-
419.
[17]Xiao S, Liu L, Qin X, et al. Cycloastragenol targets Fpr2 to inhibit the TLR4/NF-κB signaling pathway and alleviate neuroinflammation in Parkinson’s disease[J]. Phytomedicine. 2025(4): 156462.
[18]Wang X, Ji X, Sun Y. Inhibition of NLRP3 inflammasomemediated pyroptosis in macrophage by cycloastragenol contributes to amelioration of imiquimod-induced psoriasis-like skin inflammation
in mice[J]. Int Immunopharmacol. 2019(9): 105682.
[19]Zhang P, Chen Y, Jiang X, et al. Tumor-targeted efficiency of shRNA vector harboring chimera hTERT/U6 promoter[J]. Oncol Rep. 2010(5): 1309-16
[20]Wang T, Ruan J, Li X, et al. Bioactive cyclolanstane-type saponins from the stems of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao[J]. Nat Med. 2016(4): 198-206.
[21]Deng G, Zhou L, Wang B, et al. Targeting cathepsin B by cycloastragenol enhances antitumor immunity of CD8 T cells via inhibiting MHC-I degradation[J]. Immunother Cancer. 2022(10):e004874.
[22]Hwang ST, Kim C, Lee JH, et al. Cycloastragenol can negate constitutive STAT3 activation and promote paclitaxel-induced apoptosis in human gastric cancer cells[J]. Phytomedicine. 2019(6):152907.
[23]Park D, Jung JH, Ko HM, et al. Antitumor Effect of Cycloastragenol in Colon Cancer Cells via p53 Activation[J]. Mol Sci. 2022(12): 15213.
[24]Qian W, Liu W, Zhu D, et al. Natural skin-whitening compounds for the treatment of melanogenesis (Review)[J]. Exp Ther Med.2020(7): 173-185.
[25]Zhao W, Yang A, Wang J, et al. Potential application of natural bioactive compounds as skin-whitening agents: A review[J]. Cosmet Dermatol. 2022(12): 6669-6687.
[26]Mansoor K, Aburjai T, Al-Mamoori F, et al. Plants with cosmetic uses[J]. Phytother Res. 2023(12): 5755-5768.
[27]Saechan C, Nguyen UH, Wang Z, et al. Potency of bisresorcinol from Heliciopsis terminalis on skin aging: in vitro bioactivities and molecular interactions[J]. PeerJ. 2021(6): e11618.
[28]Pillaiyar T, Manickam M, Namasivayam V. Skin whitening agents:medicinal chemistry perspective of tyrosinase inhibitors[J]. Enzyme Inhib Med Chem. 2017(12): 403-425.
[29]Pillaiyar T, Manickam M, Jung SH. Inhibitors of melanogenesis: a patent review (2009 - 2014)[J]. Expert Opin Ther Pat. 2015(7): 775-88.
[30]Agarwal S, Mazhar M, Saha H, et al.“Skin Whitening Creams:Cosmetovigilance[J]. Curr Pharm Biotechnol. 2025(1): 15.
[31]Raposo G, Marks MS. Melanosomes--dark organelles enlighten endosomal membrane transport[J]. Nat Rev Mol Cell Biol. 2007(10):786-97.
[32]Schiaffino MV. Signaling pathways in melanosome biogenesis and pathology[J]. Biochem Cell Biol. 2010(7): 1094-104.
[33]Jo YJ, Yoo DH, Lee IC,et al. Antioxidant and Skin Whitening Activities of Sub- and Super-Critical Water Treated Rutin[J]. Molecules. 2022(8): 5441.
[34]Susilawati Y, Chaerunisa AY, Purwaningsih H. Phytosome drug delivery system for natural cosmeceutical compounds: Whitening agent and skin antioxidant agent[J]. Adv Pharm Technol Res. 2021(12): 327-
334.
[35]Guo S, Yang L, Zhang Q,et al. Metabolomics combined with serum pharmacochemistry discovering the potential effective compounds of Fangji Huangqi Tang against nephrotic syndrome[J]. Chromatogr B
Analyt Technol Biomed Life Sci. 2023(1): 123532.
[36]Mhiri W, Ceylan M, Turgut-Kara N, et al. Transcriptomic analysis reveals responses to Cycloastragenol in Arabidopsis thaliana[J]. PLoS One. 2020(12): e0242986.
[37]Yang MH, Hwang ST, Um JY, et al. Cycloastragenol exerts protective effects against UVB irradiation in human dermal fibroblasts and HaCaT keratinocytes[J]. Dermatol Sci. 2023(8): 60-67.
[38]Hao LY, Armanios M, Strong MA, et al. Short telomeres, even in the presence of telomerase, limit tissue renewal capacity[J]. Cell. 2005(12): 1121-31.
[39]Zhao Y, Simon M, Seluanov A, et al. DNA damage and repair in age-related inflammation[J]. Nat Rev Immunol. 2023(2): 75-89.
[40]Zhao Q, Liu J, Deng H, et al. Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output[J]. Cell.2020(10): 76-93.
[41]Xie N, Zhang L, Gao W, et al. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential[J]. Signal Transduct Target Ther.2020(10): 227.
[42]Kalamakis G, Brüne D, Ravichandran S, et al. Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain[J]. Cell. 2019(3):1407-1419.
[43]Holwerda AM, Paulussen KJM, Overkamp M, et al. Dose-Dependent Increases in Whole-Body Net Protein Balance and Dietary Protein-Derived Amino Acid Incorporation into Myofibrillar Protein
During Recovery from Resistance Exercise in Older Men[J]. Nutr.2019(2)221-230.
[44]Li Y, Tian X, Luo J, et al. Molecular mechanisms of aging and anti-aging strategies[J]. Cell Commun Signal. 2024(5): 285.
[45]Quan T. Human Skin Aging and the Anti-Aging Properties of Retinol[J]. Biomolecules. 2023(11): 1614.
[46]Costa EF, Magalhães WV, Di Stasi LC. Recent Advances in Herbal-Derived Products with Skin Anti-Aging Properties and Cosmetic Applications[J]. Molecules. 2022(11): 7518.
[47]de Magalhães JP, Stevens M, Thornton D. The Business of Anti- Aging Science[J]. Trends Biotechnol. 2017(11): 1062-1073.
[48]Stojić V, Štrbac T, Stanimirović A. New anti-aging strategies: a narrative review[J]. Acta Dermatovenerol Alp Pannonica Adriat. 2023(12): 159-164.
[49]Duman S, Ekiz G, Yılmaz S, et al. Telomerase activators from 20(27)-octanor-cycloastragenol via biotransformation by the fungal endophytes[J]. Bioorg Chem. 2021(4): 104708.
[50]Yu Y, Zhou L, Yang Y, et al Cycloastragenol: An exciting novel candidate for age-associated diseases. Exp Ther Med[J]. 2018(9): 2175-2182.
[51]Wang FC, Hudson PL, Burk K, et al. Encapsulation of cycloastragenol in phospholipid vesicles enhances transport and
delivery across the skin barrier[J]. Colloid Interface Sci. 2022(2): 1222-1228.
[52]Yilmaz S, Bedir E, Ballar Kirmizibayrak P. The role ofcycloastragenol at the intersection of NRF2/ARE, telomerase, and proteasome activity[J]. Free Radic Biol Med. 2022(8): 105-116.
[53]Ip FC, Ng YP, An HJ, et al. Cycloastragenol is a potent telomerase activator in neuronal cells: implications for depression management[J].
Neurosignals. 2014(7): 52-63.
[54]Weiss RA, Weiss MA. Evaluation of a novel anti-aging topical formulation containing cycloastragenol, growth factors, peptides, and antioxidants[J]. Drugs Dermatol. 2014(9): 1135-9.
[55]Bernardes de Jesus B, Schneeberger K, Vera E, et al. The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence[J]. Aging Cell.
2011(8): 604-21.
[56]Rastmanesh R. Potential of melatonin to treat or prevent agerelated macular degeneration through stimulation of telomerase activity[J]. Med Hypotheses. 2011(1): 79-85.
[57]Molgora B, Bateman R, Sweeney G, et al. Functional assessment of pharmacological telomerase activators in human T cells[J]. Cells. 2013(1): 57-66.
[58]McCully KS. Review: Chemical Pathology of Homocysteine VI.Aging, Cellular Senescence, and Mitochondrial Dysfunction[J]. Ann Clin Lab Sci. 2018(9): 677-687.
[59]Gravitz L. Skin[J]. Nature. 2018(11): S83.
[60]Lin TK, Zhong L, Santiago JL. Anti-Inflammatory and Skin Barrier Repair Effects of Topical Application of Some Plant Oils[J]. Mol Sci. 2017(12): 70.
[61]Yosipovitch G, Misery L, Proksch E, et al. Skin Barrier Damage and Itch: Review of Mechanisms, Topical Management and Future Directions[J]. Acta Derm Venereol. 2019(12): 1201-1209.
[62]Schwartz J, Friedman AJ. Exogenous Factors in Skin Barrier Repair[J]. Drugs Dermatol. 2016(11): 1289-1294.
[63]Chiang C, Maibach HI. How many skin barriers haveth we: Percutaneous egression of ions? [J].Skin Res Technol. 2022(3): 382- 387.
[64]Mandlik DS, Mandlik SK. Atopic dermatitis: new insight into the etiology, pathogenesis, diagnosis and novel treatment strategies[J]. Immunopharmacol Immunotoxicol. 2021(4): 105-125.
[65]Ekiz Dinçman G, Aytaç Z, Çalış İ. Turkish Astragalus Species:Botanical Aspects, Secondary Metabolites, and Biotransformation[J].Planta Med. 2025(1): 40-61.
[66]Sevimli-Gür C, Onbaşılar I, Atilla P,et al. In vitro growth stimulatory and in vivo wound healing studies on cycloartane-type saponins of Astragalus genus[J]. Ethnopharmacol. 2011(4): 844-50.
[67]Lee SY, Chang WL, Li ZX, et al Astragaloside VI and cycloastragenol-6-O-beta-D-glucoside promote wound healing in vitro and in vivo[J]. Phytomedicine. 2018(1): 183-191.
[68]Cao Y, Xu L, Yang X, et al. The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro[J]. Biomed Res Int. 2019(12): 7023950.
[69]Subash J, Alexander T, Beamer V, et al. A proposed mechanism for central centrifugal cicatricial alopecia[J]. Exp Dermatol. 2020(2): 190-195.
[70]Zhou C, Li X, Wang C, et al. Alopecia Areata: an Update on Etiopathogenesis, Diagnosis, and Management[J]. Clin Rev Allergy Immunol. 2021(12): 403-423.
[71]Devjani S, Ezemma O, Kelley KJ, et al. Androgenetic Alopecia: Therapy Update[J]. Drugs. 2023(6): 701-715.
[72]Starace M, Orlando G, Alessandrini A, et al. Female Androgenetic Alopecia: An Update on Diagnosis and Management[J]. Clin Dermatol.2020(2): 69-84.
[73]Gupta AK, Talukder M, Venkataraman M, et al. Minoxidil: a comprehensive review[J]. J Dermatolog Treat. 2022(6): 1896-1906.
[74]Chen G, Wang W, Guan B, et al. Cycloastragenol reduces inflammation in CLP-induced septic MICE by suppressing TLR4 signaling pathways[J]. Phytomedicine. 2025(7): 156645.
[75]Salvador L, Singaravelu G, Harley CB, et al. A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized,
Double Blind, and Placebo Controlled Study[J]. Rejuvenation Res. 2016(12): 478-484.
[77]Song X, Luo Y, Zhao W,et al. Preparation and Characterization of Lutein Co-Amorphous Formulation with Enhanced Solubility and Dissolution[J]. Foods. 2024(6): 2029.
[78]Shoviantari F, Erawati T, Soeratri W. Coenzyme Q10 nanostructured lipid carriers as an inducer of the skin fibroblast cell and its irritability test in a mice model[J]. Basic Clin Physiol Pharmacol. 2019(12): 30.
[79]Chen D, Song T, Liu Y, et al. Effective Hydrogel Vascular Patch Dual-Loaded with Cycloastragenol Nanostructured Lipid Carriers and Doxycycline for Repairing Extravascular Injury in Abdominal Aortic
Aneurysm[J]. Adv Healthc Mater. 2025(4): 2402497.
[80]Pozos-Nonato S, Domínguez-Delgado CL, Campos-Santander KA, et al. Novel Nanotechnological Strategies for Skin Anti-aging[J].Curr Pharm Biotechnol. 2023(11): 1397-1419.
[81]Kwak G, Grewal A, Slika H, et al. Brain Nucleic Acid Delivery and Genome Editing via Focused Ultrasound-Mediated Blood-Brain
Barrier Opening and Long-Circulating Nanoparticles[J]. ACS Nano.2024(9): 24139-24153.
[82]Tang L, Li X, Qin Y, et al. The construction of oligonucleotidecycloastragenol and the renoprotective effect study[J]. Front Bioeng Biotechnol. 2022(11):1027517.