(-)-α-Bisabolol inhibits D-Gal-induced HSF cellular senescence in vitro and prevents skin aging in vivo by reducing SASP

Document Type : Original Article

Authors

1 The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China

2 Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China

3 Research and Development Department, Guangzhou Qinglan Biotechnology Company Limited, Guangzhou, China

4 State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China

5 Guangdong Academy of Traditional Chinese Medicine, Research Team of Bio-molecular and System Biology of Chinese Medicine, Guangzhou, China

6 Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China

7 Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China

Abstract

Objective(s): To study the anti-aging effect of (-)-α-bisabolol ((-)-α-bis) on the skin and preliminarily clarify its mechanism. 
Materials and Methods: Human skin fibroblasts (HSF) were induced senescence by D-Galactose. Senescence β-galactosidase staining was utilized to evaluate the senescence of HSF. TNF-α, IL-6, IL-8, IL-1β, CCL-2, CCL-5, and MMP-9 in senescence-as-sociated secretory phenotype (SASP) were detected by RT-qPCR. Meanwhile, aged BALB/c mice were applied topically with 0.5% and 2%(-)-α-bis gel for 30 days continuously to evaluate anti-aging parameters on the skin such as surface measurement, the Trans Epidermal Water Loss (TEWL), and skin barrier index of dorsal skin. Then, HE staining, Masson staining, and IHC were applied to measure epidermal thickness, collagen fiber content in the dermis, and content of dermal collagen I, respectively. Last, SOD, MDA, and HYP contents of the back skin tissue of mice were also detected. 
Results: (-)-α-Bis reduced the expression of senescence-associated β-galactosidase (SA-β-gal) and expression levels of SASP in HSF cells stimulated by D-Gal (P<0.05). Mice aged 9 months were applied locally with (-)-α-bis gel to improve skin aging, the TEWL and skin barrier index of dorsal skin, and ameliorate the epidermal thickness and contents of dermal collagen fibers and collagen I (P<0.05). Furthermore, (-)-α-bis up-regulated the mRNA expression levels of elastin and collagen III effectively (P<0.05). 
Conclusion: (-)-α-Bis can delay the senescence of HSF cells by reducing the expression of SA-β-gal and SASP factors in vitro. Improved skin barrier function as well as SASP is responsible for the delay of skin aging in vivo.

Keywords

Main Subjects

References

1. Zouboulis CC, Ganceviciene R, Liakou AI, Theodoridis A, Elewa R, Makrantonaki E. Aesthetic aspects of skin aging, prevention, and local treatment. Clin Dermatol 2019; 37: 365-372.
2. Guida S, Pellacani G, Ciardo S, Longo C. Reflectance confocal microscopy of aging skin and skin cancer. Dermatol Pract Concept 2021; 11: e2021068.
3. Franco AC, Aveleira C, Cavadas C. Skin senescence: Mechanisms and impact on whole-body aging. Trends Mol Med 2022; 28: 97-109.
4. Qian J, Wang X, Cao J, Zhang W, Lu C, Chen X. Dihydromyricetin attenuates D-galactose-induced brain aging of mice via inhibiting oxidative stress and neuroinflammation. Neurosci Lett 2021; 756: 135963.
5. Meeran MFN, Laham F, Al-Taee H, Azimullah S, Ojha S. Protective effects of α-bisabolol on altered hemodynamics, lipid peroxidation, and nonenzymatic antioxidants in isoproterenol-induced myocardial infarction: In vivo and in vitro evidences. J Biochem Mol Toxicol 2018; 32: e22200.
6. Maurya AK, Singh M, Dubey V, Srivastava S, Luqman S, Bawankule DU. α-(-)-bisabolol reduces pro-inflammatory cytokine production and ameliorates skin inflammation. Curr Pharm Biotechnol 2014; 15: 173-181.
7. Nagoor Meeran MF, Azimullah S, Laham F, Tariq S, Goyal SN, Adeghate E, et al. α-Bisabolol protects against β-adrenergic agonist-induced myocardial infarction in rats by attenuating inflammation, lysosomal dysfunction, NLRP3 inflammasome activation and modulating autophagic flux. Food Funct 2020; 11: 965-976.
8. Wu S, Peng L, Sang H, Ping Li Q, Cheng S. Anticancer effects of α-bisabolol in human non-small cell lung carcinoma cells are mediated via apoptosis induction, cell cycle arrest, inhibition of cell migration and invasion and upregulation of P13K/AKT signalling pathway. J BUON 2018; 23: 1407-1412.
9. Leong HJ, Jang I, Hyun KS, Jung SK, Hong GH, Jeong HA, et al. Preparation of alpha-bisabolol and phenylethyl resorcinol/TiO2 hybrid composites for potential applications in cosmetics. Int J Cosmet Sci 2016; 38: 524–534.
10. Cao C, Xiao Z, Wu Y, Ge C. Diet and skin aging-from the perspective of food nutrition. Nutrients 2020; 12: 870-894.
11. Gu Y, Han J, Jiang C, Zhang Y. Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 2020; 59: 101036.
12. Shin S, Cho SH, Park D, Jung E. Anti-skin aging properties of protocatechuic acid in vitro and in vivo. J Cosmet Dermatol 2020; 19: 977-984.
13. Api AM, Belsito D, Biserta S, Botelho D, Bruze M, Burton GA Jr, et al. RIFM fragrance ingredient safety assessment, α-bisabolol, CAS registry number 515-69-5. Food Chem Toxicol 2020; 141: 111238.
14. Noren Hooten N, Evans MK. Techniques to induce and quantify cellular senescence. J Vis Exp 2017; 123: 55533.
15. Waldera Lupa DM, Kalfalah F, Safferling K, Boukamp P, Poschmann G, Volpi E, et al. Characterization of skin aging-associated secreted proteins (SAASP) produced by dermal fibroblasts isolated from intrinsically aged human skin. J Invest Dermatol 2015; 135: 1954-1968.
16. Hari P, Acosta JC. Detecting the senescence-associated secretory phenotype (SASP) by high content microscopy analysis. Methods Mol Biol 2017; 1534: 99-109.
17. Jiang Y, Dong G, Song Y. Nucleus pulposus cell senescence is alleviated by resveratrol through regulating the ROS/NF-κB pathway under high-magnitude compression. Biosci Rep 2018; 38: BSR20180670.
18. Lim TG, Kim YA, Kim JE, Baek S, Lee SY, Lee CC, et al. PKCι is a target of 7,8,4’-trihydroxyisoflavone for the suppression of UVB-induced MMP-1 expression. Exp Dermatol 2018; 27: 449-452.
19. Obrador E, Liu-Smith F, Dellinger RW, Salvador R, Meyskens FL, Estrela JM. Oxidative stress and antioxidants in the pathophysiology of malignant melanoma. Biol Chem 2019; 400: 589-612.
20. Kong SZ, Li DD, Luo H, Li WJ, Huang YM, Li JC, et al. Anti-photoaging effects of chitosan oligosaccharide in ultraviolet-irradiated hairless mouse skin. Exp Gerontol 2018; 103: 27-34.
21. Gendrisch F, Esser PR, Schempp CM, Wölfle U. Luteolin as a modulator of skin aging and inflammation. Biofactors 2021; 47: 170-180.
22. Borodkina AV, Deryabin PI, Giukova AA, Nikolsky NN. “Social Life” of senescent cells: what is SASP and why study it? Acta Naturae 2018; 10: 4-14.
23. Wu X, Yang J, Na T, Zhang K, Davidoff AM, Yuan BZ, et al. RIG-I and IL-6 are negative-feedback regulators of STING induced by double-stranded DNA. PLoS One 2017; 12: e0182961.
24. Kovtonyuk LV, Caiado F, Garcia-Martin S, Manz EM, Helbling P, Takizawa H, et al. IL-1 mediates microbiome-induced inflammaging of hematopoietic stem cells in mice. Blood 2022; 139: 44-58.
25. Storer M, Mas A, Robert-Moreno A, Pecoraro M, Ortells MC, Di Giacomo V, et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 2013; 155: 1119-1130.
26. Franco AC, Aveleira C, Cavadas C. Skin senescence: mechanisms and impact on whole-body aging. Trends Mol Med 2022; 28: 97-109.
27. Zhao XD, Huang C, Wang RX, Wang SA. DUSP22 promotes senescence of HS-1 skin cancer cells through triggering MAPK signaling pathway. Eur Rev Med Pharmacol Sci 2021; 25: 1163.
28. Jin XJ, Kim EJ, Oh IK, Kim YK, Park CH, Chung JH. Prevention of UV-induced skin damages by 11,14,17-eicosatrienoic acid in hairless mice in vivo. J Korean Med Sci 2010; 25: 930-937. 
29. Rittié L, Fisher GJ. Natural and sun-induced aging of human skin. Cold Spring Harb Perspect Med 2015; 5: a015370. 
30. Kim JA, Lee JE, Kim JH, Lee HJ, Kang NJ. Penta-1,2,3,4,6-O-Galloyl-β-D-Glucose inhibits UVB-induced photoaging by targeting PAK1 and JNK1. Antioxidants (Basel) 2019; 8: 561-580.
Iranian Journal of Basic Medical Sciences
Volume 27, Issue 9
September 2024
Pages 1105-1114

Files

Share

How to cite

Statistics