Protective Effects of Lanostane Triterpenoids from Chaga Mushroom in Human Keratinocytes, HaCaT Cells, Against Inflammatory and Oxidative Stresses

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Aug 26

PMID 37628993

Authors

Jihyun Park

Thi Minh Nguyet Nguyen

Hyun-Ah Park

My Tuyen Thi Nguyen

Nan-Young Lee

So-Young Ban

Kyu-Been Park

Chang-Kyu Lee

Jaehan Kim

Jong-Tae Park

Affiliations

Soon will be listed here.

Abstract

Inotodiol, a lanostane-type triterpenoid, and many phytochemicals from Chaga mushrooms have been investigated for various allergic diseases. However, the anti-aging and anti-inflammatory activities of inotodiol under different types of oxidative stress and the impact of inotodiol on collagen and hyaluronan synthesis have not been sufficiently studied. Lanostane triterpenoids-rich concentrate, which contained 10% inotodiol as major (inotodiol concentrate), was prepared from Chaga and compared with pure inotodiol in terms of anti-inflammatory activities on a human keratinocyte cell line, HaCaT cells, under various stimulations such as stimulation with ultraviolet (UV) B or tumor necrosis factor (TNF)-α. In stimulation with TNF-α, interleukin (IL)-1β, IL-6, and IL-8 genes were significantly repressed by 0.44~4.0 μg/mL of pure inotodiol. UVB irradiation induced the overexpression of pro-inflammatory cytokines, but those genes were significantly suppressed by pure inotodiol or inotodiol concentrate. Moreover, pure inotodiol/inotodiol concentrate could also modulate the synthesis of collagen and hyaluronic acid by controlling COL1A2 and HAS2/3 expression, which implies a crucial role for pure inotodiol/inotodiol concentrate in the prevention of skin aging. These results illuminate the anti-inflammatory and anti-aging effects of pure inotodiol/inotodiol concentrate, and it is highly conceivable that pure inotodiol and inotodiol concentrate could be promising natural bioactive substances to be incorporated in therapeutic and beautifying applications.

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References

Sinova R, Pavlik V, Ondrej M, Velebny V, Nesporova K . Hyaluronan: A key player or just a bystander in skin photoaging?. Exp Dermatol. 2021; 31(4):442-458. DOI: 10.1111/exd.14491. View

Subedi L, Lee T, Wahedi H, Baek S, Kim S . Resveratrol-Enriched Rice Attenuates UVB-ROS-Induced Skin Aging via Downregulation of Inflammatory Cascades. Oxid Med Cell Longev. 2017; 2017:8379539. PMC: 5576414. DOI: 10.1155/2017/8379539. View

Glamoclija J, Ciric A, Nikolic M, Fernandes A, Barros L, Calhelha R . Chemical characterization and biological activity of Chaga (Inonotus obliquus), a medicinal "mushroom". J Ethnopharmacol. 2015; 162:323-32. DOI: 10.1016/j.jep.2014.12.069. View

Nguyet Nguyen T, Ban S, Park K, Lee C, Lee S, Lee Y . Evaluation of Toxicity and Efficacy of Inotodiol as an Anti-Inflammatory Agent Using Animal Model. Molecules. 2022; 27(15). PMC: 9331631. DOI: 10.3390/molecules27154704. View

Nomura M, Takahashi T, Uesugi A, Tanaka R, Kobayashi S . Inotodiol, a lanostane triterpenoid, from Inonotus obliquus inhibits cell proliferation through caspase-3-dependent apoptosis. Anticancer Res. 2008; 28(5A):2691-6. View

Podgorski R, Wojasinski M, Ciach T . Nanofibrous materials affect the reaction of cytotoxicity assays. Sci Rep. 2022; 12(1):9047. PMC: 9156782. DOI: 10.1038/s41598-022-13002-w. View

Fernandes A, Rodrigues P, Pintado M, Tavaria F . A systematic review of natural products for skin applications: Targeting inflammation, wound healing, and photo-aging. Phytomedicine. 2023; 115:154824. DOI: 10.1016/j.phymed.2023.154824. View

Valeri M, Raffatellu M . Cytokines IL-17 and IL-22 in the host response to infection. Pathog Dis. 2016; 74(9). PMC: 5975231. DOI: 10.1093/femspd/ftw111. View

Kim J, Gao D, Cho C, Hwang I, Kim H, Kang J . A Novel Bioanalytical Method for Determination of Inotodiol Isolated from Inonotus Obliquus and Its Application to Pharmacokinetic Study. Plants (Basel). 2021; 10(8). PMC: 8401913. DOI: 10.3390/plants10081631. View

10.

Fulop T, Larbi A, Pawelec G, Khalil A, Cohen A, Hirokawa K . Immunology of Aging: the Birth of Inflammaging. Clin Rev Allergy Immunol. 2021; 64(2):109-122. PMC: 8449217. DOI: 10.1007/s12016-021-08899-6. View

11.

Pajak J, Nowicka D, Szepietowski J . Inflammaging and Immunosenescence as Part of Skin Aging-A Narrative Review. Int J Mol Sci. 2023; 24(9). PMC: 10178737. DOI: 10.3390/ijms24097784. View

12.

Bosch R, Philips N, Suarez-Perez J, Juarranz A, Devmurari A, Chalensouk-Khaosaat J . Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals. Antioxidants (Basel). 2016; 4(2):248-68. PMC: 4665475. DOI: 10.3390/antiox4020248. View

13.

Kristensen M, Chu C, Eedy D, Feldmann M, Brennan F, Breathnach S . Localization of tumour necrosis factor-alpha (TNF-alpha) and its receptors in normal and psoriatic skin: epidermal cells express the 55-kD but not the 75-kD TNF receptor. Clin Exp Immunol. 1993; 94(2):354-62. PMC: 1534247. DOI: 10.1111/j.1365-2249.1993.tb03457.x. View

14.

Alves G, de Souza R, Rogez H, Masaki H, Fonseca M . Cecropia obtusa extract and chlorogenic acid exhibit anti aging effect in human fibroblasts and keratinocytes cells exposed to UV radiation. PLoS One. 2019; 14(5):e0216501. PMC: 6505949. DOI: 10.1371/journal.pone.0216501. View

15.

Park Y, Won J, Kim Y, Choi J, Park H, Lee K . In vivo and in vitro anti-inflammatory and anti-nociceptive effects of the methanol extract of Inonotus obliquus. J Ethnopharmacol. 2005; 101(1-3):120-8. DOI: 10.1016/j.jep.2005.04.003. View

16.

Zhang X, Bao C, Zhang J . Inotodiol suppresses proliferation of breast cancer in rat model of type 2 diabetes mellitus via downregulation of β-catenin signaling. Biomed Pharmacother. 2018; 99:142-150. DOI: 10.1016/j.biopha.2017.12.084. View

17.

Ferrucci L, Fabbri E . Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018; 15(9):505-522. PMC: 6146930. DOI: 10.1038/s41569-018-0064-2. View

18.

Nguyen P, Thi Nguyen M, Truong B, Kim D, Shin S, Kim J . Isolation, Physicochemical Characterization, and Biological Properties of Inotodiol, the Potent Pharmaceutical Oxysterol from Chaga Mushroom. Antioxidants (Basel). 2023; 12(2). PMC: 9952744. DOI: 10.3390/antiox12020447. View

19.

Hu L, Nomura S, Sato Y, Takagi K, Ishii T, Honma Y . Anti-inflammatory effects of differential molecular weight Hyaluronic acids on UVB-induced calprotectin-mediated keratinocyte inflammation. J Dermatol Sci. 2022; 107(1):24-31. DOI: 10.1016/j.jdermsci.2022.06.001. View

20.

Qin Z, Okubo T, Voorhees J, Fisher G, Quan T . Elevated cysteine-rich protein 61 (CCN1) promotes skin aging via upregulation of IL-1β in chronically sun-exposed human skin. Age (Dordr). 2013; 36(1):353-64. PMC: 3889915. DOI: 10.1007/s11357-013-9565-4. View