Paeoniflorin inhibits proliferation and promotes autophagy and apoptosis of sweat gland cells

Xu,Yuan; He,Hong; Li,Ping; Liu,Hongwei

doi:10.3892/etm.2021.10975

Paeoniflorin inhibits proliferation and promotes autophagy and apoptosis of sweat gland cells

Authors:
- Yuan Xu
- Hong He
- Ping Li
- Hongwei Liu
View Affiliations

Affiliations: Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China, Health Care and Physical Examination Center, The First Affliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Plastic Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
Published online on: November 16, 2021 https://doi.org/10.3892/etm.2021.10975
Article Number: 53
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Axillary bromhidrosis is sweat excreted by apocrine glands in the armpits, mouth corners and other parts. The clinical manifestation includes excessive sweating and heavy odor, leading to the growth of bacteria and skin disease. The present study investigated the mechanism underlying the effect of paeoniflorin (PF) in the treatment of bromhidrosis. PF was injected into the feet of rats, and the foot skin was dissected for histological analysis. Primary human sweat gland cells (hSGCs) were isolated from patients with bromhidrosis. After 24 h treatment with PF or 3‑methyladenine, the production of reactive oxygen species (ROS), autophagy, apoptosis, proliferation and cell cycle distribution were determined. PF induced nuclear pyknosis in rat SGCs. In vitro PF treatment inhibited cell proliferation with a 25% inhibitory concentration of 9.530 µM. Treatment with 9.530 µM PF for 24 h significantly increased apoptosis, ROS production and autophagy in hSGCs. PF promoted LC3B and Beclin 1 expression, but inhibited p62, phosphorylated (p)‑PI3K and p‑Akt expression. 3‑methyladenine treatment reversed PF‑induced changes in hSGCs. PF‑induced inhibition of hSGC proliferation was associated with ROS production, apoptosis, and autophagy. These findings provide a basis for treating bromhidrosis.

View Figures

View References

1	Hsu KC and Wang KY: Sparing subcutaneous septa avoids skin necrosis in the treatment of axillary bromhidrosis with suction-curettage shaving. J Cosmet Dermatol. 18:892–896. 2019.PubMed/NCBI View Article : Google Scholar
2	Ardon CB, Molenaar C, van Straalen KR, Scholtes VC, Prens EP and van der Zee HH: High prevalence of hidradenitis suppurativa in patients with perianal fistula. Int J Colorectal Dis. 34:1337–1339. 2019.PubMed/NCBI View Article : Google Scholar
3	Van TN, Manh TN, Minh PPT, Minh TT, Huu ND, Cao KP, Huu QN, Cam VT, Huyen ML, Hau KT, et al: The Effectiveness of Local Surgical Technique in Treatment of Axillary Bromhidrosis. Open Access Maced J Med Sci. 7:187–191. 2019.PubMed/NCBI View Article : Google Scholar
4	He J, Wang T and Dong J: A close positive correlation between malodor and sweating as a marker for the treatment of axillary bromhidrosis with Botulinum toxin A. J Dermatolog Treat. 23:461–464. 2012.PubMed/NCBI View Article : Google Scholar
5	Kataoka A: Surgical treatment of bromhidrosis. Rev Bras Cir Plást. 32:377–382. 2001.
6	Coronado MS and Opi JT: Assessment of axillary hyperhidrosis and bromhidrosis treatment with microwave technology. J Surg Med. 3:447–451. 2019.
7	Mao GY, Yang SL and Zheng JH: Etiology and management of axillary bromidrosis: A brief review. Int J Dermatol. 47:1063–1068. 2008.PubMed/NCBI View Article : Google Scholar
8	Mancini M, Panasiti V, Devirgiliis V, Pietropaolo V, Fioriti D, Nicosia R, Curzio M, Roberti V, Gobbi S, Bottoni U, et al: Bromhidrosis induced by sphingomonas paucimobilis: A case report. Int J Immunopathol Pharmacol. 22:845–848. 2009.PubMed/NCBI View Article : Google Scholar
9	Hashmonai M, Cameron AEP, Connery CP, Perin N and Licht PB: The etiology of primary hyperhidrosis: A systematic review. Clin Auton Res. 27:379–383. 2017.PubMed/NCBI View Article : Google Scholar
10	Zhang Y, Hu S, Ge S, Wang J and He L: Paeoniflorin inhibits IgE-mediated allergic reactions by suppressing the degranulation of mast cells though binding with FcεRI alpha subunits. Eur J Pharmacol. 886(173415)2020.PubMed/NCBI View Article : Google Scholar
11	Qian X, Shi X and Wang H: Effect of paeoniflorin on the calcium ion concentration in salivary gland cells using confocal laser scanning microscopy. Am J Transl Res. 8:3678–3688. 2016.PubMed/NCBI
12	Manayi A, Omidpanah S, Barreca D, Ficarra S, Daglia M, Nabavi SF and Nabavi SM: Neuroprotective effects of paeoniflorin in neurodegenerative diseases of the central nervous system. Phytochem Rev. 16:1173–1181. 2017.
13	Cao B-Y, Yang Y-P, Luo W-F, Mao CJ, Han R, Sun X, Cheng J and Liu CF: Paeoniflorin, a potent natural compound, protects PC12 cells from MPP+ and acidic damage via autophagic pathway. J Ethnopharmacol. 131:122–129. 2010.PubMed/NCBI View Article : Google Scholar
14	Wu X, Sun X, Zhao C, Zhang J and Wang X, Zhang A and Wang X: Exploring the pharmacological effects and potential targets of paeoniflorin on the endometriosis of cold coagulation and blood stasis model rats by ultra-performance liquid chromatography tandem mass spectrometry with a pattern recognition approach. RSC Advances. 9:20796–20805. 2019.
15	Hu H, Zhu Q, Su J, Wu Y, Zhu Y, Wang Y, Fang H, Pang M, Li B, Chen S, et al: Effects of an enriched extract of paeoniflorin, a monoterpene glycoside used in Chinese herbal medicine, on cholesterol metabolism in a hyperlipidemic rat model. Med Sci Monit. 23:3412–3427. 2017.PubMed/NCBI View Article : Google Scholar
16	Zhang L, Yang B and Yu B: Paeoniflorin protects against nonalcoholic fatty liver disease induced by a high-fat diet in mice. Biol Pharm Bull. 38:1005–1011. 2015.PubMed/NCBI View Article : Google Scholar
17	Chen J-Y, Wu H-X, Chen Y, Zhang LL, Wang QT, Sun WY and Wei W: Paeoniflorin inhibits proliferation of fibroblast-like synoviocytes through suppressing G-protein-coupled receptor kinase 2. Planta Med. 78:665–671. 2012.PubMed/NCBI View Article : Google Scholar
18	Qian G, Cao J, Chen C, Wang L, Huang X, Ding C, Cai X, Yin F, Chu J, Li G, et al: Paeoniflorin inhibits pulmonary artery smooth muscle cells proliferation via upregulating A2B adenosine receptor in rat. PLoS One. 8(e69141)2013.PubMed/NCBI View Article : Google Scholar
19	Ferry B, Gervasoni D and Vogt C: Regulatory and Ethical Considerations. In: Stereotaxic Neurosurgery in Laboratory Rodent. Springer, Paris, pp1-18, 2014.
20	Turkki R, Linder N, Kovanen PE, Pellinen T and Lundin J: Identification of immune cell infiltration in hematoxylin-eosin stained breast cancer samples: texture-based classification of tissue morphologies. In: Proceedings of SPIE - The International Society for Optical Engineering 9791. Medical Imaging 2016: Digital Pathology, San Diego, p9791, 2016.
21	Park Y-J and Shin M-S: What is the best method for treating osmidrosis? Ann Plast Surg. 47:303–309. 2001.PubMed/NCBI View Article : Google Scholar
22	Huang Z, Zhen Y, Yin W, Ma Z and Zhang L: Shh promotes sweat gland cell maturation in three-dimensional culture. Cell Tissue Bank. 17:317–325. 2016.PubMed/NCBI View Article : Google Scholar
23	Kolakshyapati P, Li X, Chen C, Zhang M, Tan W, Ma L and Gao C: Gene-activated matrix/bone marrow-derived mesenchymal stem cells constructs regenerate sweat glands-like structure in vivo. Sci Rep. 7(17630)2017.PubMed/NCBI View Article : Google Scholar
24	Kurata R, Futaki S, Nakano I, Fujita F, Tanemura A, Murota H, Katayama I, Okada F and Sekiguchi K: Three-dimensional cell shapes and arrangements in human sweat glands as revealed by whole-mount immunostaining. PLoS One. 12(e0178709)2017.PubMed/NCBI View Article : Google Scholar
25	Huang J, Qiu L, Ding L, Wang S, Wang J, Zhu Q, Song F and Hu J: Ginsenoside Rb1 and paeoniflorin inhibit transient receptor potential vanilloid-1-activated IL-8 and PGE₂ production in a human keratinocyte cell line HaCaT. Int Immunopharmacol. 10:1279–1283. 2010.PubMed/NCBI View Article : Google Scholar
26	Wen J, Xu B, Sun Y, Lian M, Li Y, Lin Y, Chen D, Diao Y, Almoiliqy M and Wang L: Paeoniflorin protects against intestinal ischemia/reperfusion by activating LKB1/AMPK and promoting autophagy. Pharmacol Res. 146(104308)2019.PubMed/NCBI View Article : Google Scholar
27	Wang Y, Che J, Zhao H, Tang J and Shi G: Paeoniflorin attenuates oxidized low-density lipoprotein-induced apoptosis and adhesion molecule expression by autophagy enhancement in human umbilical vein endothelial cells. J Cell Biochem. 120:9291–9299. 2019.PubMed/NCBI View Article : Google Scholar
28	Sun X, Cao Y-B, Hu L-F, Yang YP, Li J, Wang F and Liu CF: ASICs mediate the modulatory effect by paeoniflorin on α-synuclein autophagic degradation. Brain Res. 1396:77–87. 2011.PubMed/NCBI View Article : Google Scholar
29	Chen Y, Du X, Zhou Y, Zhang Y, Yang Y, Liu Z, Liu C and Xie Y: Paeoniflorin protects HUVECs from AGE-BSA-induced injury via an autophagic pathway by acting on the RAGE. Int J Clin Exp Pathol. 8:53–62. 2015.PubMed/NCBI
30	Li W, Zhi W, Liu F, Zhao J, Yao Q and Niu X: Paeoniflorin inhibits VSMCs proliferation and migration by arresting cell cycle and activating HO-1 through MAPKs and NF-κB pathway. Int Immunopharmacol. 54:103–111. 2018.PubMed/NCBI View Article : Google Scholar
31	Zheng Y-B, Xiao G-C, Tong S-L, Ding Y, Wang QS, Li SB and Hao ZN: Paeoniflorin inhibits human gastric carcinoma cell proliferation through up-regulation of microRNA-124 and suppression of PI3K/Akt and STAT3 signaling. World J Gastroenterol. 21:7197–7207. 2015.PubMed/NCBI View Article : Google Scholar
32	Zhao Y, Zhou G, Wang J, Jia L, Zhang P, Li R, Shan L, Liu B, Song X, Liu S, et al: Paeoniflorin protects against ANIT-induced cholestasis by ameliorating oxidative stress in rats. Food Chem Toxicol. 58:242–248. 2013.PubMed/NCBI View Article : Google Scholar
33	Wagner G, Lindroos-Christensen J, Einwallner E, Husa J, Zapf TC, Lipp K, Rauscher S, Gröger M, Spittler A, Loewe R, et al: HO-1 inhibits preadipocyte proliferation and differentiation at the onset of obesity via ROS dependent activation of Akt2. Sci Rep. 7(40881)2017.PubMed/NCBI View Article : Google Scholar
34	Mittler R: ROS are good. Trends Plant Sci. 22:11–19. 2017.PubMed/NCBI View Article : Google Scholar
35	Wang X, Liu JZ, Hu JX, Wu H, Li YL, Chen HL, Bai H and Hai CX: ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation. Free Radic Biol Med. 51:539–551. 2011.PubMed/NCBI View Article : Google Scholar
36	Ruiz-Ramos R, Lopez-Carrillo L, Rios-Perez AD, De Vizcaya-Ruíz A and Cebrian ME: Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-kappaB activation and cell proliferation in human breast cancer MCF-7 cells. Mutat Res. 674:109–115. 2009.PubMed/NCBI View Article : Google Scholar
37	Kadowaki H, Nishitoh H, Urano F, Sadamitsu C, Matsuzawa A, Takeda K, Masutani H, Yodoi J, Urano Y, Nagano T, et al: Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation. Cell Death Differ. 12:19–24. 2005.PubMed/NCBI View Article : Google Scholar
38	Poillet-Perez L, Despouy G, Delage-Mourroux R and Boyer-Guittaut M: Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy. Redox Biol. 4:184–192. 2015.PubMed/NCBI View Article : Google Scholar
39	Li HY, Zhang J, Sun LL, Li BH, Gao HL, Xie T, Zhang N and Ye ZM: Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells: An in vitro and in vivo study. Cell Death Dis. 6(e1604)2015.PubMed/NCBI View Article : Google Scholar
40	Liu D, Lin J, Su J, Chen X, Jiang P and Huang K: Glutamine deficiency promotes PCV2 infection through induction of autophagy via activation of ROS-mediated JAK2/STAT3 signaling pathway. J Agric Food Chem. 66:11757–11766. 2018.PubMed/NCBI View Article : Google Scholar
41	Borodkina AV, Shatrova AN, Deryabin PI, Griukova AA, Abushik PA, Antonov SM, Nikolsky NN and Burova EB: Calcium alterations signal either to senescence or to autophagy induction in stem cells upon oxidative stress. Aging (Albany NY). 8:3400–3418. 2016.PubMed/NCBI View Article : Google Scholar