Home Food Science and Human Wellness Article
PDF (7.2 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Figures (5)

Tables (3)
Table 1
Table 2
Table 3
Open Access

Dendrobium officinale flowers flavonoids enriched extract protects against acute ethanol-induced gastric ulcers via AMPK/PI3K signaling pathways

Zhiyu Zhanga, Hualing Xiea, Mohamed A. Faragb, Zhenhao Lic, Qingping Wud, Ping Shaoa,e()
Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014, China
Pharmacognosy Department, College of Pharmacy, Cairo University, Cairo 12613, Egypt
Zhejiang ShouXianGu Botanical Drug Institute Co., Ltd., Hangzhou 321200, China
Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China
Eco-Industrial Innovation Institute Zhejiang University of Technology, Quzhou 324000, China

Peer review under responsibility of Tsinghua University Press.

Show Author Information

Highlights

• Dendrobium officinale flowers flavonoids (DOFF) prevent alcoholic gastric ulcers through antioxidant and regulates autophagy.

• DOFF (< 640 μg/mL) showed no toxicity effect on GES-1 cells with protective effect in ethanol damage model.

• DOFF regulates autophagy through AMPK/mTOR/ULK1 and PI3K/AKT signaling pathways.

Graphical Abstract

View original image Download original image

Abstract

Gastric ulcer is a widespread disease caused by various etiologies. Dendrobium officinale flowers exert several health benefits owing to their rich flavonoid content. In this study, protective effects and possible action mechanisms of D. officinale flowers’ flavonoid enriched extract (DOFF) were assessed against gastric ulcer. The result of sodium nitrite-aluminum nitrate colorimetry showed that 52.34% of the total extractive was flavonoid, and ultra-high performance liquid chromatography time of flight mass spectrometer (UPLC-Q-TOF/MS) revealed the presence of 28 components in DOFF of which 14 belonged to flavonoids. In addition, in vivo assay revealed DOFF potential in reducing the formation of ethanol-induced gastric mucosal lesions, with drop-in ulcer index from 64.33 ± 8.76 to 32.00 ± 4.47. Similar results were revealed in human gastric mucosal epithelia cells, with cells viability to increase from 27.2% to 61.6% post DOFF administration. To analyzed the protect effect of DOFF, we used Western blotting and immunofluorometric assay to revealed the expression levels of key proteins in cell pathways. The results showed that DOFF (320 μg/mL) could increase the level of oxidation marker protein (HO-1), apoptosis regulatory protein (Bcl-2) and autophagy marker (LC3β) by 50.84%, 43.85%, and 59.21% compared with ethanol-treated group respectively. Further analyzed of the mitochondrial activity and apoptosis pathway, we found that DOFF appeared to mitigate against ethanol-induced gastric mucosal injury via AMPK/mTOR/ULK1 and PI3K/AKT autophagy signaling pathways.

Keywords

Dendrobium officinale flowerEthanolFlavonoidsGastric injuryAutophagy

Electronic Supplementary Material

Download File(s)
fshw-13-6-3661_ESM.docx (68.5 KB)

References

[1]

R.M. Aman, R.A. Zaghloul, M.S. El-Dahhan, Formulation, optimization and characterization of allantoin-loaded chitosan nanoparticles to alleviate ethanol-induced gastric ulcer: in-vitro and in-vivo studies, Sci. Rep. 11(1) (2021) 2216. https://doi.org/10.1038/s41598-021-81183-x.

Crossref Google Scholar
[2]

C. Harsha, K. Banik, D. Bordoloi, et al., Antiulcer properties of fruits and vegetables: a mechanism based perspective, Food Chem. Toxicol. 108 (2017) 104-119. https://doi.org/10.1016/j.fct.2017.07.023.

Crossref Google Scholar
[3]

R.Q. Yang, H. Mao, L.Y. Huang, et al., Effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality: a clinical observation study, World J. Gastroenterol. 23(7) (2017) 1268-1277. https://doi.org/10.3748/wjg.v23.i7.1268.

Crossref Google Scholar
[4]

B. Liu, X. Feng, J. Zhang, et al., Preventive effect of Anji White tea flavonoids on alcohol-induced gastric injury through their antioxidant effects in kunming mice, Biomol. 9(4) (2019) 137. https://doi.org/10.3390/biom9040137.

Crossref Google Scholar
[5]

J.L. Wallace, Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? Physiol. Rev. 88(4) (2008) 1547-1565. https://doi.org/10.1152/physrev.00004.2008.

Crossref Google Scholar
[6]

X. Piao, S. Li, X. Sui, et al., 1-Deoxynojirimycin (DNJ) Ameliorates indomethacin-induced gastric ulcer in mice by affecting NF-kappaB signaling pathway, Front. Pharmacol. 9 (2018) 372. https://doi.org/10.3389/fphar.2018.00372.

Crossref Google Scholar
[7]

X. Chang, F. Luo, W. Jiang, et al., Protective activity of salidroside against ethanol-induced gastric ulcer via the MAPK/NF-κB pathway in vivo and in vitro, Int. Immunopharmacol. 28(1) (2015) 604-615. https://doi.org/10.1016/j.intimp.2015.07.031.

Crossref Google Scholar
[8]

E. Yuan, Y. Lian, Q. Li, et al., Roles of Adinandra nitida (Theaceae) and camellianin A in HCl/ethanol-induced acute gastric ulcer in mice, Food Sci. Hum. Wellness 11(4) (2022) 1053-1063. https://doi.org/10.1016/j.fshw.2022.03.032.

Crossref Google Scholar
[9]
M. Abebaw, B. Mishra, D.A. Gelayee, Evaluation of anti-ulcer activity of the leaf extract of Osyris quadripartita Decne.(Santalaceae) in rats, J. Exp. Pharmacol. 9 (2017) 1-11. https://doi.org/10.2147%2FJEP.S125383.
Crossref
[10]

A.I. Elshamy, A.R.H. Farrag, I.M. Ayoub, et al., UPLC-qTOF-MS phytochemical profile and antiulcer potential of Cyperus conglomeratus Rottb. alcoholic extract, Molecules 25(18) (2020) 4234. https://doi.org/10.3390/molecules25184234.

Crossref Google Scholar
[11]

L. Yan, X. Wang, H. Liu, et al., The genome of Dendrobium officinale illuminates the biology of the important traditional Chinese orchid herb, Mol. Plant 8(6) (2015) 922-934. https://doi.org/10.1016/j.molp.2014.12.011.

Crossref Google Scholar
[12]

S.G. Zheng, Y.D. Hu, R.X. Zhao, et al., Genome-wide researches and applications on Dendrobium, Planta 248(4) (2018) 769-784. https://doi.org/10.1007/s00425-018-2960-4.

Crossref Google Scholar
[13]

T. Zhao, S. Zheng, Y. Hu, et al., Classification of interspecific and intraspecific species by genome-wide SSR markers on Dendrobium, S. Afr. J. Bot. 127 (2019) 136-146. https://doi.org/10.1016/j.sajb.2019.08.051.

Crossref Google Scholar
[14]

T. Takamiya, P. Wongsawad, N. Tajima, et al., Identification of Dendrobium species used for herbal medicines based on ribosomal DNA internal transcribed spacer sequence, Biol. Pharm. Bull. 34(5) (2011) 779-782. https://doi.org/10.1248/bpb.34.779.

Crossref Google Scholar
[15]

G.Y. Lv, M.Q. Yan, S.H. Chen, Review of pharmacological activities of Dendrobium officinale based on traditional functions, China J. Chin. Mater Med. 38(4) (2013) 489-493.

Google Scholar
[16]

Y. Lam, T.B. Ng, R.M. Yao, et al., Evaluation of chemical constituents and important mechanism of pharmacological biology in Dendrobium plants, Evid. Based. Complement. Alternat. Med. 2015 (2015) 1-25. https://doi.org/10.1155/2015/841752.

Crossref Google Scholar
[17]

T.B. He, Y.P. Huang, L. Yang, et al., Structural characterization and immunomodulating activity of polysaccharide from Dendrobium officinale, Int. J. Biol. Macromol. 83 (2016) 34-41. https://doi.org/10.1016/j.ijbiomac.2015.11.038.

Crossref Google Scholar
[18]

H. Tang, T. Zhao, Y. Sheng, et al., Dendrobium officinale Kimura et Migo: a review on its ethnopharmacology, phytochemistry, pharmacology, and industrialization, Evid. Based. Complement. Alternat. Med. 2017 (2017) 1-19. https://doi.org/10.1155/2017/7436259.

Crossref Google Scholar
[19]

J.A. Teixeira da Silva, E.A. Tsavkelova, S. Zeng, et al., Symbiotic in vitro seed propagation of Dendrobium: fungal and bacterial partners and their influence on plant growth and development, Planta 242(1) (2015) 1-22. https://doi.org/10.1007/s00425-015-2301-9.

Crossref Google Scholar
[20]

M. Zhao, J. Fan, Q. Liu, et al., Phytochemical profiles of edible flowers of medicinal plants of Dendrobium officinale and Dendrobium devonianum, Food Sci. Nutr. 9(12) (2021) 6575-6586. https://doi.org/10.1002/fsn3.2602.

Crossref Google Scholar
[21]

J. Zhang, Z. Fu, Z. Chu, et al., Gastroprotective activity of the total flavones from Abelmoschus manihot (L.) medic flowers, Evid. Based Complement. Alternat. Med. 2020 (2020) 6584945. https://doi.org/10.1155/2020/6584945.

Crossref Google Scholar
[22]

Q. Zeng, C.H. Ko, W.S. Siu, et al., Polysaccharides of Dendrobium officinale Kimura & Migo protect gastric mucosal cell against oxidative damage-induced apoptosis in vitro and in vivo, J. Ethnopharmacol. 208 (2017) 214-224. https://doi.org/10.1016/j.jep.2017.07.006.

Crossref Google Scholar
[23]

Z. Rahman, D. Dwivedi, G. Jena, Ethanol-induced gastric ulcer in rats and intervention of tert-butylhydroquinone: involvement of Nrf2/HO-1 signalling pathway, Hum. Exp. Toxicol. 39(4) (2020) 547-562. https://doi.org/10.1177/0960327119895559.

Crossref Google Scholar
[24]

M. Kanter, O. Coskun, H. Uysal, The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage, Arch. Toxicol. 80 (2006) 217-224. https://doi.org/10.1007/s00204-005-0037-1.

Crossref Google Scholar
[25]

D. Dokmeci, M. Akpolat, N. Aydogdu, et al., L-Carnitine inhibits ethanol-induced gastric mucosal injury in rats, Pharmacol. Rep. 57(4) (2005) 481-488.

Google Scholar
[26]

Y. Yang, B. Yin, L. Lv, et al., Gastroprotective effect of aucubin against ethanol-induced gastric mucosal injury in mice, Life Sci. 189 (2017) 44-51. https://doi.org/10.1016/j.lfs.2017.09.016.

Crossref Google Scholar
[27]

R. Al Batran, F. Al-Bayaty, M.M. Jamil Al-Obaidi, et al., In vivo antioxidant and antiulcer activity of Parkia speciosa ethanolic leaf extract against ethanol-induced gastric ulcer in rats, PLoS ONE 8(5) (2013) e64751. https://doi.org/10.1371/journal.pone.0064751.

Crossref Google Scholar
[28]

S. Yamamoto, K. Watabe, H. Araki, et al., Protective role of adiponectin against ethanol-induced gastric injury in mice, Am. J. Physiol.Gastrointest. Liver Physiol. 302(8) (2012) G773-G780. https://doi.org/10.1152/ajpgi.00324.2011.

Crossref Google Scholar
[29]

H.H. Ye, K.J. Wu, S.J. Fei, et al., Propofol participates in gastric mucosal protection through inhibiting the toll-like receptor-4/nuclear factor kappa-B signaling pathway, Clin. Res. Hepatol. Gastroenterol. 37(1) (2013) e3-e15. https://doi.org/10.1016/j.clinre.2012.03.004.

Crossref Google Scholar
[30]

W. Chang, J. Bai, S. Tian, et al., Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway, Exp. Biol. Med. 242(10) (2017) 1025-1033. https://doi.org/10.1177/1535370216686221.

Crossref Google Scholar
[31]

D. Wu, A.I. Cederbaum, Inhibition of autophagy promotes CYP2E1-dependent toxicity in HepG2 cells via elevated oxidative stress, mitochondria dysfunction and activation of p38 and JNK MAPK, Redox Biol. 1(1) (2013) 552-565. https://doi.org/10.1016/j.redox.2013.10.008.

Crossref Google Scholar
[32]

Y. Ke, L. Zhan, T. Lu, et al., Polysaccharides of Dendrobium officinale Kimura & Migo leaves protect against ethanol-induced gastric mucosal injury via the AMPK/mTOR signaling pathway in vitro and vivo, Front. Pharmacol. 11 (2020) 526349. https://doi.org/10.3389/fphar.2022.948569.

Crossref Google Scholar
[33]

H.H. Arab, A.M. Ashour, A.M. Gad, et al., Activation of AMPK/mTOR-driven autophagy and inhibition of NLRP3 inflammasome by saxagliptin ameliorate ethanol-induced gastric mucosal damage, Life Sci. 280 (2021) 119743. https://doi.org/10.1016/j.lfs.2021.119743.

Crossref Google Scholar
[34]

Q. He, M. Liu, Z. Rong, et al., Rebamipide attenuates alcohol-induced gastric epithelial cell injury by inhibiting endoplasmic reticulum stress and activating autophagy-related proteins, Eur. J. Pharmacol. 922 (2022) 174891. https://doi.org/10.1016/j.ejphar.2022.174891.

Crossref Google Scholar
[35]

W. Cao, J. Li, K. Yang, et al., An overview of autophagy: mechanism, regulation and research progress, Bull. Cancer. 108(3) (2021) 304-322. https://doi.org/10.1016/j.bulcan.2020.11.004.

Crossref Google Scholar
[36]

L. Gong, Q. Pan, N. Yang, Autophagy and inflammation regulation in acute kidney injury, Front. Physiol. 11 (2020) 576463. https://doi.org/10.3389/fphys.2020.576463.

Crossref Google Scholar
[37]

Z. Xu, X. Han, D. Ou, et al., Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy, Appl. Microbiol. Biotechnol. 104(2) (2020) 575-587. https://doi.org/10.1007/s00253-019-10257-8.

Crossref Google Scholar
[38]

C. Cao, W. Huang, N. Zhang, et al., Narciclasine induces autophagy-dependent apoptosis in triple-negative breast cancer cells by regulating the AMPK-ULK1 axis, Cell Prolif. 51(6) (2018) e12518. https://doi.org/10.1111/cpr.12518.

Crossref Google Scholar
[39]

T. Kimura, A. Takahashi, Y. Takabatake, et al., Autophagy protects kidney proximal tubule epithelial cells from mitochondrial metabolic stress, Autophagy 9(11) (2013) 1876-1886. https://doi.org/10.4161/auto.25418.

Crossref Google Scholar
[40]

C.Y. Chen, H.C. Hsu, M.F. Chen, The reduced autophagic response by oxidative stress in angiotensin Ⅱ-induced hypertrophic H9C2 cells causes more apoptotic cell death, Exp. Biol. Med. 239(12) (2014) 1688-1698. https://doi.org/10.1177/1535370214542071.

Crossref Google Scholar
[41]

Z. Luo, Z. Guo, T. Xiao, et al., Enrichment of total flavones and licochalcone A from licorice residues and its hypoglycemic activity, J. Chromatogr. B 1114-1115 (2019) 134-145. https://doi.org/10.1016/j.jchromb.2019.01.026.

Crossref Google Scholar
[42]

X. Ruan, L.M. Zhan, X.X. Gao, et al., Separation and purification of flavonoid from Taxus remainder extracts free of taxoids using polystyrene and polyamide resin, J. Sep. Sci. 36(12) (2013) 1925-1934. https://doi.org/10.1002/jssc.201201189.

Crossref Google Scholar
[43]

X.M. Liu, Y. Liu, C.H. Shan, et al., Effects of five extraction methods on total content, composition, and stability of flavonoids in jujube, Food Chem.: X 14 (2022) 100287. https://doi.org/10.1016/j.fochx.2022.100287.

Crossref Google Scholar
[44]

X.Q. Zhao, S. Guo, H. Yan, et al., Analysis of phenolic acids and flavonoids in leaves of Lycium barbarum from different habitats by ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry, Biomed. Chromatogr. 33(8) (2019) e4552. https://doi.org/10.1002/bmc.4552.

Crossref Google Scholar
[45]

Y.M. Belayneh, G.G. Amare, B.G. Meharie, et al., Evaluation of the antiulcerogenic activity of hydromethanol extracts of Solanum incanum L.(Solanaceae) leaves and roots in mice; single and repeated dose study, Metab. Open 11 (2021) 100119. https://doi.org/10.1016/j.metop.2021.100119.

Crossref Google Scholar
[46]

O.J. Olatunji, H. Chen, Y. Zhou, Anti-ulcerogenic properties of Lycium chinense mill extracts against ethanol-induced acute gastric lesion in animal models and its active constituents, Molecules 20(12) (2015) 22553-22564. https://doi.org/10.3390/molecules201219867.

Crossref Google Scholar
[47]

K. Lin, Y. Wang, J. Gong, et al., Protective effects of total flavonoids from Alpinia officinarum rhizoma against ethanol-induced gastric ulcer in vivo and in vitro, Pharm. Biol. 58(1) (2020) 854-862. https://doi.org/10.1080/13880209.2020.1803370.

Crossref Google Scholar
[48]

P. Guth, D. Aures, G. Paulsen, Topical aspirin plus HCl gastric lesions in the rat: cytoprotective effect of prostaglandin, cimetidine, and probanthine, Gastroenterol 76(1) (1979) 88-93. https://doi.org/10.1016/S0016-5085(79)80133-X.

Crossref Google Scholar
[49]

E. Gugliandolo, M. Cordaro, R. Fusco, et al., Protective effect of snail secretion filtrate against ethanol-induced gastric ulcer in mice, Sci. Rep. 11(1) (2021) 3638. https://doi.org/10.1038/s41598-021-83170-8.

Crossref Google Scholar
[50]

R. Naz, Z. Ahmed, M. Shahzad, et al., Amelioration of rheumatoid arthritis by Anacardium occidentale via inhibition of collagenase and lysosomal enzymes, Evid. Based. Complement. Alternat. Med. 2020 (2020) 8869484. https://doi.org/10.1155/2020/8869484.

Crossref Google Scholar
[51]

N. Nordin, S.M. Salama, S. Golbabapour, et al., Anti-ulcerogenic effect of methanolic extracts from Enicosanthellum pulchrum (King) Heusden against ethanol-induced acute gastric lesion in animal models, PLoS ONE 9(11) (2014) e111925. https://doi.org/10.1371/journal.pone.0111925.

Crossref Google Scholar
[52]

J. Sedlak, R.H. Lindsay, Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent, Anal. Biochem. 25 (1968) 192-205. https://doi.org/10.1016/0003-2697(68)90092-4.

Crossref Google Scholar
[53]

Y. Wang, X. Liu, L. Liang, et al., The protective effect of quinoa on the gastric mucosal injury induced by absolute ethanol, J. Sci. Food Agric. (2022). https://doi.org/10.1002/jsfa.12208.

Crossref Google Scholar
[54]

B. Liao, C. Zhou, T. Liu, et al., A novel Hericium erinaceus polysaccharide: Structural characterization and prevention of H2O2-induced oxidative damage in GES-1 cells, Int. J. Biol. Macromol. 154 (2020) 1460-1470. https://doi.org/10.1016/j.ijbiomac.2019.11.027.

Crossref Google Scholar
[55]

S. Fang, X. Wan, X. Zou, et al., Arsenic trioxide induces macrophage autophagy and atheroprotection by regulating ROS-dependent TFEB nuclear translocation and AKT/mTOR pathway, Cell Death Dis. 12(1) (2021) 1-18. https://doi.org/10.1038/s41419-020-03357-1.

Crossref Google Scholar
[56]

X.J. Luo, B. Liu, Z. Dai, et al., Expression of apoptosis-associated microRNAs in ethanol-induced acute gastric mucosal injury via JNK pathway, Alcohol 47(6) (2013) 481-493. https://doi.org/10.1016/j.alcohol.2013.05.005.

Crossref Google Scholar
[57]

E.L. McConnell, A.W. Basit, S. Murdan, Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments, J. Pharm. Pharmacol. 60(1) (2008) 63-70. https://doi.org/10.1211/jpp.60.1.0008.

Crossref Google Scholar
[58]

M. Beiranvand, S. Bahramikia, Ameliorating and protective effects mesalazine on ethanol-induced gastric ulcers in experimental rats, Eur. J. Pharmacol. 888 (2020) 173573. https://doi.org/10.1016/j.ejphar.2020.173573.

Crossref Google Scholar
[59]

C. Zhang, F. Gao, S. Gan, et al., Chemical characterization and gastroprotective effect of an isolated polysaccharide fraction from Bletilla striata against ethanol-induced acute gastric ulcer, Food Chem. Toxicol. 131 (2019) 110539. https://doi.org/10.1016/j.fct.2019.05.047.

Crossref Google Scholar
[60]

P.C. Gupta, A. Kar, N. Sharma, et al., Protective effect of standardised fruit extract of Garcinia cowa Roxb. ex Choisy against ethanol induced gastric mucosal lesions in Wistar rats, Ann. Med. 53(1) (2021) 1696-1708. https://doi.org/10.1080/07853890.2021.1981548.

Crossref Google Scholar
[61]

H.L. Wu, X. Gao, Z.D. Jiang, et al., Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation, Toxicol. 304 (2013) 41-48. https://doi.org/10.1016/j.tox.2012.11.020.

Crossref Google Scholar
[62]

W.C. Zhao, Y.S. Xu, G. Chen, et al., Veronicastrum axillare alleviates ethanol-induced injury on gastric epithelial cells via downregulation of the NF-κB signaling pathway, Gastroenterol. Res. Pract. 2017 (2017) 7395032. https://doi.org/10.1155/2017/7395032.

Crossref Google Scholar
[63]

T.Y. Wu, J. Liang, J.Y. Ai, et al., Mulberry ethanol extract and rutin protect alcohol-damaged GES-1 cells by inhibiting the MAPK pathway, Molecules 27(13) (2022) 4266. https://doi.org/10.3390/molecules27134266.

Crossref Google Scholar
[64]

Q. Li, Z. Dong, W. Lian, et al., Ochratoxin A causes mitochondrial dysfunction, apoptotic and autophagic cell death and also induces mitochondrial biogenesis in human gastric epithelium cells, Arch. Toxicol. 93(4) (2019) 1141-1155. https://doi.org/10.1007/s00204-019-02433-6.

Crossref Google Scholar
[65]

L. Wang, X. Li, Z. Yang, et al., Crotonaldehyde induces autophagy-mediated cytotoxicity in human bronchial epithelial cells via PI3K, AMPK and MAPK pathways, Environ Pollut. 228 (2017) 287-296. https://doi.org/10.1016/j.envpol.2017.03.083.

Crossref Google Scholar
[66]

D.J. Stewart, R. Ackroyd, Peptic ulcers and their complications, Surgery 29(11) (2011) 568-574. https://doi.org/10.1016/j.mpsur.2011.08.006.

Crossref Google Scholar
[67]

P.A. Rodrigues, S.M. Morais, C.M. Souza, et al., Gastroprotective effect of Byrsonima sericea DC leaf extract against ethanol-induced gastric injury and its possible mechanisms of action, An. Acad. Bras. Cienc. 84 (2012) 113-122. https://doi.org/10.1590/S0001-37652012000100011.

Crossref Google Scholar
[68]

S. Murugesu, J. Selamat, V. Perumal, Phytochemistry, pharmacological properties, and recent applications of Ficus benghalensis and Ficus religiosa, Plants 10(12) (2021) 2749. https://doi.org/10.3390/plants10122749.

Crossref Google Scholar
[69]

A.A. Mariyam, R. Isaac, P. Praseetha, Phytochemical profile and pharmacognistic properties of adhatoda species: a review, Adv. Sci. Eng. Med. 8(9) (2016) 669-675. https://doi.org/10.1166/asem.2016.1898.

Crossref Google Scholar
[70]

M. Indran, A. Mahmood, U. Kuppusamy, Protective effect of Carica papaya L. leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats, West Indian Med. J. 57(4) (2008) 323-326.

Google Scholar
[71]

P.P. Lowe, B. Gyongyosi, A. Satishchandran, et al., Correction: Alcohol-related changes in the intestinal microbiome influence neutrophil infiltration, inflammation and steatosis in early alcoholic hepatitis in mice, PLoS ONE 12(3) (2017) e0174544. https://doi.org/10.1371/journal.pone.0174544.

Crossref Google Scholar
[72]

W. Li, X. Wang, W. Zhi, et al., The gastroprotective effect of nobiletin against ethanol-induced acute gastric lesions in mice: impact on oxidative stress and inflammation, Immunopharmacol. Immunotoxicol. 39(6) (2017) 354-363. https://doi.org/10.1080/08923973.2017.1379088.

Crossref Google Scholar
[73]

C. Yu, X.T. Mei, Y.P. Zheng, et al., Gastroprotective effect of taurine zinc solid dispersions against absolute ethanol-induced gastric lesions is mediated by enhancement of antioxidant activity and endogenous PGE2 production and attenuation of NO production, Eur. J. Pharmacol. 740 (2014) 329-336. https://doi.org/10.1016/j.ejphar.2014.07.014.

Crossref Google Scholar
[74]

D. Gazzieri, M. Trevisani, J. Springer, et al., Substance P released by TRPV1-expressing neurons produces reactive oxygen species that mediate ethanol-induced gastric injury, Free Radical Biol. Med. 43(4) (2007) 581-589. https://doi.org/10.1016/j.freeradbiomed.2007.05.018.

Crossref Google Scholar
[75]

S. Qin, J. Yin, S. Huang, et al., Astragaloside IV protects ethanol-induced gastric mucosal injury by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway apoptosis in rats, Front. Pharmacol. 10 (2019) 894. https://doi.org/10.3389/fphar.2019.00894.

Crossref Google Scholar
[76]

H. Wang, Y. Chen, N. Zhai, et al., Ochratoxin A-induced apoptosis of IPEC-J2 cells through ROS-mediated mitochondrial permeability transition pore opening pathway, J. Agric. Food Chem. 65(48) (2017) 10630-10637. https://doi.org/10.1021/acs.jafc.7b04434.

Crossref Google Scholar
[77]

A. Kumari, P. Kakkar, Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade, Life Sci. 90(15/16) (2012) 561-570. https://doi.org/10.1016/j.lfs.2012.01.012.

Crossref Google Scholar
[78]

D.R. Green, F. Llambi, Cell death signaling, Cold Spring Harbor Perspect. Biol. 7(12) (2015) a006080. https://doi.org/10.1101/cshperspect.a006080.

Crossref Google Scholar
[79]

M.L. Würstle, M.A. Laussmann, M. Rehm, The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome, Exp. Cell Res. 318(11) (2012) 1213-1220. https://doi.org/10.1016/j.yexcr.2012.02.013.

Crossref Google Scholar
[80]

M.C. Maiuri, E. Zalckvar, A. Kimchi, et al., Self-eating and self-killing: crosstalk between autophagy and apoptosis, Nat. Rev. Mol. Cell Biol. 8(9) (2007) 741-752. https://doi.org/10.1038/nrm2239.

Crossref Google Scholar
[81]

S.Y. Lu, S. Guo, S.B. Chai, et al., Autophagy in gastric mucosa: the dual role and potential therapeutic target, BioMed Res. Int. 2021 (2021) 2648065. https://doi.org/10.1155/2021/2648065.

Crossref Google Scholar
[82]

A.K. Abdel-Aziz, C. Stalling, C.K. Tong, Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition), Autophagy 17(1) (2021) 1-382. https://doi.org/10.1080/15548627.2020.1797280.

Crossref Google Scholar
[83]

K. Hou, Q. Yu, X. Hu, et al., Protective effect of Ganoderma atrum polysaccharide on acrolein-induced macrophage injury via autophagy-dependent apoptosis pathway, Food Chem. Toxicol. 133 (2019) 110757. https://doi.org/10.1016/j.fct.2019.110757.

Crossref Google Scholar
[84]

D. Egan, J. Kim, R.J. Shaw, et al., The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR, Autophagy 7(6) (2011) 643-644. https://doi.org/10.4161/auto.7.6.15123.

Crossref Google Scholar
[85]

D. Park, H. Jeong, M.N. Lee, et al., Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition, Sci. Rep. 6 (2016) 21772. https://doi.org/10.1038/srep21772.

Crossref Google Scholar
[86]

W.Q. Cao, X.Q. Zhai, J.W. Ma, et al., Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway, Pharm. Biol. 58(1) (2020) 72-79. https://doi.org/10.1080/13880209.2019.1703756.

Crossref Google Scholar
[87]

S. Ren, Y. Wei, R. Wang, et al., Rutaecarpine ameliorates ethanol-induced gastric mucosal injury in mice by modulating genes related to inflammation, oxidative stress and apoptosis, Front. Pharmacol. 11 (2020) 600295. https://doi.org/10.3389/fphar.2020.600295.

Crossref Google Scholar
[88]

H.H. Arab, S.A. Salama, A.H. Eid, et al., Targeting MAPKs, NF-κB, and PI3K/AKT pathways by methyl palmitate ameliorates ethanol-induced gastric mucosal injury in rats, J. Cell. Physiol. 234(12) (2019) 22424-22438. https://doi.org/10.1002/jcp.28807.

Crossref Google Scholar
[89]

W.T. Jeong, H.B. Lim, Determination and chemical profiling of toxic pyrrolizidine alkaloids in botanical samples with UPLC-Q-TOFMS, Chromatographia 82(11) (2019) 1653-1664. https://doi.org/10.1007/s10337-019-03785-y.

Crossref Google Scholar
[90]

J. Yang, X. Dong, X.T. Zhen, et al., Rapid analysis and identification of flavonoid and organic acid metabolites in Hawthorn using an on-line flow injection assisted electrochemical microreactor combined with quadrupole time-of-flight tandem mass spectrometry, J. Food Compost. Anal. 96 (2021) 103700. https://doi.org/10.1016/j.jfca.2020.103700.

Crossref Google Scholar
[91]

Y.B. Cheng, M.T. Chang, Y.W. Lo, et al., Oxygenated lignans from the fruits of Schisandra arisanensis, J. Nat. Prod. 72(9) (2009) 1663-1668. https://doi.org/10.1021/np9003678.

Crossref Google Scholar
[92]

M. Sui, S. Feng, G. Liu, et al., Deep eutectic solvent on extraction of flavonoid glycosides from Dendrobium officinale and rapid identification with UPLC-triple-TOF/MS, Food Chem. 401 (2023) 134054. https://doi.org/10.1016/j.foodchem.2022.134054.

Crossref Google Scholar
[93]

Z. Ye, J.R. Dai, C.G. Zhang, et al., Chemical differentiation of Dendrobium officinale and Dendrobium devonianum by using HPLC fingerprints, HPLC-ESI-MS, and HPTLC analyses, Evid. Based. Complement. Alternat. Med. 2017 (2017) 9. https://doi.org/10.1155/2017/8647212.

Crossref Google Scholar
[94]

C.B.B. Cazarin, A. Rodriguez-Nogales, F. Algieri, et al., Intestinal anti-inflammatory effects of Passiflora edulis peel in the dextran sodium sulphate model of mouse colitis, J. Funct. Foods 26 (2016) 565-576. https://doi.org/10.1016/j.jff.2016.08.020.

Crossref Google Scholar
[95]

J. Wan, X. Gong, F. Wang, et al., Comparative analysis of chemical constituents by HPLC-ESI-MSn and antioxidant activities of Dendrobium huoshanense and Dendrobium officinale, Biomed. Chromatogr. 36(1) (2022) e5250. https://doi.org/10.1002/bmc.5250.

Crossref Google Scholar
[96]

Y. Tao, H. Cai, W. Li, et al., Ultrafiltration coupled with high-performance liquid chromatography and quadrupole-time-of-flight mass spectrometry for screening lipase binders from different extracts of Dendrobium officinale, Anal. Bioanal. Chem. 407 (2015) 6081-6093. https://doi.org/10.1007/s00216-015-8781-4.

Crossref Google Scholar
[97]

M. Li, Z.Y. Huang, S.S. Cui, et al., Characterization of chemical components and the potential anti-influenza mechanism of Fructus Arctii by a strategy integrating pharmacological evaluations, chemical profiling, serum pharmacochemistry, and network pharmacology, New J. Chem. 46(38) (2022) 18426-18446. https://doi.org/10.1039/D2NJ02799B.

Crossref Google Scholar
[98]

M.A. Farag, D.M. Rasheed, M. Kropf, et al., Metabolite profiling in Trigonella seeds via UPLC-MS and GC-MS analyzed using multivariate data analyses, Anal. Bioanal. Chem. 408 (2016) 8065-8078. https://doi.org/10.1007/s00216-016-9910-4.

Crossref Google Scholar
[99]

G.N.d.M. e Silva, E.S.B. Rodrigues, I.Y.L. de Macêdo, et al., Blackberry jam fruit (Randia formosa (Jacq.) K. Schum): an Amazon superfruit with in vitro neuroprotective properties, Food Biosci. 50 (2022) 102084. https://doi.org/10.1016/j.fbio.2022.102084.

Crossref Google Scholar
[100]

Q. Li, T. Lan, S. He, et al., A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model, Chin. Med. 16(1) (2021) 1-21. https://doi.org/10.1186/s13020-021-00507-1.

Crossref Google Scholar
Food Science and Human Wellness
Volume 13 Issue 6,
November 2024
Pages 3661-3679
DOI: 10.26599/FSHW.2023.9250048
Cite this article:
Zhang Z, Xie H, Farag MA, et al. Dendrobium officinale flowers flavonoids enriched extract protects against acute ethanol-induced gastric ulcers via AMPK/PI3K signaling pathways. Food Science and Human Wellness, 2024, 13(6): 3661-3679. https://doi.org/10.26599/FSHW.2023.9250048
Metrics & Citations  
Article History
Copyright
Rights and Permissions
Return

Antibody protein and manufacturing company.

Reagent name Name of production company Serial Number Place of production
HO-1 antibody Wanleibio WL02400 Shenyang, China
LC3B II/I antibody Wanleibio WL01506 Shenyang, China
Bcl-2 antibody Wanleibio WL01556 Shenyang, China
p-PI3K p85 antibody Affinity Biosciences AF3241 Changzhou, China
PI3K p85 antibody Wanleibio WL02240 Shenyang, China
p-AKT antibody Wanleibio WLP001a Shenyang, China
AKT antibody Wanleibio WL0003b Shenyang, China
p-AMPK antibody Wanleibio WL05103 Shenyang, China
AMPK antibody Wanleibio WL02254 Shenyang, China
p-mTOR antibody Wanleibio WL03694 Shenyang, China
mTOR antibody Wanleibio WL02477 Shenyang, China
p-ULK1 antibody Affinity Biosciences AF4387 Changzhou, China
ULK1 antibody Affinity Biosciences DF7588 Changzhou, China
Beclin-1 antibody Wanleibio WL02508 Shenyang, China
p62 antibody Wanleibio WL02385 Shenyang, China
Goat Anti-Rabbit IgG/HRP Wanleibio WLA023 Shenyang, China
β-Actin Wanleibio WL01372 Shenyang, China

MS data for characterization of compounds in the flowers of D. officinale by UPLC-Q-TOF/MS.

No. Retention time (s) [M–H]– (m/z) Formula Name Class Reference
Note: – Means that the corresponding name was not found in the literature.
1 0.78 293.0968 C17H26O4 Unknown phenol Phenol
2 1.41 312.0952 C16H27NO5 Heliotrine Alkaloid [89]
3 1.83 164.0715 C9H8O3 3-Hydroxycinnamic acid Phenolic acid [90]
4 1.84 328.1402 C16H27NO6 Heliotrine, N-oxide Alkaloid [89]
5 2.18 341.0876 C20H22O5 Arisantetralone A Phenol [91]
6 2.48 325.0922 C18H14O6 5-Hydroxy-7-acetoxy-8-methoxyflavone Flavone
7 3.00 577.1543 C27H30O14 Violanthin Flavone [92-94]
8 3.03 609.1430 C27H30O16 Rutin Flavone [63,92,93,95,96]
9 3.28 593.1485 C27H30O15 Kaempferol-3-O-rutinoside Flavone [63,92]
10 3.30 271.0247 C15H12O5 Naringenin Flavone [92,93,95,96]
11 3.39 563.1390 C26H28O14 Schaftoside Flavone [92-96]
12 3.68 739.1851 C32H34O20 Apigenin-6-C-pentosyl-8-C-(2’’-O-quinoyl)-glucoside Flavonoid [95]
13 4.74 921.2828 – – –
14 4.93 905.2856 – – –
15 5.25 329.2332 C19H22O5 Dihydroconiferyl-dihydro-p-coumarate Phenolic acid [95]
16 5.53 535.2999 C30H32O9 Isolappaol A Phenol [97]
17 5.80 329.2338 C19H22O5 Dihydroconiferyl-dihydro-p-coumarate Phenolic acid [95]
18 6.79 311.2214 C18H16O5 3’, 4’, 7-Trimethoxyflavone Flavone
19 7.89 564.3311 C26H28O14 Vicenin-3 Flavone [98]
20 8.56 566.3461 C26H30O14 Pyrroside B Flavonoid
21 8.63 347.1704 C17H16O8 Hydroxysulochrin Arene
22 9.86 339.2321 C19H16O6 Unknown flavonoid Flavonoid
23 10.11 379.2321 C17H16O10 8-Hydroxy-5-O-β-D-glucopyranosylpsoralen Phenolic glycoside [99]
24 10.91 423.3260 C25H28O6 Unknown flavonoid Flavonoid
25 11.29 327.2892 C19H20O5 Unknown flavonoid Flavonoid
26 11.38 654.3358 – – –
27 12.82 433.2643 C21H22O10 Isoengelitin Flavonoid [100]
28 16.30 595.2889 C32H36O11 9-O-Feruloyl-5,5’-dimethoxylariciresil Lignan

The effects of different dosages of DOFF and Omeprazole on ethanol-induced gastric ulcer.

Group pH UI Ulcer inhibition rate (%)
Note: - Means that the data is not applicable. Data are presented as means ± SD of 6 mice per group. #P < 0.05, ##P < 0.01, ###P < 0.001 vs. Model group; ***P < 0.001 vs. Control group.
Control 3.92 ± 0.58 – –
Model 2.25 ± 0.52*** 64.33 ± 8.76*** –
DOFF (200 mg/kg) 2.67 ± 0.61 44.33 ± 9.31 31.09 ± 14.47
DOFF (400 mg/kg) 2.92 ± 0.58# 32.00 ± 4.47 50.84 ± 6.95#
OME 3.33 ± 0.41## 19.00 ± 7.46## 70.47 ± 11.59###