Novel anti‑hepatitis B virus flavonoids sakuranetin and velutin from<em> Rhus retinorrhoea</em>

Ahmed,Sarfaraz; Parvez,Mohammad K.; Al-Dosari,Mohammed S.; Abdelwahid,Mazin A.S.; Alhowiriny,Tawfeq A.; Al-Rehaily,Adnan J.

doi:10.3892/mmr.2023.13063

Novel anti‑hepatitis B virus flavonoids sakuranetin and velutin from Rhus retinorrhoea

Authors:
- Sarfaraz Ahmed
- Mohammad K. Parvez
- Mohammed S. Al-Dosari
- Mazin A.S. Abdelwahid
- Tawfeq A. Alhowiriny
- Adnan J. Al-Rehaily
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Affiliations: Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980‑8678, Japan
Published online on: August 1, 2023 https://doi.org/10.3892/mmr.2023.13063
Article Number: 176

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Abstract

Drug‑resistance in hepatitis B virus (HBV), especially due to prolonged treatment with nucleoside analogs, such as lamivudine (LAM), remains a clinical challenge. Alternatively, several plant products and isolated phytochemicals have been used as promising anti‑HBV therapeutics with no sign of resistance. Among all known Rhus species, R. coriaria, R. succedanea and R. tripartite have been widely studied for their anti‑HBV efficacy, however, the effects of R. retinorrhoea have not been previously investigated. The current study reported the isolation of two flavonoids, namely sakuranetin (SEK) and velutin (VEL), from the dichloromethane fraction of R. retinorrhoea aerial parts using chromatography and spectral analyses. The two flavonoids (6.25‑50 µg/ml) were pre‑tested for non‑hepatocytotoxicity using an MTT assay and their dose‑ and time‑dependent inhibitory activities against HBV [hepatitis B surface antigen (HBsAg) and hepatitis B ‘e’ antigen (HBeAg)] in cultured HepG2.2.15 cells were assessed by ELISA. SEK and VEL at the selected doses (12.5 µg/ml) significantly inhibited HBsAg by ~58.8 and ~56.4%, respectively, and HBeAg by ~55.5 and ~52.4%, respectively, on day 5. The reference drugs LAM and quercetin (anti‑HBV flavonoids), suppressed the production of HBsAg/HBeAg by ~86.4/~64 and ~84.5/~62%, respectively. Furthermore, molecular docking of the flavonoids with HBV polymerase and capsid proteins revealed the formation of stable complexes with good docking energies, thus supporting their structure‑based antiviral mechanism. In conclusion, the present study was the first to demonstrate the anti‑HBV therapeutic activities of SEK and VEL isolated from R. retinorrhoea.

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1	Rayne S and Mazza G: Biological activities of extracts from sumac (Rhus spp.): A review. Plant Foods Hum Nutr. 62:165–175. 2007. View Article : Google Scholar : PubMed/NCBI
2	Van Wyk BE and Wink M: Medicinal plants of the world. Portland, Oregon, USA: Timber Press; pp. pp4252004
3	Opiyo SA, Njoroge PW, Ndirangu EG and Kuria KM: A review of biological activities and phytochemistry of Rhus species. Am J Chem. 11:28–36. 2021.
4	Itidel C, Chokri M, Mohamed B and Yosr Z: Antioxidant activity, total phenolic and flavonoid content variation among Tunisian natural populations of Rhus tripartite (Ucria) Grande and Rhus pentaphylla desf. Ind Crops Prod. 51:171–177. 2013. View Article : Google Scholar
5	El-Mokasabi FM: The state of the art of traditional herbal medicine in the eastern mediterranean coastal region of Libya. Middle East J Sci Res. 21:575–582. 2014.
6	Shahat AA, Alsaid MS, Rafatullah S, Al-Sohaibani MO, Parvez MK, Al-Dosari MS, Exarchou V and Pieters L: Treatment with Rhus tripartita extract curtails isoproterenol-elicited cardiotoxicity and oxidative stress in rats. BMC Complement Altern Med. 16:3512016. View Article : Google Scholar : PubMed/NCBI
7	Erichsen-Brown C: Medicinal and other uses of North American plants: A historical survey with special reference to the Eastern Indian Tribes. Mineola, New York, USA: Dover Publications; 1989
8	Sezik E, Tabata M, Yeşilada E, Honda G, Goto K and Ikeshiro Y: Traditional medicine in Turkey. I. Folk medicine in northeast Anatolia. J Ethnopharmacol. 35:191–196. 1991. View Article : Google Scholar : PubMed/NCBI
9	Jang JY, Shin H, Lim JW, Ahn JH, Jo YH, Lee KY, Hwang BY, Jung SJ, Kang SY and Lee MK: Comparison of antibacterial activity and phenolic constituents of bark, lignum, leaves and fruit of Rhus verniciflua. PLoS One. 13:e02002572018. View Article : Google Scholar : PubMed/NCBI
10	Kang SY, Kang JY and Oh MJ: Antiviral activities of flavonoids isolated from the bark of Rhus verniciflua stokes against fish pathogenic viruses in vitro. J Microbiol. 50:293–300. 2012. View Article : Google Scholar : PubMed/NCBI
11	Ahmed MS, Galal AM, Ross SA, Ferreira D, ElSohly MA, Ibrahim AS, Mossa JS and El-Feraly FS: A weakly antimalarial biflavanone from Rhus retinorrhoea. Phytochemistry. 58:599–602. 2001. View Article : Google Scholar : PubMed/NCBI
12	Mahjoub MA, Ammar S and Mighri Z: A new biflavonoid and an isobiflavonoid from Rhus tripartitum. Nat Prod Res. 19:723–729. 2005. View Article : Google Scholar : PubMed/NCBI
13	Alimi H, Mbarki S, Barka ZB, Feriani A, Bouoni Z, Hfaeidh N, Sakly M, Tebourbi O and Rhouma KB: Phytochemical, antioxidant and protective effect of Rhus tripartitum root bark extract against ethanol-induced ulcer in rats. Gen Physiol Biophys. 32:115–127. 2013. View Article : Google Scholar : PubMed/NCBI
14	Mohammed AESI: Phytoconstituents and the study of antioxidant, antimalarial and antimicrobial activities of Rhus tripartite growing in Egypt. J Pharmacogn Phytochem. 4:276–281. 2015.
15	Alqahtani AS, Abdel-Mageed WM, Shahat AA, Parvez MK, Al-Dosari MS, Malik A, Abdel-Kader MS and Alsaid MS: Proanthocyanidins from the stem bark of Rhus tripartita ameliorate methylgloxal-induced endothelial cell apoptosis. J Food Drug Anal. 27:758–765. 2019. View Article : Google Scholar : PubMed/NCBI
16	Collenetle S: An illustrated guide to the flowersof Saudi Arabia. Scorpion Publishing LTD; London: pp. 45–49. 1985
17	Mothana RA, Gruenert R, Bednarski PJ and Lindequist U: Evaluation of the in vitro anticancer, antimicrobial and antioxidant activities of some Yemeni plants used in folk medicine. Pharmazie. 64:260–268. 2009.PubMed/NCBI
18	Mossa JS, Abdel Sattar E, Abou-Shoer M and Galal AM: Free flavonoids from Rhus retinorrhoea steud, ex olive. Int J Pharmacog. 34:198–201. 1996. View Article : Google Scholar
19	Alam P, Parvez MK, Arbab AH, Siddiqui NA, Al-Dosary MS, Al-Rehaily AJ, Ahmed S, Kalam MA and Ahmad MS: Inter-species comparative antioxidant assay and HPTLC analysis of sakuranetin in the chloroform and ethanol extracts of aerial parts of Rhus retinorrhoea and Rhus tripartita. Pharm Biol. 55:1450–1457. 2017. View Article : Google Scholar : PubMed/NCBI
20	Adewusi E and Afolayan AJ: A review of natural products with hepatoprotective activity. J Med Plants Res. 4:1318–1334. 2010.
21	Tang LSY, Cover E, Wilson E and Kottilil S: Chronic hepatitis B infection: A review. JAMA. 319:1802–1813. 2018. View Article : Google Scholar : PubMed/NCBI
22	World Health Organisation, . Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-bFebruary 18–2023
23	Devi U and f Locarnini S, . Hepatitis B antivirals and resistance. Curr Opin Virol. 3:495–500. 2013. View Article : Google Scholar : PubMed/NCBI
24	Wang G, Zhang L and Bonkovsky HL: Chinese medicine for treatment of chronic hepatitis B. Chin J Integr Med. 18:253–255. 2012. View Article : Google Scholar : PubMed/NCBI
25	Parvez MK, Arbab AH and Al-Dosari MS: An update on natural or herbal drugs against hepatitis B virus. In Hepatitis B: Diagnosis, Prevention and Treatment. NOVA Science Publishers; USA: pp. 159–184. 2021
26	Parvez MK, Rehman MT, Alam P, Al-Dosari MS, Alqasoumi SI and Alajmi MF: Plant-derived antiviral drugs as novel hepatitis B virus inhibitors: Cell culture and molecular docking study. Saudi Pharm J. 27:389–400. 2019. View Article : Google Scholar : PubMed/NCBI
27	Parvez MK, Al-Dosari MS, Alam P, Rehman MT, Alajmi MF and Alqahtani AS: The anti-hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera. Phytother Res. 33:1960–1970. 2019. View Article : Google Scholar : PubMed/NCBI
28	Parvez MK, Al-Dosari MS, Arbab AH, Al-Rehaily AJ and Abdelwahid MAS: Bioassay-guided isolation of anti-hepatitis B virus flavonoid myricetin-3-O-rhamnoside along with quercetin from Guiera senegalensis leaves. Saudi Pharm J. 28:550–559. 2020. View Article : Google Scholar : PubMed/NCBI
29	Parvez MK, Ahmed S, Al-Dosari MS, Abdelwahid MAS, Arbab AH, Al-Rehaily AJ and Al-Oqail MM: Novel anti-hepatitis B virus activity of Euphorbia schimperi and its quercetin and kaempferol derivatives. ACS Omega. 6:29100–29110. 2021. View Article : Google Scholar : PubMed/NCBI
30	Ahmed S, Parvez MK, Zia K, Nur-e-Alam M, Ul-Haq Z, Al-Dosari MS and Al-Rehaily AJ: Natural anti-hepatitis B virus flavones isolated from Stachys schimperi Vatke growing in Saudi Arabia. Pharmacog Mag. 18:386–392. 2022.
31	Gharabolagh AF, Sabahi F, Karimi M, Kamalinejad M, Mirshahabi H, Dawood S, Nasab M and Ahmadi NA: Effects of Rhus Coriaria L. (Sumac) extract on hepatitis B virus replication and HBs Ag secretion. J Rep Pharm Sci. 7:100–107. 2018.
32	Zembower DE, Lin YM, Flavin MT, Chen FC and Korba BE: Robustaflavone, a potential non-nucleoside anti-hepatitis B agent. Antiviral Res. 39:81–88. 1998. View Article : Google Scholar : PubMed/NCBI
33	Parvez MK, Al-Dosari MS, Abdelwahid MAS, Alqahtani AS and Alanzi AR: Novel anti-hepatitis B virus-active catechin and epicatechin from Rhus tripartita. Exp Ther Med. 23:3982022. View Article : Google Scholar : PubMed/NCBI
34	Zhou Z, Hu T, Zhou X, Wildum S, Garcia-Alcalde F, Xu Z, Wu D, Mao Y, Tian X, Zhou Y, et al: Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) inhibit hepatitis B virus replication by different molecular mechanisms. Sci Rep. 7:423742017. View Article : Google Scholar : PubMed/NCBI
35	Bertoletti N, Chan AH, Schinazi RF, Yin YW and Anderson KS: Structural insights into the recognition of nucleoside reverse transcriptase inhibitors by HIV-1 reverse transcriptase: First crystal structures with reverse transcriptase and the active triphosphate forms of lamivudine and emtricitabine. Protein Sci. 28:1664–1675. 2019. View Article : Google Scholar : PubMed/NCBI
36	Bietz S and Rarey M: SIENA: Efficient compilation of selective protein binding site ensembles. J Chem Inf Model. 56:248–259. 2016. View Article : Google Scholar : PubMed/NCBI
37	Maestro, . Schrödinger Release 2021-3. Maestro, Schrödinger, LLC; New York, NY: 2021
38	Pettersen EF, Goddard TD, Huang CC, Meng EC, Couch GS, Croll TI, Morris JH and Ferrin TE: UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci. 30:70–82. 2021. View Article : Google Scholar : PubMed/NCBI
39	Eberhardt J, Santos-Martins D, Tillack AF and Forli S: AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J Chem Inf Model. 61:3891–3898. 2021. View Article : Google Scholar : PubMed/NCBI
40	Hollman PCH: Absorption, bioavailability and metabolism of flavonoids. Pharm Biol. 42:74–83. 2004. View Article : Google Scholar
41	Badshah SL, Faisal S, Muhammad A, Poulson BG, Emwas AH and Jaremko M: Antiviral activities of flavonoids. Biomed Pharmacother. 140:1115962021. View Article : Google Scholar : PubMed/NCBI
42	Zakaryan H, Arabyan E, Oo A and Zandi K: Flavonoids: Promising natural compounds against viral infections. Arch Virol. 162:2539–2551. 2017. View Article : Google Scholar : PubMed/NCBI
43	Parvez MK and Rishi V: Herb-drug interactions and hepatotoxicity. Curr Drug Metab. 20:275–282. 2019. View Article : Google Scholar : PubMed/NCBI
44	Wang L, Song J, Liu A, Xiao B, Li S, Wen Z, Lu Y and Du G: Research progress of the antiviral bioactivities of natural flavonoids. Nat Prod Bioprospect. 10:271–283. 2020. View Article : Google Scholar : PubMed/NCBI
45	Stompor M: A review on sources and pharmacological aspects of sakuranetin. Nutrients. 12:5132020. View Article : Google Scholar : PubMed/NCBI
46	Soarse DG, Andreazza AC and Salvador M: Evaluation of compounds with antioxidant activity in Sachhromyces cerevisiae yeast cells. Rev Bras Cienc Farm. 41:95–100. 2005.
47	Zhang X, Hung TM, Phuong PT, Ngoc TM, Min BS, Song KS, Seong YH and Bae K: Anti-inflammatory activity of flavonoids from Populus davidiana. Arch Pharm Res. 29:1102–1108. 2006. View Article : Google Scholar : PubMed/NCBI
48	Cruz MP, Andrade CM, Silva KO, de Souza EP, Yatsuda R, Marques LM, David JP, David JM, Napimoga MH and Clemente-Napimoga JT: Antinoceptive and anti-inflammatory activities of the ethanol extract, fractions and flavones isolated from Mimosa tenuiflora (Willd.) Poir (Leguminosae). PLoS One. 11:e01508392016. View Article : Google Scholar : PubMed/NCBI
49	Charles C, Nachtergael A, Ouedraogo M, Belayew A and Duez P: Effects of chemopreventive natural products on non-homologous end-joining DNA double-strand break repair. Mutat Res Genet Toxicol Environ Mutagen. 768:33–41. 2014. View Article : Google Scholar : PubMed/NCBI
50	Kwon DH, Ji JH, Yim SH, Kim BS and Choi HJ: Suppression of influenza B virus replication by sakuranetin and mode of its action. Phytother Res. 32:2475–2479. 2018. View Article : Google Scholar : PubMed/NCBI
51	Choi HJ: In vitro antiviral activity of sakuranetin against human rhinovirus 3. Osong Public Health Res Perspect. 8:415–420. 2017. View Article : Google Scholar : PubMed/NCBI
52	Kang J, Xie C, Li Z, Nagarajan S, Schauss AG, Wu T and Wu X: Flavonoids from acai (Euterpe oleracea Mart.) pulp and their antioxidant and anti-inflammatory activities. Food Chem. 128:152–157. 2011. View Article : Google Scholar : PubMed/NCBI
53	Xie CH, Kang J, Li ZM, Schauss AG, Badger TM, Nagarajan S, Wu T and Wu XL: The açaí flavonoid velutin is a potent anti-inflammatory agent: Blockade of LPS-mediated TNF-α and IL-6 production through inhibiting NF-κB activation and MAPK pathway. J Nutr Biochem. 23:1184–1191. 2012. View Article : Google Scholar : PubMed/NCBI
54	Hassan S, Hamed S, Almuhayawi M, Hozzein W, Selim S and AbdElgawad H: Bioactivity of ellagic acid and velutin: Two phenolic compounds isolated from marine algae. Egypt J Botany. 16:219–231. 2012.
55	Rangsinth P, Sillapachaiyaporn C, Nilkhet S, Tencomnao T, Ung AT and Chuchawankul S: Mushroom-derived bioactive compounds potentially serve as the inhibitors of SARS-CoV-2 main protease: An in silico approach. J Tradit Complement Med. 11:158–172. 2021. View Article : Google Scholar : PubMed/NCBI