Ethnomedicinal bioprospecting of Rhizophora apiculata leaves through in silico and in vitro approaches as antioxidant, ?-glucosidase inhibitor and anticancer

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MADA TRIANDALA SIBERO
RUDHI PRIBADI
AMBARIYANTO
DWI HARYANTI
VIOL DHEA KHARISMA
ARIYANTI S. DEWI
GINTUNG PATANTIS PATANTIS
DEWI S. ZILDA
RETNO MURWANI

Abstract

Abstract. Sibero MT, Pribadi R, Ambariyanto A, Haryanti D, Kharisma VD, Dewi AS, Patantis G, Zilda DS, Murwani R. 2022. Ethnomedicinal bioprospecting of Rhizophora apiculata leaves through in silico and in vitro approaches as antioxidant, a-glucosidase inhibitor and anticancer. Biodiversitas 23: 6437-6447. Investigating marine natural products for biopharmaceutical development leads to a massive study of mangrove metabolites. Rhizophora apiculata is utilized as a traditional medicine by the local community in Indonesia. However, only a few studies reported the lead compounds. The aim of this study was to discover the biological properties of R. apiculata metabolites from the leaves as an antioxidant, a-glucosidase inhibitor, and anticancer agent through in vitro and in silico approaches. The leaves of R. apiculata were extracted and then fractionated using the silica-OCC method. All fractions were screened for antioxidant, a-glucosidase inhibitors, and cytotoxicity assays. Then the bioactive compounds in prospective fractions were identified using LC-HRMS. The selected compounds with ppm error <10 were applied for in silico analysis. The result of biological properties screening indicated Fr. 5 and Fr. 6 as the most potent sources of antioxidants, a-glucosidase inhibitors, and cytotoxic compounds. In total, 19 compounds were selected from two prospective fractions. The drug-likeness and bioavailability prediction results indicated that all selected compounds act as drug-like molecules. In addition, 17 were predicted to have antioxidant activity, and 15 compounds had antidiabetic activity. Moreover, 15 compounds had a more negative affinity binding than cytarabine. Molecular docking analysis showed that the mechanism of cytotoxicity against P388 Murine Leukaemia Cells was through the interaction of apigenin with protein tyrosine kinase (c-Kit) with a stronger inhibitory activity than the control drug (Cytarabine) and had the same binding site as the control (Cytarabine).

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References
Adriani A, Noorhamdani N, Ardyati T, & Winarsih S. 2022. Non-targeted screening with LC-HRMS and In-Silico Study on Diabetic activity of ethyl acetate extract of Sanrego (Lunasia amara Blanco). Res. J. Pharm. Technol. 1077–1084. DOI: 10.52711/0974-360X.2022.00180
Alam F, Shafique Z, Amjad ST, & Asad MHH Bin. 2019. Enzymes inhibitors from natural sources with antidiabetic activity: A review. Phyther. Res. 33(1): 41–54. DOI: 10.1002/ptr.6211
Aldakinah A-AA, Al-Shorbagy MY, Abdallah DM, & El-Abhar HS. 2017. Trigonelline and vildagliptin antidiabetic effect: improvement of insulin signalling pathway. J. Pharm. Pharmacol. 69(7): 856–864. DOI: 10.1111/jphp.12713
Alexandre ACS, Albergaria FC, e Silva LM dos SF, Fernandes LAC, Gomes ME de S, & Pimenta CJ. 2022. Effect of natural and synthetic antioxidants on oxidation and storage stability of mechanically separated tilapia meat. LWT 154: 112679. DOI: 10.1016/j.lwt.2021.112679
Allahghadri T, Rasooli I, Owlia P, Nadooshan MJ, Ghazanfari T, Taghizadeh M, & Astaneh SDA. 2010. Antimicrobial Property, Antioxidant Capacity, and Cytotoxicity of Essential Oil from Cumin Produced in Iran. J. Food Sci. 75(2): H54–H61. DOI: 10.1111/j.1750-3841.2009.01467.x
Ansori A, Kharisma V, Parikesit A, Dian F, Probojati R, Rebezov M, Scherbakov P, Burkov P, Zhdanova G, Mikhalev A, Antonius Y, Pratama M, Sumantri N, Sucipto T, & Zainul R. 2022. Bioactive Compounds from Mangosteen (Garcinia mangostana L.) as an Antiviral Agent via Dual Inhibitor Mechanism against SARSCoV- 2: An In Silico Approach. Pharmacogn. J. 14(1): 85–90. DOI: 10.5530/pj.2022.14.12
Ansori ANM, Fadholly A, Proboningrat A, Hayaza S, Susilo RJK, Naw SW, Posa GAV, Yusrizal YF, Sibero MT, Sucipto TH, & Soegijanto S. 2021a. In Vitro Antiviral Activity of Pinus merkusii (Pinaceae) Stem Bark and Cone against Dengue Virus Type-2 (DENV-2). Res. J. Pharm. Technol. 3705–3708. DOI: 10.52711/0974-360X.2021.00641
Ansori ANM, Kharisma VD, Fadholly A, Tacharina MR, Antonius Y, & Parikesit AA. 2021b. Severe Acute Respiratory Syndrome Coronavirus-2 Emergence and Its Treatment with Alternative Medicines: A Review. Res. J. Pharm. Technol. 5551–5557. DOI: 10.52711/0974-360X.2021.00967
Ansori ANM, Kharisma VD, Solikhah TI. 2021c. Medicinal properties of Muntingia calabura L.: A Review. Res. J. Pharm. Technol. 4509–4512. DOI: 10.52711/0974-360X.2021.00784
Brenton AG, & Godfrey AR. 2010. Accurate mass measurement: Terminology and treatment of data. J. Am. Soc. Mass Spectrom. 21(11): 1821–1835. DOI: 10.1016/j.jasms.2010.06.006
Carroll AR, Copp BR, Davis RA, Keyzers RA, & Prinsep MR. 2020. Marine natural products. Nat. Prod. Rep. 37(2): 175–223. DOI: 10.1039/C9NP00069K
Chernonosov A, Aksenova L, & Koval V. 2021. The Development of a Liquid Chromatography High-Resolution Mass Spectrometric Method for Apixaban Quantification in Dried Plasma Spots in Parallel Reaction Monitoring Mode. Processes 9(3): 450. DOI: 10.3390/pr9030450
Christina YI, Nafisah W, Atho’illah MF, Rifai M, Widodo N, & Djati MS. 2021. Anti-breast cancer potential activity of Phaleria macrocarpa (Scheff.) Boerl. leaf extract through in silico studies. J. Pharm. Pharmacogn. Res. 9(6):.
Di Francia R, Crisci S, De Monaco A, Cafiero C, Re A, Iaccarino G, De Filippi R, Frigeri F, Corazzelli G, Micera A, & Pinto A. 2021. Response and Toxicity to Cytarabine Therapy in Leukemia and Lymphoma: From Dose Puzzle to Pharmacogenomic Biomarkers. Cancers (Basel). 13(5): 966. DOI: 10.3390/cancers13050966
Dibha AF, Wahyuningsih S, Kharisma VD, Ansori ANM, Widyananda MH, Parikesit AA, Rebezov M, Matrosova Y, Artyukhova S, Kenijz N, Kiseleva M, Jakhmola V, & Zainul R. 2022. Biological activity of kencur (Kaempferia galanga L.) against SARS-CoV-2 main protease. Int. J. Health Sci. (Qassim). 6(S1): 468–480. DOI: 10.53730/ijhs.v6nS1.4779
Fadholly A, Ansori ANM, Kharisma VD, Rahmahani J, & Tacharina MR. 2021. Immunobioinformatics of rabies virus in various countries of Asia: Glycoprotein gene. Res. J. Pharm. Technol. 14(2): 883–886. DOI: 10.5958/0974-360X.2021.00157.8
Fahmi M, Kharisma VD, Ansori ANM, & Ito M. 2021. Retrieval and Investigation of Data on SARS-CoV-2 and COVID-19 Using Bioinformatics Approach (pp. 839–857). DOI: 10.1007/978-3-030-63761-3_47
Husen SA, Ansori ANM, Hayaza S, Susilo RJK, Zuraidah AA, Winarni D, Punnapayak H, & Darmanto W. 2019. Therapeutic Effect of Okra ( Abelmoschus esculentus Moench) Pods Extract on Streptozotocin-Induced Type-2 Diabetic Mice. Res. J. Pharm. Technol. 12(8): 3703. DOI: 10.5958/0974-360X.2019.00633.4
IDF. 2021. IDF Diabetes Atlas 10th edition. www.diabetesatlas.org
Johari MA, & Khong HY. 2019. Total Phenolic Content and Antioxidant and Antibacterial Activities of Pereskia bleo. Adv. Pharmacol. Sci. 2019: 1–4. DOI: 10.1155/2019/7428593
Kedare SB, & Singh RP. 2011. Genesis and development of DPPH method of antioxidant assay. J. Food Sci. Technol. 48(4): 412–422. DOI: 10.1007/s13197-011-0251-1
Kharisma VD, Agatha A, Ansori ANM, Widyananda MH, Rizky WC, Ding TGA, Derkho M, Lykasova I, Antonius Y, Rosadi I, & Zainul R. 2022. Herbal combination from Moringa oleifera Lam. and Curcuma longa L. as SARS-CoV-2 antiviral via dual inhibitor pathway: A viroinformatics approach. J. Pharm. Pharmacogn. Res. 10(1): 138–146. DOI: 10.56499/jppres21.1174_10.1.138
Kharisma VD, Ansori ANM, Fadholy A, & Sucipto TH. 2020. Molecular Mechanism of Caffeine-Aspirin Interaction in Kopi Balur 1 as Anti-Inflammatory Agent: A Computational Study. Indian J. Forensic Med. Toxicol. DOI: 10.37506/ijfmt.v14i4.12274
Kharisma VD, Kharisma SD, Ansori ANM, Kurniawan HP, Witaningrum AM, Fadholly A, & Tacharina MR. 2021. Antiretroviral effect simulation from black tea (Camellia sinensis) via dual inhibitors mechanism in HIV-1 and its social perspective in Indonesia. Res. J. Pharm. Technol. 14(1): 455–460. DOI: 10.5958/0974-360X.2021.00083.4
Lichota A, & Gwozdzinski K. 2018. Anticancer Activity of Natural Compounds from Plant and Marine Environment. Int. J. Mol. Sci. 19(11): 3533. DOI: 10.3390/ijms19113533
Luo Q, Cai Y, Yan J, Sun M, & Corke H. 2004. Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum. Life Sci. 76(2): 137–149. DOI: 10.1016/j.lfs.2004.04.056
Luqman A, Kharisma VD, Ruiz RA, & Götz F. 2020. In Silico and in Vitro Study of Trace Amines (TA) and Dopamine (DOP) Interaction with Human Alpha 1-Adrenergic Receptor and the Bacterial Adrenergic Receptor QseC. Cell. Physiol. Biochem. 54(5): 888–898. DOI: 10.33594/000000276
Mitra S, Naskar N, & Chaudhuri P. 2021. A review on potential bioactive phytochemicals for novel therapeutic applications with special emphasis on mangrove species. Phytomedicine Plus 1(4): 100107. DOI: 10.1016/j.phyplu.2021.100107
Neha K, Haider MR, Pathak A, & Yar MS. 2019. Medicinal prospects of antioxidants: A review. Eur. J. Med. Chem. 178: 687–704. DOI: 10.1016/j.ejmech.2019.06.010
Nielsen JB, Leppin A, Gyrd-Hansen D e, Jarbøl DE, Søndergaard J, & Larsen PV. 2017. Barriers to lifestyle changes for prevention of cardiovascular disease – a survey among 40–60-year old Danes. BMC Cardiovasc. Disord. 17(1): 245. DOI: 10.1186/s12872-017-0677-0
Nimse SB, & Pal D. 2015. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv. 5(35): 27986–28006. DOI: 10.1039/C4RA13315C
Nugraha AP, Rahmadhani D, Puspitaningrum MS, Rizqianti Y, Kharisma VD, & Ernawati DS. 2021. Molecular docking of anthocyanins and ternatin in Clitoria ternatea as coronavirus disease oral manifestation therapy. J. Adv. Pharm. Technol. Res. 12(4): 362. DOI: 10.4103/japtr.japtr_126_21
Nugraha AP, Sibero MT, Nugraha AP, Puspitaningrum MS, Rizqianti Y, Rahmadhani D, Kharisma VD, Ramadhani NF, Ridwan RD, Noor TNE binti TA, & Ernawati DS. 2022. Anti-Periodontopathogenic Ability of Mangrove Leaves (Aegiceras corniculatum) Ethanol Extract: In silico and in vitro study. Eur. J. Dent. DOI: 10.1055/s-0041-1741374
Padmi H, Kharisma VD, Ansori ANM, Sibero MT, Widyananda MH, Ullah ME, Gumenyuk O, Chylichcova S, Bratishko N, Prasedya ES, Sucipto TH, & Zainul R. 2022. Macroalgae Bioactive Compounds for the Potential Antiviral of SARS-CoV-2: An In Silico Study. J. Pure Appl. Microbiol. 16(2): 1018–1027. DOI: 10.22207/JPAM.16.2.26
Pandurangan P, Chanakya B, Rajarabu N, Shobana, Uthralaksmi N, Saigeetha S, & Samrot A V. 2021. Evaluation of Antioxidants, Antidiabetic, Antiinflammatory Active Compounds from Leptogium rivurale Through In-Vitro and In-Silico Studies. Lett. Appl. NanoBioScience 11(4): 4192–4200. DOI: 10.33263/LIANBS114.41924200
Peng F, Tao Q, Wu X, Dou H, Spencer S, Mang C, Xu L, Sun L, Zhao Y, Li H, Zeng S, Liu G, & Hao X. 2012. Cytotoxic, cytoprotective and antioxidant effects of isolated phenolic compounds from fresh ginger. Fitoterapia 83(3): 568–585. DOI: 10.1016/j.fitote.2011.12.028
Prahasanti C, Nugraha AP, Kharisma VD, Ansori ANM, Devijanti R, Ridwan, Putri TPS, Ramadhani NF, Narmada IB, Ardani IGAW, & Noor TNEBA. 2021. A bioinformatic approach of hydroxyapatite and polymethylmethacrylate composite exploration as dental implant biomaterial. J. Pharm. Pharmacogn. Res. 9(5): 746–754.
Proboningrat A, Kharisma VD, Ansori ANM, Rahmawati R, Fadholly A, Posa GAV, Sudjarwo SA, Rantam FA, & Achmad AB. 2022. In silico Study of Natural inhibitors for Human papillomavirus-18 E6 protein. Res. J. Pharm. Technol. 1251–1256. DOI: 10.52711/0974-360X.2022.00209
Purnobasuki H. 2019. Potensi Mangrove Sebagai Tanaman Obat (Short Communication). Biota J. Ilm. Ilmu-Ilmu Hayati. DOI: 10.24002/biota.v9i2.2901
Purwaningsih S, Salamah E, Sukarno AYP, & Deskawati E. 2013. Antioxidant Activity of Mangrove (Rhizophora mucronata Lamk.) Fruits at Different Temperatures. J. Pengolah. Has. Perikan. Indones. 16(3): 199–206. DOI: 10.17844/jphpi.v16i3.8057
Purwanti R. 2016. Studi Etnobotani Pemanfaatan Jenis-Jenis Mangrove Sebagai Tumbuhan Obat di Sulawesi. Proceeding Mulawarman Pharm. Conf. 3: 340–348. DOI: 10.25026/mpc.v3i2.131
Ramalingam V, & Rajaram R. 2018. Enhanced antimicrobial, antioxidant and anticancer activity of Rhizophora apiculata: An experimental report. 3 Biotech 8(4): 200. DOI: 10.1007/s13205-018-1222-2
Ravi S, Young T, Macinnis-Ng C, Nyugen T V., Duxbury M, Alfaro AC, & Leuzinger S. 2020. Untargeted metabolomics in halophytes: The role of different metabolites in New Zealand mangroves under multi-factorial abiotic stress conditions. Environ. Exp. Bot. 173: 103993. DOI: 10.1016/j.envexpbot.2020.103993
Riyadi P, Romadhon, Anggo A, Suharto S, Tanod W, & Aryani A. 2021. Anti-Inflammatory Potential from Tilapia (Oreochromis niloticus) Viscera Hydrolysate with Bioinformatics Analysis (Prediction of Activity Spectra for Substances – PASS). IOP Conf. Ser. Earth Environ. Sci. 750(1): 012044. DOI: 10.1088/1755-1315/750/1/012044
Sachithanandam V, Lalitha P, Parthiban A, Mageswaran T, Manmadhan K, & Sridhar R. 2019. A Review on Antidiabetic Properties of Indian Mangrove Plants with Reference to Island Ecosystem. Evidence-Based Complement. Altern. Med. 2019: 1–21. DOI: 10.1155/2019/4305148
Sadeer NB, Mahomoodally MF, Zengin G, Jeewon R, Nazurally N, Rengasamy KRR, Albuquerque RDDG, & Shunmugiah KP. 2019. Ethnopharmacology, Phytochemistry, and Global Distribution of Mangroves?A Comprehensive Review. Mar. Drugs 17(4): 231. DOI: 10.3390/md17040231
Sadeer NB, Rocchetti G, Senizza B, Montesano D, Zengin G, Uysal A, Jeewon R, Lucini L, & Mahomoodally MF. 2019. Untargeted Metabolomic Profiling, Multivariate Analysis and Biological Evaluation of the True Mangrove (Rhizophora mucronata Lam.). Antioxidants 8(10): 489. DOI: 10.3390/antiox8100489
Safitri A, Putri AS, Octavianty TD, & Sari DRT. 2020. Metabolomic Profiles of Curcuma longa L and Cosmos caudatus Extracts and Their In-Silico Anti-cancer Activity. J. Phys. Conf. Ser. 1665(1): 012022. DOI: 10.1088/1742-6596/1665/1/012022
Salazar-Aranda R, Pérez-López LA, López-Arroyo J, Alanís-Garza BA, & Waksman de Torres N. 2011. Antimicrobial and Antioxidant Activities of Plants from Northeast of Mexico. Evidence-Based Complement. Altern. Med. 2011: 1–6. DOI: 10.1093/ecam/nep127
Sancheti S, Sancheti S, & Seo S-Y. 2009. Chaenomeles Sinensis: A Potent ?-and ?-Glucosidase Inhibitor. Am. J. Pharmacol. Toxicol. 4(1): 8–11. DOI: 10.3844/ajptsp.2009.8.11
Selvaraj G, Kaliamurthi S, & Thirugnasambandan R. 2016. Effect of Glycosin alkaloid from Rhizophora apiculata in non-insulin dependent diabetic rats and its mechanism of action: In vivo and in silico studies. Phytomedicine 23(6): 632–640. DOI: 10.1016/j.phymed.2016.03.004
Sethi S, Joshi A, Arora B, Bhowmik A, Sharma RR, & Kumar P. 2020. Significance of FRAP, DPPH, and CUPRAC assays for antioxidant activity determination in apple fruit extracts. Eur. Food Res. Technol. 246(3): 591–598. DOI: 10.1007/s00217-020-03432-z
Sharma AR, Zhou T, Harunari E, Oku N, Trianto A, & Igarashi Y. 2019. Labrenzbactin from a coral-associated bacterium Labrenzia sp. J. Antibiot. (Tokyo). 72(8): 634–639. DOI: 10.1038/s41429-019-0192-x
Shinde P, Banerjee P, & Mandhare A. 2019. Marine natural products as source of new drugs: a patent review (2015–2018). Expert Opin. Ther. Pat. 29(4): 283–309. DOI: 10.1080/13543776.2019.1598972
Sibero MT, Siswanto AP, Pribadi R, Sabdono A, Radjasa OK, Trianto A, Frederick EH, Wijaya AP, Haryanti D, Triningsih DW, Hayuningrat SJ, & Igarashi Y. 2020. The effect of drying treatment to metabolite profile and cytotoxic potential of Rhizophora apiculata leaves. Biodiversitas J. Biol. Divers. 21(5):. DOI: 10.13057/biodiv/d210546
Sibero MT, Trianto A, Frederick EH, Wijaya AP, Ansori ANM, & Igarashi Y. 2022. Biological Activities and Metabolite Profiling of Polycarpa aurata (Tunicate, Ascidian) from Barrang Caddi, Spermonde Archipelago, Indonesia. Jordan J. Biol. Sci. 15(01): 15–20. DOI: 10.54319/jjbs/150103
Sibero MT, Zhou T, Fukaya K, Urabe D, Radjasa OKK, Sabdono A, Trianto A, & Igarashi Y. 2019. Two new aromatic polyketides from a sponge-derived Fusarium. Beilstein J. Org. Chem. 15: 2941–2947. DOI: 10.3762/bjoc.15.289
Sibero MT, Zhou T, Igarashi Y, Radjasa OK, Sabdono A, Trianto A, Bachtiarini TU, & Bahry MS. 2020. Chromanone-type compounds from marine sponge-derived Daldinia eschscholtzii KJMT FP 4.1. J. Appl. Pharm. Sci. 10(1): 1–7. DOI: 10.7324/JAPS.2020.101001
Sidik F, Supriyanto B, Krisnawati H, & Muttaqin MZ. 2018. Mangrove conservation for climate change mitigation in Indonesia. WIREs Clim. Chang. 9(5):. DOI: 10.1002/wcc.529
Sudirman S, Nurjanah N, & Jacoeb AM. 2014. Proximate compositions, bioactive compounds and antioxidant activity from large-leafed mangrove (Bruguiera gymnorrhiza) fruit. Int. Food Res. J. 21(6): 2387–2391. http://ifrj.upm.edu.my/21 (06) 2014/46 IFRJ 21 (06) 2014 Sudirman 287.pdf
Susanto H, Kharisma VD, Listyorini D, Taufiq A, Sunaryono, & Aulanni’am. 2018. Effectivity of Black Tea Polyphenol in Adipogenesis Related IGF-1 and Its Receptor Pathway Through In Silico Based Study. J. Phys. Conf. Ser. 1093: 012037. DOI: 10.1088/1742-6596/1093/1/012037
Tamalene MN, Sen UK, Bhakat RK, Vianti E, Bahtiar, & Suparman. 2021. Utilization of mangrove plants as a source of Malaria medicine in North Maluku Province, Indonesia. Asian J. Ethnobiol. 4(2): 86–92.
Tomlinson PB. 1986. The botany of mangrove. J. Trop. Ecol. 3(2): 188–189. DOI: 10.1017/S0266467400002017
van Oudenhoven APE, Siahainenia AJ, Sualia I, Tonneijck FH, van der Ploeg S, de Groot RS, Alkemade R, & Leemans R. 2015. Effects of different management regimes on mangrove ecosystem services in Java, Indonesia. Ocean Coast. Manag. 116: 353–367. DOI: 10.1016/j.ocecoaman.2015.08.003
WHO. 2018. Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018.
WHO. 2019a. Classification of diabetes mellitus. http://apps.who.int/bookorders
WHO. 2019b. Indonesia Source GLOBOCAN 2018. International Agency for Research on Cancer. http://gco.iarc.fr/
WHO. 2022. Estimated age-standardized incidence rates (World) in 2020, all cancers, both sexes, all ages, WHO South-East Asia Region. http://gco.iarc.fr/
Widyastuti A, Yani E, Nasution EK, & Rochmatino R. 2018. Diversity of mangrove vegetation and carbon sink estimation of Segara Anakan Mangrove Forest, Cilacap, Central Java, Indonesia. Biodiversitas J. Biol. Divers. 19(1): 246–252. DOI: 10.13057/biodiv/d190133
Wijaya RM, Hafidzah MA, Kharisma VD, Ansori ANM, & Parikesit AA. 2021. COVID-19 In Silico Drug with Zingiber officinale Natural Product Compound Library Targeting the Mpro Protein. Makara J. Sci. 25(3):. DOI: 10.7454/mss.v25i3.1244
Xiao F, Xu T, Lu B, & Liu R. 2020. Guidelines for antioxidant assays for food components. Food Front. 1(1): 60–69. DOI: 10.1002/fft2.10
Yamaoka T, Kusumoto S, Ando K, Ohba M, & Ohmori T. 2018. Receptor Tyrosine Kinase-Targeted Cancer Therapy. Int. J. Mol. Sci. 19(11): 3491. DOI: 10.3390/ijms19113491
Zhang H, Jacob JA, Jiang Z, Xu S, Sun K, Zhong Z, Varadharaju N, & Shanmugam A. 2019. Hepatoprotective effect of silver nanoparticles synthesized using aqueous leaf extract of Rhizophora apiculata. Int. J. Nanomedicine Volume 14: 3517–3524. DOI: 10.2147/IJN.S198895

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