In Vivo Anticancer Evaluation of Neferine from Nelumbo nucifera in Ehrlich Ascites Carcinoma-Bearing Mice

Authors

  • Sravani Batchu
  • Bhavya E
  • C. Ronald Darwin

DOI:

https://doi.org/10.52783/jns.v14.1794

Keywords:

Neferine, Ehrlich Ascites Carcinoma, antitumour activity, haematological parameters, mean survival time, life span

Abstract

The current study reports the isolation and in vivo anticancer evaluation of neferine, a bisbenzylisoquinoline alkaloid, extracted from Nelumbo nucifera seeds. Neferine was purified through solvent extraction and chromatographic separation using a mixture of chloroform, methanol, and ammonium hydroxide (95:4.5:0.5), resulting in a nearly pure fraction. The antitumour activity of neferine was assessed in Ehrlich Ascites Carcinoma (EAC)-bearing mice, evaluating body weight, haematological parameters, mean survival time (MST), and percentage increase in life span (% ILS). Mice treated with neferine showed dose-dependent antitumour activity, with significant reductions in body weight and tumour burden observed at higher doses (75–150 mg/kg). At 100 mg/kg and above, neferine demonstrated comparable efficacy to 5-Fluorouracil in reducing tumour burden while exhibiting a favourable safety profile, as indicated by lower body weight loss. Neferine also modulated haematological parameters, increasing haemoglobin and red blood cell counts while reducing white blood cell counts and neutrophil levels. These improvements correlated with reduced tumour-induced inflammation and enhanced immune function. Furthermore, neferine extended the MST and % ILS of EAC-bearing mice, with the highest dose (150 mg/kg) resulting in a 64.25% increase in life span, closely matching the efficacy of 5-Fluorouracil. These findings suggest that neferine holds promise as a potential anticancer agent, warranting further investigation for its clinical application.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Debela DT, Muzazu SG, Heraro KD, Ndalama MT, Mesele BW, Haile DC, Kitui SK, Manyazewal T. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021 Aug 12;9:20503121211034366. doi: 10.1177/20503121211034366. PMID: 34408877; PMCID: PMC8366192.

Bishayee A, Patel PA, Sharma P, Thoutireddy S, Das N. Lotus (Nelumbo nucifera Gaertn.) and Its Bioactive Phytocompounds: A Tribute to Cancer Prevention and Intervention. Cancers (Basel). 2022 Jan 21;14(3):529. doi: 10.3390/cancers14030529. Erratum in: Cancers (Basel). 2022 Apr 24;14(9):2116. doi: 10.3390/cancers14092116. PMID: 35158798; PMCID: PMC8833568.

Menéndez-Perdomo IM, Facchini PJ. Benzylisoquinoline Alkaloids Biosynthesis in Sacred Lotus. Molecules. 2018 Nov 6;23(11):2899. doi: 10.3390/molecules23112899. PMID: 30404216; PMCID: PMC6278464.

Bharathi Priya L, Huang CY, Hu RM, Balasubramanian B, Baskaran R. An updated review on pharmacological properties of neferine-A bisbenzylisoquinoline alkaloid from Nelumbo nucifera. J Food Biochem. 2021 Dec;45(12):e13986. doi: 10.1111/jfbc.13986. Epub 2021 Nov 14. PMID: 34779018.

Kadioglu O, Law BYK, Mok SWF, Xu SW, Efferth T, Wong VKW. Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumour Cells. Frontiers in Pharmacology [Internet]. 2017 May 5;8.

Talib WH, Alsayed AR, Barakat M, Abu-Taha MI, Mahmod AI. Targeting Drug Chemo-Resistance in Cancer Using Natural Products. Biomedicines. 2021 Sep 29;9(10):1353. doi: 10.3390/biomedicines9101353. PMID: 34680470; PMCID: PMC8533186.

Asma ST, Acaroz U, Imre K, Morar A, Shah SRA, Hussain SZ, Arslan-Acaroz D, Demirbas H, Hajrulai-Musliu Z, Istanbullugil FR, Soleimanzadeh A, Morozov D, Zhu K, Herman V, Ayad A, Athanassiou C, Ince S. Natural Products/Bioactive Compounds as a Source of Anticancer Drugs. Cancers (Basel). 2022 Dec 15;14(24):6203. doi: 10.3390/cancers14246203. PMID: 36551687; PMCID: PMC9777303.

Manogaran P, Beeraka NM, Padma VV. The Cytoprotective and Anti-cancer Potential of Bisbenzylisoquinoline Alkaloids from Nelumbo nucifera. Curr Top Med Chem. 2019;19(32):2940-2957. doi: 10.2174/1568026619666191116160908. PMID: 31738137.

Dasari S, Bakthavachalam V, Chinnapaka S, Venkatesan R, Samy ALPA, Munirathinam G. Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro-oxidant anticancer mechanism. Phytother Res. 2020 Sep;34(9):2366-2384. doi: 10.1002/ptr.6687. Epub 2020 May 4. PMID: 32364634; PMCID: PMC7511448.

Deng G, Zeng S, Ma J, Zhang Y, Qu Y, Han Y, et al. The anti-tumour activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma. Scientific Reports [Internet]. 2017 Jan 30;7(1). Available from: https://doi.org/10.1038/srep41616.

Kadioglu O, Law BYK, Mok SWF, Xu SW, Efferth T, Wong VKW. Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumour Cells. Front Pharmacol. 2017 May 5;8:238. doi: 10.3389/fphar.2017.00238. PMID: 28529482; PMCID: PMC5418350.

Poornima P, Weng CF, Padma VV. Neferine, an alkaloid from lotus seed embryo, inhibits human lung cancer cell growth by MAPK activation and cell cycle arrest. BioFactors [Internet]. 2013 Aug 24;40(1):121–31.

Yoon JS, Kim HM, Yadunandam AK, Kim NH, Jung HA, Choi JS, Kim CY, Kim GD. Neferine isolated from Nelumbo nucifera enhances anti-cancer activities in Hep3B cells: molecular mechanisms of cell cycle arrest, ER stress induced apoptosis and anti-angiogenic response. Phytomedicine. 2013 Aug 15;20(11):1013-22. doi: 10.1016/j.phymed.2013.03.024. Epub 2013 Jun 6. PMID: 23746959.

Feitosa IB, Mori B, Teles CBG, Da Costa AG. What are the immune responses during the growth of Ehrlich’s tumour in ascitic and solid form? Life Sciences [Internet]. 2020 Oct 12;264:118578.

Radulski DR, Stipp MC, Galindo CM, Acco A. Features and applications of Ehrlich tumour model in cancer studies: a literature review. Translational Breast Cancer Research [Internet]. 2023 Jul 1;4:22. Available from: https://doi.org/10.21037/tbcr-23-32

Chen Y, Fan G, Wu H, Wu Y and Mitchell A 2007 Separation, identification and rapid determination of liensine, isoliensinine and neferine from embryo of the seed of Nelumbo nucifera Gaertn. by liquid chromatography coupled to diode array detector and tandem mass spectrometry Journal of Pharmaceutical and Biomedical Analysis 43 99-104.

Liu S, Liang Y-Z, Luo J, Cao D-S, Li X-Z, Lei P and Yuan D-L 2008 Optimization of Liensinine, Isoliensinine and Neferine Extraction from the Embryo of the Seed of Nelumbo nucifera GAERTN Separation Science and Technology 43 3637-51.

Elsadek MF, El-Din MME, Ahmed BM. Evaluation of anticarcinogenic and antioxidant properties of Eruca sativa extracts versus Ehrlich ascites carcinoma in mice. Journal of King Saud University - Science [Internet]. 2021 Apr 5;33(4):101435.

Srinivasan, S., Mohanprasanth, A., Nadeem, A., & Saravanan, M. (2024). Exploring the anti-cancer and Antimetastatic effect of Silymarin Against Lung Cancer. Toxicology Reports, 101746.

Velayutham, M.; Sarkar, P.; Sudhakaran, G.; Al-Ghanim, K.A.; Maboob, S.; Juliet, A.; Guru, A.; Muthupandian, S.; Arockiaraj, J. Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of Aphanomyces invadans, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model. Molecules 2022, 27, 7333.

Bharadwaj, N., Manimuthu, M. S., Vimal, S., & Radhakrishnan, N. (2024). Evaluation of In vitro Anti-Cancer Activity of Methanolic Leaf Extract of Phoenix pusilla on Colon Cancer Cell Line. Journal of Pharmacy and Bioallied Sciences, 16(Suppl 2), S1181-S1185.

Downloads

Published

2025-02-21

How to Cite

1.
Batchu S, E B, Darwin CR. In Vivo Anticancer Evaluation of Neferine from Nelumbo nucifera in Ehrlich Ascites Carcinoma-Bearing Mice. J Neonatal Surg [Internet]. 2025Feb.21 [cited 2025Sep.21];14(4S):312-8. Available from: https://jneonatalsurg.com/index.php/jns/article/view/1794

Similar Articles

You may also start an advanced similarity search for this article.