Author(s):
Sugiharto, Debby Faradila, Kurnia Rizqi Aningrum, Farra Dibha Nur Hakiki, Alfi Zahrotus Sa'adah, Ummi Fatimatuz Zahroh, Hari Soepriandono, Yosephine Sri Wulan Manuhara
Email(s):
sugiharto@fst.unair.ac.id
DOI:
10.52711/0974-360X.2024.00562 
Address:
Sugiharto1,2*, Debby Faradila1, Kurnia Rizqi Aningrum1, Farra Dibha Nur Hakiki1, Alfi Zahrotus Sa'adah1, Ummi Fatimatuz Zahroh1, Hari Soepriandono1, Yosephine Sri Wulan Manuhara1,2
1Department of Biology, Faculty of Science and Technology, Airlangga University, Surabaya, Indonesia.
2Biotechnology of Tropical Medicinal Plants Research Group, Faculty of Science and Technology, Airlangga University, Surabaya, Indonesia.
*Corresponding Author
Published In:
Volume - 17,
Issue - 8,
Year - 2024
ABSTRACT:
The rhizomes of jahe merah (Zingiber officinale) and temu kunci (Boesenbergia rotunda) contain lots of flavonoids and phenolics. So far, Indonesian people have used Z. officinale and B. rotunda as a mixture of cooking ingredients and as traditional medicine that are known as "jamu". This research was conducted to determine the potential antioxidant activity rhizome extracts of Z. officinale (Zo), B. rotunda (Br) and their combination (Zo+Br) in mice exposed to Pb. Furthermore, it is also to determine the anticancer activity in the hepatocyte carcinoma cell line (HepG2). Twenty-five male mice were to divide into 5 treatment groups, namely P1 = control, P2 = Pb 100mg/mL, P3 = Zo 100mg/mL + Pb 100mg/mL, P4 = Br 100mg/mL + Pb 100mg/mL, P5 = combination Zo+Br (ratio 1:1) 100mg/mL + Pb 100mg/mL. Treatment was given for 30 days and on the last day the mice were anesthetized and sacrificed. Their livers were taken to observe histologically changes in hepatocyte morphology, MDA levels, as well as the activity of the antioxidant enzymes SOD and CAT. In vitro antioxidant activity was also tested using the DPPH assay and anticancer activity was tested on HepG2 cells. The results showed that range of antioxidant activity was in the strong to very strong because it has an IC50 value of Zo = 47µg/mL, Br = 67µg/mL and their combination (Zo+Br) = 100µg/mL. Treatment using Zo, Br and their combination can also prevent a significant increase in MDA levels and also significant decrease in SOD and CAT enzyme activity due to Pb administration. This is in line with the increase in normal cells and decrease in abnormal hepatocyte cells. In addition, administration of Zo, Br and their combination can inhibit the proliferation of HepG2 cells in the moderate cytotoxic range (IC50 value ranges from 42.97 to 86.94µg/mL). The conclusion of this research showed Z. officinale, B. rotunda and their combination have potential as antioxidants and can be used as drug candidates to inhibit the growth of cancer cells.
Cite this article:
Sugiharto, Debby Faradila, Kurnia Rizqi Aningrum, Farra Dibha Nur Hakiki, Alfi Zahrotus Sa'adah, Ummi Fatimatuz Zahroh, Hari Soepriandono, Yosephine Sri Wulan Manuhara. Potential of Jahe Merah (Zingiber officinale) and Temu Kunci (Boesenbergia rotunda): As Stimulator of Antioxidant Enzyme Activity and Anticancer in HepG2 Cell Line. Research Journal of Pharmacy and Technology. 2024; 17(8):3599-6. doi: 10.52711/0974-360X.2024.00562
Cite(Electronic):
Sugiharto, Debby Faradila, Kurnia Rizqi Aningrum, Farra Dibha Nur Hakiki, Alfi Zahrotus Sa'adah, Ummi Fatimatuz Zahroh, Hari Soepriandono, Yosephine Sri Wulan Manuhara. Potential of Jahe Merah (Zingiber officinale) and Temu Kunci (Boesenbergia rotunda): As Stimulator of Antioxidant Enzyme Activity and Anticancer in HepG2 Cell Line. Research Journal of Pharmacy and Technology. 2024; 17(8):3599-6. doi: 10.52711/0974-360X.2024.00562 Available on: https://rjptonline.org/AbstractView.aspx?PID=2024-17-8-10
REFERENCES:
1. Chahyadi A, Hartati R, Wirasutisna KR, Elfahmi. Boesenbergia pandurata Roxb., An Indonesian medicinal plant: phytochemistry, biological activity, plant biotechnology. Procedia Chem. 2014; 13: 13–37. https://doi.org/10.1016/j.proche.2014.12.003
2. Styawan AA, Susidarti RA, Purwanto, Windarsih, Rahmawati N, Sholikhah IKM, et al. Review on ginger (Zingiber officinale Roscoe): phytochemical composition, biological activities and authentication analysis. Food Res. 2022; 6(4): 443–54.
3. Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T, et al. Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Vol. 8, Foods. MDPI Multidisciplinary Digital Publishing Institute; 2019. https://doi.org/10.3390/foods8060185
4. Liu Y, Liu J, Zhang Y. Research progress on chemical constituents of Zingiber officinale Roscoe. Vol. 2019, BioMed Research International. Hindawi Limited; 2019. https://doi.org/10.1155/2019/5370823
5. San HT, Khine HEE, Sritularak B, Prompetchara E, Chaotham C, Che CT, et al. Pinostrobin: An adipogenic suppressor from fingerroot (Boesenbergia rotunda) and its possible mechanisms. Foods. 2022 Oct 1;11(19). https://doi.org/10.3390/foods11193024
6. Widyananda MH, Wicaksono ST, Rahmawati K, Puspitarini S, Ulfa SM, Jatmiko YD, et al. A Potential anticancer mechanism of finger root (Boesenbergia rotunda) extracts against a breast cancer cell line. Scientifica (Cairo). 2022;(Article ID 9130252):1–17. https://doi.org/10.1155/2022/9130252
7. Sharma P, Mansoori S. Quantitative and qualitative analysis of Zingiber officinale as a crude drug. Res J Pharm Technol. 2019; 12(5): 2157–9. https://doi.org/10.5958/0974-360X.2019.00358.5
8. Manuhara YSW, Sugiharto, Kristanti AN, Aminah NS, Wibowo AT, Wardana AP, et al. Antioxidant activities, total phenol, flavonoid, and mineral content in the rhizome of various Indonesian herbal plants. Rasayan Journal of Chemistry. 2022; Oct 1; 15(4): 2724–30. https://doi.org/10.31788/RJC.2022.1548024
9. Kim JM, Kim HG, Son CG. Tissue-specific profiling of oxidative stress-associated transcriptome in a healthy mouse model. Int J Mol Sci. 2018; 19(10). https://doi.org/10.3390/ijms19103174
10. Kim HH, Ha SE, Vetrivel P, Bhosale PB, Kim SM, Kim GS. Potential antioxidant and anti-inflammatory function of Gynura procumbens polyphenols ligand. Int J Mol Sci. 2021; 22(16). https://doi.org/10.3390/ijms22168716
11. Kumar A, Khushboo, Pandey R, Sharma B. Modulation of superoxide dismutase activity by mercury, lead, and arsenic. Biol Trace Elem Res. 2020; Aug 10; 196(2): 654–61. https://doi.org/10.1007/s12011-019-01957-3
12. Lillo C, Lea US, Ruoff P. Nutrient depletion as a key factor for manipulating gene expression and product formation in different branches of the flavonoid pathway. Plant Cell Environ. 2008; May; 31(5): 587–601. https://doi.org/10.1111/j.1365-3040.2007.01748.x
13. Kumar TR, Kumar P, Nand SP. Magnesium deficiency induced oxidative stress and antioxidant responses in mulberry plants. Sci Hortic. 2006; Mar; 108(1): 7–14. https://doi.org/10.1016/j.scienta.2005.12.006
14. Sugiharto, Wibowo AT, Ummi Z, Annisa DS, Faukib MS, Navy SS, et al. Biological properties of Gynura procumbens leaves extract to MDA levels and antioxidant activities in liver of mice. Res. J. Pharm. Technol. 2022; Dec 24; 5829–34. https://doi.org/10.52711/0974-360X.2022.00984
15. Sugiharto, Winarni D, Islamatasya U, Muhsyi AH, Merpati AB, Manuhara YSW. The protective effect of Gynura procumbens adventitious root against lead acetate toxicity in mice. J Trop Biodivers Biotechnol. 2022; 7(2): 1–9. https://doi.org/10.22146/jtbb.69453
16. Sugiharto, Zubaidah U, Winarni D, Manuhara YSW. Gynura procumbens methanolic extracts suppresses proliferation of hepatocellular carcinoma: In vitro assay. In: The 8th International Conference and Workshop on Basic and Applied Science (ICOWOBAS) 2021. AIP Publishing; 2023. p. 090007. https://doi.org/10.1063/5.0104809
17. Harun NH, Mohamad FM. The immunomodulatory effects of Zingiber officinale (ginger): A systematic review. Res J Pharm Technol. 2022; Aug 30; 15(8): 3776–81. https://doi.org/10.52711/0974-360X.2022.00634
18. Patil SD, Vinayak K, Balsubraniyan, Anwar S. Docking studies and synthesis of novel flavones screened for biological activities like anticancer and antioxidant activity. Asian Journal of Research in Chemistry. 2015; 8(6): 399–406. https://doi.org/10.5958/0974-4150.2015.00066.8
19. Höferl M, Stoilova I, Wanner J, Schmidt E, Jirovetz L, Trifonova D, et al. Composition and comprehensive antioxidant activity of ginger (Zingiber officinale) essential oil from Ecuador. Nat Prod Commun. 2015; 10(6). https://doi.org/10.1177/1934578X1501000672
20. Wresdiyati T, Astawan M, Muchtadi D, Nurdiana Y. Antioxidant activity of ginger (Zingiber officinale) oleoresin on the profile of superoxide dismutase (SOD) in the kidney of rats under stress condition. Jurnal Teknologi dan Industri Pangan. 2007; 18(2): 118–25.
21. Rosdianto AM, Puspitasari IM, Lesmana R, Levita J. Bioactive compounds of Boesenbergia sp. and their anti-inflammatory mechanism: A review. J Appl Pharm Sci. 2020; Jul 1; 10(7): 116–26. https://doi.org/10.7324/JAPS.2020.10715
22. Rosdianto A, Puspitasari I, Lesmana R, Sumiwi S, Megantara S, Jiranusornkul S, et al. Inhibitory effects of Indonesian temu kunci (Boesenbergia rotunda ) rhizome extract on nitric oxide synthase production and on the kidneys of Wistar rats . World Acad Sci J. 2022; 4(5): 1–7. https://doi.org/10.3892/wasj.2022.173
23. Widyananda MH, Kurniasari CA, Alam FM, Rizky WC, Dings TGA, Ansori ANM, et al. Exploration of potentially bioactive compounds from fingerroot (Boesenbergia rotunda L.) as inhibitor of atherosclerosis-related proteins (CETP, ACAT1, OSC, sPLA2): An in silico Study. Jordan Journal of Pharmaceutical Sciences. 2023; 16(3): 550–64. https://doi.org/10.35516/jjps.v16i3.1609
24. Leone A, Roca MS, Ciardiello C, Costantini S, Budillon A. Oxidative stress gene expression profile correlates with cancer patient poor prognosis: Identification of crucial pathways might select novel therapeutic approaches. Oxid Med Cell Longev. 2017; 2017. https://doi.org/10.1155/2017/2597581
25. Hong J, Bae M, Kim B. Effects of bilberry extract on hepatic cholesterol metabolism in HepG2 cells. Applied Sciences. 2022; 13(1): 516. https://doi.org/10.3390/app13010516
26. Bardi AD, Halabi MF, Abdullah NA, Rouhollahi E, Hajrezaie M, Abdulla MA. In vivo evaluation of ethanolic extract of Zingiber officinale rhizomes for its protective effect against liver cirrhosis. Biomed Res Int. 2013; 1–10. https://doi.org/10.1155/2013/918460
27. Thusyanthan J, Wickramaratne NS, Senathilake KS, Rajagopalan U, Tennekoon KH, Thabrew I, et al. Cytotoxicity against human hepatocellular carcinoma (HepG2) cells and anti-oxidant activity of selected endemic or medicinal plants in Sri Lanka. Adv Pharmacol Pharm Sci. 2022; 1–9. https://doi.org/10.1155/2022/6407688
28. Soraya M, Sievers J, Denis D, Bowolaksono A, Sasmono RT. α-Mangostin effectively inhibits chikungunya virus replication in HepG2 cells. Hayati. 2023; 30(6): 1187–93. https://doi.org/10.4308/hjb.30.6.1187-1193
29. Parida R, Nayak S. Anti-proliferative activity of in vitro Zingiberaceae essential oil against human cervical cancer (HeLa) cell line. Res J Pharm Technol. 2022; 15(1): 325–8. https://doi.org/10.52711/0974-360X.2022.00053
30. Danciu C, Vlaia L, Fetea F, Hancianu M, Coricovac DE, Ciurlea SA, et al. Evaluation of phenolic profile, antioxidant and anticancer potential of two main representants of Zingiberaceae family against B164A5 murine melanoma cells. Biol Res. 2015; 48: 1–9. https://doi.org/10.1186/0717-6287-48-1
31. Break MK Bin, Chiang M, Wiart C, Chin CF, Khoo ASB, Khoo TJ. Cytotoxic activity of Boesenbergia rotunda extracts against nasopharyngeal carcinoma cells (HK1). Cardamonin, a Boesenbergia rotunda constituent, inhibits growth and migration of HK1 cells by inducing caspase-dependent apoptosis and G2/M-Phase arrest. Nutr Cancer. 2021; 73(3): 473–83. https://doi.org/10.1080/01635581.2020.1751217
32. Widyananda MH, Pratama SK, Ansori ANM, Antonius Y, Kharisma VD, Murtadlo AAA, et al. Quercetin as an anticancer candidate for glioblastoma multiforme by targeting AKT1, MMP9, ABCB1, and VEGFA: An in silico study. Karbala International Journal of Modern Science. 2023; 9(3): 450–9. https://doi.org/10.33640/2405-609X.3312
33. Arvindganth R, Anupriya KV, Kathiravan. G. Enhancement of anticancer drug Annona muricata against HT-29 cell line using silver nano particles. Res J Pharm Technol. 2017; 10(2): 529–32. https://doi.org/10.5958/0974-360X.2017.00105.6
34. Balabhaskar R, Vijayalakshmi K. Evaluation of anticancer activity of ethanol extract of Bauhinia tomentosa Linn. on A549, human lung carcinoma cell lines. Res J Pharm Technol. 2019; 12(6): 2748–52. https://doi.org/10.5958/0974-360X.2019.00460.8
35. Sugiharto, Winarni D, Wibowo AT, Islamatasya U, Bhakti IN, Nisa N, et al. Gynura procumbens adventitious root extract altered expression of antioxidant genes and exert hepatoprotective effects against cadmium-induced oxidative stress in mice. Hayati. 2022; 29(4): 479–86. https://doi.org/10.4308/hjb.29.4.479-486
36. Sugiharto, Darmanto W, Wahyuningsih SPA, Hayati A, Martha Y, Olivia P, et al. Antioxidant activities of curcumin to MDA blood serum concentration and lead levels in liver of mice. Malaysian Journal of Science. 2019; 38(3): 21–9. https://doi.org/10.22452/mjs.sp2019no3.3
37. Sugiharto, Ariff A, Ahmad S, Hamid M. Properties of kojic acid and curcumin: Assay on cell B16-F1. AIP Conf Proc. 2016; 1718: 10–5. https://doi.org/10.1063/1.4943328
38. Jun M, Fu HY, Hong J, Wan X, Yang CS, Ho CT. Comparison of antioxidant activities of isoflavones from kudzu root (Pueraria lobata Ohwi). J Food Sci. 2003; 68(6): 2117–22. https://doi.org/10.1111/j.1365-2621.2003.tb07029.x
39. Supu RD, Diantini A, Levita J. Red ginger (Zingiber officinale var. rubrum): Its chemical constituents, pharmacological activities and safety. Fitofarmaka Jurnal Ilmiah Farmasi. 2018; 8(1): 25–31. https://doi.org/10.33751/jf.v8i1.11768
40. Ghasemzadeh A, Jaafar HZE, Rahmat A. Antioxidant activities, total phenolics and flavonoids content in two varieties of Malaysia young ginger (Zingiber officinale Roscoe). Molecules. 2010;15(6):4324–33. https://doi.org/10.3390/molecules15064324
41. Atun S, Handayani S, Rakhmawati A. Potential bioactive compounds isolated from Boesenbergia rotunda as antioxidant and antimicrobial agents. Pharmacognosy Journal. 2018; 10(3): 513–8. https://doi.org/10.5530/pj.2018.3.84
42. Razak AM, Tan JK, Mohd Said MM, Makpol S. Modulating effects of Zingiberaceae phenolic compounds on neurotrophic factors and their potential as neuroprotectants in brain disorders and age-associated neurodegenerative disorders: A review. Nutrients. 2023; 15(11): 2564. https://doi.org/10.3390/nu15112564
43. Isa NM, Abdelwahab SI, Mohan S, Abdul AB, Sukari MA, Taha MME, et al. In vitro anti-inflammatory, cytotoxic and antioxidant activities of Boesenbergin A, a chalcone isolated from Boesenbergia rotunda (L.) (fingerroot). Brazilian Journal of Medical and Biological Research. 2012; 45(6): 524–30. https://doi.org/10.1590/S0100-879X2012007500022
44. Wallace DR, Taalab YM, Heinze S, Tariba Lovaković B, Pizent A, Renieri E, et al. Toxic-metal-induced alteration in miRNA expression profile as a proposed mechanism for disease development. Cells. 2020; 9(4). https://doi.org/10.3390/cells9040901
45. Metwally ASAM, Negm FA, El-din RAS, Nabil EM. Anatomical and histological study of the effect of lead on hepatocytes of albino rats. International Journal of Biomedical Materials Research. 2015; 3(4): 34–45. https://doi.org/10.11648/j.ijbmr.20150304.11
46. Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A. The effects of cadmium toxicity. Int J Environ Res Public Health. 2020; 17(3782): 1–24. https://doi:10.3390/ijerph17113782
47. Sawant R, Baghkar A, Jagtap S, Harad L, Chavan A, Khan NA, et al. A Review on-herbs in anticancer. Asian Journal of Research in Pharmaceutical Science. 2018; 8(4): 179–84. https://doi.org/10.5958/2231-5659.2018.00031.0
48. Yadav AR, Mohite SK. Anticancer activity of Psidium guajava leaf extracts on breast cancer cell line. Research Journal of Pharmaceutical Dosage Forms and Technology. 2020; 12(4): 298–300. https://doi.org/10.5958/0975-4377.2020.00049.X
49. Selvam R, Anandhi D, Saravanan D, Revathi K. Antioxidant properties of Punica grantum fruit rind extract against liver hepatocellular carcinoma studied in HepG2 cell line. Res J Pharm Technol. 2019; 12(10): 4719–23. https://doi.org/10.5958/0974-360X.2019.00813.8
50. Gupta P, Yaqub Khan M, Kumar Verma V, Pathak A. Beating cancer with natural plant sources. Asian J Pharm Tech. 2013; 3(2): 39–44. Available from: www.asianpharmaonline.org
51. Kumar S, Nair R, Gupta S, Abdullah A, Talwar P, Ravanan P. Anti-cancer and neuro-protective effect of Cuminum cyminum extracts on IMR32 human neuroblastoma cell lines. Res J Pharm Technol. 2018; 11(4): 1547–52. https://doi.org/10.5958/0974-360X.2018.00288.3
52. Fadholly A, Ansori ANM, Utomo B. Anticancer effect of naringin on human colon cancer (WiDr cells): In vitro study. Res J Pharm Technol. 2022; 15(2): 885–8. https://doi.10.52711/0974-360X.2022.00148