Skip to content
2000
image of The Therapeutic Potentials of Chemo-Herbal Combination: Enhancing Anti-tumor immunity and Anti-cancer activity against Ehrlich Ascites Carcinoma

Abstract

Introduction

The combinational chemo-herbal therapy effectively suppresses tumors and reduces their chemoresistance.

Objective

This study evaluated the anti-cancer and anti-tumor immunity properties of a chemo-herbal therapy combination of Curcumin (Cur), Ginger (Gin), Clove (Clov), Ginger (Gin), and Amygdalin (Amyg) with Doxorubicin (DOX) against the Ehrlich Ascites Carcinoma (EAC) cell line.

Methods

The study examined the anti-tumor effects of herbal extracts from Cur, Gin, Clov, and Amyg alone and with DOX against EAC using the MTT assay. It evaluated anti-cancer and anti-tumoral immunity, cell counts, growth rates, and apoptosis of EAC cells, phenotypic expression of T lymphocytes (CD4+T and CD8+T) and natural killer (NK) cells, splenocyte and leucocyte counts, as well as Liver and kidney functions in EAC-challenged mice treated with extracts from Cur, Gin, Clov, and Amyg alone and with DOX.

Results

Chemo-herbal therapy using extracts of Cur, Gin, Clov, and Amyg combined with DOX showed significant anti-proliferative effects on EAC . , this combined treatment in tumor-challenged mice reduced EAC cell proliferation by decreasing cell counts and increasing apoptosis rates. Furthermore, it enhanced the expression of CD4+T and CD8+T lymphocytes and NK cells, while slightly increasing total leukocyte counts, neutrophils, and monocytes, but reducing total lymphocytes and eosinophils. Additionally, the combination therapy mitigated EAC-induced liver and kidney damage, restoring normal organ function.

Discussion

The integration of herbal extracts derived from Cur, Gin, Clov, and Amyg with the chemotherapy drug DOX may improve the effectiveness of chemotherapy in combating tumors and strengthen the immune response of the host against cancer.

Conclusion

Chemo-herbal therapy combining Cur, Gin, Clov, and Amyg with DOX may improve anti-tumor effects, enhance immune response, and reduce chemotherapy side effects, but requires additional studies for validation.

Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266374075251103144517
2026-01-22
2026-01-31
Loading full text...

Full text loading...

References

  1. Torigoe T. Izumi H. Ishiguchi H. Yoshida Y. Tanabe M. Yoshida T. Igarashi T. Niina I. Wakasugi T. Imaizumi T. Momii Y. Kuwano M. Kohno K. Cisplatin resistance and transcription factors. Curr. Med. Chem. Anticancer Agents 2005 5 1 15 27 10.2174/1568011053352587 15720258
    [Google Scholar]
  2. Siegel R.L. Miller K.D. Fuchs H.E. Jemal A. Cancer Statistics, 2021. CA Cancer J. Clin. 2021 71 1 7 33 10.3322/caac.21654 33433946
    [Google Scholar]
  3. Hong W.K. Sporn M.B. Recent advances in chemoprevention of cancer. Science 1997 278 5340 1073 1077 10.1126/science.278.5340.1073 9353183
    [Google Scholar]
  4. Ma L. Zhang M. Zhao R. Wang D. Ma Y. Ai L. Plant natural products: Promising resources for cancer chemoprevention. Molecules 2021 26 4 933 10.3390/molecules26040933 33578780
    [Google Scholar]
  5. De Flora S. Ferguson L.R. Overview of mechanisms of cancer chemopreventive agents. Mutat Res. 2005 591 1-2 8 15 10.1016/j.mrfmmm.2005.02.029 16107270
    [Google Scholar]
  6. George B.P. Chandran R. Abrahamse H. Role of phytochemicals in cancer chemoprevention: Insights. Antioxidants 2021 10 9 1455 10.3390/antiox10091455 34573087
    [Google Scholar]
  7. Ramos S. Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways. Mol. Nutr. Food. Res. 2008 52 5 507 526 10.1002/mnfr.200700326 18435439
    [Google Scholar]
  8. Surh Y.J. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 2003 3 10 768 780 10.1038/nrc1189 14570043
    [Google Scholar]
  9. Noureini S.K. Wink M. Antiproliferative effects of crocin in HepG2 cells by telomerase inhibition and hTERT down-regulation. Asian Pac J. Cancer Prev 2012 13 5 2305 2309 10.7314/APJCP.2012.13.5.2305 22901211
    [Google Scholar]
  10. Elsayed E.A. Sharaf-Eldin M.A. El-Enshasy H.A. Wadaan M. In vitro assessment of anticancer properties of Moringa peregrine essential seed oil on different cell lines. Pak J. Zool. 2016 48 853 859
    [Google Scholar]
  11. Xu D.P. Li Y. Meng X. Zhou T. Zhou Y. Zheng J. Zhang J.J. Li H.B. Natural antioxidants in foods and medicinal plants: Extraction, assessment and resources. Int. J. Mol. Sci. 2017 18 1 96 10.3390/ijms18010096 28067795
    [Google Scholar]
  12. Ouyang L. Luo Y. Tian M. Zhang S.Y. Lu R. Wang J.H. Kasimu R. Li X. Plant natural products: from traditional compounds to new emerging drugs in cancer therapy. Cell. Prolif. 2014 47 6 506 515 10.1111/cpr.12143 25377084
    [Google Scholar]
  13. Pai M.P. Cottrell M.L. Kashuba A.D. Bertino J.S. Pharmacokinetics and pharmacodynamics of anti-infective agents Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Amsterdam, The Netherlands Elsevier 2015 252 262
    [Google Scholar]
  14. Hu X.Q. Sun Y. Lau E. Zhao M. Su S.B. Advances in synergistic combinations of Chinese herbal medicine for the treatment of cancer. Curr. Cancer Drug Targets 2016 16 4 346 356 10.2174/1568009616666151207105851 26638885
    [Google Scholar]
  15. Zhang X. Chen L.X. Ouyang L. Cheng Y. Liu B. Plant natural compounds: targeting pathways of autophagy as anti‐cancer therapeutic agents. Cell..... Prolif. 2012 45 5 466 476 10.1111/j.1365‑2184.2012.00833.x 22765290
    [Google Scholar]
  16. Lin S.R. Fu Y.S. Tsai M.J. Cheng H. Weng C.F. Natural compounds from herbs that can potentially execute as autophagy inducers for cancer therapy. Int. J. Mol. Sci. 2017 18 7 1412 10.3390/ijms18071412 28671583
    [Google Scholar]
  17. Chen T. Xiao Z. Liu X. Wang T. Wang Y. Ye F. Su J. Yao X. Xiong L. Yang D.H. Natural products for combating multidrug resistance in cancer. Pharmacol. Res. 2024 202 107099 10.1016/j.phrs.2024.107099 38342327
    [Google Scholar]
  18. Pathak K. Pathak M.P. Saikia R. Gogoi U. Sahariah J.J. Zothantluanga J.H. Samanta A. Das A. Cancer chemotherapy via natural bioactive compounds. Curr. Drug Discov. Technol. 2022 19 4 e310322202888 10.2174/1570163819666220331095744 35362385
    [Google Scholar]
  19. Serafini M. Stanzione A. Foddai S. Anton R. Delmulle L. The European role on traditional herbal medicinal products and traditional plant food supplements. J. Clin. Gastroenterol. 2012 46 S93 S94 (Suppl.) 10.1097/MCG.0b013e318266b08f 22955367
    [Google Scholar]
  20. Aung T. Qu Z. Kortschak R. Adelson D. Understanding the effectiveness of natural compound mixtures in cancer through their molecular mode of action. Int. J. Mol. Sci. 2017 18 3 656 10.3390/ijms18030656 28304343
    [Google Scholar]
  21. Koh Y.C. Ho C.T. Pan M.H. Recent advances in cancer chemoprevention with phytochemicals. Yao Wu Shi Pin Fen Xi 2020 28 1 14 37 10.38212/2224‑6614.1219 31883602
    [Google Scholar]
  22. Shukla Y. Pal S.K. Dietary cancer chemoprevention: An overview. Int. J. Hum. Genet. 2004 4 4 265 276 10.1080/09723757.2004.11885905
    [Google Scholar]
  23. Tavakoli J. Miar S. Majid Zadehzare M. Akbari H. Evaluation of effectiveness of herbal medication in cancer care: a review study. Iran J. Cancer Prev 2012 5 3 144 156 25628834
    [Google Scholar]
  24. Ayaz M. Nawaz A. Ahmad S. Mosa O.F. Eisa Hamdoon A.A. Khalifa M.A. Sadiq A. Ullah F. Wadood A. Kabra A. Ananda Murthy H.C. Underlying anticancer mechanisms and synergistic combinations of phytochemicals with cancer chemotherapeutics: potential benefits and risks. J. Food. Qual 2022 2022 1 1 15 10.1155/2022/1189034
    [Google Scholar]
  25. Gill C.I.R. Boyd A. McDermott E. McCann M. Servili M. Selvaggini R. Taticchi A. Esposto S. Montedoro G. McGlynn H. Rowland I. Potential anti-cancer effects of virgin olive oil phenolson colorectal carcinogenesis modelsin vitro. Int. J. Cancer 2005 117 1 1 7 10.1002/ijc.21083 15880398
    [Google Scholar]
  26. Gomez-Cadena A. Urueña C. Prieto K. Martinez-Usatorre A. Donda A. Barreto A. Romero P. Fiorentino S. Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model. Cell Death Dis. 2016 7 6 e2243 10.1038/cddis.2016.134 27253407
    [Google Scholar]
  27. Saetang J. Tedasen A. Sangkhathat S. Sangkaew N. Dokduang S. Prompat N. Taraporn S. Graidist P. Low piperine fractional piper nigrum extract enhanced the antitumor immunity via regulating the Th1/Th2/Treg cell subsets on NMU-induced tumorigenesis rats. Planta Med. 2022 88 7 527 537 10.1055/a‑1458‑5646 33902130
    [Google Scholar]
  28. Lee D.J. Han I.M. Kim W.J. Cho I.S. Anti-microbial, antiinflammatory and anti-oxidative effects of herbal medicine extracts as anti-gingivitis ingredients. J. Dent. Hyg Sci. 2010 10 1 25 29 10.17135/jdhs.2020.20.1.25
    [Google Scholar]
  29. Moghadamtousi S.Z. Kadir H.A. Paydar M. Rouhollahi E. Karimian H. Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB. BMC Complement Altern Med. 2014 14 1 299 10.1186/1472‑6882‑14‑299 25127718
    [Google Scholar]
  30. Kim J.H. Do E.J. Lee G. Investigation of anti-microbial activity of herbal medicines used as natural preservatives based on the analysis of papers and patents. Dongui Saengli Byeongli Haghoeji 2015 29 1 101 113 10.15188/kjopp.2015.02.29.1.101
    [Google Scholar]
  31. Patil K. Guledgud M.V. Kulkarni P. KeShari D, Tayal S. Use of curcumin mouthrinse in radio-chemotherapy induced oral mucositis patients: A pilot study. J. Clin. Diagn. Res. 2015 9 8 59 62
    [Google Scholar]
  32. Newman D.J. Cragg G.M. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod. 2007 70 3 461 477 10.1021/np068054v 17309302
    [Google Scholar]
  33. Bose S. Panda A.K. Mukherjee S. Sa G. Curcumin and tumor immune-editing: resurrecting the immune system. Cell. Div 2015 10 1 6 10.1186/s13008‑015‑0012‑z 26464579
    [Google Scholar]
  34. Churchill M. Chadburn A. Bilinski R.T. Bertagnolli M.M. Inhibition of intestinal tumors by curcumin is associated with changes in the intestinal immune cell profile. J. Surg. Res. 2000 89 2 169 175 10.1006/jsre.2000.5826 10729246
    [Google Scholar]
  35. Li M. Jiang Y. Hou Q. Zhao Y. Zhong L. Fu X. Potential pre-activation strategies for improving therapeutic efficacy of mesenchymal stem cells: current status and future prospects. Stem Cell. Res. Ther. 2022 13 1 146 10.1186/s13287‑022‑02822‑2 35379361
    [Google Scholar]
  36. Bhattacharyya S. Md Sakib Hossain D. Mohanty S. Sankar Sen G. Chattopadhyay S. Banerjee S. Chakraborty J. Das K. Sarkar D. Das T. Sa G. Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts. Cell. Mol. Immunol. 2010 7 4 306 315 10.1038/cmi.2010.11 20305684
    [Google Scholar]
  37. Bhattacharyya S. Mandal D. Saha B. Sen G.S. Das T. Sa G. Curcumin prevents tumor-induced T cell apoptosis through Stat-5a-mediated Bcl-2 induction. J. Biol. Chem. 2007 282 22 15954 15964 10.1074/jbc.M608189200 17392282
    [Google Scholar]
  38. Zhao G. Lu Z. Tang L. Wu Z. Wang D. Zheng J. Qiu Q. Curcumin inhibits suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro. Int. Immunopharmacol. 2012 14 1 99 106 10.1016/j.intimp.2012.06.016 22749847
    [Google Scholar]
  39. Duan S. Hu Y. Zhao Y. Tang K. Zhang Z. Liu Z. Wang Y. Guo H. Miao Y. Du H. Yang D. Li S. Zhang J. Nanomaterials for photothermal cancer therapy. RSC Advances 2023 13 21 14443 14460 10.1039/D3RA02620E 37180014
    [Google Scholar]
  40. Liao F. Liu L. Luo E. Hu J. Curcumin enhances anti-tumor immune response in tongue squamous cell carcinoma. Arch. Oral Biol. 2018 92 32 37 10.1016/j.archoralbio.2018.04.015 29751146
    [Google Scholar]
  41. Liu L. Lim M.A. Jung S.N. Oh C. Won H.R. Jin Y.L. Piao Y. Kim H.J. Chang J.W. Koo B.S. The effect of Curcumin on multi-level immune checkpoint blockade and T cell dysfunction in head and neck cancer. Phytomedicine 2021 92 153758 10.1016/j.phymed.2021.153758 34592487
    [Google Scholar]
  42. Chang Y.F. Chuang H.Y. Hsu C.H. Liu R.S. Gambhir S.S. Hwang J.J. Immunomodulation of curcumin on adoptive therapy with T cell functional imaging in mice. Cancer Prev. Res. 2012 5 3 444 452 22135043
    [Google Scholar]
  43. Yu C. Yang B. Najafi M. Targeting of cancer cell death mechanisms by curcumin: Implications to cancer therapy. Basic Clin. Pharmacol. Toxicol. 2021 129 6 397 415 34473898
    [Google Scholar]
  44. Srivastava R.M. Singh S. Dubey S.K. Misra K. Khar A. Immunomodulatory and therapeutic activity of curcumin. Int. Immunopharmacol. 2011 11 3 331 341 20828642
    [Google Scholar]
  45. Grudzien M. Rapak A. Effect of Natural Compounds on NK Cell Activation. J. Immunol. Res. 2018 2018 4868417 30671486
    [Google Scholar]
  46. Xu L. Zhang Y. Tian K. Chen X. Zhang R. Mu X. Wu Y. Wang D. Wang S. Liu F. Wang T. Zhang J. Liu S. Zhang Y. Tu C. Liu H. Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic effects. J. Exp. Clin. Cancer Res. 2018 37 1 261 30373602
    [Google Scholar]
  47. Tejasari D. Evaluation of Ginger (Zingiber officinale Roscoe) Bioactive Compounds in Increasing the Ratio of T-cell Surface Molecules of CD3+CD4+:CD3+CD8+ In-Vitro. Malays J. Nutr. 2007 13 2 161 170 22691754
    [Google Scholar]
  48. Wael S. Watuguly T. Arini I. Smit A. Matdoan N. Prihati D. Potential of Syzygium aromaticum (Clove) Leaf Extract on Immune Proliferation Response in Balb/c Mice Infected with Salmonella typhimurium. Case Rep Clin. Med. 2018 7 613 627
    [Google Scholar]
  49. Samuchiwal S.K. Boyce J.A. Role of lipid mediators and control of lymphocyte responses in type 2 immunopathology. J. Allergy Clin. Immunol. 2018 141 4 1182 1190 29477727
    [Google Scholar]
  50. Halder S. Mehta A.K. Mediratta P.K. Sharma K.K. Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity. Phytother Res. 2011 25 8 1254 1256 21796701
    [Google Scholar]
  51. Dibazar S.P. Fateh S. Daneshmandi S. Immunomodulatory effects of clove (Syzygium aromaticum) constituents on macrophages: in vitro evaluations of aqueous and ethanolic components. J. Immunotoxicol. 2015 12 2 124 131 24873744
    [Google Scholar]
  52. Farooqui T. Farooqui AA Curcumin: Historical Background, chemistry, pharmacological action, and potential therapeutic valuecurcumin for neurological and psychiatric disorders. Academic Press 2019 23 44 10.1016/B978‑0‑12‑815461‑8.00002‑5
    [Google Scholar]
  53. Toden S. Tran H.M. Tovar-Camargo O.A. Okugawa Y. Goel A. Epigallocatechin-3-gallate targets cancer stem-like cells and enhances 5-fluorouracil chemosensitivity in colorectal cancer. Oncotarget 2016 7 13 16158 16171 26930714
    [Google Scholar]
  54. Lee Y.J. Lee Y.J. Im J.H. Won S.Y. Kim Y.B. Cho M.K. Nam H.S. Choi Y.J. Lee S.H. Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells. Food Chem. Toxicol. 2013 52 61 68 23146690
    [Google Scholar]
  55. Shanmugam M.K. Dai X. Kumar A.P. Tan B.K. Sethi G. Bishayee A. Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies. Biochem. Pharmacol. 2013 85 11 1579 1587 23499879
    [Google Scholar]
  56. Mamindla S. Prasad K.V.S.R.G. Koganti B. Herb-drug interactions: an overview of mechanisms and clinical aspects. Int. J. Pharm. Sci. Res. 2016 7 9 3576
    [Google Scholar]
  57. Konga A.K. Muchandi A.S. Ponnaiah G.P. Soxhlet extraction of Spirogyra sp. algae: An alternative fuel. Biofuels 2017 8 1 29 35
    [Google Scholar]
  58. Borodulin D. Prosin M. Bakin I. Lobasenko B. Potapova M. Shalev A. The use of Soxhlet extractor for the production of tinctures from plant raw materials. E3S Web of Conferences 2020 p.10 10.1051/e3sconf/202017508010
    [Google Scholar]
  59. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983 65 1-2 55 63 10.1016/0022‑1759(83)90303‑4 6606682
    [Google Scholar]
  60. Halle W. Halder M. Worth A. Genschow E. The Registry of Cytotoxicity: toxicity testing in cell cultures to predict acute toxicity (LD50) and to reduce testing in animals. Altern Lab. Anim. 2003 31 2 89 198 10.1177/026119290303100204 15612878
    [Google Scholar]
  61. Gothoskar S.V. Ranadive K.J. Anticancer screening of SAN-AB: an extract of marking nut, Semecarpus anacardium. Indian J. Exp. Biol. 1971 9 3 372 375 5144337
    [Google Scholar]
  62. Abdel Salam S.R. Salem M. Nassef M. Abdu S. El-Adl R. Efficacy of combined administration of chemoimmunotherapy with bone marrow cells or granulocyte-colony stimulating factor-mobilized stem cells on expansion of myeloid and stem cells. Clin. Cancer Investig. J. 2017 6 1 73 80 10.4103/ccij.ccij_4_17
    [Google Scholar]
  63. Nassef M. Immunobiochemical modulations caused by clomazone in Swiss albino mice. J. Basic Appl. Zool. 2017 78 1 8
    [Google Scholar]
  64. Gomaa S. Adverse effects induced by diclofenac, ibuprofen, and paracetamol toxicity on immunological and biochemical parameters in Swiss albino mice. J. Basic Appl. Zool. 2018 79 1 1 9
    [Google Scholar]
  65. Gomaa S. Nassef M. Tabl G. Zaki S. Abdel-Ghany A. Doxorubicin and folic acid-loaded zinc oxide nanoparticles-based combined anti-tumor and anti-inflammatory approach for enhanced anti-cancer therapy. BMC Cancer 2024 24 1 34 10.1186/s12885‑023‑11714‑4 38178054
    [Google Scholar]
  66. Siegel R.L. Miller K.D. Jemal A. Jemal A. Cancer statistics, 2017. CA Cancer J. Clin. 2017 67 1 7 30 10.3322/caac.21387 28055103
    [Google Scholar]
  67. Chen S. Flower A. Ritchie A. Liu J. Molassiotis A. Yu H. Lewith G. Oral Chinese herbal medicine (CHM) as an adjuvant treatment during chemotherapy for non-small cell lung cancer: A systematic review. Lung Cancer 2010 68 2 137 145 10.1016/j.lungcan.2009.11.008 20015572
    [Google Scholar]
  68. Fu B. Wang N. Tan H.Y. Li S. Cheung F. Feng Y. Multi-component herbal products in the prevention and treatment of chemotherapy-associated toxicity and side effects: A review on experimental and clinical evidences. Front. Pharmacol. 2018 9 1394 10.3389/fphar.2018.01394 30555327
    [Google Scholar]
  69. Lee S. Han S. Park J.S. Jeong A.L. Jung S.H. Choi K.D. Han T-Y. Han I-Y. Yang Y. Herb mixture C5E aggravates doxorubicin-induced apoptosis of human breast cancer cell lines. J. Korean Soc. Appl. Biol. Chem. 2013 56 5 567 573 10.1007/s13765‑013‑3195‑5
    [Google Scholar]
  70. Wang Z. Xie C. Huang Y. Lam C.W.K. Chow M.S.S. Overcoming chemotherapy resistance with herbal medicines: Past, present and future perspectives. Phytochem Rev. 2014 13 1 323 337 10.1007/s11101‑013‑9327‑z
    [Google Scholar]
  71. Chen S. Wang Z. Huang Y. O’Barr S.A. Wong R.A. Yeung S. Chow M.S. Ginseng and anticancer drug combination to improve cancer chemotherapy: A critical review. Evid Based Complement. Alternat. Med. 2014 2014 168940 10.1155/2014/168940 24876866
    [Google Scholar]
  72. Ng C.X. Affendi M.M. Chong P.P. Lee S.H. The potential of plant-derived extracts and compounds to augment anticancer effects of chemotherapeutic drugs. Nutr. Cancer 2022 74 9 3058 3076 10.1080/01635581.2022.2069274 35675271
    [Google Scholar]
  73. Mbaveng A.T. Kuete V. Mapunya B.M. Beng V.P. Nkengfack A.E. Meyer J.J.M. Lall N. Evaluation of four Cameroonian medicinal plants for anticancer, antigonorrheal and antireverse transcriptase activities. Environ. Toxicol. Pharmacol. 2011 32 2 162 167 10.1016/j.etap.2011.04.006 21843795
    [Google Scholar]
  74. Lin X. Yang F. Huang J. Jiang S. Tang Y. Li J. Ameliorate effect of pyrroloquinoline quinone against cyclophosphamide-induced nephrotoxicity by activating the Nrf2 pathway and inhibiting the NLRP3 pathway. Life. Sci. 2020 256 117901 10.1016/j.lfs.2020.117901 32504759
    [Google Scholar]
  75. Devassy J.G. Nwachukwu I.D. Jones P.J.H. Curcumin and cancer: Barriers to obtaining a health claim. Nutr. Rev. 2015 73 3 155 165 10.1093/nutrit/nuu064 26024538
    [Google Scholar]
  76. Shanmugam M. Rane G. Kanchi M. Arfuso F. Chinnathambi A. Zayed M. Alharbi S. Tan B. Kumar A. Sethi G. The multifaceted role of curcumin in cancer prevention and treatment. Molecules 2015 20 2 2728 2769 10.3390/molecules20022728 25665066
    [Google Scholar]
  77. Shiri S. Alizadeh A.M. Baradaran B. Farhanghi B. Shanehbandi D. Khodayari S. Khodayari H. Tavassoli A. Dendrosomal curcumin suppresses metastatic breast cancer in mice by changing m1/m2 macrophage balance in the tumor microenvironment. Asian Pac J. Cancer Prev 2015 16 9 3917 3922 10.7314/APJCP.2015.16.9.3917 25987060
    [Google Scholar]
  78. Bimonte S. Barbieri A. Palma G. Rea D. Luciano A.D. Aiuto M. Dissecting the role of curcumin in tumor growth and angiogenesis in mouse model of human breast cancer. BioMed Res. Int. 2015 2015 1 7
    [Google Scholar]
  79. Sanlier N. Kocabas Ş. Erdogan K. Sanlier N.T. Effects of curcumin, its analogues, and metabolites on various cancers: Focusing on potential mechanisms. Food. Rev. Int. 2022 ••• 1 21
    [Google Scholar]
  80. Grzanna R. Lindmark L. Frondoza C.G. Ginger--an herbal medicinal product with broad anti-inflammatory actions. J. Med. Food. 2005 8 2 125 132 10.1089/jmf.2005.8.125 16117603
    [Google Scholar]
  81. Plengsuriyakarn T. Viyanant V. Eursitthichai V. Picha P. Kupradinun P. Itharat A. Na-Bangchang K. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models. BMC Complement. Altern Med 2012 12 1 23 10.1186/1472‑6882‑12‑23 22448640
    [Google Scholar]
  82. El-Saber Batiha G. Alkazmi L.M. Wasef L.G. Beshbishy A.M. Nadwa E.H. Rashwan E.K. Syzygium aromaticum L. (Myrtaceae): Traditional Uses, bioactive chemical constituents, pharmacological and toxicological activitiesf. Biomolecules 2020 10 2 202 10.3390/biom10020202 32019140
    [Google Scholar]
  83. Pistritto G. Trisciuoglio D. Ceci C. Garufi A. D’Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging 2016 8 4 603 619 10.18632/aging.100934 27019364
    [Google Scholar]
  84. Lakshminarayanan R. Chi-Jin E.O. Loh X.J. Kini R.M. Valiyaveettil S. Purification and characterization of a vaterite-inducing peptide, pelovaterin, from the eggshells of Pelodiscus sinensis (Chinese soft-shelled turtle). Biomacromolecules 2005 6 3 1429 1437 10.1021/bm049276f 15877362
    [Google Scholar]
  85. Mohanty S. Saha S. Md S. Hossain, D.; Adhikary, A.; Mukherjee, S.; Manna, A.; Chakraborty, S.; Mazumdar, M.; Ray, P.; Das, K.; Chakraborty, J.; Sa, G.; Das, T. ROS-PIASγ cross talk channelizes ATM signaling from resistance to apoptosis during chemosensitization of resistant tumors. Cell. Death Dis. 2014 5 1 e1021 10.1038/cddis.2013.534 24457965
    [Google Scholar]
  86. Zheng J. Zhou Y. Li Y. Xu D.P. Li S. Li H.B. Spices for Prevention and Treatment of Cancers. Nutrients 2016 8 8 495 10.3390/nu8080495 27529277
    [Google Scholar]
  87. Duvoix A. Blasius R. Delhalle S. Schnekenburger M. Morceau F. Henry E. Dicato M. Diederich M. Chemopreventive and therapeutic effects of curcumin. Cancer Lett. 2005 223 2 181 190 10.1016/j.canlet.2004.09.041 15896452
    [Google Scholar]
  88. Liu H. Chen Y. Cui G. Zhou J. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation. Acta Pharmacol. Sin. 2005 26 5 603 609 10.1111/j.1745‑7254.2005.00081.x 15842781
    [Google Scholar]
  89. Fujiwara H. Hosokawa M. Zhou X. Fujimoto S. Fukuda K. Toyoda K. Nishi Y. Fujita Y. Yamada K. Yamada Y. Seino Y. Inagaki N. Curcumin inhibits glucose production in isolated mice hepatocytes. Diabetes Res. Clin. Pract. 2008 80 2 185 191 18221818
    [Google Scholar]
  90. Cho M-L. Jung Y.O. Moon Y-M. Min S-Y. Yoon C-H. Lee S-H. Park S.H. Cho C.S. Jue D.M. Kim H.Y. Interleukin-18 induces the production of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts via AP-1-dependent pathways. Immunol. Lett. 2006 103 2 159 166 16368150
    [Google Scholar]
  91. Balar H. Shah T.YKA. Rheumatoid arthritis: Conjugating basics with drug delivery. Curr. Rheumatol. Rev. 2011 7 3 253 262
    [Google Scholar]
  92. Pulido-Moran M. Moreno-Fernandez J. Ramirez-Tortosa C. Ramirez-Tortosa M. Curcumin and Health. Molecules 2016 21 3 264 26927041
    [Google Scholar]
  93. Qadir M.I. Naqvi S.T.Q. Muhammad S.A. Qadir M. Naqvi S.T. Curcumin: A polyphenol with molecular targets for cancer control. Asian Pac. J. Cancer Prev. 2016 17 6 2735 2739 27356682
    [Google Scholar]
  94. Padhy I. Paul P. Sharma T. Banerjee S. Mondal A. molecular mechanisms of action of eugenol in cancer: Recent trends and advancement. Life. 2022 12 11 1795 36362950
    [Google Scholar]
  95. Liu H. Schmitz J.C. Wei J. Cao S. Beumer J.H. Strychor S. Cheng L. Liu M. Wang C. Wu N. Zhao X. Zhang Y. Liao J. Chu E. Lin X. Clove extract inhibits tumor growth and promotes cell cycle arrest and apoptosis. Oncol. Res. 2014 21 5 247 259 10.3727/096504014X13946388748910 24854101
    [Google Scholar]
  96. Zari A.T. Zari T.A. Hakeem K.R. Anticancer properties of eugenol: A review. Molecules 2021 26 23 7407 10.3390/molecules26237407 34885992
    [Google Scholar]
  97. Arshi A. Hosseini S.M. Hosseini F.S.K. Amiri Z.Y. Hosseini F.S. Sheikholia Lavasani M. Kerdarian H. Dehkordi M.S. The anti-cancer effect of amygdalin on human cancer cell lines. Mol. Biol. Rep. 2019 46 2 2059 2066 10.1007/s11033‑019‑04656‑3 30725348
    [Google Scholar]
  98. Jaszczak-Wilke E. Polkowska Ż. Koprowski M. Owsianik K. Mitchell A.E. Bałczewski P. Amygdalin: Toxicity, Anticancer Activity and Analytical Procedures for Its Determination in Plant Seeds. Molecules 2021 26 8 2253 10.3390/molecules26082253 33924691
    [Google Scholar]
  99. Zadorozhna M. Mangieri D. Mechanisms of chemopreventive and therapeutic proprieties of ginger extracts in cancer. Int. J. Mol. Sci. 2021 22 12 6599 10.3390/ijms22126599 34202966
    [Google Scholar]
  100. Lechner J.F. Stoner G.D. Gingers and their purified components as cancer chempreventative agents. Molecules 2019 24 16 2859 10.3390/molecules24162859 31394732
    [Google Scholar]
  101. Wee L.H. Morad N.A. Aan G.J. Makpol S. Ngah W.Z.W. Yusof Y.A.M. Mechanism of Chemoprevention against Colon Cancer Cells Using Combined Gelam Honey and Ginger Extract via mTOR and Wnt/β-catenin Pathways. Asian Pac J. Cancer Prev 2015 16 15 6549 6556 10.7314/APJCP.2015.16.15.6549 26434873
    [Google Scholar]
  102. Vemuri S.K. Banala R.R. Subbaiah G.P.V. Srivastava S.K. Reddy A.V.G. Malarvili T. Anti-cancer potential of a mix of natural extracts of turmeric, ginger and garlic: A cell-based study. Egyptian Journal of Basic and Applied Sciences 2017 4 4 332 344 10.1016/j.ejbas.2017.07.005
    [Google Scholar]
  103. Bain B.J. Structure and function of red and white blood cells and platelets. Medicine (Abingdon) 2021 49 4 183 188 10.1016/j.mpmed.2021.01.001
    [Google Scholar]
  104. Kolaczkowska E. Kubes P. Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 2013 13 3 159 175 10.1038/nri3399 23435331
    [Google Scholar]
  105. Puga I. Cols M. Barra C.M. He B. Cassis L. Gentile M. Comerma L. Chorny A. Shan M. Xu W. Magri G. Knowles D.M. Tam W. Chiu A. Bussel J.B. Serrano S. Lorente J.A. Bellosillo B. Lloreta J. Juanpere N. Alameda F. Baró T. de Heredia C.D. Torán N. Català A. Torrebadell M. Fortuny C. Cusí V. Carreras C. Diaz G.A. Blander J.M. Farber C.M. Silvestri G. Cunningham-Rundles C. Calvillo M. Dufour C. Notarangelo L.D. Lougaris V. Plebani A. Casanova J.L. Ganal S.C. Diefenbach A. Aróstegui J.I. Juan M. Yagüe J. Mahlaoui N. Donadieu J. Chen K. Cerutti A. B cell–helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat. Immunol. 2012 13 2 170 180 10.1038/ni.2194 22197976
    [Google Scholar]
  106. Hashem S. Ali T.A. Akhtar S. Nisar S. Sageena G. Ali S. Al-Mannai S. Therachiyil L. Mir R. Elfaki I. Mir M.M. Jamal F. Masoodi T. Uddin S. Singh M. Haris M. Macha M. Bhat A.A. Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents. Biomed. Pharmacother. 2022 150 113054 10.1016/j.biopha.2022.113054 35658225
    [Google Scholar]
  107. Alhazmi H.A. Najmi A. Javed S.A. Sultana S. Al Bratty M. Makeen H.A. Meraya A.M. Ahsan W. Mohan S. Taha M.M.E. Khalid A. Medicinal plants and isolated molecules demonstrating immunomodulation activity as potential alternative therapies for viral diseases including COVID-19. Front. Immunol. 2021 12 637553 10.3389/fimmu.2021.637553 34054806
    [Google Scholar]
  108. Shakeri F. Soukhtanloo M. Boskabady M.H. The effect of hydro-ethanolic extract of Curcuma longa rhizome and curcumin on total and differential WBC and serum oxidant, antioxidant biomarkers in rat model of asthma. Iran. J. Basic Med. Sci. 2017 20 2 155 165 28293392
    [Google Scholar]
  109. Sugihartini N Prabandari R Yuwono T The anti-inflammatory activity of essential oil of clove (Syzygium Aromaticum) in absorption base ointment with addition of oleic acid and propylene glycol as enhancer. Int. J. Appl. Pharm. 2019 11 5 10.22159/ijap.2019.v11s5.T0081
    [Google Scholar]
  110. Mirkov I. Popov Aleksandrov A. Ninkov M. Tucovic D. Kulas J. Zeljkovic M. Popovic D. Kataranovski M. Immunotoxicology of cadmium: Cells of the immune system as targets and effectors of cadmium toxicity. Food Chem. Toxicol. 2021 149 112026 10.1016/j.fct.2021.112026 33508420
    [Google Scholar]
  111. Uchewa O.O. Ude C.I. Egwu O.A. Ibegbu A.O. Role of Clove oil in Cadmium-Induced changes in tumor necrosis factor (TNFα) and Lymphatic tissues of wistar rats. J. Trace Elem Miner 2023 3 100040 10.1016/j.jtemin.2022.100040
    [Google Scholar]
  112. Cherian A Velmurugan V. Phytocompounds as Immunomodulators Immunosuppression and Immunomodulation 2022
    [Google Scholar]
  113. İşeri S. Ercan F. Gedik N. Yüksel M. Alican İ. Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicology 2007 230 2-3 256 264 10.1016/j.tox.2006.11.073 17196726
    [Google Scholar]
  114. Mohamad R.H. El-Bastawesy A.M. Zekry Z.K. Al-Mehdar H.A. Al-Said M.G.A.M. Aly S.S. Sharawy S.M. El-Merzabani M.M. The role of Curcuma longa against doxorubicin (adriamycin)-induced toxicity in rats. J. Med. Food 2009 12 2 394 402 19459743
    [Google Scholar]
  115. Devi H.P. Mazumder P.B. Methanolic extract of Curcuma caesia Roxb prevents the toxicity caused by cyclophosphamide to bone marrow cells, liver and kidney of mice. Pharmacognosy Res. 2016 8 1 43 49 26941535
    [Google Scholar]
  116. Fetoni A.R. Eramo S.L. Paciello F. Rolesi R. Podda M.V. Troiani D. Paludetti G. Curcuma longa (curcumin) decreases in vivo cisplatin-induced ototoxicity through heme oxygenase-1 induction. Otol Neurotol 2014 35 5 e169 e177 24608370
    [Google Scholar]
  117. Memarzia A. Khazdair M.R. Behrouz S. Gholamnezhad Z. Jafarnezhad M. Saadat S. Boskabady M.H. Experimental and clinical reports on anti-inflammatory, antioxidant, and immunomodulatory effects of Curcuma longa and curcumin, an updated and comprehensive review. Biofactors 2021 47 3 311 350 33606322
    [Google Scholar]
  118. Atia M.M. Abdel-Tawab H.S. Mostafa A.M. Mobarak S.A. Nanocurcumin and curcumin prevent N, N′-methylenebisacrylamide-induced liver damage and promotion of hepatic cancer cell growth. Sci. Rep. 2022 12 1 8319 35585174
    [Google Scholar]
  119. Ramadan A. Kamel G. Awad N.E. Shokry A.A. Fayed H.M. The pharmacological effect of apricot seeds extracts and amygdalin in experimentally induced liver damage and hepatocellular carcinoma. Journal of Herbmed Pharmacology 2020 9 4 400 407
    [Google Scholar]
  120. Hamza A.A. Heeba G.H. Hamza S. Abdalla A. Amin A. Standardized extract of ginger ameliorates liver cancer by reducing proliferation and inducing apoptosis through inhibition oxidative stress/inflammation pathway. Biomed. Pharmacother. 2021 134 111102 33338743
    [Google Scholar]
  121. Hamed MA Ali SA Saba El-Rigal, N Therapeutic potential of ginger against renal injury induced by carbon tetrachloride in rats. Sci. World J 2012 840421 10.1100/2012/840421 22566780
    [Google Scholar]
  122. Badawi M.S. Histological study of the protective role of ginger on piroxicam-induced liver toxicity in mice. J. Chin. Med. Assoc. 2019 82 1 11 18 30839397
    [Google Scholar]
  123. Huang Y.S. The hepatoprotective effect of ginger. J. Chin. Med. Assoc. 2019 82 11 805 806 31693531
    [Google Scholar]
  124. Attyah A.M. Ismail S.H. Protective Effect of Ginger Extract Against Cisplatin-Induced Hepatotoxicity and Cardiotoxicity in Rats. Iraqi J. Pharm. Sci. 2012 21 1 27 33
    [Google Scholar]
  125. Shojaeifard M.B. Hojjati S. Vojdani S. Keshavarz S. Protective Effect of Hydroalcoholic Extract of Clove on Thioacetamide-Induced Hepatotoxicity Animal Model: Effects Hydroalcoholic Extract of Clove Against Hepatotoxicity. Galen Med. J. 2022 11 e1603 36660448
    [Google Scholar]
  126. Abdelrahman MT Maina EN Elshemy HA Clove (Syzygium aromaticum) and honey extracts significantly reduce inflammatory cytokines and liver function enzymes in experimental rats fed on carbon tetrachloride (CCl4). J. Radiat. Res. Appl. Sci. 2018 11 4 416 422 10.1016/j.jrras.2018.08.003
    [Google Scholar]
  127. Ali S. Prasad R. Mahmood A. Routray I. Shinkafi T.S. Sahin K. Kucuk O. Eugenol-rich fraction of Syzygium aromaticum (clove) reverses biochemical and histopathological changes in liver cirrhosis and inhibits hepatic cell proliferation. J. Cancer Prev 2014 19 4 288 300 25574464
    [Google Scholar]
  128. Heidari-Soreshjani S. Asadi-Samani M. Yang Q. Saeedi-Boroujeni A. Phytotherapy of nephrotoxicity-induced by cancer drugs: an updated review. J. Nephropathol 2017 6 3 254 263 28975109
    [Google Scholar]
  129. Moslehi A. Komeili-movahed T. Moslehi M. Antioxidant effects of amygdalin on tunicamycin-induced endoplasmic reticulum stress in the mice liver: Cross talk between endoplasmic reticulum stress and oxidative stress. Journal of Reports in Pharmaceutical Sciences 2019 8 2 298
    [Google Scholar]
  130. Sheriff M.H. Abas A.S.M. Abd-El-Rahman B.M. Protective effect of ginger extract against cisplatin-induced nephrotoxicity in rats. Biochemistry Letters 2017 13 1 230 247
    [Google Scholar]
  131. Trujillo J. Chirino Y.I. Molina-Jijón E. Andérica-Romero A.C. Tapia E. Pedraza-Chaverrí J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol. 2013 1 1 448 456 24191240
    [Google Scholar]
  132. Fiqardina A. Yusrini Djabir Y. Santoso A. Nurul Salsabil S. Ismail I. The nephroprotective effect of clove oil (Oleum caryophylli) against levofloxacin toxicity in rats. Iranian Journal of Toxicology 2022 16 1 27 34
    [Google Scholar]
  133. Aboelwafa H.R. Ramadan R.A. Ibraheim S.S. Yousef H.N. Modulation effects of eugenol on nephrotoxicity triggered by silver nanoparticles in adult rats. Biology 2022 11 12 1719 10.3390/biology11121719 36552229
    [Google Scholar]
  134. Atanasov A.G. Waltenberger B. Pferschy-Wenzig E.M. Linder T. Wawrosch C. Uhrin P. Temml V. Wang L. Schwaiger S. Heiss E.H. Rollinger J.M. Schuster D. Breuss J.M. Bochkov V. Mihovilovic M.D. Kopp B. Bauer R. Dirsch V.M. Stuppner H. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv. 2015 33 8 1582 1614 26281720
    [Google Scholar]
  135. Sflakidou E. Leonidis G. Foroglou E. Siokatas C. Sarli V. Recent advances in natural product-based hybrids as anti-cancer agents. Molecules 2022 27 19 6632 36235168
    [Google Scholar]
  136. Dubikovskaya E.A. Thorne S.H. Pillow T.H. Contag C.H. Wender P.A. Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters. Proc Natl Acad. Sci. USA 2008 105 34 12128 12133 18713866
    [Google Scholar]
  137. Micale N. Molonia M.S. Citarella A. Cimino F. Saija A. Cristani M. Speciale A. Natural product-based hybrids as potential candidates for the treatment of cancer: focus on curcumin and resveratrol. Molecules 2021 26 15 4665 34361819
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266374075251103144517
Loading
/content/journals/ctmc/10.2174/0115680266374075251103144517
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: EAC ; Anti-cancer ; Anti-tumor immunity ; Chemotherapy ; DOX ; Herbal extracts
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test