Revisiting the therapeutic potential of gingerols against different pharmacological activities (original) (raw)

• Abdel-Aziz H, Windeck T, Ploch M, Verspohl EJ (2006) Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. Eur J Pharmacol 530:136–143. https://doi.org/10.1016/j.ejphar.2005.10.049
  Article CAS PubMed Google Scholar
• Abdu SB, Abdu F, Khalil WK (2017) Ginger nanoparticles modulate the apoptotic activity in male rats exposed to dioxin-induced cancer initiation. Int J Pharmacol 13:946–957. https://doi.org/10.3923/ijp.2017.946.957
  Article CAS Google Scholar
• Akimoto M, Iizuka M, Kanematsu R, Yoshida M, Takenaga K (2015) Anticancer effect of ginger extract against pancreatic cancer cells mainly through reactive oxygen species-mediated autotic cell death. PLoS ONE 10:e0126605. https://doi.org/10.1371/journal.pone.0126605
  Article CAS PubMed PubMed Central Google Scholar
• Ali BH, Blunden G, Tanira MO, Nemmar A (2008) Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol 46:409–420. https://doi.org/10.1016/j.fct.2007.09.085
  Article CAS PubMed Google Scholar
• Al-Sanea MM, Abelyan N, Abdelgawad MA, Musa A et al (2021) Strawberry and ginger silver nanoparticles as potential inhibitors for SARS-CoV-2 assisted by in silico modeling and metabolic profiling. Antibiotics 10:824. https://doi.org/10.3390/antibiotics10070824
  Article CAS PubMed PubMed Central Google Scholar
• Amar BS, Nilendra S, Rakesh M, Arvind KS (2009) Anti-hyperglycaemic, lipid lowering and anti-oxidant properties of [6]-gingerol in db/db mice. Int J Med Med Sci 1:536–544
  Google Scholar
• Andallu B, Radhika B, Suryakantham V (2003) Effect of aswagandha, ginger and mulberry on hyperglycemia and hyperlipidemia. Plant Foods Hum Nutr 58:1–7. https://doi.org/10.1023/B:QUAL.0000040352.23559.04
  Article Google Scholar
• Anh NH, Kim SJ, Long NP et al (2020) Ginger on human health: a comprehensive systematic review of 109 randomized controlled trials. Nutrients 12:157. https://doi.org/10.3390/nu12010157
  Article CAS PubMed PubMed Central Google Scholar
• Apte RN, Voronov E (2002) Interleukin-1-a major pleiotropic cytokine in tumor-host interactions. Semin Cancer Biol 12:277–290. https://doi.org/10.1016/s1044-579x(02)00014-7
  Article CAS PubMed Google Scholar
• Bakr AF, Abdelgayed SS, El-Tawil OS, Bakeer AM (2020) Ginger extract and ginger nanoparticles; characterization and applications. Int J Vet Sci 9:203–209. https://doi.org/10.37422/IJVS/20.021
  Article Google Scholar
• Bhardwaj S, Verma R, Gupta J (2018) Challenges and future prospects of herbal medicine. Int Res Med Health Sci 1:12–15. https://doi.org/10.36437/irmhs.2018.1.1.D
  Article Google Scholar
• Bhargava S, Dhabhai K, Batra A, Sharma A, Malhotra B (2012) Zingiber officinale: chemical and phytochemical screening and evaluation of its antimicrobial activities. J Chem Res 4:360–364
  CAS Google Scholar
• Bhattarai S, Tran VH, Duke CC (2001) The stability of gingerol and shogaol in aqueous solutions. J Pharm Sci 90:1658–1664. https://doi.org/10.1002/jps.1116
  Article CAS PubMed Google Scholar
• Black CD, O’Connor PJ (2008) Acute effects of dietary ginger on quadriceps muscle pain during moderate-intensity cycling exercise. Int J Sport Nutr Exerc Metab 18:653–664. https://doi.org/10.1123/ijsnem.18.6.653
  Article CAS PubMed Google Scholar
• Bode AM, Dong Z (2004) Herbal and traditional medicine: biomolecular and clinical aspects. In: Packer L, Ong CN, Halliwell B (eds) The amazing and mighty ginger. CRC Press, New York, pp 131–156
  Google Scholar
• Bode AM, Dong Z (2008) Modulation of cell signal transduction by tea and ginger. In: Dong Z, Surh YJ (eds) Dietary modulation of cell signaling pathways, 1st edn. CRC Press/Taylor & Francis, Boca Raton (FL), pp 45–74
  Google Scholar
• Bode AM, Dong Z (2011) The amazing and mighty ginger. In: Benzie IFF, Wachtel-Galor S (eds) Herbal medicine: biomolecular and clinical aspects, 2nd edn. CRC Press/Taylor & Francis, Boca Raton (FL), pp 129–154
  Google Scholar
• Bode AM, Ma WY, Surh YJ, Dong Z (2001) Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol. Cancer Res 61:850–853
  CAS PubMed Google Scholar
• Butt MS, Sultan MT (2011) Ginger and its health claims: molecular aspects. Crit Rev Food Sci Nutr 51:383–393. https://doi.org/10.1080/10408391003624848
  Article CAS PubMed Google Scholar
• Cady RK, Goldstein J, Nett R, Mitchell R, Beach ME, Browning R (2011) A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic™M) in the treatment of migraine. Headache 51:1078–1086. https://doi.org/10.1111/j.1526-4610.2011.01910.x
  Article PubMed Google Scholar
• Chakraborty D, Mukherjee A, Sikdar A, Paul A, GhoshA K-B (2012) [6]-Gingerol isolated from ginger attenuates sodium arsenite induced oxidative stress and plays a corrective role in improving insulin signaling in mice. Toxi Letters 210:34–43 ((PMID: 22285432))
• Chen XY, Zhou Y, Yu JJ (2019) Exosome-like nanoparticles from ginger rhizomes inhibited NLRP3 inflammasome activation. Mol Pharm 16:2690–2699 ((PMID: 31038962))
• Chopra A, Saluja M, Tillu G, Sarmukkaddam S et al (2013) Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: A randomized, double-blind, controlled equivalence drug trial. Rheumatology 52:1408–1417 ((PMID: 23365148))
• Cohen RJ, Ek K, Pan CX (2002) Complementary and alternative medicine (CAM) use by older adults: A comparison of self-report and physician chart documentation. J Gerontol A Biol Sci Med Sci 57:223–227 ((PMID: 11909887))
• Cosmas S, Joshua PE, Durojaye OA (2018) In-silico structure-activity relationship and molecular docking studies of Monosubstitted 6-Gingerol against Streptococcus pneumoniae Phosphomevalonate kinase. Internat J Sci Eng Res 9:1733–1742
  Google Scholar
• Croft KD (1999) Antioxidant effects of plant phenolic compounds. In: Basu TK, Temple NJ, Garg ML (eds) Antioxidants in Human Health and Disease. CABI Publishing, New York, pp 109–121
  Google Scholar
• Dabaghzadeh F, Khalili H, Dashti-Khavidaki S, Abbasian L, Moeinifard A (2014) Ginger for prevention of antiretroviral-induced nausea and vomiting: a randomized clinical trial. Expert Opin Drug Saf 13:859–866 ((PMID: 24820858))
• Danwilai K, Konmun J, Sripanidkulchai BO, Subongkot S (2017) Antioxidant activity of ginger extract as a daily supplement in cancer patients receiving adjuvant chemotherapy: a pilot study. Cancer Manag Res 9:11–18 ((PMID: 28203106))
• Denniff P, Macleod I, Whiting DA (1980) Studies in the biosynthesis of [6]-gingerol, pungent principle of ginger (Zingiber officinale). J Chem Soc Perkin Trans 1:2637–2644. https://doi.org/10.1039/p19800002637
  Article Google Scholar
• Ding GH, Naora K, Hayashibara M, Katagiri Y, Kano Y, Iwamoto K (1991) Pharmacokinetics of [6]-gingerol after intravenous administration in rats. Chem Pharm Bull (tokyo) 39:1612–1614 ((PMID: 1934184))
• Drozdov VN, Kim VA, Tkachenko EV, Varvanina GG (2012) Influence of a specific ginger combination on gastropathy conditions in patients with osteoarthritis of the knee or hip. J Altern Complement Med 18:583–588 ((PMID: 22784345))
• Farthing JE, O’neill MJ, (1990) Isolation of gingerols from powdered root ginger by countercurrent chromatography. J Liq Chromatogr 13:941–950. https://doi.org/10.1080/01483919008049223
  Article CAS Google Scholar
• Fleming SA, Dyer CW, Eggington J (1999) A convenient one-step gingerol synthesis. Synth Commun 29:1933–1939. https://doi.org/10.1080/00397919908086182
  Article CAS Google Scholar
• Ghasemzadeh A, Jaafar HZ, Rahmat A, Wahab PE, Halim MR (2010) Effect of different light intensities on total phenolics and flavonoids synthesis and anti-oxidant activities in young ginger varieties (Zingiber officinale Roscoe). Int J Mol Sci 11:3885–3897 ((PMID: 21152306))
• Ghayur MN, Gilani AH, Afridi MB, Houghton P (2005) Cardiovascular effects of ginger aqueous extract and its phenolic constituents are mediated through multiple pathways. Vascul Pharmacol 43:234–241 ((PMID: 16157513))
• Giacosa A, Morazzoni P, Bombardelli E, Riva A, Porro GB, Rondanelli M (2015) Can nausea and vomiting be treated with ginger extract? Eur Rev Med Pharmacol Sci 19:1291–1296 ((PMID: 25912592))
• Girhepunje NS, Dumore NG, Swati U, Deepali TV, Shende SN (2017) Indian J of Med Res & Pharmace Sci 4:24–28
  Google Scholar
• Habib SH, Makpol S, Abdul Hamid NA et al (2008) Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats. Clinics (sao Paulo) 63:807–813. https://doi.org/10.1590/s1807-59322008000600017
  Article PubMed Google Scholar
• Haniadka R1, Rajeev AG, Palatty PL, Arora R, Baliga MS (2012) Zingiber officinale ginger as an anti-emetic in cancer chemotherapy: a review. J Altern Complement Med 18(440):444. https://doi.org/10.1089/acm.2010.0737
  Article Google Scholar
• HanX ZY, Liang Y, Zhang J, Li M, Zhao Z, Zhang X, Xue Y, Zhang Y, Xiao J, Chu L (2019) 6-Gingerol, an active pungent component of ginger, inhibits L-type Ca2+ current, contractility, and Ca2+ transients in isolated rat ventricular myocytes. Food SciNutr 7:1344–1352 ((PMID: 31024707))
• Hiserodt RD, Franzblau SG, Rosen RG (1998) Isolation of 6-, 8-, and 10-gingerol from ginger rhizome by HPLC and preliminary evaluation of inhibition of Mycobacterium avium and Mycobacterium tuberculosis. J Agric Food Chem 46:2504–2508. https://doi.org/10.1021/jf970948l
  Article CAS Google Scholar
• Ho SC, Chang KS, Lin CC (2013) Anti-neuroinflammatory capacity of fresh ginger is attributed mainly to 10-gingerol. Food Chem 141:3183–3191 ((PMID: 23871076))
• Huang QR, Iwamoto M, Aoki S, Tanaka N, Tajima K, Yamahara J, Takaishi Y, Yoshida M, Tomimatsu T, Tamai Y (1991) Anti-5-hydroxytryptamine3 effect of galanolactone, diterpenoid isolated from ginger. Chem Pharm Bull (tokyo) 39:397–399 ((PMID: 2054863))
• Ishiguro K, Ando T, Maeda O, Ohmiya N, Niwa Y, Kadomatsu K, Goto H (2007) Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms. Biochem Biophys Res Commun 362:218–223. https://doi.org/10.1016/j.bbrc.2007.08.012
  Article CAS PubMed Google Scholar
• Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90. https://doi.org/10.3322/caac.20107
  Article PubMed Google Scholar
• Jenabi E (2013) The effect of ginger for relieving of primary dysmenorrhoea. J Pak Med Assoc 63:8–10 ((PMID: 23865123))
• Jindal DK, Sah P, Bisht D, Lalhlenmawia H, Kumar D, Kumar D (2021). Role of Medicinal Plants in Pulmonary Hypertension. In: Dua K, Nammi S, Chang D, Chellappan DK, Gupta G, Collet T. (eds) Medicinal Plants for Lung Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-33-6850-7_13
• Jolad SD, Lantz RC, Chen GJ, Bates RB, Timmermann BN (2005) Commercially processed dry ginger (Zingiber officinale): composition and effects on LPS-stimulated PGE2 production. Phytochemistry 66:1614–1635. https://doi.org/10.1016/j.phytochem.2005.05.007
  Article CAS PubMed Google Scholar
• Jung MY, Lee MK, Park HJ, Oh EB, Shin JY, Park JS, Jung SY, Oh JH, Choi DS (2018) Heat-induced conversion of gingerols to shogaols in ginger as affected by heat type (dry or moist heat), sample type (fresh or dried), temperature and time. Food Sci Biotechnol 27:687–693. https://doi.org/10.1007/s10068-017-0301-1
• Kashefi F, Khajehei M, Tabatabaeichehr M, Alavinia M, Asili J (2014) Comparison of the effect of ginger and zinc sulfate on primary dysmenorrhea: a placebo-controlled randomized trial. Pain Manag Nurs 15:826–833. https://doi.org/10.1016/j.pmn.2013.09.001
  Article PubMed Google Scholar
• Katiyar SK, Agarwal R, Mukhtar H (1996) Inhibition of tumor promotion in SENCAR mouse skin by ethanol extract of Zingiber officinale rhizome. Cancer Res 56:1023–1030 ((PMID: 8640756))
• Kawai T, Kinoshita K, Koyama K, Takahashi K (1994) Anti-emetic principles of Magnolia obovata bark and Zingiber officinale rhizome. Planta Med 60:17–20. https://doi.org/10.1055/s-2006-959399
  Article CAS PubMed Google Scholar
• Kelly K (2009) History of medicine. Facts on file, New York, pp 29–50
  Google Scholar
• Khalil WK, El-Bassyouni GT, Booles HF (2016) Nano-encapsulated form of citrus medica for osteoporosis treatment in animal model. Int J Pharm Clin Res 8:49–59
  Google Scholar
• Kim EC, Min JK, Kim TY, Lee SJ, Yang HO, Han S, Kim YM, Kwon YG (2005) [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo. Biochem Biophys Res Commun 335:300–308. https://doi.org/10.1016/j.bbrc.2005.07.076
  Article CAS PubMed Google Scholar
• Kim SO, Kim MR (2013) [6]-Gingerol prevents disassembly of cell junctions and activities of MMPs in invasive human pancreas cancer cells through ERK/NF-κ B/Snail signal transduction pathway. Evid Based Complement Alternat Med 2013:761852. https://doi.org/10.1155/2013/761852
  Article PubMed PubMed Central Google Scholar
• Konmun J, Danwilai K, Ngamphaiboon N, Sripanidkulchai B, Sookprasert A, Subongkot S (2017) A phase II randomized double-blind placebo-controlled study of 6-gingerol as an anti-emetic in solid tumor patients receiving moderately to highly emetogenic chemotherapy. Med Oncol 34:69. https://doi.org/10.1007/s12032-017-0931-4
  Article CAS PubMed Google Scholar
• Koo KL, Ammit AJ, Tran VH, Duke CC, Roufogalis BD (2001) Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation. Thromb Res 103:387–397. https://doi.org/10.1016/s0049-3848(01)00338-3
  Article CAS PubMed Google Scholar
• Kumar G, Karthik K, Rao B (2011) Review on pharmacological and phytochemical properties of Zingiber officinale Roscoe (Zingiberaceae). J Phar Res 4:2963–2969
  CAS Google Scholar
• Kumar NV, Srinivas P, Bettadaiah BK (2012) New scalable and eco-friendly synthesis of gingerols. Tetrahedron Lett 53:2993–2995. https://doi.org/10.1016/j.tetlet.2012.03.092
  Article CAS Google Scholar
• Lee C, Park GH, Kim CY, Jang JH (2011) [6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system. Food Chem Toxicol 49:1261–1269. https://doi.org/10.1016/j.fct.2011.03.005
  Article CAS PubMed Google Scholar
• Lee HS, Seo EY, Kang NE, Kim WK (2008) [6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells. J Nutr Biochem 19:313–319. https://doi.org/10.1016/j.jnutbio.2007.05.008
  Article CAS PubMed Google Scholar
• Li C, Zhou L (2015) Inhibitory effect 6-gingerol on adipogenesis through activation of the Wnt/β-catenin signaling pathway in 3T3-L1 adipocytes. Toxicol in Vitro 30:394–401. https://doi.org/10.1016/j.tiv.2015.09.023
  Article CAS PubMed Google Scholar
• Li X, Kristine CYM, Van HT, Li Y, Duke CC, Roufogalis BD, Heather AK (2013) Attenuation of proinflammatory responses by S-[6]-gingerol via inhibition of ROS/NF-kappa B/COX2 activation in HuH7 cells. Evid Based Complement Alternat Med pp 1–8. https://doi.org/10.1155/2013/146142
• Lin CB, Lin CC, Tsay GJ (2012) 6-Gingerol inhibits growth of colon cancer cell LoVo via induction of G2/M arrest. Evid Based Complement Alternat Med. https://doi.org/10.1155/2012/326096
  Article PubMed PubMed Central Google Scholar
• Liu Q, Liu J, Guo H, Sun S, Wang S, Zhang Y, Li S, Qiao Y (2013) [6]-Gingerol: a novel AT1 antagonist for the treatment of cardiovascular disease. Planta Med 79:322–326. https://doi.org/10.1055/s-0032-1328262
  Article CAS PubMed Google Scholar
• Ma J, Jin X, Yang L, Liu ZL (2004) Diarylheptanoids from the rhizomes of Zingiber officinale. Phytochem 65:1137–1143. https://doi.org/10.1016/j.phytochem.2004.03.007
  Article CAS Google Scholar
• Ma S, Zhang S, Duan W, Wang W (2009) An enantioselective synthesis of (+)-(S)-[n]-gingerols via the l-proline-catalyzed aldol reaction. Bioorg Med Chem Lett 19:3909–3911. https://doi.org/10.1016/j.bmcl.2009.03.081
  Article CAS PubMed Google Scholar
• Mahady GB, Pendland SL, Yun GS, Lu ZZ, Stoia A (2003) Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag A+ strains of Helicobacter pylori. Anticancer Res 23:3699 ((PMID: 14666666))
• Mahluji S, Attari VE, Mobasseri M, Payahoo L, Ostadrahimi A, Golzari SE (2013) Effects of ginger (Zingiber officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients. Int J Food SciNutr 64:682–686. https://doi.org/10.3109/09637486.2013.775223
  Article CAS Google Scholar
• Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T, Bin LH (2019) Bioactive compounds and bioactivities of ginger (zingiber officinale roscoe). Foods 8:185. https://doi.org/10.3390/foods8060185
  Article CAS PubMed PubMed Central Google Scholar
• Markam R, Bajpai AK (2020) Functionalization of ginger derived nanoparticles with chitosan to design drug delivery system for controlled release of 5-amino salicylic acid (5-ASA) in treatment of inflammatory bowel diseases: An in vitro study. React Funct Polym 149:104520. https://doi.org/10.1016/j.reactfunctpolym.2020.104520
  Article CAS Google Scholar
• Marx W, Ried K, McCarthy AL, Vitetta L, Sali A, McKavanagh D, Isenring L (2017) Ginger—Mechanism of action in chemotherapy-induced nausea and vomiting: a review. Crit Rev Food Sci Nutr 57:141–146. https://doi.org/10.1080/10408398.2013.865590
  Article CAS PubMed Google Scholar
• Yuki M, Kikuzaki H, Hisamoto M, Nakatani N (2004) Antioxidant properties of gingerol related compounds from ginger. BioFactors 21:293–296. https://doi.org/10.1002/biof.552210157
• Matsumura MD, Zavorsky GS, Smoliga JM (2015) The effects of pre-exercise ginger supplementation on muscle damage and delayed onset muscle soreness. Phytother Res 29:887–893. https://doi.org/10.1002/ptr.5328
  Article PubMed Google Scholar
• Miri P, Bae J, Lee DS (2008) Antibacterial activity of [10]-gingerol and [12]-gingerol isolated from ginger rhizome against periodontal bacteria. Phytothery Res 22:1446–1449. https://doi.org/10.1002/ptr.2473
  Article CAS Google Scholar
• Mohammad YA (2016) Gingerol and its role in chronic diseases. Adv Exp Med & Bio 929:177–207. https://doi.org/10.1007/978-3-319-41342-6_8
• Mohammad M. Al-Sanea, Narek Abelyan, Mohamed A. Abdelgawad, Arafa Musa et al (2021) Strawberry and Ginger Silver Nanoparticles as Potential Inhibitors for SARS-CoV 2 Assisted by In Silico Modeling and Metabolic Profiling. Antibiotics 10:824. https://doi.org/10.3390/antibiotics10070824
• Morán A, Ortega P, de Juan C, Fernández-Marcelo T, Frías C, Sánchez-Pernaute A, Torres AJ, Díaz-Rubio E, Iniesta P, Benito M (2010) Differential colorectal carcinogenesis: molecular basis and clinical relevance. World J Gastrointest Oncol 2:151. https://doi.org/10.4251/wjgo.v2.i3.151
  Article PubMed PubMed Central Google Scholar
• Moran A, Ortega P, de Juan C et al (2010) Differential colorectal carcinogenesis: molecular basis and clinical relevance. World J Gastrointest Oncol 2:151–158. https://doi.org/10.4251/wjgo.v2.i3.151
  Article PubMed PubMed Central Google Scholar
• Naderi Z, Mozaffari-Khosravi H, Dehghan A, Nadjarzadeh A, Huseini HF (2016) Effect of ginger powder supplementation on nitric oxide and C-reactive protein in elderly knee osteoarthritis patients: a 12-week double-blind randomized placebo-controlled clinical trial. J Tradit Complement Med 6:199–203. https://doi.org/10.1016/j.jtcme.2014.12.007
  Article PubMed Google Scholar
• Nazim UM, Jeong JK, Seol JW, Hur J, Eo SK, Lee JH, Park SY (2015) Inhibition of the autophagy flux by gingerol enhances TRAIL-induced tumor cell death. Oncol Rep 33:2331–2336. https://doi.org/10.3892/or.2015.3869
  Article CAS PubMed Google Scholar
• Nieman DC, Shanely RA, Luo B, Dew D, Meaney MP, Sha W (2013) A commercialized dietary supplement alleviates joint pain in community adults: a double-blind, placebo-controlled community trial. Nutr J 12:1–9. https://doi.org/10.1186/1475-2891-12-154
  Article Google Scholar
• Niempoog S, Siriarchavatana P, Kajsongkram T (2012) The efficacy of Plygersic gel for use in the treatment of osteoarthritis of the knee. J Med Assoc Thai 1:113–119 ((PMID: 23451449))
• Nigam N, Bhui K, Prasad S, George J, Shukla Y (2009) [6]-Gingerol induces reactive oxygen species regulated mitochondrial cell death pathway in human epidermoid carcinoma A431 cells. Chem Biol Interact 181:77–84. https://doi.org/10.1016/j.cbi.2009.05.012
  Article CAS PubMed Google Scholar
• Nigam N, George J, Srivastava S, Roy P, Bhui K, Singh M, Shukla Y (2010) Induction of apoptosis by [6]-gingerol associated with the modulation of p53 and involvement of mitochondrial signaling pathway in B [a] P-induced mouse skin tumorigenesis. Cancer Chemother Pharmacol 65:687–696. https://doi.org/10.1007/s00280-009-1074-x
  Article CAS PubMed Google Scholar
• Nonn L, Duong D, Peehl DM (2007) Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells. Carcinogen 28:1188–1196. https://doi.org/10.1093/carcin/bgl241
  Article CAS Google Scholar
• Norhidayah A, Noriham A, Rusop MD (2015) Assessment of antimicrobial activity of nanoparticle ginger rhizome water extract. IJSRP 11:665–669
  Google Scholar
• Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, Tran VH, Duke CC (2003) Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res 111:259–265. https://doi.org/10.1016/j.thromres.2003.09.009
  Article CAS PubMed Google Scholar
• Okamoto M, Irii H, Tahara Y, Ishii H, Hirao A, Udagawa H, Hiramoto M, Yasuda K, Takanishi A, Shibata S (2011) Synthesis of a new [6]-gingerol analogue and its protective effect with respect to the development of metabolic syndrome in mice fed a high-fat diet. J Med Chem 54:6295–6304. https://doi.org/10.1021/jm200662c
  Article CAS PubMed Google Scholar
• Ozgoli G, Goli M, Moattar F (2009) Comparison of effects of ginger, Mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea. J Altern Complement Med 15:129–132. https://doi.org/10.1089/acm.2008.0311
  Article PubMed Google Scholar
• Palatty PL, Haniadka R, Valder B, Arora R, Baliga MS (2013) Ginger in the prevention of nausea and vomiting: a review. Crit Rev Food Sci Nutr 53:659–669. https://doi.org/10.1080/10408398.2011.553751
  Article PubMed Google Scholar
• Park EJ, Pezzuto JM (2011) Botanicals in cancer chemoprevention. Cancer Metastasis Rev 21:231–255. https://doi.org/10.1023/A:1021254725842
  Article Google Scholar
• Park M, Bae J, Lee DS (2008) Antibacterial activity of 10-gingerol and 12-gingerol isolated from ginger rhizome against periodontal bacteria. Phytotherapy Res 22:1446–1449. https://doi.org/10.1002/ptr.2473
  Article CAS Google Scholar
• Pillai AK, Sharma KK, Gupta YK, Bakhshi S (2011) Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving high emetogenic chemotherapy. Pediatr Blood Cancer 56:234–238. https://doi.org/10.1002/pbc.22778
  Article PubMed Google Scholar
• Poltronieri J, Becceneri B, A, M Fuzer A, Cesar C Filho J, Martin CB, Cezar Vieira P, Pouliot N, R Cominetti M, (2014) [6]-gingerol as a cancer chemopreventive agent: a review of its activity on different steps of the metastatic process. Mini Rev Med Chem 14:313–321. https://doi.org/10.2174/1389557514666140219095510
  Article CAS PubMed Google Scholar
• Prasad S, Tyagi AK (2015) Ginger and its constituents: role in prevention and treatment of gastrointestinal cancer. Gastroenterol Res Practice. https://doi.org/10.1155/2015/142979
  Article Google Scholar
• Radhakrishnan R, Wilkinson ST, D’Souza DC (2014) Gone to pot–a review of the association between cannabis and psychosis. Front Psychiatry 22:54. https://doi.org/10.3389/fpsyt.2014.00054
  Article Google Scholar
• Rahnama P, Montazeri A, Huseini HF, Kianbakht S, Naseri M (2012) Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med 12:1–7. https://doi.org/10.1186/1472-6882-12-92
  Article Google Scholar
• Ramirez-Ahumada MC, Timmermann BN, Gang DR (2006) Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger (Zingiber officinale): identification of curcuminoid synthase and hydroxycinnamoyl-CoA thioesterases. Phytochem 67:2017–2029. https://doi.org/10.1016/j.phytochem.2006.06.028
  Article CAS Google Scholar
• Rani MP, Krishna MS, Padmakumari KP, Raghu KG, Sundaresan A (2012) Zingiber officinale extract exhibits antidiabetic potential via modulating glucose uptake, protein glycation and inhibiting adipocyte differentiation: an in vitro study. J Sci Food Agric 92:1948–1955. https://doi.org/10.1002/jsfa.5567
  Article CAS PubMed Google Scholar
• Rani PM, Padmakumari KP, Sankarikutty B, Lijo Cherian O, Nisha VM, Raghu KG (2011) Inhibitory potential of ginger extracts against enzymes linked to type 2 diabetes, inflammation and induced oxidative stress. Int J Food Sci Nutr 62:106–110. https://doi.org/10.3109/09637486.2010.515565
  Article CAS PubMed Google Scholar
• Regassa H, Sourirajan A, Kumar V, Pandey S, Kumar D, Dev K (2022) A Review of Medicinal Plants of the Himalayas with Anti-Proliferative Activity for the Treatment of Various Cancers. Cancers 14:3898. https://doi.org/10.3390/cancers14163898
• Rundhaug JE (2005) Matrix metalloproteinases and angiogenesis. J Cell Mol Med 9:267–285. https://doi.org/10.1111/j.1582-4934.2005.tb00355.x
  Article CAS PubMed PubMed Central Google Scholar
• Samad MB, Mohsin MN, Razu BA, Hossain MT, Mahzabeen S (2017) Glucose-stimulated insulin secretion pathway in pancreatic β-glucose-stimulated insulin secretion pathway in pancreatic-cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporters in skeletal muscle to improve hyperglycemia in Leprdb/db type 2 diabetic mice. BMC Complement Altern Med 17:395–407. https://doi.org/10.1186/s12906-017-1903-0
  Article CAS PubMed PubMed Central Google Scholar
• Saraswat M, Suryanarayana P, Reddy PY, Patil MA, Balakrishna N, Reddy GB (2010) Antiglycating potential of Zingiber officinalis and delay of diabetic cataract in rats. Mol vis 16:1525–1537 ((PMID: 20806076))
• Saravanan G, Ponmurugan P, Deepa MA, Senthilkumar B (2014) Anti-obesity action of gingerol: effect on lipid profile, insulin, leptin, amylase and lipase in male obese rats induced by a high-fat diet. J Sci Food Agric 94:2972–2977. https://doi.org/10.1002/jsfa.6642
  Article CAS PubMed Google Scholar
• Sekiya K, Ohtani A, Kusano S (2004) Enhancement of insulin sensitivity in adipocytes by ginger. BioFactors 22:153–156. https://doi.org/10.1002/biof.5520220130
  Article CAS PubMed Google Scholar
• Semwal RB, Semwal DK, Combrinck S, Viljoen AM (2015) Gingerols and shogaols: important nutraceutical principles from ginger. Phytochem Lett 117:554–568. https://doi.org/10.1016/j.phytochem.2015.07.012
  Article CAS Google Scholar
• Singh AB, Akanksha, Singh N, Maurya R, Srivastava AK (2009) Anti-hyperglycaemic, lipid lowering and anti-oxidant properties of [6]-gingerol in db/db mice. Int J Med Med Sci 1:536–544
• Shukla Y, Singh M (2007) Cancer preventive properties of ginger: a brief review. Food Chem Toxicol 45:683–690. https://doi.org/10.1016/j.fct.2006.11.002
  Article CAS PubMed Google Scholar
• Shukla MK, Singh SK, Pandey S, Gupta PK, Choudhary A, Jindal DK, Dua K, Kumar D (2022) Potential Immunomodulatory Activities of Plant Products. S Afr J Bot 149:937–943. https://doi.org/10.1016/j.sajb.2022.04.055
• Son MJ, Miura Y, Yagasaki K (2015) Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice. Cytotech 67:641–652. https://doi.org/10.1007/s10616-014-9730-3
  Article CAS Google Scholar
• Stojanoski N (1999) Development of health culture in Veles and its region from the past to the end of the 20th century. Veles Soc of Sci and Art pp13–34
• Surh YJ, Lee E, Lee JM (1998) Chemoprotective properties of some pungent ingredients present in red pepper and ginger. Mutat Res 402:259–267. https://doi.org/10.1016/S0027-5107(97)00305-9
  Article CAS PubMed Google Scholar
• Teng Y, Ren YI, Sayed M, Hu X, Lei C, Kumar A, Hutchins E, Mu J, Deng Z, Luo C, Sundaram K (2018) Plant-derived exosomal microRNAs shape the gut microbiota. Cell Host Microbe 24:637–652. https://doi.org/10.1016/j.chom.2018.10.001
  Article CAS PubMed PubMed Central Google Scholar
• Li T, Qian W, Qian Q, Zhang W, Cai X (2020) Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems. J Nat Med 74:353–370. https://doi.org/10.1007/s11418-019-01372-x
• Tzeng TF, Chang CJ, Liu IM (2014) 6-gingerolinhibits rosiglitazone-induced adipogenesis in 3T3-L1adipocytes. Phytother Res 28:187–192. https://doi.org/10.1002/ptr.4976
  Article CAS PubMed Google Scholar
• Tzeng TF, Liu IM (2013) 6-Gingerol prevents adipogenesis and the accumulation of cytoplasmic lipid droplets in 3T3-L1 cells. Phytomedicine 20:481–487. https://doi.org/10.1016/j.phymed.2012.12.006
  Article CAS PubMed Google Scholar
• Wang CC, Chen LG, Lee LT, Yang LL (2003) Effects of 6-gingerol, an antioxidant from ginger, on inducing apoptosis in human leukemic HL-60 cells. In Vivo 17:641–645 ((PMID: 14758732))
• Wang S, Zhang C, Yang G, Yang Y (2014) Biological properties of 6-gingerol: a brief review. Nat Prod Commun 9:1934578X1400900736. https://doi.org/10.1177/1934578X1400900736
  Article Google Scholar
• Wei QY, Ma JP, Cai YJ, Yang L, Liu ZL (2005) Cytotoxic and apoptotic activities of diarylheptanoids and gingerol-related compounds from the rhizome of Chinese ginger. J Ethnopharmacol 102:177–184. https://doi.org/10.1016/j.jep.2005.05.043
  Article CAS PubMed Google Scholar
• Weng CJ, Chou CP, Ho CT, Yen GC (2012) Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol. Mol Nutr Food Res 56:1304–1314. https://doi.org/10.1002/mnfr.201200173
  Article CAS PubMed Google Scholar
• Weng CJ, Wu CF, Huang HW, Ho CT, Yen GC (2010) Anti-invasion effects of 6-shogaol and 6-gingerol, two active components in ginger, on human hepatocarcinoma cells. Mol Nutr Food Res 54:1618–1627. https://doi.org/10.1002/mnfr.201000108
  Article CAS PubMed Google Scholar
• Wu WK, Wang XJ, Cheng AS, Luo MX, Ng SS, To KF, Chan FK, Cho CH, Sung JJ, Yu J (2013) Dysregulation and crosstalk of cellular signaling pathways in colon carcinogenesis. Crit Rev Oncol Hematol 86:251–277. https://doi.org/10.1016/j.critrevonc.2012.11.009
  Article PubMed Google Scholar
• Yadav AK, Garg A (2019) Antidiabetic effects of [10]-gingerol in streptozotocin- and high-fat diet-induced diabetic rats. Asian J Pharmaceu & Clinical Res 12:77–80
  Article CAS Google Scholar
• Yagihashi S, Miura Y, Yagasaki K (2008) Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture. Cytotech 57:129–136. https://doi.org/10.1007/s10616-008-9121-8
  Article CAS Google Scholar
• Yamahara J, Rong HQ, Iwamoto M, Kobayashi G, Matsuda H, Fujimura H (1989) Active components of ginger exhibiting anti-serotonergic action. Phytother Res 3:70–71. https://doi.org/10.1002/ptr.2650030208
  Article CAS Google Scholar
• Yang G, Wang S, Zhong L et al (2012) [6]-gingerol induces apoptosis through lysosomal-mitochondrial axis in human hepatoma G2 cells. Phytother Res 26:1667–1673. https://doi.org/10.1002/ptr.4632
  Article CAS PubMed Google Scholar
• Yang G, Zhong L, Jiang L, Geng C, Cao J, Sun X, Liu X, Chen M, Ma Y (2011) 6-Gingerol prevents patulin-induced genotoxicity in HepG2 cells. Phytother Res 25:1480–1485. https://doi.org/10.1002/ptr.3446
  Article CAS PubMed Google Scholar
• Yip YB, Tam AC (2008) An experimental study on the effectiveness of massage with aromatic ginger and orange essential oil for moderate-to-severe knee pain among the elderly in Hong Kong. Complement Ther Med 16:131–138. https://doi.org/10.1016/j.ctim.2007.12.003
  Article PubMed Google Scholar
• Yusof M, Anum Y (2016) Gingerol and its role in chronic diseases. Drug discovery from mother nature 177–207. https://doi.org/10.1007/978-3-319-41342-6_8
• Yusof Y, Ahmad N, Das S, Sulaiman S, Murad N (2009) Chemopreventive efficacy of ginger (Zingiber officinale) in ethionine induced rat hepatocarcinogenesis. Afr J TraditComplem Altern Med 6:87–93. https://doi.org/10.4314/ajtcam.v6i1.57078
  Article CAS Google Scholar
• Zahmatkash M, Vafaeenasab MR (2011) Comparing analgesic effects of a topical herbal mixed medicine with salicylate in patients with knee osteoarthritis. Pak J Biol Sci 14:715–719. https://doi.org/10.3923/pjbs.2011.715.719
  Article PubMed Google Scholar
• Zhang M, Collins JF, Merlin D (2016a) Do ginger-derived nanoparticles represent an attractive treatment strategy for inflammatory bowel diseases? Nanomedicine 12:3035–3037. https://doi.org/10.2217/nnm-2016-0353
  Article CAS Google Scholar
• Zhang M, Viennois E, Xu C, Merlin D (2016b) Plant derived edible nanoparticles as a new therapeutic approach against diseases. Tissue Barriers 4:e1134415. https://doi.org/10.1080/21688370.2015.1134415
  Article CAS PubMed PubMed Central Google Scholar
• Zhang M, Xu C, Liu D, Han MK, Wang L, Merlin D (2018) Oral delivery of nanoparticles loaded with ginger active compound, 6-shogaol, attenuates ulcerative colitis and promotes wound healing in a murine model of ulcerative colitis. J Crohns Colitis 12:217–229. https://doi.org/10.1093/ecco-jcc/jjx115
  Article PubMed Google Scholar
• Zhuang X, Deng ZB, Mu J, Zhang L, Yan J, Miller D, Feng W, McClain CJ, Zhang HG (2015) Ginger-derived nanoparticles protect against alcohol-induced liver damage. J Extracell Vesicles 4:28713. https://doi.org/10.3402/jev.v4.28713
  Article CAS PubMed Google Scholar
• Zick SM, Djuric Z, Ruffin MT, Litzinger AJ, Normolle DP, Alrawi S, Feng MR, Brenner DE (2008) Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev 17:1930–1936. https://doi.org/10.1158/1055-9965.EPI-07-2934
  Article CAS PubMed PubMed Central Google Scholar