Ginger (Zingiber officinale, Zingiberis rhizome)
Derived from the rhizome of the plant, ginger is native to Asia and is used both as food and as medicine. Ginger is in the family Zingiberaceae, which also includes turmeric (Curcuma longa), cardamom (Elettaria cardamomum), and galangal. Ginger originated in Maritime Southeast Asia and was likely domesticated first by the Austronesian peoples. The first written record of ginger comes from the Analects of Confucius, written in China during the Warring States period (475–221 BC). In it, Confucius was said to eat ginger with every meal. It was transported with them throughout the Indo-Pacific during the Austronesian expansion (c. 5,000 BP), reaching as far as Hawaii. Ginger is one of the first spices to have been exported from Asia, arriving in Europe with the spice trade, and was used by ancient Greeks and Romans. The distantly related dicots in the genus Asarum are commonly called wild ginger because of their similar taste.
Usos
In traditional Chinese medicine, ginger is used to expel “cold”, “wind” and “dampness”, and is believed to stop the reverse flow of Qi (vital energy). Western use has been primarily for gastrointestinal symptoms and respiratory ailments. Preclinical studies indicate that ginger has antiemetic, anticancer, anti-inflammatory, anti-drug-dependence, and hypoglycemic effects. It may also protect against Alzheimer’s disease. Ginger influences gastric emptying in healthy individuals and may promote feelings of satiety. Systematic reviews suggest its effectiveness for treating dysmenorrhea, with a study showing it to be comparable to standard treatment, and moderate efficacy against osteoarthritic and chronic low back pain. As an adjunct to standard care, ginger may also be beneficial for treating migraine.
As a culinary flavoring fresh ginger can be substituted for ground ginger at a ratio of six to one, although the flavors of fresh and dried ginger are somewhat different. Powdered dry ginger root is typically used as a flavoring for recipes such as gingerbread, cookies, crackers and cakes, ginger ale, and ginger beer.
Química/Farmacología
Chemical analysis of ginger shows that it contains over 400 different compounds. The major constituents in ginger rhizomes are carbohydrates (50–70%), lipids (3–8%), terpenes, and phenolic compounds. Terpene components of ginger include zingiberene, β-bisabolene, α-farnesene, β-sesquiphellandrene, and α-curcumene, while phenolic compounds include gingerol, paradols, and shogaol. These gingerols (23–25%) and shogaol (18–25%) are found in higher quantity than others. Besides these, amino acids, raw fiber, ash, protein, phytosterols, vitamins (e.g., nicotinic acid and vitamin A), and minerals are also present.
The aromatic constituents include zingiberene and bisabolene, while the pungent constituents are known as gingerols and shogaols. Other gingerol- or shogaol-related compounds (1–10%), which have been reported in ginger rhizome, include 6-paradol, 1-dehydrogingerdione, 6- gingerdione and 10-gingerdione, 4- gingerdiol, 6-gingerdiol, 8-gingerdiol, and 10-gingerdiol, and diarylheptanoids. The characteristic odor and flavor of ginger are due to a mixture of volatile oils like shogaols and gingerols.
Estudios clínicos
Clinical studies revealed that ginger has potential for the prevention and treatment of different GI related disorders. Study in human subjects showed that ginger delays the nausea which is stimulated during chemotherapy. In one clinical study, patients with cancer receiving chemotherapy were given normal diet, protein drink with ginger, and additional high protein with ginger twice daily. They found that protein meals with ginger reduced and delayed nausea due to chemotherapy and reduced the use of antiemetic medications.
Thus, in oncology settings, ginger has been reported useful for preventing chemotherapy-induced nausea and vomiting. Another study suggested that adjuvant ginger supplementation may improve CIN-related quality of life and cancer-related fatigue. 6-gingerol, a bioactive compound in ginger, was also shown to improve overall CINV, appetite, and quality of life. Supplementation may also have chemopreventive effects for those at increased risk for colon cancer with normal-appearing colonic mucosa.
Ginger and its constituents are also effective against pancreatic cancer. Park et al. have shown that 6-gingerol inhibits the growth of pancreatic cancer HPAC and BxPC-3 cells through cell cycle arrest at G1 phase and independent of p53 status. Further they found that 6-gingerol decreased both cyclin A and cyclin-dependent kinase (Cdk) expression followed by reduction in retinoblastoma (Rb) phosphorylation and blocking of S phase entry.
Another study by Kim et al. showed that 6-gingerol regulates tight junction-related proteins and suppresses invasion and metastasis of pancreatic cancer cells. These functions of 6-gingerol were mediated through NF-κB/Snail inhibition via inhibition of the extracellular signal-regulated kinases (ERK) pathway. Thus, 6-gingerol suppresses the invasive activity of PANC-1 cells.
Overall, a significant number of in vitro and laboratory animal studies provide substantial evidence that ginger and its organic pungent vallinoid compounds are effective inhibitors of the carcinogenic process. The use of this ancient medicine for gastrointestinal problems (stimulation of digestion) has been given scientific approval.
Mecanismo biomecánico
The antiemetic action of ginger is attributed to shogaol and gingerol, compounds present in the rhizome, which stimulate the flow of saliva, bile, and gastric secretions, and galanolactone that can act as a competitive antagonist at serotonin 5-HT3 receptors. Additional activities include the stimulation of antral contractions, reduction of postprandial antral area, and acceleration of gastric emptying. Ginger inhibits thromboxane formation and platelet aggregation. However, these effects appear to be dose- and formulation-dependent (eg., dried, fresh, or extract).
In vitro studies suggest that fresh ginger stimulates mucosal cells to secrete IFN-β to combat viral infection, while certain ginger preparations reduced lipopolysaccharide-induced secretion of IL-8 in human bronchial epithelial cells, along with inhibiting human telomerase reverse transcriptase (hTERT) and c-Myc expression in human lung cancer cells.
In other studies, gingerol induced apoptosis of gastric cancer cells through TRAIL-dependent caspase 3/7 activation and inhibited cell-cycle progression by reducing cyclin D1 expression. It also inhibited secretion of angiogenic cytokines such as VEGF and IL-8 in ovarian cancer cells. In animal models, shogaol reduced in vivo tumor growth by damaging microtubules and by inducing mitotic arrest. Increased levels of circulating antioxidant and phase II enzymes, and reduced lipid peroxidation levels are also mechanisms by which ginger protects against DMH-induced colon cancers.
Anticancer activities of ginger against colorectal cancer have been well documented. Numerous in vitro studies showed that ginger and its active components inhibit growth and proliferation of colorectal cancer cells. In a study, 6-gingerol inhibited growth of colon cancer HCT116 cells. The suppression of tumor growth was found to be linked with the inhibition of leukotriene A4 hydrolase activity, which was further confirmed by in silico approach. Besides these, various other mechanisms were reported to be involved in 6-gingerol-induced cell growth inhibition and apoptosis in human colorectal cancer cells. These include protein degradation as well as downregulation of cyclin D1, NAG-1 beta-catenin, PKCepsilon, and GSK-3β pathways. Radhakrishnan et al. reported that the anticancer activity of 6-gingerol could be associated with the inhibition of ERK1/2/JNK/AP-1 pathway.
Lastly, [6]-gingerol suppresses anchorage-independent cancer cell growth by inhibiting LTA4H activity in HCT116 colorectal cancer cells.
Fuentes/Artículos
Adib Rad H, Basirat Z, Bakouei F, et al. Effect of Ginger and Novafen on menstrual pain: A cross-over trial.Taiwan J Obstet Gynecol. 2018 Dec;57(6):806-809.
Ali, Badreldin H., Gerald Blunden, Musbah O. Tanira, and Abderrahim Nemmar. "Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research." Food and chemical Toxicology 46, no. 2 (2008): 409-420. Some_phytochemical_pharmacological_and_t20160322-8287-17m1vhn-with-cover-page-v2.pdf
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Bossi P, Cortinovis D, Fatigoni S, et al. A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin. Ann Oncol. Oct 1 2017;28(10):2547-2551.
Chang JS, Wang KC, Yeh CF, et al. Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol. Jan 9 2013;145(1):146-151.
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Citronberg J, Bostick R, Ahearn T, et al. Effects of ginger supplementation on cell-cycle biomarkers in the normal-appearing colonic mucosa of patients at increased risk for colorectal cancer: results from a pilot, randomized, and controlled trial. Cancer Prev Res (Phila). Apr 2013;6(4):271-281.
Daily JW, Zhang X, Kim da S, Park S. Efficacy of Ginger for Alleviating the Symptoms of Primary Dysmenorrhea: A Systematic Review and Meta-analysis of Randomized Clinical Trials. Pain Med. 2015 Dec;16(12):2243-55.
Darvishzadeh-Mahani F, Esmaeili-Mahani S, Komeili G, et al. Ginger (Zingiber officinale Roscoe) prevents the development of morphine analgesic tolerance and physical dependence in rats. J Ethnopharmacol. Jun 14 2012;141(3):901-907
Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth. Mar 2000;84(3):367-371.
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Ishiguro K, Ando T, Maeda O, et al. Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms. Biochem Biophys Res Commun. Oct 12 2007;362(1):218-223.
Jeena, Kottarapat, Vijayastelter B. Liju, and Ramadasan Kuttan. "Antioxidant, anti-inflammatory and antinociceptive activities of essential oil from ginger." Indian J Physiol Pharmacol 57, no. 1 (2013): 51-62. 1-jul (naturalingredient.org)
Jeong, Chul-Ho, Ann M. Bode, Angelo Pugliese, Yong-Yeon Cho, Hong-Gyum Kim, Jung-Hyun Shim, Young-Jin Jeon, Honglin Li, Hualiang Jiang, and Zigang Dong. "[6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase." Cancer research 69, no. 13 (2009): 5584-5591. https://watermark.silverchair.com/5584.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA-IwggPeBgkqhkiG9w0BBwagggPPMIIDywIBADCCA8QGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMEMT-tsj0nCjbO7yPAgEQgIIDlTe6zAwAOTXqyLdqrdvtz0sIqYV_QfKRBKe7ghln1DWWJVcHj6em1UXog5WxJmD6LqLnkhFzd79krdMcyawILqdkQOaOBBWAQU_cX9bY8UUWBBB75z6rDDnr5tBczzhXbv8jGj74Qre0efbRhAbFF82-YEqpF6npzeW8L3TL_iLQpXey6cI8bdDmJb_IVkzJlyaBtajbuir1PJpE2hAmLp8abigiXUWJnoOEA68h4O9XnKKh4HiffphK-G-KucgIy-kTT_NX10S_p-R_Q3zVnrtTMroVbkiySaxPjAG__hzMOnl6YsXlSbDYNJtCtoxPzSe0dhko-tUbQBR2-GHv9XAzsHYw7qs7TR4qQftlLqerE5ghOnxdYAQOiFoRqqlncyTcB0QzPp9rxt9pcPYcYEFzRosVWv5bwydca9qxQBEy1EN5uPXnWdnH5122kewH2-3DvS2QxcbIiGG8Mu9FELnYvgjCToJy2BM86YbSgBUW0VVPltSn03WINDfZAdzsPfMsjEKjOgRBFNqA71pJDZbZds477xdEuElhE7ZmL10rOzMQl3B61j2Gg4KBa4oFRPF8_0wMpnSXvzUOELy07z2Rf9QpeqAj9hhFm43x7XN8dirSq7k2qifjAzWs_fOlxrxvjjZ70W_EpkbEzyKU9gCTWsvxpZfwuktxJ1QtxP4TsXsyXpC5waZbJWMh_QkXx4Gc5F8pzzByWeDnKFrzoJbZjdlWY8-efbq-Y8M-d8sH8i8HIJT-sCOkb-0_CnXl48d_V6KbTpdSkTeAMUyw_vIEaTwuFGscDwwEb2leTs-BfjsNG48NOzPEv6jKZdkRPvt7vvAw_aVop6t0NbmtFGoV1YkDs-oCmB_u3KydCpjAHshZFeITVxWlOFXAInLYhCnK23daeA6UZGYAKDkBEVySrXLRNuEGHEkWKKzvqtbbhmgZ5L8f4TSaXoSmcgPN4dEegi5s8jfzmgTDhEOGtsfbDCRZKN9Q_RNO4illeXxhspQaOEMDtQKknlLoXB35AVN2Nrwti3YNT7ReCiBKmUWlJaQHJsI_bf-GZEhCjbgscqv4LpXfd4D2moqGpXQZEIM88P0nGJuS7TYakrOBbpZc3d739pMmJra__RoG8USxYui3Vu3ShXGT70FtNh2I-7ZHMm1yJNE1sAV3jIhNwQDy33I_nwA3htVSN4TAP4MKLo51dmseJLep6CB-4kZnMftccXHw
Kim DS, Kim DS, Oppel MN. Shogaols from Zingiber officinale protect IMR32 human neuroblastoma and normal human umbilical vein endothelial cells from beta-amyloid(25-35) insult. Planta Med. Apr 2002;68(4):375-376.
Kim, Sung Ok, and Mi Ryeo Kim. "[6]-gingerol prevents disassembly of cell junctions and activities of MMPs in invasive human pancreas cancer cells through ERK/NF-κB/snail signal transduction pathway." Evidence-Based Complementary and Alternative Medicine 2013 (2013). https://www.hindawi.com/journals/ecam/2013/761852/
Konmun J, Danwilai K, Ngamphaiboon N, et al. 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. Apr 2017;34(4):69.
Lee SH, Cekanova M, Baek SJ. Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells. Mol Carcinog. Mar 2008;47(3):197-208.
Levine ME, Gillis MG, Koch SY, et al. Protein and ginger for the treatment of chemotherapy-induced delayed nausea. J Altern Complement Med. Jun 2008;14(5):545-551.
Lien HC, Sun WM, Chen YH, et al. Effects of ginger on motion sickness and gastric slow-wave dysrhythmias induced by circular vection. Am J Physiol Gastrointest Liver Physiol. Mar 2003;284(3):G481-489.
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Mansour MS, Ni YM, Roberts AL, et al. Ginger consumption enhances the thermic effect of food and promotes feelings of satiety without affecting metabolic and hormonal parameters in overweight men: a pilot study. Metabolism. Oct 2012;61(10):1347-1352.
Martins LB, Rodrigues AMDS, Rodrigues DF, et al. Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) addition in migraine acute treatment. Cephalalgia. 2019 Jan;39(1):68-76.
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Oboh G, Ademiluyi AO, Akinyemi AJ. Inhibition of acetylcholinesterase activities and some pro-oxidant induced lipid peroxidation in rat brain by two varieties of ginger (Zingiber officinale). Exp Toxicol Pathol. May 2012;64(4):315-319.
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Park, Yon Jung, Jing Wen, Seungmin Bang, Seung Woo Park, and Si Young Song. "[6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells." Yonsei Medical Journal 47, no. 5 (2006): 688-697.
https://synapse.koreamed.org/articles/1030061
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Radhakrishnan, E. K., Smitha V. Bava, Sai Shyam Narayanan, Lekshmi R. Nath, Arun Kumar T. Thulasidasan, Eppurathu Vasudevan Soniya, and Ruby John Anto. "[6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling." PloS one 9, no. 8 (2014): e104401. [6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling (plos.org)
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