Organ Location Map/System Distribution of Pungent Flavor Compounds’ Targets

Gingerol possessed analgesic, anti-inflammatory, antioxidant, anti-bacterial, anti-tumor-promoting, anti-angiogenic, anti-cancerous, antipyretic, cardiotonic, cardioprotection activities, hepatoprotective cholagogue. It could also relieve pain, antifatigue, relieve itching, protect myocardium, strengthen the stomach and regulate blood pressure.

In recent years, it has been reported that gingerol may also play a role in weight loss,provide protection against acute mercuric chloride-intoxication,endothelial protective effects, reduced blood sugar levels, ameliorative effect on cardiac dysfunction induced by diabetes, improvement of cognitive abilitprotective effect against ethanol-induced teratogenicityattenuated septic Acute kidney injury (AKI),possess hepatoprotective effects, anti-emetic in solid tumor patients, etc.

1. Samad M B, Mohsin M N A B, Razu B A, et al. 6-Gingerol, from Zingiber officinale, potentiates GLP-1 mediated 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 Lepr db/db type 2 diabetic miceJ. BMC complementary and alternative medicine, 2017, 17(1): 395.

2. El-Bakly W M, Louka M L, El-Halawany A M, et al. 6-gingerol ameliorated doxorubicin-induced cardiotoxicity: role of nuclear factor kappa B and protein glycationJ. Cancer chemotherapy and pharmacology, 2012, 70(6): 833-841.

3. Wang S, Tian M, Yang R, et al. 6-Gingerol Ameliorates Behavioral Changes and Atherosclerotic Lesions in ApoE?/? Mice Exposed to Chronic Mild StressJ. Cardiovascular toxicology, 2018: 1-11.

4. Fan J, Yang X, Bi Z. 6-Gingerol inhibits osteosarcoma cell proliferation through apoptosis and AMPK activationJ. Tumor Biology, 2015, 36(2): 1135-1141.

5. 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 chemotherapyJ. Medical Oncology, 2017, 34(4): 69.

6. Surh Y J. Cancer chemoprevention with dietary phytochemicalsJ. Nature Reviews Cancer, 2003, 3(10): 768.

7. Zhang H, Ma S, Feng Z, et al. Cardiovascular disease chemogenomics knowledgebase-guided target identification and drug synergy mechanism study of an herbal formulaJ. Scientific reports, 2016, 6: 33963.

8. Yusof Y A M. Gingerol and its role in chronic diseasesM//Drug discovery from mother nature. Springer, Cham, 2016: 177-207.

9. Qian Q, Yue W, Wang Y, et al. Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minksJ. Archives of pharmacal research, 2009, 32(4): 565-573.

10. Algandaby M M, El-Halawany A M, Abdallah H M, et al. Gingerol protects against experimental liver fibrosis in rats via suppression of pro-inflammatory and profibrogenic mediatorsJ. Naunyn-Schmiedeberg's archives of pharmacology, 2016, 389(4): 419-428.

11. de Paulo Rodrigues F A, da Concei??o Santos A D, de Medeiros P H Q S, et al. Gingerol suppresses sepsis-induced acute kidney injury by modulating methylsulfonylmethane and dimethylamine productionJ. Scientific reports, 2018, 8(1): 12154.

12. Nigam N, George J, Srivastava S, et al. 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 tumorigenesisJ. Cancer chemotherapy and pharmacology, 2010, 65(4): 687-696.

13. Goto C, Kasuya S, Koga K, et al. Lethal efficacy of extract fromZingiber officinale (traditional Chinese medicine) or 6-shogaol and 6-gingerol inAnisakis larvae in vitroJ. Parasitology Research, 1990, 76(8): 653-656.

14. Bode A M, Ma W Y, Surh Y J, et al. Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by 6-gingerolJ. Cancer research, 2001, 61(3): 850-853.

15. Yon J M, Baek I J, Lee S R, et al. Protective effect of [6]-gingerol on the ethanol-induced teratogenesis of cultured mouse embryos[J]. Archives of pharmacal research, 2012, 35(1): 171-178.

16. Li M, Chen P, Yue Q, et al. Pungent ginger components modulates human cytochrome P450 enzymes in vitro[J]. Acta Pharmacologica Sinica, 2013, 34(9): 1237.

17. Kim E C, Min J K, Kim T Y, et al. [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo[J]. Biochemical and biophysical research communications, 2005, 335(2): 300-308.

19. Zhang F, Zhang J G, Yang W, et al. 6-Gingerol attenuates LPS-induced neuroinflammation and cognitive impairment partially via suppressing astrocyte overactivation[J]. Biomedicine & Pharmacotherapy, 2018, 107: 1523-1529.

20. Lee T Y, Lee K C, Chen S Y, et al. 6-Gingerol inhibits ROS and iNOS through the suppression of PKC- and NF-B pathways in lipopolysaccharide-stimulated mouse macrophages[J]. Biochemical and biophysical research communications, 2009, 382(1): 134-139.

21. Isa Y, Miyakawa Y, Yanagisawa M, et al. 6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF- mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes[J]. Biochemical and Biophysical Research Communications, 2008, 373(3): 429-434.

22. Young H Y, Luo Y L, Cheng H Y, et al. Analgesic and anti-inflammatory activities of [6]-gingerol[J]. Journal of ethnopharmacology, 2005, 96(1-2): 207-210.

23. El-Bassossy H M, Elberry A A, Ghareib S A, et al. Cardioprotection by 6-gingerol in diabetic rats[J]. Biochemical and biophysical research communications, 2016, 477(4): 908-914.

24. Dugasani S, Pichika M R, Nadarajah V D, et al. Comparative antioxidant and anti-inflammatory effects of [6]-gingerol,[8]-gingerol,[10]-gingerol and [6]-shogaol[J]. Journal of ethnopharmacology, 2010, 127(2): 515-520.

25. Hashem R M, Rashed L A, Hassanin K M A, et al. Effect of 6-gingerol on AMPK-NF-B axis in high fat diet fed rats[J]. Biomedicine & Pharmacotherapy, 2017, 88: 293-301.

26. Sampath C, Sang S, Ahmedna M. In vitro and in vivo inhibition of aldose reductase and advanced glycation end products by phloretin, epigallocatechin 3-gallate and [6]-gingerol[J]. Biomedicine & Pharmacotherapy, 2016, 84: 502-513.

27. Lee E, Surh Y J. Induction of apoptosis in HL-60 cells by pungent vanilloids,[6]-gingerol and [6]-paradol[J]. Cancer letters, 1998, 134(2): 163-168.

28. Park K K, Chun K S, Lee J M, et al. Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice[J]. Cancer letters, 1998, 129(2): 139-144.

29. Abdel-Aziz H, Windeck T, Ploch M, et al. 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[J]. European journal of pharmacology, 2006, 530(1-2): 136-143.

30. Liu D, Wu M, Lu Y, et al. Protective effects of 6-Gingerol on vascular endothelial cell injury induced by high glucose via activation of PI3K-AKT-eNOS pathway in human umbilical vein endothelial cells[J]. Biomedicine & Pharmacotherapy, 2017, 93: 788-795.

31. Gan Z, Liang Z, Chen X, et al. Separation and preparation of 6-gingerol from molecular distillation residue of Yunnan ginger rhizomes by high-speed counter-current chromatography and the antioxidant activity of ginger oils in vitro[J]. Journal of Chromatography B, 2016, 1011: 99-107.

32. Ueki S, Miyoshi M, Shido O, et al. Systemic administration of [6]-gingerol, a pungent constituent of ginger, induces hypothermia in rats via an inhibitory effect on metabolic rate[J]. European Journal of Pharmacology, 2008, 584(1): 87-92.

34. Joshi D, Srivastav S K, Belemkar S, et al. Zingiber officinale and 6-gingerol alleviate liver and kidney dysfunctions and oxidative stress induced by mercuric chloride in male rats: A protective approach[J]. Biomedicine & Pharmacotherapy, 2017, 91: 645-655.

35. Young H Y, Luo Y L, Cheng H Y, et al. Analgesic and anti-inflammatory activities of 6-gingerolJ. Journal of ethnopharmacology, 2005, 96(1-2): 207-210.

36. Surh Y J. Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short reviewJ. Food and Chemical Toxicology, 2002, 40(8): 1091-1097.

37. Zhang F, Zhang J G, Qu J, et al. Assessment of anti-cancerous potential of 6-gingerol (Tongling White Ginger) and its synergy with drugs on human cervical adenocarcinoma cellsJ. Food and Chemical Toxicology, 2017, 109: 910-922.

38. Dugasani S, Pichika M R, Nadarajah V D, et al. Comparative antioxidant and anti-inflammatory effects of 6-gingerol,8-gingerol,10-gingerol and 6-shogaolJ. Journal of ethnopharmacology, 2010, 127(2): 515-520.

39. Snitker S, Fujishima Y, Shen H, et al. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implicationsCJ. The American journal of clinical nutrition, 2008, 89(1): 45-50.

42. Sun, J., Pu, Y., Wang, P., Chen, S., Zhao, Y., Liu, C., ... & Liu, D. (2013). TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction. Cardiovascular diabetology, 12(1), 69.

43. Meng-Qi Y, Lin-Lan Y E, Xiao-Ling L, et al. Gingerol activates noxious cold ion channel TRPA1 in gastrointestinal tract[J]. Chinese journal of natural medicines, 2016, 14(6): 434-440.

44. Chakraborty D, Bishayee K, Ghosh S, et al. [6]-Gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells: drugCDNA interaction and expression of certain signal genes in HeLa cells[J]. European journal of pharmacology, 2012, 694(1-3): 20-29.

45. Niv D, Maltsman\Tseikhin A. Postherpetic neuralgia: The never\ending challengeJ. Pain Practice, 2005, 5(4): 327-340.

46. Birder, L. A., Wolf\Johnston, A. S., Sun, Y., & Chai, T. C. (2013). Alteration in TRPV 1 and Muscarinic (M3) receptor expression and function in idiopathic overactive bladder urothelial cells. Acta physiologica, 207(1), 123-129.

47. Bod, E., Br, T., Telek, A., Czifra, G., Griger, Z., Tth, B. I., ... & Paus, R. (2005). A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control. The American journal of pathology, 166(4), 985-998.

48. Pezzoli M, Elhamdani A, Camacho S, et al. Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spicesJ. Scientific reports, 2014, 4: 6825.

49. Michlig S, Merlini J M, Beaumont M, et al. Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjectsJ. Scientific reports, 2016, 6: 20795.

50. Steinmetz K A, Potter J D. Vegetables, fruit, and cancer prevention: a reviewJ. Journal of the american dietetic association, 1996, 96(10): 1027-1039.

51. Mukkavilli R, Yang C, Tanwar R S, et al. Pharmacokinetic-pharmacodynamic correlations in the development of ginger extract as an anticancer agent[J]. Scientific reports, 2018, 8(1): 3056.

52. Goff S A, Klee H J. Plant volatile compounds: sensory cues for health and nutritional value?[J]. Science, 2006, 311(5762): 815-819.

53. Pournaderi P S, Yaghmaei P, Khodaei H, et al. The effects of 6-Gingerol on reproductive improvement, liver functioning and Cyclooxygenase-2 gene expression in estradiol valerateCInduced polycystic ovary syndrome in Wistar rats[J]. Biochemical and biophysical research communications, 2017, 484(2): 461-466.

54. Niv D, Maltsman\Tseikhin A. Postherpetic neuralgia: The never\ending challenge[J]. Pain Practice, 2005, 5(4): 327-340.