Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol.
BACKGROUND
Zingiber officinale Rosc. (Zingiberaceae) has been traditionally used in Ayurvedic, Chinese and Tibb-Unani herbal medicines for the treatment of various illnesses that involve inflammation and which are caused by oxidative stress. Although gingerols and shogaols are the major bioactive compounds present in Zingiber officinale, their molecular mechanisms of actions and the relationship between their structural features and the activity have not been well studied.


OBJECTIVE
The aim of the present study was to examine and compare the antioxidant and anti-inflammatory activities of gingerols and their natural analogues to determine their structure-activity relationship and molecular mechanisms.


METHODS
The in vitro activities of the compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol were evaluated for scavenging of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibition of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), inhibition of lipopolysaccharide induced nitrite and prostaglandin E(2) production in RAW 264.7 cells.


RESULTS
In the antioxidant activity assay, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol exhibited substantial scavenging activities with IC(50) values of 26.3, 19.47, 10.47 and 8.05 microM against DPPH radical, IC(50) values of 4.05, 2.5, 1.68 and 0.85 microM against superoxide radical and IC(50) values of 4.62, 1.97, 1.35 and 0.72 microM against hydroxyl radical, respectively. The free radical scavenging activity of these compounds also enhanced with increasing concentration (P<0.05). On the other hand, all the compounds at a concentration of 6 microM have significantly inhibited (P<0.05) f-MLP-stimulated oxidative burst in PMN. In addition, production of inflammatory mediators (NO and PGE(2)) has been inhibited significantly (P<0.05) and dose-dependently.


CONCLUSIONS
6-Shogaol has exhibited the most potent antioxidant and anti-inflammatory properties which can be attributed to the presence of alpha,beta-unsaturated ketone moiety. The carbon chain length has also played a significant role in making 10-gingerol as the most potent among all the gingerols. This study justifies the use of dry ginger in traditional systems of medicine.
Dugasani
Swarnalatha
S
Department of Pharmacognosy & Phytochemistry, College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, Andhra Pradesh, India.
Pichika
Mallikarjuna Rao
MR
Nadarajah
Vishna Devi
VD
Balijepalli
Madhu Katyayani
MK
Tandra
Satyanarayana
S
Korlakunta
Jayaveera Narsimha
JN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002396:Catechols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D005233:Fatty Alcohols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020939:Zingiber officinale; D006801:Humans; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002396:Catechols; D005233:Fatty Alcohols; D010936:Plant Extracts; C040115:shogaol; C007845:gingerol; C534464:8-gingerol