Zingiber officinale attenuates retinal microvascular changes in diabetic rats via anti-inflammatory and antiangiogenic mechanisms.
OBJECTIVE
Diabetic retinopathy is a common microvascular complication of long-standing diabetes. Several complex interconnecting biochemical pathways are activated in response to hyperglycemia. These pathways culminate into proinflammatory and angiogenic effects that bring about structural and functional damage to the retinal vasculature. Since Zingiber officinale (ginger) is known for its anti-inflammatory and antiangiogenic properties, we investigated the effects of its extract standardized to 5% 6-gingerol, the major active constituent of ginger, in attenuating retinal microvascular changes in rats with streptozotocin-induced diabetes.


METHODS
Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels.


RESULTS
Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract-treated group compared to the vehicle-treated group.


CONCLUSIONS
The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation.
Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India.
Shirish
S
Dongare
Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India.
Suresh K
SK
Gupta
Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India.
Rajani
R
Mathur
Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Rohit
R
Saxena
Department of Pathology, AIIMS, New Delhi, India.
Sandeep
S
Mathur
Department of Pharmacology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia.
Renu
R
Agarwal
Department of Anatomy, AIIMS, New Delhi, India.
Tapas C
TC
Nag
Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India.
Sushma
S
Srivastava
Department of Anatomy, AIIMS, New Delhi, India.
Pankaj
P
Kumar
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002396:Catechols / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D003930:Diabetic Retinopathy / Q000097:blood / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005233:Fatty Alcohols / Q000494:pharmacology*; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry*; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015861:Retinal Neovascularization / Q000097:blood / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects* / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D002396:Catechols; D005233:Fatty Alcohols; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C007845:gingerol