AGEs are heterogeneous substances generated from sugars and proteins via Hodge pathway or Wolf and Namiki pathways. Amadori’s product, such as A1C and fructosamine, are produced in the early phase of Hodge pathway. This phase remains blood glucose dependent and partially reversible while the late phase to generate AGEs is blood glucose Antidiabetic Compound Library independent and irreversible. 10 and 11 AGEs accumulation correlates with long term

diabetic microvascular complications as retinopathy and nephropathy. 12, 13, 14, 15 and 16 These substances may enhance diabetes complications through endothelial cell damage and intracellular protein dysfunction, leading to cell and organ deterioration. 17, 18, 19, 20 and 21 Kubola and colleagues reported the reduction of AGEs Epigenetics Compound Library by MC fruits in an in vitro experiment, 22 but this action has not been studied in human. Since there has been no study of MC dried-fruit pulp on long-term glycemic control including antiglycation activity in type 2 diabetic patients. The present pilot study aimed to investigate the effects of this herb on these issues. Bitter melon or Mara-kheenok (in Thai) was cultivated in Suphan Buri and Kanchanaburi provinces, Thailand, and harvested during April–June 2010. The voucher specimen (WTR-002) was deposited

at Department of Pharmacognosy, Faculty of Pharmacy, Silpakorn University, Thailand. Unripe fruits with seeds removed were collected and dried under the sun light for 6 h and in hot air oven at 60 °C for another 6 h. MC not and placebo capsules were manufactured at U-Thong Hospital, Suphan Buri, Thailand. Each MC capsule contained 400 mg of dried fruit pulp. Placebo was made of microcrystalline cellulose grade 102 (Flocel® 102, Gujarat Microwax Private Limited, India). Charantin, an analytical

marker of MC, was analyzed by HPLC method with modification from Ref.23 at Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. The content of charantin was 0.42 ± 0.02 mg/capsule. Capsules were tested for weight variation. Contaminations of pesticide residues, heavy metals and microorganisms of finished product were analyzed by Medicinal Plant Research Institute, Department of Medical Science, Ministry of Public Health, Thailand. All tests were acceptable with respect to the criteria of Thai Herbal Pharmacopoeia (THP) 2000 and Supplement to Thai Herbal Pharmacopoeia (THP Supplement) 2004.24 and 25 A two-arm, parallel, randomized, placebo-controlled trial was conducted at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. The protocol was approved by the Ethics Committee of Faculty of Medicine, Ramathibodi Hospital, Mahidol University. Eligible volunteers were T2DM patients with at least 20 years of age, A1C ≥ 6.5%, and informed consents were provided.