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Antihyperglycemic potentials of a threatened plant, Helonias dioica: antioxidative stress responses and the signaling cascade.

Abstract
Helonias dioica (HD) is a threatened species of herb growing in North America. It is used as a traditional medicine for treating various ailments particularly related to reproductive issues. The root is reported to contain approximately 10% of a saponin (chamaelirin; C(36)H(62)O(18)) apart from certain other fatty acids. As saponins are known to have hypoglycemic effects, we suspected its possible antihyperglycemic potentials. We injected intraperitoneally alloxan (ALX) at the dose of 200 mg/kg body weight (bw) to induce hyperglycemia in mice and tested possible hypoglycemic effects of HD in vivo by deploying two doses (100 and 200 mg/kg bw, respectively). We also tested its effects on the isolated pancreatic islets cells in vitro. We used various standard protocols like reactive oxygen species (ROS) generation and DNA damage, activities of biomarkers like catalase (CAT), superoxide dismutase (SOD), lipid peroxidase (LPO), reduced glutathione (GSH) of the pancreas tissue and glucokinase and glycogen content of the liver of hyperglycemic mice. With a mechanistic approach, we also tracked down the possible signaling pathway involved. We found an elevated level of ROS generation, LPO and overexpression of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), p38 Map kinase (p38 MAPK), nuclear factor (NF)-κβ, interferon gamma (IFN-γ), cytochrome c, caspase 3, poly [ADP ribose] polymerase (PARP) and cyclo oxygenase 2 (COX2) in ALX-induced diabetic mouse. Treatment of hyperglycemic mice with both the doses of HD showed a significant decrease with respect to all these parameters of study. Thus, our results suggest that HD prevents ALX-induced islet cell damage and possesses antihyperglycemic and antioxidative potentials.
AuthorsDebrup Chakraborty, Asmita Samadder, Suman Dutta, Anisur Rahman Khuda-Bukhsh
JournalExperimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 237 Issue 1 Pg. 64-76 (Jan 2012) ISSN: 1535-3699 [Electronic] England
PMID22169161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hypoglycemic Agents
  • Lipid Peroxides
  • Liver Glycogen
  • NF-kappa B
  • Plant Extracts
  • Reactive Oxygen Species
  • Saponins
  • Tumor Necrosis Factor-alpha
  • Alloxan
  • Cytochromes c
  • Catalase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • Poly(ADP-ribose) Polymerases
  • Glucokinase
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3
  • Glutathione
Topics
  • Alloxan
  • Animals
  • Caspase 3 (biosynthesis)
  • Catalase (metabolism)
  • Cells, Cultured
  • Cyclooxygenase 2 (biosynthesis)
  • Cytochromes c (biosynthesis)
  • DNA Damage
  • Endangered Species
  • Glucokinase (metabolism)
  • Glutathione (metabolism)
  • Hyperglycemia (chemically induced, drug therapy)
  • Hypoglycemic Agents (administration & dosage, pharmacology)
  • Islets of Langerhans (drug effects)
  • Lipid Peroxides (metabolism)
  • Liver Glycogen (analysis)
  • Magnoliopsida (chemistry)
  • Mice
  • NF-kappa B (biosynthesis)
  • Nitric Oxide Synthase Type II (biosynthesis)
  • Oxidative Stress (drug effects)
  • Pancreas (metabolism)
  • Phytotherapy
  • Plant Extracts (administration & dosage, pharmacology)
  • Plant Roots (chemistry)
  • Plants, Medicinal (metabolism)
  • Poly(ADP-ribose) Polymerases (biosynthesis)
  • Reactive Oxygen Species (metabolism)
  • Saponins (analysis, pharmacology)
  • Signal Transduction
  • Superoxide Dismutase (metabolism)
  • Tumor Necrosis Factor-alpha (biosynthesis)
  • p38 Mitogen-Activated Protein Kinases (biosynthesis)

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