title: Protective effect of a phenolic extract containing indoline amides from Portulaca oleracea against cognitive impairment in senescent mice induced by large dose of D-galactose /NaNO2.
abstract: BACKGROUND
  Portulaca oleracea L. is a potherb and also a widely used traditional Chinese medicine. In accordance with its nickname "longevity vegetable", pharmacological study demonstrated that this plant possessed antioxidant, anti-aging, and cognition-improvement function. Active principles pertaining to these functions of P. oleracea need to be elucidated.
  
  
  OBJECTIVE
  The present study evaluated the effect of a phenolic extract (PAAs) from P. oleracea which contained specific antioxidant indoline amides on cognitive impairment in senescent mice.
  
  
  METHODS
  PAAs was prepared through AB-8 macroporous resin column chromatography. Total phenol content was determined using colorimetric method, and contents of indoline amides were determined using HPLC-UV method. Senescent Kunming mice with cognitive dysfunction were established by intraperitoneal injection of D-galactose (D-gal, 1250mg/kg/day) and NaNO2(90mg/kg/day) for 8 weeks, L-PAAs (360mg/kg/day), H-PAAs (720mg/kg/day), and nootropic drug piracetam (PA, 400mg/kg/day) as the positive control were orally administered. Spatial learning and memory abilities were evaluated by Morris water maze experiment. Activities of AChE, SOD, CAT, and levels of GSH and MDA in the brain or plasma were measured. Hippocampal morphology was observed by HE staining.
  
  
  RESULTS
  Chronic treatment of large dose of D-gal/NaNO2significantly reduced lifespan, elevated AChE activity, decreased CAT activity, compensatorily up-regulated SOD activity and GSH level, increased MDA level, induced neuronal damage in hippocampal CA1, CA3 and CA4 regions, and impaired cognitive function. Similar to PA, PAAs prolonged the lifespan and improved spatial memory ability. Moreover, PAAs improved learning ability. H-PAAs significantly reversed compensatory increase in SOD activity to the normal level, elevated serum CAT activity, and reduced MDA levels in brain and plasma, more potent than L-PAAs. Besides these, PAAs evidently inhibited hippocampal neuronal damage. However, it had no effect on brain AChE activity.
  
  
  CONCLUSIONS
  PAAs as the bioactive principles of P. oleracea attenuated oxidative stress, improved survival rate, and enhanced cognitive function in D-gal/NaNO2-induced senile mice, similar to piracetam. This phenolic extract provides a promising candidate for prevention of aging and aging-related cognitive dysfunction in clinic.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; Suzhou Psychiatric Hospital, Suzhou 215008, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Dianyu
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Zezhao
authors.initials: Z
authors.lastname: Jiao
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Su
authors.initials: S
authors.lastname: Yue
authors.affiliation: School of Medicine, Shandong University, Jinan 250012, China.
authors.forename: Xiuquan
authors.initials: X
authors.lastname: He
authors.affiliation: Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xia
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ji
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. Electronic address: xianglan02@sdu.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiang
mesh_terms: D000375:Aging; D000577:Amides / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D060825:Cognitive Dysfunction / Q000517:prevention & control*; D004195:Disease Models, Animal; D005690:Galactose / Q000633:toxicity; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D010889:Piracetam / Q000494:pharmacology; D010936:Plant Extracts; D031822:Portulaca / Q000737:chemistry*; D012977:Sodium Nitrite / Q000633:toxicity; D015996:Survival Rate
chemical_list: D000577:Amides; D000975:Antioxidants; D007211:Indoles; D018697:Nootropic Agents; D010636:Phenols; D010936:Plant Extracts; C057812:indoline; D012977:Sodium Nitrite; D005690:Galactose; D010889:Piracetam
keywords: Cognitive enhancement; D-galactose/NaNO(2); Indoline amides; Phenolic extract; Portulaca oleracea