Abstract
Besides the classical hormonal effect, estrogen possesses neuroprotective effects in the brain, which leads to the searching of novel treatments for neurodegenerative diseases such as Alzheimer's disease. Scutellarin is a major flavone derived from Herba Erigerontis, a Chinese medicine derived from Erigeron breviscapus , which has been shown here to possess both estrogenic and neuroprotective properties. Scutellarin showed the estrogenic effects by activating the estrogen responsive elements and phosphorylation of estrogen receptor α in cultured MCF-7 cells: the activation was in a dose-dependent manner. On the other hand, scutellarin inhibited the aggregation of β-amyloid in vitro , and prevented the cell death mediated by β-amyloid when applied to cultured neuronal PC12 cells. These results therefore suggested that Herba Erigerontis and its component scutellarin might have therapeutic effects against postmenopausal symptoms and Alzheimer's disease.
Key words
β‐amyloid - scutellarin -
Erigeron breviscapus
- Compositae - estrogen - neuroprotection
References
1
Glazier M G, Bowman M A.
A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy.
Arch Intern Med.
2001;
161
1161-1172
2
Bren L.
The estrogen and progestin dilemma: new advice, labeling guidelines.
FDA Consum.
2003;
37
10-11
3
Brinton L A, Brogan D R, Coates R J, Swanson C A, Potischman N, Stanford J L.
Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy.
Menopause.
1998;
15
145-151
4
Henderson V W, Paganini-Hill A, Miller B L, Elble R J, Reyes P F, Shoupe D, McCleary C A, Klein R A, Hake A M, Farlow M R.
Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial.
Neurology.
2000;
54
295-301
5
Amantea D, Russo R, Bagetta G, Corasaniti M T.
From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens.
Pharmacol Res.
2005;
52
119-132
6
Tanzi R E, Bertram L.
Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective.
Cell.
2005;
120
545-555
7
Miksicek R J.
Commonly occurring plant flavonoids have estrogenic activity.
Mol Pharmacol.
1993;
44
37-43
8
Zhu J T, Choi R C, Chu G K, Cheung A W, Gao Q T, Li J, Jiang Z Y, Dong T T, Tsim K W.
Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death.
J Agric Food Chem.
2007;
55
2438-2445
9
Zhang H F, Hu X M, Wang L X, Xu S Q, Zeng F D.
Protective effects of scutellarin against cerebral ischemia in rats: evidence for inhibition of the apoptosis-inducing factor pathway.
Planta Med.
2009;
75
121-126
10
Lin L L, Liu A J, Yu X H, Qin L P, Su D F.
Protective effects of scutellarin and breviscapine on brain and heart ischemia in rat.
J Cardiovasc Pharmacol.
2005;
50
327-332
11
Jin M, Jin F, Zhang L, Chen Z, Huang H.
Two estrogen replacement therapies differentially regulate expression of estrogen receptors alpha and beta in the hippocampus and cortex of ovariectomized rat.
Brain Res Mol Brain Res.
2005;
142
107-114
12
Hall J M, McDonnell D P.
Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting.
Mol Interv.
2005;
5
343-357
13
Watson C S, Alyea R A, Hawkins B E, Thomas M L, Cunningham K A, Jakubas A A.
Estradiol effects on the dopamine transporter-protein levels, subcellular location, and function.
J Mol Signal.
2006;
1
5
14
Wakeling A E.
Similarities and distinctions in the mode of action of different classes of antioestrogens.
Endocr Relat Cancer.
2000;
7
17-28
15
Singh M, Arseneault M, Sanderson T, Murthy V, Ramassamy C.
Challenges for research on polyphenols from foods in Alzheimer's disease: bioavailability, metabolism, and cellular and molecular mechanisms.
J Agric Food Chem.
2008;
56
4855-4873
16
Gafner S, Bergeron C, Batcha L L, Angerhofer C K, Sudberg S, Sudberg E M, Guinaudeau H, Gauthier R.
Analysis of Scutellaria lateriflora and its adulterants Teucrium canadense and Teucrium chamaedrys by LC‐UV/MS, TLC, and digital photomicroscopy.
J AOAC Int.
2003;
86
453-460
17
Hong H, Liu G Q.
Protection against hydrogen peroxide-induced cytotoxicity in PC12 cells by scutellarin.
Life Sci.
2004;
74
2959-2973
18
Li X L, Li Y Q, Yan W M, Li H Y, Xu H, Zheng X X, Guo D W, Tang L K.
A study of the cardioprotective effect of breviscapine during hypoxia of cardiomyocytes.
Planta Med.
2004;
70
1039-1044
19
Raz L, Khan M M, Mahesh V B, Vadlamudi R K, Brann D W.
Rapid estrogen signaling in the brain.
Neurosignals.
2008;
16
140-153
20
Brinton R D.
Cellular and molecular mechanisms of estrogen regulation of memory function and neuroprotection against Alzheimer's disease: recent insights and remaining challenges.
Learn Mem.
2001;
8
121-133
Prof. Dr. Karl W. K. Tsim
Department of Biology The Hong Kong University of Science and Technology
Clear Water Bay Road
Hong Kong
People's Republic of China
Telefon: + 8 52 23 58 73 32
Fax: + 8 52 23 58 15 59
eMail: botsim@ust.hk