title: Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro.
abstract: Axonal regeneration is important for functional recovery following nerve damage. Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth factor (NGF). However, a water extract of Centella was ineffective at 100 microg mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel chromatography, were tested (100 microg mL-1) for neurite elongation in the presence of NGF. Greatest activity was found with a non-polar fraction (GKF4). Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less than GKF4. Thus, Centella contains more than one active component. Asiatic acid (AA), a triterpenoid compound found in Centella ethanolic extract and GKF4, showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to GKF13, further indicating that other active components must be present. Neurite elongation by AA was completely blocked by the extracellular-signal-regulated kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily) demonstrated more rapid functional recovery and increased axonal regeneration (larger calibre axons and greater numbers of myelinated axons) compared with controls, indicating that the axons grew at a faster rate. Taken together, our findings indicate that components in Centella ethanolic extract may be useful for accelerating repair of damaged neurons.
authors.affiliation: Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland OR 97239, USA.
authors.forename: Amala
authors.initials: A
authors.lastname: Soumyanath
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Zhong
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Gold
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Yu
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Koop
authors.forename: Dennis
authors.initials: D
authors.lastname: Bourdette
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Gold
mesh_terms: D000284:Administration, Oral; D000818:Animals; D045744:Cell Line, Tumor; D028041:Centella / Q000737:chemistry*; D004195:Disease Models, Animal; D000431:Ethanol / Q000737:chemistry; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008297:Male; D008515:Medicine, Ayurvedic; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D014315:Triterpenes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; D000431:Ethanol; C017032:asiatic acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one