Secoiridoid Glycosides from the Twigs of <i>Ligustrum obtusifolium</i> Possess Anti-inflammatory and Neuroprotective Effects

Abstract

Key words Ligustrum obtusifolium; secoiridoid glycoside; anti-inflammation; nerve growth factor (NGF) regulation Glial cells are major defence cells present in the central nervous system (CNS). Microglia and astrocytes are major defending glia cells. In normal condition microglia gets activated and tries to protect the neuron from hazardous conditions or specially pathogens and CNS injury etc. However, under pathological conditions, microglia cells are over-activated and produce a variety of proinflammatory mediators, including nitric oxide (NO). Lipopolysaccharide (LPS) is being used as a neuroinflammation inducer for in vitro experiments. 1) LPS induced neuroinflammation is also responsible for the induction of neuronal apoptosis characterized by neurodegeneration. LPS is a toll like receptor 4 (TLR4) agonist, that can initiate the TLR4 mediated inflammatory cascades during inflammation as well as neuroinflammation. LPS-TLR4 mediated neuroinflammation induce the expression of inducible nitric oxide synthase (iNOS) protein which is responsible to increase the production of nitric oxide.2) NO is a major biomarker against inflammatory conditions, so we did the screening of the compound to inhibit the nitrite production that proves the antiinflammatory activity of our compounds. Additionally, nerve growth factor (NGF) is an important neurotrophin that helps neuron to survive and differentiate during brain development. It is also believed that, NGF helps to improve neurodegeneration and shows its neuroprotective role in the developing brain. It protects neuron against toxin induced neuronal death and cholinergic cell loss. Hence in this study we screened our compounds to increase NGF production through astrocyte. In this way inhibition of NO production and increased NGF production are responsible for anti-inflammatory and neuroprotective effects. 3)Ligustrum obtusifolium, known as Ibota privet, is a shrub that is widely distributed in East Asia. 4) L. obtusifolium has been used as a Korean traditional medicine, and it has been known that fruits have a cardiac and roborant effect, and the trunks have been used for the treatment of diabetes, and hypertension. Additionally, leaves of this plant have been used for oropharyngeal inflammation, rheumatic condition and diuretic conditions in the traditional medicine of southern Europe.5) Taken together we hypothesized that, the compounds present in this plant may play important role in the treatment of neuroinflammation as well as neurodegenerative conditions. Previous phytochemical investigations on L. obtusifolium re ported the isolation of secoiridoid glycosides, phenolic glycosides, and lignans. [6][7][8] In particular, several secoiridoid glycosides isolated from L. obtusifolium were associated with lysine decreasing activity and anti-hyperglycemic activities. 9,10) However, only a few phytochemical studies on L. obtusifolium have been reported. As a part of our continuing search for bioactive constituents from Korean medicinal plants, we investigated methanol (MeOH) ...

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