The Neuroprotective Effect of Zingiber cassumunar Roxb. Extract on LPS-Induced Neuronal Cell Loss and Astroglial Activation within the Hippocampus

Abstract

The systemic administration of lipopolysaccharide (LPS) has been recognized to induce neuroinflammation which plays a significant role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this study, we aimed to determine the protective effect of Zingiber cassumunar (Z. cassumunar) or Phlai (in Thai) against LPS-induced neuronal cell loss and the upregulation of glial fibrillary acidic protein (GFAP) of astrocytes in the hippocampus. Adult male Wistar rats were orally administered with Z. cassumunar extract at various doses (50, 100, and 200 mg/kg body weight) for 14 days before a single injection of LPS (250 μg/kg/i.p.). The results indicated that LPS-treated animals exhibited neuronal cell loss and the activation of astrocytes and also increased proinflammatory cytokine interleukin- (IL-) 1β in the hippocampus. Pretreatment with Z. cassumunar markedly reduced neuronal cell loss in the hippocampus. In addition, Z. cassumunar extract at a dose of 200 mg/kg BW significantly suppressed the inflammatory response by reducing the expression of GFAP and IL-1ß in the hippocampus. Therefore, the results suggested that Z. cassumunar extract might be valuable as a neuroprotective agent in neuroinflammation-induced brain damage. However, further investigations are essential to validate the possible active ingredients and mechanisms of its neuroprotective effect.

Phytochemicals and Bioactivities of Zingiber cassumunar Roxb

“…Phathong et al [7] discovered (E)-4-(3 ,4 -dimethoxyphenyl)but-3-en-2-ol (17) in Z. cassumunar [4]. In our previous phytochemical studies on Z. cassumunar [8,9], a new dimer type, trans-3-(4hydroxy-3 -methoxyphenyl)-4-[(E)-3 ,4 -dimethoxystyryl]cyclohex-1-ene (18), and a new glycoside type, (E)-4-(3 ,4 -dimethoxyphenyl)but-3-en-1-O-β-D -glucopyranoside (19), were isolated from the rhizomes of Z. cassumunar collected from Indonesia. Since the naturally occurring phenylbutenoid dimers were identified as racemic mixtures, but biological evaluations have been limited due to their low natural abundance, our research group carried out a total synthesis of optically active phenylbutenoid dimers and produced phenylbutenoid dimers with absolute configurations such as 3S- (3,4- (21); and 3R- (3,4- 22) [30].…”

“…In an assessment of the protective effect of the ethanol extract of Z. cassumunar against LPS-induced neuronal cell loss and the activation of astrocytes in the hippocampus [ 19 ], pretreatment with Z. cassumunar extract (200 mg/kg, i.p.) in adult male Wistar rats reduced neuronal cell loss in the hippocampus and suppressed the inflammatory response by reducing the expression of the glial fibrillary acidic protein and IL-1ss in the hippocampus.…”

“…Their pharmacological and nutraceutical properties as derived from the results of the bioassay, in vitro mechanism of action, or in vivo experiments are described in detail below. Methanol extract Anti-inflammatory Carrageenin-induced hind-paw edema test in rats; acetic acid-induced vascular permeability and writhing test in mice [46] Ethanol extract Antioxidant SOD enzyme activity in rat induced by HFD [44] Anti-asthma PMA-induced mucin production in NCI-H292 cells [47] Neuroprotective LPS-induced neuronal cell loss and astroglial activation within the hippocampus using adult male Wistar rats [19] Ether fraction Anti-inflammatory Carrageenin-induced hind-paw edema test in rats; acetic acid-induced vascular permeability and writhing test in mice [46] Hexane fraction…”

“…Phenylbutenoids are characteristic compounds of this plant and have been isolated using various isolation technics [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], including silica gel or reverse phase column chromatography [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ], recrystallization [ 3 , 4 ], preparative thin-layer chromatography [ 6 ], countercurrent chromatography [ 11 , 12 ], and preparative high-performance liquid chromatography [ 10 , 13 , 14 ]. Other constituents include curcuminoids, including a high content of curcumin as a yellow pigment in the rhizome [ 13 , 14 , 15 , 16 , 17 ], two quinones [ 3 , 4 , 18 ], phenolic compounds [ 13 , 17 ], and sesquiterpenoids such as (−)-β-sesquiphellandrene and zerumbone [ 12 , 19 , 20 , 21 ]. The essential oils included sabinene and terpinen-4-ol as major volatile terpenes [ 22 , 23 , 24 , 25 ].…”

“…The essential oils included sabinene and terpinen-4-ol as major volatile terpenes [ 22 , 23 , 24 , 25 ]. The extracts and constituents of Z. cassumunar have diverse bioactivities, including antioxidant [ 21 , 26 , 27 , 28 ], anti-inflammatory [ 7 , 9 , 12 , 19 , 23 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], anticancer [ 8 , 13 , 15 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], neuroprotective/neurotrophic [ 14 , 19 , 20 ], cosmeceutical [ 17 , 21 ], and antifungal/antibacterial [ 22 , 23 , 24 ] activities. Although there has been a review of the clinical effects of various formulations using Plai ( Z. cassumunar ) on were pain relief, acne treatment, and antihistamine [ 1 ], there has been no previous report summarizing the accumulated studies in the literature on the phytochemicals and in vitro and in vivo biological properties of Z. cassumunar , including our previous studies that have contributed to discovering the chemical diversity and biological activities of this plant […”