Inhibitory effects of armepavine against hepatic fibrosis in rats

Abstract

Activation of hepatic stellate cells (HSCs) plays a crucial role in liver fibrogenesis. armepavine (Arm, C 19 H 23 O 3 N), an active compound from Nelumbo nucifera, has been shown to exert immunosuppressive effects on T lymphocytes and on lupus nephritic mice. The aim of this study was to investigate whether Arm could exert anti-hepatic fibrogenic effects in vitro and in vivo. A cell line of rat HSCs (HSC-T6) was stimulated with tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS) to evaluate the inhibitory effects of Arm. An in vivo therapeutic study was conducted in bile duct-ligated (BDL) rats. BDL rats were given Arm (3 or 10 mg/kg) by gavage twice daily for 3 weeks starting from the onset of BDL. Liver sections were taken for fibrosis scoring, immuno-fluorescence staining and quantitative real-time mRNA measurements. In vitro, Arm (1-10 μM) concentration-dependently attenuated TNF-α-and LPS-stimulated α-SMA protein expression and AP-1 activation by HSC-T6 cells without adverse cytotoxicity. Arm also suppressed TNF-α-induced collagen collagen deposition, NFκB activation and MAPK (p38, ERK1/2, and JNK) phosphorylations. In vivo, Arm treatment significantly reduced plasma AST and ALT levels, hepatic α-SMA expression and collagen contents, and fibrosis scores of BDL rats as compared with vehicle treatment. Moreover, Arm attenuated the mRNA expression levels of col 1α2, TGF-β1, TIMP-1, ICAM-1, iNOS, and IL-6 genes, but up-regulated metallothionein genes. Our study results showed that Arm exerted both in vitro and in vivo antifibrotic effects in rats, possibly through anti-NF-κB activation pathways.

Modulation of metallothionein isoforms is associated with collagen deposition in proliferating keloid fibroblasts in vitro

“…(31) who found that TNF‐α up‐regulated 15% of NF‐κB signal pathway–related genes in KF compared to their normal skin counterparts. It was also recently reported that armepavine derived from the medicinal plant, Nelumbo nucifera, suppressed NF‐κB activation and up‐regulated MT gene expression in inhibiting hepatic fibrosis (30). As silencing of the MT‐2A gene in KF did not modulate Collagen 1A and Collagen 3A gene expression, it is plausible that reduction of MT‐2A facilitates NF‐κB activation, thereby promoting survival of KF and potentiating inflammation, and indirectly enhancing keloid formation.…”

Antimalarial activities of medicinal plants traditionally used in the villages of Dharmapuri regions of South India

“…Nelumbo nucifera has been used for various medicinal purposes in oriental medicine and two compounds, (R)-roemerine and N-methylasimilobine isolated from its leaf exhibited good in vitro antimalarial activity (IC 50 = 0.2 g/mL) (Agnihotri et al, 2008). Armepavine, a compound from Nelumbo nucifera, was found to exert immunosuppressive effects on T-lymphocytes in lupus nephritic mice (Weng et al, 2009). Liensinine, negferine, and isoliensinine isolated from the leaves and embryo of Nelumbo nucifera showed potent anti-HIV activity (IC 50 : 0.8 g/mL) (Kashiwada et al, 2005).…”

Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach

“…The dry powder prepared from its flowers has recently been used in the treatment of Diabetes mellitus by Ayurvedic physicians. Armepavine (Arm), an active compound from N. nucifera, has been shown to exert immunosuppressive effects both in vitro and in vivo through inhibition of NF-κB activation pathways [203]. In vitro , Arm suppressed NF-κB activation and MAPK (p38, ERK1/2, and JNK) phosphorylations and in vivo , Arm attenuated the mRNA expression levels of col1α2, TGF-β1, TIMP-1, ICAM-1, iNOS, and IL-6 genes.…”