eupatilin and Inflammation

Neuroinflammation and apoptosis play a crucial role in Parkinson's disease (PD) pathogenesis. Eupatilin is a lipophilic flavonoid isolated from Artemisia species and exerts anti-apoptotic and anti-inflammatory activities. In this study, we investigated the effects of Eupatilin on a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).. The rotarod test and traction test were constructed to examine the motor function. Immunofluorescent staining was performed to detect the expression of TH, Iba-1 and GFAP. Apoptosis was examined by the TUNEL assay. Real-time PCR was used to determine the mRNA expression and Western blot and ELISA were used to determine the protein expression.. Eupatilin improved behavioral impairment caused by MPTP. A loss of TH positive neurons was observed in the substantia nigra pars compacta of MPTP-lesioned brain, while it was rescued by Eupatilin. Moreover, MPTP administration increased the cell number of microglia and astrocytes and the expression of inflammatory factors TNF-α, IL-1β, and IL-6. Whereas Eupatilin suppressed the activation of neuroinflammation. Eupatilin also decreased cell apoptosis enhanced by MPTP/MPP. We demonstrate that Eupatilin alleviates behavioral impairment and dopaminergic neuron loss induced by MPTP through inhibition of neuroinflammation and apoptosis. Our research provides more evidence for Eupatilin as a potential preventative drug for PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Apoptosis; Astrocytes; Behavior, Animal; Dopaminergic Neurons; Flavonoids; Inflammation; Male; Mice; Mice, Inbred C57BL; Microglia; Nerve Degeneration; Parkinsonian Disorders; Pars Compacta; Rotarod Performance Test

BACKGROUND Eupatilin, an active flavone separated from Artemisia species, has various biological activity such as anti-inflammatory activity. The aim of the present study was to find out the influence of eupatilin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. MATERIAL AND METHODS The administration of LPS was used to induce ALI; eupatilin was given 1 hour before the LPS administration. Lung structural damage of rats was analyzed by hematoxylin and eosin staining and the wet/dry lung ratio. The related inflammatory factors and lung injury markers were examined by enzyme-linked immunosorbent assay. The oxidative stress factors were analyzed by corresponding kits. The expression of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) was assayed by western blot and immunohistochemical staining. RESULTS The results showed that eupatilin alleviated LPS-induced structural damage and decreased the wet/dry lung ratio concentration-dependently. Eupatilin decreased the level of surfactant protein (SP)-A, SP-D, and inflammatory factors such as interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and monocyte chemo-attractant protein (MCP)-1. LPS trigged nitric oxide (NO) generation, improved the production of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and decreased the activity of superoxide dismutase (SOD), which were reversed when rats treated with eupatilin in a concentration-dependent way. Besides, the expression of PPAR-a was increased under the treatment of eupatilin. CONCLUSIONS Collectively, eupatilin alleviated LPS-induced ALI through inhibiting inflammation and oxidative stress in a concentration-dependent way, which was likely to be closely related with the activation of PPAR-alpha.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Flavonoids; Inflammation; Interleukin-6; Lipopolysaccharides; Lung; Male; Malondialdehyde; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Tumor Necrosis Factor-alpha

The CC chemokine eotaxin contributes to epithelium-induced inflammation in airway diseases such as asthma. Eupatilin (5,7-dihydroxy-3',4',6'-trimethoxyflavone), a bioactive component of Artemisia asiatica Nakai (Asteraceae), is reported to inhibit the adhesion of eosinophils to bronchial epithelial cells. However, little is known about the molecular mechanism of eupatilin-induced attenuation of bronchial epithelium-induced inflammation. In this study, we investigated the effect of eupatilin on expression of eotaxin-1 (CCL11), a potent chemoattractant for eosinophils. Eupatilin significantly inhibited eotaxin expression in bronchial epithelial cells stimulated with TNF-α, while NF-κB and IκBα kinase (IKK) activities declined concurrently. Eupatilin also inhibited mitogen-activated protein kinase (MAPK) activity; however, all of these anti-inflammatory activities were reversed by MAPK overexpression. In contrast, eupatilin did not affect the signal transducer and activator of transcription 6 (STAT6) signalling in bronchial epithelial cells stimulated with IL-4. Furthermore, eupatilin significantly attenuated TNF-α-induced eosinophil migration. These results suggest that the eupatilin inhibits the signalling of MAPK, IKK, NF-κB and eotaxin-1 in bronchial epithelial cells, leading to inhibition of eosinophil migration.

Topics: Asthma; Cell Adhesion; Cell Line; Cell Movement; Chemokine CCL11; Drugs, Chinese Herbal; Eosinophils; Epithelial Cells; Flavonoids; Humans; I-kappa B Kinase; Inflammation; Interleukin-4; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Respiratory Mucosa; STAT6 Transcription Factor; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-α and then treated with eupatilin, and the levels of IL-6 and IL-1β mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-α treatment of synoviocytes increased the expression of IL-6 and IL-1β mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Differentiation; Cells, Cultured; Collagen Type II; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Female; Flavonoids; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Lymph Nodes; Mice; Mice, Inbred DBA; Monocytes; Osteoclasts; Plant Extracts; RNA, Messenger; Synovial Membrane; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha

Artemisia princeps Pampanini (family Asteraceae) is an herbal medicine widely used as a hepatoprotective, antioxidative, anti-inflammatory, and antibacterial agent in Korea, China, and Japan.. This study aimed to elucidate the anti-inflammatory effect of the main constituents, eupatilin and jaceosidin, isolated from Artemisia princeps.. We used carrageenan-induced inflammation in an air pouch on the back of mice and carrageenan-induced hind paw edema in rats to determine the anti-inflammatory effects of eupatilin and jaceosidin. Inflammatory makers, such as expression of pro-inflammatory cytokines and cyclooxygenase (COX)-2, and activation of nuclear factor-kappa B (NF-kappaB), were measured by enzyme-linked immunosorbent assays and immunoblot analyses.. Eupatilin and jaceosidin blocked carrageenan-induced increase in leukocyte number and protein levels in air pouch exudates. Eupatilin and jaceosidin inhibited COX-2 expression and NF-kappaB activation, and markedly reduced TNF-alpha, IL-1beta, and prostaglandin E2 (PGE(2)) levels. They also inhibited hind paw edema induced by carrageenan. Eupatilin and jaceosidin had similar activity.. These findings suggest that eupatilin and jaceosidin may reduce inflammation by inhibiting NF-kappaB activation, and that Artemisia princeps inhibits inflammation because of these constituents.

Topics: Animals; Artemisia; Carrageenan; Cyclooxygenase 2; Cytokines; Flavonoids; Inflammation; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Rats; Rats, Sprague-Dawley