ovatodiolide and Disease-Models--Animal

Ovatodiolide (OVA), a bioactive substance extracted from the bioactive component of Anisomeles indica, is reported to be endowed with anti-inflammatory properties. Nonetheless, its function in ischemia-reperfusion (I/R)-induced neurological deficits and microglial inflammation remains unclear.. A middle cerebral artery occlusion (MCAO) model was set up in SD rats, which were then dealt with varying doses of OVA. The rats' neurological functions were estimated at diverse periods postoperatively. The dry and wet method, triphenyl tetrazolium chloride (TTC) staining, and Nissl's staining were conducted to measure brain edema, cerebral infarction area and neuronal damage, respectively. Immunohistochemistry (IHC) was performed to detect neuronal apoptosis and microglial activation, and the profiles of inflammatory factors in the cerebral tissues were estimated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In-vitro assays were implemented on HT22 neuronal cells and BV2 microglia to elaborate the effect of OVA against oxygen-glucose deprivation (OGD)-mediated effects.. OVA relieved HT22 cell apoptosis and eased inflammation in BV2 microglia, which were induced by OGD. OVA mitigated NF-κB phosphorylation in BV2 cells, whereas boosted SIRT1 expression. However, inhibiting SIRT1 abolished the anti-inflammatory effects of OVA in BV2 microglia under OGD stimulation. The condition medium (CM) of OGD-treated BV2 cells enhanced HT22 cell apoptosis and damage. OVA treatment in BV2 cells relieved BV2-mediated injury on HT22 cells, which was reversed by SIRT1 inhibitor. In-vivo results revealed that OVA dose-dependently attenuated I/R rats' neurological deficits, reduced brain edema, cerebral infarction area, neuronal apoptosis and microglial overactivation. Additionally, OVA inactivated the NF-κB pathway and up-regulated SIRT1 in the I/R rat model.. OVA prevented rats from brain I/R damage by hampering neuronal apoptosis and microglial inflammation via the SIRT1-NF-κB pathway.. The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

Topics: Animals; Anti-Inflammatory Agents; Brain Ischemia; Cells, Cultured; Disease Models, Animal; Diterpenes; Infarction, Middle Cerebral Artery; Microglia; Neuroinflammatory Diseases; NF-kappaB-Inducing Kinase; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Sirtuin 1

Stepwise modification of ovatodiolide revealed a prodrug, NMP-diepoxyovatodiolide, which can provide sustained release of an active compound, substantial metabolic stability and a unique accumulation profile in the liver. Besides, NMP-diepoxyovatodiolide demonstrated therapeutic benefits in an acute autoimmune hepatitis mouse model and a broad safety window. Therefore, NMP-diepoxyovatodiolide is a very promising candidate for further development of liver-related drugs.

Topics: Animals; Disease Models, Animal; Diterpenes; Hepatitis, Autoimmune; Mice; Mice, Inbred C57BL; Microsomes, Liver; Molecular Structure; Prodrugs; Rats; Rats, Sprague-Dawley

The hierarchical tumor propagation or cancer stem cells (CSCs) model of carcinogenesis postulates that like physiologic adult stem cell (ASC), the CSCs positioned at the apex of any tumor population form the crux of tumor evolution with a constitutive regenerative capacity and differentiation potential. The propagation and recurrence of the characteristically heterogeneous and therapy-resistant hepatocellular carcinoma (HCC), adds to accumulating evidence to support this CSCs model. Based on the multi-etiologic basis of HCC formation which among others, focuses on the disruption of the canonical Wnt signaling pathway, this study evaluated the role of cembrane-type phytochemical, Ovatodiolide, in the modulation of the Wnt/[Formula: see text]-catenin pathway, and its subsequent effect on liver CSCs' activities. Our fluorescence-activated cell sorting (FACS) and quantitative RT-PCR analyses of side population (SP) indicated that CD133+ cells were [Formula: see text]-catenin-overexpressing, more aggressive, and resistant to the conventional anticancer agents, Cisplatin and Doxorubicin, when compared to [Formula: see text]-catenin-downregulated group. We demonstrated that marked upregulation of [Formula: see text]-catenin and its downstream targets effectively enhanced hepatosphere formation, with an associated induction of CD133, OCT4 and Sox2 expression and also caused an significant enhancement of HCC proliferation. However, treatment with Ovatodiolide induced downregulation of [Formula: see text]-catenin and its downstream effector genes, abolished hepatosphere formation and reversed the [Formula: see text]-catenin-associated enhancement of HCC growth. In summary, we demonstrated for the first time that Ovatodiolide suppressed the canonical Wnt signaling pathway, and inhibited the generation of liver CSCs; Thus, projecting Ovatodiolide as a putatively effective therapeutic agent for anti-HCC target therapy.

Topics: Animals; beta Catenin; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Disease Models, Animal; Diterpenes; Down-Regulation; Gene Expression; Humans; Liver Neoplasms; Mice; Neoplastic Stem Cells; Phytochemicals; Phytotherapy; Wnt Signaling Pathway

Asthma, a complex pulmonary allergic disease, major therapy is applied of drugs to control the disease, but quickly recur after the drugs are stopped. In patients with severe asthma may show steroid resistance and would benefit from the development of novel therapeutic drugs. Ovatodiolide, a unique macrocyclic diterpenoid isolated from Anisomeles indica, showed therapeutic potential for the treatment of allergic asthma. As a model of allergic inflammation, we used ovalbumin (OVA)-immunized mice, which displayed T helper cell type 2 (T

Topics: Animals; Asthma; Disease Models, Animal; Diterpenes; Down-Regulation; GATA3 Transcription Factor; Immunoglobulin E; Interleukin-33; Lung; Mice; Th2 Cells

Helicobacter pylori is associated with the majority of gastric disorders and the antibiotic resistant rates have increased annually worldwide. Anisomeles indica and its constituent, ovatodiolide (OVT), were shown to have bactericide activity against Helicobacter pylori. The aim of this study was to manufacture extracts containing the effective constituent, OVT, and evaluate their bactericidal function and the inhibition of inflammatory responses to Helicobacter pylori infection.. Various concentrations of ethanol for extraction of Anisomeles indica were performed and the content of OVT was analyzed by high-performance liquid chromatography (HPLC). The anti-bacterial activity of Anisomeles indica ethanol extracts and the constituent OVT were determined. Additional experiments were performed to investigate the Anisomeles indica ethanol extracts and OVT to inhibit the Helicobacter pylori-induced inflammation of both gastric epithelial cells and macrophages.. Amongst the extracts tested, 50% and 95% ethanol extracts contained large amount of OVT and showed potent anti-Helicobacter pylori activity. An in vitro Helicobacter pylori-infection model revealed that 95% ethanol extract attenuated Helicobacter pylori-induced nuclear factor kappa B (NF-κB) activity and interleukin (IL)-8 secretion of gastric epithelial cells. In addition, 95% ethanol extract significantly inhibited lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS), as well as production of nitric oxide (NO) and tumor necrosis factor α (TNF-α) by macrophages.. This study reveals that Anisomeles indica ethanol extracts containing OVT may be a potent and economic therapeutic agent for Helicobacter pylori infection and attenuation of Helicobacter pylori-mediated inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Diterpenes; Epithelial Cells; Ethanol; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Inflammation Mediators; Interleukin-8; Lamiaceae; Macrophages; Mice; Microbial Sensitivity Tests; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Phytotherapy; Plant Extracts; Plant Stems