The constituents of Anisomeles indica and their anti-inflammatory activities

Ethnopharmacological relevance

Anisomeles indica (L.) Kuntze. (Labiatae), popularly known as ‘yu-chen-tsao’, has been traditionally used as anti-inflammatory agent.

Aim of the study

Investigate the chemical constituents from the whole plants of Anisomeles indica, and evaluate their in vitro anti-inflammatory activities.

Results

The combined MeOH extract was successively partitioned with CHCl₃ and n-butanol, then submitted to several column chromatographic, and HPLC purification procedures which led to the isolation of one cembrane-type diterpenoid (3), two benzenoids (4 and 5), five flavonoids (1, 2, 6, 7 and 14), and six phenyl propanoids (8–13). The compounds 1–14 were examined for their inhibitory effects on inflammatory mediator's enhanced production from LPS/IFN-γ-stimulated macrophages. Among these, ovatodiolide (3) exhibited potent inhibition on NO, TNF-α and IL-12 enhanced production at a concentration of 5 μM, followed by pedalitin (1), scutellarein 7-O-β-d-glucuronide methyl ester (6), and acteoside (12) at 40 μM (P < 0.05). Furthermore, 2 μM of 3, and 20 μM of 1 and 6 significantly (P < 0.05) arrested the cell cycle of Con A-stimulated spleen cells at the G0/G1 stage.

Conclusion

This is the first report on the presence of compounds 1 and 4–13 in this plant and of the potent anti-inflammatory activity of 1, 3, 6 and 12in vitro. These compounds may account for the use of Anisomeles indica in folk medicine to treat inflammation.     

Combined differential gene expression profile and pathway enrichment analyses to elucidate the molecular mechanisms of uterine leiomyoma after gonadotropin-releasing hormone treatment

Composite regulatory signature database (CRSD), a self-developed comprehensive Web server for composite regulatory signature discovery, used to compare the published microarray data with our data on patients with uterine leiomyoma treated with or without GnRH analogue (GnRH-a), revealed that the focal adhesion, mitogen-activated protein kinase (MAPK), CXC chemokine receptor 4/stromal-derived factor-1 (CXCR4/SDF-1), T-cell receptor, integrin, vascular endothelial growth factor (VEGF), GnRH, and transforming growth factor-beta (TGF-beta) signaling pathways are highly expressed in uterine leiomyoma and significantly down-regulated after GnRH-a treatment. According to the results these signaling pathways could be involved in inflammation, proliferation, and remodeling processes of leiomyoma development and possibly in the regression of leiomyoma after GnRH-a treatment, which might improve our understanding of the mechanisms of leiomyoma formation and help us to find novel drug targets or specific markers for diagnosis and prognosis in uterine leiomyoma.     

Inhibition of pro-inflammatory mediators and tumor cell proliferation by Anisomeles indica extracts

Anisomeles indica (L.) Kuntze (Labiatae), is a traditional anti-inflammatory herb used in Taiwan. The aqueous and methanolic extracts of whole plants, leaves, flowers and stems; and chloroform and n-butanol fractions of methanol extract, from A. indica were investigated for their anti-inflammatory activity on murine peritoneal macrophages. In addition, the tumor cells proliferation inhibition activities of these extracts were also evaluated against a panel of tumor cell lines such as Colon 205, PC 3, HepG2 and MCF 7. Treatment with A. indica extracts did not reduce cell viability at any dose used. However, all the extracts significantly inhibited the enhanced production of NO radicals, and pro-inflammatory cytokines (TNF-alpha, and IL-12) induced by LPS/IFN-gamma in a dose-dependent manner. Furthermore, methanolic extracts of leaves and flowers significantly and dose-dependently arrest mitogen-stimulated spleen cells in G0/G1 stage, in addition to their cell proliferation inhibition against Colon 205, MCF 7 and PC 3 by 94, 82; 98, 71; 82, 98%, respectively, at 200 microg/mL concentration. This is the first report on A. indica extracts for their growth inhibitory activities, against inflammatory mediator production, and human tumor cell lines, colon, prostate, hepatoma and breast cells proliferation.     

Can the Internal Iliac Artery Be Safely Covered during Endovascular Repair of Abdominal Aortic and Iliac Artery Aneurysms?

Aneurysmal involvement of the common iliac (CIA) or the internal iliac arteries (IIA) have been relative contraindications for safe endovascular aortic aneurysm (AAA) repair. Our goal was to review our experience in dealing with this problem by performing permanent coverage of one or both IIA during endoluminal repair of aneurysms of the aortoiliac region and to develop a safe, durable strategy. Of the 228 consecutive patients who had endoluminal repair of abdominal aortic (AAA) and iliac artery (IAA) aneurysms between 4/1999 and 4/2001 at our institution, 49 patients underwent coverage and/or coil embolization of one or both IIA during repair because of complex aortoiliac anatomy. These patients were evaluated prospectively for short-term adverse outcome. These results showed that CIA or IIA aneurysms can be managed safely during endoluminal repair of AAA. The IIA can be covered or embolized with minimum adverse consequences in patients who have inadequate CIA for deployment of the aortic or iliac endograft. Unilateral IIA occlusion is well tolerated. We advocate that whenever bilateral IIA occlusion is necessary during endovascular aneurysm repair, one of the IIAs should be revascularized if it is not aneurysmal.     

Adenovirus-mediated gene transfer of human inducible nitric oxide synthase in porcine vein grafts inhibits intimal hyperplasia.

OBJECTIVE: The aim of this study is to determine whether adenoviral inducible nitric oxide synthase (iNOS) gene transfer could inhibit intimal hyperplasia (IH) in porcine internal jugular veins interposed into the carotid artery circulation. METHODS: Porcine internal jugular veins were transduced passively with 1 x 10(11) particles of an adenoviral vector carrying either the human iNOS (AdiNOS) or beta-galactosidase (AdlacZ) cDNA for 30 minutes and then interposed into the carotid artery circulation. Segments of each vein graft were maintained in an ex vivo organ culture to measure nitrite accumulation, a marker of nitric oxide synthesis. The grafts were analyzed immunohistochemically for the presence of neutrophils, macrophages, and leukocytes by staining for myeloperoxidase, ED1, and CD45, respectively, at 3 (n = 4) and 7 (n = 4) days. Morphometric analyses and cellular proliferation (Ki67 staining) were assessed at 3 (n = 4), 7 (n = 4), and 21 days (n = 8). RESULTS: AdlacZ-treated vein grafts demonstrated high levels of beta-galactosidase expression at 3 days with a gradual decline thereafter. Nitrite production from AdiNOS-treated vein grafts was approximately fivefold greater than AdlacZ-treated grafts (P =.00001). AdiNOS or AdlacZ treatment was associated with minimal graft inflammation. Cellular proliferation rates were significantly reduced in AdiNOS-treated grafts as compared with controls at both 3 (41%, P =.000004) and 7 days (32%, P =.0001) after bypass. This early antiproliferative effect was most pronounced at the distal anastomosis (65%, P =.0005). The iNOS gene transfer reduced the intimal/medial area ratio in vein grafts at 7 (36%, P =.009) and 21 days (30%, P =.007) versus controls. This inhibition of IH was again more prominent in the distal segments of the grafts (P =.01). CONCLUSION: Adenovirus-mediated iNOS gene transfer to porcine internal jugular vein grafts effectively reduced cellular proliferation and IH. Although iNOS gene transfer reduced IH throughout the entire vein graft, the most pronounced effect was measured at the distal anastomosis. These results suggest potential for iNOS-based genetic modification of vein grafts to prolong graft patency.     

Association of DRD4 uVNTR and TP53 codon 72 polymorphisms with schizophrenia: a case-control study

Background  

The tumour supressor gene TP53 is thought to be involved in neural apoptosis. The polymorphism at codon 72 in TP53 and the long form variants of the upstream variable number of tandem repeats (uVNTR) polymorphism in the dopamine D4 receptor (DRD4) gene are reported to confer susceptibility to schizophrenia.