Effects of Plantago major Extracts and Its Chemical Compounds on Proliferation of Cancer Cells and Cytokines Production of Lipopolysaccharide-activated THP-1 Macrophages.

BACKGROUND: Plantago major has been reported to have anticancer and anti-inflammatory properties. However, its antiproliferative and anti-inflammatory mechanisms have not been fully elucidated. Moreover, which plant parts are more suitable as starting materials has not been explored. OBJECTIVES: To investigate the antiproliferative activity of P. major extracts against MCF-7, MDA-MB-231, HeLaS3, A549, and KB cancer cell lines as well as their effects on inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1ß, IL-6, and interferon [IFN]-γ) production by lipopolysaccharide (LPS)-stimulated THP-1 macrophages. MATERIALS AND METHODS: The methanol and aqueous extracts of P. major from different plant parts and its chemical compounds, i.e., ursolic acid (UA), oleanolic acid (OA), and aucubin were tested in this experiment. RESULTS: Methanol and aqueous extracts of P. major seeds exhibited the greatest antiproliferative activity. The methanol extracts of seeds also demonstrated the highest inhibition of TNF-α, IL-1ß, IL-6, and IFN-γ production. Interestingly, the roots, which were commonly discarded, exhibited comparable activities to those of leaves and petioles. Furthermore, UA exhibited stronger activities than OA and aucubin. CONCLUSIONS: The seeds are being proposed as the main source for further development of anticancer and anti-inflammatory products, whereas the roots could be included in the preparation of P. major derived products with respect to anti-inflammatory. SUMMARY: Amongst the parts of Plantago major, seeds exhibited the greatest antiproliferative activity against MCF-7, MDA-MB-231, HeLaS3, A549, and KB cell lines as well as the highest inhibition on TNF-α, IL-1ß, IL-6, and IFN-γ productionThe roots, which were commonly discarded, exhibited comparable antiproliferative and cytokines inhibition activities to those of leaves and petiolesUrsolic acid, a chemical compound of Plantago major, exhibited stronger activities than oleanolic acid and aucubinThe seeds are being proposed as the main source for further development of anticancer and anti inflammatory products, whereas the roots could be included in the preparation of Plantago major derived products with respect to anti inflammatory. Abbreviations used: TNF: Tumor Necrosis Factor; IL: Interleukin; IFN: Interferon; HPTLC: High Performance Thin Layer Chromatography; UA: Ursolic Acid; OA: Oleanolic Acid; AUC: Aucubin.

Isolation of a new compound, 2-butanone 4-glucopyranoside 6'-O-gallate and other 8 compounds from the anti-inflammatory leave extracts of Memecylon edule Roxb.

This present study was designed to isolate the compounds of Memecylon edule. The chemical compounds were purified by chromatographic methods and their structures were established on the basis of spectroscopic analyses (UV, MS and NMR). The major isolated compounds were tested for anti-inflammatory activity. The methanolic extracts of M. edule leaves gave a new compound 2-butanone 4-glucopyranoside 6'-O-gallate (1) with eight known compounds, namely, 3,3'-di-O-methylellagic acid 4-O-ß-d-glucopyranoside (2), epigallocatechin-3-O-gallate (EGCG) (3), (2R, 3R)-dihydromyricetin-4'-ß-d-glucopyranoside (4), myricetin-3-O-α-l-rhamnopyranoside (5), benzyl-(6-O-α-L arabinofuranosyl) O-ß-d-glucopyranoside (6), benzyl-(6-O-α-l-rhanmopyranosyl) O-ß-d-glucopyranoside (7), 2-phenylethyl-(6-O-ß-d-apiofuranosyl)-O-ß-d-glucopyranoside (8) and methyl benzoate 2-(6-O-α-l-rhamnosyl)-O-ß-d-glucopyranoside (9). All compounds were isolated for the first time from this plant. The major compounds (2, 3 and 5) exhibited significant anti-inflammatory activity. In conclusion, M. edule was recognised to be a good source for phenolic compounds and these compounds may contribute to anti-inflammatory activity of the extract.

Total Phenolics and Total Flavonoids Contents and Hypnotic Effect in Mice of Ziziphus mauritiana Lam. Seed Extract.

The seeds of Ziziphus mauritiana Lam. have been traditionally used for treatment of various complications including insomnia and anxiety. They are popularly used as sedative and hypnotic drugs in China, Korea, Myanmar, Vietnam, and other Asian countries. However, no scientific proof on hypnotic activity of Z. mauritiana seeds (ZMS) was reported. In this study, the hypnotic activity of 50% ethanolic extract from ZMS was observed on the loss of righting reflex in mice using pentobarbital-induced sleep mice method. The contents of total phenolics and total flavonoids in the extract were also determined. The results showed that the 50% ethanolic extract from ZMS contained total phenolics 27.62 ± 1.43 mg gallic acid equivalent (GAE)/g extract and total flavonoids 0.74 ± 0.03 mg quercetin equivalent (QE)/g extract. Oral administration of the extract at the dose of 200 mg/kg significantly increased the sleeping time in mice intraperitoneally administered with sodium pentobarbital (50 mg/kg body weight). These results supported the traditional use of ZMS for the treatment of insomnia. The seeds of Z. mauritiana should be further developed as an alternative sedative and/or hypnotic product.

Effect of Siam weed extract and its bioactive component scutellarein tetramethyl ether on anti-inflammatory activity through NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Siam weed (Chromolaena odorata (L.) King and Robinson) is a medicinal herb used for wound healing and inflammation-related diseases. AIM OF THE STUDY: In this study, we evaluated the molecular mechanism by which Siam weed extract (SWE) and its bioactive components, scutellarein tetramethyl ether (scu), stigmasterol, and isosakuranetin affect anti-inflammatory activity. MATERIALS AND METHODS: The expression of several inflammatory proteins in RAW 264.7 (murine) macrophages was assessed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Biochemical assays including prostaglandin E2 (PGE2) and nitric-oxide (NO) quantification were performed. Luciferase promoter activity and immunocytochemistry of Nuclear factor-κB (NF-κB) were investigated. RESULTS: Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are critical pro-inflammatory proteins. The level of protein and mRNA expression of these enzymes induced by lipopolysaccharide (LPS) was dramatically suppressed by treatment with SWE, scu, or stigmasterol compounds in a dose-dependent manner. They also reduced PGE2 and NO release. We further analyzed the NF-κB pathway and found that the scu compound suppressed IκB kinase complex alpha/beta (IKKα/ß) and Inhibitory-kappa-B-alpha (IκBα), thereby suppressing COX-2 and iNOS expression. CONCLUSION: This is the first report of the anti-inflammatory molecular mechanism in SWE and/or its bioactive component scu, indicating alteration NF-κB pathway and further providing potential uses in the treatment of inflammatory-related diseases.

In vivo and in vitro hemostatic activity of Chromolaena odorata leaf extract.

CONTEXT: Chromolaena odorata (L.) R.M.King & H.Rob. (Asteraceae) or Siam weed has long been used to stop bleeding in Thailand and many countries. Only the aqueous leaf extract was investigated in in vivo and there have been conflicting results of in vitro hemostatic mechanisms of this plant. OBJECTIVE: The most appropriate C. odorata leaf extract that promoted the highest hemostatic activity and the hemostatic mechanisms of these plant extracts will be investigated. MATERIALS AND METHODS: The lyophilized aqueous leaf extract and alcoholic (50, 70, and 95% ethanol) extracts from the fresh and dried leaves were investigated both in vivo and in vitro. The bleeding time in male Wistar rats was measured to investigate the hemostatic effect. The hemostatic mechanisms were tested using in vitro platelet aggregation and blood coagulation tests in sheep plasma. RESULTS: All extracts displayed significantly reducing bleeding time (<2.5 min) in rats but did not induce platelet aggregation or blood clotting in the in vitro study. The in vitro blood clotting times of all extracts were >0.6 min. Ethanol extract (70%) from the dried leaves proved to be the extract producing the highest hemostatic activity in vivo with the bleeding time of 1.85 min. DISCUSSION AND CONCLUSION: The in vivo study with rats confirmed the significant ability of this plant extract to stop bleeding. However, the sufficient amount of calcium and active compounds which are aggregating and clotting agents to enhance blood coagulation and platelet aggregation in in vitro tests should be further studied.

Anti-inflammatory, analgesic and wound healing activities of the leaves of Memecylon edule Roxb.

AIM OF THE STUDY: To determine the anti-inflammatory, analgesic and antioxidant activities of the leaves of Memecylon edule Roxb. used traditionally in Thailand. MATERIALS AND METHODS: Hexane, (Hex), ethyl acetate (EtOAc), methanol (MeOH) and 50% methanol (MeOH50) fractions of the dry leaves were tested in vitro for their interleukin-10 production; the most active fraction was further studied in vivo for its anti-inflammatory and analgesic activities using the ethylphenylpropiolate (EPP)-induced mouse ear edema and the writhing test with mice. All fractions except Hex were tested for their radical scavenging activity towards 1'-diphenyl-2-picrylhydrazyl radical (DPPH). RESULTS: The EtOAc showed the highest stimulation for interleukin-10 production. In the EPP test, this fraction was significantly active 30 min after topical application at all doses used (0.5, 1.0, 2.0mg/ear); after 4h and at 1.0mg/ear EtOAc was slightly less active (inhibition 47.8%) than the reference, indomethacin, at the same dose (62.4%). At 200mg/kg orally, the EtOAc caused a significant inhibition of the writhing response by 56.6% which was like indomethacin at 10mg/kg. EtOAc, MeOH and MeOH50 exhibited radical scavenging activity. The order of IC(50) values was: ascorbic acid (9.1 microg/mL)>trolox (11.6 microg/mL)>MeOH (46.9 microg/mL)>MeOH50 (152.1 microg/mL)>EtOAc (1742.2 microg/mL). CONCLUSION: The results provide support for the traditional use of Memecylon edule leaves in relieving inflammation and pain.

Inhibitory effect of Thai plant extracts on P-glycoprotein mediated efflux.

Curcuminoids from Curcuma longa L. and extracts of Psidium guajava L., Andrographis paniculata (Burm. f.) Nees, Phyllanthus emblica L. and Solanum trilobatum L. were investigated for their inhibitory effect on P-glycoprotein (P-gp) on the efflux transport of rhodamine 123 (Rho-123 ) in Caco-2 cells and rat ileum. Of the five tested samples, curcuminoids and an extract of P. guajava showed the highest inhibitory effect on P-gp mediated efflux of Rho-123 in Caco-2 cells. Additionally, they were found to have equal potential in inhibiting Rho-123 efflux transport from serosal to mucosal surfaces of the rat ileum.