Limonium duriusculum (de Girard) Kuntze Exhibits Anti-inflammatory Effect Via NF-κ B Pathway Modulation

HIGHLIGHTS L. duriusculum n-BuOH extract reduces inflammatory responses both in vitro and in vivo. L. duriusculum n-BuOH extract inhibits NF-κB-dependent transcriptional responses. L. duriusculum n-BuOH extract decreases the expression of TNF-α and IL-6 genes.

Abstract Limonium duriusculum is used in folk medicine to treat inflammatory disorders and has gained attention due to its richness in apigenin. The present investigation was performed to evaluate and confirm its anti-inflammatory properties, in cell lines and animal models. The potential anti-inflammatory properties of n-butanol (n-BuOH) extract of L. duriusculum (BEL) and isolated apigenins were examined on NF-κB transcriptional activity in TNFα- or LPS-stimulated cells, and on in vivo acute inflammatory models (carrageenan induced paw edema and peritonitis). BEL treatment was able to inhibit the activity of an NF-κB reporter gene in HCT116 cells both in the absence and in the presence of exogenous TNFα, used as NF-κB pathway inducer. This anti-inflammatory effect was even more potent compared to Apigenin (APG1) and was confirmed using monocyte-derived THP-1 cells treated with LPS to stimulate NF-κB-dependent transcription of IL-6 and TNFα mRNAs. Apigenin7-O-β-(6''-methylglucuronide) (APG2) was instead inactive both in HCT116 and THP-1 cells. BEL (oral, 200 mg/kg) led to paw swelling inhibition, vascular permeability and peritoneal leukocyte and PN migration diminution. Apigenins (intraperitoneal, APG1, APG2: 20 mg/kg) also evoked a significant anti-edema effect, early vascular permeability and leukocyte influx reduction. Collectively, this study demonstrates for the first time the effectiveness of L. duriusculum to inhibit NF-κB-dependent transcriptional responses in HCT116 and THP-1 cells. In vivo studies also established that L. duriusculum possesses a potential anti-inflammatory effect, confirm its traditional, empirical use, that could be attributed to its richness in apigenin.

In vitro Antiproliferative and inhibition of oxidative DNA damage activities of n-butanol extract of Limonium bonduelli from Algeria

Abstract Plants are the main sources of natural antioxidants in the form of phenolic compounds, which help human beings to deal with oxidative stress, caused by free radical damage. For this reason, the present study was carried out to evaluate the antiproliferative, antioxidant and inhibition of oxidative DNA damage activities of n-butanol extract obtained from aerial parts of Limonium bonduelli. The antioxidant potential was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and inhibition of lipid peroxidation assay. Antiproliferative activity was evaluated using xCELLigence RTCA instrument on two tumor cell lines; HT-29 (human colon adenocarcinoma) and HeLa (human cervix carcinoma). DNA damage inhibition was evaluated using photolyzing 46966 plasmid. Also, total phenolic and total flavonoid contents were determined using a spectrophotometric method. Total phenolic (343 ± 0.05 µg/mg) and flavonoid (220.5 ± 0.04 µg/mg) were indicated as gallic acid and quercetin equivalents respectively. The extract exhibited significant IC50 values in lipid peroxidation (IC50= 181.18 ± 0.65 µg/mL) and DPPH radical scavenging assays (IC50= 14.92 ± 0.032 µg/mL). The extract also partially protected 46966 plasmid DNA from free radical-mediated oxidative stress in a DNA damage inhibition assay and showed concentration-dependent antiproliferative effects. n-butanol extract of L. bonduelli is a rich source of natural antioxidants and anticancer agents.

Comparison of Biological Activities of Korean Halophytes

Halophytes are expected to possess abundant secondary metabolites and various biological activities because of habitat in extreme environments. In this study, we collected 14 halophytes (Asparagus oligoclonos, Calystegia soldanella, Carex pumila, Chenopodium glaucum, Elymus mollis, Glehnia littoralis, Limonium tetragonum, Messerschmidia sibirica, Rosa rugosa, Salsola komarovii, Spergularia marina, Suaeda glauca, Suaeda maritima, and Vitex rotundifolia) native to Korea and compared their total polyphenol contents, antioxidant and anti-inflammatory activities. The total polyphenol contents of R. rugosa (27.28%) and L. tetragonum (13.17%) were significantly higher than those of the other 12 halophytes and L. tetragonum, R. rugosa, and M. sibirica showed significantly greater antioxidant activities than the other 11 halophytes, as determined by DPPH (2,2-diphenyl-1-picrylhydrazyl). A. oligoclonos, E. mollis, and C. pumila showed significantly greater anti-inflammatory activities than the other 11, as determined by NO (Nitric oxide) and PGE₂ (Prostaglandin E₂) levels. In contrast, these three extracts had normal and low total polyphenol contents among the 14 halophytes. Consequently, the total polyphenol content in the 14 studied halophytes appeared to be related to antioxidant, but not anti-inflammatory activity levels.

In silico pharmacodynamics, toxicity profile and biological activities of the Saharan medicinal plant Limoniastrum feei

ABSTRACT In-silico study was performed to find the pharmacodynamics, toxicity profiles and biological activities of three phytochemicals isolated from Limoniastrum feei (Plumbagenaceae). Online pharmacokinetic tools were used to estimate the potential of Quercetin, kaempferol-3-O-ß-D-glucopyranoside (astragalin) and quercitin-7-O-ß-D-glucopyranoside as specific drugs. Then the prediction of potential targets of these compounds were investigated using PharmMapper. Auto-Dock 4.0 software was used to investigate the different interactions of these compounds with the targets predicted earlier. The permeability of quercetin was found within the range stated by Lipinski ׳s rule of five. Hematopoietic prostaglandin (PG) D synthase (HPGDS), farnesyl diphosphate synthetase (FPPS) and the deoxycytidine kinase (DCK) were potential targets for quercetin, astragalin and quercetin 7, respectively. Quercetin showed antiallergic and anti-inflammatory activity, while astragalin and quercetin 7 were predicted to have anticancer activities. The activity of Astragalin appeared to be mediated by FPPS inhibition. The inhibition of DCK was predicted as the anticancer mechanisms of quercetin 7. The compounds showed interesting interactions and satisfactory binding energies when docked into their targets. These compounds are proposed to have activities against a variety of human aliments such as allergy, tumors, muscular dystrophy, and diabetic cataracts.

The Extract of Limonium tetragonum Protected Liver against Acute Alcohol Toxicity by Enhancing Ethanol Metabolism and Antioxidant Enzyme Activities

The protective effect of EtOAc fraction of Limonium tetragonum extract (EALT) against alcoholinduced hepatotoxicity was assessed following acute ethanol intoxication in Spraque-Dawley rats. EALT (200 mg/kg p.o.) was administrated once before alcohol intake (8 g/kg, p.o.). Blood ethanol concentration, and the activities of alcohol metabolic enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver were measured. Also, the formation of malondialdehyde (MDA) and the activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase were determined after acute alcohol exposure. Pretreatment of rats received ethanol with EALT significantly decreased blood ethanol concentration and elevated the activities of ADH and ALDH in liver. The increased MDA level was decreased, and the reduced activities of SOD, GSH-px and catalase were markedly preserved by the treatment with EALT. This study suggests that EALT prevent hepatic injury induced by acute alcohol which is likely related to its modulation on the alcohol metabolism and antioxidant enzymes activities.

Diversity and Plant Growth Promoting Capacity of Endophytic Fungi Associated with Halophytic Plants from the West Coast of Korea

Five halophytic plant species, Suaeda maritima, Limonium tetragonum, Suaeda australis, Phragmites australis, and Suaeda glauca Bunge, which are native to the Muan salt marsh of South Korea, were examined for fungal endophytes by sequencing the internal transcribed spacer (ITS) region containing ITS1, 5.8S rRNA, and ITS2. In total, 160 endophytic fungal strains were isolated and identified from the roots of the 5 plant species. Taxonomically, all 160 strains belonged to the phyla Ascomycota, Basidiomycota, and Zygomycota. The most dominant genus was Fusarium, followed by the genera Penicillium and Alternaria. Subsequently, using 5 statistical methods, the diversity indices of the endophytes were determined at genus level. Among these halophytic plants, P. australis was found to host the greatest diversity of endophytic fungi. Culture filtrates of endophytic fungi were treated to Waito-C rice seedlings for plant growth-promoting effects. The fungal strain Su-3-4-3 isolated from S. glauca Bunge provide the maximum plant length (20.1 cm) in comparison with wild-type Gibberella fujikuroi (19.6 cm). Consequently, chromatographic analysis of the culture filtrate of Su-3-4-3 showed the presence of physiologically active gibberellins, GA(1) (0.465 ng/mL), GA(3) (1.808 ng/mL) along with other physiologically inactive GA(9) (0.054 ng/mL) and GA(24) (0.044 ng/mL). The fungal isolate Su-3-4-3 was identified as Talaromyces pinophilus.

In vitro callus induction and estimation of plumbagin content from Plumbago auriculata Lam.

The medicinal plant Plumbago contains a very potent secondary metabolite, plumbagin having many therapeutic properties. Callus culture was induced using explants, leaf, stem and shoot apex, from P. auriculata. Murashige and Skoog media fortified with various growth hormones like NAA, IAA, IBA and 2, 4-D individually and in various combinations were checked for callus induction. Among the growth hormones used, 1 mg/L 2, 4-D showed best callusing. The hormonal combinations of 1 mg/L IAA and 1.5 mg/L NAA in the media exhibited best callus induction using stem internode as an explant. Plumbagin content from root, stem, leaf and callus was analyzed by using thin layer chromatographic technique. The callus derived from stem showed comparable plumbagin content to the in vivo plant parts. Quantitative spectrophotometric analysis of plumbagin from plant samples and callus indicated that plumbagin content was maximum in roots which was followed by callus, stem and leaf samples respectively. Generation of in vitro sources for plumbagin, for therapeutic applications will serve as a continuous supply and will contribute to preserve the natural plant recourses.

Assessment of pharmacological activities of two medicinal plant of Bangladesh: Launaea sarmentosa and Aegialitis rotundifolia roxb in the management of pain, pyrexia and inflammation

BACKGROUND: The current study aims at evaluating the analgesic, anti-pyretic and anti-inflammatory properties of methanolic extract of the stem, bark and leaves of Launaea sarmentosa and Aegialitis rotundifolia roxb. RESULTS: The AELS and AEAR extract presented a significant (***p < 0.001) dose dependent increase in reaction time in writhing method and showed inhibition of 63.1% and 57.1% respectively at the doses of 400 mg/kg body weight while standard drug showed (P < 0.001) inhibition of 69.23%. In tail immersion method, AELS and AEAR showed maximum time of tail retention at 30 min in hot water i.e. 6.93 sec and 6.54 sec respectively at highest doses of 400 mg/kg body weight than lower dose while standard pentazocine showed reaction time of 7.62 sec. The AELS and AEAR extract also exhibited promising anti-inflammatory effect as demonstrated by statistically significant inhibition of paw volume by 32.48% and 26.75% respectively at the dose of 400 mg/kg body weight while the value at the dose of 200 mg/kg body weight were linear to higher dose at the 3rd hour of study. On the other hand, Standard indomethacin inhibited 40.13% of inflammation (***P < 0.001). In Cotton-pellet granuloma method, AELS and AEAR extract at the dose of 400 mg/kg body weight exhibited inhibition of inflammation of 34.7% and 29.1% respectively while standard drug showed (P < 0.001) inhibition of 63.22%. Intraperitoneal administration of AELS and AEAR showed dose dependent decrease in body temperature in brewer's yeast induced hyperthermia in rats at both doses. However, AELS significantly decreased body temperature (***p < 0.001) at 400 mg/kg compared to control. CONCLUSIONS: Present work propose that the methanolic extract of Launaea sarmentosa and Aegialitis rotundifolia roxb possesses dose dependent pharmacological action which supports its therapeutic use in folk medicine possibly mediated through the inhibition or blocking of release of prostaglandin and/or actions of vasoactive substances such as histamine, serotonin and kinins.

Chemical composition fluctuations in roots of Plumbago scandens L. in relation to floral development

Plumbago scandens L. is a Brazilian tropical/subtropical species that occurs along the coast. Chemically it is mainly represented by naphthoquinones, flavonoids, terpenoids and steroids. The aim of the present work is to study quantitative changes in the root metabolic production of Plumbago scandens during different physiologic developmental stages relative to floration. The results indicated the presence of four substances in the extracts: plumbagin, epi-isoshinanolone, palmitic acid and sitosterol, independent on developmental stage. The naphthoquinone plumbagin has always showed to be the major component of all extracts. Naphthoquinones exhibited their highest content during floration, while the content of the two others components decreased during this stage, revealing an inverse profile. The chemical composition changed depending on the plant requirements.

Plumbago scandens L. é uma espécie brasileira tropical/subtropical que ocorre ao longo da costa. Quimicamente, é principalmente representada por naftoquinonas, flavonóides, terpenóides e esteróides. objetivo do presente trabalho é estudar mudanças quantitativas da produção metabólica nas raízes de Plumbago scandens durante diferentes estágios de desenvolvimento fisiológico, relativos à floração. Os resultados indicaram a presença de quatro substâncias nos extratos: plumbagina, epi-isoshinanolona, ácido palmítico e sitosterol, independente do estágio de desenvolvimento. A naftoquinona plumbagina tem sempre mostrado ser o componente majoritário de todos os extratos. Naftoquinonas exibiram seus maiores conteúdos durante a floração, enquanto o conteúdo dos dois outros componentes decresceu durante este estágio, revelando um perfil inverso. A composição química modificou dependendo das necessidades da planta.

Actividad biológica de Plumbago scandens L. sobre cepas multidrogoresistente de Mycobacterium tuberculosis / Biological activity of Plumbago scandens L. against multidrug-resistance strains of Mycobacterium tuberculosis

Tuberculosis control is a high priority for the Ministry of Health from Peru. In the present work the inhibitory effect of both metanolic (MeOH) and ethyl acetate (AcOEt) crude extracts and the minimum inhibitory concentration (MIC) of both wild plants and in vitro plantlets of Plumbago scandens L. -Plumbaginaceae- against multidrug-resistance (MDR) strains of Mycobacterium tuberculosis were determined. The plant material was constituted by roots and seeds, collected in the Motupe (Lambayeque) area. The in vitro plantlets were obtained from seedlings and micropropagated by shoot tips and nodal segments in Murashige and Skoog (MS) culture medium. The microbiological material consisting of one control strain and two strains of Mycobacterium tuberculosis resistant to isoniazid (INH) and rifampicin (RIF) was cultivated using the Lowenstein–Jensen culture medium. The MIC values varied from 0,65 to 1,3 mg/mL. Bacterial strains showed more sensitivite to the AcOEt crude extract. The GC analysis of the plant material showed the presence of the naphtoquinone plumbagin and other aromatic compounds. In conclusion, the MeOH y AcOEt crude extracts from roots of the wild plants and MeOH crude extract of in vitro plantlets of P. scandens showed a strong inhibitory activity against MDR strains of M. tuberculosis.

El control de la tuberculosis es un objetivo de alta prioridad para el Ministerio de Salud del Perú. En el presente trabajo se determinó el efecto inhibitorio de los extractos crudos metanólico (MeOH) y de acetato de etilo (AcOEt), expresados como concentración mínima inhibitoria (CMI) de plantas silvestres y plántulas in vitro de Plumbago scandens L. (Plumbaginaceae) sobre cepas multidrogoresistente (MDR) de Mycobacterium tuberculosis. El material vegetal estuvo constituido por raíces de plantas silvestres, en tanto que las plántulas in vitro fueron obtenidas de semillas y micropropagadas en medio de cultivo Murashige y Skoog (MS). El material microbiológico, constituido por una cepa control y dos cepas resistentes a isoniacida (INH) y rifampicina (RIF), fue cultivado en medio de cultivo Lowenstein-Jensen. Los valores CMI variaron entre 0,65 y 1,3 mg/mL, mostrándose más sensibles las cepas bacterianas frente al extracto crudo de AcOEt de plantas silvestres. El análisis cromatografía de gases (GC) determinó la presencia de la naftoquinona plumbagina y otros compuestos aromáticos. En conclusión, los extractos crudos de MeOH y AcOEt de raíces de plantas silvestres y extracto crudo de MeOH de plántulas in vitro de P. scandens ejercieron una fuerte acción inhibitoria sobre cepas MDR de M. tuberculosis.

Effect of plumbagin free alcohol extract of Plumbago zeylanica Linn. root on reproductive system of female Wistar rats

OBJECTIVE@#To assess the effect of plumbagin-free alcohol extract (PFAE) of Plumbago zeylanica Linn. (Plumbaginaceae) (P. zeylanica) root, on female reproductive system and fertility of adult female wistar rats.@*METHODS@#After the oral acute toxicity study, the PFAE was administered at two dose levels to perform the estrous cycle study, anti-implantation and abortifacient activity and hormonal analysis. However, the estrogenic/antiestrogenic activity was evaluated at only one most effective dose.@*RESULTS@#LD(50) cut-off was 5,000 mg/kg body weight. The extract exhibited significant anti-implantation and abortifacient activity at the tested dose levels (300 and 500 mg/kg, p.o.) (P<0.01). The extract dose-dependently decreased the levels of serum progesterone, follicle stimulating hormone and luteinizing hormone, while a dose-dependent increase was observed in the concentration of serum prolactin. The extract did not show any significant changes in structure and function of uterus when given alone, but when given along with ethinyl estradiol, it exhibited significant antiestrogenic activity in immature overiectomized female rats(P<0.001). Biochemical parameters in the serum/blood and haematological parameters did not show appreciable changes throughout and after the course of investigation. However, all the altered parameters returned to normalcy within 30 days following withdrawal of treatment.@*CONCLUSIONS@#All findings suggest that the antifertility activity of extract could possibly be through the changes in the implantation site, altered hormonal levels, prolonged estrous cycle and anti-estrogenic activity. Hence, the extract possesses reversible antifertility activity without adverse toxicity in female rats.

Larvicidal activity of extracts from three Plumbago spp against Anopheles gambiae

Three Plumbago spp have been tested for mosquito larvicidal activity. The crude extracts exhibiting the highest larvicidal activity against Anopheles gambiae were hexane (LC50 = 6.4 μg/mL) and chloroform (LC50 = 6.7 μg/mL) extracts from Plumbago zeylanica Linn, chloroform (LC50 = 6.7 ug/mL) extract from Plumbago stenophylla Bull and ethyl acetate (LC50 = 4.1 μg/mL) extract from Plumbago dawei Rolfe. These LC50 values were within 95 percent confidence limits. 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin) 1 (LC50 = 1.9 μg/mL) and β-sitosterol 2 were characterised from ethyl acetate extract of root bark of P. dawei, a native medicinal plant growing in Kenya, based on spectral analysis and comparisons with data in literature.

Study on qualitative and quantitatire methods for Ceratostigma willmottianum / 中国中药杂志

<p><b>OBJECTIVE</b>To establish the qualitative and quantitative methods of Caratostigma willmottianum.</p><p><b>METHOD</b>The roots of Radix Ceratostigmae were identified by TLC with the authentic medicinal material and plumbagin as the reference. The contents of plumbagin in Radix Ceratostigmae were determined by HPLC.</p><p><b>RESULT</b>The TLC method was simple and specific. A Diamonsil C18 column was used. The mobile phase was methanol-water (75:25). Plumbagin in the sawple extract was separated well. The linear range of plumbagin was 33.6-313.6 ng. The average recovery of plumbagin was 100.3% and RSD was 1.9%.</p><p><b>CONCLUSION</b>The methods can be used for identification and determination of plumbagin in C. willmottianum.</p>

Determination of plumbagin in different parts of Plumbago zeylanica by RP-HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a RP-HPLC method to determine plumbagin in Plumbago zeylanica, and to investigate contents of plumbagin in different parts of. P. zeylanica.</p><p><b>METHOD</b>The analysis was carried out at 30 degrees C on a Kromasil C18, column eluted with a mobile phase consisting of a mixture of methanol-water (65: 35). The flow rate was 1 mL x min(-1), the detector wavelength was 213 nm.</p><p><b>RESULT</b>The calibration curve was linear within the concentration ranges of 0.020 8-0. 104 microg (r = 0. 9999). The average recovery was 98.7%. The contents in the root, stem and leaf were 0.394 5%, 0.050 8%, 0.031 4% respectively.</p><p><b>CONCLUSION</b>This method is simple, accurate, replicate and suitable for the determination of plumbagin in P. zeylanica.</p>