Toxic pyrrolizidine alkaloids provide a warning sign to overuse of the ethnomedicine Arnebia benthamii.

ETHNOPHARMACOLOGICAL RELEVANCE: From early times man has used medicinal plants for the treatment of various ailments and basic health care needs. The use of herbal medicines has increased day by day and with this, so do reports of adverse events, poisoning, and suspected toxicity. Similarly, the indigenous communities of Neelum Valley in Azad Kashmir commonly use Arnebia benthamii (Wall. ex G.Don) I.M.Johnst. for medicinal purposes to treat various human aliments. Besides their medicinal uses, it also contains hepatotoxic pyrrolizidine alkaloids (PAs). AIM OF THE STUDY: This explorative study underscores two major aspects about this herbal medicine. Firstly we aimed to document the traditional therapeutic uses of Arnebia benthamii in Neelum Valley, Azad Kashmir. Secondly, to determine the presence or absence of hepatotoxic pyrrolizidine alkaloids and if they are within the suggested limit for the use of herbs in excess. MATERIALS AND METHODS: Interviews, group discussions, and inquiries were carried out from July to September 2016 with local indigenous and elder people. In the laboratory, the plant was investigated for pyrrolizidine alkaloids by using high performance liquid chromatography (HPLC). RESULTS: A total of 30 respondents were interviewed. They explained the preferred preparation, parts used, and treatment indications. Treatment of fever along with kidney and liver problems are the three principle uses. Among the different parts of Arnebia benthamii, 43% respondents preferred aerial parts for the herbal formulation, followed by whole plants, and leaves. Decoction was the major mode of preparation and all herbal preparations were administrated orally. This study reports, for the first time according to our literature review, a study of Arnebia benthamii with regard to PA determination. By using column Zorbax SB-Aq and acetonitrile-water gradient as the mobile phase, HPLC results showed that the aerial parts of the plant were PA positive, and (1) Europine, Heliotrine (2), Lycopsamine (3), and Echimidine (4) were identified. CONCLUSIONS: This study has revealed two new findings of significance to herbal medicine producers, practitioners, and consumers of Arnebia benthamii First, local knowledge regarding the medicinal uses of Arnebia benthamii were documented in five sites of Neelum Valley, Azad Kashmir. The use of this plant by a large part of the population in the study area shows the importance for their therapeutic benefits. Unfortunately, the second finding of this study shows that Arnebia benthamii contains hepatotoxic PAs. Hence, we advised to the government regulatory authorities and non-governmental organizations that use of this plant as herbal medicine should be excluded before more accurate quality control tests.

Pillar of strength: Columnar cactus as a key factor in Yoreme heritage and wildland preservation.

The persistence of traditional cultures and modes of land use within rapidly changing, globalized societies is a central issue in understanding ecological and cultural change in the Anthropocene. Located in the heart of the Green Revolution, the Yoreme (Mayo) people of the Mayo Valley in Mexico still obtain a significant proportion of their sustenance from wild ecosystems in the midst of this intensive technological and agricultural development. They live in and around the thornscrub dominated by pitaya (Stenocereus thurberi (Engelm.) Buxb.). In this study, we hypothesize that pitaya supports Yoreme heritage and sustenance amidst anthropogenic changes to the landscape, and we asked three specific questions: What is the land-use status of the S. thurberi habitat? What are its potential uses? Does S. thurberi provide economic value? To address these questions, we conducted interviews, vegetation surveys, and land-use analysis based on geographic information systems. We found that (a) land conversion of the pitaya-rich thornscrub is occurring at a precipitous rate, (b) local producers preserve and adapt their traditions, and (c) S. thurberi supports Yoreme heritage while providing economic benefit. The resulting land-use projections along with the cultural value of pitaya products shows the importance of conserving land and promoting sustainable projects instead of clearing land for other uses. If habitat shrinking continues at the current rate, it is likely that both Yoreme livelihoods and continued cultural practices will suffer.

Ethnopharmacological documentation of medicinal plants used for hypertension among the local communities of DIR Lower, Pakistan.

ETHNOPHARMACOLOGICAL RELEVANCE: Local communities of the Dir Lower district in Northwest Khyber Pakhtunkhwa, Pakistan rely on botanical anti-hypertensive preparations. Insights into the traditional uses of local flora can direct investigation into phytochemical screening. AIM OF THE STUDY: This ethnobotanical study aims to identify plant species and recipes used by the local people for the treatment of hypertension in the district of Dir Lower. MATERIALS AND METHODS: Inquiries and interviews were carried out from November 2012 to December 2013 from local herbalist and indigenous communities including village elders. RESULTS: A total of 46 plant species (43 genera and 29 botanical families) used by local people of study area to treat hypertension. Family Lamiaceae dominated with the highest percentage 15.21% (7 species). With respect to growth form, herbs constituted (63.05%), shrubs (30.43%) and trees (6.52%). Leaves (37.25%) were the most frequently used part in herbal preparations. The major mode of preparation was decoction (46.66%) and almost all recipes were orally administered. Use values (UV) revealed that the most preferred species for the treatment of hypertension by the indigenous community are Paeonia emodi Wall. ex Royle., followed by Sarcococca saligna (D. Don) Muell. Arg., Fumaria indica (Hausskn.) Pugsley and Teucrium stocksianum Boiss. Amongst the 46 medicinal plants, antihypertensive activity of 16 plants included Artemisia vulgiris L., Artemisia annua L., Sisymbrium brassiciforme C. A. Mey., T. stocksianum Boiss, Cichorium intybus L., Rosa brunonii Lindl., Chenopodium botrys L., Olea ferruginea Royle, Cotoneaster acuminatus Lindl, S. saligna (D. Don) Muell. Arg., Viola canescens Wall. ex Roxb, P. emodi Wall. ex Royle, Asparagus gracilis Royle, Maytenus royleanus (Wall. ex Lawson), Allium jacquemontii Kunth and Onosma hispidum Wall has not been reported previously in the scientific literature. CONCLUSIONS: Dir lower is a rich and biodiverse area of medicinal plant. The large number of plant species used for hypertension in this area shows the importance of herbal medicine in the primary health care of this remote area. In future studies, the plant should be further screened for phytochemical and new medicinal properties.

Contribution of increased VEGF receptors to hypoxic changes in fetal ovine carotid artery contractile proteins.

Recent studies suggest that vascular endothelial growth factor (VEGF) can modulate smooth muscle phenotype and, consequently, the composition and function of arteries upstream from the microcirculation, where angiogenesis occurs. Given that hypoxia potently induces VEGF, the present study explores the hypothesis that, in fetal arteries, VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins. Pregnant ewes were acclimatized at sea level or at altitude (3,820 m) for the final 110 days of gestation. Endothelium-denuded carotid arteries from full-term fetuses were used fresh or after 24 h of organ culture in a physiological concentration (3 ng/ml) of VEGF. After 110 days, hypoxia had no effect on VEGF abundance but markedly increased abundance of the Flk-1 (171%) and Flt-1 (786%) VEGF receptors. Hypoxia had no effect on smooth muscle α-actin (SMαA), decreased myosin light chain (MLC) kinase (MLCK), and increased 20-kDa regulatory MLC (MLC(20)) abundances. Hypoxia also increased MLCK-SMαA, MLC(20)-SMαA, and MLCK-MLC(20) colocalization. Compared with hypoxia, organ culture with VEGF produced the same pattern of changes in contractile protein abundance and colocalization. Effects of VEGF on colocalization were blocked by the VEGF receptor antagonists vatalanib (240 nM) and dasatinib (6.3 nM). Thus, through increases in VEGF receptor density, hypoxia can recruit VEGF to help mediate remodeling of fetal arteries upstream from the microcirculation. The results support the hypothesis that VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins.

Chronic hypoxia and VEGF differentially modulate abundance and organization of myosin heavy chain isoforms in fetal and adult ovine arteries.

Chronic hypoxia increases vascular endothelial growth factor (VEGF) and thereby promotes angiogenesis. The present study explores the hypothesis that hypoxic increases in VEGF also remodel artery wall structure and contractility through phenotypic transformation of smooth muscle. Pregnant and nonpregnant ewes were maintained at sea level (normoxia) or 3,820 m (hypoxia) for the final 110 days of gestation. Common carotid arteries harvested from term fetal lambs and nonpregnant adults were denuded of endothelium and studied in vitro. Stretch-dependent contractile stresses were 32 and 77% of normoxic values in hypoxic fetal and adult arteries. Hypoxic hypocontractility was coupled with increased abundance of nonmuscle myosin heavy chain (NM-MHC) in fetal (+37%) and adult (+119%) arteries. Conversely, hypoxia decreased smooth muscle MHC (SM-MHC) abundance by 40% in fetal arteries but increased it 123% in adult arteries. Hypoxia decreased colocalization of NM-MHC with smooth muscle α-actin (SM-αA) in fetal arteries and decreased colocalization of SM-MHC with SM-αA in adult arteries. Organ culture with physiological concentrations (3 ng/ml) of VEGF-A(165) similarly depressed stretch-dependent stresses to 37 and 49% of control fetal and adult values. The VEGF receptor antagonist vatalanib ablated VEGF's effects in adult but not fetal arteries, suggesting age-dependent VEGF receptor signaling. VEGF replicated hypoxic decreases in colocalization of NM-MHC with SM-αA in fetal arteries and decreases in colocalization of SM-MHC with SM-αA in adult arteries. These results suggest that hypoxic increases in VEGF not only promote angiogenesis but may also help mediate hypoxic arterial remodeling through age-dependent changes in smooth muscle phenotype and contractility.

Contributions of VEGF to age-dependent transmural gradients in contractile protein expression in ovine carotid arteries.

The present study explores the hypothesis that arterial smooth muscle cells are organized into layers with similar phenotypic characteristics that vary with the relative position between the lumen and the adventitia due to transmural gradients in vasotrophic factors. A corollary hypothesis is that vascular endothelial growth factor (VEGF) is a factor that helps establish transmural variations in smooth muscle phenotype. Organ culture of endothelium-denuded ovine carotid arteries with 3 ng/ml VEGF-A(165) for 24 h differentially and significantly influenced potassium-induced (55% increase) and stretch-induced (36% decrease) stress-strain relations in adult (n = 18) but not term fetal (n = 21) arteries, suggesting that smooth muscle reactivity to VEGF is acquired during postnatal maturation. Because inclusion of fetal bovine serum significantly inhibited all contractile effects of VEGF (adult: n = 11; fetus: n = 11), it was excluded in all cultures. When assessed in relation to the distance between the lumen and the adventitia in immunohistochemically stained coronal artery sections, expression of smooth muscle α-actin (SMαA), myosin light chain kinase (MLCK), and 20-kDa regulatory myosin light chain exhibited distinct protein-dependent and age-dependent gradients across the artery wall. VEGF depressed regional SMαA abundance up to 15% in adult (n = 6) but not in fetal (n = 6) arteries, increased regional MLCK abundance up to 140% in fetal (n = 8) but not in adult (n = 10) arteries, and increased regional MLC(20) abundance up to 28% in fetal arteries (n = 7) but decreased it by 17% in adult arteries (n = 9). Measurements of mRNA levels verified that VEGF receptor transcripts for both Flt-1 and kinase insert domain receptor (KDR) were expressed in both fetal and adult arteries. Overall, the present data support the unique hypothesis that smooth muscle cells are organized into lamina of similar phenotype with characteristics that depend on the relative position between the lumen and the adventitia and involve the direct effects of growth factors such as VEGF, which acts independently of the vascular endothelium in an age-dependent manner.