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Abstract

Cell suspension and Agrobacterium rhizogenes-transformed hairy root cultures of Devil’s claw (Harpagophytum procumbens), an African plant with high medicinal value, were cultivated in shake-flasks. A purification scheme to isolate their main active constituents (the phenylethanoid glycosides verbascoside, leucosceptoside A, β-OH-verbascoside and martynoside; structurally identified by NMR and LC–MS) was then developed, and their concentrations in the cultures were determined by UV spectrometry following HPLC separation. Preparations, extracts and the isolated phenylethanoid glycosides from the H. procumbens in vitro systems were tested on isolated murine macrophages to study their effects on nitric oxide (NO) and cytokine (TNF-α, IL-6) release and the expression of COX-1 and COX-2. They were also added to human serum to investigate their effects on the classical pathway of complement activation. The results indicate that the extracts and preparations of the in vitro systems, and pure verbascoside (their main active constituent), had strong anti-inflammatory properties, comparable to or even higher than that of pure harpagoside (a major anti-inflammatory constituent of intact Devil’s claw tubers). Thus, they have potential as new anti-inflammatory agents.

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... This clinical trial was conducted to assess the safety and efficacy of a herbal remedy from Pet Wellbeing, called Agile Joints (McDonough, Georgia, USA), on the clinical signs associated with naturally occurring osteoarthritis in client-owned dogs. This proprietary herbal blend contains devil's claw tuber (Harpagophytum procumbens), sarsaparilla root (Smilax officinalis), dandelion root (Taraxacum officinale), yucca root (Yucca glauca), boswellia gum (Boswellia serrata), turmeric root extract standardized to 10% curcuminoids (Curcuma longa), and bromelain as active herbal ingredients: all of which demonstrate mild to moderate anti-inflammatory properties in both in vitro and in vivo human studies (6)(7)(8)(9)(10)(11)(12)(13). In particular, devil's claw, boswellia, curcumin, and bromelain have been studied as to their effective use for management of OA. ...
... In particular, devil's claw, boswellia, curcumin, and bromelain have been studied as to their effective use for management of OA. Devil's claw has strong anti-inflammatory properties, with effects on cellular release of nitric oxide (NO) and cytokines, as well as the expression of cyclooxygenase (COX)-1 and COX-2 (6). It has been shown to specifically reduce cytokine expression in human osteoarthritic chondrocytes (14). ...
... A systematic review of long-term NSAID use in the treatment of canine osteoarthritis concluded that there is evidence of progressive decreases in pain with long-term NSAID use for dogs with chronic OA (20). Given that the herbs in the PWB decoction used in this study have similar mechanisms of action of decreasing inflammation as NSAIDs (6)(7)(8)(9)(10)(11)(12)(13), it is possible the same effect would be noted with longer-term use. The fact that the PWB decoction may affect the same mediators of inflammation as NSAIDs may have confounded results, as 55% of dogs in this study were receiving NSAIDs. ...
Article
Osteoarthritis is the most common joint disease in dogs. Despite the use of nonsteroidal anti-inflammatory drugs (NSAIDs), many owners seek natural therapies; either to augment the response to NSAIDs, or as a replacement. Substantial research has been directed to investigation of novel therapies. A randomized, double-blinded, controlled study was conducted to assess the efficacy of a herbal remedy for treatment of canine osteoarthritis pain. Client-owned dogs (N = 24) with osteoarthritis were enrolled between 2 veterinary hospitals. Each dog underwent veterinary and owner assessment at 0, 4, and 8 weeks, using the Canine Brief Pain Inventory and Hudson activity scale. Blood was collected for a complete blood (cell) count (CBC) and serum chemistry analysis. The product was deemed to be safe and well-tolerated at the manufacturer recommended dosage, with no significant changes seen in the CBC or serum biochemical analyses. Aside from1 dog that developed gastrointestinal upset, all other dogs tolerated the supplement without complication. The supplement did not statistically improve clinical signs in dogs based on veterinary or owner assessments of lameness. There was a treatment/time effect when assessing veterinary pain scores; however, post-hoc analysis suggests no observable benefit of treatment compared with the placebo group at any time point.
... Improvements in total symptom score and the stiffness, and physical function dimensions were significantly greater in the high-dose (400 mg per day) compared with the low-dose group (200 mg per day) [15]. The results indicate that the extracts and preparations of the in vitro systems had strong anti-inflammatory properties, comparable to or even higher than that of pure harpagoside (a major anti-inflammatory constituent of intact Devil's claw tubers) [16,17]. Silymarin during evaluation exhibited significant anti-inflammatory and anti-arthritic activities in the papaya latex induced model of inflammation and mycobacterial adjuvant induced arthritis in rats [18]. ...
... The doses of active ingredients were chosen according to scientific research and publications [11][12][13][14][15][16][17][18]. Herbal anti-inflammatory medicines provide a broad-spectrum mechanism of action such as interaction with the inflammatory cascade, cytokine production, inhibition of elastase or hyaluronidase, increased anti-oxidative effectiveness and other still unidentified effects that may contribute to joint protective effects [6]. ...
... Concerns about the safety and efficacy of many drugs used for the treatment of autoimmune diseases have persisted for many years and researchers put high efforts to find the new drugs with fewer side effects. During the past years many research groups throughout the world have concentrated on finding biologically active substances from various plants and efficacy of various natural products against inflammation, and arthritis has been explored [11][12][13][14][15][16][17][18]. Our previous investigations also have shown that administration of herbal preparation tinctures, such as Filipendula ulmaria Maxim (L) and Aesculus hippocastanum (L), exerts a therapeutic effect on AA and osteoarthritis in rats [31,32]. ...
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Background and objective: The purpose of the present study was to examine the anti-arthritic and antioxidant effects of herbal and active organic ingredient complex (EM 1201) in rats with experimental adjuvant arthritis (AA). Materials and methods: AA was induced in 30 male Wistar rats by intradermal injection of complete Freund's adjuvant into the left hind paw. The course of disease in 30 rats in response to the treatment with EM 1201 and diclofenac, the parameters including body weight, joint swelling, blood indices pro-/antioxidant status of blood serum, and histology of joints and the liver, were investigated. Results: Preparation EM 1201 showed anti-inflammatory effect analogous to diclofenac, improved blood indices, significantly decreased joint swelling and histological changes in them. Joint swelling was suppressed by 29%–42.8% and 9.3%–34.4% in response to administration of EM 1201 and diclofenac during the entire experiment. Both preparations significantly suppressed pannus formation, general inflammatory reaction and edema in soft periarticular tissues and synovium, diminished MDA level and elevated AOA in the blood serum. Significantly lower absolute and relative weight of the liver and lower dystrophic processes in it, and general inflammatory infiltration of hepatic stroma proved the positive effect of treatment with EM 1201. Conclusions: The present study suggests that EM 1201 has protective activity against arthritis and demonstrated its potential beneficiary effect analogical to diclofenac. Anti-inflammatory and anti-oxidative effect of EM 1201 in rats with AA support the need of further investigations by using it as supplementary agent alone or together with other anti-arthritic drugs in the treatment of rheumatoid arthritis.
... In particular, this derivative product is able to decrease the prostaglandin production derived from cyclo-oxygenase 2 by acting as a competitive inhibitor of the active domain of the enzyme since its structure resembles much that of prostaglandine E2 which is known as one of its strongest selective inhibitors. Additional experiments on expression of both COX-1 and COX-2 were performed by Gyurkovska et al. [115] who measured a strong inhibition of their expression in macrophages. The effect on proinflammatory mediators has been also investigated [7,115,198]: harpagide did not significantly affect the release of cytokines (TNF-α and IL-6) in macrophages whereas controversial results on nitric oxide (NO) release have been obtained. ...
... Additional experiments on expression of both COX-1 and COX-2 were performed by Gyurkovska et al. [115] who measured a strong inhibition of their expression in macrophages. The effect on proinflammatory mediators has been also investigated [7,115,198]: harpagide did not significantly affect the release of cytokines (TNF-α and IL-6) in macrophages whereas controversial results on nitric oxide (NO) release have been obtained. When harpagide was tested at a concentration of 0.25 mg/mL, NO accumulation in the supernatants of LPS-stimulated macrophages decreased. ...
... Lastly, harpagide shows moderate inhibitory effects at the concentration of 1 mg/mL on the CP complement activity in human serum in vitro [115]. ...
Article
In this review article, the occurrence of harpagide in the plant kingdom and its associated biological activities are presented and detailed for the first time. The presence of harpagide has been reported in several botanical families within Asteridae, and harpagide has been observed to exert a wide number of biological activities such as cytotoxic, anti-inflammatory, and neuroprotective. These results show how harpagide can be recovered from several natural sources for several pharmacological purposes even if there is a lot to still be studied. Nowadays, the interest is related to its presence in phytomedicines. Threfore, these studies are useful to support and validate the large use of several plants in the folklore medicine.
... The phenolic glycosides that have been identified in H. procumbens are 8-feruloyharpagide, verbascoside, leuxosceptoside, pagoside, illustrated in Figure 4A-C [65]. Among these, verbascoside, also known as acteoside, was found to have a strong anti-inflammatory effect which was either comparable or even higher than that of harpagoside [66]. The other phenolic glycosides of H. procumbens either have a strong antioxidant activity or antimicrobial activities [43]. ...
... Murine peritoneal macrophages and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) were used to investigate the cytotoxicity of H. procumbens extracts and their purified substances. Compound harpagide demonstrated the highest toxic result at 1 mg/mL concentration by decreasing the number of viable cells as compared with β-OH-verbascoside and martynoside [66]. In a recent study, Joshi and colleagues [26] conducted a toxicological study of H. procumbens aqueous-alcohol root tuber extract using a rat model. ...
Article
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Harpagophytum procumbens subsp. procumbens (Burch.) DC. ex Meisn. (Sesame seed Family—Pedaliaceae) is a popular medicinal plant known as Devil’s claw. It is predominantly distributed widely over southern Africa. Its impressive reputation is embedded in its traditional uses as an indigenous herbal plant for the treatment of menstrual problems, bitter tonic, inflammation febrifuge, syphilis or even loss of appetite. A number of bioactive compounds such as terpenoids, iridoid glycosides, glycosides, and acetylated phenolic compounds have been isolated. Harpagoside and harpagide, iridoid glycosides bioactive compounds have been reported in countless phytochemical studies as potential anti-inflammatory agents as well as pain relievers. In-depth studies have associated chronic inflammation with various diseases, such as Alzheimer’s disease, obesity, rheumatoid arthritis, type 2 diabetes, cancer, and cardiovascular and pulmonary diseases. In addition, 60% of chronic disorder fatalities are due to chronic inflammatory diseases worldwide. Inflammation and pain-related disorders have attracted significant attention as leading causes of global health challenges. Articles published from 2011 to the present were obtained and reviewed in-depth to determine valuable data findings as well as knowledge gaps. Various globally recognized scientific search engines/databases including Scopus, PubMed, Google Scholar, Web of Science, and ScienceDirect were utilized to collect information and deliver evidence. Based on the literature results, there was a dramatic decrease in the number of studies conducted on the anti-inflammatory and analgesic activity of Devil’s claw, thereby presenting a potential research gap. It is also evident that currently in vivo clinical studies are needed to validate the prior massive in vitro studies, therefore delivering an ideal anti-inflammatory and analgesic agent in the form of H. procumbens products.
... Harpagoside is an iridoid glycoside present in several plant families, mainly the Lamiaceae, Pedaliaceae, Scrophulariaceae and Plantaginaceae (Georgiev et al., 2013), and rarely in the Orobanchaceae. It exhibits anti-inflammatory properties, through the inhibition of the COX-1/2 expression and NO production by peritoneal macrophages (Gyurkovska et al., 2011;Georgiev et al., 2013). Similarly to aucubin, harpagoside has not been found to be present in the untransformed control roots of R. elata plants (Piątczak et al., 2015a). ...
... In addition to iridoid glycosides, the R. elata hairy root lines also produced two phenylethanoid glycosides, viz. verbascoside and isoverbascoside, which exhibit a range of strong biological activities, including cytotoxic activities against a murine cell line, as well as antiradical, antibacterial (against Staphylococcus aureus), antitumor, anti hyperalgesic and anti-inflammatory activities (Pettit et al., 1990;Herbert et al., 1991;Avila et al., 1999;Georgiev et al., 2011;Gyurkovska et al., 2011;Isacchi et al., 2011). In the present study, verbascoside content in R. elata hairy root lines ranged between 8.9 mg/g DW in line L9 and 17.3 mg/g DW in line S1 (Table 3). ...
Article
Hairy root lines were established through the infection of Agrobacterium rhizogenes strain (A4) from shoot tips and leaves of Rehmannia elata N. E. Brown ex Prain (Orobanchaceae). Seven lines of hairy roots were selected on the basis of morphology and biomass increase in liquid Woody Plant Medium (WPM) supplemented with sucrose (30 g/L) without growth regulators. The transgenic status of the roots was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR) using rolB and rolC specific primers. After 30 days of growth the highest fresh weight (FW) and dry weight (DW) were determined in the S1 hairy root line (9.97 g/flask and 0.88 g/flask, respectively). UHPLC was then used to measure the accumulation of iridoid glycosides (aucubin, harpagide, harpagoside) and phenylethanoid glycosides (verbascoside and isoverbascoside) in selected hairy root lines. Among the iridoid glycosides, the highest amounts of aucubin (0.2 mg/g DW) and harpagide (1.57 mg/g DW) were detected in the S1 line, and harpagoside (0.09 mg/g DW) in the L14 line. Among the phenylethanoid glycosides, the highest levels of verbascoside (17.35 mg/g DW) and isoverbascoside (˜ 2 mg/g DW) were identified in the S1 root line. Catalpol, catalposide and loganin could not be detected in any tested hairy root line.
... Thanks to the presence of the phenylethanoid glycoside components, their leaf extracts are also active against Type I Herpes virus and exhibit antibacterial and antifungal activity (McCutcheon et al. 1993(McCutcheon et al. , 1994(McCutcheon et al. , 1995. Specifically, the anti-inflammatory and anti-irritant action of verbascoside is attributed to the ability of decreasing the expression of cyclooxygenase-2 (Gyurkovska et al. 2011), inhibiting nitric oxide synthase, as well as inducing and releasing NO from bacterial lipopolysaccharide stimulated macrophages (Picerno et al. 2005). ...
... and holds potential as natural preservative agent for foods. Moreover, leucosceptoside A is endowed with good anti-inflammatory, radical scavenging and anticancer effects (Wang et al. 1996;Zhou et al. 1998;Gyurkovska et al. 2011) while leucosceptoside B, similarly to leucosceptoside A, is mainly known to exhibit anti-inflammatory activities (Dimitrova et al. 2012). Moreover, leucosceptoside B was detected for the first time in calli and cell suspension cultures derived from plants, and iso-verbascoside was observed for the first time to be present in larger amount than verbascoside. ...
Article
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In this work an effective method to start axenic cultures of Verbascum thapsus L. was developed. This allowed to obtain a high percentage of callus generation from leaf explants (around 70%) and to start the cultivation of suspension cultured cells rapidly growing in liquid culture medium. Moreover, the production in these materials of the phenylethanoid glycoside compound verbascoside was verified and quantified ascertaining that both calli and cultured cells maintain the ability to accumulate it at levels similar or superior to those found in plant leaves. Moreover, since HPLC–UV chromatograms of extracts of both calli and suspension cultured cells revealed the presence of other relevant peaks close to the verbascoside one, an HPLC–DAD–MS analysis was carried out leading to identify and quantify three further phenylethanoid glycosides i.e. iso-verbascoside, leucosceptoside A and leucosceptoside B, compounds which had been previously detected and identified also in extracts from leaves. On the whole, the above summarized findings confirm and reinforce the attractiveness and reliability of using in vitro cultures as a convenient source of this class of natural plant products, particularly taking into account that a number of biotechnological approaches allowing to increase the yield of the synthesized phytochemicals are currently available and can be applied in plant tissue culture.
... Neurological Disorders and Imaging Physics, Volume 2 [ [149][150][151] Olea europaea L. ...
... Aqueous H. procumbens extracts suppress PGE2 and NO production by inhibiting the expression of COX-2 and nitric oxide synthase (iNOS) enzymes, without significantly affecting cellular viability [150]. Further studies have confirmed that H. procumbens root extracts significantly inhibit COX-2 and iNOS expression in murine macrophages by approximately 70% and 40%, respectively [151]. That study also reported substantial inhibition of NO, TNF-α and IL-6 (by approximately 20%, 45% and 32%, respectively, compared to the untreated control). ...
Chapter
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The current methods of treating multiple sclerosis (MS) do not address the early phases of the disease progression and instead merely treat the later phase symptoms. Whilst this approach may help to alleviate many of the symptoms and much of the discomfort associated with MS, it does not stop the disease progression and the destruction of neuronal tissue still occurs. Furthermore, a number of serious side effects are associated with the current treatment modalities. A better strategy may be to eradicate the cause of the disease, thereby bypassing the later phase events. Until recently, this has not been possible due to a lack of understanding of the etiology of MS. However, recent advances have identified Acinetobacter baylyi and Pseudomonas aeruginosa as bacterial triggers of the disease in genetically susceptible people, and have provided some understanding of the disease progression. An understanding of the early phases of the disease has identified a variety of new targets for anti-MS drug development which may allow for the development of new treatment regimens with increased efficacy and/or less serious side effects. This chapter examines the bacterial triggers of rheumatoid arthritis (RA) and how they may induce self-reactive antibody production. In so doing, this report highlights some targets for drug treatments aimed at blocking the early phases of MS before the more serious later phase events occur. Whilst it is unlikely that any single drug will be able to treat all aspects of this disease, resveratrol and other stilbenes are highlighted as a class of compounds which may have beneficial effects on several phases of MS disease progression. Similarly, several natural therapeutics with activities against several phases of MS progression are discussed.
... Harpagoside was first isolated from the tubers of Hp (Tunman and Lux 1962) and is thought, together with one or more iridoid and phenylethanoid/phenylpropanoid glycosides to be responsible for the anti-inflammatory properties of the various extracts, salves, and tinctures made from this and related plants (Abdelouahab and Heard 2008;Anauate et al. 2010;Galindez et al. 2002;Garcia et al. 1996;Georgiev et al. 2013;Gyurkovska et al. 2011;Mncwangi et al. 2012;Tundis et al. 2008;Viljoen et al. 2012). Whether harpagoside alone may not be sufficient for anti-inflammatory activity toward many conditions, it is a useful molecular marker required by the European Pharmacopoeia for Hp products. ...
... In bioassays, 8-O-acetylharpagide isolated from Scrophularia deserti and Scrophularia scorodonia has been shown to possess weak to moderate anti-inflammatory activities in comparison to harpagoside (Tundis et al. 2008). Verbascoside isolated from Hp tubers also possesses similar anti-inflammatory properties to harpagoside (Abdelouahab and Heard 2008;Gyurkovska et al. 2011). ...
Article
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Introduction Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain. Objectives We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America. Methods Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI. Results Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus. Conclusions Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.
... Little data is currently available regarding the antiinflammatory activity of phytoextracts on PMNs of domestic animals (Kori et al., 2009). The present study indicated that in vitro harpagoside was able to suppress the respiratory burst of porcine PMNs, as was previously described by other authors in a macrophage cell line (Huang et al., 2006) and murine peritoneal macrophages (Gyurkovska et al., 2011). The molecular basis of harpagoside's effect on the respiratory burst is still largely unknown, but it is unlikely to be related to any scavenger property towards ROS (Grant et al., 2009). ...
... In agreement with previous studies (Qi et al., 2006;Gyurkovska et al., 2011), we observed a significant effect of harpagoside at concentrations of ≥100 µg/ml, which are much higher when compared with the plasma levels (25-55 ng/ml) detected in experimental animal studies (Axmann et al., 2019). However, as prolonged duration therapy is recommended for humans, the cumulative dosing effects must be considered in-vivo (Grant et al., 2009). ...
... Abou-Mandour (1977) has established callus tissue of H. procumbens but the cultures did not produce any iridoids. The metabolites were not found in cell suspension cultures of the plant although they biosynthesized phenylethanoid glycosides (Georgiev et al., 2010b;Gyurkovska et al., 2011;Stancheva et al., 2011). ...
... Verbascoside was also detected in cell suspension cultures of H. procumbens. Its quantity varied from 3.5 mg g −1 DW to 28.4 mg g −1 DW, depending on the culture conditions (Georgiev et al., 2010bGyurkovska et al., 2011;Stancheva et al., 2011). No published information on the presence of isoverbascoside in unorganized cultures of H. procumbens was found in a review of extant literature. ...
Article
Three cotyledon-derived callus lines of Harpagophytum procumbens were established on agar-solidified Schenk and Hildebrandt (SH) medium supplemented with 0.2mgL-1 α-naphthaleneacetic acid (NAA) and 1mgL-1 6-benzylaminopurine (BAP) (CNB line), 0.5mgL-1 picloram (CP0.5 line) or 2mgL-1 picloram (CP2 line). They were maintained in three different culture vessels: culture tubes, Erlenmeyer flasks and Magenta vessels. Hormonal treatment and type of culture vessel influenced callus growth and morphology. The highest biomass (64- to 130-fold increase in fresh and dry weights within 4weeks) was achieved in Erlenmeyer flasks. The contents of major phenylethanoid and iridoid glycosides in the calli were determined by high performance liquid chromatography (HPLC). Harpagoside, harpagide, verbascoside and isoverbascoside were identified and the ability to produce these bioactive compounds sustained for over 3years. H. procumbens calli were also analyzed by colorimetric methods for total contents of phenolics, flavonoids and anthocyanins. The extracts of CNB callus had the highest antiradical activity against DPPH and ABTS and capacity to reduce metal ions (Ferric Reducing Antioxidant Power-FRAP). The same extracts were also characterized by the highest total content of phenolics and flavonoids.
... Phenylethanoid glycosides are secondary plant metabolites which contain hydroxyphenylethyl moiety linked to a ␤-glucopyranose (apiose, galactose, rhamnose or xylose) via a glycosidic bond. These substances have a wide range of biological activities (Gyurkovska et al., 2011). Verbascoside is the most common phenylethanoid glycoside in Verbascum genus with a wide spectrum of biological activities (Alipieva et al., 2014a) including strong antioxidant activity (D'Imperio et al., 2014), anti-inflammatory (Diaz et al., 2004), cytotoxic activity against a murine P-388 lymphocytic leukemia cell line (Pettit et al., 1990), and cholinesterase inhibitory activity (Georgiev et al., 2011b). ...
Article
The aim of this study was to determine the content of major secondary metabolites, namely, verbascoside, harpagoside, phenolic acids and flavonoids in Verbascum nigrum, Verbascum phlomoides and Verbascum thapsus methanol and water extracts by HPLC analysis and their antioxidant capacity. Also, the in vitro digestion simulation studies were performed on these extracts. Stability of individual compounds present in the extracts to digestive conditions was assessed using a simulated gastric and small intestinal model. Based on the obtained results, V. nigrum was marked as a plant with different secondary metabolites content, the highest total phenolics and phenolic acids amounts. Also, V. nigrum methanol extract showed the strongest antioxidant activity in different in vitro antioxidant methods. The main secondary metabolite in all species was verbascoside and its concentration was the highest in V. nigrum extract (118.60 mg/g of dry extract). Verbascoside exhibited strong antioxidant activity and was identified as the major contributor to the antioxidant activity of Verbascum species. After simulated in vitro digestion, verbascoside contents and antioxidant activities of the extracts were significantly decreased, whereas phenolic acids were quite stable during simulated digestion. This work provides valuable information about Verbascum plants and their pharmacologically important secondary metabolites suggesting that V. nigrum could serve as attractive source of antioxidants for application in food and pharmaceutical industry in forthcoming research.
... More recent studies have confirmed and extended these findings. One study used H. procumbens root cultures grown under controlled sterile conditions to standardise the plant material examined and minimise the influence of external factors (Gyurkovska et al. 2011). Methanolic extracts of the plant material were prepared and tested on murine macrophages for their effects on COX-1 and COX-2 expression, as well as on NO, TNF-α, and IL-6 release. ...
Article
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Drug discovery and development is heavily biased towards the development of monotherapies. Screening, testing, and evaluation of mono-entity drugs are generally much simpler than drug combinations, and are generally easier to get approval from the regulatory authorities for their clinical use. However, monotherapy drugs may not have optimal activity, may have associated toxicities, or may lose activity over time as their target develops resistance. Drug combinations, often developed from existing monotherapies, may have improved efficacy and/or be less toxic. Furthermore, the existing drugs which have lost efficacy due to the development of resistance can often be re-activated by combining them with other chemical entities. Thus, whilst the current climate for drug approval, registration, and clinical use drives the majority of drug development research towards the development of monotherapies, combinations are often a substantial improvement on the original drug. This commentary examines monotherapy and combinational therapy models and discusses the benefits and limitations of each model.
... Acute inflammation is a response in injured tissue that is characterized by increased blood flow, increased temperature, redness, swelling, and pain [1,2]. Inflammatory responses are mediated by a variety of cytokines. ...
Article
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Undaria pinnatifida is a well-known traditional Korean food with a variety of biological activities. Carrageenan (carr) is commonly used to induce paw edema in animal models. This study was designed to elucidate the processes underlying the anti-inflammatory effect of fucoxanthin isolated from the sporophyll of U. pinnatifida in carr-induced paw edema in ICR mice. Fucoxanthin significantly decreased carr-induced increased nitric oxide levels in the plasma of mice with carr-induced paw edema. Fucoxanthin protected catalase (CAT) and superoxide dismutase (SOD) activity against disruption in mice with carr-induced paw edema. In addition, fucoxanthin repressed carr-induced activation of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa B, as well as carr-induced phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and protein kinase B/Akt. These results suggest that fucoxanthin may have therapeutic potential as a treatment for patients with inflammatory diseases.
... Many bioactivities, including antioxidant, anti-inflammatory, immunomodulating, and antimicrobial, were assigned to the iridoids [32,[37][38][39]. Recently, it was shown that lamalbid, at a concentration of 125 µg·mL −1 (corresponding to 296 µM), inhibited ROS generation by 57%, but did not affect iNOS and NF-kB activity [40]. ...
Article
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The traditional role of Lamium album L. (white dead nettle, Lamiaceae) in providing relief from pain in rheumatism as well as vaginal and cervical inflammation was described. The aim of the study was to screen for the anti-inflammatory bioactivity of compounds isolated from aqueous-methanolic extract of Lamium album herb in human neutrophils (PMNs). The effect of the compounds on the inhibition of selected inflammatory markers released by neutrophils, such as cytokines (IL-8, TNF-α), was studied. The molecular masses and the purity of compounds were determined using high-performance liquid chromatography coupled with diode array detection and mass spectrometry (HPLC-DAD-MSn). The level of cytokines production after incubation with the compounds (1–25 µM) was measured by ELISA. Two derivatives of quercetin, not previously described, were isolated in this study. Phenylpropanoids (verbascoside and phlinoside D), as well as iridoids (lamalbid, and shanzhiside methyl ester), and flavonoids revealed to be more significant inhibitors of IL-8 secretion than TNF-α. The compounds at a concentration of 25 µM, except for shanzhiside methyl ester (6), inhibited secretion of IL-8 in the range from 29.1 to 50.0%. In conclusion, L. album might be a valuable source of bioactive compounds and may provide constituents to limit noninfectious inflammation associated with the aforementioned diseases.
... Verbascoside, also known as acteoside, is an ester structurally formed by phenylpropanoid caffeic acid, phenylethanoid hydroxytyrosol and sugar alpha-L-rhamnopyranosyl-(1-> 3)-β-D-glucopyranose. Belonging to caffeoyl phenylethanoid glycoside group, it is found in numerous plant families, including Plantaginaceae, and therefore is one of the most studied compounds in Plantago (Li et al., 2014;Zhang et al., 2015;Wen et al., 2016). Pharmacologically, verbascoside has antigenotoxic, gastric antiulcer, anti-inflammatory and healing activities (Fleer and Verspohl, 2007;Korkina et al., 2007;Fabiani et al., 2008;Speranza et al., 2010;Gyurkovska et al., 2011;Ambrosone et al., 2014;Sperotto et al., 2018). ...
... The production of the anti-inflammatory phenylethanoid verbascoside (Figure 22.3) from hairy root cultures of Devil's claw (Harpagophytum procumbens; Pedaliaceae) has been reported (Gyurkovska et al., 2011;Georgiev et al., 2012). Hairy root culture of Ophiorrhiza alata (Rubiaceae) produced twice as much camptothecin (Figure 22.3) than soil-grown Ophiorrhiza alata plants (Ya-ut et al., 2011). ...
... Iso-verbascoside (2) possesses antioxidant, anti-inflammatory and antiviral properties (Kernan et al. 1998;Cardinali et al. 2012;Gao et al. 2017). Leucosceptoside A (3) shows anti-inflammatory, radical scavenging and anticancer activities (Wang et al. 1996;Zhou et al. 1998;Gyurkovska et al. 2011). Martynoside (4) is a good antioxidant, antiproliferative, cytotoxic, antimetastastic, antiestrogenic and immunomodulatory compound (Saracoglu et al. 1995;Li et al. 1997;Akbay et al. 2002;Ohno et al. 2002;Miao et al. 2003;Papoutsi et al. 2006). ...
Article
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In this work the HPLC and NMR analysis of the phenyl-ethanoid glycosides (PhGs) pattern of a cultivated exemplar of Verbascum thapsus L. (Scrophulariaceae) from the Etnean area (Sicily, Italy) was performed in order to verify their possible presence. Wild V. thapsus is well-known in ethnopharmacology due to the several beneficial effects that it is able to exert and which are primarily due to these compounds. So, it’s extremely important that also cultivated exemplars of this species biosynthesize them in order to maintain their pharmacological properties. This study revealed the presence of seven PhGs in an unusual novel pattern. Thus, this exemplar is a very good potential source of this class of natural products and may be employed for several beneficial ethnopharmacological purposes.
... Used topically, capsaicin has been well researched for the treatment of neuropathic pain in a variety of conditions, including postherpetic neuralgia, neuropathy in connection mechanism, 85 inhibition of COX-1 and COX-2 expression, and inhibition of TNF-α and NO 86 as well as a protective effect for cartilage that is particularly related to its use in OA. [87][88][89] This protective effect is supported by in vitro testing of isolated fractions of devil's claw, showing inhibition of COX-1, COX-2, NO, NF-κB, TNF-α, and leukotriene. 84,86,88,90,91 Overall, the in vitro data suggest a range of potential mechanisms to reduce inflammation and protect cartilage from destruction, although clinical effectiveness is mixed. More robust research into this herb is needed. ...
Setting: The study took place in the School of Health and Human Sciences at Southern Cross University (Lismore, New South Wales, Australia). Interventions • A growing body of evidence supports the use of a variety of complementary therapies to treat chronic pain, including curcumin, capsaicin, vitamin D, omega-3 fatty acids, lipoic acid, acupuncture, yoga, meditation, and mindfulness meditation. These therapies vary with respect to the mechanisms by which they act and the potential areas of effect along the pain pathway. Results • The literature review showed a number of complementary therapies may be efficacious in reducing chronic pain and/or the need for analgesics, which may offer a reduced adverse effect profile. These therapies include curcumin, capsaicin, vitamin D, omega-3 fatty acids, lipoic acid, acupuncture, yoga, meditation, and mindfulness meditation. Response rates to treatment are likely to vary between people and within therapies. Conclusions • The available evidence suggests that efficacious complementary therapies exist that target all 3 orders of neurons and, therefore, the authors recommend multimodal individualized treatment for each patient. There is high interindividual variability between patients in responses to treatments.
... As such, pharmaceutical companies have shown interest in isolating and standardizing the constituents of this plant for the development of novel therapeutics. The plant and its main iridoid, harpagoside (HA), exhibit antiinflammatory effects via the reduction of nitric oxide levels (Gyurkovska et al., 2011;Kojima et al., 2011). The iridoids are a group of monoterpenes that are present in high concentrations in a variety of plants used in folk medicine. ...
Article
Harpagophytum procumbens (Hp) has been used as antiinflammatory and analgesic agent for the treatment of rheumatic diseases. The principal active component of Hp is harpagoside (HA). We tested the toxicity of this new therapeutic agent in a hepatic cell line (HepG2/C3A). Hp was found to be cytotoxic, and HA was found to decrease the number of cells in S phase, increase the number of cells in G2/M phase and induce apoptosis. Neither Hp nor HA was genotoxic. The expression of CDK6 and CTP3A4 was reduced by Hp, and both HA and Hp caused a significant reduction of CYP1A2 and CYP3A4 expression. It is possible that the cytotoxicity caused by HA and Hp does not involve transcriptional regulation of the cyclins and CDKs tested but is instead related to the inhibition of metabolism. This is evidenced by the results of an MTT assay and changes in the expression of genes related to drug metabolism, leading to cell death. Indeed, the cells exhibited decreased proliferation upon exposure to Hp and HA. The data show that treatment with either Hp or HA can be cytotoxic, and this should be taken into consideration when balancing the risks and benefits of treatments for rheumatic diseases. Copyright © 2016 John Wiley & Sons, Ltd.
... The common phytoconstituents which have shown antiinflammatory activity are alkaloids [203], resins [204], essential oils [205], polysaccharides [206], flavonoids [207][208][209], phenolic compounds [210,211], cannabinoids [212,213], steroids [214], fatty acids [215], plant glycoproteins [216] and lignans [217,218]. However, there are many phytoconstituents which are believed to be having antiinflammatory activity like Azadiradione [64], phenolic compounds [62], flavonoids, polyphenols [53], curcumin [219][220][221], rosmarinic acid [223,224], gamma linoleic acid (GLA) [8,224,225], GLA, linear aliphatic alcohols (e.g., tetracosanol), and phenolic compound (ferulic acid), sterols such assitosterol and campesterol [226][227][228][229][230][231], harpagoside [232][233][234], galactolipid [235,236], carnosol and carnosic acid are phenolic diterpenes [237], anthocyanins [238], n-6 polyunsaturated fatty acid (PUFA), -linoleic acid, and -linoleic acid [239]. Cannabinoids are present in family Cannabis sativa (Cannabinaceae). ...
Article
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BACKGROUND: Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life-threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases. OBJECTIVE: To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patiens regardless of their background on equality basis. RESULTS: Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogen-activated protein, nuclear factor, etc. Considering all the above-mentioned factors, further research from molecular to cellular level will enable a better understanding of the mechanisms. Common anti-inflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppressant used for controlling and suppressing inflammatory crisis. A proper phytochemical, pharmacological and physiological evaluation will enable their safe and effective use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal preparations have been patented with some under consideration. CONCLUSION: Natural herbs are safe, effective and better options as anti-inflammatory agents than synthetic ones. The phytoconstituents are as effective with the comparable mechanism of action as synthetic molecules. Future research should focus on molecular mechanisms of different beneficial applications of these herbal plants in various diseases. Recent patents on anti-inflammatory drugs and herbal plants have been covered which provide insight into the current status and future prospects in this field.
... As reported by Park et al. (19) and Anauate et al. (20), some iridoids, including those present in the tested extracts of R. glutinosa, showed inhibition of cyclooxygenase-1/2 activity in human erythroleukemia cells (aucubin) a murine macrophage cell line (loganin) and a whole-blood assay (harpagoside). Of the phenylethanoids, verbascoside, also detected in the extracts of R. glutinosa (5), demonstrates anti-inflammatory activity in several models, including inhibition of cyclooxygenase-2 activity (20)(21)(22)(23). Based on these observations, the effect of the plant extracts on cyclooxygenase activity will be the subject of future studies. ...
Article
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The antioxidant activity of methanolic extracts derived from shoots (HR-shoots) and roots (HR-roots) of pRi-transformed Rehmannia glutinosa plants were determined. The activity was indicated by the ability of the plant extracts to inhibit superoxide anion (O2(-·)) generation and thiobarbituric acid reactive substances (TBARS) production in resting blood platelets and platelets activated by thrombin. The strongest activity was exhibited by the HR-shoot extract (50 μg/mL). The present study also examines the antioxidant properties of the plant extracts against human plasma lipid peroxidation induced by strong biological oxidants: hydrogen peroxide (H2O2) and H2O2/Fe. The study shows that extracts from transformed R. glutinosa plants may be a promising source of natural antioxidants, which would be valuable in various cardiovascular diseases. The extracts may also protect lipids against oxidative modifications.
... The main chemical compounds found in this species are: iridoids glycosides such as aucubin, the phenylethanoid glycosides (PhGs) verbascoside and isoverbascoside and flavonoids such as quercetin-type glycosides and apigenin (Gómez, 2011). PhGs are watersoluble natural occurring compounds, absorbable by human intestinal cells and with a wide spectrum of biological activities including anti-fungal (Funari et al., 2012), anti-inflammatory (Gyurkovska et al., 2011), antiradical (López-Laredo et al., 2012, cytotoxic (Pettit et al., 1990), and gastroprotective (Singh et al., 2010) among others. ...
Article
Phenylethanoid glycosides (PhGs) are promising natural products for the treatment of chronic diseases because of their wide range of biological activities. Biotic stress as pathogen attack (fungi) may stimulate the synthesis of PhGs through activation of phenylalanine ammonia-lyase (PAL). Castilleja tenuiflora Benth. (Orobanchaceae) in vitro cultures are alternative sources of PhGs, however in that conditions, cultures have a diminished synthesis of these compounds. To increase the yields of PhGs, the identification of factors affecting their biosynthesis is required. Here, weshow that elicitation with cell wall oligosaccharides (CWOs) from Fusarium oxysporum f. sp. lycopersici race 3 (Hyphomycetes) stimulates biosynthesis of PhGs by increasing the activity of PAL. Upon elicitation with CWOs (13 μg/mL) the production of PhGs was enhanced by 5-fold compared with untreated control. The maximum PAL activity in shoots cultured under CWOs elicitation were also increased. Elicitation did not affect the shoot growth (length and biomass) but induced chlorosis, and delayed root formation of C. tenuiflora shoots. Our results demonstrate that elicitation with CWOs increases PhGs biosynthesis in C. tenuiflora shoot culture.
... Among its abundant metabolites, Harpagoside has been substantiated as an anti-inflammatory component [39]. Root's extract of Devil's claw has been claimed to possess inhibition potential of NO, inflammatory cytokines (IL-6, IL-1 , and TNF-), and PGE 2 , as well as prevention of arachidonic acid metabolism and eicosanoid biosynthesis, leading to COX-2 inhibition and reducing inflammation [40][41][42]. In another preclinical study, devil's claw has shown no efficacy in improving carrageenaninduced edema in the hind foot of the rat [43]. ...
Article
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Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis , evening primrose, and Devil’s claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle.
... These polyphenols, including ethyl gallate, pentagalloylglucose and galloyl paeoniflorin, have been shown to significantly protect against ALI induced by LPS in vitro and in vivo [37][38][39]. Harpagoside also has anti-inflammatory activity [40]. ...
Article
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Qingwen Baidu Decoction (QBD) is an extraordinarily "cold" formula. It was traditionally used to cure epidemic hemorrhagic fever, intestinal typhoid fever, influenza, sepsis and so on. The purpose of this study was to discover relationships between the change of the constituents in different extracts of QBD and the pharmacological effect in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). The study aimed to discover the changes in constituents of different QBD extracts and the pharmacological effects on acute lung injury (ALI) induced by LPS. The results demonstrated that high dose and middle dose of QBD had significantly potent anti-inflammatory effects and reduced pulmonary edema caused by ALI in rats (p < 0.05). To explore the underlying constituents of QBD, we assessed its influence of six different QBD extracts on ALI and analyzed the different constituents in the corresponding HPLC chromatograms by a Principal Component Analysis (PCA) method. The results showed that the pharmacological effect of QBD was related to the polarity of its extracts, and the medium polarity extracts E2 and E5 in particular displayed much better protective effects against ALI than other groups. Moreover, HPLC-DAD-ESI-MS n and PCA analysis showed that verbascoside and angoroside C played a key role in reducing pulmonary edema. In addition, the current study revealed that ethyl gallate, pentagalloylglucose, galloyl paeoniflorin, mudanpioside C and harpagoside can treat ALI mainly by reducing the total cells and infiltration of activated polymorphonuclear leukocytes (PMNs).
... The anti-inflammatory activity of harpagoside has been mainly evaluated in in vivo models of carrageenan-induced edema models, in which intraperitoneal treatment with 10À20 mg/kg body weight (mice or rats) doses significantly abolished paw swelling [21]. Pure harpagoside was also reported to inhibit cyclooxygenases (COX-1/2) expression and nitric oxide (NO) production by peritoneal macrophages [34]. Moreover, harpagoside inhibited the release of the RANTES (Regulated on Activation, Normal T cell Expressed and Secreted), an inflammatory mediator, by stimulated human bronchial epithelial cells, highlighting its potential for treatment of respiratory conditions. ...
Chapter
Terpenoids, also known as isoprenoids, are the most numerous and structurally diverse natural products found in many plants. Several studies, in vitro, preclinical, and clinical have confirmed that this class of compounds displays a wide array of very important pharmacological properties. The diverse collection of terpenoid structures and functions have provoked increased interest in their commercial use resulting in some with established medical applications being registered as drugs on the market. This chapter herewith outlines the classification of terpenoids providing brief descriptions of each group, outlines the methods of extraction and their chemical identification, and discusses their range of pharmacological activities and pharmaceutical applications.
... The hairy roots cultures of different plants were reported to enhance the production of diverse metabolites (Srivastava and Srivastava 2007;Goel et al. 2011;Mehrotra et al. 2013;Gabr et al. 2016a;Alok et al. 2016). Furthermore, hairy roots cultures are advised as a promising source of biological active compounds that are not detectable even in parental plants (Berkov et al. 2003;Weathers et al. 2005;Gyurkovska et al. 2011;Pollier et al. 2011). ...
Article
Transformed hairy root culture in common buckwheat (Fagopyrum esculentum Moench Rubra cultivar) was investigated for accumulation of amino acids and specific flavonoids. Leaves and stems of F. esculentum were used a starting material for induction of hairy roots via the Agrobacterium rhizogenes A4 strain. The transformed lines were confirmed by PCR detection of rol B gene, and their capability to continuously form hairy roots. Three lines from each explant types depending upon growth kinetics were observed. The hairy root lines were used to measure the contents of 17 amino acids and 3 flavonoids. Overall, the hairy root lines exhibited elevated accumulation of semi-essential amino acids such as lysine, isoleucine, valine, histidine and phenylalanine. Content of proline was increased 3-5 times, likely due to the biotic stress reaction induced with A. rhizogenes. Determination of flavonoids by high-performance liquid chromatography, hesperidine and kaempferol-3-rutinoside, were accumulated in hairy root cultures and didn't detected in non-transformed root. The increase in flavonoids positively correlated with the antiox-idant capacity of the hairy root cultures.
... Verbascoside (known as acteoside, kusaginin or orobanchin) exhibits a wide spectrum of biological activities, including antileukemic and cytotoxic activity against a murine cell line (Pettit et al. 1990). It demonstrates anti-inflammatory activity through inhibition of cyclooxygenase-2 (COX-2) expression and inhibition of complement activity in human serum (Gyurkovska et al. 2011), and also possesses diuretic (Herbert et al. 1991) and antibacterial properties (Pennacchio 2005). In turn, isoverbascoside has been found to demonstrate antibacterial and anti-inflammatory activities (Shikanga et al. 2010). ...
Article
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This study is the first description of a procedure for shoot organogenesis from calli derived from various seedling explants. The frequency of shoot induction and number of shoots per explant were measured on Murashige and Skoog (MS) medium with 0.2-3.0 mg L−1 6-benzylaminopurine (BAP) alone or combined with auxin [0.1 mg L−1 indole-3-acetic acid (IAA) or 1-naphthalenacetic acid]. The highest organogenic response where 90 % of explants formed a regenerative callus with a mean number of nine shoots was achieved after 6 weeks of culture when hypocotyl explants and 1.0 mg L−1 BAP was used together with 0.1 mg L−1 IAA. The shoots regenerated from hypocotyl-derived calli were rooted for 6 weeks on MS medium lacking growth regulators or containing auxin (IAA or indole-3-butyric acid). The plantlets were successfully acclimatized in a greenhouse. Micropropagated plants subjected to random amplified polymorphic DNA and inter simple sequence repeat (ISSR) marker based profiling revealed a uniform banding pattern identical with that of donor plants. The iridoid and phenylethanoid glycoside content of the organogenic callus culture and in vitro-raised plants was determined using UHPLC. In the tested samples catalpol, aucubin, harpagid, harpagoside, verbascoside, isoverbascoside and traces of loganin and catalposide were identified. The leaves produced the highest levels of catalpol (43-45 mg g−1 DW). Organogenic callus and 6-week-old in vitro grown plantlets were characterized by the highest accumulation of aucubin, verbascoside and isoverbascoside. The work also demonstrated the regenerative ability of hypocotyl-derived calli and production of bioactive metabolites to be stable for 4 years of culture.
... [42] Its compounds, alone or in combination, also have proven antioxidant, anticancer, and anti-inflammatory activity, as well as an antinociceptive and hepatoprotective effect. [43][44][45][46] ...
Article
Eugenia pyriformis Cambess, commonly known as uvaia, is a native Brazilian plant. Among its benefits are the high concentration of vitamin C, carotenoids and sources of phytochemicals such as phenolic compounds. Many of these phytochemicals have been linked to the prevention and management of several chronic and degenerative diseases including cancer, cardiovascular diseases, type 2 diabetes mellitus, obesity, among other disorders. The uvaia compounds started to be isolated and characterized to provide a better understanding of the chemical mechanisms related to the biological activities of their extracts. As the identification of compounds progresses, studies investigating the potential of extract are receiving more attention. Some biological activities identified in the different uvaia compounds are antioxidants, antimicrobials, and anti-inflammatories. Previous research has pointed out that the uvaia fruit extract can be used as a potent anti-inflammatory for inhibited carrageenan-induced paw edema in rats. In this context, this review summarizes the nutritional composition of uvaia and describes the main biological activities reported for this plant, revealing some of its beneficial effects on health and highlighting how much remains to be elucidated.
... Compound 6 was found in several terrestrial and epiphytic species from families such as Bignoniaceae (Martin et al., 2009), Lamiaceae (Nguyen et al., 2018), Magnoliaceae (Wang et al., 2011), Orobanchaceae (Chu et al., 2011), Pedaliaceae (Gyurkovska et al., 2011) Compound 7 has so far only been found in Clerodendron brachyanthum Schauer (Lin and Kuo, 1992). ...
Article
Clerodendrum infortunatum L. (syn.: Clerodendrum viscosum Vent.), a member of the Lamiaceae, yielded one undescribed jasmonic acid derivative, ten acteosides, and two flavonoids. The jasmonic acid derivative was identified as 6'-O-caffeoyl-12-glucopyranosyloxyjasmonic acid. The acteosides were identified as isoacteoside, acteoside, 2''-O-acetyl-martyonside, 3''-O-acetyl-martyonside, martynoside, brachynoside, leucosceptoside A, jionoside C, jionoside D, incanoside C. The flavonoids were identified as apigenin 7-O-glucuronide and acacetin 7-O-glucuronide. The structures of the isolated components have been identified by UHPLC-HRMS, 1D and 2D NMR spectroscopic analyses, spectrometric techniques, and in comparison with published NMR data. The absolute sugar configuration was determined by GLC-MS/MS analysis of the octylated derivative of the sugar moiety after hydrolysis. Among the known compounds, ten are reported for the first time from this species, while the acteoside leucosceptoside A and the two flavonoids have been isolated for the first time from the genus Clerodendrum. The chemophenetic significance of the compounds obtained from C. infortunatum is summarized in comparison to those found in other Clerodendrum species.
... Inflammation is a complex pathological process of immune defense made by organisms to counteract noxious stimulation, such as bacterial pathogens, viruses and chemicals (Medzhitov, 2010). Inflammation is usually manifested by redness, swelling, heat, pain and dysfunction, in which many kinds of cells (macrophages and dendritic cells) and active ingredients (cytokines, chemokines and bioactive amines) participate (Gyurkovska et al., 2011). Excessive and prolonged inflammation can be a challenge to the normal function of the body and is closely related to the pathogenesis of various diseases, such as ulcerative colitis, cancer and diabetes (Li, Cai, Qin, & Wu, 2008;Reuter, Gupta, Chaturvedi, & Aggarwal, 2010). ...
Article
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Grape seed proanthocyanidin (GSP), a major polyphenol in grape seed, has several remarkable physiological activities beneficial to human health. However, the hydrophilicity of GSP hampers its cellular absorption and thus limits the bio-efficiency in vivo. In order to enhance the lipophilicity of GSP for improved bio-efficiency, lipophilic grape seed proanthocyanidin (LGSP) was synthesized by enzymatic esterification of GSP. The anti-inflammatory activity of LGSP was evaluated in lipopolysaccharides-stimulated RAW 264.7 cells in vitro and a zebrafish tail-amputated model in vivo. LGSP exhibited strong inhibitory effects on the production of NO and pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in RAW 264.7 cells. Further mechanistic studies showed that LGSP achieved the aforementioned effects by inhibiting the activation of MAPKs and NF-κB signaling pathways. In the zebrafish model, LGSP effectively suppressed the aggregation of neutrophils. Our findings suggest that LGSP may be effective as a complementary agent for the prevention/treatment of inflammation-mediated diseases.
... Inflammation is part of the host defense mechanism against infectious agents and injury and it is also involved in the pathophysiology of many diseases when left unresolved. Acute inflammation is a short-term process which is characterized by typical signs of inflammation, such as swelling, redness, heat, pain and loss of function due to the infiltration of the tissues by leukocytes and plasma [34,35]. ...
Article
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This study aimed to evaluate the anti-inflammatory activities of eight different types of Yemeni honey using an acute inflammation rat model. Ten groups were employed in this study (n = 8 rats for each group), Rats paw edema was induced by sub plantar injection of 1% carrageenan into the right hind paw. Rats were pre-treated with different types of Yemeni honey (Osaimi sider, Athel, Al-Akhawain, Salam, Somar, Majra, Acacia and Algasas) at a dose (5mg/kg b.w) and NSAID as Indomethacin (10 mg/kg, p.o.) for 7 days. The diameter of the hind paw was measured for assessment of the edema size at 1, 2, 4, 6 and 24 hours. The different types of Yemeni honey significant anti-inflammatory efficacies against carrageenan-induced paw edema in rats. Besides, the different types of Yemeni honey, elevate numbers of RBCs, Hb and PCV with a reduction in WBCs numbers. Marked reduction in percentages of neutrophil, lymphocyte and basophils. Moreover, they succeeded to reduce the elevated serum AST level. Algasas honey and osaimi sider honey possesses a better anti-inflammatory activity which was almost similar to the effect of the Indomethacin, followed Dam Al-Akhawain honey (Acacia honey). Where Athel, Salam and Somar honey, their anti-inflammatory activity differed according to the source and the level of honey. Therefore, these discrepancies could be attributed to the differences of botanical sources of honey and also to the presence of different compounds of anti-inflammatory that have different anti-inflammation effects. Conclusion: The different types of Yemeni honey (Osaimi sider, Athel, Dam Al-Akhawain, Salam, Somar, Majra, Acacia and Algasas) possess anti-inflammatory activity. Also, they were safe at the doses used.
... Verbascoside production using in vitro cultures were reported in several plants including Harpagophytum procumbens Georgiev et al. 2011a;Grąbkowska et al. 2010;Grąbkowska et al. 2016;Grąbkowska et al. 2014;Gyurkovska et al. 2011;Homova et al. 2010), Scutellaria lateriflora (Grzegorczyk-Karolak et al. 2015;Kawka et al. 2017;Marsh et al. 2014 (Piątczak et al. 2015a(Piątczak et al. , 2016, Rehmannia elata (Piątczak et al. 2015b), Verbascum xanthophoeniceum (Georgiev et al. 2011b) Verbena officinalis (Kubica et al. 2017), Verbascum Thapsus (Temporiti et al. 2020), and Catalpa ovata (Wysokińska et al. 2001). Moreover, addition of chemical elicitors such as methyl jasmonate (Marsh et al. 2014;Piątczak et al. 2016), cyclodextrin (Marsh et al. 2014), and salicylic acid (Piątczak et al. 2016) or alteration the light sources (Kawka et al. 2017;Kubica et al. 2017;Marsh et al. 2014) could enhance verbascoside production in the in vitro culture. ...
Article
Verbascoside is an antioxidant compound that can be used in cosmeceutical and pharmaceutical products. It is found in various plants of order Lamiales. Clerodendrum indicum and Acanthus ebracteatus are Thai medicinal plants that accumulate verbascoside. There is no report on practical use of these two plants as the source of verbascoside production to date. Here we reported the sustainable and efficient verbascoside production from in vitro cultures of both plants by culturing under white, blue, and red LEDs. Furthermore, the optimum exposure time and concentration of methyl jasmonate were evaluated. Culturing both plants under blue LEDs for 6 weeks significantly enhanced verbascosides in C. indicum for 1.6-fold and A. ebracteatus for 1.8-fold. Elicitation with methyl jasmonate enhanced the production to 31.41 ± 3.10 mg/g DW (4.2-fold) in C. indicum and 51.44 ± 0.10 mg/g DW in A. ebracteatus (3.2-fold). The appropriate conditions for elicitation were 100 µM methyl jasmonate and 8 days exposure time. In addition, this is the first report of in vitro verbascoside production from these two plants. In vitro culture accumulated verbacoside up to 44.8-fold higher than intact plants. Thus, they can be the efficient and sustainable alternatives for production of verbascoside.
... For the phenolics of OMWW and their putative chemo-preventive activities, studies on HT and oleuropein showed anti-proliferative activity on MCF-7 human breast cancer cells [44]. VB showed anti-inflammatory activity on isolated murine macrophages [45] and the ability to reduce in vivo the effects of colitis induced in rats [46], including the inhibition of the enzymatic activity of matrix metalloproteinases (MMPs), which are also involved in skin aging. Tyrosol was able to restore the basal level of the anoxia-induced expression of the MMP-9 and MMP-2 and to reduce the expression of TNFα in EAhy926 human endothelial cells exposed to anoxic stress [47]. ...
Article
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A wide variety of polyphenols are reported to have considerable antioxidant and skin photoprotective effects, although the mechanisms of action are not fully known. Environmentally friendly and inexpensive sources of natural bioactive compounds, such as olive mill wastewater (OMWW), the by-product of olive-oil processing, can be considered an economic source of bioactive polyphenols, with a range of biological activities, useful as chemotherapeutic or cosmeceutical agents. Green strategies, such as the process based on membrane technologies, allow to recover active polyphenols from this complex matrix. This study aims to evaluate the antioxidant, pro-oxidant, and photoprotective effects, including the underlying action mechanism(s), of the ultra-filtered (UF) OMWW fractions, in order to substantiate their use as natural cosmeceutical ingredient. Six chemically characterized UF-OMWW fractions, from Italian and Greek olive cultivar processing, were investigated for their antioxidant activities, measured by Trolox Equivalent Antioxidant Capacity (TEAC), LDL oxidation inhibition, and ROS-quenching ability in UVA-irradiated HEKa (Human Epidermal Keratinocytes adult) cultures. The photoprotective properties of UF-OMWW were assayed as a pro-oxidant-mediated pro-apoptotic effect on the UVA-damaged HEKa cells, which can be potentially involved in the carcinogenesis process. All the UF-OMWW fractions exerted an effective antioxidant activity in vitro and in cells when administered together with UV-radiation on HEKa. A pro-oxidative and pro-apoptotic effect on the UVA-damaged HEKa cells were observed, suggesting some protective actions of polyphenol fraction on keratinocyte cell cultures.
... Compounds in oil of Rheumax® were isolated from devil's claw, inhibit COX-1/2 activity in whole human blood (7,32). The anti-inflammation effect of coumaroylquinic acid, a chlorogenic acid, was demonstrated by the reduced expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) (33). ...
Article
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The aim of the study was to challenge the common techniques utilized in the quality control of herbal products for the authentication of the two selected polyherbal products. Two polyherbal formulations, Voltarit® and Rheumax® commonly trade in the market to treat arthritis and related disorders, had been investigated regarding their quality control through selecting representative marker components from each drug. Different chromatographic procedures had been applied of which, a new validated HPLC method was developed for the simultaneous quantification of three active components (curcumin, demethoxycurcumin, bisdemethoxycurcumin, quercetin, and myristicin). Additionally, GC-FID was used for the relative quantification of fatty acids known for their anti-inflammatory activity in the hexane extract of the selected products. LC-MS-MS and GC-MS techniques were applied to tentatively identify some naturally occurring COX-2 inhibitors in methanol extract and fatty acid of the selected products, respectively. One of the products was adulterated by curcumin and surprisingly had no limonene or myristicin even it had celery seed as the pharmaceutical company said. The validation showed good linearity (R is between 0.9990 and 0.9998), sensitivity (LODs 0.1-0.4 μg), precision (RSD < 2%), and accuracy (99.82-101.4%) of the method. The developed HPLC method was proved to be a useful tool in the quality control of complex matrices of the selected polyherbal formulations. Many active components with anti-inflammatory effects were identified in the fixed oils, methanol, and hexane extracts of the HMs, so patients could take these herbal products with confidence about good quality and no chemical adulteration.
... Although clinical trials have demonstrated the efficacy of H. procumbens for musculoskeletal pain relief [19][20][21][22], animal and in vitro studies have produced conflicting results [23][24][25][26][27]. The suspected active compounds-harpagoside, harpagide, 8-p-coumaroyl-harpagide, and acteoside-inhibit cyclooxygenase (COX) 1 and 2 [28][29][30] and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-Iβ (IL-Iβ), and interleukin-6 (IL-6) [31,32]. Harpagoside is the main anti-inflammatory agent, but it is less effective in isolation [31] and thus the constituents of H. procumbens are thought to have synergistic effects [33]. ...
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... The oxidation rate of NADH is determined whereas SGPT was forming the pyruvate during the reaction is further concerted to the lactate by the lactate dehydrogenase. [24] Estimation of antioxidant enzymes ...
... As with H. procumbens, metabolite analysis of several endemic North American Scrophularia species suggests the traditional use of these plants for pain and inflammation may be due to their iridoid and phenylethanoid/phenylpropanoid glycoside content [15]. This includes the metabolite harpagoside (found in H. procumbens, as well as both S. lanceolata and S. marilandica), which has been shown to possess anti-inflammatory and anti-nociceptive properties [2][3][4][16][17][18][19][20]. While harpagoside is thought to be primarily responsible for the bioactivity of H. procumbens, two other anti-inflammatory metabolites, verbascoside (synonyms: acteoside and kusaginin) and harpagide, have been detected in this species (reviewed in Mncwangi, et al. [11]). ...
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... Gyurkovska et al. [296] LPS-stimulated human monocytes and mouse RAW264.7 macrophages; molecular targets; H. procumbens ethanolic extract (2.9% harpagoside); dose-dependent inhibition of TNF-α, IL-6, IL-1β, PGE2, and COX-2, inhibition of activator protein (AP)-1 pathway without affecting NF-κB and mitogen-activated protein (MAP) kinase pathways. ...
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Cell suspension and Agrobacterium rhizogenes-transformed hairy root cultures of Devil’s claw (Harpagophytum procumbens), an African plant with high medicinal value, were cultivated in shake-flasks. A purification scheme to isolate their main active constituents (the phenylethanoid glycosides verbascoside, leucosceptoside A, b-OH-verbascoside and martynoside; structurally identified by NMR and LC–MS) was then developed, and their concentrations in the cultures were determined by UV spectrometry following HPLC separation. Preparations, extracts and the isolated phenylethanoid glycosides from the H. procumbens in vitro systems were tested on isolated murine macrophages to study their effects on nitric oxide (NO) and cytokine (TNF-a, IL-6) release and the expression of COX-1 and COX-2. They were also added to human serum to investigate their effects on the classical pathway of complement activation. The results indicate that the extracts and preparations of the in vitro systems, and pure verbascoside (their main active constituent), had strong anti-inflammatory properties, comparable to or even higher than that of pure harpagoside (a major anti-inflammatory constituent of intact Devil’s claw tubers). Thus, they have potential as new anti-inflammatory agents.
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A novel bioside, β-(3′,4′-dihydroxyphenyl)ethyl-O-α-L-rhamnopyranosyl(1 → 3)-D-glucopyranoside, was obtained from the secondary roots of Harpagophytum procumbens. It is accompanied by the known iridoid glucosides harpagoside, procumbide, and its 6′-O-p-coumaroyl ester, and phenolic glycosides, acteoside and isoacteoside, the latter pair being obtained from H. procumbens for the first time. The structures of these metabolites were differentiated by high resolution NMR studies, while that of the bioside is additionally supported by synthesis.
Article
Iridoids discussed in this review were chosen based on their anti-inflammatory activity and their having various different bioactivities. Harpagoside is the major iridoid glycoside (0.5-1.6%) in Harpagophytum procumbens, an herbal medicine for rheumatologic conditions. The stem bark of C. ovata is used as an anti-inflammatory drug and catalposide is the main constituent. Geniposide is a main iridoid glucoside of Gardenia jasmoides, 56.2 mg / 500 mg extract. Gardenia fruits are used for the treatment of anti-inflammatory, hepatic and gall bladder diseases. Catalpol, known for its neuroprotective activity, is the major constituent of the roots of Rehmannia glutinosa, which are traditionally used for the treatment of auditory diseases such as tinnitus. Aucubin, which is frequently found as a natural constituent of many traditional medicinal plants, is used in the alleviation of chronic allergic inflammatory disease. PicroLiv, an anti-inflammagen, is a standardized fraction from the root and rhizome of Picrorhiza kurroa containing picrosides I and II and kutkoside. Both aucubin and PicroLiv have potent hepatoprotective activity.
Article
Harpagophytum procumbens (Devil's claw) is an important medicinal plant, which tubers are used for the treatment of different inflammatory diseases. In this study, the time courses of growth of Devil's claw hairy roots and accumulation of intracellular total iridoids and phenolics were investigated during cultivation under submerged conditions. After 21 days of growth in liquid hormone-free MS medium, a growth index of 81.3 was achieved and the accumulated biomass reached 0.58 g/flask. It was found that the time courses of total iridoids and phenolics production showed almost the same patterns with a maximum on day 21 from the beginning of cultivation (15.93 mg harpagoside equivalents/L and 261 mg gallic acid equivalents/L, respectively). The methanolic extracts possessed relatively high DPPH-radical scavenging properties (IC50 4.08 mg/mL), while for the culture media no antiradical activity was detected. According to our best knowledge, the present report is the first one dealing with the investigation of transformed root cultures from Harpagophytum procumbens plants.
Article
The antiinflammatory activities of aqueous extracts prepared from the aerial parts of ten Hungarian Stachys species were investigated in vivo in the carrageenan-induced paw oedema test after intraperitoneal and oral administration to rats. Some of the extracts were found to display significant antiphlogistic effects when administered intraperitoneally and orally; in particular, the extracts of S. alpina, S. germanica, S. officinalis and S. recta demonstrated high activity following intraperitoneal administration. At the same dose of 5.0 mg/kg, these extracts exhibited similar or greater potency than that of the positive control diclofenac-Na. The main iridoids present in the investigated extracts, ajugoside, aucubin, acetylharpagide, harpagide and harpagoside, were also assayed in the same test, and high dose-dependent antiphlogistic effects were recorded for aucubin and harpagoside. These results led to the conclusion that most probably iridoids are responsible for the antiinflammatory effect of Stachys species, but other active constituents or their synergism must also be implicated in the antiinflammatory effect.
Article
The genus Verbascum L. (mulleins) comprises of about 360 species of flowering plants in the Scrophulariaceae family. Mulleins have been used in the traditional folk medicine for centuries, for treatment of a wide range of human ailments, inter alia bronchitis, tuberculosis, asthma, and different inflammations. Despite all applications the knowledge of the metabolites, accumulated in different mullein species, is still limited and based mainly on determination of the major compounds. Here we report the application of 1H NMR metabolic fingerprinting in combination with principal component analyses (PCA) in five different Verbascum species. Based on the obtained results mulleins were divided in two groups: group A (Verbascum phlomoides and Verbascum densiflorum) and group B (Verbascum xanthophoeniceum, Verbascum nigrum and Verbascum phoeniceum). Further it was found that the plants in group B accumulate higher amounts of bioactive iridoid and phenylethanoid glycosides. V. xanthophoeniceum and V. nigrum accumulate higher amounts of the pharmaceutically-important harpagoside (∼0.5% on dry weight basis) and verbascoside, forsythoside B and leucosceptoside B (in total 5.6-5.8% on dry weight basis), which underlines the possibility for their application in pharmaceutical industry. To the best of our knowledge this is the first report on the analyses of Verbascum sp. leaf metabolome.
Article
The isolation of acteoside and coniferin from Paulownia tomentosa bark along with the previously reported phenolic glucoside syringin is described. The structure of both, acteoside and coniferin, have been assigned by (1)H- and (13)C-NMR spectroscopy.
Article
Plant flavonoids show anti-inflammatory activity in vitro and in vivo. Although not fully understood, several action mechanisms are proposed to explain in vivo anti-inflammatory action. One of the important mechanisms is an inhibition of eicosanoid generating enzymes including phospholipase A2, cyclooxygenases, and lipoxygenases, thereby reducing the concentrations of prostanoids and leukotrienes. Recent studies have also shown that certain flavonoids, especially flavone derivatives, express their anti-inflammatory activity at least in part by modulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase, and several pivotal cytokines. Due to these unique action mechanisms and significant in vivo activity, flavonoids are considered to be reasonable candidates for new anti-inflammatory drugs. To clearly establish the therapeutic value in inflammatory disorders, in vivo anti-inflammatory activity, and action mechanism of varieties of flavonoids need to be further elucidated. This review summarizes the effect of flavonoids on eicosanoid and nitric oxide generating enzymes and the effect on expression of proinflammatory genes. In vivo anti-inflammatory activity is also discussed. As natural modulators of proinflammatory gene expression, certain flavonoids have a potential for new anti-inflammatory agents.
Article
An efficient protocol for the establishment of transformed root culture of Verbascum xanthophoeniceum using sonication-assisted Agrobacterium rhizogenes-mediated transformation is reported. Only 10 days after the inoculation with A. rhizogenes ATCC 15834 and 45 s ultrasound exposure, hairy roots appeared on 75% of the Verbascum leaves. Ten hairy root lines were isolated, although only half of them were free of bacterial contamination and started growing when excised from mother explants. The transgenic nature of the most vigorously growing hairy root clones (VX1 and VX6) was confirmed by polymerase chain reaction. Under submerged cultivation both hairy root clones accumulated high biomass amounts (12.8 and 14.3 g L(-1), respectively) and significant amounts of bioactive phenylethanoid glycoside verbascoside (over 6-times more than in mother plant leaves). LC-APCI-MS analyses confirmed verbascoside accumulation in hairy root clones along with three other phenylethanoid glycosides (forsythoside B, leucosceptoside B and martynoside) and an iridoid glycoside aucubin. This is the first report on the induction of hairy roots of Verbascum plants.
Article
The present study evaluates the effect of isolated fractions of Harpagophytum procumbens (devil's claw) on cyclooxygenase (COX-1 and COX-2) activities and NO production using a whole blood assay. The activity of COX-1 was quantified as platelet thromboxane B(2) production in blood clotting and COX-2 as prostaglandin E(2) production in LPS-stimulated whole blood. Total NO(2) (-)/NO(3) (-) concentration was determined by Griess reaction in LPS stimulated blood. Assays were performed by incubation of isolated fractions obtained by flash chromatography monitored with HPLC, TLC and identified by (1)HNMR, containing different amounts of harpagoside with blood from healthy donors. Indomethacin and etoricoxib were the positive controls of COX-1 and COX-2 Inhibition. Data shows that fraction containing the highest concentration of harpagoside inhibited indistinctively COX-1 and COX-2 (37.2 and 29.5% respectively) activity and greatly inhibited NO production (66%). In contrast the fraction including iridoid pool increased COX-2 and did not alter NO and COX-1 activities. The fraction containing cinnamic acid was able to reduce only NO production (67%). Our results demonstrated that the harpagoside fraction is the main responsible for the effect of devils claw on these enzyme activities. However, other components from devil's claw crude extract could antagonize or increase the synthesis of inflammatory mediators.
Article
Devil's Claw (Harpagophytum procumbens) a plant native to Southern Africa, has historically been used in traditional medicine to treat a wide range of diseases and currently is widely employed as anti-inflammatory and pain-relieving natural remedy in Europe and other parts of the world. Little is known about possible herb-drug interactions arising from effects of Devil's Claw on the major drug metabolizing enzymes or transporters. This study evaluated in vitro the effects of Devil's Claw on the multidrug transporter ABCB1/P-glycoprotein. The effects of three commercially available Devil's Claw preparations and that of pure harpagoside were studied in the human kidney (HK-2) proximal tubule cell line, constitutively expressing ABCB1/P-glycoprotein (P-gp). Pgp activity and expression were tested by the calcein-AM test and by Western blotting, respectively. Commercial preparations inhibited P-gp activity, even if to a different extent, while pure harpagoside was almost ineffective. In cells cultured for three days in the presence of Devil's Claw preparations or pure harpagoside, a dose-dependent P-gp upregulation was found. Our results demonstrate for the first time that Devil's Claw may interact with the multidrug transporter ABCB1/P-gp, the effect not appearing strictly related to the harpagoside relative content. Modulation of both P-gp activity and P-gp expression by Devil's Claw raise the possibility of herb-drug interactions, to be further explored in depth.
Article
The southwestern Indian paintbrush, Castilleja linariaefolia, yielded extracts that displayed in vivo activity against murine P-388 (PS) lymphocytic leukemia. Separation guided by PS cell line inhibition led to isolation of cytotoxic compounds that were identified as the known glycosides acteoside [1] (ED50 2.6 micrograms/ml) and isoacteoside [2] (ED50 10 micrograms/ml). The identifications were established by spectral measurements and degradation studies. Mannitol was also found in this plant.