Appraising the Phytochemical and Therapeutic Perspectives of Bryonia laciniosa: A Literature Metasynthesis.

BACKGROUND: Nature has bestowed mother Earth with an array of herbals utilized as therapeutics for various human ailments since the origin of life. Bryonia laciniosa (family: Cucurbitaceae) is one such herb, which finds its mention in various traditional systems of medicine and has attracted current researchers due to its significant therapeutic value. OBJECTIVE: The current article aims to present a literature metasynthesis on Bryonia laciniosa. METHODS: The authors performed scholarly searches for peer-reviewed findings on Bryonia laciniosa and incorporated all the data related to the phytochemical and therapeutic profile of the drug. RESULTS: This compilation comprises of Phytochemical and Pharmacological profile of Bryonia laciniosa elaborating its traditional significance and recent researches related to its biological activities. The plant exhibits its potential as an antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsant, anti-asthmatic, anticancer, antioxidant, antidiabetic, and aphrodisiac agent. It also displays its benefits in wound healing and ulcerative colitis. CONCLUSION: The presence of flavonoids, saponins, terpenoids, anthocyanins, coumarins, alkaloids, polyphenols, tannins and emodins in this plant is responsible for its various pharmacological activities. The retrospective study provides direction for existing research as well as future studies to support the domain of pharmaceutical and medical sciences.

Antitumor Effect of Bryonia dioïca Methanol Extract: In Vitro and In Vivo Study.

Aim: A large number of plant-derived products have been approved for the treatment of numerous types of cancer, and these products have also shown to reduce the effects of metastatic cancer. The aim of this study is to evaluate the anticancer effects of a methanolic extract of Bryonia dioïca root (M extract) against B16F10 melanoma cancer cells in vitro as well as in vivo.Results: It was shown to induce apoptosis, in vitro, and to inhibit cell growth by arresting cell cycle progression in SubG1 phase. Mice bearing the melanoma cells were used to confirm any in vivo effectiveness of the M extract as an antitumor promoting agent. In mice dosed with 50 mg M/kg/d (for 28 days), tumor weight was inhibited by 65.03% compared to that in mice that did not receive the product. Our results demonstrate on the one hand, that this inhibition was accompanied by a drastic decrease regulation of complex FAK, Src, ERK, p130Cas and paxillin. On the other hand, it was marked by a measurable decrease of the metastatic descent in the lungs.Conclusions: These effects could be ascribed to the presence of bryoniosides and cucurbitacins such as cucurbitacin A and cucurbitacin G in M extract.

Bryonia dioica aqueous extract induces apoptosis and G2/M cell cycle arrest in MDA­MB 231 breast cancer cells.

Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancer. The present study aimed to evaluate the apoptogenic activity and phytochemical composition of the aqueous extract of B. dioica roots growing in Algeria. The cytotoxic effect of B. dioica aqueous decoction against breast cancer MDA­MB­231 cells was evaluated by an MTT assay. Apoptosis induction was assessed by an Annexin V­fluorescien iosthiocyanate assay. Propidium iodide staining of cell DNA was used to assess the effects on the cell cycle. In addition to UV­Visible (UV­vis) analysis, the major compounds of the extracts were determined using liquid chromatography­mass spectrometric analyses. Our results showed that the B. dioica aqueous extract induced cell death in a time­dependent manner. The highest inhibitory effect was produced at concentrations of 50 µg/ml or higher after 72 h of treatment (91.15±0.71%). Furthermore, the extract induced apoptosis of MDA­MB­231 cells. At 250 µg/ml, 64.61% of the treated MDA­MB­231 cells were apoptotic. This was accompanied by cell cycle arrest at G2/M phase. The percentage of cells in G2/M increased from 15.7% (untreated cells) to 59.13% (50 µg/ml) and 58.51% (250 µg/ml). The UV­vis absorption spectra of B. dioica aqueous extract showed two absorption bands characteristic of the flavonol skeleton; 350­385 nm (Band I) and 250­280 nm (Band II). Myricetin (2,5,7,3,4,5­pentahydroxylflavonol) was found to be the major compound in the B. dioica aqueous extract. These findings suggest that B. dioica could be considered a promising source for developing novel therapeutics against breast cancer.

Flavonoid composition, cellular antioxidant activity and (myelo)peroxidase inhibition of a Bryonia alba L. (Cucurbitaceae) leaves extract.

OBJECTIVES: The aim of the present study consisted in the isolation of flavonoids from the leaves of Bryonia alba L. and evaluation of their antioxidant activity and inhibition on peroxidase-catalysed reactions. METHODS: Flavonoids were isolated by preparative HPLC-DAD and their structures were elucidated by MS and NMR. Inhibitory effect was tested by the horseradish peroxidase and the myeloperoxidase assays. Cellular antioxidant assays consisted in testing the inhibitory activity on the reactive oxygen species released upon activation of neutrophils freshly isolated ex vivo from equine blood and of human monocytes-derived macrophages in vitro. Whole organism toxicity was assessed on zebrafish larvae. KEY FINDINGS: Four flavonoids (lutonarin, saponarin, isoorientin and isovitexin) were isolated. The performed assays showed significant antioxidant activity and inhibition for the peroxidase-catalysed reactions. Absence of cellular and zebrafish toxicity was confirmed. CONCLUSIONS: Bryonia alba L. leaves are particularly interesting for their flavonoids content and showed significant inhibitory effect on peroxidase-catalysed oxidation of substrates (Amplex Red and L012), as well as antioxidant/antiradical activity, proving that this species has a medicinal potential. Moreover, the present study highlights the absence of the toxicity of these leaves and offers though a novel perspective on the species, previously known as being toxic.

Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology.

INTRODUCTION: Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. AIM OF THE STUDY: The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola rosea, Eleutherococcus senticosus, Withania somnifera, Rhaponticum carthamoides, and Bryonia alba. MATERIALS AND METHODS: To investigate the underlying molecular mechanisms of adaptogens, we conducted RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of adaptogens and analyzed the relevance of deregulated genes to adaptive stress-response signaling pathways using in silico pathway analysis software. RESULTS AND DISCUSSION: At least 88 of the 3516 genes regulated by adaptogens were closely associated with adaptive stress response and adaptive stress-response signaling pathways (ASRSPs), including neuronal signaling related to corticotropin-releasing hormone, cAMP-mediated, protein kinase A, and CREB; pathways related to signaling involving CXCR4, melatonin, nitric oxide synthase, GP6, Gαs, MAPK, neuroinflammation, neuropathic pain, opioids, renin-angiotensin, AMPK, calcium, and synapses; and pathways associated with dendritic cell maturation and G-coupled protein receptor-mediated nutrient sensing in enteroendocrine cells. All samples tested showed significant effects on the expression of genes encoding neurohormones CRH, GNRH, UCN, G-protein-coupled and other transmembrane receptors TLR9, PRLR, CHRNE, GP1BA, PLXNA4, a ligand-dependent nuclear receptor RORA, transmembrane channels, transcription regulators FOS, FOXO6, SCX, STAT5A, ZFPM2, ZNF396, ZNF467, protein kinases MAPK10, MAPK13, MERTK, FLT1, PRKCH, ROS1, TTN), phosphatases PTPRD, PTPRR, peptidases, metabolic enzymes, a chaperone (HSPA6), and other proteins, all of which modulate numerous life processes, playing key roles in several canonical pathways involved in defense response and regulation of homeostasis in organisms. It is for the first time we report that the molecular mechanism of actions of melatonin and plant adaptogens are alike, all adaptogens tested activated the melatonin signaling pathway by acting through two G-protein-coupled membrane receptors MT1 and MT2 and upregulation of the ligand-specific nuclear receptor RORA, which plays a role in intellectual disability, neurological disorders, retinopathy, hypertension, dyslipidemia, and cancer, which are common in aging. Furthermore, melatonin activated adaptive signaling pathways and upregulated expression of UCN, GNRH1, TLR9, GP1BA, PLXNA4, CHRM4, GPR19, VIPR2, RORA, STAT5A, ZFPM2, ZNF396, FLT1, MAPK10, MERTK, PRKCH, and TTN, which were commonly regulated by all adaptogens tested. We conclude that melatonin is an adaptation hormone playing an important role in regulation of homeostasis. Adaptogens presumably worked as eustressors ("stress-vaccines") to activate the cellular adaptive system by inducing the expression of ASRSPs, which then reciprocally protected cells from damage caused by distress. Functional investigation by interactive pathways analysis demonstrated that adaptogens activated ASRSPs associated with stress-induced and aging-related disorders such as chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, metabolic disorders, and cancer. CONCLUSION: This study has elucidated the genome-wide effects of several adaptogenic herbal extracts in brain cells culture. These data highlight the consistent activation of ASRSPs by adaptogens in T98G neuroglia cells. The extracts affected many genes playing key roles in modulation of adaptive homeostasis, indicating their ability to modify gene expression to prevent stress-induced and aging-related disorders. Overall, this study provides a comprehensive look at the molecular mechanisms by which adaptogens exerts stress-protective effects.

Anthroposophic medicine in the treatment of pediatric pseudocroup: A systematic review.

BACKGROUND: In Europe only few integrative pediatric wards exists and there are two German hospitals focusing on anthroposophic medicine as part of complementary and alternative medicine (CAM). Whilst the most common pediatric diseases are treated here, pseudocroup patients make up a large group in these hospitals, receiving conventional as well as anthroposophic therapies. However, effectiveness of these therapy concepts mostly based on physicians' experiences but clinical studies are hitherto missing. METHODS: A systematic literature search identifying therapy approaches for pseudocroup in children was conducted in general electronic databases (Cochrane Library, PubMed, OVID) and in CAM-specific databases (CAMbase, CAM-QUEST®, Anthromedics). Search results were screened for anthroposophic therapy options. In addition, anthroposophic guidebooks were handsearched for relevant information. RESULTS: Among 157 articles fulfilling search criteria one retrospective study, and five experience reports describing anthroposophic treatments were identified. Several medications for the treatment of pseudocroup were mentioned such as Aconitum, Apis, Bryonia, Hepar sulfuris, Lavender, Pyrit, Sambucus and Spongia. During appropriate use no adverse effects were reported. CONCLUSION: Anthroposophic medicine harbors a broad spectrum of remedies for the treatment of pseudocroup in children. In particular, Aconitum, Bryonia and Spongia are frequently recommended; however, clinical trials investigating the effectiveness are sparse. Therefore, development and validation of therapy strategies are required.

Fatty Acids Composition and Antibacterial Activity of Aristolochia longa L. and Bryonia dioïca Jacq. Growing Wild in Tunisia.

The composition of the fatty acids of the roots and aerial parts of Aritolochia longa (Aristolacheae) and Bryonia dioïca (Cucurbutaceae) was analyzed by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The oils extracted from the aerial parts of both species were rich in polyunsaturated fatty acids with the essential linolenic and linoleic acids being the most prominent compounds. Oleic and linoleic acids were the majors fatty acids in the roots of both species. Whatever the plant part analyzed and the species, the saturated fatty acids were predominantly composed of palmitic and stearic acids. The antibacterial activity, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the lipid extracts were determined against a panel of five bacterial strains. The results showed that the sensitivity to the lipid extracts was different for the test bacterial strains, and the susceptibility of gram positive bacteria was found to be greater than gram negative bacteria. The antibacterial activity of the root lipid extracts was particularly important against Enterococcus feacium (CMI value of 125 µg/mL; CMB values > 250 µg/mL) and Streptococcus agalactiae (CMI value of 125 µg/mL; CMB values 250 µg/mL for A. longa roots). These results indicate that A. longa and B. dioïca could be considered as good sources of essential fatty acids which can act as natural antibacterial agents.

Substitution between Aristolochia and Bryonia genus in North-Eastern Morocco: toxicological implications.

ETHNOPHARMACOLOGICAL RELEVANCE: Although acknowledged as toxic herbs, Aristolochia species are still widely used worldwide. The aristolochic acids (AA) they contain can induce the so-called "aristolochic acid nephropathy", leading to renal fibrosis and upper urinary tract cancer. Traditional Moroccan medicine still often uses Aristolochia species under the vernacular name of Bereztem for the treatment of numerous ailments, notably cancer, diabetes or digestive tract disorders. As the botanical identity and renal toxicity of used species remain unexplored, the safety of patients may be threatened. MATERIAL AND METHODS: Ethnopharmacological data were collected from herbalists from the provinces of Oujda and Berkane, located in North-Eastern Morocco. Samples of Bereztem were collected at herbalist shops and checked for their content in AA using TLC and LC-MS methods. The toxicity of crude methanolic extracts of each herb was assessed on a HK-2 cell-based in vitro model by measurement of the cell survival to evaluate cytotoxicity and by assessment of renal-specific toxicity via (i) the evaluation of genes (E-cadherin and α-smooth muscle actin) expression by RT-qPCR; (ii) the quantities of ß-catenin and vimentin by immunofluorescence microscopy; (iii) the secretion of fibronectin; and (iv) the excretion of interleukin-6. RESULTS: The survey indicated that, among 42 herbalists visited, 33 were retailers of Bereztem, which was generally sold as a cancer treatment. Botanical investigations revealed that Aristolochia longa was frequently substituted by Bryonia dioica, which was associated with a higher cytotoxicity. Parameters specific to renal toxicity were also found to be enhanced, as compared to Aristolochia baetica and A. longa: down-regulation of ß-catenin and E-cadherin and up-regulation of vimentin and α-smooth muscle actin, and secretion of fibronectin and interleukin-6. CONCLUSION: In accordance with the Moroccan regulations, the use of so-called Aristolochia species should be discontinued. On one hand, the correctly identified aristolochia contain nephrotoxic aristolochic acids; on the other hand, aristolochia are massively substituted in North-Eastern Morocco and adulterated by a well-known toxic herb, B. dioica. Our data indicate that the bryony renal toxicity may be deleterious in shorter time periods than aristolochia. Reinforced on-site controls are needed to remind herbalists and harvesters that these herbs should be prohibited.

Carotenoid content of wild edible young shoots traditionally consumed in Spain (Asparagus acutifolius L., Humulus lupulus L., Bryonia dioica Jacq. and Tamus communis L.).

BACKGROUND: Wild vegetables have traditionally been consumed as part of the Mediterranean diet, being valuable sources of nutrients and bioactive compounds. The objective of this work was to analyse the carotenoid content of the edible young shoots of four species (Asparagus acutifolius L., Humulus lupulus L., Bryonia dioica Jacq. and Tamus communis L.) as part of a wider study on the characterisation of the nutritional composition of wild edible plants commonly consumed in Spain. Samples were gathered from two locations in Central Spain for two consecutive years. RESULTS: Lutein, ß-carotene, neoxanthin and violaxanthin were quantified by high-performance liquid chromatography with a photodiode array detector. Median concentration ranges (µg g(-1) edible wet weight) were: ß-carotene, 3.39-6.69, lutein, 5.44­19.13;neoxanthin, 5.17-17.37; and violaxanthin, 2.08-8.93. The highest carotenoid content was that of B. dioica (59.01 µg g(-1)) and the lowest was found in A. acutifolius (17.58 µg g(-1)) [corrected]. CONCLUSION: Our results show that these wild young shoots are richer sources of carotenoids than many of the commercially available leafy vegetables.

Bryonia dioica aqueous extract induces apoptosis through mitochondrial intrinsic pathway in BL41 Burkitt's lymphoma cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancers; it belongs to the genus Bryonia (Cucurbitaceae). AIM OF THE STUDY: To investigate the cytotoxic and apoptogenic activities, the phytochemical composition and acute toxicity of the aqueous extract of Bryonia dioica roots growing in Algeria. MATERIALS AND METHODS: Dried roots of Bryonia dioica were extracted with water (decoction). The cytotoxic effects of the aqueous extract in the Burkitt's lymphoma BL41 cell lines were evaluated by flow cytometry. Apoptosis induction was assessed by two corroborative assays; propidium iodide (PI) staining of cell DNA and flow cytometric light scatter analysis. The mitochondria membrane potential was investigated using a fluorescent dye DIOC6. The expression of caspases-3, -8, -9 and PARP was assessed by Western blot. The phytochemical screening of the roots of Bryonia dioica was performed using qualitative phytochemical standard procedures. RESULTS: The Bryonia dioica aqueous extract induced cell death in a dose-dependent manner. The IC50 of Bryonia dioica aqueous extract was estimated to be approximately 15, 63µg/ml. This was accompanied by induction of apoptosis, activation of caspase-3 and -9, cleavage of PARP and loss of mitochondria membrane potential. Furthermore, the phytochemical screening of roots of Bryonia dioica showed the presence of various bioactive such as polyphenols, sterols and triterpenes, alkaloids, c-heterosides, carbohydrates and saponins. CONCLUSION: The aqueous extract of Bryonia dioica induces apoptosis in the Burkitt's lymphoma BL41 cell lines via the mitochondrial pathway. The flavonoids, sterols and triterpens detected could be responsible for the cytotoxic and apoptogenic activities of the aqueous extract of Bryonia dioica. These findings suggest that Bryonia dioica could be considered as a promising source for developing novel therapeutics against Burkitt's lymphoma.

Cucurbitane-type triterpenes with anti-proliferative effects on U937 cells from an egyptian natural medicine, Bryonia cretica: structures of new triterpene glycosides, bryoniaosides A and B.

The 90% aqueous ethanol extract of an Egyptian natural medicine, the roots of Bryonia cretica L., was found to exhibit a strong inhibitory effect on the proliferation of human leukemia U937 cells. By bioassay-guided fractionation, we isolated two new cucurbitane-type triterpene glycosides, bryoniaosides A and B, were isolated from the roots of Bryonia cretica L. together with 16 known cucurbitane-type triterpenes and glycosides. The chemical structures of bryoniaosides A and B were determined on the basis of chemical and spectroscopic evidence. Effects of principal cucurbitane-type triterpenes (cucurbitacins B, D, E, and J, 23,24-dihydrocucurbitacins B and E, and hexanorcucurbitacin D) on proliferation of the cells were examined. Cucurbitacins B and E showed the greater cytotoxic effects with IC(50) values of 9.2 and 16 nM after 72 h, and their IC(50) values were equivalent to that of camptothecin. An alpha,beta-conjugated ketone moiety at the 22-24-positions and an acetoxy group at the 25-position are essential for the strong activity.

New cucurbitane-type triterpenoids from Bryonia aspera.

Phytochemical investigation of the chloroform extract of BRYONIA ASPERA roots resulted in the isolation and structure elucidation of two new cucurbitacins (1, 2) together with eight known cucurbitane derivatives (6-13), the pentacyclic triterpene bryonolic acid (5) and two hydroxybenzoic acid amides (3, 4). Their structures were elucidated by spectroscopic analysis, including 2D NMR techniques.

Effects of Bryonia laciniosa seeds on sexual behaviour of male rats.

Ethanolic extract of seeds of Bryonia laciniosa Linn was administered orally to groups of male albino rats at the dose levels of 50, 100, and 150 mg kg(-1) body weight per day for 28 days. The changes in sexual behaviour, reproductive organ weights, histology of testis and epididymis, epididymal sperm density, and androgenic hormone levels were evaluated. The sexual behaviour parameters studied such as mount frequency, intromission frequency, mount latency, intromission latency were significantly affected. Increase in body weight as well as weight of testis, prostate, seminal vesicle, and epididymis was noticed. Transverse sections of testis exhibited increased spermatogenesis and a significant increase in sperm count in epididymis. The fructose content of seminal vesicle was also increased. The extract treatment also brought a significant increase in serum testosterone and luteinizing hormone levels. The studies clearly reflect androgenic activity of the extract and its effects on hypothalamic pituitary gonadal axis.

Evaluation of anti-inflammatory activity of chloroform extract of Bryonia laciniosa in experimental animal models.

The anti-inflammatory effect of the leaves of Bryonia laciniosa was evaluated using carrageenan, dextran, histamine, serotonin induced rat paw oedema and cotton pellet induced granuloma (chronic) models in rats. In mice, carrageenan peritonitis test was performed for the extract by oral administration. The chloroform extract of Bryonia laciniosa (CEBL) exhibited significant anti-inflammatory effect at the dose 50, 100 and 200 mg/kg. Maximum inhibition (52.4%) was noted at the dose of 200 mg/kg after 3 h of drug treatment in carrageenan induced paw oedema, whereas the indomethacin (standard drug) produced 62.1% of inhibition. The extract exhibited significant anti-inflammatory activity in dextran induced paw oedema in a dose dependent manner. The extract also exhibited significant inhibition on the hind paw oedema in rats caused by histamine and serotonin respectively. In the chronic model (cotton pellet induced granuloma) the CEBL (200 mg/kg) and standard drug showed decreased formation of granuloma tissue by 50.1 and 57.3% (p<0.001) respectively. The extract also inhibited peritoneal leukocyte migration in mice. Thus, the present study revealed that the chloroform extract of Bryonia laciniosa exhibited significant anti-inflammatory activity in the tested models.

Anti-inflammatory and anti-tumor-promoting effects of cucurbitane glycosides from the roots of Bryonia dioica.

Seven new triterpene glycosides, bryoniosides A-G (1-7), have been isolated along with two known triterpene glycosides, cabenoside D (8) and bryoamaride (9), from a methanol extract of the roots of Bryoniadioica. The structures of 1-7 were determined on the basis of spectroscopic and chemical methods. Six compounds, 2, 3, 5, and 7-9, and 11 compounds, 1-9, bryodulcosigenin (10), and bryosigenin (11), respectively, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice and on Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA. All compounds tested showed marked anti-inflammatory effects, with 50% inhibitory doses (ID(50)) of 0.2-0.6 mg per ear. In addition, all of the compounds tested except for compound 5 showed potent inhibitory effects on EBV-EA induction (100% inhibition at 1 x 10(3) mol ratio/TPA).