Inhibition of Seizure-Like Paroxysms and Toxicity Effects of Securidaca longepedunculata Extracts and Constituents in Zebrafish Danio rerio.

Plants used in traditional medicine in the management of epilepsy could potentially yield novel drug compounds with antiepileptic properties. The medicinal plant Securidaca longepedunculata is widely used in traditional medicine in the African continent, and epilepsy is among several indications. Limited knowledge is available on its toxicity and medicinal effects, such as anticonvulsant activities. This study explores the potential in vivo inhibition of seizure-like paroxysms and toxicity effects of dichloromethane (DCM) and ethanol (EtOH) extracts, as well as isolated xanthones and benzoates of S. longepedunculata. Ten phenolic compounds were isolated from the DCM extract. All of the substances were identified by nuclear magnetic resonance spectroscopy. Assays for toxicity and inhibition of pentylenetetrazole (PTZ)-induced seizure-like paroxysms were performed in zebrafish larvae. Among the compounds assessed in the assay for maximum tolerated concentration (MTC), benzyl-2-hydroxy-6-methoxy-benzoate (MTC 12.5 µM), 4,8-dihydroxy-1,2,3,5,6-pentamethoxyxanthone (MTC 25 µM), and 1,7-dihydroxy-4-methoxyxanthone (MTC 6.25 µM) were the most toxic. The DCM extract, 1,7-dihydroxy-4-methoxyxanthone and 2-hydroxy-1,7-dimethoxyxanthone displayed the most significant inhibition of paroxysms by altering the locomotor behavior in GABAA receptor antagonist, PTZ, which induced seizures in larval zebrafish. The EtOH extract, benzyl benzoate, and benzyl-2-hydroxy-6-methoxy-benzoate unexpectedly increased locomotor activity in treated larval zebrafish and decreased locomotor activity in nontreated larval zebrafish, seemingly due to paradoxical excitation. The results reveal promising medicinal activities of this plant, contributing to our understanding of its use as an antiepileptic drug. It also shows us the presence of potentially new lead compounds for future drug development.

Effectiveness of Hydroalcoholic Seed Extract of Securigera securidaca on Pancreatic Local Renin-Angiotensin System and Its Alternative Pathway in Streptozotocin-Induced Diabetic Animal Model.

Background: Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Methods: Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. Results: HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Conclusions: Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.

Xanthones from Securidaca inappendiculata antagonized the antirheumatic effects of methotrexate in vivo by promoting its secretion into urine.

BACKGROUND: This study was designed to characterize the interaction between Securidaca inappendiculata Hassk. derived xanthones and methotrexate (MTX). METHODS: Collagen-induced arthritis (CIA) was induced in rats, which were treated with MTX, a xanthone-rich fraction (XRF), or MTX+XRF by gavage for 30 days. Clinical efficacy was assessed based on arthritis scores, serological analysis, and histological examination. Protein expression was investigated by either immunohistochemical or immunoblotting methods. MTX concentrations were determined by HPLC or LC-MS methods. Obtained results were further validated by in vitro assays using 1,7-dihydroxy-3,4-dimethoxyxanthone and HEK 293 T cells. RESULTS: XRF antagonized the antirheumatic effects of MTX in vivo, suggested by higher levels of proinflammatory cytokines, and severer swelling and deformation of joints in CIA rats in the MTX+XRF group compared with MTX monotherapy. XRF reduced MTX concentration in plasma and promoted its excretion into urine. As a result, XRF attenuated MTX-induced edema of the proximal tubule. Furthermore, XRF restored the decreased expression of organic anion transporter three (OAT3), which accounts for MTX secretion in the kidney. Consistently, 1,7-dihydroxy-3,4-dimethoxyxanthone promoted the cellular intake of MTX by increasing OTA3 expression. CONCLUSION: It is suggested that the combined use of S. inappendulata with MTX should be optimized to avoid the antagonistic effects and improve the safety of the MTX regimen.

Bioactive fractions from Securidaca inappendiculata alleviated collagen-induced arthritis in rats by regulating metabolism-related signaling.

Securidaca inappendiculata is a xanthone rich medicinal plant that has been used in the treatment of inflammation and autoimmune diseases like rheumatoid arthritis (RA) for centuries; however, the material base and mechanism of action responsible for its anti-arthritis effect still remains elusive. The objective of this study is to evaluate the therapeutic effects of xanthone-enriched extract of the plant against collagen-induced arthritis (CIA) in rats and explore the underlying mechanisms. The xanthone-deprived fraction (XDF) and xanthone-rich fraction (XRF) were obtained by using a resin adsorption coupled with acid-base treatment method, and their chemical composition difference was characterized by UPLC-MS/MS analysis. Effects of the two on CIA were analyzed using radiographic, histological, and immunohistochemical analyses. The results indicated that XRF alleviated joint structures destructions with the higher efficacy than XDF, and decreased levels of TNF-α, IL-6, and anti-cyclic citrullinated peptide antibody in CIA rats significantly. Furthermore, XRF inhibited nicotinamide phosphoribosyl transferase (NAMPT) mediated fat biosynthesis and utilization indicated by clinical evidences and metabonomics analysis, which thereby disrupted energy-metabolism feedback. In addition, Toll-like Receptor 4 and High Mobility Group Protein 1 expressions were downregulated in XRF-treated CIA rats. Collective evidences suggest NAMPT could be an ideal target for RA treatments and reveal a novel antirheumatic mechanism of S. inappendiculata by regulating NAMPT controlled fat metabolism.

Chemical constituents from the stems of Securidaca inappendiculata Hassk.

Three new neolignan glycosides, (7R,8S)-4-hydroxy-3,3'-dimethoxy-8,4'-oxyneoligna-7,9,9'-triol-4-O-ß-d-glucopyranosyl-(1 → 4)-ß-D-glucopyranoside (1), (7R,8S)-4-hydroxy-3,5'-dimethoxy-4',7-epoxy-8,3'-neoligna-9,9'-diol-9'-O-ß-d-glucopyranosyl-4-O-[ß-d-glucopyranosyl-(1 → 4)]-ß-D-glucopyranoside (2), and (7R,8S)-4-hydroxy-3,5,5'-trimethoxy-4',7-epoxy-8,3'-neoligna-9,9'-diol-9'-O-ß-d-glucopyranosyl-4-O-[ß-d-glucopyranosyl-(1 → 4)]-ß-D-glucopyranoside (3), one new phenolic glycoside, securiphenoside B (4) and two new hemiterpene glycosides, securiterpenoside E-F (5-6) were isolated from the stems of Securidaca inappendiculata Hassk. Their structures were elucidated on the basis of 1D and 2D NMR, HRESIMS, CD and chemical evidence. Furthermore, compound 2 showed moderate hepatoprotective activity compared with bicyclol in vitro.

Ethanol Extract of Securidaca longipedunculata Induces Apoptosis in Brain Tumor (U87) Cells.

Incidence of cancer is estimated to be on the increase and current anticancer drugs are characterized by narrow margin of safety and side effects. There is the need to explore new drugs especially from plants since plants serve as major source of drugs. Securidaca longipedunculata Fresen plant is called the mother of all medicines in northern Nigeria and is used traditionally in the treatment of cancers by most traditional medicine practitioners in the region. This study is aimed at evaluating the anticancer activity of the plant extract using U87 brain tumor cell line. Ethanol extract of its root bark was prepared and fractionated by silica gel column chromatography. In vitro activity of the extract and fractions were assessed on the viability of U87 malignant brain tumor cell line by using hemacytometer, annexin V-PE and 7AAD flow cytometry and western blot detection of Poly-ADP-Ribose-Polymerase (PARP) cleavage. The results showed that the extract significantly (p<0.01) inhibited proliferation of U87 cell line with IC50 of 20.535 µg/ml. Apoptosis was induced by the extract (41.53 ± 10.33%) and the polar fraction (47.3 ± 2.7%) via cleavage of PARP. It was concluded that the ethanol extract of S. longipedunculata root bark inhibited proliferation of U87 cell line and induced apoptosis by cleavage of PARP, thus supporting folkloric use of the plant in the management of cancers.

Fatty oil from Securidaca inappendiculata exerted therapeutic effects on adjuvant-induced arthritis in mice via suppression on fibroblast-like synoviocyte.

Securidaca inappendiculata Hassk. (SI) is a medicinal plant used to treat rheumatoid arthritis (RA) in South China. A substantial amount of fatty oil was isolated from SI (SIF), however little knowledge about its chemical composition and medicinal potentials was obtained. In this study, we analyzed its chemical composition with methyl esterification based GC-MS method, and investigated the therapeutic potentials on adjuvant-induced arthritis (AA) in mice. MTT and western-blot methods were employed to investigate its effects on proliferation rate and protein expressions in MH7A cells, respectively. It was revealed SIF was mainly comprised of saturated and monosaturated fatty acids, and the two predominant compounds were palmitic acid (36.89%) and oleic acid (31.12%). Treatment with SIF at 100 mg/kg resulted in significant alleviation of AA severity in mice, together with reduced synovial hyperplasia and inflammatory infiltration in joints, and decreased levels of sialic acid, malondialdehyde and alkaline phosphatase in serum. Results from immunohistochemical assays hinted the protective effects of SIF on joints were associated to the inhibition on production of some pathological factors in synovium, including IL-1ß, TNF-α and MMP-9. SIF inhibited the proliferation of MH7A cells in a concentration dependent manner, and abrogated phosphorylation of p65 in vitro. These evidences collectively suggested SIF could suppress the pathological functions of fibroblast-like synoviocyte, and protect joints from destruction under AA conditions.

Molecular-trapping in Emulsion's Monolayer: A New Strategy for Production and Purification of Bioactive Saponins.

Saponins from defatted root-extract of Securidaca longipedunculata were systematically entrapped in emulsion monolayer-barrier and finally recovered in pure form through demulsification. First, their molecules were dispersed in water to engineer a monomolecular film architecture, via self-assembly. Emulsifying with ethyl-ether resulted in swollen micelles and engendered phase-inversion and phase-separation, by disrupting the thermodynamic equilibrium. As positive outcome, a Winsor II system was obtained, having saponin-rich upper phase (ethyl-ether) and impurities bound lower phase (aqueous). Saponin particles underwent transition in insoluble ethyl-ether, precipitated and recovered as solids. The entire process was bioactivity-guided and validated using pooled fractions of securidaca saponins, purified by TLC (RP-C18, F254S). TEM and SEM revealed interesting morphologies and particle sizes between nanometer and micron. At the end, purity output of 90% and total recovery of 94% were achieved. Here we show that "molecular-trapping in emulsion's monolayer" is an effective method for recovery, production and purification of saponins of plant origin.

[Lignan glycosides and sucrose esters from roots of Securidaca inappendiculata].

Nine compounds, including five lignan glycosides (1-5), three sucrose esters (6-8), and one organic acid ester (9), were isolated from the ethanol extract of the roots of Securidaca inappendiculata by various chromatographic methods including silica gel, MPLC and preparative HPLC. Their structures were elucidated as acernikol-4″-O-ß-D-glucopyranoside (1), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranoside (2), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside (3), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 9'-O-ß-D-glucopyranoside (4), (7R, 8S)-5-methoxydihydrodehy-drodiconiferyl alcohol 4-O-ß-D-glucopyranoside (5), 3, 6'-O-diferuloylsucrose (6), 3-O-feruloyl-6'-O-sinapoylsucrose (7), sibricose A5 (8), and mehyl ferulate (9) on the basis of 1H-, 13C-NMR and MS experiments. Compounds 1-5, 8, and 9 were isolated from the Securidaca genus for the first time. Compounds 2, 3, and 7 exhibited weak cytotoxic activities against Hela and MCF-7 cell lines.

Securigenin glycosides as hypoglycemic principles of Securigera securidaca seeds.

Seeds of Securigera securidaca (Fabaceae) are used in Iranian folk medicine as an antidiabetic treatment. In this study, the antihyperglycemic activity of chloroform and methanol fractions (CF and MF) from S. securidaca seed extract was investigated and their bioactive constituents were identified. The antidiabetic effects of fractions were assessed by streptozocin-induced diabetic Naval Medical Research Institute mice. The hypoglycemic activity of MF at 100 mg/kg and CF at 400 mg/kg was comparable with glibenclamide (3 mg/kg). MF at 400 mg/kg and CF at 600 mg/kg showed equal hypoglycemic responses to 12.5 IU/kg insulin (P > 0.05). Three cardiac glycosides were isolated as active constituents responsible for the hypoglycemic activity. Securigenin-3- O -ß-glucopyranosyl-(1 â†’ 4)-ß-xylopyranoside (1) was a major compound in seeds. Securigenin-3- O -inositol-(1 â†’ 3)-ß-glucopyranosyl-(1 â†’ 4)-ß-xylopyranoside (2) and securigenin-3- O -α-rhamnopyranosyl-(1 â†’ 4)-α-glucopyranoside (3) were found as new natural products. When 1-3 were tested at 10 mg/kg there was a significant reduction of blood glucose levels in diabetic mice, comparable to that of 3 mg/kg glibenclamide (P > 0.05). The hypoglycemic effect was due to an increase in insulin secretion; the insulin levels in the diabetic mice significantly improved and were comparable with those in healthy animals (P > 0.05). Compounds responsible for the hypoglycemic properties of S. securidaca seeds were identified as cardiac glycosides and were found to act via an increase of insulin levels in a diabetic mouse model.

Aqueous extract of Securidaca longipendunculata Oliv. and Olax subscropioidea inhibits key enzymes (acetylcholinesterase and butyrylcholinesterase) linked with Alzheimer's disease in vitro.

CONTEXT: Plants have historically been used to treat neurodegerative diseases which include Alzheimer's disease. OBJECTIVE: This study investigated the antioxidant properties and inhibitory effect of aqueous extracts of Securidaca longipendunculata root and Olax subscropioidea leaf on the cholinergic system in rat brain in vitro. MATERIALS AND METHODS: Aqueous extracts (1:20 w/v) of S. longipendunculata root and O. subscropioidea leaf was prepared and the ability of the extract to inhibit the activities of acetylcholinesterase and butyrylcholinesterase was evaluated as well as antioxidants as typified by 2,2-azino-bis-(3-ethylbenthiazoline-6-sulphonic acid (ABTS•) radical scavenging ability and Fe chelation spectophotometrically. RESULTS: ABTS• radical scavenging ability showed that S. longipendunculata (0.075 Mmol TEAC/100 g) had a higher scavenging ability than O. subscropioidea (0.07 Mmol TEAC/100 g). Also, the Fe2+ chelating ability of both extracts revealed that S. longipendunculata (IC50 = 105.57 g/mL) had a significantly (p < 0.05) higher Fe2+ chelating ability than O. subscropioidea (IC50 = 255.84 g/mL). Extracts of S. longipendunculata and O. subscropioidea inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities. However, S. longipendunculata (IC50 = 108.02 g/mL) has the higher AChE inhibitory activity than O. subscropioidea (IC50 = 110.35 g/mL). Also, both extracts inhibit BChE activity in vitro but S. longipendunculata (IC50 = 82.55 g/mL) had a higher BChE inhibitory activity than O. subscropioidea (IC50 = 108.44 g/mL). DISCUSSION AND CONCLUSIONS: The mechanism by which S. longipendunculata root and O. subscropioidea leaf perform their anti-Alzheimer's disease activity may be by their inhibition on the key enzymes linked to this disease.

The Effects of Solvent Polarity on Hypoglycemic and Hypolipidemic Activities of Securigera Securidaca (L.) Seeds.

The search for indigenous natural antidiabetic and antilipidemec agents is still ongoing. Medicinal plants are widely used for this purpose. These herbs are very rich sources of bioactive compounds as flavonoids, polyphenols, tannins, alkaloids which have been reported as effective role to reduce blood glucose and lipid levels. Securigera securidaca seed is reputed in folk medicine for their value as antidiabetic and antilipidemec drugs. In this research, the effect of solvent polarity in bioactive extraction contents of this plant was evaluated by GC-MS analysis. Then antidiabetic and antilipidemic activies of different extracts were investigated in streptozotocine-induced diabetic rats and compared to glibenclamide as known chemical drug for diabetes.The results indicated that, carbon tetrachloride extract of Securigera securidaca seeds showed the best and significant hypoglycemic and hypolipidemic activities compared to other extracts because of its more sterols and fatty acids content with beta cells protecting effect from high glucose-induced apoptosis and also increasing in insulin level and sensitivity.

[Saponins from roots of Securidaca inappendiculata with cytotoxic activities].

Seven acylated triterpene saponins were isolated from the roots of Securidaca inappendiculata by means of various chromatographic techniques such as silica gel, MPLC, preparative HPLC, and semi-preparative HPLC. Their chemical structures were identified as securioside A(1), securioside B(2), 3-O-ß-D-glucopyranosyl presenegenin 28-O-ß-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-[ß-D-glucopyranosyl-(1-->3)]-4-O-[(E)-3,4-dimethoxycinnamoyl]-ß-D-fucopyranosyl ester(3), 3-O-ß-D-glucopyranosyl presenegenin 28-O-ß-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-[ß-D-glucopyranosyl-(1-->3) ] -4-O-[(E/Z)-3, 4-dimethoxycinnamoyl]-ß-D-fucopyranosyl ester(3/4), 3-O-ß-D-glucopyranosyl presenegenin 28-O-α-L-arabinopyranosyl-(1-->3)-ß-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-4-O-[(E)-3,4-dimethoxycinnamoyl]-ß-D-fucopyranosyl ester(5), polygalasa- ponin XLV(6), and polygalasaponin XLVI (7) on the basis of spectroscopic data analysis and physicochemical properties. Among them, compounds 5-7 were isolated from the plants in genus Securidaca for the first time and compounds 3, 3/4 were isolated from the species for the first time. The cytotoxicity assay showed that compounds 2, 3/4, 5 have moderate cytotoxic activities against Lewis lung carcinoma LLC cells with IC50 values of 41.10, 38.17, and 48.92 µmol · L(-1), respectively; compound 2 exhibited moderate cytotoxic activities against human breast cancer MCF-7 cells with an IC50 value of 47.93 µmol · L(-1).

Securidaca longipedunculata Fresen (Polygalaceae): a review of its ethnomedicinal uses, phytochemistry, pharmacological properties and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Securidaca longipedunculata Fresen (Polygalaceae) is a multi-purpose plant with a long history of use in African traditional medicine to treat various sexually transmitted infections, hernias, coughs, fever, ascariasis, constipation, headaches, rheumatism, stomach ache, malaria, tuberculosis, pain, epilepsy, pneumonia, skin infections, and it is also used as an aphrodisiac for men. The current paper provides an overview of the present phytochemistry, toxicology, ethnomedicinal uses and pharmacological properties of S. longipedunculata. MATERIALS AND METHODS: The information reported in this paper was collected from a literature search using various computerised databases including ScienceDirect, Scopus, Scielo, PubMed and Google Scholar. The extra information was sourced from various academic dissertations, theses and botanical books. RESULTS: Phytochemically, extracts from various parts of S. longipedunculata, especially the root bark, contain numerous valuable compounds including xanthones, some benzyl benzoates and triterpene saponins amongst others. Toxicity studies, both in vivo and in vitro, revealed that extracts are only toxic at relatively high concentrations. Furthermore, extracts have antimicrobial, antioxidant, antiparasitic, anti-diabetic, anti-inflammatory, antimalarial, insecticidal, pesticidal, and anticonvulsant properties. CONCLUSIONS: S. longipedunculata is an important plant species with potential benefits in the treatment of transmissible and infectious diseases, including malaria, tuberculosis, and those caused by community acquired microorganisms. Although extracts from this species generally have little toxicity at low concentrations, further efforts are required to investigate the potential toxicity of S. longipedunculata. The antimicrobial properties of extracts and purified compounds against microorganisms causing sexually transmitted infections are also deserving of further research. Moreover, the pharmacokinetic properties of extracts and compounds of the species need to be explored as there is insufficient data available on these aspects.

Muchimangins G-J, fully substituted xanthones with a diphenylmethyl substituent, from Securidaca longepedunculata.

Four highly oxygenated xanthones, muchimangins G-J (1-4), have been isolated from the roots of Securidaca longepedunculata collected in Democratic Republic of Congo. Their structures were elucidated by analyses of spectroscopic data to be fully substituted xanthones with a diphenylmethyl substituent at C-2.

Xanthones as α-glucosidase inhibitors from the antihyperglycemic extract of Securidaca inappendiculata.

CONTEXT: Securidaca inappendiculata Hassk. (SI) is used to cure fractures and rheumatoid arthritis in China. Also, it is a potential antidiabetes drug; however, there are no reports on this. OBJECTIVE: The study was designed to evaluate the antihyperglycemic activities of fractions and compounds from SI, and attempt to explore the mechanism. MATERIALS AND METHODS: Antihyperglycemic activities were evaluated by the suppression on serum glucose levels in vivo and α-glucosidase inhibition assays in vitro. Fractions were given to mice by gastric intubation for 8 d. The high, medium, and low doses of fractions were equal to 10, 5, and 2.5 g/kg of the herb [SID (dichloromethane fraction) and SIE (ethyl acetate fraction) were doubled]. The serum glucose was monitored at 1 and 12 h after feeding. The silica gel and LH-20 chromatography were used to isolate active compounds. Structure-activity relationship analysis was based on IC50s and structures. RESULTS: The IC50s of SID, SIE, SIA (acetone fraction), SIM (methanol fraction), and acarbose were 712, 446, 1123, 1418, and 735 µg/mL. The postprandial and fasting serum glucose levels of SID, SIE, SIA, and SIM (high dose) were 5.5, 5.9, 6.2, 6.3 and 3.7, 3.5, 4.0, 5.0 mmol/L, while those of vehicle control were 7.5 and 5.6 mmol/L. Eleven xanthones isolated all exhibited inhibitory activities, mainly in a non-competitive reversible manner. The IC50s varied from 3.2 to 77.3 µg/mL. Structure-activity relationship analysis exhibited free hydroxyls contributed the most importance to the activity. CONCLUSION: The results indicated that xanthones from SI were powerful agents for antidiabetes.

Heptaoxygenated xanthones as anti-austerity agents from Securidaca longepedunculata.

In a course of our search for anticancer agent based on a novel anti-austerity strategy, we found that the CHCl3 extract of the roots of Securidaca longepedunculata (Polygalaceae), collected at Democratic Republic of Congo, killed PANC-1 human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM). Phytochemical investigation on the CHCl3 extract led to the isolation of 28 compounds including five new polymethoxylated xanthones [1,6,8-trihydroxy-2,3,4,5-tetramethoxyxanthone (1), 1,6-dihydroxy-2,3,4,5,8-pentamethoxyxanthone (2), 8-hydroxy-1,4,5,6-tetramethoxy-2,3-methylenedioxyxanthone (3), 4,6,8-trihydroxy-1,2,3,5-tetramethoxyxanthone (4), 4,8-dihydroxy-1,2,3,5,6-pentamethoxyxanthone (5)] and a new benzyl benzoate [benzyl 3-hydroxy-2-methoxybenzoate (6)]. Among them, 1,6,8-trihydroxy-2,3,4,5-tetramethoxyxanthone (1) and 1,6-dihydroxy-2,3,4,5,8-pentamethoxyxanthone (2) displayed the potent preferential cytotoxicity with PC50 of 22.8 and 17.4 µM, respectively. They triggered apoptosis-like PANC-1 cell death in NDM with a glucose-sensitive mode.

Anthelmintic activity of Securidaca longepedunculata (Family: Polygalaceae) root extract in mice, in vitro and in vivo.

OBJECTIVE: To elucidate the pharmacological bases of oral administration of Securidaca longepedunculata (S. longepedunculata) root extract as an anthelmintic in folkloric medicine. METHODS: Albino mice were infected with infective third (L3) larval stage of Heligmosomoides polygyrus (H. polygyrus) by esophageal intubation. Following establishment of the adult worms in the intestine, the mice were treated with 0-2 000 mg/kg body weight (bw) of methanolic root extract of S. longepedunculata and 100 mg/kg bw of pyrantel embonate, the reference drug in vivo. Bioactivity and larvicidal effects of the extract were tested by exposing brine shrimps (Artemia salina) to 0.00-1.00 mg/mL and the L3 stage of Heligmosomoidescontortus (H. contortus) and H. polygyrus to 0.00-2.50 mg/mL of the extract in vitro. RESULTS: The percentage yield of the extract was 7.13% w/w dry matter. The brine shrimps toxicity bioassay resulted in an LC50 of 74.18 µg/mL. The extract had a significant, dose-dependent larvicidal effect on the L3 stage of H. contortus and H. polygyrus with the terminal effect of 75% and 70% at the highest exposure concentrations, respectively. The extract however, did not affect the number of worm eggs per gram (epg) of fecal materials (P<0.05) and total worm burden (twb) of adult H. polygyrus in infected mice. Treatment with pyrantel embonate significant reduced both the fecal egg count and twb to 0 compared to the untreated control (P<0.05). CONCLUSIONS: These results indicate that S. longepedunculata root extract contains potent bioactive compounds and has larvicidal effect on L3 stage of H. contortus and H. polygyrus, substantiating its use as anthelmintic in alternative medicine.

Acylated triterpene saponins from the roots of Securidaca longepedunculata.

Four triterpene saponins, 3-O-beta-D-glucopyranosylpresenegenin 28-O-beta-D-apiofuranosyl-(1-->3)-beta-d-xylopyranosyl-(1-->4)-[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosylpresenegenin 28-O-beta-D-apiofuranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-[(6-O-acetyl)-beta-D-glucopyranosyl-(1-->3)]-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-beta-D-fucopyranosyl ester, 3-O-beta-D-glucopyranosylpresenegenin 28-O-beta-D-apiofuranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-galactopyranosyl-(1-->3)]-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-beta-D-fucopyranosyl ester, and 3-O-beta-D-glucopyranosylpresenegenin 28-O-beta-D-apiofuranosyl-(1-->3)-[alpha-L-arabinopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-beta-D-fucopyranosyl ester, were isolated from the roots of Securidaca longepedunculata, together with three known compounds. Their structures were established mainly by 2D NMR techniques and mass spectrometry.

[Antioxidant xanthones from Securidaca inappendiculata].

OBJECTIVE: To study the antioxidant constituents from the roots of Securidaca inappendiculata. METHOD: The bioassay-guided isolation of antioxidant constituents was carried out by the column chromatographic techniques. The combination of IR, MS, NMR and 2D-NMR spectroscopics methods was used to identify their structures. RESULT: Two new xanthones, 1, 2, 5-trihydroxy-6, 8-dimethoxy-9H-xanthen-9-one(1), 1, 5-dihydroxy-2, 6, 8-trimethoxy-9H-xanthen-9-one (2), along with seven known ones, 3, 8-dihydroxy-1, 4-dimethoxy-9H-xanthen-9-one(3), 4, 6-dihydroxy-1, 5, 7-trimethoxy-9H-xanthen-9-one(4), 7-hydroxy-1, 2, 3, 8-tetramethoxy-9H-xanthen- 9-one(5), 1, 7-dihydroxy-9H-xanthen-9-one(6), 4-hydroxy-3, 7-dimethoxy-9H-xanthen-9-one(7), 1,7-dimethoxy-9H-xanthen-9-one(8) and aucuparin(9), were isolated from the roots of S. inappendiculata. CONCLUSION: Compounds 1 and 2 were new xanthones, and compound 3 was isolated as a natural product for the first time, and compounds 4 and 6 were isolated for the first time from this genus. The antioxidant activities of all compounds were evaluated by ABTS, FRAP and DPPH assays respectively. Compound 9 showed significant activity by the ABTS and FRAP assays. Compound 1 showed significant activity with IC50 value of 0.31 mg x L(-1) in DPPH assay. Scavenging capacity of all compounds determined by all assays were well correlated between ABTS and FRAP assay (r = 0.9555).