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Bauhinia holophylla leaves, also known as "pata-de-vaca", are traditionally used in Brazil to treat diabetes. Although the hypoglycemic activity of this medicinal plant has already been described, the active compounds responsible for the hypoglycemic activity have not yet been identified. To rapidly obtain two fractions in large amounts compatible with further in vivo assay, the hydroalcoholic extract of B. holophylla leaves was fractionated by Vacuum Liquid Chromatography and then purified by medium pressure liquid chromatography combined with an in vivo Glucose Tolerance Test in diabetic mice. This approach resulted in the identification of eleven compounds (1-11), including an original non-cyanogenic cyanoglucoside derivative. The structures of the isolated compounds were elucidated by nuclear magnetic resonance and high-resolution mass spectrometry. One of the major compounds of the leaves, lithospermoside (3), exhibited strong hypoglycemic activity in diabetic mice at the doses of 10 and 20 mg/kg b.w. and prevents body weight loss. The proton nuclear magnetic resonance (1H NMR) quantification revealed that the hydroalcoholic leaves extract contained 1.7% of lithospermoside (3) and 3.1% of flavonoids. The NMR analysis also revealed the presence of a high amount of pinitol (4) (9.5%), a known compound possessing in vivo hypoglycemic activity. The hypoglycemic properties of the hydroalcoholic leaves extract and the traditional water infusion extracts of the leaves of B. holophylla seem thus to be the result of the activity of three unrelated classes of compounds. Such results support to some extent the traditional use of Bauhinia holophylla to treat diabetes., Competing Interests: The authors have declared that no competing interests exist.

Gamma-aminobutyric acid type A (GABA A ) receptors are major inhibitory neurotransmitter receptors in the central nervous system and a target for numerous clinically important drugs used to treat anxiety, insomnia, and epilepsy. A series of allosteric GABA A receptor agonists was identified previously with the aid of HPLC-based activity profiling, whereby activity was tracked with an electrophysiological assay in Xenopus laevis oocytes. To accelerate the discovery process, an approach has been established for HPLC-based profiling using a larval zebrafish (Danio rerio) seizure model induced by pentylenetetrazol (PTZ), a pro-convulsant GABA A receptor antagonist. The assay was validated with the aid of representative GABAergic plant compounds and extracts. Various parameters that are relevant for the quality of results obtained, including PTZ concentration, the number of larvae, the incubation time, and the data analysis protocol, were optimized. The assay was then translated into an HPLC profiling protocol, and active compounds were tracked in extracts of Valeriana officinalis and Magnolia officinalis. For selected compounds the effects in the zebrafish larvae model were compared with data from in silico blood-brain barrier (BBB) permeability predictions, to validate the use for discovery of BBB-permeable natural products.

Ethnopharmacological Relevance: Waltheria indica L. is traditionally used in several countries against inflammatory related diseases and cancer, mainly as a decoction of the aerial parts., Aim of the Study: The transcription factor NF-κB is known to induce tumor promotion and progression and is considered a major player in inflammation-driven cancers. Therefore, inhibitors of this pathway possess cancer chemopreventive and chemotherapeutic activities. This study aimed first to confirm the use of Waltheria indica as a traditional anti-inflammatory remedy by assessing the NF-κB inhibitory activity and then to identify the major bioactive compounds. The isolated compounds were also tested for their QR inducing property, a complementary strategy in cancer chemoprevention able to target tumor initiation. Finally, the relevance of in vitro results was examined by investigating the occurrence of the active compounds in traditional preparations., Materials and Methods: Compounds were isolated from the dichloromethane extract of the aerial parts using flash chromatography and semi-preparative HPLC. NF-κB inhibitory activity of pure compounds from Waltheria indica was assessed using a luciferase reporter assay in HEK293 cells. Their QR inducing activity was also assessed in Hepa1c1c7 cells., Results: Twenty-nine compounds, of which 5 are new, were obtained from the dichloromethane extract and tested for their cancer chemoprevention activity. Eleven compounds inhibited NF-κB and/or induced QR in the low to mid µM range. Chrysosplenol E (20) was active in both tests. Two of the most potent NF-κB inhibitors, waltherione A (4) and waltherione C (5), as well as 20 were found in the traditional decoction, in which 4 and 5 were major compounds., Conclusion: The presence of potent NF-κB inhibitors and QR inducing compounds in the decoction of the aerial parts of Waltheria indica supports its traditional use in inflammatory-related diseases and cancer chemoprevention., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

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 -β-glucopyranosyl-(1 → 4)-β-xylopyranoside (1) was a major compound in seeds. Securigenin-3- O -inositol-(1 → 3)-β-glucopyranosyl-(1 → 4)-β-xylopyranoside (2) and securigenin-3- O -α-rhamnopyranosyl-(1 → 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.

Laserpitium carduchorum is frequently used as a spice, and in Bane folk medicine, the aerial parts of this are used to treat urinary infections. Variation in the quantity and quality of the essential oil of Iranian L. carduchorum at different developmental growth stages including vegetative, flowering, and seed ripening is reported. In total, 33 compounds were identified and quantified in the oils of vegetative, flowering, and seed ripening stages, representing 97.8%, 98.8%, and 98.7% of the oils, respectively. α-Pinene (45.1, 61.4, and 46.4%), sabinene (16.5, 10.3, and 17.5%), and limonene (6.4, 8.5, and 20.4%) were the main compounds in all samples. The antioxidant activities of different extracts of L. carduchorum at different developmental growth stages were examined by employing various established in vitro experiments including DPPH, FRAP, and TEAC assays. The amounts of total phenolics were also determined spectrophotometerically. Antimicrobial activities of different extracts and essential oils of L. carduchorum at different developmental growth stages were examined against five Gram-positive and four Gram-negative bacteria, as well as two fungi. The results showed that maximum antioxidant and antimicrobial activity of extracts were at the flowering stage of the plant. Maximum antimicrobial activity of essential oils was at seed ripening stage., (© 2016 Wiley-VHCA AG, Zürich.)

In natural product research, the efficient purification of molecules from large amounts of complex extracts is a key element. In this regard, an integrative strategy for efficient MS-guided isolation of antifungal compounds has been developed. First, off-line HPLC antifungal activity-based profiling and HPLC-PDA-MS profiling were used to localize the compounds of interest on the analytical scale. Then, the analytical gradient was geometrically transferred to the flash chromatographic level. Finally, an MS-triggered isolation of the localized bioactive molecules was realized using high-resolution flash chromatographic columns (15 µm spherical particles) coupled to a single quadrupole mass spectrometer via a splitter system. This isolation strategy was applied for the MS-targeted purification of antifungal principles from the liverwort Chiloscyphus polyanthos. This rational methodology has high potential for the targeted large-scale purification of bioactive compounds, avoiding the need to repeat a given bioassay at each isolation step. Seven sesquiterpene lactones were isolated, of which five were found to be bioactive and one was reported as a new compound. The absolute configuration of some compounds was established for the first time by electronic circular dichroism spectroscopy., (Georg Thieme Verlag KG Stuttgart · New York.)

Medicinal plants as a therapeutic agent with osteogenic properties can enhance fracture-healing process. In this study, the osteo-inductive potential of Asian Panax Ginseng root extract within electrospun polycaprolactone (PCL) based nanofibers has been investigated. Scanning electron microscopy images revealed that all nanofibers were highly porous and beadles with average diameter ranging from 250 to 650 nm. The incorporation of ginseng extract improved the physical characteristics (i.e., hydrophilicity) of PCL nanofibers, as well as the mechanical properties. Although ginseng extract increased the degradation rate of pure PCL nanofibers, the porous structure and morphology of fibers did not change significantly after 42 days. It was found that nanofibrous scaffolds containing ginseng extract had higher proliferation (up to ~1.5 fold) compared to the pristine PCL. The qRT-PCR analysis demonstrated the addition of ginseng extract into PCL nanofibers induced significant expression of osteogenic genes (Osteocalcin, Runx-2 and Col-1) in MSCs in a concentration dependent manner. Moreover, higher calcium content, alkaline phosphatase activity and higher mineralization of MSCs were observed compared to the pristine PCL fibers. Our results indicated the promising potential of ginseng extract as an additive to enhance osteo-inductivity, mechanical and physical properties of PCL nanofibers for bone tissue engineering application.

Ethnopharmacological Relevance: Leaf decoctions of Carica papaya have been traditionally used in some parts of Indonesia to treat and prevent malaria. Leaf extracts and fraction have been previously shown to possess antiplasmodial activity in vitro and in vivo., Materials and Methods: Antiplasmodial activity of extracts was confirmed and the active fractions in the extract were identified by HPLC-based activity profiling, a gradient HPLC fractionation of a single injection of the extract, followed by offline bioassay of the obtained microfractions. For preparative isolation of compounds, an alkaloidal fraction was obtained via adsorption on cationic ion exchange resin. Active compounds were purified by HPLC-MS and MPLC-ELSD. Structures were established by HR-ESI-MS and NMR spectroscopy. For compounds 5 and 7 absolute configuration was confirmed by comparison of experimental and calculated electronic circular dichroism (ECD) spectroscopy data, and by X-ray crystallography. Compounds were tested for bioactivity in vitro against four parasites (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum), and in the Plasmodium berghei mouse model., Results: Profiling indicated flavonoids and alkaloids in the active time windows. A total of nine compounds were isolated. Four were known flavonols--manghaslin, clitorin, rutin, and nicotiflorin. Five compounds isolated from the alkaloidal fraction were piperidine alkaloids. Compounds 5 and 6 were inactive carpamic acid and methyl carpamate, while three alkaloids 7-9 showed high antiplasmodial activity and low cytotoxicity. When tested in the Plasmodium berghei mouse model, carpaine (7) did not increase the survival time of animals., Conclusions: The antiplasmodial activity of papaya leaves could be linked to alkaloids. Among these, carpaine was highly active and selective in vitro. The high in vitro activity could not be substantiated with the in vivo murine model. Further investigations are needed to clarify the divergence between our negative in vivo results for carpaine, and previous reports of in vivo activity with papaya leaf extracts., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)