The genus Balanophora J. R. Forst. & G. Forst. - Its use in traditional medicine, phytochemistry, and pharmacology: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Natural products, particularly medicinal plants, have been utilized in traditional medicine for millennia to treat various diseases. The genus Balanophora (Balanophoraceae) consists of 23 accepted species. These species are the most controversial flowering plants, with highly reduced morphologies and are found parasitizing on the roots of their host. They have been used in traditional medicine as a remedy for stomach pain, detumescence, uterine prolapse, wounds, syphilis, gonorrhea, treating injuries from falls, and other conditions. However, there is no review of this genus on its traditional uses, phytochemistry, and pharmacology. AIM: The present narrative review discusses the scientific data supporting the traditional uses of Balanophora species. The available information on its botanical properties, traditional uses, chemical contents, pharmacological activities, and toxicity was summarized to help comprehend current research and offer a foundation for future research. MATERIALS AND METHODS: The materials used in combining data on the genus Balanophora comprises online sources such as Web of Science, Google Scholar, Science Direct, and Chinese National Knowledge Infrastructure (CNKI) for Chinese-related materials. World Flora online was used in validating the scientific names of this genus while ChemBio Draw Ultra Version 22.2 software was employed in drawing the phytochemical compounds. RESULTS: Nine Balanophora species including B. harlandii, B. japonica, B. polyandra, B. fungosa, B. fungosa subsp. indica, B. laxiflora, B. abbreviata, B. tobiracola, and B. involucrata have been documented as vital sources of traditional medicines in different parts of Asia. A total of 159 secondary metabolites have been isolated and identified from the ten species of this genus comprising tannins, flavonoids, sterols, lignans, chalcones, terpenes, and phenylpropanoids. Among these compounds, tannins, lignans, terpenoids, chalcones and phenolic acids contribute to the pharmacological activities of the species in this genus with several biological activities both in vitro and in vivo such as anti-inflammatory, anti-oxidant, hypoglycemic activity, cytotoxicity, anti-microbial, melanin synthesis etc. CONCLUSION: This review summarizes the available literature on the traditional uses, pharmacological properties, and phytoconstituents of Balanophora species indicating that they contain fascinating chemical compounds with diverse biological activities. The traditional uses of the species in this genus have been confirmed by scientific data such as antimicrobial, hemostatic effect, gastroprotective activity and others. However, many species in this genus are yet unknown in terms of their botanical uses, chemical composition and biological activities. Thus, more research into the scientific connections between traditional medicinal uses and pharmacological activities, mode of action of the isolated bioactive constituents, and toxicity of other Balanophora species is needed to determine their efficacy and therapeutic potential for safe clinical application.

GC-MS/MS Quantification of EGFR Inhibitors, ß-Sitosterol, Betulinic Acid, (+) Eriodictyol, (+) Epipinoresinol, and Secoisolariciresinol, in Crude Extract and Ethyl Acetate Fraction of Thonningia sanguinea.

Medicinal plants are widely used in folk medicine to treat various diseases. Thonningia sanguinea Vahl is widespread in African traditional medicine, and exhibits antioxidant, antibacterial, antiviral, and anticancer activities. T. sanguinea is a source of phytomedicinal agents that have previously been isolated and structurally elucidated. Herein, gas chromatography combined with tandem mass spectrometry (GC-MS/MS) was used to quantify epipinoresinol, ß-sitosterol, eriodictyol, betulinic acid, and secoisolariciresinol contents in the methanolic crude extract and its ethyl acetate fraction for the first time. The ethyl acetate fraction was rich in epipinoresinol, eriodictyol, and secoisolariciresinol at concentrations of 2.3, 3.9, and 2.4 mg/g of dry extract, respectively. The binding interactions of these compounds with the epidermal growth factor receptor (EGFR) were computed using a molecular docking study. The results revealed that the highest binding affinities for the EGFR signaling pathway were attributed to eriodictyol and secoisolariciresinol, with good binding energies of -19.93 and -16.63 Kcal/mol, respectively. These compounds formed good interactions with the key amino acid Met 769 as the co-crystallized ligand. So, the ethyl acetate fraction of T. sanguinea is a promising adjuvant therapy in cancer treatments.

An UHPLC/LC-MS illustrated the dynamic profiling of balanophorin B, gallic acid, and 4-hydroxycinnamic acid in rat as 3 molecular entities from Balanophora simaoensis.

An UHPLC/LC-MS was founded to detect balanophorin B (B), gallic acid (GA), 4-hydroxycinnamic acid (HC), and their in vivo profiling in rats, after oral administration of the ethanol extract of Balanophora simaoensis S. Y. Chang et Tam. The in vivo dynamic existence of 3 molecular entities in rats and the multistep biotransformation of GA were elucidated by their sensitive mass spectrometry response after efficient UHPLC and/or HPLC separation, through analyzing the bio-samples of rat plasma, bile, liver, kidneys, and excreta. The method was validated with satisfactory calibration curves having correlation coefficients r from 0.996 to 0.999 for concentration scaled from 0.100 nM to 0.100 µM, internal standard normalized matrix factors ranged from 0.923 to 0.993, sextuplicate recoveries valued from 95.0% to 103.6%, as well as accuracy and precision varied from 95.6% to 103.7%. The content of B, GA, and HC in the whole herb was of 4.66, 63.5, and 10.4 µmol/kg in dry weight, respectively. The Cmax for B, GA, and HC in rat systemic circulation was of 76.0 nM, 2.30 µM, and 51.0 µM, with tmax at 3, 2, and 2 h, respectively. B and GA stayed in rat liver over 4 hs to present a material base for the pharmacology and pharmacodynamics of the whole herb. The biotransformation of GA indicated a complicated scheme in rats. As a final metabolite from GA with total biotransformation conversion over 20%, 4-hydroxybenzaldehyde resourced from two steps of dehydroxylation and one step of reduction of GA, but not concerned with HC.

ITS1 Barcode and Phytochemical Analysis by Gas Chromatography-Mass Spectrometry of Corynaea crassa Hook. f (Balanophoraceae) from Ecuador and Peru.

The use of medicinal plants is the basis of traditional healthcare. Recently, the use of herbal medicine has been increasing among consumers due to availability, economy, and less side effect. For instance, the hemiparasite plant Corynaea crassa has medicinal properties and could be found in some regions of America, from Costa Rica to Bolivia. Phytochemical and genetic characterization of medicinal plants is needed for proper identification of metabolites responsible for medicinal properties and for genotyping, respectively. Moreover, characterization of medicinal plants through the use of DNA barcodes is an important tool for phylogenetic analysis and identification of species; furthermore, complemented with phytochemical analysis, both are useful for identification of plant species and quality control of medicinal products. The objective of this study was to analyze the species of C. crassa collected in Ecuador and Peru from the phylogenetic and phytochemical point of view. Polymerase chain reaction (PCR) was performed for amplification of the internal transcribed spacer 1 (ITS1) region after DNA extraction of samples of C. crassa. Blast analysis was performed in the GenBank database with the ITS1 sequences obtained from two accessions of C. crassa from Ecuador (GenBank accession numbers OM471920 and OM471919 for isolates CIBE-17 and CIBE-18, respectively) and three from Peru (GenBank accession numbers OM471921, OM471922, and OM471923 for isolates CIBE-13, CIBE-14, and CIBE-15, respectively). The accessions available in the GenBank were used for phylogenetic analysis. For the phytochemical analysis, hydroalcoholic extracts were obtained by maceration using 80% ethanol as solvent, followed by a derivatization process and analysis by gas chromatography-mass spectrometry. Based on the phylogenetic analysis of the C. crassa samples, the ITS1 sequence could be used to differentiate C. crassa of different locations. The samples of C. crassa from Ecuador and Peru are more similar between them than with other clades including Helosis spp. The phytochemical study revealed differences in the presence and relative abundance of some metabolites; mainly eugenol, 1,4-lactone arabinonic acid, dimethoxyrabelomycin and azelaic acid, which are reported for the first time for the species under study and the genus Corynaea. These results are the first findings on the combined analysis using genetic and phytochemical analysis for C. crassa, which could be used as a useful tool for quality control of the C. crassa species in medicinal products.

Phytochemical composition and biological screening of two Lophophytum species / Composición fitoquímica y cribado biológico de dos especies de Lophophytum

Lophophytum species are holoparasites that grow on tree roots. The objectives of the work were to explore the chemical composition of the tubers of two Lophophytum species and to analyze the antioxidant, anti-inflammatory and antilithiatic activity of their extracts using in vitro methods. The chemical composition was determined by histochemical, phytochemical and TLC tests. In addition, the profile of phenolic compounds was determined by HPLC-MS. The presence of secondary metabolites of recognized activity was demonstrated. The results of the HPLC-MS/MS allowed the tentative identification of catechin, luteolin and glycosides of eriodictyol, naringenin and luteolin in the extract of Lophophytum leandriand eriodictyol, naringenin, luteolin and their glycosylated derivatives in Lophophytum mirabile. The extracts showed promising antioxidant (DPPH, ABTS and ß-carotene-linoleic acid), anti-inflammatory (inhibition of 5-LOX) and anti-urolytic (by bioautographic TLC) activity. It is noteworthy that these are the first results of the phytochemical composition and biological activity of L. mirabile. However, in vivo studies are required to corroborate these activities.

Las especies de Lophophytumson holoparásitas que crecen en raíces de árboles. Los objetivos del trabajo fueron explorar la composición química del túber de dos especies de Lophophytum y analizar la actividad antioxidante, antiinflamatoria y antilitiásica de sus extractos usando métodos in vitro. La composición química se determinó mediante pruebas histoquímicas, fitoquímicas y por TLC. Además, se determinó el perfil de compuestos fenólicos por HPLC-MS/MS. Se demostró presencia de metabolitos secundarios de reconocida actividad. Los resultados del HPLC-MS/MS permitieron identificar tentativamente catequina, luteolina y glucósidos de eriodictiol, naringenina y luteolina en el extracto de Lophophytum leandriy eriodictiol, naringenina, luteolina y sus derivados glicosilados en Lophophytum mirabile. Los extractos mostraron prometedora actividad antioxidante (DPPH, ABTS y ß-caroteno-ácido linoleico), antiinflammatoria (inhibición de la 5-LOX) y antiurolitiásica (por TLC bioautográfica). Es de destacar que estos son los primeros resultados de composición fitoquímica y actividad biológica de L. mirabile. Sin embargo, se requieren estudios in vivo para corroborar dichas actividades.

Balanophorin B inhibited glycolysis with the involvement of HIF-1α.

AIMS: Cancer cells exhibit a metabolic change called aerobic glycolysis compared with normal cells. Balanophorin B is a terpenoid ingredient reported from the genus Balanophora. In this research, we studied the effect of balanophorin B on glycolysis of HepG2 cells and Huh-7 cells under hypoxia. MAIN METHODS: The Warburg effect was monitored by assessing glucose uptake, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Key enzymes in the glycolytic pathway and HIF-1α protein expression and degradation were analyzed by real-time PCR and western blotting. The anti-cancer effect of balanophorin B in vivo was also investigated. KEY FINDINGS: Balanophorin B inhibited the proliferation, glucose uptake, and ECAR in both HepG2 cells and Huh-7 cells. In addition, balanophorin B inhibited the protein level of HIF-1α and its downstream targets LDHA and HKII under hypoxia, whereas HIF-1α mRNA level did not change after balanophorin B treatment. The HIF-1α plasmid reversed the inhibition of balanophorin B on glycolysis, and the proteasome inhibitor MG132 attenuated the effect of balanophorin B on HIF-1α protein expression, suggesting that balanophorin B might post-transcriptionally affect HIF-1α. Moreover, balanophorin B increased the expression of VHL and PHD2. HIF-1α siRNA also greatly attenuated the inhibitory effect of balanophorin B on HepG2 cells glucose uptake. Balanophorin B significantly inhibited tumor growth in vivo, without causing obvious toxicity to mice. SIGNIFICANCE: These data suggest that balanophorin B inhibits glycolysis probably via an HIF-1α-dependent pathway, and the ubiquitin-proteasome pathway was greatly involved in the induction of balanophorin B on HIF-1α degradation.

New butenolides with anti-inflammatory activity from Balanophora fungosa.

Two new butenolides, balanolides A (1) and B (1), were isolated from the aerial parts of the parasitic plant Balanophora fungosa. Their structures were established by comprehensive spectroscopic analysis and quantum chemical ECD calculation. The new butenolides were evaluated for their inhibitory effects against nitric oxide (NO) production in LPS-induced RAW 264.7 macrophage cells. Compounds 1 and 2 displayed moderate anti-inflammatory activity with IC50values of 11.8 and 12.9 µM, respectively.

Phenolics from the Bolivian highlands food plant Ombrophytum subterraneum (Aspl.) B. Hansen (Balanophoraceae): Antioxidant and α-glucosidase inhibitory activity.

The Balanophoraceae Ombrophytum subterraneum is an endemic highland food plant occurring in Bolivia, northern Argentina and Chile. The upper part of this parasitic plant is eaten fresh. The aim of this work was to characterize the compounds occurring in the edible part and to assess any differences between the inflorescence and tuber. Ethanol extracts of the different plant parts were analyzed for antioxidant activity by the ORAC, TEAC, FRAP, CUPRAC and DPPH methods as well as for the effect on enzymes related to metabolic syndrome (α-amylase, α-glucosidase and pancreatic lipase). The main constituents were isolated by a combination of gel permeation in Sephadex LH-20 and countercurrent chromatography (CCC). Five compounds were isolated and fully identified by spectroscopic and spectrometric means. The new 3',5,5',7-tetrahydroxyflavanone 7-O-ß-D-1 â†’ 6 diglucoside was isolated for the first time. HPLC-ESI-MS/MS analysis allowed the identification of 19 compounds, including flavanones, flavanols, flavonols, dehydroflavonols and lignans, mainly as glycosides. A strong inhibition towards α-glucosidase was observed for the edible parts (IC50: 1.46 µg/mL) as well as for the tuber and inflorescence (IC50: 1.56 µg/mL and 0.87 µg/mL, respectively). A significant correlation was established between the total phenolic and the antioxidant capacity of the extracts as well as with the content of the new flavanone diglucoside. This is the first comprehensive report on the naturally occurring antioxidants and enzyme inhibitors from this native highland food resource.

Anti-neuraminidase activity of chemical constituents of Balanophora involucrata.

Balanophora involucrata J. D. Hooker has been known to possess potential anti-inflammatory and antibacterial activities; however, its antiviral activity has not been evaluated so far. In order to find new neuraminidase inhibitors (NAIs), the neuraminidase (NA) inhibition activity of different B. involucrata extracts was evaluated. In this study, an in vitro NA inhibition assay was performed to identify which extract of B. involucrata exhibits (maximal) inhibitory activity against NA. Ultra high performance liquid chromatography/quadrupole time-of-flight-tandem mass spectroscopy (MS/MS) and molecular docking techniques were used to identify the specific compounds responsible for the anti-influenza activity of the extract, and to explore the potential natural NAIs. The ethyl acetate extract of B. involucrata exhibited significant inhibitory activity against NA with 50% inhibitory concentration (IC50 ) value of 159.5 µg/mL. Twenty compounds were identified according to the MS/MS spectra; among them two compounds (quercitrin and phloridzin) showed obvious inhibitory activity against NA, with IC50 of 311.76 and 347.32 µmol/L, respectively. This study suggested that B. involucrata can be a potential natural source of NAIs and may be useful in the fight against ferocious influenza viruses.

Balanophora polyandra Griff. prevents dextran sulfate sodium-induced murine experimental colitis via the regulation of NF-κB and NLRP3 inflammasome.

Balanophora polyandra Griff. (B. polyandra) is a folk medicine used as an antipyretic, antidote, haemostatic, dressing and haematic tonic, for the treatment of gonorrhea, syphilis, wounds, and the bleeding of the alimentary tract by the local people in China. This study was designed to investigate the effects of B. polyandra on dextran sulfate sodium (DSS)-treated colitis mice in vivo and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro. Mice were induced with B. polyandra total extract (BPE, 250 and 1000 mg kg-1) and B. polyandra polysaccharides (BPP, 100 and 400 mg kg-1) for 22 days and treated with 3.5% DSS in their drinking water for the last 7 days and the LPS-induced RAW264.7 macrophages were treated with BPE (100 µg ml-1) and BPP (100 µg ml-1). Mice treated with DSS developed severe mucosal colitis, with a marked distortion and crypt loss of colonic surface epithelium and a colonic shortening. B. polyandra significantly inhibited colonic shortening and reduced the severity of colitis in the colon and lowered the colonic inflammation score (p < 0.05) and decreased the expression of interleukin (IL)-1ß, tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), and anti-serum amyloid A3 (SAA3) as well as the pro-inflammatory chemokine C-X-C motif chemokine 10 (CXCL10). B. polyandra also significantly suppressed the activation of nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome and the nuclear factor kB (NF-κB). These results suggest that dietary intake of B. polyandra ameliorates colitis. Such activities of B. polyandra in humans remain to be investigated.

Polysaccharides derived from Balanophora polyandra significantly suppressed the proliferation of ovarian cancer cells through P53-mediated pathway.

Ovarian cancer (OC) is ranked the first among the cancers threatening women's health. It attracts tremendous attention of cancer researchers because of its extremely high mortality rate. Recent studies have indicated that traditional herbal medicines (THMs) can play a pivotal role in cancer prevention and treatment. THMs are gaining popularity as a source of anti-cancer agents. The plant of Balanophora polyandra, which has been used as a traditional herbal medicine, has been known for exhibiting potential haemostatic, analgesic, anti-inflammatory and anti-cancer properties. However, few studies on inhibitory effect of B. polyandra on OC have been performed. In the present study, we found that B. polyandra polysaccharides (BPP) induced cell cycle arrest at S phase, triggered apoptosis and inhibited migration and invasion of OC cells. Furthermore, we also found that there was a potential and close relationship between BPP and P53-mediated pathway. Overall, these findings suggest that BPP can be a potential therapeutic agent for the treatment of OC.

Purification of thonningianins A and B and four further derivatives from Thonningia sanguinea by one- and two-dimensional centrifugal partition chromatography.

Thonningia sanguinea is a parasitic herb widely used in traditional African medicine. Dihydrochalcone glucosides (unsubstituted, substituted with hexahydroxydiphenoyl or galloyl moieties) are the main constituents in the subaerial parts of this plant. In the present study, purification of the six major compounds from a methanol extract of the plant's subaerial parts was achieved by centrifugal partition chromatography. A first dimension centrifugal partition chromatography separation with the solvent system methyl tert-butyl ether/1,2-dimethoxyethane/water (1:2:1) in the ascending mode enabled the isolation of the two major bioactive compounds thonningianin A and B from 350 mg of methanol extract within only 16 min with respectable yields (25.7 and 21.1 mg), purities (87.1 and 85%), and recoveries (71.2 and 70.4%). Using a multiple heart-cutting strategy, the remaining four major dihydrochalcone glucosides of the extract were further separated in a second dimension centrifugal partition chromatography with the solvent system ethyl acetate/1,2-dimethoxyethane/water (2:1:1) in the descending mode with high purities (88.9-98.8%).

Development and Validation of a UHPLC-DAD Method for the Quantitative Analysis of Major Dihydrochalcone Glucosides from Thonningia sanguinea VAHL.

Thonnigia sanguinea is a plant widely used in traditional African medicine against a variety of diseases. The obligate parasite is growing throughout tropical African forests and utilizes a large variety of hosts. Dihydrochalcone glucoside derivatives isolated from the subaerial parts of this plant were identified as potential antidiabetic lead compounds. In this study, an ultrahigh-performance liquid chromatographic method coupled with a photodiode array detector was developed for the quantitation of six major dihydrochalcone derivatives. The analytes were baseline separated in complex samples within 14 minutes on a Phenomenex Luna Omega 1.6 µm C18 column using a mobile phase consisting of water and acetonitrile (each + 0.01% trifluoroacetic acid) in gradient elution. Method validation confirmed the selectivity, linearity (R2 ≥ 0.9992), precision (inter-day ≤ 1.98%, intraday ≤ 2.00%), and accuracy (recovery rates of 97.4 - 106.3% for all analytes). At 280 nm, the LODs and LOQs were found to be lower than 1.42 and 4.30 µg/mL, respectively. Eight plant batches from the northern Angolan province of Uíge (collected in the wild or bought on markets) were extracted with methanol using an ultrasound-assisted extraction protocol and subsequently analyzed with the validated method. Results indicated high contents of dihydrochalcone glucosides in all eight samples. Most notably, the two bioactive constituents thonningianin A and B were present in fairly large amounts (2.42 - 5.35 w%).

Efecto del extracto de Corynaea crassa y selenio en la disfunción sexual inducida en Rattus norvegicus albinus / Effect of Corynaea crassa and Selenium extract on sexual dysfunction induced in rats

Introducción. Corynaea crassa es una planta hemiparásita usada como afrodisíaco en la medicina tradicional. Objetivo. Determinar el efecto erectógeno del extracto etanólico de las raíces de Corynaea crassa (EECC) y selenio en la disfunción sexual inducidas en roedores. Materiales y métodos. Investigación de diseño experimental, preclínico, in vivo, llevado a cabo en el Laboratorio de Farmacología Experimental de la Facultad de Medicina Humana-UNMSM, Lima, Perú. Se emplearon raíces de «viagra macho¼ colectada en el departamento de Cajamarca; ratas machos de dos meses, de 150 ­ 200 g; 42 animales se dividieron al azar en siete grupos: 1). SSF 5 mL/kg; 2). Sildenafilo 5 mg/kg/día; 3). EECC 100mg/kg; grupo 4 EECC 200 mg/kg; grupo 5 EECC 400 mg/kg; grupo 6 EECC 200mg/kg + Se 1 ug/kg y grupo 7 EECC 400 mg/kg + Se 1 ug/kg. Se evaluaron los parámetros del comportamiento sexual, reflejos del pene y nivel de testosterona. Resultados. Por análisis cualitativo se identificaron alcaloides, compuestos fenólicos, esteroides/terpenoides, flavonoides, lactonas, saponinas y taninos. El comportamiento sexual fue dosis dependiente; la administración de 400 mg/kg de EECC + Se 1 ug/kg por vía oral incrementó la frecuencia de monta, en tanto que la dosis de 100 mg/kg aumentó la frecuencia de intromisión (p<0,05), así como los parámetros de los reflejos del pene e incremento significativo de los niveles de testosterona. Conclusiones. Se ha demostrado efecto erectógeno del extracto etanólico de las raíces de Corynaea crassa más selenio en la disfunción sexual inducidas en ratas.

Introduction. Corynaea crassa, a hemiparasitic plant used as an aphrodisiac in traditional medicine. Objective. To determine the erectógeno effect of the ethanolic extract of the roots of Corynaea crassa (EECC) and Selenio in the sexual dysfunction induced in rats. Design. Experimental, Pre-clinical, "In vivo". Setting. Laboratory of Experimental Pharmacology, Faculty of Human Medicine-UNMSM, Lima, Peru. Biological material. Roots of "male Viagra", male rats of 2 months, 150-200 g. Interventions. The plant was collected in the department of Cajamarca; 42 animals divided randomly into 7 groups: 1) SSF 5 mL / kg; 2) Sildenafil 5 mg / kg / day; 3) EECC 100 mg / kg; groups 4 EECC 200mg / kg; groups 5 EECC 400 mg/kg; groups 6 EECC 200 mg / kg + Se 1ug / kg and groups 7 EECC 400 mg / kg + Se 1ug/kg. Main outcome measures. The parameters of sexual behavior, penile reflexes and testosterone level were evaluated. Results. For qualitative analysis, alkaloids, phenolic compounds, steroids / terpenoids, flavonoids, lactones, saponins and tannins were identified. The sexual behavior was dose dependent; the administration of 400 mg / kg of EECC + Se 1ug / kg orally increased the frequency of mounting, while the dose of 100 mg / kg increased the frequency of intrusion (p <0.05), as well as the parameters of the reflexes of the penis and significant increase in testosterone levels. Conclusions. The best results were observed in the doses of 200 mg / kg and 400 mg / kg of the EECC in combination with Selenium.

Dihydrochalcone Glucosides from the Subaerial Parts of Thonningia sanguinea and Their in Vitro PTP1B Inhibitory Activities.

Six new and four known dihydrochalcone glucoside derivatives (1-10), the phenylpropanoid coniferin (11), and the lignans (+)-pinoresinol (12) and lariciresinol (13) were isolated from the subaerial plant parts of Thonningia sanguinea in the course of a screening campaign for new antidiabetic lead compounds. The structures of the new substances were elucidated by HRESIMS, NMR, GC-MS, and ECD data evaluation. 2'- O-(3-Galloyl-4,6- O- Sa-hexahydroxydiphenoyl-ß-d-glucopyranosyl)-3-hydroxyphloretin (4), 2'- O-(4,6- O- Sa-hexahydroxydiphenoyl-ß-d-glucopyranosyl)phloretin (5), 2'- O-(3- O-galloyl-4,6- O- Sa-hexahydroxydiphenoyl-ß-d-glucopyranosyl)phloretin (6), and thonningianin B (9) showed moderate protein tyrosine phosphatase-1B inhibition in an enzyme assay (IC50 values ranging from 19 to 25 µM), whereas thonningianin A (10) was identified as a more potent inhibitor (IC50 = 4.4 µM). The observed activity differences could be explained by molecular docking experiments. The activity of 10 could further be confirmed in HEPG2 liver carcinoma cells, where the compound was able to increase the level of phosphorylated insulin receptors in a concentration-dependent manner.

Phenolic acids from Balanophora involucrata and their bioactivities.

The bioactive substance investigation of Balanophora involucrata obtained 15 phenolic acids, including 5 new compounds (1-3, 8, 9), which were determined by various spectroscopic data analyses. Most isolated compounds displayed inhibitory effects on α-Glucosidase in vitro. For the potential inhibitors 8 (1.95µM) and 10 (9.02µM), the inhibition kinetics have been studied, which gave the Ki values as 0.68, 3.15µM respectively. And, in silico docking analyses have been performed to investigate the inhibitory mechanism of compounds 8 and 10. Additionally, most isolated compounds showed anti-oxidant activities in the DPPH scavenging assay. New compound 8 also could inhibit the acetyl transfer activity of GlmU moderately with the IC50 value of 18.21µM, which was a new antibacterial target.

A lost link between a flightless parrot and a parasitic plant and the potential role of coprolites in conservation paleobiology.

Late Quaternary extinctions and population fragmentations have severely disrupted animal-plant interactions globally. Detection of disrupted interactions often relies on anachronistic plant characteristics, such as spines in the absence of large herbivores or large fruit without dispersers. However, obvious anachronisms are relatively uncommon, and it can be difficult to prove a direct link between the anachronism and a particular faunal taxon. Analysis of coprolites (fossil feces) provides a novel way of exposing lost interactions between animals (depositors) and consumed organisms. We analyzed ancient DNA to show that a coprolite from the South Island of New Zealand was deposited by the rare and threatened kakapo (Strigops habroptilus), a large, nocturnal, flightless parrot. When we analyzed the pollen and spore content of the coprolite, we found pollen from the cryptic root-parasite Dactylanthus taylorii. The relatively high abundance (8.9% of total pollen and spores) of this zoophilous pollen type in the coprolite supports the hypothesis of a former direct feeding interaction between kakapo and D. taylorii. The ranges of both species have contracted substantially since human settlement, and their present distributions no longer overlap. Currently, the lesser short-tailed bat (Mystacina tuberculata) is the only known native pollinator of D. taylorii, but our finding raises the possibility that birds, and other small fauna, could have once fed on and pollinated the plant. If confirmed, through experimental work and observations, this finding may inform conservation of the plant. For example, it may be possible to translocate D. taylorii to predator-free offshore islands that lack bats but have thriving populations of endemic nectar-feeding birds. The study of coprolites of rare or extinct taxonomic groups provides a unique way forward to expand existing knowledge of lost plant and animal interactions and to identify pollination and dispersal syndromes. This approach of linking paleobiology with neoecology offers significant untapped potential to help inform conservation and restoration plans.

BACE inhibitory flavanones from Balanophora involucrata Hook. f.

One new flavanone (S)-5,7,3',5'-tetrahydroxy-flavanone-7-O-(6″-galloyl)-ß-D-glucopyranose (1), together with one known flavanone and four known dihydrochalcones were isolated from the ethyl acetate partitions from an alcoholic extract of the whole plant of Balanophora involucrata Hook. f. All of the compounds were characterized by spectroscopic methods. Their in vitro BACE inhibitory effects were evaluated. Compounds 1, 2, 4, and 5 were found to be a little more active than the positive control, although all of which are below 50% inhibition at 10µM.

Diuretic activity of Lophophytum leandri.

A bioassay-oriented study was carried-out in order to validate the traditional uses of Lophophytum leandri, a parasitic plant used as a diuretic in traditional medical practices of Argentina. Four known flavonoids have been isolated from the active fraction. Quercetin-3-O-beta-D-glucopyranoside was identified as the active principle of the fraction. However, the diuretic activity of the extract and of the most active fraction had greater activity than that of the pure isolated compounds.

Melanin synthesis inhibitors from Balanophora fungosa.

Tyrosinase, trypsin, and tryptase are known to play important roles in melanin production of human skin. This paper describes the study of the inhibitory effect of Balanophora fungosa on melanin. The 50% EtOH extract obtained from B. fungosa indicated an inhibitory effect on mushroom tyrosinase activity with an IC(50) value of 15 µg/mL. Bioassay-guided fractionation of the active extract resulted in the isolation of four known compounds. Their structures were identified as 1-O-(E)-caffeoyl-3-O-galloyl-4,6-(S)-HHDP-ß-d-glucopyranose (1), 1-O-(E)-caffeoyl-3,4,6-tri-O-galloyl-ß-d-glucopyranose (2), caffeoyl-ß-d-glucopyranose (3), and abietin (4) on the basis of spectroscopic analyses and comparison of their spectral data with those in the literature. Compounds 1 and 2 prevented pigmentation of melanin in a three-dimensional cultured human skin model. Furthermore, compounds 1 and 2 indicated inhibitory activities against trypsin and tryptase.