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Abstract Background Owing to antibiotic resistance, alternative antimicrobials from medicinal plants are receiving attention as leads for anti-infective agents. This study aimed to investigate selected tree species and their constituents for activity against bacterial foodborne pathogens, particularly Salmonella serovars. Methods Antibacterial activity of ten plant species was determined by serial microdilution against bacteria implicated in causing gastrointestinal ailments. Active compounds were isolated from Loxostylis alata using bioassay-guided fractionation. Antioxidant activity was determined using free-radical scavenging assays. Cytotoxicity and genotoxicity of the extracts was ascertained on Vero cells, and using the Ames assay respectively. Results Extracts had low to moderate MIC values from 0.04 to 2.5 mg/mL. Protorhus longifolia and Loxostylis alata were most active and L. alata had the highest selectivity index value (2.51) against Salmonella Typhimurium, as well as high antioxidant activity. Cytotoxicity values ranged from 0.02 to 0.47 mg/mL, while tested extracts were not genotoxic. Bioactive compounds isolated from L. alata included delicaflavone and a polymethoxyflavone. Conclusions The Loxostylis alata leaf extract had strong activity against Salmonella serovars but isolated compounds were less active, indicating likely synergistic effects. Extracts of L. alata are promising candidates for development of antimicrobial preparations or food additives against microbial contamination.

Objectives: The present study was to isolate the biflavonoid (a bimolecular kaemferol structured molecule) and test its efficacy on oxidative stress and carbohydrate metabolic key enzymes in control and high fat diet and streptozotocin -induced diabetic rats. Methods: Type 2 diabetes was induced in male albino wistar rats by feeding them with high fat diet comprising of 84.3% standard laboratory chow, 5% lard, 10% yolk powder, cholesterol 0.2%, and 0.5% bile salt for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (35 mg/kg, dissolved in 0.1 M sodium citrate buffer, pH 4.5). Results: At the end of the experimental period, diabetic control rats showed significant increase in plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c) with concomitant decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism, lipid peroxidation markers, antioxidant enzymes, glycogen content and glycogen synthase and glycogen phosphorylase were also altered in diabetic rats. Discussion: Oral administration of biflavonoid to diabetic rats significantly ameliorated all the biochemical alterations to near normal levels. The effect produced by the biflavonoid on various parameters was comparable to that of metformin.

Background: Activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in gout. Selaginella moellendorffii has been confirmed effective for the treatment of gout in hospital preparations. Flavonoids, such as amentoflavone (AM), are the main active components of this medicine.Purpose: We aimed to investigate the flavonoid extract (TF) and AM's effects on NLRP3 inflammasome in vitro and their preventive effects on gout in vivo.Methods: LC-MS method was employed to investigate the chemical profile of TF. The cellular inflammation model was established by lipopolysaccharide (LPS) or monosodium urate (MSU) stimulation. The cell membrane integrality and morphological characteristics were determined by using Lactate dehydrogenase (LDH) assay kits, propidium iodide (PI) stain, and scanning electron microscopy (SEM). The inflammatory cytokines and NLRP3 inflammasome activation were determined using enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-PCR), immunofluorescence staining, and western blotting. The acute gout mouse model was induced by MSU injection into footpads, and then the paw edema, inflammatory mediators, and histological examination (HE) were analyzed.Results: The main constituents in TF are AM and robustaflavone. In the cellular inflammation model, TF down-regulated the levels of nitric oxide (NO), TNF-α, and LDH, suppressed NLRP3 inflammasome-derived interleukin-1β (IL-1β) secretion, decreased caspase-1 activation, repressed mature IL-1β expression, inhibited ASC speck formation and NLRP3 protein expression. In an acute gout mouse model, oral administration of TF to mice effectively alleviated paw edema, reduced inflammatory features, and decreased the levels of IL-1β in mouse foot tissue. Similarly, the characteristic constituent AM was also able to down-regulated the levels of NO, TNF-α, and LDH, down-regulate the mRNA expression of IL-1β, TNF-α, caspase-1, and NLRP3. Besides, the foot thickness, lymphocyte infiltration, and IL-1β level were also prevented by AM.Conclusion: The results indicated that TF and its main constituent AM alleviate gout arthritis via NLRP3/ASC/Caspase-1 axis suppression.

The methanolic extract from the flowers of Mesua ferrea Linn. (Calophyllaceae) showed significant hyaluronidase inhibitory activity. Following a bioassay-guided separation of the extract, two biflavonoids, viz., mesuaferrone-A (1) and mesuaferrone-B (2), were isolated, along with ten flavonoids (3–12), two xanthones (13 and 14), three triterpenes (15–17), a phenylpropanoid (18), and five aromatics (19–24). Among the isolates, 1 and 2 (IC50 = 51.1 µM and 54.7 µM, respectively) exhibited hyaluronidase inhibitory activity equivalent to that of the commercially available antiallergic agents disodium cromoglycate (64.8 μM) and ketotifen fumarate (76.5 μM). These biflavonoids (1 and 2) are 8-8″ linked dimers that are composed of naringenin (1a) or apigenin (3), with their corresponding monomers lacking inhibitory activity (IC50 > 300 μM). In addition, 1 and 2 (IC50 = 49.4 µM and 49.2 µM, respectively) inhibited the release of β-hexosaminidase, which is a marker of antigen-IgE-mediated degranulation, in rat basophilic leukemia (RBL-2H3) cells. These inhibitory activities were more potent than those of the antiallergic agents tranilast and ketotifen fumarate (IC50 = 282 μM and 158 μM, respectively), as well as one of the corresponding monomers (1a; IC50 > 100 μM). Nonetheless, these effects were weaker than those of the other monomer (3; IC50 = 6.1 μM).

Treatment of leishmaniasis is a challenging subject. Although available, chemotherapy is limited, presenting toxicity and adverse effects. New drugs with antileishmanial activity are being investigated, such as antiparasitic compounds derived from plants. In this work, we investigated the antileishmanial activity of the biflavonoid amentoflavone on the protozoan Leishmania amazonensis. Although the antileishmanial activity of amentoflavone has already been reported in vitro, the mechanisms involved in the parasite death, as well as its action in vivo, remain unknown. Amentoflavone demonstrated activity on intracellular amastigotes in macrophages obtained from BALB/c mice (IC50 2.3 ± 0.93 μM). No cytotoxicity was observed and the selectivity index was estimated as greater than 10. Using BALB/c mice infected with L. amazonensis we verified the effect of an intralesional treatment with amentoflavone (0.05 mg/kg/dose, in a total of 5 doses every 4 days). Parasite quantification demonstrated that amentoflavone reduced the parasite load in treated footpads (46.3% reduction by limiting dilution assay and 56.5% reduction by Real Time Polymerase Chain Reaction). Amentoflavone decreased the nitric oxide production in peritoneal macrophages obtained from treated animals. The treatment also increased the expression of ferritin and decreased iNOS expression at the site of infection. Furthemore, it increased the production of ROS in peritoneal macrophages infected in vitro. The increase of ROS in vitro, associated with the reduction of NO and iNOS expression in vivo, points to the antioxidant/prooxidant potential of amentoflavone, which may play an important role in the balance between inflammatory and anti-inflammatory patterns at the infection site. Taken together these results suggest that amentoflavone has the potential to be used in the treatment of cutaneous leishmaniasis, working as an ally in the control and development of the lesion.

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, with approximately 6–7 million people infected worldwide, becoming a public health problem in tropical countries, thus generating an increasing demand for the development of more effective drugs, due to the low efficiency of the existing drugs. Aiming at the development of a new antichagasic pharmacological tool, the density functional theory was used to calculate the reactivity descriptors of amentoflavone, a biflavonoid with proven anti-trypanosomal activity in vitro, as well as to perform a study of interactions with the enzyme cruzain, an enzyme key in the evolutionary process of T-cruzi. Structural properties (in solvents with different values of dielectric constant), the infrared spectrum, the frontier orbitals, Fukui analysis, thermodynamic properties were the parameters calculated from DFT method with the monomeric structure of the apigenin used for comparison. Furthermore, molecular docking studies were performed to assess the potential use of this biflavonoid as a pharmacological antichagasic tool. The frontier orbitals (HOMO-LUMO) study to find the band gap of compound has been extended to calculate electron affinity, ionization energy, electronegativity electrophilicity index, chemical potential, global chemical hardness and global chemical softness to study the chemical behaviour of compound. The optimized structure was subjected to molecular Docking to characterize the interaction between amentoflavone and cruzain enzyme, a classic pharmacological target for substances with anti-gas activity, where significant interactions were observed with amino acid residues from each one's catalytic sites enzyme. These results suggest that amentoflavone has the potential to interfere with the enzymatic activity of cruzain, thus being an indicative of being a promising antichagasic agent.

3CL protease is one of the key proteins expressed by SARS-Coronavirus-2 cell, the potential to be targeted in the discovery of antivirus during this COVID-19 pandemic. This protein regulates the proteolysis of viral polypeptide essential in forming RNA virus. 3CL protease (3CLpro) was commonly targeted in the previous SARS-Coronavirus including bat and MERS, hence, by blocking this protein activity, the coronavirus should be eradicated. This study aims to review the potency of biflavonoid as the SARS-Coronavirus-2 3CLpro inhibitor. The review was initiated by describing the chemical structure of biflavonoid and followed by listing its natural source. Instead, the synthetic pathway of biflavonoid was also elaborated. The 3CLpro structure and its function were also illustrated followed by the list of its 3D-crystal structure available in a protein data bank. Lastly, the pharmacophores of biflavonoid have been identified as a protease inhibitor, was also discussed. This review hopefully will help researchers to obtain packed information about biflavonoid which could lead to the study in designing and discovering a novel SARS-Coronavirus-2 drug by targetting the 3CLpro enzyme.

Acute systemic inflammatory diseases, including sepsis, usually result in cytokine disorder and multiple-organ failure. 7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus x media var. Hicksii, has previously been evaluated for its antiproliferative and antineoplastic effects in cancer cells. In this study, the effects of DMGF on the cytokine production and cell migration of inflammatory macrophages were investigated. The inhibition of cytokine and chemokine production by DMGF in LPS-treated macrophages was analyzed by a multiplex cytokine assay. Then, the integrin molecules used for cell adhesion and regulators of actin polymerization were observed by RT-PCR and recorded using confocal imaging. The DMGF interaction with estrogen receptor α (ERα) was modeled structurally by molecular docking and validated by an ERα reporter assay. DMGF inhibited TNF-α, IL-1β, and IL-6 production in LPS-induced macrophages. DMGF also inhibited inflammatory macrophage migration by downregulating the gene and protein expression of adhesion molecules (LFA-1 and VLA4) and regulators of actin assembly (Cdc42-Rac1 pathway). DMGF might interact with the ligand-binding domain of ERα and downregulate its transcriptional activity. These results indicated that DMGF effectively inhibited the production of proinflammatory cytokines and the recruitment of inflammatory cells through downregulating ERα signaling.

Four new biflavonoids (1–4) were isolated from Selaginella doederleinii together with a known biflavonoid derivative (5). Their structures contained a rare linker of individual flavones to each other by direct C-3-O-C-4′′′ bonds, and were elucidated by extensive spectroscopic data, including HRESIMS, NMR and ECD data. All isolates significantly inhibited the proliferation of NSCLC cells (IC50 = 2.3–8.4 μM) with low toxicity to non-cancer MRC-5 cells, superior to the clinically used drug DDP. Furthermore, the most active compound 3 suppressed XIAP and survivin expression, promoted upregulation of caspase-3/cleaved-caspase-3, as well as induced cell apoptosis and cycle arrest in A549 cells. Together, our findings suggest that 3 may be worth studying further for intervention of NSCLC.

Members of the Psilotales (whisk ferns) have a unique anatomy, with conducting tissues but lacking true leaves and roots. Based on recent phyogenies, these features appear to represent a reduction from a more typical modern fern plant rather than the persistence of ancestral features. In this study, extracts of several Psilotum organs and tissues were analyzed by Gas Chromatography – Mass Spectrometry (GC-MS) and High Performance Liquid Chromatography – Quadrupole Time of Flight – Mass Spectrometry (HPLC-QTOF-MS). Some arylpyrones and biflavonoids had previously been reported to occur in Psilotum and these metabolite classes were found to be prominent constituents in the present study. Some of these were enriched and further characterized by Nuclear Magnetic Resonance (NMR) spectroscopy. HPLC-QTOF-MS and NMR data were searched against an updated Spektraris database (expanded by incorporating over 300 new arylpyrone and biflavonoid spectral records) to aid significantly with peak annotation. Principal Component Analysis (PCA) with combined GC-MS and HPLC-QTOF-MS data sets obtained with several Psilotum organs and tissues indicated a clear separation of the sample types. The principal component scores for below-ground rhizome samples corresponded to the vectors for carbohydrate monomers and dimers and small organic acids. Above-ground rhizome samples had principal component scores closer to the direction of vectors for arylpyrone glycosides and sucrose (which had high concentrations in above-and below-ground rhizomes). The unique position of brown synangia in a PCA plot correlated with the vector for biflavonoid glycosides. Principal component scores for green and yellow synangia correlated with the direction of vectors for arylpyrone glycosides and biflavonoid aglycones. Localization studies with cross sections of above-ground rhizomes, using Matrix-Assisted Laser Desorption/Ionization – Mass Spectrometry (MALDI-MS), provided evidence for a preferential accumulation of arylpyrone glycosides and biflavonoid aglycones in cells of the chlorenchyma. Our results indicate a differential localization of metabolites with potentially tissue-specific functions in defenses against biotic and abiotic stresses. The data are also a foundation for follow-up work to better understand chemical diversity in the Psilotales and other members of the fern lineage.

Like flavonoids, biflavonoids, dimeric flavonoids, and polyphenolic plant secondary metabolites have antioxidant, antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. However, there is limited data on their effects on cytochrome P450 (P450) and uridine 5′-diphosphoglucuronosyl transferase (UGT) enzyme activities. In this study we evaluate the inhibitory potential of five biflavonoids against nine P450 activities (P450s1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A) in human liver microsomes (HLMs) using cocktail incubation and liquid chromatography-tandem mass spectrometry (LC–MS/MS). The most strongly inhibited P450 activity was CYP2C8-mediated amodiaquine N-dealkylation with IC50 ranges of 0.019~0.123 μM. In addition, the biflavonoids—selamariscina A, amentoflavone, robustaflavone, cupressuflavone, and taiwaniaflavone—noncompetitively inhibited CYP2C8 activity with respective Ki values of 0.018, 0.083, 0.084, 0.103, and 0.142 μM. As selamariscina A showed the strongest effects, we then evaluated it against six UGT isoforms, where it showed weaker inhibition (UGTs1A1, 1A3, 1A4, 1A6, 1A9, and 2B7, IC50 > 1.7 μM). Returning to the P450 activities, selamariscina A inhibited CYP2C9-mediated diclofenac hydroxylation and tolbutamide hydroxylation with respective Ki values of 0.032 and 0.065 μM in a competitive and noncompetitive manner. However, it only weakly inhibited CYP1A2, CYP2B6, and CYP3A with respective Ki values of 3.1, 7.9, and 4.5 μM. We conclude that selamariscina A has selective and strong inhibitory effects on the CYP2C8 and CYP2C9 isoforms. This information might be useful in predicting herb-drug interaction potential between biflavonoids and co-administered drugs mainly metabolized by CYP2C8 and CYP2C9. In addition, selamariscina A might be used as a strong CYP2C8 and CYP2C9 inhibitor in P450 reaction-phenotyping studies to identify drug-metabolizing enzymes responsible for the metabolism of new chemicals.

Stellera chamaejasme L. (Thymelaeaceae) is widely distributed in Mongolia, Tibet and the northern parts of China. Its roots are commonly used as “Langdu”, which is embodied in the Pharmacopoeia of the P.R. China (2010) as a toxic Traditional Chinese Medicine. It is claimed to have antivirus, antitumor and antibacterial properties in China and other Asian countries. Studies were carried out to characterize the inhibition of neochamaejasmin B (NCB) on P-glycoprotein (P-gp, ABCB1, MDR1). Rhodamine-123 (R-123) transport and accumulation studies were performed in MDCK-hMDR1 cells. ABCB1 (MDR1) mRNA gene expression and P-gp protein expression were analyzed. Binding selectivity studies based on molecular docking were explored. R-123 transport and accumulation studies in MDCK-hMDR1 cells indicated that NCB inhibited the P-gp-mediated efflux in a concentration-dependent manner. RT-PCR and Western blot demonstrated that the P-gp expression was suppressed by NCB. To investigate the inhibition type of NCB on P-gp, Ki and Ki’ values were determined by double-reciprocal plots in R-123 accumulation studies. Since Ki was greater than Ki’, the inhibition of NCB on P-gp was likely a mixed type of competitive and non-competitive inhibition. The results were confirmed by molecular docking in our current work. The docking data indicated that NCB had higher affinity to P-gp than to Lig1 ((S)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one).

The accumulation of oxidized ApoB-100-containing lipoproteins in the vascular intima and its subsequent recognition by macrophages results in foam cell formation and inflammation, key events during atherosclerosis development. Agents targeting this process are considered potentially atheroprotective. Since natural biflavonoids exert antioxidant and anti-inflammatory effects, we evaluated the atheroprotective effect of biflavonoids obtained from the tropical fruit tree Garcinia madruno. To this end, the pure biflavonoid aglycones morelloflavone (Mo) and volkensiflavone (Vo), as well as the morelloflavone’s glycoside fukugiside (Fu) were tested in vitro in primary macrophages, whereas a biflavonoid fraction with defined composition (85% Mo, 10% Vo, and 5% Amentoflavone) was tested in vitro and in vivo. All biflavonoid preparations were potent reactive oxygen species (ROS) scavengers in the oxygen radical absorbance capacity assay, and most importantly, protected low-density lipoprotein particle from both lipid and protein oxidation. In biflavonoid-treated macrophages, the surface expression of the oxidized LDL (oxLDL) receptor CD36 was significantly lower than in vehicle-treated macrophages. Uptake of fluorescently labeled oxLDL and cholesterol accumulation were also attenuated in biflavonoid-treated macrophages and followed a pattern that paralleled that of CD36 surface expression. Fu and Vo inhibited oxLDL-induced ROS production and interleukin (IL)-6 secretion, respectively, whereas all aglycones, but not the glucoside Fu, inhibited the secretion of one or more of the cytokines IL-1β, IL-12p70, and monocyte chemotactic protein-1 (MCP-1) in lipopolysaccharide (LPS)-stimulated macrophages. Interestingly, in macrophages primed with low-dose LPS and stimulated with cholesterol crystals, IL-1β secretion was significantly and comparably inhibited by all biflavonoid preparations. Intraperitoneal administration of the defined biflavonoid fraction into ApoE−/− mice was atheroprotective, as evidenced by the reduction of the atheromatous lesion size and the density of T cells and macrophages infiltrating the aortic root; moreover, this treatment also lowered the circulating levels of cholesterol and the lipid peroxidation product malondialdehyde. These results reveal the potent atheroprotective effects exerted by biflavonoids on key events of the oxLDL–macrophage interphase: (i) atheroligand formation, (ii) atheroreceptor expression, (iii) foam cell transformation, and (iv) prooxidant/proinflammatory macrophage response. Furthermore, our results also evidence the antioxidant, anti-inflammatory, hypolipemiant, and atheroprotective effects of Garcinia madruno’s biflavonoids in vivo.

(+)-Morelloflavone (MF) is an antitumor biflavonoid that is found in the Garcinia species. Recently, we reported MF as a novel inhibitor of ATPase and microtubules-gliding activities of the kinesin spindle protein (Eg5) in vitro. Herein, we provide dynamical insights into the inhibitory mechanisms of MF against Eg5, which involves binding of the inhibitor to the loop5/α2/α3 allosteric pocket. Molecular dynamics simulations were carried out for 100 ns on eight complexes: Eg5-Adenosine diphosphate (Eg5-ADP), Eg5-ADP-S-trityl-l-cysteine (Eg5-ADP-STLC), Eg5-ADP-ispinesib, Eg5-ADP-MF, Eg5-Adenosine triphosphate (Eg5-ATP), Eg5-ATP-STLC, Eg5-ATP-ispinesib, and Eg5-ATP-MF complexes. Structural and energetic analyses were done using Umbrella sampling, Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) method, GROMACS analysis toolkit, and virtual molecular dynamics (VMD) utilities. The results were compared with those of the known Eg5 inhibitors; ispinesib, and STLC. Our data strongly support a stable Eg5-MF complex, with significantly low binding energy and reduced flexibility of Eg5 in some regions, including loop5 and switch I. Furthermore, the loop5 Trp127 was trapped in a downward position to keep the allosteric pocket of Eg5 in the so-called “closed conformation„, comparable to observations for STLC. Altered structural conformations were also visible within various regions of Eg5, including switch I, switch II, α2/α3 helices, and the tubulin-binding region, indicating that MF might induce modifications in the Eg5 structure to compromise its ATP/ADP binding and conversion process as well as its interaction with microtubules. The described mechanisms are crucial for understanding Eg5 inhibition by MF.

As a new and green solvent, ionic liquids (ILs) have received more attention during the green extraction and separation process for natural medicines. In this paper, IL-ultrasound-assisted extraction (IL-UAE) of total biflavonoids (TBFs) from Selaginella helvetica was firstly developed, and different ILs were employed and compared. Based on single-factor experiment, solid⁻liquid ratio (1:10⁻1:14 g/mL), IL concentration (0.6⁻1.0 mmol/mL), and extract temperature (40⁻60 °C) were further explored, according to response surface methodology (RSM), with TBF yields as the index. Moreover, antioxidant activity of TBF extract was analyzed by four methods, i.e., 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzth-iazoline-6-sulphonate (ABTS) free radical scavenging assay, ferric ion reducing power assay, and chelation of ferrous ions assay. The results indicated that [C6mim]PF6 had a high selectivity and efficiency. Moreover, important parameters for the extraction process were investigated and optimized. Through parameter optimization (0.8 mmol/L, 250 W, 40 min, 1:12.7 g/mL, and 47 °C), a yield of 18.69 mg/g biflavonoids was obtained from the extract of S. helvetica. Compared with ethanol-UAE, heat-reflux extraction, Soxhlet extraction, and percolation extraction, IL-UAE could not only obtain higher yield in a shorter time, but also reduce the solvent consumption. In addition, TBF extract showed potential antioxidant activity based on the above four antioxidant methods. In short, IL-UAE was first employed to develop a novel and green extraction method for TBF content, and this experiment provides valuable references for further utilization of S. helvetica.

Shells are by-products of oil production from Camellia oleifera which have not been harnessed effectively. The purpose of this research is to isolate flavonoid from shells of Camellia oleifera and evaluate its anti-inflammatory and analgesic effects. The flavonoid was identified as bimolecular kaempferol structure by UV, MS, 1H NMR and 13C NMR spectra, which is a new biflavonoid and first found in Camellia oleifera. It showed dose-dependent anti-inflammatory activity by carrageenin-induced paw oedema in rats and croton oil induced ear inflammation in mice, and analgesic activity by hot plate test and acetic acid induced writhing. The mechanism of anti-inflammation of biflavonoid is related to both bradykinin and prostaglandins synthesis inhibition. The biflavonoid showed both central and peripheral analgesic effects different from aspirin, inhibition of the synthesis or action of prostaglandins may contribute to analgesic effect of biflavonoid. The biflavonoid significantly decreased malonaldehyde (MDA) and increased superoxidase dismutase (SOD) and Glutathione peroxidase (GSH-Px) activity in serum (p < 0.01), revealed strong free radical scavenging activity in vivo. It indicates the biflavonoid can control inflammation and pain by eliminating free radical so as to inhibit the mediators and decrease the prostaglandins. The biflavonoid can be used as a prospective medicine for inflammation and pain.

The methanol extract of the leaves of Garcinia nervosa var. pubescens King, which showed strong inhibitory effects on platelet-activating factor (PAF) receptor binding, was subjected to bioassay-guided isolation to obtain a new biflavonoid, II-3,I-5, II-5,II-7,I-4',II-4'-hexahydroxy-(I-3,II-8)-flavonylflavanonol together with two known flavonoids, 6-methyl-4'-methoxyflavone and acacetin. The structures of the compounds were elucidated by spectroscopic methods. The compounds were evaluated for their ability to inhibit PAF receptor binding to rabbit platelets using 3H-PAF as a ligand. The biflavonoid and acacetin showed strong inhibition with IC50 values of 28.0 and 20.4 µM, respectively. The results suggest that these compounds could be responsible for the strong PAF antagonistic activity of the plant.

For a long time, people in West Java, Indonesia have used Selaginella as a traditional cure for several ailments including fever, minor wounds, broken bones, women’s health disorders or postnatal bleeding. However, information on the active compounds of the plant from Java Island has not been fully expounded. The objective of the research was to reveal the diversity of bioactive compounds and amentoflavone content of Selaginella from Java Island in order to optimize the use of this plant as a medicinal plant. Selaginella plants collected from 29 locations in Java were extracted and subjected to colorimetric and thin layer chromatography test to qualitatively analyze the bioactive compounds of alkaloid, phenol, and steroid. In addition, high performance liquid chromatography was performed to analyze the amentofalvone content of Selaginella extract. The research result showed that all the examined Selaginella species contained alkaloid, flavonoid, saponin, tannin, and steroid, but they did not contain hydroquinone. Seven of them contained the biflavonoid type of amentoflavone. The highest amentoflavone concentration, 6.87 ppm, was found in S. subalpina that originated from Gedung Songo, Central Java. Those results indicated that more than one Selaginella species originating from Java Island had marked potential for use as medicinal plants.

Three new biflavonoids, wikstaiwanones A–C (1–3), along with four known compounds (4–7) were isolated from the stems of Wikstroemia taiwanensis (Thymelaeaceae). Their structures were elucidated by spectroscopic analysis. Compounds 4 and 5 showed antitubercular activity against Mycobacterium tuberculosis with MIC values of 15 μg/mL, respectively.

Garcinia xanthochymus (Guttiferae) commonly known as gamboge, is a perennial medicinal plant native to the north of Thailand and Myanmar. Gamboge is used in watercolors, as a yellow fabric dye and traditional medicine for treating diarrhea and dysentery, dispelling worms clearing away fire and removing food toxin. Phytochemical investigations on the methanol extract of the stem bark of Garcinia xanthochymus resulted in isolation of one biflavonoid compound (+)-morelloflavon. The structure of this compound was deduced on basis of spectroscopic data including 1H NMR, 13C NMR, HMQC and HMBC and comparison with the reported data. This compound has been reported from others species of Garcinia.

Roots of Boesenbergia rotunda (L.) Mansf. are prominent ingredients in the cuisine of several Asian countries, including Thailand, Malaysia, Indonesia, India, and China. An extract prepared from the roots of this plant showed strong inhibitory activity against enzymes α-glucosidase and pancreatic lipase and was subjected to chromatographic separation to identify the active components. Three new biflavonoids of the flavanone-chalcone type (9, 12, and 13) were isolated, along with 12 known compounds. Among the 15 isolates, the three new compounds showed stronger inhibitory activity against α-glucosidase than the drug acarbose but displayed lower pancreatic lipase inhibitory effect than the drug orlistat. The results indicated the potential of B. rotunda roots as a functional food for controlling after-meal blood glucose levels.

Amentoflavone (C30H18O10) is a well-known biflavonoid occurring in many natural plants. This polyphenolic compound has been discovered to have some important bioactivities, including anti-inflammation, anti-oxidation, anti-diabetes, and anti-senescence effects on many important reactions in the cardiovascular and central nervous system, etc. Over 120 plants have been found to contain this bioactive component, such as Selaginellaceae, Cupressaceae, Euphorbiaceae, Podocarpaceae, and Calophyllaceae plant families. This review paper aims to profile amentoflavone on its plant sources, natural derivatives, pharmacology, and pharmacokinetics, and to highlight some existing issues and perspectives in the future.