The first mitochondrial genome of Calophyllum soulattri Burm.f.

Calophyllum soulattri Burm.f. is traditionally used to treat skin infections and reduce rheumatic pain, yet genetic and genomic studies are still limited. Here, we present the first complete mitochondrial genome of C. soulattri. It is 378,262 bp long with 43.97% GC content, containing 55 genes (30 protein-coding, 5 rRNA, and 20 tRNA). Repeat analysis of the mitochondrial genome revealed 194 SSRs, mostly mononucleotides, and 266 pairs of dispersed repeats ( ≥ 30 bp) that were predominantly palindromic. There were 23 homologous fragments found between the mitochondrial and plastome genomes. We also predicted 345 C-to-U RNA editing sites from 30 protein-coding genes (PCGs) of the C. soulatrii mitochondrial genome. These RNA editing events created the start codon of nad1 and the stop codon of ccmFc. Most PCGs of the C. soulattri mitochondrial genome underwent negative selection, but atp4 and ccmB experienced positive selection. Phylogenetic analyses showed C. soulattri is a sister taxon of Garcinia mangostana. This study has shed light on C. soulattri's evolution and Malpighiales' phylogeny. As the first complete mitochondrial genome in Calophyllaceae, it can be used as a reference genome for other medicinal plant species within the family for future genetic studies.

Phytochemicals from the Stem Bark of Calophyllum havilandii P.†F. Stevens and their Biological Activities.

The genus Calophyllum from the family Calophyllaceae has been extensively investigated in the past due to its rich source of bioactive phenolics such as coumarins, chromanones, and xanthones. In this study, phytochemical investigation on the stem bark of Calophyllum havilandii has afforded a new 4-propyldihydrocoumarin derivative, havilarin (1) together with calolongic acid (2), caloteysmannic acid (3), isocalolongic acid (4), euxanthone (5), and ß-sitosterol (6). The chemical structure of compound 1 was elucidated and established based on detailed spectroscopic techniques, including MS, IR, UV, 1D and 2D NMR. The results of anti-bacillus study indicated that the chloroform extract showed promising activities with MIC value ranging between 0.5 to 1 µg/mL on selected bacillus strains. Besides, the plant extracts and compounds 1-4 were assessed for their cytotoxicity potential on HL-7702 cell line. All the tested plant extracts and respective chemical constituents displayed non-cytotoxic activity on HL-7702 cell line.

Phenolics and triterpenoids from stem bark of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens and their cytotoxic activities.

Genus Calophyllum is well-known for its phenolic constituents, especially coumarins, which have shown to have a wide range of significant biological activities. In this study, four known phenolic constituents and two triterpenoids have been isolated from the stem bark of Calophyllum lanigerum. The compounds were two pyranochromanone acids are known as caloteysmannic acid (1), isocalolongic acid (2), a simple dihydroxyxanthone, namely euxanthone (3), one coumarin named calanone (4), and two common triterpenoids, friedelin (5), and stigmasterol (6). Chromanone acids were reported for the first time in this Calophyllum species. Cytotoxic evaluations were carried out on n-hexane extract (87.14 ± 2.04 µg/mL; 81.46 ± 2.42 µg/mL) followed by the chromanone acids (1 [79.96 ± 2.39 µM; 83.41 ± 3.39 µM] & 2 [57.88 ± 2.34; 53.04 ± 3.18 µM]) against two cancerous cell lines, MDA-MB-231 and MG-63 cell lines, respectively. The results showed that all tested samples exhibited moderate cytotoxicity.

Characteristic chromanone acids from Calophyllum membranaceum: Determination of C-3 configuration and anti-inflammatory activity.

One undescribed homologous furanochromanone (1) featuring a 6/6/5/3 tetracyclic skeleton and four highly oxidized pyranochromanones (2-5), along with a set of four pyranochromanone stereoisomers [(±)-6a and (±)-6b], were isolated from the leaves of Calophyllum membranaceum Gardn. Et Champ. Their structures were elucidated by using spectroscopic data, Snatzke's method, quantum-chemical calculations, and X-ray crystallographic analysis. The correlation of characteristic Cotton effects and specific chemical shifts with C-3 configuration provided a convenient approach to assign the C-3 configuration of 2,3-dimethylchromanones. The stereochemical assignments of 3-OH substituted pyranochromanones by quantum-based NMR methods following single/double MTPA derivatization were consistent with the ECD/NMR prediction, which verified the feasibility and reliability of the proposed empirical rule. The underlying mechanism was further clarified by conformational and molecular orbital analyses. Moreover, biological evaluation and binding assays demonstrated that compound 3 (KD = 0.45 µM) tightly binds to the TLR4-MD2 target, thereby inhibiting the TLR4/MyD88-dependent and -independent signal pathways. This study provides the first evidence that Calophyllum chromanones are a novel structural type of TLR4 inhibitors, exerting their anti-inflammatory effects by disrupting the binding between TLR4 and MD2.

A new chromanone acid derivative from the nut oil resin of Calophyllum inophyllum.

One novel chromanone acid derivative, namely inocalophylline C (1), together with one known compound calophyllolide (2), were isolated from the methanolic extract of nut oil resin of Calophyllum inophyllum L., a medicinal plant widely distributed in Vietnam. The isolated compound structures were elucidated by spectroscopic methods and the absolute configuration of 1 was established by the single-crystal X-ray crystallography as ethyl (R) 3-((2 R,3R,6R)-4-hydroxy-2,3-dimethyl-6-((R)-5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-yl)-6-(3-methylbut-2-en-1-yl)-5,7-dioxo-3,5,6,7-tetrahydro-2H-chromen-8-yl)-3-phenylpropanoate.

The production of activated biochar using Calophyllum inophyllum waste biomass and use as an adsorbent for removal of diuron from the water in batch and fixed bed column.

The Calophyllum inophyllum species annually produces a large volume of cylindrical fruits, which accumulate on the soil because they do not have nutritional value. This study sought to enable the use of this biomass by producing activated biochar with zinc chloride as an activating agent for further application as an adsorbent in batch and fixed bed columns. Different methodologies were used to characterize the precursor and the pyrolyzed material. Morphological changes were observed with the emergence of new spaces. The carbonaceous material had a surface area of 468 m2 g-1, Dp = 2.7 nm, and VT = 3.155 × 10-1 cm3 g-1. Scientific and isothermal studies of the adsorption of the diuron were conducted at the natural pH of the solution and adsorbent dosage of 0.75 g L-1. The kinetic curves showed a good fit to the Avrami fractional order model, with equilibrium reached after 150 min, regardless of the diuron concentration. The Liu heterogeneous surface model well represented the isothermal curves. By raising the temperature, adsorption was encouraged, and at 318 K, the Liu Qmax was reached at 250.1 mg g-1. Based on the Liu equilibrium constant, the nonlinear van't Hoff equation was employed, and the ΔG° were < 0 from 298 to 328 K; the process was exothermic nature (ΔH0 = -46.40 kJ mol-1). Finally, the carbonaceous adsorbent showed good removal performance (63.45%) compared to a mixture containing different herbicides used to control weeds. The stoichiometric column capacity (qeq) was 13.30 and 16.61 mg g-1 for concentrations of 100 and 200 mg L-1, respectively. The length of the mass transfer zone was 5.326 cm (100 mg L-1) and 4.946 cm (200 mg L-1). This makes employing the leftover fruits of the Calophyllum inophyllum species as biomass for creating highly porous adsorbents a very effective and promising option.

Phytochemicals from Calophyllum canum Hook f. ex T. Anderson and their neuroprotective effects.

Previous phytochemical investigations reported that Calophyllum spp have biosynthesized a wide range of bioactive phenolics such as xanthones and coumarins. The phytochemical study conducted on the stem bark of C. canum has led to the isolation of eight trioxygenated xanthones namely: 5-methoxytrapezifolixanthone (1), 5-methoxyananixanthone (2), caloxanthone C (3), 1,5-dihydroxy-3-methoxy-4-isoprenylxanthone (4), 6-deoxyisojacareubin (5), euxanthone (6), trapezifolixanthone (7), ananixanthone (8), together with three common triterpenoids, ß-sitosterol (9), friedelin (10), and stigmasterol (11). Furthermore, xanthones 1 and 2 were isolated for the first time as naturally occurring xanthones from the plant extract. The structures of these compounds were identified and elucidated using advanced spectroscopic techniques such as 1 D & 2 D NMR, MS, and FTIR. The neuroprotective property of selected compounds was tested through in vitro stroke model. Among all tested compounds, 1 µm of compounds 8, 9, and 10 showed significant neuroprotective activity via reduction of apoptosis by ∼ 50%.

Optimisation of Calophyllum inophyllum seed oil nanoemulsion as a potential wound healing agent.

BACKGROUND: Efficient delivery systems of Calophyllum inophyllum seed oil (CSO) in the form of nanoemulsion were optimised to enhance its stability and ensure its therapeutic efficiency as a potential agent for various biomedical applications. METHOD: Response Surface Methodology (RSM) was used to determine the effects of independent variables (oil, surfactant, water percentage and homogenisation time) on physicochemical characteristics, including droplet size, polydispersity index and turbidity. RESULTS: The optimised CSO nanoemulsion (CSONE) has a 46.68 nm particle size, 0.15 Polydispersity index value and 1.16 turbidity. After 4 weeks of storage at 5 ± 1 °C and 25 ± 1 °C, the CSONE was physically stable. The optimised CSO nanoemulsion showed enhancement in cell viability and wound healing in baby hamster kidney a clone BHK-21 (BSR) cells as compared to the CSO. The wound healing property of CSONE was higher than CSO. CONCLUSION: Thus, our in vitro wound healing results demonstrated that CSO in the nanoemulsion form can promote wound healing by enhancing the proliferation and migration of epidermal cells. The coarse emulsion of Calophyllum inophyllum seed oil nano emulsion was prepared using high shear homogeniser techniques. The optimised CSONE with the droplet size of 46.68 nm was prepared from a mixture of CSO, Tween 80, and high pure water (HPW), then used for the biological investigation. The in vitro cell monolayer scratch assay revealed that CSONE in the lowest concentration of CSO resulted in 100% wound closure after 48 hrs. The optimised CSO nanoemulsion was found to be a promising and effective approach in the treatment of wounds by boosting the proliferation and migration of epidermal cells.

Calofolic Acid-A from Calophyllum scriblitifolium Bark Has Vasorelaxant Activity via Indirect PKA Activation Caused by PI-3 Kinase Inhibition in Rat Vascular Smooth Muscle Cells.

Previously, we isolated 2R,3S,15R-calofolic acids (CAs) from Calophyllum scriblitifolium bark, which showed vasorelaxant activity on phenylephrine (PE)-precontracted rat aortic rings. Although the effect was suggested to be induced via an extracellular Ca2+-independent manner and mainly acts on vascular smooth muscle, the exact mechanism of action of CAs remained unclear. Thus, this study investigated the detailed mechanism of calofolic acid-A (CA-A) induced vasorelaxation in an aortic ring specimen using rat vascular smooth muscle cells (VSMCs). The levels of PE-induced phosphorylation on MLC Ser19 decreased in VSMCs pretreated with CA-A. CA-A also decreased the phosphorylation of MYPT1 Thr696 and MYPT1 Thr853. On the other hand, CA-A increased the PE-induced phosphorylation of MYPT1 Ser695 and MYPT1 Ser668, which are reported to be phosphorylated by a cAMP-dependent protein kinase (PKA). CA-A slightly increased PKA substrate phosphorylation in a concentration-dependent manner. Furthermore, CA-A enhanced isoproterenol (ISO)-induced cAMP accumulation and PKA substrate phosphorylation. Treatment with PI-3 kinase (PI3K) inhibitor, LY294002, enhanced ISO-induced cAMP accumulation and PKA substrate phosphorylation in the same manner as CA-A treatment. Furthermore, CA-A was found to directly inhibit PI3K enzyme activity in a dose-dependent manner. Taken together, the present study indicated that CA-A induces vasorelaxation through an indirectly activated PKA-MYPT1 pathway caused by inhibition of PI3K activity.

Pyranochromones with Anti-Inflammatory Activities in Arthritis from Calophyllum membranaceum.

Eleven new pyranochromones, calomembranone A-K (1-11), two new pyranocoumarins, calopolyanolide E and F (12 and 13), together with six known analogues (14-19) were isolated from the leaves of Calophyllum membranaceum. Their structures and absolute configurations were elucidated by analysis of spectroscopic data, computational calculations, as well as X-ray crystallography of 4 and 9. The anti-inflammatory activities of all the isolates were evaluated by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Structure-activity relationships are also discussed. Compound 7 showed the strongest NO inhibition (IC50 = 0.92 µM). Oral administration of 7 dose-dependently reduced the paw swelling and downregulated neutrophil-to-lymphocyte ratio in the carrageenan-induced acute arthritis mice model. Molecular dynamics simulation and cellular thermal shift assay results indicated that 7 participated in a robust and stable interaction with the active site of TLR4. Compound 7 also suppressed the inflammation in arthritis through the regulation of TLR4 mediated signal transduction via IKK/NF-κB signaling pathway and the consequent reduction of IL-2, IL-4, and IL-5.

Xanthones from Calophyllum Polyanthum Wallich ex Choisy with CYP1 Enzymes Inhibitory Activity.

Three new xanthone compounds, 1,3,5-trihydroxy-2-(2-hydroxy-3-methylbut-3-enyl)-4-(3-methylbut-2-enyl)xanthone (1), toxyloxanthone E (2), dehydrocycloguanandin B (3) along with 15 known xanthones (4-18) were isolated from the aerial parts of Calophyllum polyanthum Wall. ex Choisy. Their structures were fully characterised using spectroscopic data, as well as comparison with the previous literature data. All isolated compounds had inhibitory effects against CYP1A1, CYP1A2 and CYP1B1 enzymes at working concentration of 10 µM, 1 µM and 10 µM, respectively. Among them, compounds 10, 11, and 12 exhibited better CYP1A2 enzyme inhibitory effects than that of the positive control α-naphthoflavone, with 51.05 %, 56.82 % and 44.93 % inhibition, respectively.

Two New Xanthones from the Twigs of Calophyllum membranaceum and Their Anti-Inflammatory Activities in HESC Cells.

Two new xanthones, calmemxanthone A (1) and calmemxanthone B (2), along with eleven known compounds were isolated from the dried twigs of Calophyllum membranaceum Gardn. et Champ. The structures of compounds 1 and 2 were established by analysis of spectra and mass spectrometry data. The absolute configuration of compound 1 was confirmed by electronic circular dichroism (ECD) spectral analysis. The anti-inflammation action of these compounds were evaluated on lipopolysaccharide (LPS)-induced inflammatory damage to human endometrial stromal cells (HESCs), and the structure-activities of 1-13 were also discussed. Compound 10 presented the anti-inflammation action with an IC50 value of 20.3 µM, that might be relevant to the regulation of NF-κB signaling pathway via the suppression of TRIF, IKKα, and IκBα.

Xanthones from the stems of Calophyllum membranaceum Gardn. et Champ. and their anti-inflammatory activity.

Eighteen undescribed xanthones, including six pairs of xanthone enantiomers, three xanthones, and three xanthone glycosides, together with one pair of known xanthone enantiomers and 12 known xanthones, were isolated from the stems of Calophyllum membranaceum Gardn. et Champ. Their structures were elucidated by spectroscopic analysis, and the absolute configuration of the enantiomers was determined by using experimental and calculated electronic circular dichroism data. All compounds were screened for their anti-inflammatory effects on LPS-induced BV-2 microglial cells. Among them, six compounds showed remarkable activities with IC50 values of 7.8-36.0 µM.

Bioassay-guided isolation of anti-tumor polyprenylphloroglucinols from Calophyllum polyanthum and primary mechanism.

Five compounds were isolated from Calophyllum polyanthum leaves (10.09 g) by bioassay-guided fractionation to evaluate their anti-tumor activity. Among these compounds, apetalic acid (1) demonstrated significant inhibitory activity against 8 types of tumor cells (MHCC97H, CNE1, CNE2, B16, LOVO, SW480, A549, 1299), especially against two colon cancer cells (LOVO, SW480). Apetalic acid could inhibit cell proliferation, migration, invasion and induce apoptosis. It could significantly up-regulate the expression levels of apoptosis-related genes (BAX, Caspase-9,) and proteins (BAX, Cleaved-caspase-9, Cleaved-caspase-3) and down-regulated the expression of inhibitor of apoptosis gene (Bcl-2) and proteins (Bcl-2, phosphorylated AKT). Possible mechanism of the antitumor activity of apetalic acid derived from Calophyllum polyanthum supports its use in the prevention and treatment of colorectal cancer.

Caloforines A-G, coumarins from the bark of Calophyllum scriblitifolium.

Bioactivity-guided separation of the methanol extract of Calophyllum scriblitifolium bark led to the isolation of five new pyranocoumarins, caloforines A-E (1-5) and two new coumarins, caloforines F and G (6 and 7). Their structures were elucidated by 1D and 2D NMR spectroscopy, and their absolute configurations were investigated by a combination of CD spectroscopy and DFT calculation. Caloforines A-F (1-6) showed moderate antimalarial activity against Plasmodium falciparum 3D7 strain.

Exposure of Calophyllum antillanum seeds to liquid nitrogen delays seedling emergence and decreases leaf anthraquinones.

BACKGROUND: Trees within the Calophyllum genus are multi-use trees that produce valuable wood, phytochemicals with a range of biological activities, and seed oil as a source of biodiesel. As a consequence of climate change, there is a need to develop strategies to preserve valuable plant genetic resources. Cryopreservation represents the most suitable option for the long-term storage of germplasm with minimal space and maintenance requirements. OBJECTIVE: To determine appropriate methods to cryopreserve seeds of Calophyllum antillanum and maintain secondary compound production. MATERIALS AND METHODS: Seeds at a moisture content of 6% were used to evaluate two treatments: seeds immersed in liquid nitrogen and control seeds. Biosynthetic pathway efficiency was assessed post-cryo by determining anthraquinone contents in roots, stems and leaves following 30 and 75 d of seedling growth. RESULTS: The results indicated that exposure to liquid nitrogen delayed germination and seedling emergence for a period of up to 45 d after seed sowing. By 60 d of cultivation, no significant differences in plant growth were observed for cryostored and control seeds. The levels of anthraquinones, which were also measured in seeds and seedlings, were lower in plants regenerated from cryostored seeds following 30 d of growth, but there were no differences in roots and stems by 75 d of growth. Furthermore, the difference in leaf anthraquinone levels for cryopreserved and control seeds at 75 d was much smaller than at 30 d. CONCLUSION: The low initial anthraquinone levels in emerging seedlings correlated with the initial slow growth of cryopreserved seeds.

Phytochemicals from Calophyllum macrocarpum Hook.f. and its cytotoxic activities.

Species from the Genus Calophyllum are rich source for bioactive phenolic compounds such as coumarins and xanthones. Phytochemical study carried out on the plant, Calophyllum macrocarpum has led to the isolation of three known prenylated xanthones, ananixanthone (1), trapezifolixanthone (2) and 8-deoxygartanin (3) with two common triterpenoids, stigmasterol (4), and friedelin (5). The structures of these compounds were identified and determined using spectroscopic techniques such as NMR and MS. The cytotoxic activities of compounds 1 and 2 as well as the extracts were tested against HeLa Chang liver and HEK-293 cell lines. Compound 1 exhibited appreciable cytotoxicity with the IC50 value of 11.08 ± 3.09 µM against HeLa Chang liver cell line and moderate cytotoxicity against HEK-293 cell line while compound 2 showed limited toxicity against these two cell lines.

Two new pyranoxanthones from the stem bark of Calophyllum pseudomolle P.F. Stevens.

Two new pyranoxanthones, calotetrapterins D (1) and E (2), were isolated from the stem bark of Calophyllum pseudomolle P.F. Stevens along with α-mangostin (3). The structures of compounds 1-2 were determined based on 1D NMR (1H, 13C) and 2D NMR (HMQC, HMBC), as well as HRESIMS spectroscopic analysis. Compounds 1-2 showed moderate activity against HeLa and murine leukaemia P-388 cells.

Simultaneous removal of lead and cadmium ions from simulant and industrial waste water: using Calophyllum Inophyllum plant materials as sorbents.

NOVELTY STATEMENT: The merit of this investigation is that simple and effective bio-sorbents based on Calophyllum inophyllum plant materials with high sorption capacities, are developed for the simultaneous removal of the toxic Pb2+ and Cd2+ at neutral or nearly neutral pHs. These sorbents are successful in water remediation of Pb2+ and Cd2+ ions from real effluents from industries. These findings have great significance as the identified bio-sorbents are simple, effective and renewable in extracting highly toxic lead and cadmium ions from the effluents from industries or polluted water.

The Malaysian genus Calophyllum (Calophyllaceae): a review on its phytochemistry and pharmacological activities.

Genus Calophyllum from the family of Calophyllaceae is an evergreen broad-leaved tree that is endemic to Southeast Asia, especially Malaysia. They have been reported for various ethnomedicinal uses in traditional medicine. Previous studies of Malaysian Calophyllum species revealed them to be a rich source of bioactive phytoconstituents such as xanthones, coumarins, terpenoids, and chromanone acids. To date, the extracts and compounds from Malaysian Calophyllum species have shown a broad spectrum of pharmacological activities. For example, calanolide A, a coumarin isolated from Malaysian C. lanigerum, has now reached clinical development to become an anti-HIV drug. This article presents an overview of the significant phytochemical and pharmacological activities of Malaysian Calophyllum species to aid researchers in further discovery of potential benefits of various species of this genus.