3,4',5-Trihydroxy-3',7-dimethoxyflavanone was isolated from the ligroin extract of the leaves of Blumea balsamifera, while the acetone extract yielded 3',4',5-trihydroxy-7-methoxyflavanone and a new biflavonoid identifed as 3-O-7''-biluteolin (1). The isolation of 1 is significant since a biflavonoid with a C-O-C linkage of the type [I-3-O-II-7] has not been previously reported from a plant.
Five morphinoid alkaloids have been isolated from Dehaasia longipedicellata, namely (-) pallidine, a new alkaloid (+) pallidinine (1), (+)-milonine, (-) 8,14-dehydrosalutaridine and (-) sinoacutine.
A new megastigmane diglycoside was isolated from the leaves of Carallia brachiata. The structure was determined by spectroscopic methods as 3-hydroxy-5,6-epoxy-beta-ionol -3-O-beta-apiofuranosyl-(1-->6)-beta-glucopyranoside (1). Additionally, 29 known compounds consisting of two megastigmanes, one 1,2-dithiolane derivative, seven aromatic compounds, five condensed tannins, 12 flavonoids, and two glyceroglycolipids were isolated and identified.
The antinociceptive effect of the ethanolic extract of Melastoma malabathricum (MME) was investigated using acetic acid-induced abdominal writhing test and hot-plate test in mice. It was demonstrated that the extract (30-300 mg/kg, i.p.) strongly and dose-dependently inhibited the acetic acid-induced writhing with an ED(50) of 100 (78-160) mg/kg i.p. It also significantly increased the response latency period to thermal stimuli. Furthermore, the nonselective opioid receptor antagonist, naloxone blocked the antinociceptive effect of the extract in both tests, suggesting that M. malabathricum may act both at peripheral and central levels.
Giganteone E (1), a new dimeric acylphenol was isolated as a minor constituent from the bark of Myristica maxima Warb. The structure of 1 was established on the basis of 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Malabaricones A-C (2-4), giganteones A and C (5 and 6), maingayones A and B (7 and 8), maingayic acid B (9) and β-sitosteryl oleate (10) were also characterized in this plant for the first time. Compound 10 was identified for the first time in the Myristicaceae. Compounds 2 and 5 were active against human prostate cancer cell-lines, thus making this the first report on the prostate cancer inhibiting potential of acylphenols and dimeric acylphenols. Compounds 1, 4, 5, 7 and 8 exhibited potent DPPH free radical scavenging activity. This is the first report on their free radical scavenging capacity.
A phytochemical study of the EtOAc-soluble part of the methanolic extract of the bark of Endiandra kingiana led to the isolation of three new pentacyclic kingianins as racemic mixtures, kingianins O-Q (1-3), together with the known kingianins A, F, K, L, M and N (4-9), respectively. The structures of the new kingianins 1-3 were determined by 1D and 2D NMR analysis in combination with HRESIMS experiments. Kingianins A-Q were assayed for Mcl-1 binding affinity. Kingianins G and H were found to be potent inhibitors of Mcl-1/Bid interaction. A structure-activity relationship study showed that potency is very sensitive to the substitution pattern on the pentacyclic core. In addition, in contrast with the binding affinity for Bcl-xL, the levorotatory enantiomers of kingianins G, H and J exhibited similar binding affinities for Mcl-1 than their dextrorotatory counterparts, indicating that the two anti-apoptotic proteins have slightly different binding profiles.
Neuropathic pain is a chronic condition that is difficult to be treated. Current therapies available are either ineffective or non-specific thus requiring newer treatment approaches. In this study, we investigated the antiallodynic and antihyperalgesic effects of zerumbone, a bioactive sesquiterpene from Zingiber zerumbet in chronic constriction injury (CCI)-induced neuropathic pain animal model. Our findings showed that single and repeated dose of intra-peritoneal administration of zerumbone (5, 10, 50, 100 mg/kg) significantly attenuated the CCI-induced neuropathic pain when evaluated using the electronic von Frey anesthesiometer, cold plate, Randall-Selitto analgesiometer and the Hargreaves plantar test. Zerumbone significantly alleviated tactile and cold allodynia as well as mechanical and thermal hyperalgesia. Our findings are in comparison to the positive control drugs thatused gabapentin (20 mg/kgi.p.) and morphine (1 mg/kgi.p.). Together, these results showed that the systemic administration of zerumbone produced marked antiallodynic and antihyperalgesic effects in the CCI-induced neuropathic pain in mice and may serve as a potential lead compound for further analysis.
Plumbagin, isoshinanolone, epishinanolone, shinanolone, quercetin and kaempferol were isolated from the leaves of Nepenthes gracilis. Spectral data of shinanolone are presented.
Seventy-two extracts (methanol) obtained from the leaves, barks, and roots of 50 plant species used in the traditional medicine of Perak, Peninsular Malaysia, have been screened for antibacterial and antifungal activities. Peristrophe tinctoria, Polyalthia lateriflora, Knema malayana, Solanum torvum, Celosia argentea, Eclipta prostrata, Ancistrocladus tectorius, Dillenia suffruticosa, Piper stylosum and Rafflesia hasseltii displayed the broadest spectrum of activity.
Labisia pumila var. alata (Myrsinaceae) or "Kacip fatimah" is a famous Malay traditional herb used for the maintenance of women's health. The extracts of L.pumila displayed estrogenic activity in rats. Nonetheless, the estrogenic bioactives were not identified. The aim of the study is to identify estrogenic compounds contributing to the established estrogenic activity. Bioactivity-guided-isolation method guided the isolation of pure bioactives. The hexane extract was subjected to a series of silica gel flash and open column chromatography with increasing amount of ethyl acetate in hexane or methanol in chloroform. Each fraction or pure compounds were evaluated on it's estrogen receptor (ER) binding activity with the fluorescence polarization competitive ERα and ERβ binding assay kit. Cytotoxic assay using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method was used to establish the cytotoxic activity of the compounds. Four alkyl resorcinols and a dimeric 1,4-benzoquinone, namely belamcandol B (1), 5-pentadec-10'-(Z)-enyl resorcinol (2), 1,3-dihydroxy-5-pentadecylbenzene (3), 5-(heptadec-12'-(Z)-enyl) resorcinol (4) and demethylbelamcandaquinone B (5) were identified with selective binding affinities towards either ERα or ERβ exhibiting selectivity ratio from 0.15-11.9. Alkyl resorcinols (2)-(4) exhibited cytotoxic activity towards HL60 cells with IC50 values from 19.5-22.0 μM. Structural differences between compounds influence the binding affinities to ER subtypes. Further study is needed to establish the agonist or antagonist effect of these compounds on various tissues and to identify if these compounds exert cytotoxic activity through the ERs. When consuming L.pumila as a complementary medicine, careful consideration regarding it's estrogenic compound content should be given due consideration.
The last few decades have seen an alarming rise in fungal infections, which currently represent a global health threat. Despite extensive research towards the development of new antifungal agents, only a limited number of antifungal drugs are available in the market. The routinely used polyene agents and many azole antifungals are associated with some common side effects such as severe hepatotoxicity and nephrotoxicity. Also, antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. This suitation requires continuous attention. Cinnamaldehyde has been reported to inhibit bacteria, yeasts, and filamentous molds via the inhibition of ATPases, cell wall biosynthesis, and alteration of membrane structure and integrity. In this regard, several novel cinnamaldehyde derivatives were synthesized with the claim of potential antifungal activities. The present article describes antifungal properties of cinnamaldehyde and its derivatives against diverse classes of pathogenic fungi. This review will provide an overview of what is currently known about the primary mode of action of cinnamaldehyde. Synergistic approaches for boosting the effectiveness of cinnamaldehyde and its derivatives have been highlighted. Also, a keen analysis of the pharmacologically active systems derived from cinnamaldehyde has been discussed. Finally, efforts were made to outline the future perspectives of cinnamaldehyde-based antifungal agents. The purpose of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of cinnamaldehyde and its derivatives and to identify research avenues that can facilitate implementation of cinnamaldehyde as a natural antifungal.
Five new limonoids, swieteliacates A-E (1-5) and a tirucallane-type triterpenoid, swietesenin (6), together with four known compounds (7-10) were isolated from fruit of Swietenia macrophylla. Their structures were determined by spectroscopic analyses. The new compounds were tested in vitro for their cytotoxic effects against five human cancer cell lines. Compound 2 exhibited moderate cytotoxic activities against SW480 and HL-60 cancer cell lines with IC50 values of 30.6 and 32.9μM, respectively.
Usually isolated from Garcinia (Clusiaceae) or Hypericum (Hypericaceae) species, some Polycyclic Polyprenylated AcylPhloroglucinols (PPAPs) have been recently reported as potential research tools for immunotherapy. Aiming at exploring the chemodiversity of PPAPs amongst Garcinia genus, a dereplication process suitable for such natural compounds has been developed. Although less sensitive than mass spectrometry, NMR spectroscopy is perfectly reproducible and allows stereoisomers distinction, justifying the development of 13C-NMR strategies. Dereplication requires the use of databases (DBs). To define if predicted DBs were accurate enough as dereplication tools, experimental and predicted δC of natural products usually isolated from Clusiaceae were compared. The ACD/Labs commercial software allowed to predict 73% of δC in a 1.25 ppm range around the experimental values. Consequently, with these parameters, the major PPAPs from a Garcinia bancana extract were successfully identified using a predicted DB.
Wounds still pose a huge burden on human health and healthcare systems in many parts of the world. Phytomedicines are being used to heal the wounds since ancient times. Now-a-days also many researchers are exploring the wound healing activity of phytomedicines. Wound healing is a complex process thus, it is always a question mark regarding the best test model (in vivo, ex vivo and in vitro) model to assess the wound healing activity of phytomedicines. In general, the researchers would opt for in vivo model - probably because of closer physiological relevance to human wounds. However, in vivo experimental models are not suitable for high throughput screening and not ethical in terms of initial screening of the phytomedicines. The in vivo models are associated with difficulties in obtaining the ethical approvals, requires huge budget, and resources. We argue that judicious selection of cell types would serve the purpose of developing a physiologically relevant in vitro experimental model. A lot of progress has been made in molecular biology techniques to bridge the gap between in vitro models and their physiological relevance. The in vitro models are the best suited for high throughput screening and to elucidate the molecular mechanisms. The main aim of this review is to provide insights on selection of the cell types for developing physiologically relevant in vitro wound healing assays, which can be used to improve the value of phytomedicines further.
Cardamonin is a natural chalcone that has been shown to exhibit high anticancer activity. In an attempt to discover analogues of cardamonin with enhanced anticancer activity, 19 analogues were synthesized and tested against A549 and HK1 cell lines. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin's phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19). Compound 19 was the most active analogue possessing IC50 values of 13.2μM and 0.7μM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. It was also able to significantly inhibit the migration of A549 and HK1 cells. Further mode of action studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell- cycle arrest in both cell lines. These events further led to the induction of apoptosis by the compound via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Moreover, 19 inhibited the expression levels of p-mTOR and p-4EBP1, which indicated that it exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway.
Benign prostate hyperplasia (BPH) is an enlargement of the prostate gland, because of hormonal changes in aging males which contribute significantly to excessive proliferation over apoptosis of prostatic cells. The anti-proliferative and induced apoptotic activities of Eurycoma longifolia quassinoids on cancer cell lines could be promising therapeutic targets on BPH. Hitherto, no report of the quassinoids against BPH problem was available. In this study, a systematic phytochemical fractionation of the root extract, TAF2 was performed, which led to the discovery of nine previously described C20 quassinoids (1-9). Two undescribed C20 (10 and 12) and one undescribed (11) C19 quassinoids were identified by detailed NMR and HR-ESI-MS data analysis. Their absolute configurations were assigned by ECD spectral analysis. The quassinoids (1-12) were tested for inhibitory activity against the proliferation of human BPH-1 and human skin Hs27 fibroblast cells cultured in vitro. 1, 2 and 3 at 10 μM significantly reduced BPH-1 cell viability and were cytotoxic to Hs27 fibroblast cells. 2 was selected for further study of anti-BPH activity against testosterone induced BPH rats. At 5 mg/kg, 2 reduced the rat prostatic weight and prostatic index, consistent with the decrease in papillary acini number and epithelial thickness of the prostate tissues. These quassinoids may be potential anti-BPH compounds that require further studies.
Two new terrein derivatives asperterreinones A-B (1-2), one new octahydrocoumarin derivative (±)-asperterreinin A (6), along with seventeen known compounds, were isolated from Aspergillus terreus F6-3, a marine fungus associated with Johnius belengerii. The structures of 1, 2, and 6 were established on the basis of 1D and 2D NMR, mass spectroscopy, comparative electronic circular dichroism (ECD) spectra analysis, density functional theory calculation of 13C NMR, and DP4+ probability analysis. Among all the isolates, eurylene (7), a constituent of the Malaysian medicinal plant Eurycoma longifolia, was obtained from a microbial source for first time. In the in vitro bioassay, 11 and 13 showed potent inhibitory activity against the Escherichia coli β-glucuronidase (EcGUS) with IC50 values of 27.75 ± 0.73 and 17.73 ± 0.81 μM, respectively. It was the first time that questinol (11) and (±)-aspertertone B (13) were reported as potent EcGUS inhibitors.
Ficus deltoidea was known for its potent antioxidant, anti-melanogenic and photoprotective skin barrier activities. These properties are contributed by its biomarkers which are vitexin and isovitexin. This study aims to optimize the yield of methanolic extraction of Ficus deltoidea leaves (EFD) and evaluate their effects on skin barrier function and hydration. For optimization, Box-Behnken design was utilized to investigate the effects of methanol concentration, sonication time, and solvent-to-sample ratio on the yields of vitexin and isovitexin in EFD. The optimal yields obtained were 32.29 mg/g for vitexin and 35.87 mg/g for isovitexin. The optimum extraction conditions were 77.66% methanol concentration, 20.03 min sonication time, and 19.88 mL/g solvent-to-sample ratio. The quantitative real-time polymerase chain reaction was utilized to measure variant marker genes of transglutaminase-1, caspase 14, ceramide synthase 3, involucrin, and filaggrin of EFD-induced keratinocyte differentiation by in vitro study. Exposure to EFD has elevated the mRNA levels of all tested marker genes by 0.7-9.2 folds. Then, in vivo efficacy study was conducted on 20 female subjects for 14 days to evaluate skin biophysical assessment of hydration. EFD topical formulation treatment successfully increased skin hydration on day 7 (43.74%) and day 14 (47.23%). In silico study by molecular docking was performed to identify intermolecular binding interactions of vitexin and isovitexin with the interested proteins of tested marker genes. The result of molecular docking to the interested proteins revealed a similar trend with real-time PCR data. In conclusion, EFD potentially enhanced the skin barrier function and hydration of human skin cells.
A phytochemical study on the bark of Chisocheton erythrocarpus Hiern (Meliaceae) has led to the isolation of six new phragmalin-type limonoids named erythrocarpines I - N (1-6) along with one known limonoid, erythrocarpine F (7). Their structures were fully characterized by spectroscopic methods. The pre-treatment of NG108-15 cells with 1-5, 7 (2 h) demonstrated low to good protective effects against H2O2 exposure; 1 (83.77% ± 1.84 at 12.5 μM), 2 (69.07 ± 2.01 at 12.5 μM), 3 (80.38 ± 2.1 at 12.5 μM), 4 (62.33 ± 1.95 at 25 μM),5 (58.67 ± 1.85 at 50 μM) and 7 (66.07 ± 2.03 at 12.5 μM). Interestingly, 1 and 3 demonstrated comparable protective effects to positive control epigallocatechin gallate (EGCG) with similar cell viability capacity (≈ 80%), having achieved that at lower concentration (12.5 μM) than EGCG (50 μM). Collectively, the results suggested the promising use of 1 and 3 as potential neuroprotective agents against hydrogen peroxide-induced cytotoxicity in neuronal model.
Diabetes mellitus stands as a metabolic ailment marked by heightened blood glucose levels due to inadequate insulin secretion. The primary aims of this investigative inquiry encompassed the isolation of phytochemical components from the bark of Kopsia teoi, followed by the assessment of their α-amylase inhibition. The phytochemical composition of the K. teoi culminated in the discovery of a pair of new indole alkaloids; which are 16-epi-deacetylakuammiline N(4)-methylene chloride (akuammiline) (1), and N(1)-methoxycarbonyl-11-methoxy-12-hydroxy-Δ14-17-kopsinine (aspidofractinine) (2), together with five known compounds i.e. kopsiloscine G (aspidofractinine) (3), akuammidine (sarpagine) (4), leuconolam (aspidosperma) (5), N-methoxycarbonyl-12-methoxy-Δ16, 17-kopsinine (aspidofractinine) (6), and kopsininate (aspidofractinine) (7). All compounds were determined via spectroscopic analyses. The in vitro evaluation against α-amylase showed good inhibitory activities for compounds 5-7 with the inhibitory concentration (IC50) values of 21.7 ± 1.2, 34.1 ± 0.1, and 30.0 ± 0.8 μM, respectively compared with the reference acarbose (IC50 = 34.4 ± 0.1 μM). The molecular docking outputs underscored the binding interactions of compounds 5-7 ranging from -8.1 to -8.8 kcal/mol with the binding sites of α-amylase. Consequently, the outcomes highlighted the anti-hyperglycemic attributes of isolates from K. teoi.