Homalolides C-D, two new sesquiterpenoids from the rhizomes of Homalomena pendula.

Two new sesquiterpenoids, homalolides C - D (1‒2), were co-isolated from the rhizomes of Homalomena pendula (Blume) Bakh.f collected in Vietnam with five known ones, aromadendrane-4α,10α-diol (3), bullatantriol (4), 1ß,4ß,6α-trihydroxy-eudesmane (5), 1ß,4ß,6ß-trihydroxyeudesmane (6), and 1ß,4ß,7α-trihydroxy-eudesmane (7). The structures and relative configuration of new compounds were elucidated by 1 D-/2D-NMR, IR, UV and HRESIMS analyses, and by comparisons to the reported data in the literature. Homalolide C presented an unprecedented skeleton with the 4/8 bicyclic system. All isolates did not exhibit appreciable inhibitory effects on LPS-induced NO production in the RAW 264.7 macrophage cell line and on the growth of human lung cancer cell line (SK-LU-1).

Structure revision and absolute configuration of 5,7-diepi-2α-hydroxyoplopanone and anti-osteoporotic activities of sesquiterpenoids from the rhizomes of Homalomena pendula.

Five sesquiterpenoids including 2α-hydroxyoplopanone (1), oplopanone (2), 1ß,4ß,6α-trihydroxy-eudesmane (3), 1ß,4ß,7α-trihydroxy-eudesmane (4) and bullatantriol (5) were isolated from Homalomena pendula. The structure of the previously reported compound, 5,7-diepi-2α-hydroxyoplopanone (1a), has been revised to 1 by the spectroscopic evidences (1D-/2D-NMR, IR, UV and HRESIMS) and by comparison between experimental and theoretical NMR data using DP4+ protocol. Furthermore, the absolute configuration of 1 was unambiguously assigned by ECD experiments. Compounds 2 and 4 displayed a potent ability to stimulate osteogenic differentiation of MC3T3-E1 cells at 4 µg/mL (by 123.74% and 131.07%, respectively) and 20 µg/mL (by 112.45% and 126.41%, respectively) whilst 3 and 5 did not show any activities. At 20 µg/mL, 4 and 5 significantly promoted the mineralization of MC3T3-E1 cells with values of 112.95% and 116.37%, respectively, whereas 2 and 3 were inactive. The results indicated that 4 could be an excellent component for anti-osteoporosis studies from the rhizomes of H. pendula.

Sesquiterpenoids from the rhizomes of Homalomena pendula and their anti-inflammatory activities.

Sixteen sesquiterpenoids including two new ones, homalolides A - B (1‒2), were firstly isolated from the methanolic extract of the rhizomes of Homalomena pendula collected in Vietnam. The structures and relative stereochemistry of new compounds were elucidated by 1D-/2D-NMR, IR, UV and HRESIMS analyses. The GCMS experiment demonstrated that homalolide A (1) is an artifact due to the methylation during methanolic extraction process. All isolates (1‒16) were tested for their inhibitory activities against lipopolysaccharide-induced nitric oxide production in the RAW 264.7 macrophage cell line. Compounds 1, 3, 6‒8, 10‒12 displayed moderate inhibitory effect on NO production with IC50 values ranging from 35.41 to 64.06 µM.

A new spirostanol steroid and a new spirostanol steroidal saponin from Aspidistra triradiata and their cytotoxic activities.

A new spirostanol steroid, aspidiata A (1), and a new spirostanol steroidal saponin, aspidiata B (2), along with three known compounds, paris saponin VII (3), daucosterol (4), and (25R)-spirostane-1ß,2ß,3ß,4ß,5ß,6ß-hexol (5), were isolated from whole plants of Aspidistra triradiata collected in Vietnam. Their chemical structures were established by spectroscopic analysis and comparison with previously published data. Compound 3 showed strong cytotoxicity against LU-1, Hep-G2, MCF-7, and KB human cancer cell lines with half maximal inhibitory concentration (IC50) values ranging from 0.57 to 1.23 µM. Compound 5 exhibited weak cytotoxic activity against the LU-1 cell line, with an IC50 value of 95.81 µM.

Sesquiterpene derivatives from the agarwood of Aquilaria malaccensis and their anti-inflammatory effects on NO production of macrophage RAW 264.7 cells.

Nine undescribed sesquiterpenes, which include five guaiane and four humulene-type, were isolated from the agarwood of Aquilaria malaccensis. The structures of these undescribed sesquiterpenes were elucidated by spectroscopic methods including UV, HRESI-MS, 1D and 2D-NMR, ECD, and X-ray diffraction (Cu Kα). The isolated compounds were tested for their inhibitory effect against LPS-induced NO production in RAW 264.7 cells. In particular, one sesquiterpene (1α,7α-dihydroxy-8oxo-4αH,5αH-guaia-9(10),11(13)-dien-12-oate) showed significant inhibition of NO production in LPS-stimulated macrophage RAW 264.7 cells with an IC50 value of 18.8 µM.

New triterpene sulfates from Vietnamese red alga Tricleocarpa fragilis and their α-glucosidase inhibitory activity.

Three new compounds (methyl-3ß,25-dihydroxycycloart-23-en-29-oate 3-sulfate (1), methyl-3ß-hydroxy-25-methoxycycloart-23-en-29-oate 3-sulfate (2) and 3ß-hydroxy-25-methoxycycloart-23-ene 3-sulfate (3)) and a known one (3ß-hydroxycycloart-24-en-23-one 3-sulfate (4)) were isolated from Vietnamese red alga Tricleocarpa fragilis. All isolated compounds 1-4 showed potent inhibitory activity against yeast α-glucosidase with IC50 values of 16.62 ± 2.80, 36.34 ± 4.04, 30.19 ± 5.01 and 6.52 ± 0.17 µM, respectively. The docking data showed that the substitutions at C-3 and the differences in the side chain of cycloartane-skeleton could influence the interaction of molecule with enzyme, which was consistent with the experimental findings.[Formula: see text].

From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution

Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4'-ol from

In vitro metabolism of selected bioactive compounds of Eurycoma longifolia root extract to identify suitable markers in doping control.

Eurycoma longifolia Jack (Tongkat Ali, Simaroubaceae) is a medicinal plant endemic to South-East Asia. For centuries, different parts of the plant have been used as a natural remedy to treat fever, hypertension, or sexual insufficiency. Today, Eurycoma longifolia preparations are commercially available and advertised to enhance athletic performance and muscle strength. Several studies have demonstrated a testosterone-boosting effect that might be caused by the release of free testosterone from the sex-hormone-binding globulin. To date, many phytochemical constituents of Eurycoma longifolia root extracts have been identified and physiological effects have been examined, while studies on their biotransformation and monitoring are still lacking. Within this study, eurycomalide C, eurycomalactone, 5,6-dehydro-eurycomalactone, longilactone, 14,15ß-dihydroklaieanone, 11-dehydroklaieanone, 9-hydroxycanthin-6-one, and 9-methoxycanthin-6-one isolated from E. longifolia root were incubated with liver microsomes. Respective metabolites were analyzed by liquid chromatography-tandem (high-resolution) mass spectrometry. The compounds were chosen based on their potential androgenic effects (estimated by in vitro assays), their concentrations in plant extracts, and presumptive metabolic pathways. Hydroxylated phase I metabolites were only observed for 5,6-dehydro-eurycomalactone, 11-dehydroklaieanone, 9-hydroxycanthin-6-one, and 9-methoxycanthin-6-one. Moreover, an O-demethylated metabolite of 9-methoxycanthin-6-one was found. Besides, the glucuronide of 9-hydroxycanthin-6-one was detected after in vitro glucuronidation using liver microsomes. The in vitro generated metabolites were comparable to that detected in urine and serum after a single ingestion of either 9-methoxycanthin-6-one or an Eurycoma longifolia root extract. Hence, 9-methoxycanthin-6-one, its glucuronide, and the glucuronide of its O-demethylated biotransformation product are proposed to be the most suitable targets for detection of 9-methoxycanthin-6-one or Tongkat Ali application in urine and serum.

Development of a selective HPLC-DAD/ELSD method for the qualitative and quantitative assessment of commercially available Eurycoma longifolia products and plant extracts.

Aqueous extracts of the roots of Eurycoma longifolia are traditionally used to improve sexual performance, to treat infertility and other sexual dysfunctions but also to increase muscle strength. Nowadays, many different products are commercially available which are promoted as E. longifolia extracts and claim to possess beneficial aphrodisiac effects. Since such herbal aphrodisiac preparations have been recently the target of fraudulent product counterfeiting and because eurycomanone, one of the main quassinoids of E. longifolia, is suspected to possess toxic effects at higher concentrations, a highly selective HPLC-DAD/ELSD method has been established to analyze commercially available products and extracts of plant material. The presented method was established by the use of a mixture of 27 reference compounds for qualitative issues and fully validated according to the ICH guidelines for the quantification of three quassinoides: laurycolactone A, longilactone, and eurycomanone. The calibration curves of these showed a linearity over a range of 0.05 to 1.0mg/ml, with a regression coefficient not lower than R2=0.9969. The inter-day and intra-day precision (indicated as relative standard deviation) of the developed method was <2.9%. The recovery ranged from -3.3% to +6.0%. Eight randomly purchased products have been analyzed with this method, but only five of them contained E. longifolia compounds in detectable amounts. The concentration of eurycomanone in these products varied from 0.22±0.002mg eurycomanone per capsule to 1.84±0.08mg corresponding to a maximal recommended daily intake of 0.76±0.02 to 31.90±0.21mg.

Screening of Vietnamese medicinal plants for NF-κB signaling inhibitors: assessing the activity of flavonoids from the stem bark of Oroxylum indicum.

ETHNOPHARMACOLOGICAL RELEVANCE: Seventeen plants used in Vietnamese traditional medicine for the treatment of inflammatory disorders were screened for NF-κB inhibitory activity. Oroxylum indicum, which exhibited activity, was investigated in detail. MATERIALS AND METHODS: Forty plant extracts from 17 species were prepared by maceration using dichloromethane and methanol and were tested (10µg/mL) to evaluate their ability to inhibit NF-κB activation using TNF-α-stimulated HEK-293 cells stably transfected with a NF-κB-driven luciferase reporter. The active extract of Oroxylum indicum was subsequently fractionated by different chromatographic techniques. After isolation, all single compounds were identified by spectroscopic methods and assessed for NF-κB inhibitory effects. RESULTS: The dichloromethane extracts obtained from Chromolaena odorata leaves and the stem bark of Oroxylum indicum showed distinct inhibitory effects on NF-κB activation at a concentration of 10µg/mL. The active extract of Oroxylum indicum was subjected to further phytochemical studies resulting in identification of four flavonoid aglyca and six flavonoid glycosides. Pharmacological evaluation of the obtained compounds identified oroxylin A as the most active substance (IC50=3.9 µM, 95% CI: 3.5-4.4 µM), while chrysin and hispidulin showed lower activity with IC50=7.2µM (95% CI: 6.0-8.8 µM) and 9.0 µM (95% CI: 7.9-10.2 µM), respectively. Interestingly, in this study the activity of baicalein (IC50=28.1 µM, 95% CI: 24.6-32.0 µM) was weak. The isolated glycosides showed no inhibitory activity when tested at a concentration of 30 µM. Quantification of the four active flavonoids in extracts and plant materials suggested that oroxylin A contributes to the NF-κB inhibitory activity of the stem barks of Oroxylum indicum to a greater extent than baicalein which was thought to be responsible for the anti-inflammatory activity of this plant. CONCLUSIONS: The screening presented in this study identified the dichloromethane extracts of Chromolaena odorata and Oroxylum indicum as promising sources for NF-κB inhibitors. Hispidulin, baicalein, chrysin and oroxylin A, isolated from Oroxylum indicum, were identified as inhibitors of NF- κB activation.

NF-κB inhibitors from Eurycoma longifolia.

The roots of Eurycoma longifolia have been used in many countries of Southeast Asia to alleviate various diseases including malaria, dysentery, sexual insufficiency, and rheumatism. Although numerous studies have reported the pharmacological properties of E. longifolia, the mode of action of the anti-inflammatory activity has not been elucidated. Bioguided isolation of NF-κB inhibitors using an NF-κB-driven luciferase reporter gene assay led to the identification of a new quassinoid, eurycomalide C (1), together with 27 known compounds including 11 quassinoids (2-12), six alkaloids (13-18), two coumarins (19, 20), a squalene derivative (21), a triterpenoid (22), and six phenolic compounds (23-28) from the extract of E. longifolia. Evaluation of the biological activity revealed that C19-type and C20-type quassinoids, ß-carboline, and canthin-6-one alkaloids are potent NF-κB inhibitors, with IC50 values in the low micromolar range, while C18-type quassinoids, phenolic compounds, coumarins, the squalene derivative, and the triterpenoid turned out to be inactive when tested at a concentration of 30 µM. Eurycomalactone (2), 14,15ß-dihydroklaieanone (7), and 13,21-dehydroeurycomanone (10) were identified as potent NF-κB inhibitors with IC50 values of less than 1 µM.

Identification of chromomoric acid C-I as an Nrf2 activator in Chromolaena odorata.

Activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) contributes to several beneficial bioactivities of natural products, including induction of an increased cellular stress resistance and prevention or resolution of inflammation. In this study, the potential of a crude leaf extract of Chromolaena odorata, traditionally used against inflammation and skin lesions, was examined for Nrf2 activation. Guided by an Nrf2-dependent luciferase reporter gene assay, the phytoprostane chromomoric acid C-I (1) was identified as a potent Nrf2 activator from C. odorata with a CD (concentration doubling the response of vehicle-treated cells) of 5.2 µM. When tested at 1-10 µM, 1 was able to induce the endogenous Nrf2 target gene heme oxygenase 1 (HO-1) in fibroblasts. Between 2 and 5 µM, compound 1 induced HO-1 in vascular smooth muscle cells (VSMC) and inhibited their proliferation in a HO-1-dependent manner, without eliciting signs of cytotoxicity.

Switchable multiwavelength erbium doped fiber laser based on a nonlinear optical loop mirror incorporating multiple fiber Bragg gratings.

We propose and experimentally demonstrate a switchable multiwavelength erbium doped fiber laser based on a highly nonlinear dispersion shifted fiber and multiple fiber Bragg gratings. A nonlinear optical loop mirror based on a highly nonlinear dispersion shifted fiber is implemented in the ring laser cavity to stabilize the multiwavelength output at room temperature. Multiple fiber Bragg gratings with the wavelength spacing of 0.8 nm are connected with an arrayed waveguide grating to establish a multichannel filter. The high quality of the multiwavelength output with a high extinction ratio of ~60 dB and high output flatness of ~0.5 dB is realized. The nonlinear polarization rotation based on the nonlinear optical loop mirror can provide the switching performance of the proposed multiwavelength fiber laser. The lasing wavelength can be switched individually by controlling the polarization controller and the cavity loss.

Wavelength-spacing tunable multiwavelength erbium-doped fiber laser based on four-wave mixing of dispersion-shifted fiber.

We experimentally demonstrate a wavelength-spacing tunable multiwavelength erbium-doped fiber laser based on degenerate four-wave mixing in a dispersion-shifted fiber incorporating multiple-fiber Bragg gratings. We have achieved stable operation of the multiwavelength erbium-doped fiber laser, which has 0.8 nm spacing ten-channel lasing wavelengths and a high extinction ratio of more than approximately 45 dB, at room temperature. The output power of the multiwavelength erbium-doped fiber laser is stable, so the peak fluctuation is less than approximately 0.2 dB. By changing the properties such as loss and polarization state of multiple fiber Bragg grating cavities, we can exercise flexible control of the wavelength spacing of the multiwavelength output. We can also obtain switchable multiwavelength lasing operation by elimination of the effects of alternate single-fiber Bragg gratings.

Long-distance simultaneous measurement of strain and temperature based on a fiber Raman laser with a single fiber Bragg grating embedded on a quartz plate.

We propose and experimentally demonstrate long-distance remote simultaneous measurement of strain and temperature based on a Raman fiber laser with a single fiber Bragg grating embedded on a quartz plate. A Raman fiber laser output with a high extinction ratio of more than approximately 50 dB is achieved by the fiber grating cavity. In the sensing probe, half of the fiber Bragg grating is fixed steadily on the quartz plate to respond to temperature only, while the other half of the grating is free to respond to both temperature and strain. Based on the proposed scheme, lasing wavelength shift and separation occur with temperature and strain change, respectively. Efficient simultaneous measurement of strain and temperature for long-distance sensing applications of more than 50 km is readily obtained.