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Biomedical subjects

H H Fong

Publications and source records attributed to H H Fong.

At least 37 records · Page 2Linked to original sources

A lignan and four terpenoids from Brucea javanica that induce differentiation with cultured HL-60 promyelocytic leukemia cells.

A novel lignan, guaiacylglycerol-beta-O-6'-(2-methoxy)cinnamyl alcohol either, three known simaroubolides, brusatol, dehydrobrusatol, yadanziolide C, and the known terpenoid, blumenol A, were obtained as active compounds from an ethyl acetate-soluble extract of Brucea javanica, using a bioassay based on the induction of cell differentiation with human promyelocytic leukemia (HL-60) cells. Also obtained were the known coumarinolignan, cleomiscosin A, and the known quassinoid glycoside, bruceoside B, which were inactive in the HL-60 cell test system. The structure of the new lignan was determined by a combination of 1D and 2D NMR techniques.

Cell Differentiation↗

Nigranoic acid, a triterpenoid from Schisandra sphaerandra that inhibits HIV-1 reverse transcriptase.

An A ring-secocycloartene triterpenoid, nigranoic acid (3,4-secocycloarta-4(28),24-(Z)-diene-3,-26-dioic acid, (1) was isolated from the stems of Schisandra sphaerandra, a Chinese traditional medicinal plant. Its structure elucidation and unambiguous NMR spectral assignment were achieved by the combination of 1D- and 2D-NMR techniques with the aid of computer modeling. Nigranoic acid showed activity in several anti-HIV reverse transcriptase and polymerase assays.

China↗

Antitumorigenic effect of a mammalian lignan precursor from flaxseed.

Secoisolariciresinol diglycoside (SD), a mammalian lignan precursor found in high-fiber foods, was isolated from flaxseed and tested for effects on mammary tumorigenesis in rats fed a high-fat (20%) diet. Ingestion of purified SD at 1.5 mg/day for 20 weeks starting 1 week after treatment with the carcinogen dimethylbenzanthracene resulted in a 37% reduction (p < 0.05) in the number of tumors per tumor-bearing rat and a 46% reduction (p < 0.05) in the number of tumors per tumor-bearing rat and a 46% reduction (p < 0.05) in the number of tumors per number of rats in each group. Urinary mammalian lignan excretion significantly increased (p < 0.0001) with SD treatment, indicating the conversion of SD to mammalian lignans. No enlargement or gross abnormalities of the major organs were observed in the SD-treated rats. This study showed, for the first time, that SD has an antitumor effect when provided at the early promotion stage of tumorigenesis and may contribute to the health benefits of high-fiber foods.

9,10-Dimethyl-1,2-benzanthracene↗

Dose-dependent production of mammalian lignans in rats and in vitro from the purified precursor secoisolariciresinol diglycoside in flaxseed.

The mammalian lignans enterodiol (ED) and enterolactone (EL) produced from colonic bacterial action on dietary precursors have exhibited anticarcinogenic effects in vitro. The major lignan precursor in flaxseed (a rich source) has been identified as secoisolariciresinol diglycoside (SDG). The purpose of this study was to first isolate SDG and determine whether 1) SDG accounted for all the lignan production from flaxseed; 2) this production was dose-related; and 3) a relationship between in vitro production and in vivo urinary excretion existed. Extraction of flaxseed with dioxane:ethanol (1:1, v/v) followed by chromatographic separations yielded the purified SDG. Rats were fed a high fat diet without/with 2.5, 5 or 10 g/100g ground flaxseed or 1.1, 2.2 or 4.4 micromol SDG/d (equivalent to levels in the respective flaxseed diets) for 4 wk. In vitro lignan production was assessed by fermenting flaxseed or SDG for 24 h with human fecal inoculum. Urinary lignan excretion increased linearly with doses from 0-5% flaxseed and 0-2.2 micromol SDG/d followed by a plateau, indicating a threshold response. When all doses were considered, a curvilinear relationship was observed. A similar trend was seen in vitro for SDG, resulting in a high correlation between in vitro production and in vivo excretion of lignans (r = 0.990, P < 0.02). Thus in vivo response can be predicted with confidence based on in vitro results. Theoretical urinary ED + EL from the SDG present in flaxseed correlated with the actual excretion in flaxseed-fed animals (r = 0.655, P < 0.005). However, urinary ED + EL of SDG-fed rats was only 20% of levels of flaxseed-fed rats, indicating the presence of other precursors or incomplete conversion of SDG to ED and EL.

4-Butyrolactone↗

Mechanistic evaluation of new plant-derived compounds that inhibit HIV-1 reverse transcriptase.

Swertifrancheside [1], a new flavonone-xanthone glucoside isolated from Swertia franchetiana, 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2], a triterpene isolated from the roots of Maprounea africana, and protolichesterinic acid [3], an aliphatic alpha-methylene-gamma-lactone isolated from the lichen Cetraria islandica, were found to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT), with 50% inhibitory doses (IC50 values) of 43, 3.7, and 24 microM, respectively. They were not cytotoxic with cultured mammalian cells. The kinetic mechanisms by which compounds 1-3 inhibited HIV-1 RT were studied as was their potential to inhibit other nucleic acid polymerases. Swertifrancheside [1] bound to DNA and was shown to be a competitive inhibitor with respect to template-primer, but a mixed-type competitive inhibitor with respect to TTP. On the other hand, 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2] and protolichesterinic acid [3] were mixed-type competitive inhibitors with respect to template-primer and noncompetitive inhibitors with respect to TTP. Therefore, the mechanism of action of 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2] and protolichesterinic acid [3] as HIV-1 RT inhibitors involves nonspecific binding to the enzyme at nonsubstrate binding sites, whereas swertifrancheside [1] inhibits enzyme activity by binding to the template-primer.

4-Butyrolactone↗

Rotenoids mediate potent cancer chemopreventive activity through transcriptional regulation of ornithine decarboxylase.

For the discovery of new cancer chemopreventive agents, we have studied the potential of plant extracts to inhibit phorbol ester-induced ornithine decarboxylase (ODC) activity in cell culture. Four active rotenoids were obtained from the African plant Mundulea sericea (Leguminosae). These isolates were highly potent when evaluated for inhibition of chemically induced preneoplastic lesions in mammary organ culture and inhibition of papillomas in the two-stage mouse skin model, and they appear to function by a unique mechanism at the level of ODC messenger RNA expression. Based on our findings, rotenoids can be regarded as promising new chemopreventive or anticancer agents.

9,10-Dimethyl-1,2-benzanthracene↗

Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis.

As a result of bioassay-guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma-specific cytotoxic agent. In follow-up studies conducted with athymic mice carrying human melanomas, tumour growth was completely inhibited without toxicity. As judged by a variety of cellular responses, antitumour activity was mediated by the induction of apoptosis. Betulinic acid is inexpensive and available in abundant supply from common natural sources, notably the bark of white birch trees. The compound is currently undergoing preclinical development for the treatment or prevention of malignant melanoma.

Animals↗

The pregnane glycoside marsdekoiside A from Marsdenia koi.

A new pregnane glycoside, marsdekoiside A was isolated from the stems of Marsdenia koi (Asclepiadaceae) and its structure was elucidated from chemical and spectral data as 12-cinnamoyl-dihydrosarcostin-3-O-methyl-6-deoxy-beta-D-allopyr ano syl-(1----4)-O-beta-D-oleandropyranosyl-(1----4)-O-beta-D-++ +cymar opyranoside.

Carbohydrate Sequence↗

Studies on the antifertility components from Marsdenia koi.

By random screening test, Marsdenia koi was found to have antifertility activity on SD rat. From MeOH extracts of this plant two steroidal glycosides, marsdekoiside A and B, were isolated, and their structures were elucidated on the basis of spectral evidence and by comparison of the hydrolysis products with the authentic samples. Both are newly identified compounds, and marsdekoiside A has good antifertility activity.

Animals↗

Sesquiterpene lactones and other constituents from a cytotoxic extract of Michelia floribunda.

The pentane and CHCl3 fractions of a crude extract of Michelia floribunda exhibited cytotoxic activity when tested in KB and P388 tumor cell cultures. Repeated chromatography led to the isolation of three cytotoxic sesquiterpene lactones (costunolide, parthenolide, and santamarine) and a cytotoxic isoquinoline alkaloid (liriodenine). Inactive sesquiterpene lactones obtained during the course of this study included dihydroparthenolide and two new glucosides of dihydrotamaulipin A and dihydroreynosin (1 and 2). The structures of these new compounds were determined through interpretation of their spectroscopic data including 2D-NMR spectroscopy. Syringin was also isolated from the extract.

Animals↗

Identification of senecionine and senecionine N-oxide as antifertility constituents in Senecio vulgaris.

The MeOH extract of Senecio vulgaris L., administered po to rats on Days 1-10 postcoitum, significantly decreased the number of normal fetuses per pregnant rat found at autopsy on Day 16. Additional experiments showed a similar activity for its hepatotoxic constituents senecionine and senecionine N-oxide, suggesting that the latter two compounds were probably responsible for the effect seen with the extract. No antifertility effects were seen in MeOH extract-treated hamsters.

Animals↗

Studies on zoapatle. VIII: Novel cytotoxic sesquiterpene lactones from Montanoa tomentosa ssp. microcephala.

Investigation of the leaves of Montanoa tomentosa Cerv. ssp. microcephala (Sch.-Bip.) Funk (Compositae) resulted in the isolation of three novel guaianolide sesquiterpenes, montacephalin (1), tomencephalin (2), and 5-hydroxytomencephalin (3), which were shown to be cytotoxic (P-388). The structures of these sesquiterpenes were elucidated through analysis of their spectroscopic characteristics, and complete proton and carbon-13 assignments were made for the new compounds. Also isolated were the known terpenes, beta-amyrin, beta-amyrin acetate, stigmasterol, stigmasterol-3 beta-D-glucoside, (-)-kaur-16-en-19-oic acid, and monoginoic acid.

Animals↗