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Biomedical subjects

Zhizhen Zhang

Publications and source records attributed to Zhizhen Zhang.

12 recordsLinked to original sources

Anticonvulsant and neuroprotective effects of ginsenosides in rats.

A partially purified extract from American ginseng has been shown to have anticonvulsant activity. To identify the active components in this extract, the activities of the individual ginsenosides (Rb(1), Rb(3) and Rd), mixtures of the purified ginsenosides and a newly prepared Rb fraction were determined. One hour after treatment with vehicle or one of the ginseng products, seizures were induced in adult, Sprague-Dawley rats with kainic acid (KA, 10 mg/kg), pilocarpine (300 mg/kg) or pentylenetetrazole (PTZ, 50mg/kg i.p. or 90 mg/kg s.c.). Time to seizure onset, duration of seizure activity and seizure severity were determined. Weight change and neuronal damage were assessed 24h after administration of KA or pilocarpine. Mixtures of purified Rb(1), Rb(3) with or without Rd had significant anticonvulsant effects in all three models of acutely induced seizures demonstrating that the ginsenosides are the active components in the Rb extract. The individual ginsenosides significantly increased the latency to onset of seizures after administration of kainic acid. Since no one individual ginsenoside accounted for the majority of the activity of the Rb extract, the results suggest that the most effective anticonvulsant product is a combination of ginsenosides. In addition, all of the ginseng products had significant neuroprotective activity beyond the reduction in seizure severity and duration.

Animals↗

Triterpenoid saponins from the fruits of Aesculus pavia.

The compounds, named aesculiosides Ia-Ie, IIa-IId, and IVa-IVc, were isolated from an ethanol extract of the fruits of North American Aesculus pavia, along with two known compounds. Their structures were characterized as polyhydroxyoleanene pentacyclic triterpenoid saponins by spectroscopic and chemical analyses. These saponins were divided into three elution zones by chromatography according to the polarity because of the acyl substitution at C-21 and C-22 of the aglycone saponins moiety. These are structurally different from those isolated from Eurasian Aesculus hippocastanum and Aesculus chinensis in their oligosaccharide moieties.

Aesculus↗

Antifungal activity of camptothecin, trifolin, and hyperoside isolated from Camptotheca acuminata.

Leaf spots and root rots are major fungal diseases in Camptotheca acuminata that limit cultivation of the plant for camptothecin (CPT), a promising anticancer and antiviral alkaloid. Bioassays showed that pure CPT and flavonoids (trifolin and hyperoside) isolated from Camptotheca effectively control fungal pathogens in vitro, including Alternaria alternata, Epicoccum nigrum, Pestalotia guepinii, Drechslera sp., and Fusarium avenaceum, although antifungal activity of these compounds in the plant is limited. CPT inhibited mycelial growth by approximately 50% (EC50) at 10-30 microg/mL and fully inhibited growth at 75-125 microg/mL. The flavonoids were less effective than CPT at 50 microg/mL, particularly within 20 days after treatment, but more effective at 100 or 150 microg/mL. CPT, trifolin, and hyperoside may serve as leads for the development of fungicides.

Alternaria↗

Protective effects of ginseng components in a rodent model of neurodegeneration.

To test the proposed neuroprotective activity of whole ginseng extract and its components, we used 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, to produce neurodegeneration. Treatment with 3-nitropropionic acid (90 mg/kg) over a 5-day period resulted in severe impairment of movement and loss of neurons in the striatum. Pretreatment with a preparation from the whole root of American ginseng had no protective effects. Pretreatment with a preparation of ground leaves and stems, which contains greater levels of ginsenosides than ground root, improved the behavioral score and reduced the volume of the striatal lesion. A partial purification of American ginseng was performed to concentrate the putative protective components: Rb1, Rb3, and Rd (termed Rb extract). Pretreatment with the Rb extract significantly reduced the 3-nitropropionic acid-induced motor impairment and cell loss in the striatum, and it completely prevented any mortality. Significant effects on motor function, mortality, and the striatal lesion volume also were measured in animals pretreated with the individual ginsenosides, Rb1, Rb3, or Rd. The results demonstrate that some of the ginsenosides have neuroprotective activity, and that a partial purification of whole ginseng to concentrate the neuroprotective components may have utility as a neuroprotective agent.

Animals↗

Six new triterpenoid saponins from the root and stem bark of Cephalanthus occidentalis.

From the root and stem bark of Cephalanthus occidentalis L., a common American wetland species, six new triterpenoid saponins (1 - 6), together with 29 known compounds were isolated and identified. On the basis of spectroscopic analysis and chemical degradation, the structures of new compounds were elucidated as 3-O-beta-glucopyranosylcincholic acid (1), cincholic acid 28-O-beta-glucopyranosyl ester (2), 3-O-beta-glucopyranosyl-(1-->4)-beta-fucopyranosylcincholic acid (3), 3-O-beta-glucopyranosyl-(1-->4)-beta-fucopyranosylcincholic acid 28-O-beta-glucopyranosyl ester (4), 3-O-beta-glucopyranosylcincholic acid 28-O-alpha-arabinopyranosyl-(1-->2)-beta-glucopyranosyl ester (5), and 3-O-beta-glucopyranosylquinovic acid 28-O-alpha-arabinopyranosyl-(1-->2)-beta-glucopyranosyl ester (6).

Humans↗

New camptothecin and ellagic acid analogues from the root bark of Camptotheca acuminata.

As part of a study on chemical constituents of Camptotheca species, one new natural camptothecin analogue (2), two new alkaloids (3, 4), one new ellagic acid analogue (5), and 19 known compounds (1, 6-23) have been isolated from the root bark, stem bark, fruits, and leaves of Camptotheca acuminata Decaisne. The structures of 2-5 were determined from spectral data to be 10-methoxy-20-O-acetylcamptothecin (2), 20-O-beta-glucopyranosyl 18-hydroxycamptothecin (3), 20-formylbenz indolizino [1,2-b]quino-line-11(13H)-one (4), and 3,4-methylenedioxy-3'-O-methyl-5'-hydroxyellagic acid (5).

Camptotheca↗

Flavanone glycosides from Miconia trailii.

Assay-guided fractionation of the ethanol extract of the twigs and leaves of Miconia trailii yielded two new flavanone glycosides, matteucinol 7-O-alpha-l-arabinopyranosyl(1-->6)-beta-d-glucopyranoside (miconioside A, 1) and farrerol 7-O-beta-d-apiofuranosyl(1-->6)-beta-d-glucopyranoside (miconioside B, 2), along with the known compounds matteucinol 7-O-beta-d-apiofuranosyl(1-->6)-beta-d-glucopyranoside (3), matteucinol (4), 2alpha,3beta,19alpha-trihydroxyolean-12-ene-24,28-dioic acid (bartogenic acid, 5), 2alpha,3beta,23-trihydroxyolean-12-ene-28-oic acid (arjunolic acid, 6), 2alpha,3alpha,19alpha, 23-tetrahydroxyurs-12-ene-28-oic acid (myrianthic acid, 7), and stigmast-4-ene-3,6-dione (8). The structures of 1-8 were elucidated by spectroscopic methods, including 2D NMR.

Cholestenones↗

Phenolic compounds from Nymphaea odorata.

Assay-guided fractionation of the ethanol extract of Nymphaea odorata resulted in the identification of two lignans, one new (1) and one known (2), together with six known flavonol glycosides (3-8). The structures of 1-8 were established by spectroscopic analysis as nymphaeoside A (1), icariside E(4) (2), kaempferol 3-O-alpha-l-rhamnopyranoside (afzelin, 3), quercetin 3-O-alpha-l-rhamnopyranoside (4), myricetin 3-O-alpha-l-rhamnopyranoside (myricitrin, 5), quercetin 3-O-(6' '-O-acetyl)-beta-d-galactopyranoside (6), myricetin 3-O-beta-d-galactopyranoside (7), and myricetin 3-O-(6' '-O-acetyl)-beta-d-galactopyranoside (8). Compounds 3, 4, and 7 showed marginal inhibitory effect against fatty acid synthase with IC(50) values of 45, 50, and 25 microg/mL, respectively.

Enzyme Inhibitors↗

Natural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum.

Activity-guided fractionation of an ethanol extract of Lycopodium cernuum for Candida albicans secreted aspartic proteases (SAP) inhibition resulted in the identification of six new (1-6) and four known (7-10) serratene triterpenes, along with the known apigenin-4'-O-(2' ',6' '-di-O-p-coumaroyl)-beta-D-glucopyranoside (11). On the basis of spectroscopic analysis, the structures of 1-10 were established as 3beta,14alpha,15alpha,21beta,29-pentahydroxyserratane-24-oic acid (lycernuic acid C, 1), 3beta,14alpha,15alpha,21beta-tetrahydroxyserratane-24-oic acid (lycernuic acid D, 2), 3beta,14beta,21beta-trihydroxyserratane-24-oic acid (lycernuic acid E, 3), 3beta,21beta,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone A, 4), 3alpha,21beta,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone B, 5), 3alpha,21beta,24-trihydroxyserrat-14-en-16-one (lycernuic ketone C, 6), 3beta,21beta-dihydroxyserrat-14-en-24-oic acid (lycernuic acid A, 7), 3beta,21beta,29-trihydroxyserrat-14-en-24-oic acid (lycernuic acid B, 8), serrat-14-en-3beta,21beta-diol (9), and serrat-14-en-3beta,21alpha-diol (10). The 13C NMR data for the known compounds 7 and 8 are reported for the first time. Compounds 1 and 11 showed inhibitory effects against C. albicans secreted aspartic proteases (SAP) with IC50 of 20 and 8.5 microg/mL, respectively, while the other compounds were inactive.

Acetylation↗

New sesquiterpenoids from the root of Guatteria multivenia.

A phytochemical investigation of the CHCl(3) fraction of an ethanol extract of the root of Guatteria multivenia furnished nine compounds, of which four are sesquiterpenes (1-4) and five are alkaloids (5-9). Of the four sesquiterpenes, two are new (1, 3), named guatterin A (1) and dihydromadolin-K (3), and two are known (2, 4), identified as madolin-K (2) and madolin-W (4). The five known alkaloids were identified as liriodenine (5), lysicamine (6), lanuginosine (7), guadiscine (8), and O-methylpallidine (9). All the known compounds were isolated from this species for the first time. Structures of the new compounds were determined by extensive NMR studies, including DEPT, COSY, HMQC, HMBC, and NOESY. Compound 7 showed weak inhibitory effect against Candida albicans secreted aspartic proteases (SAP) with IC(50) of 45 microg/mL. Compound 5 was found to have antimicrobial activity against C. albicans, Cryptococcusneoformans, Staphylococcus aureus, and methicillin-resistant S. aureus (MRS) with IC(50)/MIC values of 3.5/6.25, 2.0/12.5, 2.0/3.13, and 2.0/3.13 microg/mL, respectively.

Alkaloids↗

Natural products inhibiting Candida albicans secreted aspartic proteases from Tovomita krukovii.

Assay-guided fractionation of the ethanol extract of Tovomita krukovii resulted in the identification of four new xanthones (1 - 4) and ten known compounds (5 - 14). The structures of compounds 1 - 14 were determined by spectral data to be 3,5-dihydroxy-4-methoxyxanthone (1), 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (2), 1,3,5-trihydroxy-8-isoprenylxanthone (3), 1,5,7-trihydroxy-8-isoprenylxanthone (4), 1,3,7-trihydroxy-2-isoprenylxanthone (5), 1,5-dihydroxyxanthone (6), 1,6-dihydroxy-5-methoxyxanthone (7), 1,3,5-trihydroxyxanthone (8), 1,3,6-trihydroxy-5-methoxyxanthone (9), 1,6-dihydroxy-3,5-dimethoxyxanthone (10), 1,3,7-trihydroxyxanthone (11), 3-geranyl-2,4,6-trihydroxybenzophenone (12), betulinic acid (13), and 3,4-dihydroxybenzoic acid (14). Compounds 2, 3, 12 and 13 showed inhibitory effects against Candida albicans secreted aspartic proteases (SAP) with IC50 values of 15 microg/ml, 25 microg/ml, 40 microg/ml, and 6.5 microg/ml, respectively, while the other compounds were inactive. In addition, compound 12 showed activity against C. albicans, C. neoformans, S. aureus and methicillin resistant S. aureus (MRS).

Antifungal Agents↗

Camptothecin accumulation and variations in camptotheca.

Camptotheca (Nyssaceae) is a major source of anticancer camptothecin (CPT). It is imperative to understand CPT accumulation and variations in Camptotheca in order to develop CPT production strategies for endangered germplasm. Our study results showed that CPT is primarily accumulated in glandular trichomes of leaves and stems, and CPT content varies among species and varieties but even more significantly within the plant (with different tissues, tissue ages, and seasons). Because of higher CPT yield and desirable biological and ecological features, 'Hicksii' and 'Katie' should be considered the major management germplasm as CPT sources in the future. Young leaves and mature fruits have higher CPT contents than other tissues in the plants. Young photosynthetic leaves and stems contain higher CPT contents than old ones, but 'sink' tissues such as wood, roots, and fruits show different patterns. CPT content also shows a great seasonal change, but is less influenced by tree age. Intact clipping of young leaves and stems should be managed for harvest for CPT production. Preservation and treatment methods influence the CPT extraction. CPT is better preserved in fresh or freeze-dried material than in air or oven-dried material. CPT can be more efficiently extracted after homogenizer treatment of plant materials because more trichome walls can be broken to allow solvent extraction.

Antineoplastic Agents, Phytogenic↗