Isolation and characterization of bioactive xanthones from Hippocratea africana (Willd.)Loes.ex Engl. (Celastraceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Hippocratea africana root is used in African folk medicine for the treatment of several ailments, including pain and inflammation. AIM OF THE STUDY: To isolate anti-inflammatory and analgesic compounds from the roots of H. africana, with accompanying antioxidant potentials. MATERIALS AND METHODS: Dichloromethane, ethyl acetate, and aqueous fractions of H. africana roots, and isolated compounds from the bioactive ethyl acetate fraction were evaluated for anti-inflammatory and analgesic activities using the xylene induced oedema in mice and thermal induced pain models, respectively. The antioxidant potentials of isolated compounds were tested in 2,2-diphenyl-1-picryhydrazyl radical and ferric reducing antioxidant power assays. Structures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR experiments, ionization mass spectrometry, and comparison with literature data. RESULTS: Isoathyriol (1,3,7-trihydroxy-6-methoxyxanthone) and norathyriol (1,3,6,7-tetrahydroxyxanthone) were isolated from the potent anti-inflammatory and analgesic ethyl acetate fraction of H. africana roots. Isoathyriol and norathyriol demonstrated good anti-inflammatory, analgesic, and antioxidant properties compared with the standards used in each assay. CONCLUSIONS: This study substantiates the use of H. africana root extract in the alleviation of inflammation and pain, and reports the characterization of secondary metabolites in H. africana and for the first time the presence of xanthones in Hippocratea genus.

Preclinical evaluation of anti-Helicobacter spp. activity of Hippocratea celastroides Kunth and its acute and sub-acute toxicity.

BACKGROUND: Hippocratea celastroides Kunth, commonly known as "cancerina", is used in Mexican Traditional Medicine for the treatment of gastric and intestinal infections, systemic and skin inflammation, injuries and gastritis. The aim of this research was to assess the anti-Helicobacter pylori activities of hydro-ethanolic root-bark extracts from Hippocratea celastroides Kunth in naturally infected dogs, after testing their acute and subacute toxicities in mice. METHODS: To determine in vivo acute toxicity, a hydro-ethanolic extract was obtained and administered orally in female and male Balb-C mice, at doses ranging from 2000 to 5000 mg/kg. For the subacute study, a hydro-ethanolic extract was given to male and female Balb-C mice at doses ranging from 200 to 2000 mg/kg body weight. The animals were observed daily over a period of 42 days for signs of toxicity. In the pre-clinical anti-Helicobacter spp. assay, 60 dogs were included. Eighteen and 19 dogs for the experimental and control groups respectively, concluded the study. The experimental treatment consisted of H. celastroides hydro-ethanolic extract and the control treatment of amoxicillin-clarithromycin-omeprazole. RESULTS: Oral LD50 (lethal dose 50) values for hydro-ethanolic extract were indeterminable at the highest tested doses. Under the subacute administration, neither mortality nor any sign of toxicity were observed when the hydro-ethanolic extract was administered. There were no significant alterations in biochemical parameters. The prevalence of Helicobacter spp. infection in dogs was 97.1 % for the experimental group and 100 % for the control group. Effectiveness was of 33.3 and 55 % in the experimental and control group respectively. The oral administration of H. celastroides was well-tolerated and safe. CONCLUSION: The root-bark of H. celastroides produced no signs of toxicity, and manifested pharmacological activity that indicated the possibility of an alternative treatment for H. pylori infection. Effectiveness is still low so it is necessary to continue research.

Anti-Helicobacter pylori, gastroprotective, anti-inflammatory, and cytotoxic activities of methanolic extracts of five different populations of Hippocratea celastroides collected in Mexico.

ETHNOPHARMACOLOGICAL RELEVANCE: The root barks of Hippocratea celastroides have been used for decades in Mexican traditional medicine to treat gastritis and ulcers. To investigate the anti-Helicobacter pylori, gastroprotective, anti-inflammatory, and cytotoxic activities of methanolic extracts obtained from the leaves, stems, and root bark of Hippocratea celastroides collected in five different localities in Mexico, during the winter of 2009, in order to establish differences in biological activities in terms of plant organs, as well as places of collection. MATERIALS AND METHODS: Whole individuals were collected in five separate localities in Mexico: La Mancha, Veracruz (VL), Yautepec, Morelos (MY), Jojutla, Morelos (MJ), Temalac, Guerrero (GT), and Landa de Matamoros, Querétaro (QL). Methanolic crude extracts from wild plant specimens were tested using in vivo ethanol-induced mice gastric ulcer model, and 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ear edema in mice assay, and in vitro anti-Helicobacter pylori model, and carcinoma cell line cytotoxic assays. RESULTS AND CONCLUSIONS: The leaves, stems, and root bark from MY specimens, as well as the leaves and root bark of materials from VL, presented the highest activity against Helicobacter pylori (MIC values ranging from 7.81 to 31.25 µg/ml). Most gastroprotective effects were displayed by the leaves of plants collected in MY, with 89.85±1.91% of protection (300 mg/kg) and an ED50=27 mg/kg, which was corroborated by histological analysis. The root bark extracts from MY achieved the highest edema inhibition values (ED50=0.18 mg/ear), which were comparable to indomethacin (ED50=0.16 mg/ear). Finally, all extracts from MY (three plant parts) were cytotoxic against nasopharyngeal (KB), breast (MCF-7), and colon (HCT-116) carcinoma cell lines with IC50 values between 1.18 and 9.77 µg/ml, except that no activity was detected for root bark extracts against HCT-116 normal fibroblasts. The activities of methanolic extracts from leaves, stems and root bark of plants collected in five different locations varied considerably, representing a notable problem facing the quality control of the plant material from Hippocratea celastroides used for medicinal purposes. The ethnomedical information of this plant in regards to treating gastritis and ulcers was strongly evidenced by the findings of the experimental models employed in this study.

Antioxidative burst and hepatoprotective effects of ethanol root extract of Hippocratea africana against paracetamol-induced liver injury.

CONTEXT: Hippocratea africana (Willd.) Loes. ex Engl. (Celastraceae) root is used traditionally as an antipoison or antidote to treat liver diseases. OBJECTIVE: To evaluate antioxidative burst and hepatoprotective potentials of H. africana against paracetamol-induced liver injury in rats. MATERIALS AND METHOD: Antioxidative burst activity of the extract (1-100 µg/ml) in whole blood, neutrophils and macrophages was investigated using a luminol/lucigenin-based chemiluminescence assay. The hepatoprotective effect of the extract (200-600 mg/kg) was evaluated by the assay of liver function parameters, antioxidant enzymes and histopathological studies of the liver. GC-MS analyses of hexane and dichloromethane fractions were also carried out. RESULTS AND DISCUSSION: The root extract/fractions exerted pronounced inhibition of oxidative burst activity in whole blood, neutrophils (intracellular and extracellular) and macrophages (3.04-99.70%). The administration of the root extract caused significant (p < 0.05-0.001) reduction of high levels of liver enzymes (AST, ALT and ALP), total cholesterol, direct and total bilirubin as well as elevation of serum levels of total protein, albumin and antioxidant enzymes (SOD, CAT, GPx and GSH). Histology of the liver sections of extract and silymarin-treated animals showed reductions in the pathological features compared to the paracetamol-treated animals. The chemical pathological changes were consistent with histopathological observations suggesting a marked hepatoprotective effect of the root extract of H. africana. The GC-MS analysis revealed some pharmacologically active compounds. CONCLUSION: The results show that the root extract of H. africana has hepatoprotective potential probably due to its antioxidative burst activity.

A theoretical investigation of cytotoxic activity of celastroid triterpenoids.

Quantum chemical calculations at the B3LYP/6-31G* level of theory have been carried out on 20 celastroid triterpenoids to obtain a set of molecular electronic properties and to correlate these with cytotoxic activities. The cytotoxic activities of these compounds can be roughly correlated with electronic effects related to nucleophilic addition to C6 of the compounds: the energies of the frontier molecular orbitals (E(HOMO) and E(LUMO)), the HOMO-LUMO energy gap, the dipole moment, the charge on C6, and the electrophilicity on C6.

Trypanocidal activity of quinonemethide triterpenoids from Cheiloclinium cognatum (Hippocrateaceae).

We report the trypanocidal activity of quinonemethide triterpenoids isolated from root extracts of Cheiloclinium cognatum, a plant of the Hippocrateaceae family, collected in the Cerrado Reserve at Universidade Federal de Goiás, Brazil. The trypanocidal activity assays showed an effect on the blood trypomastigote forms of the Y strain of Trypanosoma cruzi where tingenone and tingenol demonstrated activity on the parasite. Their structures were elucidated on the basis of spectral data, particularly COSY, HMQC and HMBC experiments, and chemical transformations.

21beta-Hydroxy-oleanane-type triterpenes from Hippocratea excelsa.

Stem bark of Hippocratea excelsa afforded six pentacyclic triterpenes, five oleanane and one ursane types. They were identified as 11beta,21beta-dihydroxy-olean-12-ene-3-one (2), 3alpha,11alpha,21beta-trihydroxy-olean-12-ene (3), 3alpha,21beta-dihydroxy-11alpha-methoxy-olean-12-ene (4), 3alpha,21beta-dihydroxy-olean-9(11),12-diene (5), 3alpha,21beta-dihydroxy-olean-12-ene (6) and 3alpha,21beta-dihydroxy-11alpha-methoxy-urs-12-ene, isolated as its diacetate derivative (7), as well as 3alpha,21beta-dihydroxy-olean-12-ene (1) previously isolated from the root bark. The known alpha- and beta-amyrin, oleanoic and ursolic acids, trans-polyisoprene, and the ubiquitous beta-sitosterol were also isolated. Structures were elucidated on the basis of spectroscopic analyses, including homo- and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC and HMBC) and comparison with literature data. The antigiardial activity of compounds 2-5 was not significant.

Antigiardial activity of triterpenoids from root bark of Hippocratea excelsa.

Two new triterpenoids, 21 beta-hydroxyolean-12-en-3-one (1) and a seco-dinor derivative of pristimerine named dzununcanone (2), were isolated from the root bark of Hippocratea excelsa. Their structures were assigned on the basis of spectroscopic evidence, mainly 1H and 13C 1D and 2D NMR including DEPT, COSY, ROESY, HSQC, and HMBC experiments, as well as EIMS and HREIMS. The known 21alpha-hydroxy-3-oxofriedelane (3), a compound new to the species, and the known methide quinones pristimerine (4) tingenone (5), and xuxuarine Ebeta (7) were also isolated. The antiprotozoal activities were determined against Giardia intestinalis. Pristimerine and tingenone were the most active antigiardial compounds, with IC50 values of 0.11 and 0.74 microM, respectively, compared with metronidazole, the current drug of choice (IC50 1.23 microM).

Antioxidant phenolic and quinonemethide triterpenes from Cheiloclinium cognatum.

The triterpenes, 22beta-hydroxypristimerin and cognatine, were isolated together with the known compounds pristimerin, maytenin, 20alpha-hydroxymaytenin, 22beta-hydroxymaytenin, netzahualcoyol, netzahualcoyondiol and netzahualcoyone from root bark of Cheiloclinium cognatum. The structures of the isolated compounds were elucidated by interpretation of their spectral data, including gHMQC and gHMBC experiments. The isolates were investigated for their radical scavenging abilities through a spectrophotometric assay involving reduction of 2,2-diphenyl-picryl hydrazyl (DPPH).

[Biological activities of Salacia chinensis originating in Thailand: the quality evaluation guided by alpha-glucosidase inhibitory activity].

In the course of our characterization studies on anti-obese and antidiabetogenic principles in medicinal foodstuffs, we found that the methanolic extract from the stems of Salacia chinensis (Hippocerateaceae) showed potent anti-hyperglycemic effects in oral sucrose or maltose-loaded rats, inhibitory effects on intestinal alpha-glucosidase, rat lens aldose reductase, formation of Amadori compounds and advanced glycation end-products, nitric oxide production from lipopolysaccharide-activated mouse peritoneal macrophage, and radical scavenging activities. Those in vivo and in vitro biological activities were compared with those of S. oblonga and S. reticulata. In addition, we isolated the principal alpha-glucosidase inhibitor, salacinol, from the stems of S. chinensis and examined alpha-glucosidase inhibitory activities of eleven samples of S. chinensis collected in Thailand.

Structures of new friedelane- and norfriedelane-type triterpenes and polyacylated eudesmane-type sesquiterpene from Salacia chinensis LINN. (S. prinoides DC., Hippocrateaceae) and radical scavenging activities of principal constituents.

Two new friedelane-type triterpenes, salasones D and E, a new norfriedelane-type triterpene, salaquinone B, and a new polyacylated eudesmane-type sesquiterpene, salasol B, were isolated from the stems of Salacia chinensis LINN. (S. prinoides DC., Hippocrateaceae) collected in Thailand. Their stereostructures were elucidated on the basis of chemical and physicochemical evidence. Some norfriedelane-type triterpene, lignan, and catechin constituents were found to show radical scavenging activity.