In vitro anticancer activity of extracted oil from Parrotiopsis jacquemontiana (Decne) Rehder.

BACKGROUND: Parrotiopsis jacquemontiana, commonly referred to as "Beranj" in the local community, is widely used traditionally and has numerous health benefits. However, no studies have been conducted to investigate its anticancer potential, particularly its extracted oil. PURPOSE: The present study was put forth to appraise the anticancer potential of Parrotiopsis jacquemontiana extracted oil against liver (hcclm3 and hepg2) and breast cancer (mda-mb 231 and mcf-7) cell lines relative to normal cell lines (lo2 and mcf-10a) via MTT assay. METHODS: Flow cytometry indicated the apoptotic effect whereas invasion and migration capabilities of oil against cancer cells were determined by Matrigel invasion chamber and wound-scratch assays. RESULTS: The results of oil revealed a time and dose-dependent increase in cell proliferation inhibition, conferring to least IC50 shown against hcclm3 (144.9 ± 0.75 µg/ml) and mda-mb 231 (145.7 ± 0.32 µg/ml) cell line at 72 h, whereas no cytotoxic effect on normal cells was observed. In addition, the oil significantly (p < 0.001) suppressed the migration and invasion of hcclm3 and mda-mb 231 cells, showing noteworthy anti-metastatic potential. Furthermore, cell death was confirmed by Annexin‒V/PI staining where the maximum apoptotic percentage was calculated for oil (200 µg/ml) alongside mda-mb 231 conferring to 15.36 ± 1.22, 26.7 ± 1.2, and 36.43 ± 1.65 at 24, 48, and 72 h whereas 12.33 ± 1.05, 19.36 ± 1.62, and 29.3 ± 0.79 was recorded alongside hcclm3 at similar time intervals, respectively. CONCLUSION: In conclusion, the extracted oil exhibited strong anti-proliferative, anti-metastatic, and apoptotic effects and therefore may have potential applications in cancer treatment, however, further studies of oil regarding the action mechanisms and compounds involved in anticancer therapy are necessary.

Rapid Analysis of the Chemical Compositions in Semiliquidambar cathayensis Roots by Ultra High-Performance Liquid Chromatography and Quadrupole Time-of-Flight Tandem Mass Spectrometry.

Semiliquidambar cathayensis Chang was a traditional medicinal plant and used to treat rheumatism arthritis and rheumatic arthritis for centuries in China with no scientific validation, while only 15 components were reported. Thus, a rapid, efficient, and precise method based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) was applied in both positive- and negative-ion modes to rapidly analysis the main chemical compositions in S. cathayensis for the first time. Finally, a total of 85 chemical compositions, including 35 alkaloids, 12 flavonoids, 7 terpenoids, 5 phenylpropanoids, 9 fatty acids, 7 cyclic peptides, and 10 others were identified or tentatively characterized in the roots of S. cathayensis based on the accurate mass within 5 ppm error. Moreover, alkaloid, flavonoid, phenylpropanoid, and cyclic peptide were reported from S. cathayensis for the first time. This rapid and sensitive method was highly useful to comprehend the chemical compositions and will provide scientific basis for further study on the material basis, mechanism and clinical application of S. cathayensis roots.

Wound healing potential of oil extracted from Parrotiopsis jacquemontiana (Decne) Rehder.

ETHNOPHARMACOLOGICAL RELEVANCE: Oil extracted from Parrotiopsis jacquemontiana stem traditionally used for wound healing, body aches and dermatitis. In this study we have evaluated oil for its phytoconstituents, antioxidant, antimicrobial and wound healing activities. METHODS: Phytochemical characterization of oil was determined by standard qualitative procedures, gas chromatography mass spectrometry technique (GC-MS) and Fourier transform infra-red spectroscopy (FT-IR). The in vitro antioxidant aptitude was determined by scavenging of DPPH radical, hydroxyl ion, nitric oxide, inhibition of ß-carotene bleaching assay and iron chelation power assay. The antimicrobial potential of oil was investigated by disc diffusion method against multidrug resistant (MDR) bacterial isolates and fungal strains. Wound healing was performed in vivo with determination of wound contraction rates, histopathology, hemostatic potential and hydroxyproline estimation. RESULTS: GC-MS analysis indicated that oil was constituted mainly of 2, 6-dimethyl-8-oxoocta-2, 6-dienoic acid, methyl ester (18.2%), syringol (17.8%), catechol (12.4%), guaiacol (5.2%), p-cresol (5.4%) and phenol, 2-propyl- (3.7%). FT-IR analysis revealed several important functional groups in its chemical composition especially phenolic O-H compound stretching. Scavenging of DPPH radical, hydroxyl ion, nitric oxide, inhibition of ß-carotene oxidation and iron chelation power assays indicated strong antioxidant activities of oil. Further it efficiently inhibited growth of multidrug resistant isolates of Staphylococcus aureus, S. lugdenesis, Klebsiella pneumoniae, Escherichia coli, Coagulase -ve staphylococci and Pseudomonas aeruginosa. The minimum inhibitory concentrations ranged between (32-256) (µg/mL) of oil. The oil also strongly inhibited the growth of various fungal isolates with low level of minimum inhibitory concentrations (64-256) µg/mL. Remarkable rate for wound closure and epithelization, hemostatic potential and marked increase (p < 0.05) in hydroxyproline content was observed for oil during wound healing in rat. CONCLUSION: The results suggested that oil can be used as a potential source of wound healing therapeutics.

Phytochemical investigation and antimicrobial appraisal of Parrotiopsis jacquemontiana (Decne) Rehder.

BACKGROUND: Parrotiopsis jacquemontiana (Decne) Rehder. is locally used for skin infections and in wound healing. In this study we have evaluated methanol extract of its leaves and derived fractions against the clinical multi-drug resistant bacterial strains. METHODS: P. jacquemontiana leaves powder extracted with 95% methanol (PJM) and fractionated in escalating polarity of solvents; n-hexane (PJH), chloroform (PJC), ethyl acetate (PJE), n-butanol (PJB) and the remaining as aqueous fraction (PJA). Clinical as well as environmental 19 bacterial strains and 8 fungal strains were screened for minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Preliminary phytochemical investigation for various phytochemical classes was also carried out. RESULTS: PJM contained the coumarins, phenols, flavonoids, tannins, alkaloids, glycosides, saponins, sterols, phlobatannins, steroids, phytosterols, triterpenoids, acids, quinones, proteins, vitamin C, betacyanins, oils and resins while anthraquinones, phytosteroids, carbohydrates and anthocyanins were not detected. Disc diffusion assay (1 mg/disc) indicated the sensitivity of all the MDR strains of bacteria with PJM, PJE and PJB, while no inhibition was recorded with PJA. PJH and PJC inhibited the growth of all the strains of Staphylococcus aureus, Pseudomonas aeruginosa and Coagulase negative staphylococci used in this study. Maximum zone of inhibition (35.5 ± 1.32 mm) was obtained with PJM against Staphylococcus lugdenesis MDR (6197). Comparatively lower MIC (8-64 µg/ml) and MBC (32-256 µg/ml) values were recorded for PJM and PJE. In case of fungal strains only PJM, PJE and PJB markedly inhibited the growth and lower MIC (8-128 µg/ml) and MFC (32-512 µg/ml) values were determined for PJM and PJE. CONCLUSION: The remarkable inhibition of various bacterial and fungal strains at low doses of the extract/fractions suggested the strong antibacterial, antifungal and anti-candidal potential of P. jacquemontiana leaves.

Protective potential of Parrotiopsis jacquemontiana (Decne) Rehder on carbon tetrachloride induced hepatotoxicity in experimental rats.

The current study aimed at exploring hepatoprotective potential of Parrotiopsis jacquemontiana leaves methanol extract (PJM) in rat. PJM constituted of significant amount of total phenolic and total flavonoid content. PJM and ethyl acetate fraction (PJE) exhibited strong antioxidant potential (DPPH, hydroxyl ion, nitric oxide, iron chelating, ß-carotene, reducing power and phosphomolybdate assay) in comparison to other extracts. CCl4 toxicity displayed significant (p<0.05) increase in level of TBARS, H2O2, nitrite while a decrease in SOD, CAT, POD and GSH in liver samples of CCl4 treated group. Serum analysis indicated significant increase in levels of ALT, AST and ALP and globulin whereas a decrease in albumin and total protein was also reported. In addition, levels of pro-inflammatory and fibrogenic cytokines (TNF-α, IL-6, TGF.ß1, and leptin) of liver serum were elevated whereas adiponectin (anti-inflammatory cytokine) level was decreased in treated rats. CCl4 induced DNA damage and histopathological architecture was also studied. However, co-administration with PJM in a dose-dependent manner reversed all the above pathological parameters caused by CCl4 toxicity. HPLC-DAD analysis confirmed the existence of rutin, gallic acid, myricetin and caffeic acid in PJM and PJE while catechin was additionally present in PJM. Based on rich-antioxidant profile and hepatoprotective outcome on various pathological parameters prompted by CCl4, it can be assumed to be a promising candidate shrub for phytomedicine development against various liver ailments and oxidative-stress related disorders.

Wound Healing Potential of Chlorogenic Acid and Myricetin-3-O-ß-Rhamnoside Isolated from Parrotia persica.

Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae) in wound repair by analyzing the regenerative effects of its two main phenolic compounds, myricetin-3-O-ß-rhamnoside and chlorogenic acid. To accomplish this, we performed phytochemical profiling and characterized the chemical structure of pure compounds isolated from P. persica, followed by an analysis of the biological effects of myricetin-3-O-ß-rhamnoside and chlorogenic acid on three cell types, including keratinocytes, fibroblasts, and endothelial cells. Myricetin-3-O-ß-rhamnoside and chlorogenic acid exhibited complementary pro-healing properties. The percentage of keratinocyte wound closure as measured by a scratch assay was four fold faster in the presence of 10 µg/mL chlorogenic acid, as compared to the negative control. On the other hand, myricetin-3-O-ß-rhamnoside at 10 µg/mL was more effective in promoting fibroblast migration, demonstrating a two-fold higher rate of closure compared to the negative control group. Both compounds enhanced the capillary-like tube formation of endothelial cells in an in vitro angiogenesis assay. Our results altogether delineate the potential to synergistically accelerate the fibroblastic and remodelling phases of wound repair by administering appropriate amounts of myricetin-3-O-ß-rhamnoside and chlorogenic acid.

Safety evaluation of styrax liquidus from the viewpoint of genotoxicity and mutagenicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Styrax liquidus is a resinous exudate (balsam) obtained from the wounded trunk of the Liquidambar orientalis Mill. (Hamamelidaceae). Styrax has been used for treatment of various ailments in Turkish folk medicine such as skin problems, peptic ulcers, nocturnal enuresis, parasitic infections, antiseptic or as expectorant. AIM OF STUDY: In spite of frequent use of styrax in Turkish folk medicine as well as once as a stabilizer in perfumery industry, negative reports have been noticed by the international authority for restriction its use based on some limited evidences from an in vitro study. The aim of the present study was to evaluate the genotoxic and cytotoxic potential of styrax and its ethanolic extract using in vivo and in vitro assays, as well as an antimutagenic assay and also to determine its phenolic constituents with chromatographic analysis. MATERIALS AND METHODS: In vitro mutagenicity and antimutagenicity of styrax and its ethanolic extract were evaluated by Ames test performed on Salmonella TA98 and TA100 strains with and without metabolic activation (10- 30,000µg/plate). The genotoxicity was also studied in vivo by chromosomal aberrations assay on bone marrow of Balb C mice with different its concentrations (500-2000mg/kg body weight). Cytotoxicity has been evaluated by the MTT assay using L929 cell line. Its phenolic constituents were determined by HPLC analysis. RESULTS: Genotoxicological investigations of styrax or its ethanolic extract showed that none of the tested concentrations induced a significant increase in the revertant number of TA98 and TA100 strains with or without metabolic activation, indicating no mutagenicity to the tested strains. Also results indicated that up to 2000mg/kg body weight, styrax is not genotoxic in mammalian bone marrow chromosome aberration test in vivo. In cytotoxicity study, the IC50 values of styrax and its ethanolic extract were found to be 50.22±1.80 and 59.69±11.77µg/mL, respectively. Among the studied reference standards the major phenolic acids in styrax balsam was found to be p-coumaric acid (2.95mg/g), while in its ethanolic extract not only p-coumaric acid (11.46mg/g), but also gallic acid (1.60mg/g) were found to the main components. CONCLUSION: The findings of the present study provide scientific basis to the safety of styrax from the viewpoint of genotoxicity risk, and in fact, it was found to be beneficial against genotoxicity.

Effects of extracts from Corylopsis coreana Uyeki (Hamamelidaceae) flos on xanthine oxidase activity and hyperuricemia.

OBJECTIVES: This study aims to investigate xanthine oxidase (XO) inhibitory activity and antihyperuricemic effects of Corylopsis coreana Uyeki flos extracts and the phytochemicals contained therein. METHODS: Ethanolic extracts of the plant were prepared, and the extraction process was optimized with respect to flavonoid content and XO inhibitory activity. The optimized ethanolic extract was tested for its XO inhibitory activity and antihyperuricemic effects in potassium oxonate-induced hyperuricemic mice. KEY FINDINGS: The 80% ethanolic extract showed the highest total flavonoid content and in-vitro XO inhibitory activity. In-vivo studies demonstrated that the optimized 80% ethanolic extract could inhibit hepatic XO activity and significantly alleviate hyperuricemia at a relatively low oral dose (50 mg/kg) in mice. Additionally, an in-vitro enzyme inhibition study showed that phytochemicals such as bergenin, isosalipurposide, quercetin and quercitrin may be the key constituents responsible for the observed antihyperuricemic effects of the extract. CONCLUSIONS: This study is the first report on the XO inhibitory and antihyperuricemic effects of C. coreana Uyeki flos extract, which can be therapeutically applied in treating hyperuricemia and gout.

HPLC Analysis, Optimization of Extraction Conditions and Biological Evaluation of Corylopsis coreana Uyeki Flos.

A method for the separation and quantification of three flavonoids and one isocoumarin by reverse-phase high performance liquid chromatography (HPLC) has been developed and validated. Four constituents present in a crude ethanolic extract of the flowers of Coryloposis coreana Uyeki, were analyzed. Bergenin, quercetin, quercitrin and isosalipurposide were used as calibration standards. In the present study, an excellent linearity was obtained with an r² higher than 0.999. The chromatographic peaks showed good resolution. In combination with other validation data, including precision, specificity, and accuracy, this method demonstrated good reliability and sensitivity, and can be conveniently used for the quantification of bergenin, quercetin, quercitrin and isosalipurposide in the crude ethanolic extract of C. coreana Uyeki flos. Furthermore, the plant extracts were analyzed with HPLC to determine the four constituents and compositional differences in the extracts obtained under different extraction conditions. Several extracts of them which was dependent on the ethanol percentage of solvent were also analyzed for their antimicrobial and antioxidant activities. One hundred % ethanolic extract from C. coreana Uyeki flos showed the best antimicrobial activity against the methicillin-resistant Staphylococcus aureus (MRSA) strain. Eighty % ethanolic extract showed the best antioxidant activity and phenolic content. Taken of all, these results suggest that the flower of C. coreana Uyeki flos may be a useful source for the cure and/or prevention of septic arthritis, and the validated method was useful for the quality control of C. coreana Uyeki.

[Chemical Constituents from Semiliquidambar cathayensis Roots].

OBJECTIVE: To study the chemical constituents from the roots of Semiliquidambar cathayensis. METHODS: The roots of Semiliquidambar cathayensis were extracted with 80% ethanol for reflux. Chemical constituents were isolated by silica gel chromatography and Sephadex LH-20 column chromatography from petrol ether part and ethyl acetate part of extracts. Their structures were identified on the basis of physico-chemical characters and spectroscopic analysis. RESULTS: Eleven compounds were obtained from the roots of Semiliquidambar cathayensis, and identified as 3-acetyl-12-ene-oleanolic acid methyl ester (1), ß-sitosterol (2), 3-acetyl-12-ene-oleanol-ic acid (3), 2α,3ß-dihydroxy-lup-20(29)-en-28-oic acid (4), (24R)-5α-stignast-3,6-dione (5), betulonic acid (6), stearic acid (7), hexadecanoic acid (8), 3-oxo-olean-12-en-28-oic acid (9), arjunolic acid (10) and daucosterol (11). CONCLUSION: Compounds 1,3 - 6 and 8 are isolated from this genus for the first time.

Isolation of new flavan-3-ol and lignan glucoside from Loropetalum chinense and their antimicrobial activities.

Phytochemical and antimicrobial activity study on the ethanol extract of the leaves and stems of Loropetalum chinense led to the isolation of a new flavan-3-ol compounds, 8-[1-(3,4-dihydroxyphenyl)-3-methoxy-3-oxopropyl]-catechin (loropetaliside A) (1) and a new lignan glucoside, 1-(5-hydroxy-3-methoxyphenyl)-2-(2-ß-glucopyranosyl-4-hydroxy-5-(1-(E)propen-3-ol)-phenyl)-propane-3-ol (loropetaliside B) (3) and several known compounds manglieside D (2), quercetin (4), kaempferol-3-O-D-glucopyranoside (5), quercetin-3-O-ß-L-rhamnoside (6) and tiliroside (7). Their structures were elucidated on the basis of extensive spectroscopic analysis.

Anti-oxidative and anti-proliferative activity on human prostate cancer cells lines of the phenolic compounds from Corylopsis coreana Uyeki.

Fifteen phenolic compounds, including three caffeoyl derivatives, four gallotannins, three ellagitannins and five flavonoids, were isolated from an 80% MeOH extract of the leaves of Corylopsis coreana Uyeki (Korean winter hazel; CL). The anti-oxidative activities [1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase superoxide scavenging activities (NBT)] and the anti-proliferative activity on human prostate cancer cell lines (DU145 and LNCaP) were also evaluated.

[Primary study of skin wound healing in rats for Loropetalum chinens].

OBJECTIVE: Cutaneous wound is a common health problem of humans. Loropetalum chinens, a medicinal plant, is widely used to treat wounds among the people. The research aims to observe whether L. chinens can promote the rats' wounds healing process, isolate the extracts primarily and commit the wound healing selection, which provide work basis for wound healing research of L. chinens. METHOD: First we analyzed the possible components with HC-MS/MS, then committed our wound healing experiments for L. chinens in the rat incision wound model and excision wound model, which are commonly used worldwide. After that, we carried on the preliminary isolation of the L. chinens and we screened the heal-promoting effects of the isolations in incision wound model. RESULT: L. chinens significantly accelerates the wound healing of rat's skin, shortens the healing period, enhances the healing intensity and promotes the cell proliferation and blood vessels formation around the wounds. The isolations, which are petroleum ether layer, ethyl acetate layer and n-butyl alcohol layer, exert heal-promoting effects. It indicates that the possible morphon that promotes wound healing may exist in these three components, with small polar. CONCLUSIONS: L. chinens possesses strong wound healing promoting effects, and the active constituent, with small polar, exists in petroleum ether layer, ethyl acetate layer and n-butyl alcohol layer, and we should focus on these three layers when carrying on further studies.

New monoterpene glycosides and phenolic compounds from Distylium racemosum and their inhibitory activity against ribonuclease H.

Two new monoterpene glycosides, distyloside A-B (1-2), and a new megastigmane glucoside, iso-dihydrodendranthemoside A (3) were isolated from twigs and leaves of Distylium racemosum, along with five known phenolic compounds (4-8). The structures were established via spectroscopic techniques and chemical transformations, and the absolute stereochemistry of 3 was determined by Mosher's esterification. A homogeneous fluorescence resonance energy transfer (FRET) quenching assay was used to determine the inhibitory activity of isolates (1-8) on the ribonuclease H enzymes from HIV-1, 2, human, and Escherichia coli. Among them, 6″-O-galloylsalidroside (6) showed potent inhibitory effects with an IC(50) value of 3.5 µM on HIV-2, and 1.7 µM on human RNase H, respectively.

Compounds with tyrosinase inhibition, elastase inhibition and DPPH radical scavenging activities from the branches of Distylium racemosum Sieb. et Zucc.

Twenty compounds were isolated from the ethanol extract of Distylium racemosum branches and their inhibitory activities on tyrosinase, elastase and free radicals evaluated. The isolated compounds were identified as dibenzofurans (1-4), abscisic acid (5), 6'-O-galloylsalidroside (6), catechin derivatives (7-11), gallic acid derivatives (12-14), tyrosol (15), flavonoids (16-18), lupeol (19) and 1,2,3,6-tetragalloylglucose (20). For study of tyrosinase inhibition activities, when compared with arbutin (IC(50) 48.8 µg/mL), four compounds (8, 11, 13, 17) showed higher activities, with IC(50) values of 4.8, 30.2, 40.5 and 37.7 µg/mL, respectively. For the elastase inhibition test, dibenzofuran 1 showed greater activity than the positive control, oleanolic acid (IC(50) 9.7 µg/mL), with an IC(50) of 7.7 µg/mL. In the studies on DPPH radical scavenging activities, five compounds (11, 12, 13, 14, 15) showed higher activities than ascorbic acid (IC(50) 5.0 µg/mL), with IC(50) values of 4.6, 3.9, 2.9, 3.8 and 4.7 µg/mL, respectively.

[Analysis of fatty acids in leaves of Loropetalum chinense and L. chinense var. rubrum by GC-MS].

OBJECTIVE: To extract and analyze fatty acids in leaves of L. chinense Oliver and L. chinense var. rubrum Yieh. METHODS: The fatty acids were extracted with Soxhlet extractor and identified by the GC-MS method. RESULTS: 31, 26 and 30 components were identified from the leaves of L. chinense, the green leaves and red leaves of L. chinense var. rubrum. There were 19, 14 and 16 kinds of fatty acid in the respective leaves, which accounted for 99.09%, 95.31% and 98.83% of the total extraction, respectively. The main components in the extraction were oleic acid (30.77%, 47.01%, 75.28%), linoleic acid (48.49%, 29.26%, 0%), hexadecanoic acid (9.83%, 8.87%, 11.71%), octadecanoic acid (3.86%, 3.18%, 4.88%) and docosanoic acid (2.37%, 2.17%, 2.58%). CONCLUSION: Many kinds of unsaturated fatty acids exist in leaves of L. chinense Oliver and L. chinense var. rubrum Yieh. The leaves of these two plants can be used as the traditional Chinese medicine.

[Chemical constituents from roots of Distylium myricoides].

OBJECTIVE: To study the chemical constituents from the roots of Distylium myricoides. METHOD: The chemical constituents were isolated and separated with chromatographic techniques, and structures were identified by spectroscopic methods. RESULT: Eight phenolic compounds were isolated and identified as: 4-hydroxy-2-methoxyphenol 1-O-beta-D-(6'-O-galloyl) glucopyranoside (1), 4-hydroxy-3-methoxy-phenol 1-O-beta-D-(6'-O-galloyl) glucopyranoside (2), 3,4,5-tri methoxyphenol 1-O-beta-D-(6'-O-galloyl) glucopyranoside (3), 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside (4), methyl gallate (5), ethyl gallate (6), 3,4-dihydroxybenzoic acid (7), gallic acid (8). CONCLUSION: All compounds were isolated from the genus Distylium for the first time.

Lupane and oleanane triterpenoids from the cones of Liquidamber styraciflua.

A new lupane- (1) and a new oleanane-type (2) triterpenoid, together with a known compound, massagenic acid G, were isolated from the cones of Liquidamber styraciflua. The structures of 1 and 2 were determined as 6beta,30-dihydroxy-3-oxolup-20(29)-en-28-oic acid and 3alpha-hydroxy-11-oxoolean-12-en-28-oic acid, respectively, on the basis of spectroscopic methods and chemical conversion. Compound 1 and several structural analogues were evaluated for cytotoxicity against the P388 (murine lymphocyte leukemia) and the A549 (human lung cancer) cell lines.

Cancer chemopreventive effect of orally administrated lupane-type triterpenoid on ultraviolet light B induced photocarcinogenesis of hairless mouse.

Ultraviolet light is the most common cause of skin cancers in human and several effects of ultraviolet light B (UVB) are thought to contribute to skin photocarcinogenesis. The generation of seven triterpenoids from the cones of Liquidamber styraciflua (Hamamelidaceae were examined for their nitric oxide (NO) scavenging activity as the first screening of an in vivo mouse skin anti-initiating assay. 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (1), which showed the strongest inhibitory effect among these compounds, was studied further for its anti-tumor initiating activity on mouse models initiated with ultraviolet-B (UVB) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). Oral administration of the compound 1 during a period before and after the three times of UVB irradiation exhibited a remarkable effect: administration of 0.0025% solution of the compound 1 given orally only to the test group, which started 1 week before and ended 1 week after the irradiation, showed approximately 50% inhibition of tumor incidence and tumor multiplicity in comparison to the control group. Thus, compound 1 could act as a potent anti-tumor initiator in UVB radiation photocarcinogenesis.

New cytotoxic oleanane-type triterpenoids from the cones of Liquidamber styraciflua.

Two new oleanane-type triterpenoids (1 and 2), together with two known compounds, 6beta-hydroxy-3-oxo-lup-20(29)-en-28-oic acid (3) and 3,11-dioxoolean-12-en-28-oic acid (4), were isolated from the stem bark of Liquidamber styraciflua. The structures of 1 and 2 were determined to be 25-acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3alpha,25-dihydroxyolean-12-en-28-oic acid (2) on the basis of spectroscopic methods and chemical conversion. Compound 1 showed strong cytotoxicity against a disease-oriented panel of 39 human cancer cell lines, although compounds 2, 3, and 4 showed weaker activity compared to 1.