Surawat Jariyawat

Cytotoxic alkaloids from stems, leaves and twigs of Dasymaschalon blumei.

Bioassay-guided fractionation of the cytotoxic ethyl acetate extract from the stems of Dasymaschalon blumei (Annonaceae) led to the isolation of four aristololactam alkaloids, including the hitherto unknown 3,5-dihydroxy-2,4-dimethoxyaristolactam (1), as well as the three known compounds, aristolactam BI, goniopedaline, and griffithinam. Additionally, the cytotoxic extract from the combined leaves and twigs of the same plant yielded three known oxoaporphine alkaloids, oxodiscoguattine, dicentrinone, and duguevalline. The structures of aristolactams and oxoaporphine alkaloids were elucidated on the basis of spectroscopic methods. All isolates were evaluated for cytotoxicity against a panel of mammalian cancer cell lines and a noncancerous human embryonic kidney cell Hek 293.

Protection of centrilobular necrosis by Curcuma comosa Roxb. in carbon tetrachloride-induced mice liver injury.

AIM OF THE STUDY To investigate the protective effect and possible mechanism of Curcuma comosa hexane extract on CCl(4)-induced liver injury in adult male mice. MATERIALS AND METHODS Hepatotoxicity was induced by an intraperitoneal injection of CCl(4) and was evaluated after 24 h from the elevations of plasma alanine transaminase (ALT) and aspartate transaminase (AST) activities, and histological analysis of liver injuries. Hexane extract of Curcuma comosa was given at different time points from 1 to 72 h, prior to CCl(4) administration and the protection from liver injury was assessed. RESULTS CCl(4)-induced damage to liver cells was resulted in elevations of plasma ALT and AST activities. Pretreatment with Curcuma comosa hexane extract 24 h at a dose of 100, 250, and 500 mg/kg BW resulted in a dose-dependent prevention of the increases in plasma ALT and AST activities as well as time dependent. The protective effect of the extract at a dose of 500 mg/kg BW was seen at 12-24 h. Pretreatment of the extract completely prevented elevation of plasma ALT and AST activities, and centrilobular necrosis. The protective effect of Curcuma comosa was associated with restoration of hepatic glutathione content, and CYP2E1 catalytic activity, and its mRNA and protein levels as well as increase in activity of glutathione-S-transferase (GST). CONCLUSION Curcuma comosa has a potent protective property against CCl(4)-induced hepatic injuries via the activation of detoxifying mechanisms (GST) as well as reduction of the bioactive toxic metabolites. Therefore, Curcuma comosa may be beneficial for prevention of hepatotoxicity.

Cleistanthoside A tetraacetate-induced DNA damage leading to cell cycle arrest and apoptosis with the involvement of p53 in lung cancer cells.

Lung cancer is the leading cause of cancer-related death worldwide and resistance to chemotherapeutic drugs is the major obstacle for effective treatment. The present study investigated the anticancer potential of cleistanthoside A tetraacetate (CAT), a derivative of cleistanthoside A from Phyllanthus taxodiifolius Beille on human lung cancer cells, LU-1. Multiple molecular approaches were used in this study and include measuring the anti-proliferative effect of CAT in LU-1 cells using flow cytometry; evaluating the induction of apoptosis by monitoring DNA fragmentation, phosphatidylserine externalization and activation of caspase-3 activity; and assaying the expression of regulatory proteins involved in cell cycle arrest and apoptosis using immunoblots. CAT potently inhibited LU-1 proliferation through an early G1 arrest with down-regulation of cdk4/6 and cyclin D1 proteins. CAT also inhibited DNA topoisomerase IIα activity resulting in DNA damage and increased the expression of the p53 protein with the subsequent induction of apoptosis. A decrease in the Bcl-2/Bax ratio, activation of caspase-3 activity and cleavage of PARP accompanied apoptosis. CAT is highly toxic to lung cancer and its primary targets are the inhibition of topoisomerase IIα activity and inducing apoptosis through a G1 arrest. These properties indicate that CAT is a promising anticancer agent for treatment of lung cancer.

Cytotoxic, antitopoisomerase IIα, and anti-HIV-1 activities of triterpenoids isolated from leaves and twigs of Gardenia carinata.

Eight new cycloartane triterpenoids (1-8), named carinatins A-H, and the known compounds secaubryolide (9) and dikamaliartane D (10) were isolated from the leaves and twigs of Gardenia carinata. Their structures were determined on the basis of spectroscopic methods. Cytotoxic, antitopoisomerase IIα, and anti-HIV-1 activities of compounds 1-7, 9, and 10 were investigated.

Polyoxygenated cyclohexene derivatives isolated from Dasymaschalon sootepense and their biological activities

Six new naturally occurring polyoxygenated cyclohexene derivatives together with eight related known derivatives, two known alkaloids, and two known flavonoid derivatives were isolated from bioassay-guided fractionation of the ethyl acetate extract of the leaves and twigs of Dasymaschalon sootepense. The structure elucidation and determination of absolute configurations were established by various spectroscopic methods, X-ray diffraction techniques as well as comparison with the literature data. Several isolated compounds were evaluated for their cytotoxic, anti-HIV-1 RT and anti-inflammatory activities.

Zederone, a Sesquiterpene from Curcuma elata Roxb, is Hepatotoxic in Mice

The present study aimed to investigate the hepatotoxicity of zederone isolated from Curcuma elata in mice. Adult male mice were intraperitoneally injected with a single dose of zederone (50-300 mg/kg body weight [BW]). Twenty-four hours after the injection, zederone induced liver enlargement with scattered white foci over the organ. The medium lethal dose (LD50) value at 24 hours of zederone was approximately 223 mg/kg BW. Hepatic centrilobular necrosis with marked increases in plasma alanine transaminase activity and total bilirubin levels was observed. Zederone at a dose of 200 mg/kg BW markedly decreased the activity of superoxide dismutase and the hepatic glutathione content, whereas the activity of catalase was not altered. The compound at this dose also increased the messenger RNA (mRNA) expression of Cyp2b10 and Cyp3a11, which are the main drug-metabolizing enzymes in the liver. The mRNA expression of proinflammatory cytokine tumor necrosis factor α was increased. The nuclear factor-E2-related factor 2 protein, which is the transcription factor regulating the antioxidant gene expression, was decreased. The histopathology of massive hepatic centrilobular necrosis with an increase in the expression of cytochrome P450 (Cyp) suggests that the possible potentiation of zederone-induced hepatotoxicity implicated the induction of Cyps, which leads to the formation of biological reactive metabolites and that cause the oxidative stress and liver cell injuries.

Cytotoxic lanostanes from fruits of Garcinia wallichii Choisy (Guttiferae)

Five new lanostanes, wallichinanes A-E (1-5) together with a known lanostane derivative 6 were isolated from the cytotoxic hexanes extract of fruits of Garcinia wallichii Choisy (Guttiferae). The structures of the isolated compounds were established by analysis of spectroscopic data, X-ray diffraction technique as well as comparison with the literature data. The cytotoxicity of all isolated compounds against a panel of cultured cancer cell lines was evaluated. Compound 4 exhibited good cytotoxicity with ED50 values ranging from 3.91 to 7.63μM.

EFFECT OF CHRONIC K+ DEFICIENCY ON CONTRACTILE PROPERTIES OF SOLEUS MUSCLE IN RATS: EVIDENCE OF SEX DIFFERENCES

1. Alterations in skeletal muscle function of chronically K+‐depleted male and female rats were investigated in isolated soleus muscles.

Polycyclic polyprenylated acylphloroglucinols and biphenyl derivatives from the roots of Garcinia nuntasaenii Ngerns. & Suddee

Seven previously undescribed compounds, including three polycyclic polyprenylated acylphloroglucinols (garcinuntins A-C), three biphenyl derivatives (garcinuntabiphenyls A-C) and a lanostane triterpene (garcinuntine), along with thirteen known compounds were isolated from the root of Garcinia nuntasaenii Ngerns. & Suddee. Their structures were elucidated on the basis of spectroscopic techniques. For garcinuntins A-C, the absolute configurations were confirmed by the combination of single X-ray crystallography and ECD calculations. Anti-HIV activity using anti-HIV-1 reverse transcriptase and syncytium inhibition assays, and cytotoxic activity against a panel of cultured mammalian cancer cell lines of isolated compounds were investigated.

Protective effect of diarylheptanoids from Curcuma comosa on primary rat hepatocytes against t-butyl hydroperoxide-induced toxicity

Abstract Context: Curcuma comosa Roxb. (Zingiberaceae) has traditionally been used as an anti-inflammatory agent in liver, and recent study has shown its hepatoprotective effect against CCl4-induced liver injury in vivo. Objective: This study further assesses the protective effect of C. comosa extracts and its isolated compounds against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in isolated primary rat hepatocytes. Materials and methods: Isolated primary hepatocytes were pretreated with either ethanol (5–50 μg/ml) or hexane extract (1–50 μg/ml), or two diarylheptanoids (4–35 μM): compound D-91 [1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol] and compound D-92 [(3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol], from C. comosa for 2 h prior to exposure to 1.5 mM t-BHP for 15 and 30 min. Their hepatoprotective activities were then determined. Results: t-BHP markedly caused the formation of MDA and ALT leakage from the hepatocytes. Pretreatment with the C. comosa ethanol extract showed greater protective effect than the hexane extract, and the effect was concentration related. Treating the hepatocytes with compound D-92 provided greater protective effect than compound D-91. IC50 values of compounds D-91, D-92, and silymarin for the protection of ALT leakage at 30 min were 32.7 ± 1.1, 9.8 ± 0.7, and 160 ± 8 μM, respectively. Further investigation showed that compound D-92 was more effective in maintaining the intracellular glutathione content in the t-BHP treated group, whereas the reduction in antioxidant enzymes, glutathione peroxidase and glutathione-S-transferase activities, were not improved. Discussion and conclusion: Results suggest that diarylheptanoids are the active principles that provide protection against t-BHP-induced injury. Their ability to maintain intracellular glutathione content is the main mechanisms underlying the protective action.