Effects of chlorogenic acid and its metabolites on the sleep-wakefulness cycle in rats

The effect of chlorogenic acid on the sleep-wakefulness cycle in rats was investigated in comparison with those of caffeic acid (the metabolite of chlorogenic acid) and dihydrocaffeic acid (the metabolite of caffeic acid). A significant prolongation of sleep latency was observed with chlorogenic acid and caffeic acid at a dose of 500 and 200 mg/kg, respectively. On the other hand, no remarkable effects were observed with dihydrocaffeic acid even at a dose of 500 mg/kg. Caffeine caused a significant increase in sleep latency and waking time and decrease in non-rapid eye movement sleep time at a dose of 10 mg/kg. In contrast, chlorogenic acid and its metabolites had no significant effects on each sleep state. From these results, it may be concluded that chrologenic acid caused a mild arousal effect compared with that of caffeine, and the effect of chlorogenic acid may have occurred through its metabolite caffeic acid.     

Quantitative assessment of content of phenolic acids in the medicinal herb showy tick trefoil

The qualitative and quantitative contents of phenolic acids in the herb showy tick trefoil (Desmodium canadense (L.) D. C., Fabaceae) collected at different growth phases at the Department of Medicinal Herbs, Kaunas Botanical Garden, Vitautas the Great University, were studied. HPLC analysis identified five phenolic acids: chlorogenic, vanillic, 4-hydroxycinnamic, ferulic, and caffeic acids). The largest quantities of phenolic acids in the herb accumulated in the budding and flowering phases. These were dominated by vanillic acid (0.240 mg/g), caffeic acid (0.178 mg/g), and chlorogenic acid (0.120 mg/g), and the quantities of these acids gradually decreased during plant growth.     

Anti-fibrotic effects of Cuscuta chinensis with in vitro hepatic stellate cells and a thioacetamide-induced experimental rat model

Context: Cuscuta chinensis Lam. (Convolvulaceae) has been used as a traditional herbal remedy for treating liver and kidney disorders.

Objective: Anti-fibrotic effects of C. chinensis extract (CCE) in cellular and experimental animal models were investigated.

Materials and methods: HSC-T6 cell viability, cell cycle and apoptosis were analysed using MTT assay, flow cytometry and Annexin V-FITC/PI staining techniques. Thioacetamide (TAA)-induced fibrosis model was established using Sprague Dawley rats (n?=?10). Control, TAA, CCE 10 (TAA with CCE 10?mg/kg), CCE 100 (TAA with CCE 100?mg/kg) and silymarin (TAA with silymarin 50?mg/kg). Fibrosis was induced by TAA (200?mg/kg, i.p.) twice per week for 13 weeks. CCE and silymarin were administered orally two times per week from the 7th to 13th week. Fibrotic related gene expression (α-SMA, Col1α1 and TGF-β1) was measured by RT-PCR. Serum biomarkers, glutathione (GSH) and hydroxyproline were estimated by spectrophotometer using commercial kits.

Results: CCE (0.05 and 0.1?mg/mL) and silymarin (0.05?mg/mL) treatment significantly (p?p?in vivo studies, CCE (10 and 100?mg/kg) treatment ameliorated the TAA-induced altered levels of serum biomarkers, fibrotic related gene expression, GSH, hydroxyproline significantly (p?Conclusions: CCE can be developed as a potential agent in the treatment of hepatofibrosis.     

7,8-Dihydroxyflavone, a TrkB agonist, attenuates behavioral abnormalities and neurotoxicity in mice after administration of methamphetamine

Rationale

It is widely recognized that methamphetamine (METH) induces behavioral abnormalities and dopaminergic neurotoxicity in the brain. Several lines of evidence suggest a role for brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), in METH-induced behavioral abnormalities.

Objective

In this study, we examined whether 7,8-dihydroxyflavone (7,8-DHF), a novel potent TrkB agonist, could attenuate behavioral abnormalities and dopaminergic neurotoxicity in mice after administration of METH.

Results

Pretreatment with 7,8-DHF (3.0, 10, or 30 mg/kg), but not the inactive TrkB compound, 5,7-dihydroxyflavone (5,7-DHF) (30 mg/kg), attenuated hyperlocomotion in mice after a single administration of METH (3.0 mg/kg), in a dose-dependent manner. The development of behavioral sensitization after repeated administration of METH (3.0 mg/kg/day, once daily for 5 days) was significantly attenuated by pretreatment with 7,8-DHF (10 mg/kg). Furthermore, pretreatment and subsequent administration of 7,8-DHF (10 mg/kg) attenuated the reduction of dopamine transporter (DAT) in the striatum after repeated administration of METH (3.0 mg/kg?×?3 at 3-hourly intervals). Treatment with ANA-12 (0.5 mg/kg), a potent TrkB antagonist, blocked the protective effects of 7,8-DHF on the METH-induced reduction of DAT in the striatum. Moreover, 7,8-DHF attenuated microglial activation in the striatum after repeated administration of METH.

Conclusions

These findings suggest that 7,8-DHF can ameliorate behavioral abnormalities as well as dopaminergic neurotoxicity in mice after administration of METH. It is likely, therefore, that TrkB agonists such as 7,8-DHF may prove to be potential therapeutic drugs for several symptoms associated with METH abuse in humans.     

Hydroalcoholic extract of Urtica circularis: A neuropharmacological profile

Abstract

Context: The genus Urtica has been known since ancient times. It has known to be useful for the treatment of different human ailments.

Objective: The present work evaluated the neuropharmacological effects of a hydroalcoholic extract of Urtica circularis (Hicken) Sorarú (Urticaceae).

Materials and method: The effect on central nervous system of U. circularis hydroalcoholic extract (from leaves and stems) administered by the intraperitoneal route in mice was evaluated by several tests: Pentobarbital- and midazolam-induced hypnosis, open field, hole board, elevated plus-maze and forced swimming. Phytochemical analysis was performed by high-performance liquid chromatography.

Results: A total of 300?mg/kg i.p. of the extract produced a significant prolongation of pentobarbital- (40?mg/kg i.p.; 60.1?min versus 25.4?min) and midazolam- (50?mg/kg i.v.; 53.4?min versus 25.1?min) induced sleeping time. The extract’s administration caused a marked reduction of the head-dipping response (DE₅₀: 373?mg/kg i.p.) in the hole-board test. Urtica circularis extract (DE₅₀: 46?mg/kg i.p.) reduced the spontaneous locomotor activity in the open field test. Flumazenil and atropine significantly antagonized the extract’s effect on the locomotor activity. No motor coordination disturbance was observed in the rota rod test at any doses. In the forced swimming test, the extract did not produce any change in the immobility time and it had no significant effects in elevated plus maze test. The phytochemical analysis revealed the presence of chlorogenic acid, vanillic acid, caffeic acid, vicenin-2, p-cumaric acid, ferulic acid, vitexin and isovitexin.

Conclusion: This study revealed that U. circularis hydroalcoholic extract possesses sedative activity, facilitating GABAergic and cholinergic transmission.     

Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice

Context: The application of bleomycin is limited due to its side effects including lung toxicity. Silymarin is a flavonoid complex isolated from milk thistle [Silybum marianum L. (Asteraceae)] which has been identified as an antioxidant and anti-inflammatory compound.

Objective: This study evaluates the effect of silymarin on oxidative and inflammatory parameters in the lungs of mice exposed to bleomycin.

Materials and methods: BALB/c mice were divided into four groups of control, bleomycin (1.5?U/kg), bleomycin plus silymarin (50 and 100?mg/kg). After bleomycin administration, mice received 10?d intraperitoneal silymarin treatment. On 10th day, blood and lung samples were collected for measurement of oxidative and inflammatory factors.

Results: Silymarin led to a decrease in lung lipid peroxidation (0.19 and 0.17?nmol/mg protein) in bleomycin-injected animals. Glutathione-S-transferase (GST) which was inhibited by bleomycin (32.4?nmol/min/mg protein) induced by higher dose of silymarin (41?nmol/min/mg protein). Silymarin caused an elevation in glutathione (GSH): 2.6 and 3.1?µmol/g lung compare with bleomycin-injected animals 1.8?µmol/g lung. Catalase (CAT) was increased due to high dose of silymarin (65.7?µmol/min/ml protein) compare with bleomycin treated-mice. Myeloperoxidase (MPO) which was induced due to bleomycin (p?p?Conclusions: Silymarin attenuated bleomycin induced-pulmonary toxicity. This protective effect may be due to the ability of silymarin in keeping oxidant–antioxidant balance and regulating of inflammatory mediator release.     

Protective effects of Ampelopsis brevipedunculata against in vitro hepatic stellate cells system and thioacetamide-induced liver fibrosis rat model

Context: Ampelopsis brevipedunculata Maxim (Vitaceae) is a traditional medicinal herb used for treating liver disorders.

Objective: The hepatoprotective effects of A. brevipedunculata ethanol extract (ABE) was investigated in experimental models of fibrosis.

Materials and methods: Hepatic stellate cells (HSCs) system in vitro and thioacetamide (TAA)-induced liver fibrosis rat model in vivo were used. Sprague–Dawley rats were divided into five groups of eight each (control, TAA, TAA with ABE 10?mg/kg, ABE 100?mg/kg and silymarin 50?mg/kg groups, respectively). Fibrosis was induced except to the control group by TAA (200?mg/kg, i.p.) twice per week for 13?weeks. ABE and silymarin was administered orally six times per week from the 7th week to the 13th week.

Results: In HSC-T6 cells, ABE (0.1?mg/mL) and silymarin (0.05?mg/mL) significantly (p?p?in vivo studies, ABE (10 and 100?mg/kg) treatment ameliorated the altered levels of serum biomarkers significantly (p?p?p?Conclusion: These results collectively indicate that ABE can potentially be developed as a therapeutic agent in the treatment of hepatic fibrosis.     

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

Context: Silymarin is the main flavonoid extracted from milk thistle, which has been used to treat liver diseases.

Objective: The in vivo effect of silymarin on HFD-induced insulin resistance and fatty liver in mice was studied.

Materials and methods: Male C57BL/6 mice were fed with high-fat diet (HFD) to induce obesity and insulin resistance and treated with 30, 60?mg/kg silymarin for 18 days. Food intake, body weight and the content/histology of epididymal fat and liver tissue were examined; the content of lipids, AST, ALT and inflammatory cytokines in serum were estimated.

Results: Administration of silymarin caused bodyweight loss in diet induced obesity (DIO) mice (HFD group: 47.7?g, 60?mg/kg group: 43.0?g) while the food intake remain unchanged. Silymarin (60?mg/kg) significantly reduced the epididymal fat mass (from 1.75?g to 1.12?g). Elevated plasma lipids (TC 6.1?mM, TG 1.3?mM, LDL 1.2?mM) in DIO mice were all suppressed by silymarin (TC 4.5?mM, TG 0.89?mM, LDL 0.9?mM), as well as insulin (5.1?ng/ml in HFD group to 2.0?ng/ml (60?mg/kg silymarin). Examination of cytokine levels (TNF-α, IL-1β and IL-6) in each group proved that silymarin treatment significantly decreased inflammation in DIO mice. Finally, silymarin effectively protected liver from HFD-induced injury as evidenced by decreasing histological damage and reducing ALT and AST levels, as follows: ALT; 47.4?U/L in HFD group to 28.4?U/L (60?mg/kg silymarin); AST; 150.1?U/L in HFD group to 88.1?U/L (60?mg/kg silymarin) in serum.

Discussion and conclusion: Our results suggested that silymarin-induced alleviation of inflammatory response could be a mechanism responsible for its benefits against liver damage and insulin resistance.     

Caffeic acid inhibits compound 48/80-induced allergic symptoms in mice

The effect of caffeic acid on scratching behavior and vascular permeability changes induced by compound 48/80 in ICR mice were investigated. An oral dose of 500 mg/kg of caffeic acid significantly inhibited scratching behavior and vascular permeability induced by compound 48/80. The inhibitory effects of daily administration of lower doses of caffeic acid, 100 and 200 mg/kg, were also investigated; and it was found that 200 mg/kg significantly inhibited compound 48/80-induced scratching behavior after the second week of consecutive administration. The effect of 200 mg/kg of caffeic acid on scratching behavior was observed up to the third week of the treatment. The decrease in histamine content induced by compound 48/80 was significantly antagonized by 200 mg/kg. The findings suggest that caffeic acid may be effective for treating itch and edema in allergic dermatitis.     

Cytotoxicity,antiviral and antimicrobial activities of alkaloids,flavonoids, and phenolic acids

Objective: Some natural products consisting of the alkaloids yohimbine and vincamine (indole-type), scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine, synephrine, and capsaicin (exocyclic amine-type); the flavonoid derivatives quercetin, apigenin, genistein, naringin, silymarin, and silibinin; and the phenolic acids namely gallic acid, caffeic acid, chlorogenic acid, and quinic acid, were tested for their in vitro antiviral, antibacterial, and antifungal activities and cytotoxicity.

Materials and methods: Antiviral activity of the compounds was tested against DNA virus herpes simplex type 1 and RNA virus parainfluenza (type-3). Cytotoxicity of the compounds was determined using Madin-Darby bovine kidney and Vero cell lines, and their cytopathogenic effects were expressed as maximum non-toxic concentration. Antibacterial activity was assayed against following bacteria and their isolated strains: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis, although they were screened by microdilution method against two fungi: Candida albicans and Candida parapsilosis.

Results: Atropine and gallic acid showed potent antiviral effect at the therapeutic range of 0.8–0.05 µg ml^?1, whilst all of the compounds exerted robust antibacterial effect.

Conclusion: Antiviral and antimicrobial effects of the compounds tested herein may constitute a preliminary step for further relevant studies to identify the mechanism of action.     

Brassica nigra plays a remedy role in hepatic and renal damage

Context: Black mustard [Brassica nigra (L.) Koch] of the Brassicaceae (Cruciferae) family is commonly used as a spice and a cheap source of antimicrobial agents for bacterial infections.

Objectives: The present investigation was to demonstrate the protective effect of the methanol extract of B. nigra leaves against d-galactosamine (d-GalN)-induced hepatic and nephrotoxicity in Wistar rats.

Methods: Activity of the methanol extract of B. nigra at doses of 200 and 400 mg/kg b.wt. against d-GalN (500 mg/kg b.wt.) induced toxicity, with silymarin used as the standard. Histological damage, activities of serum marker enzyme, hematological changes, metabolites such as bilirubin, urea, uric acid, and creatinine levels, tissue thiobarbutric acid reactive substance, enzymic and non-enzymic antioxidants and inflammatory marker enzymes such as myeloperoxidase, cathepsin D, and acid phosphatase were assessed.

Results: The d-GalN-induced toxicity was evident from a significant increase (p < 0.001) in the serum and tissue inflammatory markers in toxic rats, when compared with the control (saline alone treated animals). The B. nigra pretreated groups (200 and 400 mg/kg b.wt.) showed significant (p < 0.001) reduction in the d-GalN-induced toxicity as obvious from biochemical parameters. Histopathological observations confirm the protective effect of B. nigra leaf extract by reduction in hepatic and renal tissue damage. Experimentals extract showed a similar effect as the standard.

Conclusions: The crude methanol extract of B. nigra leaf lacks inherent toxicity and exhibits hepatic and nephroprotective effects against d-GalN-induced toxicity in Wistar rats.     

Chemical Constituents of Rubus ulmifolius Schott

Abstract

Summary

From the leaves of Rubus ulmifolius Schott, quercetin, kaempferol, trifolin (kaempferol-3-0-galactoside), hyperin (quercetin-3-0-galactoside), chlorogenic acid, caffeic acid, a kaempferol-3-0-caffeoyl-ester, and a glucose-caffeoyl ester were isolated and identified. Free fatty acids were characterised by gas chromatography of their methyl esters.     

Teratological and toxicological studies of alkaloidal and phenolic compounds from Solanum tuberosum L.

A comparative study of acute and chronic ip administration was made in pregnant and nonpregnant (female) rats of alkaloidal (α-chaconine, α-solanine total glycoalkaloidal extract (TGA-extract)) and phenolic compounds (chlorogenic and caffeic acid) from Solanum Tuberosum L. The acute LD50 and 95% confidence limits for α-chaconine, α-solanine, and the TGA-extract were 84 (65.6–107.5), 67 (52.3–85.7), and 60 mg/kg (35.7–100.8). There was no significant difference in their potency at the 95% confidence limit. Chronic adminstration of α-chaconine, α-solanine, and the TGA-extract to nonpregnant rats for 2 days (40 mg/kg/day) and 8 days (20 mg/kg/day) resulted in 40 and 42% mortality, respectively. Eight daily injections of α-chaconine (5–20 mg/kg) on Days 5–12 or 2 (40 mg/kg) on Days 5 and 6 to pregnant rats resulted in maternal (40–66%) and fetal death (15–100%), whereas α-solanine and the TGA-extract administered similarly were lethal only to the fetus (17–86%). Eight daily injections of chlorogenic (5–500 mg/kg) and caffeic acid (40–187.5 mg/kg) on Days 5–12 of gestation did not cause maternal or fetal lethality. None of the compounds tested produced neural tube defects, but a few 21-day-old fetuses had rib abnormalities.     

Rosmarinic acid and caffeic acid reduce the defensive freezing behavior of mice exposed to conditioned fear stress

Abstract Rationale. We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) and its major metabolite caffeic acid have antidepressive-like activity in the forced swimming test. Objective. The present study was designed to examine whether rosmarinic acid and caffeic acid might also be effective in other types of stress model. Methods: The conditioned fear stress paradigm was used as a stress model for assessing the effects of rosmarinic acid and caffeic acid. Results. Rosmarinic acid (0.25–4 mg/kg, IP) induced a dose-dependent, U-shaped reduction in the duration of the defensive freezing behavior of mice exposed to conditioned fear stress. Caffeic acid (1–8 mg/kg, IP) also dose-dependently reduced this freezing behavior. However, neither substance, at doses that produced a significant reduction in the freezing behavior, affected spontaneous motor activity. Conclusions. These results confirm that rosmarinic acid and caffeic acid may inhibit the emotional abnormality produced by stress. Electronic Publication     

Biosynthesis of 7,8-dihydroxyflavone glycosides via OcUGT1-catalyzed glycosylation and transglycosylation

Abstract

Herein, a flavonoid glycosyltransferase (GT) OcUGT1 was determined to be able to attack C-8 position of 7,8-dihydroxyflavone (7,8-DHF) via both glycosylation and transglycosylation reactions. OcUGT1-catalyzed glycosylation of 7,8-DHF resulted in the formation of two monoglycosides 7-O-β-D-glucosyl-8-hydroxyflavone (1a), 7-hydroxy-8-O-β-D-glucosylflavone (1b), as well as one diglycoside 7,8-di-O-β-D-glucosylflavone (1c). Under the action of OcUGT1, inter-molecular trans-glycosylations from aryl β-glycosides to 7,8-DHF to form monoglycosides 1a and 1b were observable.     

Prevention of Carbon Tetrachloride-Induced Hepatotoxicity by the Ethanol Extract of Capparis moonii Fruits in Rats

The effect of the ethanol extract of Capparis moonii Hook. f. Thoms. (Capparidaceae) fruits was studied in carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. The hepatotoxicity was induced in rats with the administration of 1 : 1 (v/v) mixture of CCl₄ in olive oil at the dose of 1 ml/kg subcutaneously on day 7. The ethanol extract of C. moonii (200 mg/kg) and the standard drug silymarin (25 mg/kg) were given orally from day 1 to day 9. The extract of C. moonii produced significant (p &lt; 0.001) lowering of the elevated Serum glutamic oxaloacetic transaminace (SGOT) Serum glutamicpyraric transaminase (SGPT), alkaline phosphatase (ALP), and a rise of depleted total protein when compared with the toxic control. The results were comparable with the standard drug silymarin.     

HPLC法测定射干抗病毒注射液中绿原酸和咖啡酸的含量

目的建立HPLC法测定射干抗病毒注射液中绿原酸和咖啡酸的含量。方法采用Hypersil ODS柱,0.01mol·L^-1磷酸二氢钠溶液（1%磷酸溶液调节pH值至3.9）-甲醇（85∶15）为流动相,流速：1.0mL·min^-1,检测波长：323nm,柱温：30℃。结果绿原酸和咖啡酸浓度分别在0.40-200mg·L^-1（r=0.9996）、0.16-160mg.L-1（r=0.9986）范围内与峰面积呈良好线性关系,平均加样回收率分别为99.8%,100.7%。结论本法简便、准确、重复性好,可用于射干抗病毒注射液中绿原酸和咖啡酸含量的同时测定。     

Hepatoprotective potential of Cassia auriculata roots on ethanol and antitubercular drug-induced hepatotoxicity in experimental models

Context: Tarvada [Cassia auriculata Linn. (Caesalpiniaceae)] is used against liver ailments in Indian folk medicine, but there is a lack of scientific evidence for this traditional claim.

Objective: The present study investigated the protective effect of methanol extract of tarvada (MECA) roots on ethanol and antitubercular drug induced hepatotoxicity in rats.

Materials and methods: In the therapeutic model, ethanol (40%, 4?g/kg b.w., p.o.) was administered to rats for 21 days and the intoxicated rats were treated with MECA (300 and 600?mg/kg, b.w.) and silymarin (100?mg/kg, b.w.) for next 7 days. In the prophylactic model, MECA and silymarin were administered simultaneously along with a combination of isoniazid (27?mg/kg, b.w.), rifampicin (54?mg/kg, b.w.) and pyrazinamide (135?mg/kg, b.w.) for 30 days. After the study duration, serum levels of AST, ALT, ALP, total bilirubin, total cholesterol, total protein, albumin were estimated along with hepatic catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and liver histopathology in each group.

Results: Administration of tarvada root extract significantly (p?p?Discussion and conclusion: Results suggest that tarvada root extract possess potent hepatoprotective activity against ethanol and antitubercular drug-induced hepatotoxicity in rats, which could be due to an inhibition of hepatic metabolizing enzymes and antioxidant activity.     

Antithrombocytopenic and immunomodulatory potential of metabolically characterized aqueous extract of Carica papaya leaves

Context: Carica papaya Linn. (Caricaceae) leaf (CPL) juice has long been traditionally used in ethnomedicine for dengue fever.

Objective: The study examines the effects of standardized CPL aqueous extract (SCPLE) on platelet count, extramedullary haematopoiesis (EMH), and immunomodulation in cyclophosphamide (CP)-induced animal model of thrombocytopenia.

Materials and methods: The extract was analyzed for myricetin, caffeic acid, trans-ferulic acid, and kaempferol using HPTLC for standardization followed by UPLC-qTOF/MS fingerprinting for metabolite signature. The effects of SCPLE (50 and 150?mg/kg p.o.) on proliferative response of platelet count and total leucocyte count (TLC) were observed up to 14?days in Wistar rat. However, delayed-type hypersensitivity (DTH), haemagglutination titre (HT), and in vivo carbon clearance were examined as immunomodulatory parameters in albino mice at 150?mg/kg p.o. against CP.

Results: The quantitative HPTLC estimation of SCPLE showed the presence of myricetin, caffeic acid, trans-ferulic acid, and kaempferol up to 280.16?±?5.99, 370.18?±?6.27, 1110.86?±?2.97, and 160.53?±?2.48 (μg/g), respectively. Twenty-four metabolites were identified using UPLC-qTOF/MS. Oral administration of SCPLE (150?mg/kg) in thrombocytopenic rats exhibited significant (p?3 cells/mm³), DTH response (0.16?±?0.004), and phagocytic index (63.15% increase) as compared to CP-induced thrombocytopenia group. Histopathological studies showed minimal fibrosis in spleen histology.

Discussion and conclusions: Results suggest CPL can mediate the release of platelets providing the means for the treatment and prevention of dengue.     

Radioprotective effects of chlorogenic acid against mortality induced by gamma-irradiation in mice

The radioprotective effects of the naturally occurring compound chlorogenic acid have been investigated against mortality induced by gamma-irradiation in mice. Chlorogenic acid was administrated at single doses of 100, 200 and 400 mg/kg 1 or 24 h prior to lethal dose of gamma-irradiation (8.5 Gy). At 30 days after treatment, the percentage of survival in each group was as follows: control, 20%; 100 mg/kg, 20% and 15%; 200 mg/kg, 45% and 15%; 400 mg/kg, 25% and 35% for 1 h and 24 h treatment prior gamma-irradiation, respectively. Survival rate was statistically increased in animals treated with this agent at 200 mg/kg at 1 h prior to irradiation as compared with the irradiation only group. Other doses of chlorogenic acid have not showed any enhanced survival when it was administrated at 1 or 24 h before irradiation. Chlorogenic acid exhibited concentration-dependent activity on 1,1-diphenyl-2-picrylhydrazyl free radical to show strong antioxidant activity. It appeared that chlorogenic acid with antioxidant activity reduced mortality induced by gamma-irradiation.