The habitats of Eurycoma longifolia Jack, a slender tree, are jungles in Malaysia and Indonesia. It belongs to the family Simaroubaceae and is a source of quassinoids with anabolic, antimalarial and cytostatic activity. In this study, conducted during 2008 in Mae Sot, Thailand, a standardized extract of E. longifolia containing three major quassinoids, eurycomanone (1), 13,21-dihydroeurycomanone (2) and 13alpha(21)-epoxyeurycomanone (3) was evaluated for antiplasmodial activity against Plasmodium falciparum and its activity has been compared with that of artemisinin, using 38 fresh parasite isolates and assessment of inhibition of schizont maturation. The IC(50), IC(90) and IC(99) values for artemisinin were 4.30, 45.48 and 310.97 microg/l, and those for the root extract from E. longifolia 14.72, 139.65 and 874.15 microg/l respectively. The GMCOC for artemisinin was 337.81 mug/l, and for the plant extract it was 807.41 microg/l. The log-concentration probit regressions were parallel. The inhibitory activity of the E. longifolia extract was higher than that expected from the three quassinoids isolated from the plant, suggesting synergism between the quassinoids or the presence of other unidentified compounds.
Following up a popular use of crude leaf preparations from Carica papaya for the treatment of dengue infections, a suspension of powdered Carica papaya leaves in palm oil has been investigated for its effect on thrombocyte counts in mice, administering by gavage 15 mg of powdered leaves per kg body weight to 5 mice. Equal numbers of animals received corresponding volumes of either palm oil alone or physiological saline solution. Thrombocyte counts before and at 1, 2, 4, 8, 10, 12, 24, 48 and 72 hours after dosing revealed significantly higher mean counts at 1, 2, 4, 8, 10 and 12 after dosing with the C. papaya leaf formulation as compared to the mean count at hour 0. There was only a non-significant rise of thrombocyte counts in the group having received saline solution, possibly the expression of a normal circadian rhythm in mice. The group having received palm oil only showed a protracted increase of platelet counts that was significant at hours 8 and 48 and obviously the result of a hitherto unknown stimulation of thrombocyte release. The results call for a dose-response investigation and for extending the studies to the isolation and identification of the C. papaya substances responsible for the release and/or production of thrombocytes.
The purpose of this study is to see the anthelmintic activity potential of papaya seeds against Hymenolepis diminuta in rats. The objectives of this study were: (1) to determine the effectiveness of papaya seeds on helminths especially H. diminuta in rats and (2) to determine the effective dose level on helminths in rats. Thirty six male rats from strain Sprague-Dawley were chosen as samples in this experiment. Two types of dose level were used for papaya seeds treatments such as 0.6 g kg-1 and 1.2 g kg-1. The geometric mean (GEM) was used to calculate mean for eggs per gram (EPG) before and after the treatment to be included in the reduction percentage calculation. After 21 days post treatment, necropsies were done to get the worm count and the GEM was used to calculate the efficacy percentage for the treatment. Results from this study showed that the reduction percentages in EPG for papaya seeds treatment for both doses level were very high which is 96.8% for 0.6g kg-1 dose level and 96.2% for 1.2 g kg-1 dose level. Whereas the efficacy percentage based on the worm counts for both doses level were also very high that was 90.77% for 0.6 g kg-1 dose level and 93.85% for 1.2 g kg-1.
Orthosiphon stamineus Benth (Family: Lamiaceae) or locally known as Misai Kucing has been widely used in Malaysia for treating kidney problems, gout, and diabetes. This study aims to evaluate the possible toxic effect after following fourteen days oral administration of methanol extract of O. stamineus in female Sprague Dawley (SD) rats. Control groups were treated orally with distilled water (vehicle) while the four test groups were treated up to fourteen days with 0.5 g/kg, 1 g/kg, 3 g/kg and 5 g/kg body weight of methanol extract of O. stamineus respectively. Toxicity of the methanol extract of O. stamineus was evaluated by the incident of lethality, side-cage observation and blood serum biochemical parameters. No lethality or adverse toxic signs were seen during the experimental period. A significant decrease in several serum biochemical parameters i.e. AST and ALT and increase in liver weight was observed in young female SD rat after being fed fourteen days with methanol extract of O. stamineus. No delayed toxic effect and lethality was observed in all rats during fourteen days of recovery period. In conclusion, methanol extract of O. stamineus within these range and treatment duration would not cause any severe toxic effects and organ damages in rats.
Eurycoma longifolia, locally known as 'Tongkat Ali' is a popular local medicinal plant that possess a lot of medicinal properties as claimed traditionally, especially in the treatment of malaria. The claims have been proven scientifically on isolated compounds from the plant. The present study is to investigate the anti malaria properties of Eurycoma longifolia standardized extract (root) (TA164) alone and in combination with artemisinin in vivo. Combination treatment of the standardized extract (TA164) with artemisinin suppressed P. yoelii infection in the experimental mice. The 4 day suppressive test showed that TA164 suppressed the parasitemia of P. yoelii-infected mice as dose dependent manner (10, 30 and 60 mg/kg BW) by oral and subcutaneous treatment. By oral administration, combination of TA164 at 10, 30 and 60 mg/kg BW each with artemisinin respectively showed a significant increase in the parasitemia suppression to 63, 67 and 80 percent as compared to artemisinin single treatment (31%). Using subcutaneous administration, at 10 mg/kg BW of TA164 in combination with 1.7 mg/kg BW of artemisinin gave a suppression of 80% of infection. This study showed that combination treatment of TA164 with artemisinin gives a promising potential anti malaria candidate using both oral and subcutaneous route, the later being the most potent.
Abelmoschus esculentus L. (ladies finger, okra) is a well-known tropical vegetable, widely planted from Africa to Asia and from South Europe to America. In the present study, we investigated the in vitro antioxidant capacity and in vivo protective effect of the aqueous and methanolic seed extracts of Abelmoschus esculentus against scopolamine-induced cognitive impairment using passive avoidance task and acute restraining stress-induced behavioural and biochemical changes using elevated plus maze (EPM) and forced swimming test (FST) in mice. Our results demonstrated that the pretreatment of mice with aqueous and methanolic seed extracts of Abelmoschus esculentus (200 mg/kg, p.o.) for seven days significantly (P < 0.01) attenuated scopolamine-induced cognitive impairment in the passive avoidance test. In addition, these extracts significantly reduced the blood glucose, corticosterone, cholesterol, and triglyceride levels elevated by acute restraint stress and also significantly increased the time spent in open arm in EPM and decreased the immobility time in FST. It has also been revealed that these extracts showed a significant antioxidant activity and no signs of toxicity or death up to a dose of 2000 mg/kg, p.o. These results suggest that the seed extracts of Abelmoschus esculentus L. possess antioxidant, antistress, and nootropic activities which promisingly support the medicinal values of ladies finger as a vegetable.
Centella asiatica is a reputed medicinal plant used in the treatment of various skin diseases in the Indian system of medicine. The objective of the study presented in this article was to evaluate the wound-healing potential of the ethanolic extract of the plant in both normal and dexamethasone-suppressed wound healing. The study was done on Wistar albino rats using incision, excision, and dead space wounds models. The extract of C asiatica significantly increased the wound breaking strength in incision wound model compared to controls (P < .001). The extract-treated wounds were found to epithelize faster, and the rate of wound contraction was significantly increased as compared to control wounds (P < .001). Wet and dry granulation tissue weights, granulation tissue breaking strength, and hydroxyproline content in a dead space wound model also increased at statistically significant levels as shown. The extract of the leaves had the effect of attenuating the known effects of dexamethasone healing in all wound models (P < .001, P < .05). The results indicated that the leaf extract promotes wound healing significantly and is able to overcome the wound-healing suppressing action of dexamethasone in a rat model. These observations were supported by histology findings.
The effect of water extracts of Euphorbia hirta on the histological features and expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the rat articular cartilage was investigated. Arthritis was induced in rats using Freund's Complete Adjuvant containing heat-killed M. tuberculosis, and treated with water extracts of E. hirta. Paraffin tissue sections of the arthritic joints were evaluated. The extent of cartilage degeneration was found to be greatest in rats treated with the highest dosage of E. hirta, followed by rats in the untreated group. Rats treated with the intermediary and low dosages of Euphorbia hirta showed improved histology. MMP-13 levels were found to be decreased with decreasing dosages of E. hirta. TIMP-1 levels were found to increase with decreasing dosages of E. hirta. MMP-3 levels fluctuated without any appreciable pattern. Low dosages of E. hirta seem to be beneficial in reducing cartilage degeneration in cases of arthritis.
Lead is known to disrupt the biological systems by altering the molecular interactions, cell signaling, and cellular function. Exposure to even low levels of lead may have potential hazardous effects on brain, liver, kidneys and testes. The efficacy of Etlingera elatior (torch ginger) to protect hepatotoxicity induced by lead acetate was evaluated experimentally in male Sprague - Dawley rats. Rats were exposed to lead acetate in drinking water (500 ppm) for 21 days and the effects of concurrent treatment with extract of E. elatior on hepatic lipid hydroperoxides (LPO), protein carbonyl content (PCC), total antioxidants (TA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione S- Transferase (GST) levels and histopathological changes in liver were evaluated. There was a significant decrease in TA and other antioxidant enzymes (p < 0.05) and increase in LPO and PCC (p < 0.05) with lead acetate ingestion. Concurrent treatment with E. elatior extract significantly reduced the LPO and PCC (p < 0.05) in serum and increased the antioxidant enzyme levels (p < 0.05) in the liver. Significant histopathological changes were seen in hepatic tissue with chronic lead ingestion. Treatment with E. elatior significantly reduced these lead-induced changes in hepatic architecture. E. elatior has also reduced the blood lead levels (BLL). Thus, there has been extensive biochemical and structural alterations indicative of liver toxicity with exposure to lead and E. elatior treatment significantly reduced these oxidative damage. Our results suggest that E. elatior has a powerful antioxidant effect against lead-induced hepatotoxicity.
In the present study, L. ferrugineus methanol extract (LFME) was evaluated for its blood pressure lowering effect in anesthetized normotensive Sprague Dawley (SD) rats and its spasmogenic effect in isolated guinea pig ileum. The possible mechanism(s) of action were also investigated. LFME was obtained by Soxhlet extraction. The rats were fasted overnight and anesthetized with sodium pentobarbitone (60 mg/kg i.p.). LFME was administered in i.v. boluses in the concentrations of 25, 50, 100 and 200 mg/kg respectively, with concomitant monitoring of mean arterial pressure (MAP). It was found that LFME dose-dependently reduced MAP. An i.v. bolus injection of atropine significantly decreased the blood pressure lowering effect of LFME. Similarly, L-NAME (Nomega-nitro-L-arginine methyl ester) significantly lowered both the MAP and the action duration. Conversely, no significant change in MAP was seen following i.v. injections of neostigmine, hexamethonium, prazosin and propranolol. LFME also produced a dose-dependent contractile effect in guinea pig ileum. This contraction was significantly reduced in atropine pre-incubated tissue segments, yet it was significantly enhanced in the presence of neostigmine. No appreciable change in the ability of LFME to contract guinea pig ileum was seen in the presence of hexamethonium. Accordingly, it can be postulated that LFME possesses a marked hypotensive effect that can be attributed to stimulation of muscarinic receptors and/or stimulation of nitric oxide (NO) release. Moreover, LFME retains a considerable spasmogenic action due to its cholinergic properties. The hypotensive and spasmogenic effects of LFME justify its traditional uses.
Senecio candicans DC. (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris, district, Tamil Nadu. The present investigation was carried out to evaluate the sub-chronic toxicity of an aqueous extract of Senecio candicans (AESC) plant in Wistar albino rats. The study was conducted in consideration of the OECD 408 study design (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and the extract was administered via gavage at doses of 250, 500 or 750 mg/kg body weight per day for 90-days. Hematological, biochemical parameters were determined on days 0, 30, 60 and 90 of administration. Animals were euthanized after 90 d treatment and its liver and kidney sections were taken for histological study. The results of sub-chronic study showed significant increase (P plant may develop kidney and liver toxicity. Further studies on the isolation and characterization of PAs are necessary to determine the safe dose level of the extract for therapeutic use in traditional medicine.
Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis. The aims of the present study were to investigate the in vivo chemopreventive effect of FALHE in rats, to identify the contributing anticancer compound in FALHE and to determine its potential mechanism of action against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment control (tamoxifen) and normal control. Breast tissues were then subjected to histopathological and immunohistochemical analyses. A bioassay-guided investigation on FALHE was performed to identify the cytotoxic compound and its mechanism of action through flow cytometry, real-time qPCR and western blotting analyses. An in vivo study showed that FALHE suppressed the expression of the tumor markers PCNA and Ki67. The tumor size was reduced from 2031 ± 281 mm3 to 432 ± 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in breast tumor cells, and this was confirmed by high expression levels of Bax, p53 and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27. The in vitro experimental results resulted in the isolation of polycerasoidin as a bioactive ingredient of FALHE with an IC50 value of 3.16 ± 0.31 μg/ml against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in breast cancer cells via caspase activation and changes in the mRNA and protein expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels. The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.
Common Gram-positive clinical pathogens are showing an increasing trend for resistance to conventional antimicrobial agents. New drugs with potent antibacterial activities are urgently needed to remediate this problem. Halogenated compounds isolated from several species of the red algae genus Laurencia were examined for their antibacterial activity against 22 strains of human pathogenic bacteria, 7 strains of which were antibiotic-resistant bacteria. Four phenolic sesquiterpenes and a polybrominated indole showed wide spectra of antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecalis and E. faecium (VRE). In addition, laurinterol and allolaurinterol displayed potent bactericidal activity against three strains of MRSA at 3.13 microg mL(-1), and three strains of vancomycin-susceptible Enterococcus, at 3.13 microg mL(-1) and 6.25 microg mL(-1), respectively.
In the present study, the rhizome essential oil from Zingiber zerumbet (Zingiberaceae) was evaluated for antinociceptive activity using chemical and thermal models of nociception, namely, the acetic acid-induced abdominal writhing test, the hot-plate test and the formalin-induced paw licking test. It was demonstrated that intraperitoneal administration of the essential oil of Z. zerumbet (EOZZ) at the doses of 30, 100 and 300 mg/kg produced significant dose-dependent inhibition of acetic acid-induced abdominal writhing, comparable to that of obtained with acetylsalicylic acid (100 mg/kg). At the same doses, the EOZZ produced significant dose-dependent increases in the latency time in the hot-plate test with respect to controls, and in the formalin-induced paw licking test, the EOZZ also significantly reduced the painful stimulus in both neurogenic and inflammatory phase of the test. In addition, the antinociceptive effect of the EOZZ in the formalin-induced paw licking test as well as hot-plate test was reversed by the nonselective opioid receptor antagonist, naloxone suggesting that the opioid system was involved in its analgesic mechanism of action. On the basis of these data, we concluded that the EOZZ possessed both central and peripheral antinociceptive activities which justifying its popular folkloric use to relieve some pain conditions.
The methanol extract from the leaves of Phyllanthus niruri L. showed oral antihyperuricemic activity in potassium oxonate- and uric acid-induced hyperuricemic rats. Fractionation of the extract by resin chromatography led to the isolation of a less polar fraction which exhibited the highest reduction of plasma uric acid. Further antihyperuricemic-guided purification of the fraction afforded three lignans, phyllanthin (1), hypophyllanthin (2) and phyltetralin (3), of which 1 significantly reversed the plasma uric acid level of hyperuricemic animals to its normal level in a dose-dependent manner, comparable to that of allopurinol, benzbromarone and probenecid which are used clinically for the treatment of hyperuricemia and gout. Thus, the lignans of P. niruri are potential antihyperuricemic agents worthy of further investigation.
Among the quassinoids isolated from Eurycoma longifolia Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of Plasmodium falciparum. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.
A validated HPLC analysis of eurycomanone (1), a bioactive quassinoid, in rat plasma following oral and intravenous administration of Eurycoma longifolia Jack extract was developed for pharmacokinetic and bioavailability studies. Relatively high plasma eurycomanone concentrations were detected after an intravenous injection of 10 mg/kg extract F2 containing 1.96 mg/kg of the quassinoid. However, it declined rapidly to zero after 8 h. Its mean elimination rate constant (k(e)), biological half-life (t(1/2)), volume of distribution (V(d)) and clearance (CL) were 0.88 +/- 0.19 h (-1), 1.00 +/- 0.26 h, 0.68 +/- 0.30 L/kg and 0.39 +/- 0.08 L/h/kg, respectively. Following oral administration of eurycomanone, its Cmax and Tmax values were detected as 0.33 +/- 0.03 microg/mL and 4.40 +/- 0.98 h, respectively. The plasma concentration of the quassinoid after oral administration was much lower than after intravenous application in spite of the oral dose being 5 times higher. The results indicate that eurycomanone is poorly bioavailable when given orally. A comparison of the AUC (0-->infinity) obtained orally to that obtained after an intravenous administration (normalized for dose differences) revealed that the absolute bioavailability of the compound was low with 10.5 %. Furthermore, the compound appeared to be well distributed in the extravascular fluids because of its relatively high V(d) value. The poor oral bioavailability was not attributed to instability problems because eurycomanone has been shown to be stable under different pH conditions. Thus, its poor oral bioavailability may be due to poor membrane permeability in view of its low P value and/or high first-pass metabolism.
Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple-blind, placebo-controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25-item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p
Bioassay guided fractionation of the roots of Cyathostemma argenteum using the brine shrimp resulted in the isolation of two uncommon flavanones, 2,5-dihydroxy-7-methoxy flavanone 1 and 2,5-dihydroxy-6,7-dimethoxy flavanone 2 while the stem bark yielded the related compounds 5-hydroxy-7-methoxy flavone 3 and 5-hydroxy-6,7-dimethoxy flavone 4. The alkaloids liriodenine 5 and discretamine 6 as well as benzyl benzoate 7 were isolated from the roots and 6 was also isolated from the stembark. In cytotoxicity tests using four human breast cancer cell lines, 1 and 2 were weakly toxic to MCF-7 cells (IC(50) = 19.6 and 19.0 microM, respectively) but showed little activity against MCF-7 cells resistant to doxorubicin or against two oestrogen receptor-deficient cell lines. Compound 5, but not 6 and 7, was moderately cytotoxic against all four cell lines. These results are discussed in the context of the traditional use of C. argenteum in the treatment of breast cancer.
The ethanol extract of leaves of Piper porphyrophyllum N.E. Br. showed a broad spectrum of antibacterial activity. The activity was increased on fractionation (hexane, dichloromethane and aqueous), particularly in the aqueous fraction. No activity was shown against tested Candida albicans.