Melanoma is the most fatal form of skin cancer. Different signalling pathways and proteins will be differentially expressed to pace with the tumour growth. Thus, these signalling molecules and proteins are become potential targets to halt the progression of cancer. The present works were attempted to investigate the underlying molecular mechanisms of anticancer effects of Phyllanthus (P.amarus, P.niruri, P.urinaria and P.watsonii) on skin melanoma, MeWo cells.
The present study evaluated the antioxidant activity and potential toxicity of 50% methanolic extract of Orthosiphon stamineus (Lamiaceae) leaves (MEOS) after acute and subchronic administration in rats. Superoxide radical scavenging, hydroxyl radical scavenging, and ferrous ion chelating methods were used to evaluate the antioxidant properties of the extract. In acute toxicity study, single dose of MEOS, 5000 mg/kg, was administered to rats by oral gavage, and the treated rats were monitored for 14 days. While in the subchronic toxicity study, MEOS was administered orally, at doses of 1250, 2500, and 5000 mg/kg/day for 28 days. From the results, MEOS showed good superoxide radical scavenging, hydroxyl radical scavenging, ferrous ion chelating, and antilipid peroxidation activities. There was no mortality detected or any signs of toxicity in acute and subchronic toxicity studies. Furthermore, there was no significant difference in bodyweight, relative organ weight, and haematological and biochemical parameters between both male and female treated rats in any doses tested. No abnormality of internal organs was observed between treatment and control groups. The oral lethal dose determined was more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of MEOS for both male and female rats is considered to be 5000 mg/kg per day.
The expression of genes regulated by estrogen in the uterus was studied in ovariectomized (OVX) rats treated with germinated brown rice (GBR) bioactives, and compared to Remifemin or estrogen at different doses to identify the regulation of these genes in the uterus and their molecular mechanisms.
The in vitro cytotoxicity tests on the extracts of Mesua beccariana, M. ferrea, and M. congestiflora against Raji, SNU-1, HeLa, LS-174T, NCI-H23, SK-MEL-28, Hep-G2, IMR-32, and K562 were achieved using MTT assay. The methanol extracts of Mesua beccariana showed its potency towards the proliferation of B-lymphoma cell (Raji). In addition, only the nonpolar to semipolar extracts (hexane to ethyl acetate) of the three Mesua species indicated cytotoxic effects on the tested panel of human cancer cell lines. Antioxidant assays were evaluated using DPPH scavenging radical assay and Folin-Ciocalteu method. The methanol extracts of M. beccariana and M. ferrea showed high antioxidant activities with low EC₅₀ values of 12.70 and 9.77 μg/mL, respectively, which are comparable to that of ascorbic acid (EC₅₀ = 5.62 μg/mL). Antibacterial tests were carried out using four Gram positive and four Gram negative bacteria on Mesua beccariana extracts. All the extracts showed negative results in the inhibition of Gram negative bacteria. Nevertheless, methanol extracts showed some activities against Gram positive bacteria which are Bacillus cereus, methicillin-sensitive Staphylococcus aureus (MSSA), and methicillin-resistant Staphylococcus aureus (MRSA), while the hexane extract also contributed some activities towards Bacillus cereus.
The present study aims to evaluate the safety of methanol extract of Cinnamomum burmannii (MECB) by acute 14-day (single dose) and sub-chronic 28-day (repeated doses) oral administration to Sprague-Dawley rats. Our results showed that no toxicity was found in either acute or sub-chronic toxicity studies. MECB (containing 0.07% and 0.20% (w/w) of coumarin and trans-cinnamaldehyde, respectively), which was given orally at doses of 500, 1000 and 2000 mg/kg caused neither visible signs of toxicity nor mortality. No significant differences were observed in general condition, growth, organ weight, hematological parameters, biochemical values, or the gross and microscopic appearance of the organs from the treatment groups as compared to the control group. In conclusion, MECB did not cause any mortality nor did it cause any abnormalities in the necropsy and histopathology findings of treated rats. The LD50 for the MECB was found to be more than 2000 mg/kg. No adverse effects were observed in the treated rats at all the doses tested. The no-observed-adverse-effect level (NOAEL) for the 28-day study was determined to be 2000 mg/kg body weight/day.
The antioxidant and anti-diabetic properties of the sequential extracts of Vernonia amygdalina based on the chemical composition of the most effective anti-diabetic extract were studied. Using DPPH and ABTS radical scavenging as well as FRAP assays, the extracts showed a consistent dose-dependent trend of potent antioxidant activity in the following solvents: water extract>methanol extract>chloroform extract>and petroleum ether extracts. In the oral glucose tolerance test, the chloroform extract exerted the highest response (33.3%), similar to metformin (27.2%), after 2h compared to the control (50.8%, P<0.05). After a 14-day administration in diabetic rats, the chloroform extract recorded the highest blood (23.5%) and serum (21.4%) glucose-lowering effects (P<0.05). GC-MS analysis of the chloroform extract revealed high levels of linoleic acid (4.72%), α-linolenic acid (10.8%) and phytols (12.0%), as well as other compounds.
BACKGROUND: Xanthones are a group of oxygen-containing heterocyclic compounds with remarkable pharmacological effects such as anti-cancer, antioxidant, anti-inflammatory, and antimicrobial activities.
METHODS: A xanthones extract (81% α-mangostin and 16% γ-mangostin), was prepared by crystallization of a toluene extract of G. mangostana fruit rinds and was analyzed by LC-MS. Anti-colon cancer effect was investigated on HCT 116 human colorectal carcinoma cells including cytotoxicity, apoptosis, anti-tumorigenicity, and effect on cell signalling pathways. The in vivo anti-colon cancer activity was also investigated on subcutaneous tumors established in nude mice.
RESULTS: The extract showed potent cytotoxicity (median inhibitory concentration 6.5 ± 1.0 μg/ml), due to induction of the mitochondrial pathway of apoptosis. Three key steps in tumor metastasis including the cell migration, cell invasion and clonogenicity, were also inhibited. The extract and α-mangostin up-regulate the MAPK/ERK, c-Myc/Max, and p53 cell signalling pathways. The xanthones extract, when fed to nude mice, caused significant growth inhibition of the subcutaneous tumor of HCT 116 colorectal carcinoma cells.
CONCLUSIONS: Our data suggest new mechanisms of action of α-mangostin and the G. mangostana xanthones, and suggest the xanthones extract of as a potential anti-colon cancer candidate.
Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. In this study, the effects of ethyl acetate extract of Zingiber zerumbet rhizome [200 mg per kg of body weight (mg/kg) and 400 mg/kg] on PCM-induced nephrotoxicity were examined. Rats were divided into five groups containing 10 rats each. The control group received distilled water while other groups were treated with extract alone (400 mg/kg), PCM alone (750 mg/kg), 750 mg/kg PCM+200 mg/kg extract (PCM+200-extract), and 750 mg/kg PCM+400 mg/kg extract (PCM+400-extract), respectively, for seven consecutive days. The Z. zerumbet extract was given intraperitoneally concurrent with oral administration of PCM. Treatment with Z. zerumbet extract at doses of 200 and 400 mg/kg prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (P<0.05) level of plasma creatinine, plasma and renal malondialdehyde (MDA), plasma protein carbonyl, and renal advanced oxidation protein product (AOPP). Furthermore, both doses were also able to induce a significant increment (P<0.05) of plasma and renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity. The nephroprotective effects of Z. zerumbet extract were confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. Moreover, Z. zerumbet extract administered at 400 mg/kg was found to show greater protective effects than that at 200 mg/kg. In conclusion, ethyl acetate extract of Z. zerumbet rhizome has a protective role against PCM-induced nephrotoxicity and the process is probably mediated through its antioxidant properties.
Eurycoma longifolia (EL) has been shown recently to protect against bone calcium loss in orchidectomised rats, the model for androgen-deficient osteoporosis. The mechanism behind this is unclear but it may be related to its ability to elevate testosterone levels or it may directly affect bone remodeling. The aim of this study is to determine the mechanism involved by investigating the effects of EL extract on serum testosterone levels, bone biomarkers, biomechanical strength and gene expression of Receptor Activator of Nuclear Factor kappa-B ligand (RANKL), Osteoprotegerin (OPG) and Macrophage-Colony Stimulating Factor (MCSF) in orchidectomised rats.
Enicosanthellum pulchrum (King) Heusden (Annonaceae) is a coniferous tree that is confined to mountain forests. The chemical constituents of this species have been studied previously; however, its biological activity has never been investigated before and is reported here for the first time.
The anti-inflammatory activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith was investigated using carrageenan-induced paw edema and cotton pellet-induced granuloma tissue formation test in mice. It was demonstrated that intraperitoneal administration of 1 at a dose of 5, 10, 50 and 100 mg/kg produced significant dose-dependent inhibition of paw edema induced by carrageenan. It was also demonstrated that 1 at similar doses significantly suppressed granulomatous tissue formation in cotton pellet-induced granuloma test.
The present investigation was carried out to evaluate the safety of standardised 50% ethanol extract of Orthosiphon stamineus plant by determining its potential toxicity after acute and subchronic administration in rats.
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.
The aqueous extract of Ficus deltoidea leaves was evaluated for possible antinociceptive activity in three models of nociception, namely, acetic acid-induced abdominal writhing, formalin and hot plate test. The results of the present study showed that intraperitoneal administration of the F. deltoidea leaves aqueous extract at the dose of 1, 50 and 100 mg/kg, 30 min prior to pain induction produced significant dose-dependent antinociceptive effect in all the models used, which indicating the presence of both central and peripherally mediated activities. Furthermore, the antinociceptive effect of the extract in the formalin and hot plate test was reversed by the non-selective opioid receptor antagonist naloxone suggesting that the endogenous opioid system is involved in its analgesic mechanism of action. Thus, the present results demonstrated that F. deltoidea leaves aqueous extract contains pharmacologically active constituents which possess antinociceptive activity justifying its popular therapeutic use in treating conditions associated with the painful conditions.
Typhonium flagelliforme (Lodd.) Blume (Araceae) is a Malaysian plant used locally to combat cancer. In order to evaluate its antiproliferative activity in vitro and to possibly identify the active chemical constituents, a bioactivity guided study was conducted on the extracts of this plant.
The anti-pyretic activity of a standardized methanol/water (50/50) extract of Orthosiphon stamineus Benth. (SEOS) was investigated for its effect on normal body temperature and yeast-induced pyrexia in Sprague Dawley (SD) rats. The SEOS showed no effect on normal body temperature. Doses of 500 and 1000 mg/kg body weight of SEOS significantly reduced the yeast-induced elevation in body temperature. This effect persisted up to 4 h following the administration of the extract. The anti-pyretic effect of SEOS was comparable with that of paracetamol (acetaminophen in U.S) (150 mg/kg p.o.), a standard anti-pyretic agent. HPLC study revealed that rosmarinic acid, sinensetin, eupatorin and tetramethoxyflavone were present in SEOS in the amounts of 7.58%, 0.2%, 0.34% and 0.24% respectively. The LD(50) of the extract in rats was higher than 5000 mg/kg body weight. Therefore, the present study ascertained that SEOS possesses a significant anti-pyretic activity.
Anti-inflammatory and analgesic activities of a standardized Orthosiphon stamineus methanol:water (50:50 vol/vol) leaf extract (SEOS) were evaluated in animal models. Oral administration of SEOS at doses of 500 and 1,000 mg/kg significantly reduced the hind paw edema in rats at 3 and 5 hours after carrageenan administration (P < .01 and P < .01; P < .01 and P < .05, respectively). SEOS (1,000 mg/kg, p.o.) also produced significant (P < .05) analgesic activity in both the acetic acid-induced writhing test and the formalin-induced licking test (late phase) in mice and rats, respectively. However, SEOS showed no effect on the tail flick and hot plate tests in mice. The results of the present study support the proposal that O. stamineus has anti-inflammatory and non-narcotic analgesic activities. These findings justify the traditional use of the plant for treating pain and inflammation.
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.