The inhibitory activities of the methanol extracts from 20 selected medicinal plants on the release of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs) were evaluated. The major compound from the most active plant extract was also investigated. The inhibitory effect of the methanol extracts on the release of pro-inflammatory cytokines was tested by incubating PBMCs with the sample and then stimulating by lipopolysaccharide at 0.1 μg/ml. The level of cytokines was determined using enzyme-linked immunosorbent assay. Among the extracts tested, Andrographis paniculata extract demonstrated the strongest inhibition of interleukin (IL)-1β, IL-1α, and IL-6 release, with IC50 values of 1.54, 1.06, and 0.74 μg/ml, respectively. The IC50 value of A. paniculata extract was significantly higher than that of andrographolide on IL-1α, IL-1β, and IL-6 (p
Eurycomanone, an active constituent isolated from Eurycoma longifolia Jack, was examined for modulatory effects on cytochrome P450 (CYP) isoforms CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 using in vitro assays. The IC50 value was determined to assess the potencies of modulation for each CYP isoform. Our results indicated that eurycomanone did not potently inhibit any of the CYP isoforms investigated, with IC50 values greater than 250 μg/ml. Hence there appears to be little likelihood of drug-herb interaction between eurycomanone or herbal products with high content of this compound and CYP drug substrates via CYP inhibition.
Dengue fever causes mortality and morbidity around the world, specifically in the Tropics and subtropic regions, which has been of major concern to governments and the World Health Organization (WHO). As a consequence, the search for new anti-dengue agents from medicinal plants has assumed more urgency than in the past. Medicinal plants have been used widely to treat a variety of vector ailments such as malaria. The demand for plant-based medicines is growing as they are generally considered to be safer, non-toxic and less harmful than synthetic drugs. This article reviews potential anti-dengue activities from plants distributed around the world. Sixty-nine studies from 1997 to 2012 describe 31 different species from 24 families that are known for their anti-dengue activities. About ten phytochemicals have been isolated from 11 species, among which are compounds with the potential for development of dengue treatment. Crude extracts and essential oils obtained from 31 species showed a broad activity against Flavivirus. Current studies show that natural products represent a rich potential source of new anti-dengue compounds. Further ethnobotanical surveys and laboratory investigations are needed established the potential of identified species in contributing to dengue control.
Loranthus parasiticus, a Chinese folk medicine, has been widely used for the treatment of brain diseases, particularly in southwest China. Hence, the present neuroprotection model was designed to investigate its neuroprotective properties against H(2)O(2)-induced oxidative stress in NG108-15 cells. L. parasiticus aqueous fraction (LPAF), which was selected in the present study, had proved to be the most active fraction among the other tested extracts and fractions in our previous screening. The restoration of depleted intracellular glutathione (GSH), a major endogenous antioxidant, by LPAF was observed after H(2)O(2) insult. Pretreatment with LPAF substantially reduced the production of intracellular reactive oxygen species generated from H(2)O(2). Apoptotic features such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential were significantly attenuated by LPAF. In addition, cell cycle analysis revealed a prominent decrease in the H(2)O(2)-induced sub-G(1) population by LPAF. Moreover, apoptotic morphological analysis by DAPI nuclear staining demonstrated that NG108-15 cells treated with H(2)O(2) exhibited apoptotic features, while such changes were greatly reduced in cells pretreated with LPAF. Taken together, these findings confirmed that LPAF exerts marked neuroprotective activity, which raises the possibility of potential therapeutic application of LPAF for managing oxidative stress-related neurological disorders and supports the traditional use of L. parasiticus in treating brain-related diseases.
The kidney is one of the critical target organs for chronic cadmium toxicity. Cadmium is a cumulative nephrotoxicant, and preferentially accumulates and persists in the kidneys. The natriuretic and antidiuretic effects of methyl alcohol extracts of Chelidonium majus L. (C. majus) leaves were evaluated in kidney of cadmium-intoxicated rats. Ninety-six male Sprague-Dawley Albino rats were divided into two major groups (toxicity and biochemical, 60 and 36 rats, respectively). There was a decrease in kidney weight and serum electrolytes, but an increase in urinary volume, excretion of electrolytes, serum urea and creatinine, after 9 weeks of cadmium chloride intoxication. Treatment of C. majus methyl alcohol extract for 10 weeks starting 1 week before cadmium administration shifted the above parameters towards the normal values. These results were supported by molecular and histological investigations. Treatment with C. majus methyl alcohol extract has natriuretic and antidiuretic effects against cadmium-induced nephrotoxicity in rats.
Obesity and overweight are associated with atherosclerosis, fatty liver, hyperlipemia, diabetes mellitus, and various types of cancer. The global prevalence of overweight and obesity has reached epidemic proportions. Here, we investigated the effect of Tamarindus indica pulp aqueous extract (TIE) in diet-induced obese Sprague-Dawley rats. The animals were divided into five groups and labeled as follows: the normal control (NC) group received normal diet; the positive control (PC) group received high-fat diet; and the TIE 5, 25, and 50 groups, after the induction of obesity via a high-fat diet, received TIE at 5, 25, or 50 mg/kg orally for 10 weeks. It was observed that TIE decreased the levels of plasma total cholesterol, low-density lipoprotein (LDL), and triglyceride, and increased high-density lipoprotein (HDL), with the concomitant reduction of body weight. Moreover, TIE decreased plasma leptin and reduced fatty acid synthase (FAS) activity and enhanced the efficiency of the antioxidant defense system. TIE exhibits antiobesity effects, as indicated by a significant reduction in adipose tissue weights, as well as lowering the degree of hepatic steatosis in the obesity-induced rats. The extract possesses hepatoprotective activity, as it reversed the plasma liver enzymes level elevation prior to the high-fat diet. In conclusion, TIE improved obesity-related parameters in blood, liver, and adipose tissue in a rat model and suppressed obesity induced by a high-fat diet, possibly by regulating lipid metabolism and lowering plasma leptin and FAS levels. A dose-dependant effect of TIE is detected, where TIE at 50 mg/kg showed the most prominent effect, followed by TIE at 25 mg/kg and, subsequently, 5 mg/kg.
We evaluated the effects of a standardized Labisia pumila var. alata (LPva) extract on body weight change, hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) expressions and corticosterone (CORT) level in ovariectomized (OVX) rats. The decoction of LPva has been used for generations among Malay women in Malaysia to maintain a healthy reproductive system.Thirty-six Sprague-Dawley OVX rats were treated orally with LPva extract (10, 20 or 50 mg/kg/day) or estrogen replacement (ERT) for 30 days. Sham operated rats were used as controls. Compared to untreated OVX rats, LPva-treated rats showed less weight gain and had significantly down-regulated HSD11B1 mRNA in liver tissues. HSD11B1 mRNA in adipose tissues increased by 55% (p < 0.05) in OVX rats but normalized in rats treated with LPva. Similarly, there was significant down-regulation (p < 0.05) of protein levels of HSD11B1 in both liver and adipose tissue of LPva and ERT groups, and CORT levels were significantly reduced in both groups of rats. This is the first study ever conducted to evaluate the beneficial effects of LPva in relation to weight gain caused by estrogen insufficiency. Results implied that the bioactive components in LPva extract affect not only HSD11B1 expressions in both adipose and liver tissues but also decrease circulating CORT. The extract should be explored for its potential use as a natural remedy for weight management.
We investigated the effects of Andrographis paniculata (AP) extracts and andrographolide on the catalytic activity of three human cDNA-expressed cytochrome P450 enzymes: CYP2C9, CYP2D6 and CYP3A4. In vitro probe-based high performance liquid chromatography assays were developed to determine CYP2C9-dependent tolbutamide methylhydroxylation, CYP2D6-dependent dextromethorphan O-demethylation and CYP3A4-dependent testosterone 6β-hydroxylation activities in the presence and absence of AP extracts and andrographolide. Our results indicate that AP ethanol and methanol extracts inhibited CYP activities more potently than aqueous and hexane extracts across the three isoforms. Potent inhibitory effects were observed on CYP3A4 and CYP2C9 activities (K (i) values below 20 μg/ml). Andrographolide was found to exclusively but weakly inhibit CYP3A4 activity. In conclusion, data presented in this study suggest that AP extracts have the potential to inhibit CYP isoforms in vitro. There was, however, variation in the potency of inhibition depending on the extracts and the isoforms investigated.
Successive extraction of the dried leaves of Melastoma malabathricum, followed by purification using repeated chromatographic techniques, yielded six compounds, including two amides, auranamide and patriscabratine, a triterpene, alpha-amyrin, and three flavonoids, quercitrin, quercetin and kaempferol-3-O-(2'',6''-di-O-p-trans-coumaroyl)-beta-glucoside. Their structures were elucidated by spectroscopic means and also by direct comparison of their spectroscopic data with respective published data. These three phenolic constituents were found to be active as free radical scavengers, with quercetin being the strongest radical scavenger, having an IC(50) value of 0.69 microM in the UV method. Quercitrin and kaempferol-3-O-(2'',6''-di-O-p-trans-coumaroyl)-beta-glucoside showed moderate radical scavenging, with IC(50) values of 74.1 and 108.8 microM, respectively.
Six prenylated flavones, including one new compound, were isolated and identified from the stem bark extracts of Artocarpus altilis. The new prenylated flavone hydroxyartocarpin (1) was characterized as 3-(gamma,gamma-dimethylallyl)-6-isopentenyl-5,8,2',4'-tetrahydroxy-7-methoxyflavone and the known compounds were artocarpin (2), morusin (3), cycloartobiloxanthone (4), cycloartocarpin A (5) and artoindonesianin V (6). The structures of the compounds were determined by spectroscopic methods (IR, MS, (1)H-NMR and (13)C-NMR) and comparison with published data for the known compounds.
Five prenylflavonoids and two prenylchalcones from Artocarpus lowii King, A. scortechinii King and A. teysmanii Miq., and acetylated derivatives of cycloheterophyllin and artonin E were investigated for their ability to inhibit arachidonic acid (AA), collagen and adenosine diphosphate (ADP)-induced platelet aggregation in human whole blood by using an electrical impedance method. Among the tested compounds, only cycloheterophyllin inhibited AA-induced platelet aggregation with an IC(50) value of 100.9 microM. It also showed strong inhibition against ADP-induced aggregation, with an IC(50) value of 57.1 microM. Isobavachalcone, 2',4'-dihydroxy-4-methoxy-3'-prenyldihydrochalcone, cycloartobiloxanthone, artonin E and artonin E triacetate showed selective inhibition against ADP-induced aggregation, with IC(50) values ranging from 55.3 to 192.0 microM, but did not show such effect against other inducers.
This study was performed to determine the antinociceptive and anti-inflammatory activities of aqueous extract of Kaempferia galanga leaves using various animal models. The extract, in the doses of 30, 100, and 300 mg/kg, was prepared by soaking (1:10; w/v) the air-dried powdered leaves (40 g) in distilled water (dH(2)O) for 72 h and administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot-plate and formalin tests, with activity observed in all tests occurring in a dose-dependent manner. Furthermore, the antinociceptive activity of K. galanga extract was significantly (P < 0.05) reversed when prechallenged with 10 mg/kg naloxone. The extract also produced a significantly (P < 0.05) dose-dependent anti-inflammatory activity when assessed using the carrageenan-induced paw-edema test. In conclusion, this study demonstrated that K. galanga leaves possessed antinociceptive and anti-inflammatory activities and thus supports the Malay's traditional uses of the plant for treatments of mouth ulcer, headache, sore throat, etc.
This study was performed out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of an aqueous extract of Dicranopteris linearis leaves in experimental animals. The antinociceptive activity was measured using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory and antipyretic activities were measured using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. The extract, obtained after 72 h soaking of the air-dried leaves in distilled water and then prepared in the doses of 13.2, 66.0, 132.0, and 660.0 mg/kg, was administered subcutaneously 30 min before subjecting the animals to the assays mentioned above. Generally, the extract, at all doses used, was found to have significant (P < 0.05) concentration-independent antinociceptive, anti-inflammatory, and anti-pyretic activity. In conclusion, the aqueous extract of D. linearis has antinociceptive, anti-inflammatory, and antipyretic activity, supporting previous claims of its traditional use by the Malays to treat various ailments, particularly fever.
A new prenylated dihydrochalcone, 2',4'-dihydroxy-4-methoxy-3'-prenyldihydrochalcone (1), along with two known compounds, 2',4',4-trihydroxy-3'-prenylchalcone (2) and 2',4-dihydroxy-3',4'-(2,2-dimethylchromene)chalcone (3) were isolated from the leaves of Artocarpus lowii. The structures of 1-3 were elucidated by spectroscopic methods and by comparison with data reported in the literature. Compounds 1-3 showed strong free radical scavenging activity towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) measured by electron spin resonance (ESR) spectrometry.
In recent years, Spirulina has gained more and more attention from medical scientists as a nutraceutical and a source of potential pharmaceuticals. The present study was conducted to elucidate the immunomodulatory effect of Spirulina fusiformis (a cyanobacterium of the family Oscillatoriaceae) in vivo and in vitro. The in vivo effect of S. fusiformis (400 or 800 mg/kg body wt.) on humoral immune response, cell-mediated immune response and tumour necrosis factor alpha was investigated in mice. We also evaluated the effect of S. fusiformis (50 or 100 microg/ml) in vitro on mitogen (phytohaemagglutinin)-induced T lymphocyte proliferation in heparinized human peripheral blood. For comparison, dexamethasone was used as a standard. In mice, S. fusiformis (400 or 800 mg/kg body wt.) administration significantly inhibited the humoral immune response, cell-mediated immune response (delayed-type hypersensitivity reaction (DTH)) and tumour necrosis factor alpha in a dose-dependent manner. In vitro, S. fusiformis (50 or 100 microg/ml) decreased the mitogen (phytohaemagglutinin)-induced T lymphocyte proliferation in a concentration-dependent manner when compared with control cells. These observations clearly suggest that S. fusiformis has a remarkable immunosuppressive effect, which provides a scientific validation for the popular use of this drug, and helped us in further work on investigating its complete mechanism of action.
Bioactivity guided separation of Reinwardtiodendron cinereum barks methanol extract led to the isolation of two new onocerane triterpenoids, reinereins A and B (1 and 2), together with three known onocerane triterpenoids. Their structures were elucidated on the basis of NMR spectroscopic data. In vitro cytotoxic activities of the isolated compounds against several type of cancer cells were evaluated.
Two new steroidal saponins, scrobiculosides A and B, were isolated from the deep-sea sponge Pachastrella scrobiculosa, collected at a depth of 200 m off Miura Peninsula, Japan. The aglycones of scrobiculosides A and B feature a vinylic cyclopropane and a ∆24,25 exomethylene on the side chains, respectively. Both saponins have a common sugar moiety composed of β-D-galactopyranosyl-(1 → 2)-6-acetyl-β-D-glucopyranoside, with the exception of an acetyl group on C6″ in scrobiculoside A. Scrobiculoside A exhibited cytotoxicity against HL-60 and P388 cells, with IC50 values of 52 and 61 μM, respectively.
The ceramicines, a series of limonoids from Chisocheton ceramicus (Meliaceae), were evaluated for anti-melanin deposition activity on α-melanocyte stimulating hormone (α-MSH) and 3-isobutyl-1-methylxanthine (IBMX)-treated B16-F10 melanoma cell, and several ceramicines were found to be active. The structure-activity relationship of ceramicines as anti-melanin deposition inhibitors was deduced. Furthermore, the mechanism of anti-melanin deposition activity of ceramicine B, a major constituent of C. ceramicus that showed potent anti-melanin deposition activity, was investigated. Tyrosinase enzymatic activity and tyrosinase mRNA expression were not affected by ceramicine B. The anti-melanin deposition activity of ceramicine B was shown to be related to the downregulation of tyrosinase protein expression. These results suggest that ceramicines have potential to be used as depigmentation agents.
We recently reported that (23R, 24E)-23-acetoxymangiferonic acid (23R-AMA), a cycloartane triterpenoid isolated by activity-guided separation from a methanol extract of Garcinia sp. bark, inhibited melanin production via inhibition of tyrosinase (TYR) expression in the B16-F10 melanoma cell line. Since 23R-AMA also inhibited microphthalmia-associated transcription factor (MITF) expression, an upstream factor of TYR, these features of 23R-AMA were thought to be appropriate for development of whitening cosmetics. However, 23R-AMA exhibited growth inhibition other than inhibition of melanin production in B16-F10 cells. Therefore, we investigated biological activities of 23R-AMA in detail, focused on its application as an anti-melanoma compound. In this study, we demonstrated that 23R-AMA inhibited cell proliferation and basic FGF (bFGF)-induced migration in B16-F10 cells. Furthermore, 23R-AMA promoted ser45/thr41 phosphorylation of β-catenin and suppressed its intranuclear accumulation, which was suggested to be related to inhibition of MITF expression. The transcriptional activity of MITF is known to be regulated by phosphorylation via activated ERK. Further investigation revealed that 23R-AMA inhibited phosphorylation of c-Raf, MEK-1, and ERK, and also that of upstream molecules including FAK and c-Src. These results suggested that 23R-AMA inhibited growth and migration of B16-F10 melanoma by regulating both MITF expression and its activity. The activities of 23R-AMA reported in this study are new aspects of cycloartane triterpenoids.