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 antinociceptive property of Centella asiatica extracts is known but the analgesic activity of its bioactive constituent asiaticoside has not been reported. We evaluated the antinociceptive activity of orally (p. o.) administered asiaticoside (1, 3, 5, and 10 mg/kg) in mice using the 0.6% acetic acid-induced writhing test, the 2.5% formalin-induced paw licking test, and the hot plate test. The capsaicin- and glutamate-induced paw licking tests were employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Asiaticoside (3, 5, and 10 mg/kg, p. o.) reduced the rate of writhing (p
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.
Angiogenesis plays an important role in tumor formation and proliferation. The development of anti-angiogenic agents to block new blood vessel growth will inhibit metastasis and induce apoptosis of the cancer cells. Nine medicinal plants, Strobilanthes crispus, Phyllanthus niruri, Phyllanthus pulcher, Phyllanthus urinaria, Ailanthus malabarica, Irvingia malayana, Smilax myosotiflora, Tinospora crispa and blumea balsamifera were screened for anti-angiogenic properties using the rat aortic ring assay. Of these, the methanol extracts of Phyllanthus species and Irvingia malayana exhibited the highest activity. At 100 microg/mL, P. pulcher, P. niruri, P. urinaria and I. malayana recorded an inhibition of 78.8 %, 59.5 %, 56.7 % and 46.4 %, respectively, against rat aortic vascular growth. Their activities were further investigated by the tube formation assay involving human umbilical vein endothelial cells (HUVEC) on Matrigel. I. malayana, P. niruri and P. urinaria showed a significant decrease of 45.5, 37.9 and 35.6 %, respectively, whilst P. pulcher showed a much lower decrease of 15.5 % when compared with that of the rat aortic ring assay. All the plant extracts were evaluated for cytotoxicity on a panel of human cancer cell lines using the MTT assay. None of them displayed acute cytotoxicity. The HPLC of P. niruri, P. urinaria and P. pulcher indicated the extracts contained some identical chromatographic peaks of lignans. Further fractionation of I. malayana yielded betulinic acid reported in this plant for the first time and at 100 microg/mL it exhibited a 67.3 % inhibition of vessel outgrowth and 46.5 % inhibition of tube formation.
Brewed green tea, green tea extract, and its primary active compound, epigallocatechin gallate, may interact with drugs and alter the drug's therapeutic effectiveness, ultimately leading to therapeutic failure or drug overdose. Several isolated reports have claimed that epigallocatechin gallate is the main active ingredient that causes these effects. While a few studies aimed to uncover evidence of epigallocatechin gallate-drug interactions, no study has thoroughly and collectively reviewed them. Epigallocatechin gallate is a potential cardioprotective agent used by many patients with cardiovascular diseases as a complementary medicine alongside conventional modern medications, either with or without the knowledge of their physicians. Therefore, this review focuses on the impact of concurrent epigallocatechin gallate supplementation on pharmacokinetics and pharmacodynamics of several commonly used cardiovascular drugs (statins, beta-blockers, and calcium channel blockers). The PubMed index was searched for key words related to this review, without year limit, and the results were analyzed for interactions of cardiovascular drugs with epigallocatechin gallate. This review concludes that epigallocatechin gallate increases systemic circulation of several statins (simvastatin, fluvastatin, rosuvastatin) and calcium channel blockers (verapamil), but decreases the bioavailability of beta-blockers (nadolol, atenolol, bisoprolol). Further studies on its clinical significance in affecting drug efficacy are required.
Antioxidants such as vitamin E may act differently on skin cells depending on the age of the skin and the level of oxidative damage induced. The effects of alpha-tocopherol (ATF) on H(2)O(2)-induced DNA damage and telomere shortening of normal human skin fibroblast cells derived from young and old individual donors were determined. Fibroblasts were divided into five groups; untreated control, H(2)O(2)-induced oxidative stress, alpha-tocopherol treatment, and pre- and post-treatment with alpha-tocopherol for H(2)O(2)-induced oxidative stress. Our results showed that H(2)O(2)-induced oxidative stress increased DNA damage, shortened the telomere length and reduced the telomerase activity (p < 0.05) in fibroblasts obtained from young and old donors. Pre- and post-treatment with alpha-tocopherol protected against H(2)O(2)-induced DNA damage in fibroblasts obtained from young individuals (p = 0.005; p = 0.01, respectively). However, in fibroblasts obtained from old individuals, similar protective effects were only seen in cells pretreated with alpha-tocopherol (p = 0.05) but not in the post-treated cells. Protection against H(2)O(2)-induced telomere shortening was observed in fibroblasts obtained from both young and old donors which were pre-treated with alpha-tocopherol (p = 0.009; p = 0.008, respectively). However, similar protective effects against telomere shortening in fibroblasts obtained from both young and old donors were not observed in the post-treated fibroblasts. Protection against H(2)O(2)-induced telomerase activity loss was observed only in fibroblasts obtained from old donors which were pretreated with alpha-tocopherol (p = 0.04) but not in fibroblasts obtained from young donors. Similar protective effects against telomerase activity loss in fibroblasts obtained from both young and old donors were not observed in the post-treated fibroblasts. In conclusion, alpha-tocopherol protected against H(2)O(2)-induced telomere shortening by restoring the telomerase activity. It also modulated H(2)O(2)-induced DNA damage and this modulation was affected by donor age.
Dichloromethane extracts of the root bark and stem bark of Kigelia pinnata collected from Zimbabwe exhibited antitrypanosomal activity against Trypanosoma brucei brucei in vitro. Activity-guided fractionation led to the isolation of four naphthoquinones from both the root and stem bark of the plant. The compounds were identified as 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-quinone (1), isopinnatal (2), kigelinol (3), and isokigelinol (4). Subsequently, the compounds were assessed for antitrypanosomal activity against T. brucei brucei and T. brucei rhodesiense bloodstream form trypomastigotes in vitro. Compound 1 with a furanonaphthoquinone structure was found to possess pronounced activity against both parasites with IC50 values of 0.12 and 0.045 microM, respectively, although it was less active than the standard drug pentamidine. Compounds 2, 3, and 4 also exhibited activity against the parasites, although to a lesser extent. The activities of the compounds were further assessed by comparison with the cytotoxic activities obtained against KB cell lines.
The rhizomes of Alpinia pahangensis yielded a new bis-labdanic diterpene for which the name pahangensin C (1) was proposed along with twelve known analogues (2-13). The structure of 1 was elucidated via spectroscopic methods including 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 2 and 12 were isolated for the first time from the genus Alpinia. This is the second occurrence of compounds 2 and 12 in the Zingiberaceae family. Selected analogues exhibited moderate to strong inhibitory activity against Staphylococcus aureus and Bacillus cereus.
A high-performance liquid chromatography assay equipped with a glassy carbon electrode for electrochemical detection (HPLC-ECD) was developed at reductive mode for the analysis of artemisinin, the antimalarial drug from Artemisia annua (Asteraceae) in human plasma. This method was selective, sensitive, and produced satisfactory recovery, precision, and accuracy. Analysis of plasma samples from 8 male volunteers given 10 mg kg-1 of artemisinin orally as an aqueous suspension showed a mean peak plasma concentration (Cmax) of 580.89 ng ml-1 +/- 88.64 SD at 2.5 h +/- 0.5 SD after dosing, and the mean area under the plasma concentration-time curve (AUC0-infinity) was 2227.57 ng h ml-1 +/- 677.22 SD. In addition, the elimination rate constant (Ke), elimination half-life (t1/2), and apparent volume of distribution (Vd) were calculated to be 0.2971 h-1 +/- 0.0644 SD, 2.42 h +/- 0.46 SD, and 16.26 l kg-1 +/- 3.44 SD, respectively.
Quassinoids, the major secondary metabolites of Eurycoma longifolia roots, improve male fertility. Hence, it is crucial to investigate their quantitative level in E. longifolia extracts. A profile was established to identify the primary metabolites and major quassinoids, and quantify quassinoids using external calibration curves. Furthermore, the metabolic discrimination of E. longifolia roots from different regions was investigated. The (1)H-NMR spectra of the quassinoids, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2-O-β-D-glycopyranoside were obtained. The (1)H-NMR profiles of E. longifolia root aqueous extracts from Perak (n = 30) were obtained and used to identify primary metabolites and the quassinoids. Selangor, Kedah, Terengganu (n = 5 for each), and Perak samples were checked for metabolic discrimination. Hotelling's T(2) plot was used to check for outliers. Orthogonal partial least-squares discriminant analysis was run to reveal the discriminatory metabolites. Perak samples contained formic, succinic, methylsuccinic, fumaric, lactic, acetic and syringic acids as well as choline, alanine, phenylalanine, tyrosine, α-glucose, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2-O-β-D-glycopyranoside. The extracts from other locations contained the same metabolites. The limit of quantification values were 1.96 (eurycomanone), 15.62 (eurycomanol), 3.91 (13,21-dihydroeurycomanone), and 31.25 (eurycomanol-2-O-β-D-glycopyranoside) ppm. The Hotelling's T(2) plot revealed no outlier. The orthogonal partial least-squares discriminant analysis model showed that choline, eurycomanol, eurycomanol-2-O-β-D-glycopyranoside, and lactic and succinic acid levels were different among regions. Terengganu and Perak samples contained higher amounts of eurycomanol and eurycomanol-2-O-β-D-glycopyranoside, respectively. The current approach efficiently detected E. longifolia root metabolites, quantified the quassinoids, and discriminated E. longifolia roots from different locations. These findings could be applicable to future research on E. longifolia where the higher content of quassinoids is required.