Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fethan normal cells, there are a large number of transferrin receptors on the tumor cell membrane. DHA can break the peroxide bridge in the presence of Fe, and the free radicals generated can play its lethal effect on tumor cells. In addition, DHA can promote endocytosis of transferrin receptor, and thus prevent cancer cells from taking Fefrom microenvironment. This article reviews the anti-tumor molecular mechanism of DHA, including accelerating oxidative damage, inducing apoptosis, inhibiting the growth, proliferation and invasion of tumor cells, reversing tumor multidrug resistance.
Antigens, CD ; drug effects ; metabolism ; Antineoplastic Agents ; pharmacokinetics ; pharmacology ; Apoptosis ; drug effects ; Artemisinins ; metabolism ; pharmacokinetics ; pharmacology ; Endocytosis ; drug effects ; Free Radicals ; chemical synthesis ; pharmacology ; Humans ; Iron ; metabolism ; Neoplasms ; drug therapy ; physiopathology ; Oxidative Stress ; drug effects ; Receptors, Transferrin ; drug effects ; metabolism

Bio-active components from Carthamus tinctorius were separated on the basis of antioxidant capacities in vitro. The antioxidant capacity was investigated on the basis of the ability to scavenge DPPH radical, ABTS radical and reduce Fe3+ of different polar fractions. Furthermore, the chemical compounds were isolated from bio-active fraction, and were evaluated for the antioxidative effects. Five major components were isolated and identified from water extract as 6-hydroxykaempferol 3,6,7-tri-O-β-D-glucoside(1), 6-hydroxykaempferol 3-O-β-rutinoside-6-O-β-D-glucoside (2), 6-hydroxykaempferol 3-O-β-D-glucoside (3), hydroxysafflor yellow A (4) and anhydrosafflor yellow B (5). By evaluating and comparing the antioxidative effects of different fractions and obtained compounds, the results showed that water extract displayed significantly high antioxidative activities and 6-hydroxykaempferol glycosides and quinochalcone C-glycosides were found as main contribution for antioxidant property.
Antioxidants ; isolation & purification ; metabolism ; pharmacology ; Benzothiazoles ; metabolism ; Biphenyl Compounds ; metabolism ; Carthamus tinctorius ; chemistry ; Chalcone ; analogs & derivatives ; isolation & purification ; metabolism ; pharmacology ; Ferric Compounds ; metabolism ; Free Radicals ; metabolism ; Kaempferols ; isolation & purification ; metabolism ; pharmacology ; Oxidation-Reduction ; drug effects ; Picrates ; metabolism ; Plant Extracts ; isolation & purification ; metabolism ; pharmacology ; Plants, Medicinal ; chemistry ; Quinones ; isolation & purification ; metabolism ; pharmacology ; Sulfonic Acids ; metabolism ; Water ; chemistry

Using sustained release tablets of gardenia extract as model drug and DPPH radical scavenging capacity as antioxidant index, the feasibility of using pharmacodynamics index was explored to evaluate sustained release tablets. Applying the established quantifiable method of DPPH radical scavenging to the dissolved liquid of model drug, release profiles and biological effects profiles were drawn, and their correlation was discussed. A good correlation was observed by linear regression and f2 actor, suggesting that the indicator could be used to evaluate sustained release tabletsofextracts of gardenia in which iridoids were mainly involved.
Antioxidants ; metabolism ; pharmacology ; Biphenyl Compounds ; metabolism ; Delayed-Action Preparations ; metabolism ; pharmacokinetics ; Free Radicals ; metabolism ; Gardenia ; chemistry ; Kinetics ; Linear Models ; Oxidation-Reduction ; drug effects ; Picrates ; metabolism ; Plant Extracts ; metabolism ; pharmacokinetics ; Tablets

OBJECTIVETo investigate the anti-inflammatory, antioxidant and anti-arthritic effects of Centella asiatica methanolfraction (CaME) on collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis.

METHODSArthritis was induced in female wistar rats by immunization with porcine type II collagen. The CIA rats were treated orally with CaME (50, 150, and 250 mg/kg/day) for 15 d (beginning on day 21 of the experimental period). The clinical, histological, biochemical, and immunological parameters were assessed.

RESULTSCaME treatment (150 and 250 mg/kg) significantly attenuated the severity of CIA and reduced the synovial inflammation, cartilage erosion, and bone erosion as evident from both histological and radiographic data. The escalated plasma levels of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-12 alongwith nitric oxide in CIA rats decreased significantly on CaME treatment. The serum levels of type-II collagen antibody were significantly lower in rats of CaME (150 and 250 mg/kg) treated group than those in the arthritic group. Furthermore, by inhibiting the above mediators, CaME also contributed towards the reversal of the disturbed antioxidant levels and peroxidative damage.

CONCLUSIONOur results clearly indicate that oral administration of CaME suppresses joint inflammation, cytokine expression as well as antioxidant imbalance, thereby contributing to an amelioration of arthritis severity in CIA rats.

Animals ; Arthritis, Experimental ; blood ; drug therapy ; Centella ; chemistry ; Cytokines ; metabolism ; Drug Evaluation, Preclinical ; Female ; Flavonoids ; analysis ; Free Radical Scavengers ; analysis ; Free Radicals ; metabolism ; Joints ; metabolism ; Lipid Peroxidation ; drug effects ; Liver ; metabolism ; Nitric Oxide ; metabolism ; Oxidative Stress ; drug effects ; Phenols ; analysis ; Phytotherapy ; Proanthocyanidins ; analysis ; Random Allocation ; Rats, Wistar ; Triterpenes ; pharmacology ; therapeutic use

Timely removal of oxidatively damaged proteins is critical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modification that may play a role in targeting oxidized proteins and remove them. In this process, DSS1 (deleted in split hand/split foot 1), an evolutionally conserved small protein, is conjugated to proteins induced by oxidative stresses in vitro and in vivo, implying oxidized proteins are DSS1 clients. A subsequent ubiquitination targeting DSS1-protein adducts has been observed, suggesting the client proteins are degraded through the ubiquitin-proteasome pathway. The DSS1 attachment to its clients is evidenced to be an enzymatic process modulated by an unidentified ATPase. We name this novel protein modification as DSSylation, in which DSS1 plays as a modifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them.
Free Radicals ; metabolism ; HeLa Cells ; Humans ; Oxidation-Reduction ; Oxidative Stress ; genetics ; Proteasome Endopeptidase Complex ; genetics ; metabolism ; Protein Binding ; Protein Modification, Translational ; genetics ; Ubiquitin ; metabolism ; Ubiquitination ; genetics

OBJECTIVETo investigate the protective effect of H2S pretreatment after cerebral schemia/reperfusion injury and its mechanisms in rats.

METHODSThe rat model of global cerebral ischemia/reperfusion injury was established by bilateral common carotid arteries occlusion combined with hemorrhagic hypotension.30 rats were randomly divided into four groups(1)sham group(n=5),in which rats received sham surgery only,with their bilateral vertebral artery and bilateral common carotid artery exposed but without ischemia treatment;(2)global cerebral ischemia/reperfusion model group(IR group,n=5),in which the global cerebral ischemia was induced by 10-min occlusion of bilateral common carotid arteries combined with hypotension;(3)H2S pretreatment group(n=15),in which H2S(12,24,48 Μmol/kg)was intraperitoneally injected before operation;(4)NaCl pretreatment group(n=5),in which the rats were intraperitoneally injected with saline 30 minutes before operation.The activities of superoxide dismutase(SOD)and the levels of malondialdeehyde(MDA)in brain were measured by spectrophotometry.Brain water content was detected.The expression of heat shock protein 70(HSP70) in the hippocampus was determined by Western blotting.

RESULTSThe SOD activities were significant increased in groups pretreated with 12Μmol/kg H2S(P=0.042),24Μmol/kg H2S(P=0.002),and 48Μmol/kg H2S(P=0.000),and the SOD activity was significantly lower in the ischemia group than in the Sham group(P=0.003).The MDA activities in the 24Μmol/kg group(P=0.026)and the 48Μmol/kg group(P=0.015)groups were significantly lower than in the IR group.The brain water content was decreased in H2S pretreatment group(24Μmol/kg and 48 Μmol/kg)compared with IR group(P=0.018,P=0.008),and it was also significantly higher in the IR group than in the sham group(P=0.009).The expression of HSP70 were decreased in H2S pretreatment group(24 Μmol/kg)compared with the IR group(P=0.000),and the expression of HSP70 were significantly higher in the IR group than in HSP70 group(P=0.000).The expression of HSP70 also significantly differed between NaCl group and HSP70 group(P=0.000).

CONCLUSIONH2S has protective effects on cerebral ischemia and reperfusion,which may be achieved by improving SOD activity,removing oxygen free radicals,inhibiting lipid peroxidation,and down-regulating the expression of HSP70 in the hippocampus.

Animals ; Brain Ischemia ; metabolism ; Free Radicals ; metabolism ; HSP70 Heat-Shock Proteins ; metabolism ; Hippocampus ; metabolism ; Hydrogen Sulfide ; administration & dosage ; therapeutic use ; Male ; Random Allocation ; Rats ; Reperfusion Injury ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism

Animals ; Drugs, Chinese Herbal ; pharmacology ; Free Radicals ; metabolism ; Male ; Myocardium ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Wistar

Animals ; Athletic Performance ; Drugs, Chinese Herbal ; pharmacology ; Free Radicals ; metabolism ; Male ; Mice ; Mice, Inbred Strains ; Morinda ; Myocardium ; metabolism ; Physical Conditioning, Animal

Free radicals are atoms, molecules or ions with unpaired electrons. In biological systems, free radicals can have a dual role, being beneficial in some situations and deleterious in others. Free radicals are required for normal cellular metabolism, but they lead to cellular degeneration if overproduced. To prevent the excessive buildup of free radicals, cells have developed an elaborate series of antioxidant enzymes that counteract oxidative stress and protect cells by maintaining the proper balance of oxidation and anti-oxidation. Therefore, when there is an oxidant/anti-oxidant imbalance, no matter what direction, cells are likely to be damaged. Numerous reports in the literature indicate that free radicals play important roles in diseases of the inner ear as a result of noise exposure, ototoxic drugs, aging, and other pathological conditions. Therefore, there have been many attempts to employ antioxidants treat inner ear damage. However, antioxidant therapy could be harmful if the improper compound or dose is employed. Effective antioxidant therapy requires prior knowledge of the type(s) of oxidative stress occurring in real time in the inner ear. Since most techniques for detecting free radicals in the inner ear are not clinically feasible, systemic anti-oxidant therapy is generally performed "blindly" and therefore likely to disrupt normal antioxidant levels in the inner ear or elsewhere in the body. If only a single anti-oxidant is used to treat a disease, it may disturb subsequent steps the oxidative/anti-oxidative chain reaction. An alternative approach, hydrogen therapy represents a promising therapeutic tool because it can selectively scavenge the strongest oxidant species, the hydroxyl radical and peroxynitrite anion, without disturbing normal oxidant/anti-oxidant cellular processes. In addition, hydrogen has no cytotoxic effects to cells so that it provides a near ideal therapy to eliminate toxic free radicals.
Animals ; Ear, Inner ; metabolism ; physiopathology ; Free Radicals ; metabolism ; Humans ; Oxidative Stress

LC-MS/MS method was used to simultaneously determine anti-oxidative active catechins EGCG, ECG, EGC and EC in plasma of rats treated with tea polyphenols (TP). The integrated plasma concentration (C') of TP was calculated by means of self-defined weighing coefficient based on percent AUC of individual components, thereby assessing integrated pharmacokinetic (PK) parameters of TP via log C'-T curve. The anti-free radical effects of TP were estimated using inhibitory rate of drug-containing serum collected at different times from rats against in vitro lipid peroxidation of mouse liver homogenate. The obtained E-T curves were used to calculate anti-free radical pharmacodynamic (PD) parameters of TP. E-logC and E-log C' plots and linear regression were carried out in order to obtain the correlation coefficient (R2). The results indicated that the log C'-T curves of TP, which could be best described by three-compartment model, corresponded to elimination rule of iv administration of drugs. The integrated PK parameters showed that TP was distributed in body rapidly and widely, and eliminated from deep compartment slowly. From comparison of R2 values and consistence of C'-T course and E-T course, it was evident that TP integrated PK behaviors correlated much better with its PD behaviors than individual active components, and thus demonstrated that integrated PK parameters could characterize to maximal extent holistic disposition of Chinese herbal drugs and reflect residence properties of holistic effective substances in biological body.
Animals ; Antioxidants ; pharmacokinetics ; pharmacology ; Area Under Curve ; Catechin ; analogs & derivatives ; pharmacokinetics ; Chromatography, Liquid ; Free Radical Scavengers ; blood ; pharmacokinetics ; pharmacology ; Free Radicals ; metabolism ; Injections, Intravenous ; Lipid Peroxidation ; drug effects ; Male ; Mice ; Polyphenols ; blood ; pharmacokinetics ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Tea ; chemistry