Analgesic,anti-inflammatory,and antipyretic activities of the ethanol extract from Desmodium caudatum

Context: In folk medicine in China, Desmodium caudatum (Thunb.) DC (Leguminosae) has been used to treat febrile diseases, rheumatic arthritis, and bacillary dysentery; nevertheless, there have been no reports on the analgesic, antipyretic, and anti-inflammatory effects of this plant in animals.

Objective: To investigate the analgesic, anti-inflammatory, and antipyretic activities of D. caudatum extract (DCE) in animals.

Materials and methods: The analgesic effect of DCE was measured in mice using the acetic acid-induced writhing test and the hot-plate test. The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model and the dimethylbenzene-induced mouse inflammation model. The antipyretic effect was estimated using the lipopolysaccharide (LPS)-induced rat fever model. In addition, the acute oral toxicity of DCE was studied.

Results: DCE significantly and dose-dependently inhibited the writhing responses in mice, increased reaction time in mice in the hot-plate test, reduced carrageenan-induced paw edema in rats and the dimethylbenzene-induced ear edema in mice, and attenuated LPS-induced fever in rats. Furthermore, no death was observed when mice were orally administered DCE up to 40?g/kg.

Discussion and conclusion: DCE possesses evident analgesic, anti-inflammatory, and antipyretic activities, and has a favorable safety, which supports the use of D. caudatum as an analgesic, anti-inflammatory and antipyretic drug in folk medicine.     

Antihepatotoxic, nephroprotective, and antioxidant activities of phenolic compounds from Satureja macrostema leaves against carbon tetrachloride-induced hepatic damage in mice

Satureja macrostema (SM) is used with culinary and medicinal purposes. Methanol extract from SM was investigated for its phenolic content, antioxidant, hepatoprotective, and kidney protective activities. Liver and kidney damage were induced in rats with CCl₄. Hepatoprotective efficacy was measured by the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, high density lipoprotein and total protein, and lipid peroxidation. Kidney function was evaluated by measuring plasma urea and creatinine. Antioxidant activity was evaluated by measuring blood glutathione content, superoxide dismutase and catalase activities, and malondialdehyde equivalent; their activity was comparable to that of silymarin, a well-known hepatoprotective agent. Methanol extracts of S. macrostema showed potent antioxidant, kidney protective, and hepatoprotective activities; in-depth chromatographic investigation resulted in the identification of six new flavonoid glycosides: 5-hydroxy-3,6,4′-trimethoxyflavonol-7-C-α-l-rhamnopyranosyl-(1 → 3)-β-d-glucopyranoside (2), 4′-methoxy-5,7,3′,5′-tetra-hydroxyflavanone-3-O-β-d-rhamnopyranosyl-(1 → 2)-β-d-rhamnopyranoside (3), 5,4′-dimethoxy-7,3′,5′-trihydroxyflavanone-3-O-β-d-rhamnopyranoside (4), 5,3′,4′,5′-tetrahydroxyflavanone-7-O-β-d-rhamnopyranoside (5), 5,3′,4′,5′-tetramethoxyflavanone-7-O-β-d-rhamnopyranoside (6), and 5,4′-dimethoxy-3′-hydroxyflavone-7-β-d-rhamnopyranoside (8) along with three known compounds: 5-hydroxy-7,4′-dimethoxyflavone (1), prunin (7), and diosmin (9) that were isolated. Structural elucidation of the new compounds was established based on the spectral data. The present study revealed that S. macrostema leaves have a significant radical scavenging and hepatoprotective activity.     

Studies on the antioxidant activities of Desmodium gangeticum

Desmodium gangeticum is herbal species which is widely used in the indigenous system of medicine and is reported to contain flavone and isoflavanoid glycosides. In view of its wide use and it's chemical composition, this study was aimed at examining the antioxidant activity of the extract of D. gangeticum. The extract was studied for diphenyl picryl hydrazyl (DPPH), nitric oxide, ferryl-bipyridyl and hypochlorous acid scavenging activity along with lipid peroxidation. Nitric oxide was generated using sodium nitroprusside and was studied using Griess reagent. In order to study the iron chelating capacity of the extract, the percentage ferryl-bipyridyl inhibition was studied. Hypochlorous acid scavenging activity was tested by measuring the inhibition of 5-thio-2-nitrobenzoic acid oxidation. The extract was also studied for lipid peroxidation assay by thiobarbituric acid-reactive substances (TBARS) method using rat brain homogenate. The results indicate that D. gangeticum extract has potent antioxidant activity.     

Anti-inflammatory and antioxidant activities of Jungia paniculata

The present study was conducted to evaluate the antioxidant and anti-inflammatory activities of Jungia paniculata (DC.) A. Gray (Asteraceae), used traditionally in Peru. The dry leaves were extracted with methanol, 50% methanol, and water. The anti-inflammatory activity of this plant was studied using in vitro (nitric oxide production in RAW 264.7 macrophages and sPLA₂ inhibition assay) and in vivo (carrageenan-induced paw edema in rats and TPA-induced ear edema in mice) model systems. The antioxidant activity of extracts was studied using three in vitro model systems (DPPH^? radical-scavenging assay, ABTS^?+ assay, and superoxide radical-scavenging activity). The results have been correlated with total phenolics and total flavonoids contents. In the NO test of the extracts of Jungia paniculata, no significant cytotoxicities were observed at the concentrations determined by MTT assay. Only the MeOH50 extract of Jungia paniculata significantly inhibited PLA₂ enzyme activity (82.3?±?2.6%). At 3?h, the 50% methanol extract of Jungia paniculata at an oral dose of 500?mg/kg showed significant suppression of carrageenan-induced rat paw edema (36.36%). The same extract induced a 93.99% reduction in TPA-induced edema in topical administration. The extracts exhibited a high antioxidant activity and contained high total levels of polyphenols and flavonoids. There was a significant linear correlation between total phenolics and flavonoids contents and antioxidant activity in the three models used. In conclusion, Jungia paniculata possesses anti-inflammatory and antioxidant properties, which confirm the use of this plant in folk medicine as a topical anti-inflammatory herbal.     

Effect of interaction between phenolic compounds and copper ion on antioxidant and pro-oxidant activities

Phenolic compounds are widely used in food and cosmetics to prevent undesirable oxidation. On the other hand, phenolic compounds are also strong reducing agents and under in vitro conditions and in the presence of copper ion, they can act as pro-oxidants. In this study, we conducted electron spin resonance (ESR) measurements for the increase in reactive oxygen species (ROS) in relation to their structure and interaction with transition metals. Moreover, the antioxidant activity was assessed with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, and the pro-oxidant effect of phenolic compounds on DNA damage was assessed by measuring 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is effectively formed during oxidative damage. In conclusion, ortho-dihydroxyl groups that can chelate with Cu²⁺ induce the greatest pro-oxidant activity. Moreover, the interaction between phenolic compounds and copper induced to H₂O₂. The obtained results indicated that ROS participated in oxidative DNA damage induced by phenolic compounds in the presence of Cu²⁺.     

Anti-inflammatory and antioxidant activities of constituents isolated from Pueraria lobata roots

In order to evaluate the anti-inflammatory and antioxidant activities of Pueraria lobata roots and its active components, in vitro inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein expression, and tert-butylhydroperoxide (t-BHP)-induced reactive oxygen species (ROS) generation in RAW 264.7 cells, as well as in vitro scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH), peroxynitrite (ONOO(-)), nitric oxide (NO·), superoxide anion (·O(2)(-)) and total ROS, and inhibitory activities against ONOO(-)-mediated tyrosine nitration, were determined. Repeated column chromatography was performed to isolate four known compounds from the anti-inflammatory and antioxidant EtOAc fraction: daidzein; genistein; puerarin; (+)-puerarol B-2-O-glucopyranoside; four known compounds from the anti-inflammatory n-hexane fraction: lupenone; lupeol; puerarol; coumestrol; seven known compounds from the antioxidant n-BuOH fraction: allantoin; 3'-hydroxypuerarin; daidzein 8-C-apiosyl-(1→6)-glucoside; puerarin; genistin; 3'-methoxypuerarin; daidzin. Among these compounds, lupenone and lupeol reduced NO production, as well as iNOS and COX-2 protein levels in LPS-stimulated RAW 264.7 cells. Furthermore, lupeol showed significant inhibitory activity against intracellular ROS generation by t-BHP. Meanwhile, 3'-hydroxypuerarin showed marked ONOO(-), NO·, total ROS scavenging activities, and weak ·O(2)(-) scavenging activity, while 3'-methoxypuerarin showed ONOO(-) scavenging activity and weak NO· and O(2)(-) scavenging activities, suggesting that existence of the 3'-hydroxyl group in puerarin plays an important role in the scavenging of ONOO(-), NO·, and total ROS, as well as inhibiting the ONOO(-)-mediated tyrosine nitration mechanism. These results indicate that P. lobata roots and its constituents may be a useful therapeutic and preventive approach to various inflammatory diseases and oxidative stress-related disease.     

Anti-inflammatory action of phenolic compounds fromGastrodia elata root

Previous screening of the pharmacological action of Gastrodia elata (GE) root (Orchidaceae) showed that methanol (MeOH) extracts have significant anti-inflammatory properties. The anti-inflammatory agents of GE, however, remain unclear. In this experiment, MeOH extracts of GE were fractionated with organic solvents for the anti-inflammatory activity-guided separation of GE. Eight phenolic compounds from the ether (EtOEt) and ethyl acetate (EtOAc) fractions were isolated by column chromatography: 4-hydroxybenzaldehyde (I), 4-hydroxybenzyl alcohol (II), benzyl alcohol (III), bis-(4-hydroxyphenyl) methane (IV), 4(4'-hydroxybenzyloxy)benzyl methylether (V), 4-hydroxy-3-methoxybenzyl alcohol (VI), 4-hydroxy-3-methoxybenzaldehyde (VII), and 4-hydroxy-3-methoxybenzoic acid (VIII). To investigate the anti-inflammatory and anti-oxidant activity of these compounds, their effects on carrageenan-induced paw edema, arachidonic acid (AA)-induced ear edema and analgesic activity in acetic acid (HAc)-induced writhing response were carried out in vivo; cyclooxygenase (COX) activity, reactive oxygen species (ROS) generation in rat basophilic leukemia (RBL 2H3) cells and 1,1-diphenyl-2-picryl-hydroazyl (DPPH) scavenging activity were determined in vitro. These phenolic compounds not only had anti-inflammatory and analgesic properties in vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner. Among these phenolic compounds, compound VII was the most potent anti-inflammatory and analgesic. Compound VII significantly inhibited silica-induced ROS generation and compound VI significantly increased DPPH radical scavenging activity. Compounds I, II and III significantly inhibited the activity of COX-I and II. These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity. Consideration of the structure-activity relationship of the phenolic derivatives from GE on the anti-inflammatory action revealed that both C-4 hydroxy and C-3 methoxy radicals of benzyl aldehyde play an important role in anti-inflammatory activities.     

4-O-Caffeoylquinic acid as an antioxidant marker for mulberry leaves rich in phenolic compounds

Mulberry (Morus alba L.) leaves are widely used as herbal tea to prevent heat stroke. Potential chemical markers of the antioxidant properties and its correlation with harvesting times and leaf location were explored in this study. A 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay guided isolation of mulberry leaves extract provided five phenolic compounds: 5-O-caffeoylquinic acid (1), 4-O-caffeoylquinic acid (2), gastrodin (3), isoquercetin (4) and rutin (5). The 50% radical-scavenging concentrations (SC₅₀) of these compounds were 32.76 ± 0.27, 11.41 ± 0.48, 404.30 ± 4.92, 10.63 ± 0.96, and 10.57 ± 0.61 μg/mL, respectively. Chromatographic fingerprinting allowed content analysis of 1–5 in samples over a 12-month period. Compounds 1–5 were abundance in apical leaves (0–10 cm) in January and February at temperatures < 20 °C. Contents of 2 and 5 were highest in these months and were strongly correlated to the antioxidant property. Therefore, we suggested that the mulberry leaves harvested during January and February have high yield of 4-O-caffeoylquinic acid and this compound can be used as antioxidative marker in mulberry leaves.     

New phenolic compounds from Camellia sinensis L. fermented leaves

Two new phenolic compounds (1 and 2, named as teasperol and teasperin, respectively) were isolated from fermented tea (Camellia sinensis L.) products, together with known phenolic compounds. Teasperol (1) was isolated from Chinese traditional post-fermented tea leaves (Liu-pao tea) and teasperin (2) was from a Japanese tea product which was selectively fermented with Aspergillus sp. The chemical structures of 1 and 2 were elucidated based on the analyses of their spectroscopic data.     

Effects of blending wheatgrass juice on enhancing phenolic compounds and antioxidant activities of traditional kombucha beverage

Traditional kombucha is a fermented black tea extract and sugar. Sweetened black tea (10% w/v) and wheatgrass juice (WGJ) were mixed in various ratios and used as fermentation substrate for enhancing phenolic compounds and antioxidant activity. Starter, comprising of yeast (Dekkera bruxellensis) and acetic acid bacteria (Gluconacetobacter rhaeticus and Gluconobacter roseus), was inoculated at 20% (v/v), and fermented statically at 29 ± 1°C for 12 days. The results showed that the total phenolic and flavonoid contents and antioxidant activity of the modified kombucha were higher than those of traditional preparations. All WGJ-blended kombucha preparations were characterized as having higher concentrations of various phenolic compounds such as gallic acid, catechin, caffeic acid, ferulic acid, rutin, and chlorogenic acid as compared to traditional ones. Addition of WGJ resulted in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability of kombucha being > 90%, while the oxygen radical absorbance capacity increased from 5.0 μmol trolox equivalents/mL to 12.8 μmol trolox equivalents/mL as the ratio of WGJ increased from 0% to 67% (v/v). The highest antioxidant activity was obtained using a 1:1 (v/v) black tea decoction to WGJ ratio and 3 days of fermentation, producing various types of phenolic acids. These results suggest that intake of fermented black tea enhanced with wheatgrass juice is advantageous over traditional kombucha formulas in terms of providing various complementary phenolics and might have more potential to reduce oxidative stress.     

Adaptive neuro-fuzzy inference system-applied QSAR with bond dissociation energy for antioxidant activities of phenolic compounds

The aim of this study was to develop quantitative structure–activity relationship (QSAR) models for predicting antioxidant activities of phenolic compounds. The bond dissociation energy of O–H bond (BDE) was calculated by semi-empirical quantum chemical methods. As a new parameter for QSAR models, sum of reciprocals of BDE of enol and phenol groups (X _BDE ) was calculated. Significant correlations were observed between X _BDE and antioxidant activities, and X _BDE was introduced as a parameter for developing QSAR models. Linear regression-applied QSAR models and adaptive neuro-fuzzy inference system (ANFIS)-applied QSAR models were developed. QSAR models by both of linear regression and ANFIS achieved high prediction accuracies. Among the developed models, ANFIS-applied models achieved better prediction accuracies than linear regression-applied models. From these results, the proposed parameter of X _BDE was confirmed as an appropriate variable for predicting and analysing antioxidant activities of phenolic compounds. Also, the ANFIS could be applied on QSAR models to improve prediction accuracy.     

Two novel dammarane-type compounds from the leaves and stems of Panax quinquefolium L.

Two new dammarane-type compounds were isolated from the leaves and stems of Panax quinquefolium L. The new compounds were named as pseudo-ginsenoside RT₆ (1) and pseudoginsengenin R₁ (2). The structures of the new compounds were elucidated by the combined analysis of NMR and HR-ESI-MS as (20S,24R)-6-O-β-d-glucopyranosyl-dammar-3-one-20,24-epoxy-6α,12β,25-triol (1) and (20S,24R)-dammar-3-one-20,24-epoxy-6α,12β,25-triol (2).     

Anti-inflammatory and anti-allergic activities of hydroxylamine and related compounds

The anti-inflammatory activities of several novel oximes and O-acyl oximes that we synthesized have been reported based on carrageenan-induced rat foot-pad swelling assay and histamine-induced rat vascular permeability assay. A cyclooxygenase (COX)-1 inhibitory effect has also been reported for 4'-piperidinoacetophenone and 4'-morpholinoacetophenone oximes and their O-acyl derivatives. To further search for more effective non-steroidal anti-inflammatory or anti-allergic drugs, 1-hydroxylamino-1-(4'-piperidinophenyl) ethane (P-HA) and 1-hydroxylamino-1-(4'-morpholinophenyl) ethane (M-HA) were synthesized from the corresponding oximes with sodium cyanoborohydride, and N,O-diacetyl hydroxylamines (P-HA-Ac and M-HA-Ac) were prepared from these hydroxylamines using acetyl chloride. These hydroxylamines and N,O-diacetyl hydroxylamines clearly exhibited inhibitory effects on mouse carrageenan-induced foot-pad swelling induced by oral administration (150, 37.5 mg/kg). An oral dose of P-HA-Ac (150 mg/kg) significantly inhibited the mouse anaphylactic reaction to ovalbumin measured by the abdominal wall (AW) method. Percutaneous administration of P-HA and M-HA significantly inhibited 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity reaction (type IV) in mice at a dose of 0.5 and 0.1 mg/ear, respectively. All tested hydroxylamines and N,O-diacetyl hydroxylamines clearly inhibited both COX-1 and COX-2 enzyme activities with IC(50) values of 1.9-28.7 and 1.6-2.9 micro M against COX-1 and COX-2, respectively. Hydroxylamines (P-HA and M-HA) also showed a 5-lipoxygenase inhibitory effect.     

Anti-inflammatory,analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid

Context 3,4-Oxo-isopropylidene-shikimic acid (ISA) is an analog of shikimic acid (SA). SA is extracted from the dry fruit of Illicium verum Hook. f. (Magnoliaceae), which has been used for treating stomachaches, skin inflammation and rheumatic pain.

Objective To investigate the anti-inflammatory, analgesic and antioxidant activities of ISA.

Materials and methods Analgesic and anti-inflammatory activities of ISA were evaluated using writhing, hot plate, xylene-induced ear oedema, carrageenan-induced paw oedema and cotton pellets-induced granuloma test, meanwhile the prostaglandin E₂ (PGE₂) and malondialdehyde (MDA) levels were assessed in the oedema paw tissue. ISA (60, 120 and 240?mg/kg in mice model and 50, 120 and 200?mg/kg in rat model) was administered orally, 30?min before induction of inflammation/pain. Additionally, ISA was administered for 12 d in rats from the day of cotton pellet implantation. The active oxygen species scavenging potencies of ISA (10^?3–10^?5 M) were evaluated by the electron spin resonance spin-trapping technique.

Results ISA caused a reduction of inflammation induced by xylene (18.1–31.4%), carrageenan (7.8–51.0%) and cotton pellets (11.4–24.0%). Furthermore, ISA decreased the production of PGE₂ and MDA in the rat paw tissue by 1.0–15.6% and 6.3–27.6%, respectively. ISA also reduced pain induced by acetic acid (15.6–48.9%) and hot plate (10.5–28.5%). Finally, ISA exhibited moderate antioxidant activity by scavenging the superoxide radical and hydroxyl radical with IC₅₀ values of 0.214 and 0.450?μg/mL, respectively.

Discussion and conclusion Our findings confirmed the anti-inflammatory, analgesic and antioxidant activities of ISA.     

Anti-inflammatory isoflavonoids from the stems of Derris scandens

Fractionation of the aqueous extract of Derris scandens stems extract using tests for eicosanoid inhibition resulted in the isolation of three isoflavonoids, genistein, its 7- O-alpha-rhamno(1-->6)-beta-glucosyl glycoside, a new compound, and two known isoprenyl derivatives 3'-gamma,gamma-dimethylallylweighteone and scandenin. The isoprenylated compounds showed a high inhibitory effect on eicosanoid production in vitro but HPLC analysis showed that the genistein accounted for most of the activity of the total extract. Antioxidant studies showed that genistein and the isoprenylated compounds showed activity comparable to standard antioxidants. Genistein and its glycoside demonstrated no cytotoxicity in the MTT test but the prenylated compounds showed some toxicity and also increased LDH release from polymorphonucleocytes, at concentrations much greater than would be encountered in an aqueous extract of D. scandens.