Effect of Semecarpus anacardium nut milk extract on rat serum alpha-fetoprotein level in aflatoxin B1-mediated hepatocellular carcinoma

An increased level of serum alpha-fetoprotein is observed in aflatoxin B₁ (AFB₁)-induced hepatocellular carcinoma (HC) in rats. Semecarpus anacardium nut milk extract (200 mg/kg, p.o., for 14 days) significantly reduced serum alpha-fetoprotein levels within the normal range, suggesting an antitumour activity against AFB₁-induced HC.     

Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of lycorine from Sternbergia fisheriana (Herbert) Rupr

The present study reports the potential antinociceptive, anti-inflammatory and hepatoprotective activities of lycorine from Sternbergia fischeriana (Herbert) Rupr. (Amaryllidaceae). Lycorine was evaluated on mice by using acetic-acid induced writhing and tail-flick tests. Lycorine exhibited stronger inhibition than aspirin in acetic-acid induced abdominal stretching at 1.0 mg/kg dose. Lycorine also showed antinociceptive activity at 1.0 mg/kg dose in tail-flick test. The anti-inflammatory activity of lycorine was not found to be significant at dose of 0.5 mg/kg. However, at doses of 1.0 mg/kg and 1.5 mg/kg, i.p. showed a significant reduction with 53.45% and 36.42%, respectively in rat paw oedema induced by carrageenan against the reference anti-inflammatory drug indomethacin (3 mg/kg, i.p.) (95.70%). The ED₅₀ of lycorine was determined as 0.514 mg/kg. Hepatoprotective activity of lycorine on carbon tetrachloride (CCl₄) induced acute liver toxicity following biochemical parameters were also evaluated. Rats were treated with lycorine at doses of 1.0 mg/kg and 2.0 mg/kg, i.p. Results of biochemical tests were confirmed by histopathological examination. Lycorine exhibited significant hepatoprotective effect at dose of 2.0 mg/kg i.p. dose.     

Flavonols attenuate the immediate and late-phase asthmatic responses to aerosolized-ovalbumin exposure in the conscious guinea pig

We previously reported that quercetin and rutin have potent, anti-asthmatic activity, but the structure-activity relationships of flavonoids and anti-asthmatic agents are still poorly understood. In the current study, the effects of kaempferol, fisetin, and morin on the immediate-phase response (IAR) and late-phase response (LAR) caused by exposure to aerosolized-ovalbumin (OA) in OA-sensitized guinea pigs were evaluated by determining the specific airway resistance (sRaw), recruitment of leukocytes and chemical mediators in bronchoalveolar lavage fluid (BALF), histopathological surveys, and determination of neutrophil chemotaxis. Fisetin and kaempherol (30 mg/kg, p.o.) significantly (P < 0.01) inhibited sRaw by 47.93% and 30.05% in IAR, and 54.45% and 40.50% in LAR, when compared to vehicle control, respectively. Furthermore, all three studied flavonols (30 mg/kg, p.o.) significantly (P < 0.05) inhibited the recruitment of total, as well as subtypes of, leukocytes into the lung BALF. This recruitment inhibition corresponded to the inhibition of leukocyte infiltration, particularly of eosinophils and neutrophils, into the lung in pathological surveys and formly-methionyl-leucyl-phenylalanine (FMLP)-induced neutrophil chemotaxis studies. Kaempferol inhibited FMLP-induced neutrophil chemotaxis in a concentration-dependent manner in a tested range of 1–100 μM. Fisetin inhibited histamine content and peroxidase (EPO) activity in BALF in a dose-dependent manner. All three tested flavonols significantly (P < 0.01) inhibited histamine content at 10 mg/kg, and phospholipase A₂ (PLA₂) and EPO activities at 30 mg/kg (p.o.) in BALF. Kaempherol had a greater anti-asthmatic effect than other flavonols. Fisetin demonstrated the greatest inhibition of sRaw, whereas morin had lesser effects. These results indicate that the lower the molecular weight, the greater the anti-asthmatic activities of these compounds.     

Membrane stabilizing activity — a possible mechanism of action for the anti-inflammatory activity of Cedrus deodara wood oil

The volatile oil of the wood of Cedrus deodara (50 and 100 mg/kg, p.o.) produced a significant inhibition of compound 48/80 and nystatin-induced rat paw edema. It also inhibited heat- as well as hypotonic solution-induced haemolysis of erythrocytes in vitro. The anti-inflammatory activity of the oil could be due to its membrane stabilizing action.     

CNS depressant activity of Lecaniodiscus cupanioides

The aqueous root extract of Lecaniodiscus cupanioides was used to study the central nervous system depressant activity pattern of the plant. The extract protected mice from strychnine-induced convulsion at 400 mg/kg p.o. and 100 mg/kg i.p. A dose-dependent prolongation of seizure latency was produced at 400 mg/kg, p.o. and 100 mg/kg i.p. for strychnine-induced seizure; and at 400 mg/kg p.o. and 100 mg/kg i.p. for picrotoxin-induced seizure. Moreover, the CNS depressant activity of the extract (200 mg/kg p.o. and 50 mg/kg i.p.) was demonstrated by a significant prolongation of 40 mg/kg, pentobarbitone sleeping time, and significant reduction in exploratory behavior of mice at a dose of 400 mg/kg p.o., with both effects comparable to effects produced by 4 mg/kg chlorpromazine. Acute oral toxicity test, up to 14 days, did not produce any visible signs of toxicity; however, acute (24 h) i.p toxicity test produced a dose-dependent mortality with LD50 of 455.2 mg/kg.     

Effects of insect growth regulators with juvenile hormone activity againstCallosobruchus maculatus (F.) (Coleoptera: Bruchidae)

Five insect growth regulators, CGA-29170, CGA-45128, MV-678, RO-20458, and fenoxycarb, that exhibit juvenile hormone activity were evaluated for biological and residual activity against the southern cowpea weevil,Callosobruchus maculatus (F.). The compounds were mixed with cowpea seeds at concentrations of 10, 25, 50, and 100 mg/kg, and the residual activity was evaluated at 2-week to 9-months posttreatment intervals. Most JHA-treatments showed high initial activity at the 2-week interval resulting in a significantly lower oviposition rate and showing a short residual life in this respect. CGA-45128, however, at all concentrations tested did not significantly affect oviposition at 2-week to 4-month posttreatment intervals, where was more active and caused high depression in oviposition at 6-month interval. The juvenoids had an inductive effect on the percent egg hatch at various intervals, especially CGA-29170 and CGA-45128 treatments extinding over a period of 9 months. At the lower concentration of 10mg/kg, CGA-45128 was highly effective as F₁-progeny suppressant ofC. maculatus at 2-week posttreatment interval extending over 9 months. MV-678, CGA-29170, and fenoxycarb applied at 50, 50, and 25 mg/kg, respectively, showed similar activity, however, the residual activity of the latter decreased after 4 months. RO-20458, however, showed high initial activity at these concentrations. Adult emergence in all treatments was significantly suppressed, where did not exceed 29.5% at the lower concentrations of 10 and/or 25 mg/kg at 9-month posttreatment interval.     

Anti-inflammatory and analgesic properties of cis-mulberroside A from Ramulus mori

This study examined the analgesic and anti-inflammatory actions of cis-mulberroside A isolated from Ramulus mori in several models of inflammatory pain in mice. Cis-mulberroside A (25 and 50 mg/kg) given by p.o. route 30 min before challenge produced a dose-dependent inhibition of the acetic acid-induced pain and Evans blue leakage in mice. In addition, this compound exhibited significant systemic anti-inflammatory activity in carrageenan-induced mouse paw edema in a concentration-related manner (33.1–68.5% inhibition), and similar results were achieved in formalin test. Suppressive effects of cis-mulberroside A on the production of NO and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Collectively, cis-mulberroside A showed high analgesic and anti-inflammatory activities. The above results will be the supporting evidence for the potential anti-rheumatoid activity of R.mori in Chinese traditional medicine.     

Four new C18-diterpenoid alkaloids with analgesic activity from Aconitum weixiense

Four new C₁₈-diterpenoid alkaloids, weisaconitines A–D (1–4), were isolated from Aconitum weixiense. Based on extensive UV, IR, MS, 1D and 2D NMR analyses, their structures were elucidated as 8-O-ethyldolaconine (1), 4-demethylgenicunine B (2), 14-oxoaconosine (3), and 8-O-ethylaconosine (4). The analgesic activity of compound 4 was studied with CH₃COOH-induced writhing model in mice. Compound 4 showed writhing inhibitions of 24% (50 mg/kg), 26% (100 mg/kg) and 34% (200 mg/kg), respectively, as compared to the reference drug aspirin (63%) at a dose of 200 mg/kg.     

Antiinflammatory activity of Solanum trilobatum

The antiinflammatory effect of solasodine (50 mg/kg p.o.), of a purified component named sobatum (50 mg/kg p.o.) and of methanol extract of Solanum trilobatum (100 mg/kg p.o.) was evaluated. All the tested articles showed significant antiinflammatory activity.     

Antitussive effect of Asparagus racemosus root against sulfur dioxide-induced cough in mice

The methanol extract of Asparagus racemosus root (200 and 400 mg/kg, p.o.) showed significant antitussive activity on sulfur dioxide-induced cough in mice, the cough inhibition (40.0 and 58.5%, respectively) being comparable to that of 10–20 mg/kg of codeine phosphate (36.0 and 55.4%, respectively).     

Thyroid inhibitory,antiperoxidative and hypoglycemic effects of stigmasterol isolated from Butea monosperma

Stigmasterol, isolated from the bark of Butea monosperma was evaluated for its thyroid hormone and glucose regulatory efficacy in mice. Its administration at 2.6 mg/kg/d for 20 days reduced serum triiodothyronine (T₃), thyroxin (T₄) and glucose concentrations as well as the activity of hepatic glucose-6-phophatase (G-6-Pase) with a concomitant increase in insulin indicating its thyroid inhibiting and hypoglycemic properties. A decrease in the hepatic lipid peroxidation (LPO) and an increase in the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) suggested its antioxidative potential. The highest concentration tested (5.2 mg/kg) evoked pro-oxidative activity.     

Theacrine,a purine alkaloid with anti-inflammatory and analgesic activities

The anti-inflammatory and analgesic effects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and λ-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. Oral administration of theacrine (8–32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. On the other hand, oral caffeine administration (8–32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD₅₀ of theacrine was 810.6 mg/kg (769.5–858.0 mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities.     

Effects of Swertia japonica extract and its main compound swertiamarin on gastric emptying and gastrointestinal motility in mice

The Swertia japonica is used clinically as a remedy for gastrointestinal symptoms in Japan. We examined the effects of a S. japonica and swertiamarin on gastric emptying and gastrointestinal motility in atropine-, dopamine-, and 5-hydroxytryptamine (5-HT)-treated mice. All three preparations inhibited reductions in gastric emptying and gastrointestinal motility induced by dopamine (1 mg/kg, intraperitoneal injection, ip). Neither the powder, swertiamarin, nor itopride had any effect on the reductions in gastric emptying and gastrointestinal motility caused by 5-HT (4 mg/kg, ip). These findings suggest that the powder and swertiamarin stimulate gastric emptying and gastrointestinal motility by inhibiting the dopamine D₂ receptor.     

(RS)-glucoraphanin purified from Tuscan black kale and bioactivated with myrosinase enzyme protects against cerebral ischemia/reperfusion injury in rats

Ischemic stroke is the result of a transient or permanent reduction in cerebral blood flow caused by the occlusion of a cerebral artery via an embolus or local thrombosis. Restoration of blood supply to ischemic tissues can cause additional damage known as reperfusion injury that can be more damaging than the initial ischemia.This study was aimed to examine the possible neuroprotective role of (R_S)-glucoraphanin, bioactivated with myrosinase enzyme (bioactive R_S-GRA), in an experimental rat model of brain ischemia/reperfusion injury (I/R). R_S-GRA is a thiosaccharidic compound found in Brassicaceae, notably in Tuscan black kale (Brassica oleracea L. var. acephala sabellica).The mechanism underlying the inhibitory effects of bioactive R_S-GRA on inflammatory and apoptotic responses, induced by carotid artery occlusion in rats, was carefully examined. Cerebral I/R was induced by the clamping of carotid artery for 1 h, followed by 40 min of reperfusion through the release of clamp.Our results have clearly shown that administration of bioactive R_S-GRA (10 mg/kg, i.p.) 15 min after ischemia, significantly reduces proinflammatory parameters, such as inducible nitric oxide synthase expression (iNOS), intercellular adhesion molecule 1 (ICAM-1), nuclear factor (NF)-kB traslocation as well as the triggering of the apoptotic pathway (TUNEL and Caspase 3 expression).Taken together our data have shown that bioactive R_S-GRA possesses beneficial neuroprotective effects in counteracting the brain damage associated to I/R. Therefore, bioactive R_S-GRA, could be a useful treatment in the cerebral ischemic stroke.     

Identification of chicoric acid as a hypoglycemic agent from Ocimum gratissimum leaf extract in a biomonitoring in vivo study

Ocimum gratissimum L. is popularly used to treat diabetes mellitus. The hypoglycemic activity of this medicinal species has been confirmed by in vivo studies. The present study conducted a chemical investigation of a leaf decoction (10% p/v) of O. gratissimum monitored by in vivo hypoglycemic activity assays. Four phenolic substances were identified: l-caftaric acid (1), l-chicoric acid (2), eugenyl-β-d-glucopyranoside (3) and vicenin-2 (4). The acute hypoglycemic activity of the O. gratissimum decoction fractions Og1-S (300 mg/kg), Og1-A (240 mg/kg) and Og1-B (80 mg/kg) was evaluated intraperitoneally in normal and streptozotocin-induced diabetic mice. They reduced glycemia by 63%, 76% and 60% (in 120 min), respectively, in the diabetic mice. Subfractions of Og1-A were also evaluated under the same conditions: Og1-AS (200 mg/kg) and Og1-AP (40 mg/kg) produced a decrease of only 37% and 39%, respectively. Among the major phenolic substances, only chicoric acid (2; 3 mg/kg) reduced significantly the glycemic levels of diabetic mice by 53%, 120 min after treatment. This is the first study describing the hypoglycemic activity of chicoric acid in an animal model of diabetes mellitus. In addition, we suggest that there may be other substances contributing to this activity. Thus, for the first time, a correlation is established between the hypoglycemic activity of O. gratissimum and its chemical composition.     

Swietenine: A potential oral hypoglycemic from Swietenia macrophylla seed

Swietenine, a tetranortriterpenoid, was isolated from the Swietenia macrophylla seeds. The in vivo hypoglycemic activity was evaluated against neonatal-streptozotocin induced type 2 diabetic rats. Oral administration of swietenine at 25 and 50 mg/kg body weight per day to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity in type 2 diabetic rats.     

A new hepoprotective saponin from Semen Celosia cristatae

A new triterpenoid saponin, named semenoside A (1), was isolated from Semen Celosia cristatae. Its structure was elucidated on the basis of 1D, 2D NMR, HR-FAB-MS and ESI-MS techniques, and physicochemical properties. The hepatoprotective activity of semenoside A with an oral dose of 1.0, 2.0 and 4.0 mg/kg, respectively, were investigated by carbon tetrachloride (CCl₄)-induced hepatotoxicity in mice. The results indicated that it had significant hepatoprotective effects (p < 0.01).     

Antinociceptive and antiplasmodial activities of cassane furanoditerpenes from Caesalpinia volkensii H. root bark

The chloroform and ethyl acetate extract (100 mg/kg) of Caesalpinia volkensii H. exhibited significant (P ≤ 0.05) antinociceptive activities using hot plate and writhing tests in mice while the later showed antiplasmodial activity (IC₅₀ 0.23 ± 0.07 and 4.39 ± 2.49 μg/ml) against chloroquine sensitive (D6) and chloroquine-resistant (W2), respectively. Two new furanoditerpenes [rel. 1β,5α-dihydroxyvoucapane (1) and rel. 1β,6β-dihydroxyvoucapane; 19β-methyl ester (2)] together with seven known compounds [voucapane (3), voucapan-5-ol (4), deoxycaesaldekarin C (5), caesaldekarin C (6), 5-hydroxyvinhaticoic acid (7), triacontanyl-(E)-ferulate (8), triacontanyl-(E)-caffaete (9) and 30′-hydroxytriacontanyl-(E)-ferulate (10)] were isolated from the two extracts. The administration of 3, 4, 5 and 6 (100 mg/kg i.p) caused a significant (P ≤ 0.05) reduction in the number of writhing episodes induced by acetic acid and (P ≤ 0.01) increased pain latency threshold in hot-plate test compared to control. However, the pure compounds indicated relatively (P ≤ 0.05) low antiplasmodial activity. The phytochemical constituents from the root bark of C. volkensii had better analgesic properties than antimalarial properties, justifying the use of the plant root bark as a remedy for pain.     

Different pharmacokinetics of the two structurally similar dammarane sapogenins,protopanaxatriol and protopanaxadiol,in rats

Dammarane Sapogenins (DS), with main ingredients of protopanaxatriol (PPT, 33%) and protopanaxadiol (PPD, 16%), is an alkaline hydrolyzed product of ginsenosides and had significant activities in improving learning and memory and decreasing chemotherapy-induced myelosuppression. In the present study, the pharmacokinetics and oral bioavailabilities of PPT and PPD were investigated when a single dose of DS was administrated orally (75 mg/kg) and intravenously (i.v., 30 mg/kg) to rats. Their in vitro stabilities in the GI tract were also investigated. PPT and PPD concentrations were measured by LC–MS. The results showed that PPT was eliminated rapidly from the body with an average t_{1/2, λz} value of 0.80 h and CL of 4.27 l/h/kg after i.v. administration, while PPD was eliminated relatively slowly with a t_{1/2, λz} of 6.25 h and CL of 0.98 l/h/kg. After oral administration, both PPD and PPT could be absorbed into the body, but their systemic exposures were quite different. PPT was absorbed into the body quickly, with a T_max of 0.58 h and a C_max of 0.13 μg/ml, while PPD was absorbed relatively slowly with a T_max of 1.82 h and a C_max of 1.04 μg/ml. The absolute bioavailabilities of PPT and PPD were estimated as 3.69% and 48.12%, respectively. The stability test found that PPT was instable in the stomach with 40% degradation after 4 h incubation at 37 °C, both in pH 1.2 buffer and in the stomach content solution. The instability in the stomach might be one of the reasons for PPT's poor bioavailability.     

Analgesic and antidiarrheal properties of Ocimum selloi essential oil in mice

Ocimum selloi essential oil (2, 20, and 200 mg/kg; p.o.) reduced, in a dose-dependent way, the abdominal contraction induced by acetic acid (0.6%; i.p.) and the diarrhea episodes induced by castor oil in mice. At the higher dose (200 mg/kg; p.o.), the essential oil significantly reduced intestinal transit (P<0.05) in the charcoal meal test. The main component detected in O. selloi essential oil was methyl chavicol (98%; GC and GC/MS).These effects seems to support the use of O. selloi against diarrhea, intestinal spasm and visceral pain.