Hepatoprotective properties of Commiphora opobalsamum ("Balessan"), a traditional medicinal plant of Saudi Arabia.

The hepatoprotective activity of an ethanolic extract of Commiphora opobalsamum ("Balessan") was investigated in rats by inducing hepatotoxicity with carbon tetrachloride:liquid paraffin (1:1). This extract has been shown to possess significant protective effect by lowering serum transaminase levels (serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase), alkaline phosphatase and bilirubin. Pretreatment with an extract of Balessan prevented the prolongation of the barbiturate sleeping time associated with carbon tetrachloride-induced liver damage in mice. On the other hand, CCl4-induced low-level nonprotein sulfhydryl concentration in the liver was replenished by the Balessan extract. These data suggest that the plant C. opobalsamum may act as an antioxidant agent and may have a hepatoprotective effect.

Triumfettoside, a new alkaloidal steroid glycoside and triumfettosterol, a new sterol from Triumfetta flavescens.

The aerial parts of Triumfetta flavescens H. (N. O. Tiliaceae) afforded a new alkaloidal steroid glycoside, characterized as stigma 5(6)-ene-7,22-dione-25-methylamino-3 beta,23 beta-diol-3-O-beta-D- glucoside and designated as triumfettoside (1); and a new sterol identified as stigma 5(6)-ene-7,22-dione-3 beta,23 beta-diol, designated as triumfettosterol (2). Their structures were elucidated on the basis of chemical and spectral analysis.

Toxicity of Nerium oleander and Rhazya stricta in Najdi sheep: hematologic and clinicopathologic alterations.

The toxic effects of oral administration of 0.25 g/kg Nerium oleander leaves, 0.25 g/kg Rhazya stricta leaves or their mixture at 0.25 g/kg N. oleander leaves plus 0.25 g/kg R. stricta leaves on Najdi sheep were investigated. Daily oral dosing of R. stricta leaves for 42 days was not fatal to sheep while single oral doses of either N. oleander leaves or the mixture with R. stricta leaves proved fatal to animals within 24 hours with dyspnea, grunting, salivation, grinding of the teeth, ruminal bloat, frequent urination, ataxia and recumbency prior to death. The main lesions were widespread congestion or hemorrhage, pulmonary cyanosis, emphysema, bronchotracheal froths, and hepatonephropathy. The clinical and pathological changes were correlated with alterations in serum LDH and AST activities and concentrations of cholesterol, bilirubin, urea, total protein, albumin, and globulin and hematological values.

Verticillarone: a new seco-fusicoccane diterpenoid ketonepoxide from Hypoestes verticillaris.

The aerial parts of Hypoestes verticillaris (L.F.) Sol. (Acanthaceae) has afforded a new seco-fusicoccane diterpenoid ketonepoxide, which was characterized as 1(10) seco-fusicocc-3 (4)-ene-5, 11, 14-trione-8 (9), 1 (7)-diepoxide (1) on the basis of spectral analysis and named as verticillarone, along with earlier reported diterpenoid, i.e. 13-hydroxy-7-oxo-labda-8, 14-diene (2).

Toxicological interactions of Cassia senna and Nerium oleander in the diet of rats.

The toxic effects of diet containing 10% of C. senna L. fruits or 10% of N. oleander L. leaves or their 1:1 mixture (5% + 5%) on male Wistar rats treated for 6 weeks were investigated. Diarrhea was a prominent sign of C. senna L. toxicosis. In both phytotoxicities, there were decreases in body weight gains, inefficiency of feed utilization, dullness and enterohepatonephropathy. These findings accompanied by leukopenia and anemia were correlated with alterations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and concentrations of total protein, albumin, urea and other serum constituents. In both phytotoxicities, the ability of the liver to excrete bilirubin remained unchanged. Feeding the mixture of C. senna L. fruits and N. oleander L. leaves caused more serious effects and death of rats. The implications of these findings are discussed.

Alkaloids from Haplophyllum tuberculatum.

Two new alkaloids, haplotubinone (3) and haplotubine (4), were isolated from the aerial parts of Haplophyllum tuberculatum together with the known lignan diphyllin. The structures of the new alkaloids were established by spectroscopic methods in conjunction with X-ray crystallographic analysis of 3. In addition, the amide N-(2-phenylethyl)-benzamide has been identified in this source for the first time.

Combined toxicity of Cassia senna and Citrullus colocynthis in rats.

Body weight loss, inefficiency of feed utilization, diarrhea, ruffled hair and enterohepatonephrotoxicity were effects on male Wistar rats fed diet containing 10% Cassia senna or 10% Citrullus colocynthis ripe fruits for 6w. Rats fed a 1:1 mixture (5% + 5%) of fruits from these plants were more adversely affected and had deaths than rats fed the individual plants. The changes associated with the macrocytic hypochromic anemia and leukopenia were increased serum AST, ALT and ALP activities, increased urea, and decreased total protein, albumin and calcium. Serum bilirubin concentration did not change.

Response of Najdi sheep to oral administration of Citrullus colocynthis fruits, Nerium oleander leaves or their mixture.

Susceptibility of sheep to oral administration of Citrullus colocynthis fruits, Nerium oleander leaves or their mixture is described in 12 sheep assigned as untreated controls, C. colocynthis-treated at 0.25g/kg/day, N. oleander-treated at 0.25g/kg and plant mixture-treated at 0.25g of C. colocynthis/kg plus 0.25g of N. oleander/kg. The daily use of 0.25g of C. colocynthis/kg for 42 days was not fatal to sheep and caused slight diarrhoea, catarrhal enteritis, centrilobular hepatocellular fatty change and degeneration of the renal tubular cells. Single oral doses of 0.25g of N. oleander/kg were lethal to sheep within 18-24h and caused uneasiness, grinding of the teeth, dyspnoea, anorexia, frequent urination, ruminal bloat, ataxia and recumbency before death. The main lesions were widespread congestion and haemorrhage, pulmonary cyanosis and emphysema and severe hepatonephropathy. Rapid death was also observed in sheep receiving single doses of the mixture of the two plants. Effects were correlated with changes in the activities of serum lactic dehydrogenase (LDH) and aspartate transaminase (AST) and concentrations of cholesterol, bilirubin, total protein, albumin, globulin and urea and haematological parameters.

Acute toxicity of various oral doses of dried Nerium oleander leaves in sheep.

The acute toxicity of dried Nerium oleander leaves to Najdi sheep is described in 12 sheep assigned as untreated controls, N. oleander-treated once at 1 and 0.25 g/kg body weight and N. oleander-treated daily at 0.06 g/kg body weight by drench. Single oral doses of 1 or 0.25 g of dried N. oleander leaves/kg body weight caused restlessness, chewing movements of the jaws, dyspnea, ruminal bloat, incoordination of movements, limb paresis, recumbency and death 4-24 hr after dosing. Lesions were widespread congestion or hemorrhage, pulmonary cyanosis and emphysema, hepatorenal fatty change and catarrhal abomasitis and enteritis. The daily oral doses of 0.06 g dried N. oleander leaves/kg body weight caused less severe signs and death occurred between days 3 and 14. In these animals, the main lesions were hepatonephropathy and gelatinization of the renal pelvis and mesentry and were accompanied by significant increases in serum AST and LDH activities, in bilirubin, cholesterol and urea concentrations and significant decreases in total protein and albumin levels, anemia and leucopenia.

Preliminary toxicity study on the individual and combined effects of Citrullus colocynthis and Nerium oleander in rats.

The toxicity of diet containing 10% of Citrullus colocynthis fruits or 10% of Nerium oleander leaves or their 1:1 mixture (5%+5%) for rats treated for 6 weeks was determined. Dullness, ruffled hair, decreased body weight gains and feed efficiency, and enterohepatonephropathy characterised treatment with C. colocynthis and N. oleander given alone. Diarrhoea was a prominent sign of C. colocynthis poisoning. Organ lesions were accompanied by leucopenia, anaemia and alterations in serum AST, ALT and ALP activities and concentrations of total protein, albumin, urea, bilirubin and other serum constituents. Feeding the mixture of C. colocynthis and N. oleander caused more marked effects and death of rats.

Cell culture assay system for the evaluation of natural product-mediated anti-Hepatitis B virus activity.

Utilizing the hepatitis B virus (HBV)-producing hepatoblastoma cell line, HepG2.2.15, which is stably transfected with the cloned HBV genome, methods were devised to examine the effects of test substances on intracellular extrachromosomal HBV DNA levels and secretion of hepatitis B surface antigen (HBsAg). The known inhibitor of HBV replication, dideoxycytosine (ddC), had a minor effect on the secretion of HBsAg, but >90% of intracellular extrachromosomal HBV DNA expression was lost at a non-cytotoxic drug concentration (25µM). This inhibitory effect was reversed when ddC was removed from the medium. Of 19 plant materials tested, extracts from the aerial parts of Clematis sinensis Lour, and Clerodendron inerme R. Br. significantly inhibited the secretion of HBsAg into the culture medium at non-cytotoxic concentrations, but had no effect on intracellular extrachromosomal HBV DNA levels. This system is useful for the evaluation of test materials, or combinations of test materials, for their potential to inhibit HBV markers.

Pharmacological and safety evaluation studies on Lepidium sativum L., Seeds.

An ethanolic extract of Cress (Lepidium sativum L.) seeds has been studied for anti-inflammatory, antipyretic and analgesic activities and to evaluate the safety of their acute and chronic use in rodents. The extract significantly inhibited carrageenan-induced paw edema and reduced the yeast-induced hyperpyrexia. It also prolonged the reaction time of mice on the hot plate. However, the extract exacerbated indomethacin-induced gastric mucosal damage. The coagulation studies showed a significant increase in fibrinogen level and an insignificant decrease in prothrombin time, confirming its coagulating property. The toxicity tests showed that the administration of extract in single doses of 0.5 to 3.0g/kg did not produce any adverse effects or mortality in mice, whereas the animals treated with extract (100 mg/kg/day) for a period of 3 months in drinking water showed no symptoms of toxicity except a statistically insignificant higher mortality rate. These findings suggest that the seeds of Cress (L. sativum) possess significant anti-inflammatory, antipyretic, analgesic and coagulant activities, and are free from serious side or toxic effects.

Protective effect of Swertia chirata against indomethacin and other ulcerogenic agent-induced gastric ulcers.

The effect of Swertia chirata has been studied on experimentally induced gastric ulcers in rats. The ethanolic extract of chirata significantly reduced the intensity of gastric mucosal damage induced by indomethacin and necrotizing agents. It produced a significant decrease in gastric secretion in pylorus-ligated rats. The extract inhibited acetylcholine-induced contraction of guinea pig ileum, suggesting its anti-cholinergic activity. Pretreatment of rats with the extract significantly prevented ethanol-induced gastric wall mucus depletion and restored the non-protein sulfhydryl (NP-SH) content in the glandular stomachs. These findings support the use of chirata for the treatment of gastric ulcers in traditional medicine.

Pharmacological studies on aerial parts of Calotropis procera.

The decoction of the aerial part of Calotropis procera is commonly used in Saudi Arabian traditional medicine for the treatment of variety of diseases including fever, joint pain, muscular spasm and constipation. The present investigation was undertaken to confirm its claimed activity in traditional medicine. The ethanol extract of the plant was tested on laboratory animals for its antipyretic, analgesic, anti-inflammatory, antibacterial, purgative and muscle relaxant activities. The results of this study showed a significant antipyretic, analgesic and neuromuscular blocking activity. On smooth muscle of guinea pig ileum, the extract produced contractions which was blocked by atropine supporting its use in constipation. The extract failed to produce significant anti-inflammatory and antibacterial activities. Our phytochemical studies on the aerial parts of C. procera showed the presence of alkaloids, cardiac glycosides, tannins, flavonoids, sterols and/or triterpenes. However, the chemical constituents responsible for the pharmacological activities remains to be investigated. The safety evaluation studies revealed that the use of extract in single high doses (up to 3 g/kg) does not produce any visible toxic symptoms or mortality. However, prolong treatment (90 days) causes significantly higher mortality as compared to control group.

Evaluation of turmeric (Curcuma longa) for gastric and duodenal antiulcer activity in rats.

An ethanol extract of turmeric was studied in rats for its ability to inhibit gastric secretion and to protect gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic-restraint stress, indomethacin, reserpine and cysteamine administration and cystodestructive agents including 80% ethanol, 0.6 M HCl, 0.2 M NaOH and 25% NaCl. An oral dose of 500 mg/kg of the extract produced significant anti-ulcerogenic activity in rats subjected to hypothermic-restraint stress, pyloruic ligation and indomethacin and reserpine administration. The extract had a highly significant protective effect against cystodestructive agents. The reduction in the intensity of ulceration of cysteamine-induced duodenal ulcers was not found to be statistically significant. Turmeric extract not only increased the gastric wall mucus significantly but also restored the non-protein sulfhydryl (NP-SH) content in the glandular stomachs of the rats.

Studies on Ruta chalepensis, an ancient medicinal herb still used in traditional medicine.

An ethanolic extract of the aerial parts of Ruta chalepensis was studied for its anti-inflammatory, antipyretic, analgesic and CNS depressant activities. The extract produced a significant inhibition of carrageenan-induced paw oedema and cotton pellet granuloma in rats. The studies on spontaneous motor activity in mice and conditioned avoidance responding (CAR) in rats showed a dose-dependent depression of the central nervous system in treated animals. Reduction of yeast-induced hyperthermia in mice confirmed its reputed antipyretic activity. The extract did not produce any significant changes in prothrombin time and fibrinogen level. It also failed to produce any analgesic activity in the hot plate reaction-time test in mice. Phytochemical screening of the aerial parts of the plant showed the presence of alkaloids, flavonoids, coumarins, tannins, volatile oil, sterols and/or triterpenes.

Preliminary toxicity studies on ethanol extracts of the aerial parts of Artemisia abyssinica and A. Inculta in mice.

Ethanolic extracts of the aerial parts of Artemisia abyssinica and A. inculta were subjected to acute toxicity observations in mice for 24 h and chronic toxicity evaluation for 3 months. External morphological changes, visceral toxicity, haematological changes, spermatogenic dysfunction and effect on body weight and vital organ weight were recorded. In both the chronically treated groups, no significant acute mortality was observed up to 3 g/kg p.o. There was no weight gain in A. abyssinica chronically-treated mice while the weight gain of A. inculta-treated animals matched that of the control group. Significant sperm damage was observed in A. abyssinica-treated mice while A. inculta failed to produce any significant spermatotoxic effect.

Effect of Trigonella foenum-graecum and Ammi majus on calcium oxalate urolithiasis in rats.

The present study was undertaken to investigate the effect of Trigonella foenum-graecum seed and Ammi majus fruit on experimentally-induced kidney stones. Oxalate urolithiasis in male rats was produced by the addition of 3% glycolic acid to their diet. After 4 weeks, highly significant deposition in the kidneys was noticed and changes in water intake and body weight recorded. Daily oral treatment with T. foenum-graecum significantly decreased the quantity of calcium oxalate deposited in the kidneys thus supporting its use in Saudi folk medicine. The effects obtained by A. majus were, however, not significant.

Cyclopeptide alkaloids: further studies on mauritine-C and sativanine-C.

The 14-membered cyclopeptide alkaloid mauritine-C and the 13-membered cyclopeptide alkaloid sativanine-C were isolated from Zizyphus spinea-christi and Zizyphus sativa commonly used in the Saudi Folklor medicine. The N-formyl derivatives of these compounds were prepared and their corresponding spectral data was analyzed. Fundamental differences were observed in the mass spectrometric fragmentation of the newly formed derivatives as compared to the parent compounds mass spectrometry was found a useful tool to substantiate the fragmentation pattern proposed for these potential natural products.

Experimental studies on antirheumatic crude drugs used in Saudi traditional medicine.

A large number of herbal drugs are used in the traditional medicine of Saudi Arabia for the treatment of rheumatism, arthritis, gout and other forms of inflammation. In the present study seven of these crude drugs, namely Francoeuria crispa, Hammada elegans, Malus pumila, Ruta chalepensis, Smilax sarsaparilla, Achillea fragrantissima and Alpinia officinarum were tested against carrageenan-induced acute inflammation in rats. The plant materials were extracted with 96% ethanol. The dried extract was dissolved in water for pharmacological testing. The rats were administered an oral dose of 500 mg/kg body weight of each extract 1 h prior to production of inflammation by carrageenan injection (0.05 ml of 1% carrageenan suspension in the planter aponeurosis of the right hind foot). The paw volume was measured at 0,2,3 and 4 h after the injection. Four of the seven plants, namely Francoeuria crispa (24%), Malus pumila (23%), Ruta chalepensis (30%) and Smilax sarsaparilla (25%), produced significant inhibition of carrageenan-induced inflammation in rats. These plants also inhibited cotton pellet-induced exudation. Further studies are suggested to isolate the active principles and for the determination of the mechanism of action of these drugs.