Safety of Oral Carica papaya L. Leaf 10% Ethanolic Extract for Acute and Chronic Toxicity Tests in Sprague Dawley Rats.

Carica papaya L. leaves, traditionally utilized in dietary supplements and pharmaceuticals, exhibit a broad spectrum of potentially therapeutic properties, including anti-inflammatory, antimalarial, and wound healing properties. This study examined the acute and chronic toxicity of 10% ethanolic-extracted C. papaya leaf in Sprague Dawley rats. The acute toxicity assessment was a single oral dose of 5000 mg/kg body weight, while the chronic toxicity assessment included daily oral doses of 100, 400, 1000, and 5000 mg/kg over 180 days. Systematic monitoring covered a range of physiological and behavioral parameters, including body and organ weights. End-point evaluations encompassed hematological and biochemical analyses, along with gross and histopathological examinations of internal organs. Findings revealed no acute toxicity in the C. papaya leaf extract group, although a significant decrease in uterine weight was observed without accompanying histopathology abnormalities. In the chronic toxicity assessment, no statistically significant differences between the control and the C. papaya leaf extract groups were detected across multiple measures, including behavioral, physiological, and hematological indices. Importantly, histopathological examination corroborated the absence of any tissue abnormalities. The study results indicate that C. papaya leaf extract exhibited no adverse effects on the rats during the 180-day oral administration period, affirming its potential safety for prolonged usage.

Anti-Inflammatory, Antinociceptive, Antipyretic, and Gastroprotective Effects of Eurycoma longifolia Jack Ethanolic Extract.

Tongkat ali (Eurycoma longifolia Jack) (ELJ) is a plant in the Simaroubaceae family. Its roots are used in traditional Thai medicine to treat inflammation, pain, and fever; however, the antiulcer abilities of its ethanolic extract have not been studied. This study examined the anti-inflammatory, antinociceptive, antipyretic, and gastroprotective effects of ethanolic ELJ extract in animal models and found that ELJ effectively reduced EPP-induced ear edema in a dose-dependent manner and that a high dose of ELJ inhibited carrageenan-induced hind paw edema formation. In cotton-pellet-induced granuloma formation, a high dose of ELJ suppressed the increases in wet granuloma weight but not dry or transudative weight. In the formalin-induced nociception study, ELJ had a significant dose-dependent inhibitory impact. Additionally, the study found that yeast-induced hyperthermia could be significantly reduced by antipyretic action at the highest dose of ELJ. In all the gastric ulcer models induced by chemical substances or physical activity, ELJ extracts at 150, 300, and 600 mg/kg also effectively prevented gastric ulcer formation. In the pyloric ligation model, however, the effects of ELJ extract on gastric volume, gastric pH, and total acidity were statistically insignificant. These findings support the current widespread use of Eurycoma longifolia Jack in traditional medicine, suggest the plant's medicinal potential for development of phytomedicines with anti-inflammatory, antinociceptive, and antipyretic properties, and support its use in the treatment of gastric ulcers due to its gastroprotective properties.

Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats.

BACKGROUND: Bacopa monnieri is a medicinal plant which has long been used in Ayurvedic medicines to augment brain function and to improve memory. The purpose of our study was to identify and evaluate possible toxic effects of B. monnieri extract in rats by assessing hematological, biochemical, and histopathological parameters. METHODS: Acute oral toxicity of Bacopa monnieri extract was studied in female rats by giving a single orally administered dose at a level of 5,000 mg/kg. The rats were monitored for toxic signs for 14 days. In the chronic toxicity test, groups of both female and male rats were given daily oral doses of B. monnieri extract at dose levels of either 30, 60, 300 or 1,500 mg/kg for 270 days. The behavior and health of the animals was then monitored. At the end of the observation period, the body and organ weights of the rats in each group were measured. Blood was collected and necropsy was performed to evaluate their hematology, blood clinical chemistry, and microanatomy. RESULTS: The acute toxicity test found no significant differences between the experimental and the control group rats. In the chronic toxicity test, animal behavior and health of the experimental groups were normal, just as in the control rats. All values of other parameters assessed remained within the normal range. CONCLUSION: A single oral administration of B. monnieri extract at the dose of 5,000 mg/kg did not cause any serious undesirable effects. B. monnieri extract at doses of 30, 60, 300 and 1,500 mg/kg given for 270 days did not produce any toxicity in rats.

Effect of Tri-sa-maw recipe on gastrointestinal regulation and motility. .

BACKGROUND: Tri-sa-maw recipe is comprised ofequal proportions of three herbal fruits, including Terminalia chebula Retz., Terminalia sp. and Terminalia bellirica Roxb. The traditional use of this recipe has been reported as a medication for fever; expectorant, relief of tightness in the stomach, laxative and antidiarrheal agent. OBJECTIVE: To study the effects of Tri-sa-maw recipe extract on gastrointestinal tract in both in vitro and in vivo. MATERIAL AND METHOD: Gastrointestinal effect of Tri-sa-maw recipe was studied by using two in vivo models (gastric emptying, gastrointestinal transit) and in vitro isolated guinea pig ileum experiment. RESULTS: Tri-sa-maw recipe showed both stimulatory and inhibitory effects on the stomach function. Not only did the extract at the dose of 1,000 mg/kg inhibit the gastric emptying time, but also stimulate the movement of the digestive tract by increasing the mobility of charcoal. In the isolated guinea pig ileum experiment, the extract at low concentration (0.1 ng/mL) induced the contraction of isolated guinea pig ileum. However the stimulation effect on contractions of isolated guineapig ileum was very much decreased at the high concentration (0.2-1 ng/mL) of the extract. CONCLUSION: The findings of this study support to traditional uses of Tri-sa-maw recipe as a laxative and antidiarrheal agent.

Acute and sub-chronic toxicity of Tri-sa-maw recipe in rats.

BACKGROUND: Tri-sa-maw recipe is a botanical preparation comprised of equal proportions ofthe three herbalfruits, namely Terminalia chebula Retz., Tenninalia sp. and Terminalia bellirica Roxb. This recipe is used for antipyretic, expectorant, periodic maintenance, and relieving stomach tight. OBJECTIVE: To evaluate the acute and sub-chronic toxicities of Tri-sa-maw recipe extract in rats. MATERIAL AND METHOD: In the present study of acute toxicity, a single oral dose 5,000 mg/kg of Tri-sa-maw recipe extract was administered to rats. Sub-chronic toxicity was studied by the daily oral administration ofthe extract at the doses of 600, 1,200 and 2,400 mg/kg body weight for consecutive 90 days. RESULTS: Tri-sa-maw recipe extract at the dose of 5,000 mg/kg showed no signs of differences as compared to the control rat. No abnormalities were found in the sub-chronic toxicity study; none of the parametersfor body and organ weights, hematol- ogy, blood chemistry, necropsy, and histopathology showed any differences between the control and all treatment groups. CONCLUSION: Tri-sa-maw recipe extract did not significantly cause acute toxicity or sub-chronic toxicity in rats.

Analgesic and antipyretic activity of Tri-sa-maw recipe.

BACKGROUND: Tri-sa-maw recipe is composed of equal proportions of the three fruits including Terminalia chebula Retz., Terminalia sp. and Terminalia bellirica Roxb. In Southeast Asia, these fruits are used as both food and medicine. In Thai traditional medicine, Tri-sa-maw recipe is well known for treating fever, expectorant, periodic maintenance, and tight stomach relief OBJECTIVE: To study anti-inflammatory, analgesic and antipyretic activities of Tri-sa-maw recipe in experimental animals. MATERIAL AND METHOD: The anti-inflammatory study was conducted by two experimental models; ethyl phenylpropiolate- induced ear edema and carrageenin-induced paw edema. For analgesic activity, the pain was induced by acetic acid or heat. In addition, yeast-induced hyperthermia was performedfor the study of antipyretic activity. RESULTS: The results showed that Tri-sa-maw recipe extract reduced ear edema ofrat induced by EPP but did not inhibit acute inflammation in the carrageenin-inducedpaw edema. However the extract at the doses of 300-1,200 mg/kg was able to inhibit the acetic acid-induced writhing response, but not the heat-induced pain. This result suggests the peripheral effect of its analgesic activity, which inhibits the biosynthesis, and/or release of some pain mediators. Finally, oral administration ofthe extract at the dose of 1,200 mg/kg body weight effectively reduced the hyperthermia, which possibly is due to the inhibition of prostaglandins. CONCLUSION: The present study has clearly demonstrated both analgesic and antipyretic activities of Tri-sa-maw recipe.

Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats.

Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P < 0.05). The weights of lung and kidney of treated females were increased (P < 0.05). Treated males were increased in spleen and epididymis weights (P < 0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females.

Acute and chronic toxicity studies of the water extract from dried fruits of Terminalia bellerica (Gaertn.) Roxb. In Spargue-Dawley rats.

Acute and chronic toxicities of the water extract from the dried fruits of Terminalia bellerica (Gaertn.) Roxb. were assessed in both female and male rats. For the study of acute toxicity, a single oral administration of the water extract at a dose of 5,000 mg/kg body weight (10 female, 10 male) was performed and the results showed no signs of toxicity such as general behavior changes, morbidity, mortality, changes on gross appearance or histopathological changes of the internal organs of rats. The study of chronic toxicity was determined by oral feeding both female and male rats (10 female, 10 male) daily with the test substance at the dose of 300, 600 and 1,200 mg/kg body weight continuously for 270 days. The examinations of signs of toxicity showed no abnormalities in the test groups compared to the controls. In addition, these rats were analyzed for final body and organ weights, necropsy, as well as hematological, blood chemical and histopathological parameters. Taken together, the water extract from the dried fruits of T. bellerica did not cause acute or chronic toxicities in either female or male rats.

Evaluation of anti-inflammatory and antinociceptive activity of Triphala recipe.

The anti-inflammatory and antinociceptive activities of Triphala recipe were studied in animal models. Triphala recipe (4 mg/ear) significantly exhibited an inhibitory effect on the ear edema formation induced by ethyl phenylpropiolate-induced, but not on the arachidonic acid-induced ear edema in rats. Furthermore, Triphala recipe at the doses of 300, 600 and 1,200 mg/kg significantly reduced carrageenan-induced hind paw edema. Next, the anti-inflammatory action in chronic inflammation was measured using the cotton pellet-induced granuloma formation assay in rats. Triphala recipe (1,200 mg/kg) reduced neither transudative weight nor granuloma formation. It also did not affect on body weight gain and thymus weight indicating that Triphala recipe does not have a steroid-like effect. In antinociceptive study, Triphala recipe (300, 600, 1,200 mg/kg), elicited significant inhibitory effect on both phases, especially in late phase, of the formalin test in mice suggesting that the antinociceptive action of Triphala recipe may be via both peripheral and at least partly centrally acting.

Toxicity studies of the water extract from the calyces of Hibiscus sabdariffa L. in rats.

Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and differences of the weights or behaviour compared to the control rats were observed. The results indicated that the single oral administration of H. sabdariffa extract in the amount of 5,000 mg/kg body weight does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with the extract at the doses of 50, 100, and 200 mg/kg body weight for 270 days. The examinations of signs, animal behaviour and health monitoring showed no defects in the test groups compared to the control groups. Both test and control groups (day 270th) and satellite group (day 298th) were analysed by measuring their final body and organ weights, taking necropsy, and examining haematology, blood clinical chemistry, and microanatomy. Results showed no differences from the control groups. Overall, our study demonstrated that an oral administration of H. sabdariffa extract at the doses of 50, 100 and 200 mg/kg body weight for 270 days does not cause chronic toxicity in rat.

Evaluation of acute and subacute oral toxicity of the ethanol extract from Antidesma acidum Retz.

Toxicity tests of 95% ethanol extract of the root of Antidesma acidum were studied in male and female rats. The oral acute toxicity test at 5,000 mg/kg revealed that the ethanol extract did not produce toxic effects on signs, general behavious, mortality and gross appearance of internal organs of rats. Furthermore, the oral sub-acute toxicity test at the dose of 1,000 mg/kg/day displayed no significant changes in body and internal organs' weights, normal hematological and clinical blood chemistry values. Histological examination also showed normal architecture of all internal organs. In conclusion, the ethanol extract of Antidesma acidum did not produce any toxicity in oral acute and suba-cute toxicity studies.

Anti-inflammatory and anti-ulcerogenic activities of Chantaleela recipe.

Chantaleela recipe is indicated for relieving fever in Thai traditional folk medicine. In the present study, Chantaleela recipe was investigated for anti-inflammatory, analgesic, antipyretic and anti-ulcerogenic activities. In preliminary investigation Chantaleela recipe was found to exert an inhibitory activity on the acute phase of inflammation as seen in ethyl phenylpropiolate-induced ear edema as well as in carrageenan-induced hind paw edema in rats. The results suggest that the anti-inflammatory activity of Chantaleela recipe may be due to an inhibition via cyclooxygenase pathway. In the analgesic test, Chantaleela recipe showed a significant analgesic activity in both the early and late phases of formalin test, but exerted the most pronounced effect in the late phase. The analgesic activity of Chantaleela recipe may act via mechanism at peripheral and partly central nervous system. In antipyretic test, Chantaleela recipe significantly decreased rectal temperature of brewer's yeast-induced hyperthermia rats, probably by inhibiting synthesis and/or release of prostaglandin E2 in the hypothalamus. Therefore, the key mechanism of anti-inflammatory, analgesic, and antipyretic activity of the Chantaleela recipe likely involves the inhibition of the synthesis and/or release of inflammatory or pain mediators, especially prostaglandins. The oral administration of the Chantaleela recipe reduced ulcer formation in acute gastric ulcer models (EtOH/HCl-, indomethacin-, and stress-induced gastric lesions). In contrast, this recipe did not reduce the secretory rate, total acidity, and increase pH in rat stomach. These results indicated that Chantaleela seem to possess anti-ulcerogenic effect. This activity may be due to the increase of gastric mucosal resistance or potentiation of defensive factors and/or the decrease of aggressive factors but did not associate the anti-secretory activity. Moreover, the high oral doses treated did not cause acute toxicity in rats and the long term oral administration did not produce gastric and ileum lesions.

Anti-diarrheal activity and toxicity of Learng Pid Samud recipe.

Learng Pid Samud (LPS) recipe is a traditional remedy in Thai folk medicine to ease the common diarrhea. The anti-diarrheal potential of LPS recipe was herein examined in vitro using a guinea-pig ileum model. The LPS exerted an inhibitory effect on acetylcholine-induced smooth muscle contraction in the guinea pig ileum. Significantly, not only did the LPS reduce the total amount of feces in the induced diarrhea rats, but also the intestinal transit in the charcoal meal test. A single oral administration with the recipe at 5,000 mg/kg did not cause acute toxicity and the daily oral administration (1,000, 2,000 and 4,000 mg/kg) for 90 days in rats did not produce any toxic signs and symptoms. In conclusion, the Learng Pid Samud recipe remedy is evidently safe and effective for the anti-diarrheal treatment which supports its therapeutic uses in the alternative medicine.

Acute and subchronic toxicity of Chantaleela recipe in rats.

Acute and subchronic toxicities of Chantaleela recipe were studied in both male and female rats. Oral administration of the extract at a single dose of 5,000 mg/kg body weight (5 females, 5 males) did not produce signs of toxicity, behavioral changes, mortality or differences on gross appearance of internal organs. The subchronic toxicity was determined by oral feeding the test substance at the doses of 600, 1,200 and 2,400 mg/kg body weight for 90 days (10 females, 10 males). No signs of abnormalities were observed in the test groups as compared to the controls. The test and control groups (on the 90(th) day) and the satellite group (on the 118(th) day) were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematological parameters, blood clinical chemistry and histopathology features. The results suggest that Chantaleela recipe did not cause acute or subchronic oral toxicities to female and male rats.

Acute and subchronic toxicity study of tud-rak-ka-sai-puu recipe in rats.

Acute and subchronic toxicities of Tud-Rak-Ka-Sai-Puu (TR) recipe were studied in male and female rats. After 14 days of a single oral administration of test substance (5,000 mg/kg body weight), measurement of the body and organs weights, necropsy and health monitoring were performed. No signs and differences in the weights and behavior were observed relative to the control rats, suggesting that TR recipe in the dose of 5,000 mg/kg body weight does not produce acute toxicity. The subchronic toxicity was determined by oral feeding in male and female rats daily with the test substance at 2, 20, 200 and 2,000 mg/kg body weight for 90 days. No defects of animal behavior were observed in the test groups. Both test and control groups (on the 90(th) day) as well as the satellite group (on the 118(th) day) were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry, and microanatomy. These results together with the information of signs, behavior and health monitoring can lead to a conclusion that an oral administration of TR recipe at 2, 20, 200 and 2,000 mg/kg body weight for 90 days did not cause subchronic toxicity.

Toxicity evaluation of sappan wood extract in rats.

BACKGROUND: The heartwood of Caesalpinia sappan L. or sappan wood has long been used in folk medicines to treat tuberculosis, diarrhea, dysentery, skin infections and anemia. OBJECTIVE: To study the acute and subacute toxicities of sappan wood extract in rats. MATERIAL AND METHOD: For studying acute toxicity, a single oral dose of 5000 mg/kg of sappan wood was administered to rats. Subacute toxicity was studied by the daily oral administration of the extract at the doses of 250, 500 and 1000 mg/kg body weight for consecutive 30 days. RESULTS: The extract of sappan wood (5000 mg/kg) showed no toxicity in terms of general behavior change, mortality, or change in gross appearance of internal organs. Subacute toxicity study showed no abnormalities in treatment groups as compared to the controls. Body and organ weights, hematological, blood chemical, necropsy, and histopathological parameter of all groups were similar. CONCLUSION: Sappan wood extract did not produce any acute or subacute toxicity in both female and male rats.

Anti-inflammatory, anti-nociceptive and antipyretic effects of the ethanol extract from root of Piper sarmentosum Roxb.

BACKGROUND: Piper sarmentosum Roxb. (Cha Phul) is a plant in the Piperaceae family which the whole plant is used as an expectorant and the leaf as a carminative. Many extracts from the plants in this family show anti-nociceptive, anti-inflammatory and antipyretic activities in various animal models. OBJECTIVE: To investigate the anti-inflammatory, anti-nociceptive and antipyretic effects of the ethanol extract from P. sarmentosum root. MATERIAL AND METHOD: In vivo study. RESULTS: P. sarmentosum extract significantly inhibited ethyl phenylpropiolate-induced ear edema as well as carrageenan-induced hind paw edema in rats. The extract reduced transudative and granuloma weights of the chronic inflammatory model using the cotton pellet-induced granuloma formation in rats. The extract exerted a pronounced inhibitory activity on the early phase and late phase of the formalin test in mice. In addition, the extract elicited an antipyretic activity on yeast-induced hyperthermia in rats. CONCLUSION: P. sarmentosum extract possessed anti-inflammatory, anti-nociceptive and antipyretic activities.