The Ameliorative Effect of Litsea martabanica (Kurz) Hook. f. Leaf Water Extract on Chlorpyrifos-Induced Toxicity in Rats and Its Antioxidant Potentials.

Litsea martabanica root's antioxidant and acetylcholinesterase (AChE) activity showed promise as a pesticide detoxification agent in our previous study. In addition to its root, leaves can help alleviate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in several countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally used leaves instead of roots. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extract from L. martabanica leaves through in vitro and in vivo investigations. In the in vitro study, L. martabanica water extract and its fractions demonstrated antioxidant activity and induced apoptosis in hepatic satellite cells. In the in vivo study, treatment with the leaf extract led to increased AChE activity, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) levels, and reduced glutathione in chlorpyrifos-exposed rats. Histopathological examination revealed that chlorpyrifos-treated rats exhibited liver cell damage, while treatment with the water extract of L. martabanica exhibited a protective effect on the liver. In conclusion, L. martabanica water extract exhibited antioxidant activity, enhanced AChE activity, and improved histopathological abnormalities in the liver.

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.

Gastroprotective effects of Pikad Tri-phol-sa-mut-than herbal remedy on multiple gastric ulcer models in rats.

In Thai traditional medicine, Pikad Tri-phol-sa-mut-than has long been used to alleviate gastrointestinal symptoms, renal disease, inflammation-related disorders, and severe malady. This recipe is composed of dried fruits of Morinda citrifolia L., Coriandrum sativum L., and Aegle marmelos (L.) Corrêa. The aim of this study was to assess the anti-gastric ulcer property of the water extract of Pikad Tri-phol-sa-mut-than (TS), using various animal models with different inducers, including restraint water immersion stress, indomethacin, and ethanol/hydrochloric acid (EtOH/HCl). Its mechanisms of anti-gastric ulcer actions were also elucidated using both in vitro and in vivo experiments. When compared with the control groups, the oral pretreatment of TS at the doses of 150, 300 and 600 mg/kg significantly reduced the gastric ulcer formation in all models. It was also found that TS at the dose of 600 mg/kg could increase gastric wall mucus in rats but could not produce the significant reduction of the gastric volume or total acidity of gastric content. Results from hematoxylin and eosin (H&E) and Periodic acid-Schiff (PAS) staining examinations of gastric tissues confirmed that TS visibly reduced gastric mucosal damage, while immunohistochemistry revealed that TS remarkably suppressed the protein expression of Bcl-2-associated X (BAX), a regulator of apoptosis, compared to those of the control group. The DPPH, ABTS, and FRAP assays showed antioxidant effects of TS. All of these findings demonstrated that TS has gastroprotective effects, which may be related to the increase in the gastric wall mucus secretion, not anti-secretory activity, as well as its antioxidant and antiapoptotic activities.

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.

Safety of the Oral Triphala Recipe from Acute and Chronic Toxicity Tests in Sprague-Dawley Rats.

BACKGROUND: The Indian Ayurvedic herbal formula Triphala (TPL) is known for its pharmacological properties for immunomodulation, anti-inflammation, antioxidant, and anti-cancer. This study aimed to investigate the acute and chronic toxicities of the Triphala recipe in a rat model. METHODS: To assess the acute toxicities, 5000 mg/kg of TPL was orally administered to Sprague-Dawley rats. For chronic toxicities, different dose levels of TPL at 600, 1200, and 2400 mg/kg/day were given daily for 270 days. General health and behaviors and the body and organ weights of the rats were monitored. At the end of the experiment, blood samples were evaluated for hematology and biochemistry profiles. The evaluation of the internal organs' appurtenance and necropsy was performed to confirm the tissue histopathology. RESULTS: The results showed that there was no sign of acute toxicity in the TPL group with a decrease in sex organ weights. No significant differences in the rats' behaviors, physical health, body, or organ weights were found between the controls and the rats receiving the 270/day of oral Triphala at 600, 1200, and 2400 mg/kg/day. However, some alterations in blood chemistries and hematology, including glucose, BUN, red blood cells, Hb, HCT, and MCV, were observed without abnormalities in histopathology. CONCLUSIONS: It has been demonstrated that the long-term use of TPL in rat models is safe. No toxic effects were found, suggesting possible safety for long-term use in humans.

Anti-inflammatory effects of Pikad Tri-phol-sa-mut-than remedy, consisting of dried fruits of Aegle marmelos (L.) Corrêa, Coriandrum sativum L., and Morinda citrifolia L.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation has been known to possess some essential roles in many diseases, especially those with chronic or severe conditions. Pikad Tri-phol-sa-mut-than, a Thai traditional herbal remedy, has long been used to treat gastrointestinal sicknesses, fever, and severe illness caused by the deformities of Tridosha. In particular, this recipe has also been applied for inflammation-related conditions including gout and rheumatoid arthritis. The Pikad Tri-phol-sa-mut-than recipe consists of dried fruits of three herbs including Aegle marmelos (L.) Corrêa, Morinda citrifolia L., and Coriandrum sativum L. Each of these plant components of Pikad Tri-phol-sa-mut-than exhibited anti-inflammatory activities. However, anti-inflammatory effect of Pikad Tri-phol-sa-mut-than remedy has not been reported. AIM OF THE STUDY: The objective of this study was to elucidate the anti-inflammatory activities of Pikad Tri-phol-sa-mut-than extract (TS) against acute and chronic inflammation in rats. MATERIALS AND METHODS: To study the effects of TS on acute inflammation, ethyl phenylpropiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid (AA)-induced hind paw edema models were carried out. In addition, cotton pellet-induced granuloma formation was performed to specify the inhibitory effects of TS on chronic inflammation. RESULTS: The topical application of TS significantly inhibited EPP-induced ear edema in rats. In the carrageenan- and AA-induced paw edema models, the oral administration of TS significantly reduced paw volumes, compared to those of the control groups. In addition, the 7-day oral treatment of TS demonstrated a significant suppressive effect on cotton pellet-induced granuloma formation. CONCLUSIONS: The current study revealed that TS possesses anti-inflammatory activities against acute and chronic inflammation. Our studies support the use of TS in traditional medicine, and the development of TS as a novel natural product for treating diseases associated with inflammation.

In Vitro Antioxidant Activity of Litsea martabanica Root Extract and Its Hepatoprotective Effect on Chlorpyrifos-Induced Toxicity in Rats.

In Thailand, people in the highland communities whose occupational exposure to pesticides used the root of Litsea martabanica as a detoxifying agent. However, the scientific data to support the traditional use of this plant are insufficient. This study aimed to evaluate the antioxidant activity and anti-pesticide potential of L. martabanica root extract. Antioxidant properties were investigated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radicals scavenging assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), and total phenolic content determination. In all assays, L. martabanica extracts and their fractions exhibited high antioxidant activities differently. The water extract is traditionally used as a detoxifying agent. Therefore, it was chosen for in vivo experiments. The rats received the extract in a way that mimics the traditional methods of tribal communities followed by chlorpyrifos for 16 days. The results showed that acetylcholinesterase activity decreases in pesticide-exposed rats. Treatment with the extract caused increasing acetylcholinesterase activity in the rats. Therefore, L. martabanica extract may potentially be used as a detoxifying agent, especially for the chlorpyrifos pesticide. The antioxidant properties of L. martabanica may provide a beneficial effect by protecting liver cells from damage caused by free radicals. Histopathology results revealed no liver cell necrosis and showed the regeneration of liver cells in the treatment group. L. martabanica extract did not cause changes in behavior, liver weight, hematological and biochemical profiles of the rats.

Mucuna pruriens (L.) DC. seed extract inhibits lipopolysaccharide-induced inflammatory responses in BV2 microglial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation caused by activated microglia is known to be associated with neurodegenerative diseases, e.g., Parkinson's disease (PD) and Alzheimer's disease (AD). Inhibiting the inflammatory process can be considered a potential strategy for the treatment of inflammation-associated diseases. Mucuna pruriens (L.) DC. (Leguminosae) has long been used in Thailand, India, China and other tropical countries to treat several diseases including PD. M. pruriens seeds have been found to possess a variety of pharmacological properties including antioxidant and anti-Parkinsonism effects. However, the anti-inflammatory effects of M. pruriens seeds during microglial activation have yet to be reported. AIM OF THE STUDY: The present study was performed to evaluate the anti-inflammatory effects of M. pruriens seed extract and elucidate its underlying mechanism using lipopolysaccharide (LPS)-stimulated BV2 microglial cells. MATERIALS AND METHODS: BV2 microglial cells were pretreated with various concentrations of M. pruriens seed extract before being stimulated with LPS. The levels of inflammatory mediators were analyzed by Griess assay and enzyme-linked immunoassay (ELISA). The protein expression levels of inflammatory cytokines were determined by Western blot analysis. The translocation of nuclear factor-kappa B (NF-κB) was assessed by immunofluorescence microscopy. RESULTS: M. pruriens seed extract significantly inhibited the release of inflammatory mediators including nitric oxide (NO), IL-1ß, IL-6, and TNF-α in LPS-stimulated BV2 microglial cells. The extract also decreased the protein expression of IL-1ß, IL-6, and TNF-α. Moreover, M. pruriens seed extract inhibited the translocation of NF-κB. CONCLUSIONS: M. pruriens seed extract could suppress inflammatory responses in LPS-activated BV2 microglial cells by inhibiting the NF-κB signaling pathway. These findings support the use of M. pruriens seeds in traditional and alternative medicine for the treatment of PD and other inflammation-associated diseases.

In Vitro and In Vivo Anti-Inflammatory Activities of Benjakul: A Potential Medicinal Product from Thai Traditional Medicine.

Benjakul (BJK) is a Thai traditional remedy consisting of five plants: Piper chaba Hunt., Piper sarmentosum Roxb., Piper interruptum Opiz., Plumbago indica Linn., and Zingiber officinale Roscoe. It is used as a first-line drug to balance patient's symptoms before other treatments. BJK ethanolic extract has been reported to show anti-inflammatory activity through various mediators, e.g., nitric oxide, TNF-α, IL-1ß, and IL-6. Therefore, BJK could serve as a potential novel anti-inflammatory herbal medicine. However, studies on prostaglandin E2 (PGE2), one of the key mediators in acute inflammation, and anti-inflammation in animal models (in vivo) have not been done. This study investigated the anti-inflammatory activity of BJK extract and some of its chemical compounds against PGE2 production in murine macrophage (RAW 264.7) cell line and two in vivo models of anti-inflammatory studies. Ethanolic extract of BJK (BJK[E]) showed high inhibitory activity against PGE2 production with an IC50 value of 5.82 ± 0.10 µg/mL but its water extract (BJK[W]) was inactive. Two chemicals from BJK[E], i.e., plumbagin and myristicin, which served as biological markers, showed strong activity with IC50 values of 0.08 ± 0.01 and 1.80 ± 0.06 µg/mL, respectively. BJK[E] was administered both topically and orally to rats inhibited with inflammation induced by ethyl phenylpropiolate (rat ear edema model) and carrageenan (hind paw edema model). Moreover, the biological activity of BJK extract did not reduce after six-month storage under accelerated condition (40°C, 75% RH). This indicated its stability and a 24-month shelf-life under normal condition. These results supported not only the use of BJK in Thai traditional medicine but also the possibility of further development of phytopharmaceutical products from BJK.

Salacia chinensis L. Stem Extract Exerts Antifibrotic Effects on Human Hepatic Stellate Cells Through the Inhibition of the TGF-ß1-Induced SMAD2/3 Signaling Pathway.

: Salacia chinensis L. (SC) stems have been used as an ingredient in Thai traditional medicine for treating patients with hepatic fibrosis and liver cirrhosis. However, there is no scientific evidence supporting the antifibrotic effects of SC extract. Therefore, this study aimed to determine the antifibrotic activity of SC stem extract in human hepatic stellate cell-line called LX-2. We found that upon TGF-ß1 stimulation, LX-2 cells transformed to a myofibroblast-like phenotype with a noticeable increase in α-SMA and collagen type I production. Interestingly, cells treated with SC extract significantly suppressed α-SMA and collagen type I production and reversed the myofibroblast-like characteristics back to normal. Additionally, TGF-ß1 also influenced the development of fibrogenesis by upregulation of MMP-2, TIMP-1, and TIMP-2 and related cellular signaling, such as pSmad2/3, pErk1/2, and pJNK. Surprisingly, SC possesses antifibrotic activity through the suppression of TGF-ß1-mediated production of collagen type 1, α-SMA, and the phosphorylation status of Smad2/3, Erk1/2, and JNK. Taken together, the present study provides accumulated information demonstrating the antifibrotic effects of SC stem extract and revealing its potential for development for hepatic fibrosis patients.

Antipsoriatic Effects of Wannachawee Recipe on Imiquimod-Induced Psoriasis-Like Dermatitis in BALB/c Mice.

Psoriasis is a common immune-mediated chronic inflammatory skin disease characterized by thick and erythema raised plaques with adherent silvery scales. T-cells are activated via the IL-23/Th17 axis which is involved in psoriasis pathogenesis. Conventional treatments of psoriasis have adverse events that influence patients' adherence. Wannachawee Recipe (WCR) is Thai traditional medicine that is known to be effective for psoriasis patients; however, preclinical evidence is still lacking. This study investigated the therapeutic potential of WCR on antiproliferant activity using imiquimod- (IMQ-) induced psoriasis-like dermatitis in a mouse model. Psoriasis-like dermatitis was induced on the shaved dorsal skin and right ear pinna of BALB/c mice by topical application of IMQ for 15 consecutive days after which WCR was administered to the mice by oral gavage for 10 days. Phenotypical observations, histopathological examinations, and ELISA of skin and blood samples were conducted. WCR significantly ameliorated development of IMQ-induced psoriasis-like dermatitis and reduced levels of Th17 cytokines (IL-17A, IL-22, and IL-23) in both serum and dorsal skin. Histopathological findings showed a decrease in epidermal thickness and inflammatory T-cell infiltration in the WCR-treated groups. The WCR has pharmacological actions which regulate Th17 related cytokines suggesting that it is a potential alternative therapeutic strategy for psoriasis.

Effects of Wannachawee Recipe with Antipsoriatic Activity on Suppressing Inflammatory Cytokine Production in HaCaT Human Keratinocytes.

Psoriasis is a chronic inflammatory and immune-mediated skin disease. The pathogenesis involves T cells activation via the IL-23/Th17 axis. Conventional treatments of psoriasis have adverse events influencing patients' adherence. Wannachawee Recipe (WCR) has been effectively used as Thai folk remedy for psoriasis patients; however, preclinical evidence defining how WCR works is still lacking. This study defined mechanisms for its antiproliferation and anti-inflammatory effects in HaCaT cells. The cytotoxicity and antiproliferation results from SRB and CCK-8 assays showed that WCR inhibited the growth and viability of HaCaT cells in a concentration-dependent manner. The distribution of cell cycle phases determined by flow cytometry showed that WCR did not interrupt cell cycle progression. Interestingly, RT-qPCR revealed that WCR significantly decreased the mRNA expression of IL-1ß, IL-6, IL-8, IL-17A, IL-22, IL-23, and TNF-α but induced IL-10 expression in TNF-α- and IFN-γ-induced HaCaT cells. At the protein level determined by ELISA, WCR significantly reduced the secretion of IL-17A, IL-22, and IL-23. The WCR at low concentrations was proved to possess anti-inflammatory effect without cytotoxicity and it did not interfere with cell cycle of keratinocytes. This is the first study to provide convincing evidence that WCR is a potential candidate for development of effective psoriasis therapies.

Thunbergia laurifolia Exhibits Antifibrotic Effects in Human Hepatic Stellate Cells.

Leaves of Thunbergia laurifolia (TL) have been reported to have antioxidation, anti-inflammatory, detoxifying, and hepatoprotective effects. However, studies relating to antifibrotic activity have not been reported. Currently, there is no standard treatment for hepatic fibrosis. This study aimed to investigate the antifibrotic activity of TL in human hepatic stellate LX-2 cells. Results from cell viability and cell death assays showed that the extract at high concentrations was toxic to LX-2 cells. TL extract reversed the transformation of LX-2 cells to myofibroblast-like characteristics in response to stimulation by transforming growth factor-beta 1. This action may be associated with the effect of TL in suppressing α-SMA and collagen-I production observed by immunofluorescence study and western blot analysis. Additionally, TL extract significantly decreased MMP-9 activity which is consistent with the reduction of MMP-9, MMP-2, and TIMP-1 gene expression. The effect of TL in suppressing fibrosis may be associated with its ability to inhibit the activation of p38 MAPK and Erk1/2 kinases as examined by western blot analysis. Our study provides convincing evidence that TL possesses antifibrotic activity which may be through the suppression of TGF-ß1-mediated production of MMPs, collagen-1, and α-SMA in hepatic stellate cells.

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.