4-methoxycinnamyl p-coumarate reduces neuroinflammation by blocking NF-κB, MAPK, and Akt/GSK-3ß pathways and enhancing Nrf2/HO-1 signaling cascade in microglial cells.

The active compound, 4-methoxycinnamyl p-coumarate (MCC), derived from the rhizome of Etlingera pavieana (Pierre ex Gagnep) R.M.Sm., has been shown to exert anti-inflammatory effects in several inflammatory models. However, its effects on microglial cells remain elusive. In the current study, we aimed to investigate the anti-neuroinflammatory activities of MCC and determine the potential mechanisms underlying its action on lipopolysaccharide (LPS)-induced BV2 microglial cells. Our results revealed that MCC significantly reduced the secretion of nitric oxide (NO) and prostaglandin E2, concomitantly inhibiting the expression levels of inducible NO synthase and cyclooxygenase-2 mRNA and proteins. Additionally, MCC effectively decreased the production of reactive oxygen species in LPS-induced BV2 microglial cells. MCC also attenuates the activation of NF-κB by suppressing the phosphorylation of IκBα and NF-κB p65 subunits and by blocking the nuclear translocation of NF-κB p65 subunits. Furthermore, MCC significantly reduced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß). In addition, MCC markedly increased the expression of heme oxygenase-1 (HO-1) by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Collectively, our findings suggest that the anti-inflammatory activities of MCC could be attributed to its ability to suppress the activation of NF-κB, MAPK, and Akt/GSK-3ß while enhancing that of Nrf2-mediated HO-1. Accordingly, MCC has promising therapeutic potential to treat neuroinflammation-related diseases.

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-arthritis Effects of Zingiberaceae Extracts on Models of Inflammatory Joint Disease.

Due to this becoming an aging society, the number of arthritis cases has been increasing. Unfortunately, some currently available medications can cause adverse effects. Using herbal remedies as a form of alternative medicine is becoming increasingly popular. Zingiber officinale (ZO), Curcuma longa (CL), and Kaempferia parviflora (KP) are herbal plants in the Zingiberaceae family that have potent anti-inflammatory effects. This study investigates the anti-inflammatory and chondroprotective effects of ZO, CL, and KP extracts on in vitro and ex vivo inflammatory models. The combinatorial anti-arthritis effect of each extract is also evaluated in an in vivo model. ZO extract preserves cartilaginous proteoglycans in proinflammatory cytokines-induced porcine cartilage explant in a fashion similar to that of CL and KP extracts and suppresses the expression of major inflammatory mediators in SW982 cells, particularly the COX2 gene. CL extract downregulates some inflammatory mediators and genes-associated cartilage degradation. Only KP extract shows a significant reduction in S-GAGs release in a cartilage explant model compared to the positive control, diacerein. In SW982 cells, it strongly suppresses many inflammatory mediators. The active constituents of each extract selectively downregulate inflammatory genes. The combined extracts show a reduction in inflammatory mediators to a similar degree as the combined active constituents. Reductions in paw swelling, synovial vascularity, inflammatory cell infiltration, and synovial hyperplasia are found in the combined extracts-treated arthritic rats. This study demonstrates that a combination of ZO, CL, and KP extracts has an anti-arthritis effect and could potentially be developed into an anti-arthritis cocktail for arthritis treatment.

Acute and subchronic oral toxicity assessment of extract from Etlingera pavieana rhizomes.

In Southeast Asia, the rhizome of Etlingera pavieana is commonly consumed and parts of the rhizomes have been used as a medicine for the treatment of several disorders. Its pharmacological effects have previously been reported. However, its potential toxicity has not been described. This study aimed to evaluate in vivo toxicity of E. pavieana rhizome extract (EPE) in Sprague Dawley rats. Acute toxicity testing of EPE at a single dose of 2,000 mg/kg produced no toxic effects in female rats after 14 days of treatment. Subchronic toxicity testing showed that all doses of EPE (500, 1,000, and 2,000 mg/kg/day) produced no sign of toxicity during 90 days of treatment. All biochemical and hematological values were within normal ranges. There were no significant histopathological differences in the internal organs among the tested groups. Therefore, the no-observed-adverse-effect level of EPE was 2,000 mg/kg/day in both male and female rats, thereby confirming the safety of EPE for use in traditional medicines.

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.

Gastroprotective Activities of Ethanol Extract of Black Rice Bran (Oryza sativa L.) in Rats.

Black rice is a type of rice in the Oryza sativa L. species. There are numerous reports regarding the pharmacological actions of black rice bran, but scientific evidence on its gastroprotection is limited. This study aimed to evaluate the gastroprotective activities of black rice bran ethanol extract (BRB) from the Thai black rice variety Hom Nil (O. sativa L. indica) as well as its mechanisms of action, acute oral toxicity in rats, and phytochemical screening. Rat models of gastric ulcers induced by acidified ethanol, indomethacin, and restraint water immersion stress were used. After pretreatment with 200, 400, and 800 mg/kg of BRB in test groups, BRB at 800 mg/kg significantly inhibited the formation of gastric ulcers in all gastric ulcer models, and this inhibition seemed to be dose dependent in an indomethacin-induced gastric ulcer model. BRB could not normalize the amount of gastric wall mucus, reduce gastric volume and total acidity, or increase gastric pH. Although BRB could not increase NO levels in gastric tissue, the tissue MDA levels could be normalized with DPPH radical scavenging activity. These results confirm the gastroprotective activities of BRB with a possible mechanism of action via antioxidant activity. The major phytochemical components of BRB comprise carotenoid derivatives with the presence of phenolic compounds. These components may be responsible for the gastroprotective activities of BRB. The 2000 mg/kg dose of oral BRB showed no acute toxicity in rats and confirmed, in part, the safe uses of BRB.

Kaempferia parviflora Extract Alleviated Rat Arthritis, Exerted Chondroprotective Properties In Vitro, and Reduced Expression of Genes Associated with Inflammatory Arthritis.

Kaempferia parviflora Wall. ex Baker (KP) has been reported to attenuate cartilage destruction in rat model of osteoarthritis. Previously, we demonstrated that KP rhizome extract and its active components effectively suppressed mechanisms associated with RA in SW982 cells. Here, we further evaluated the anti-arthritis potential of KP extract by using multi-level models, including a complete Freund's adjuvant-induced arthritis and a cartilage explant culture model, and to investigate the effects of KP extract and its major components on related gene expressions and underlying mechanisms within cells. In arthritis rats, the KP extract reduced arthritis indexes, with no significant changes in biological parameters. In the cartilage explant model, the KP extract exerted chondroprotective potential by suppressing sulfated glycosaminoglycans release while preserving high accumulation of proteoglycans. In human chondrocyte cell line, a mixture of the major components equal to their amounts in KP extract showed strong suppression the expression of genes-associated inflammatory joint disease similar to that of the extract. Additionally, KP extract significantly suppressed NF-κB and MAPK signaling pathways. The suppressing expression of necroptosis genes and promoted anti-apoptosis were also found. Collectively, these results provided supportive evidence of the anti-arthritis properties of KP extract, which are associated with its three major components.

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.

Clinical Efficacy and Safety of Thai Herbal Formulation-6 in the Treatment of Symptomatic Osteoarthritis of the Knee: A Randomized-Controlled Trial.

BACKGROUND: Osteoarthritis of the knee is the most common form of arthritis. Identifying effective and safe herbal formulations that are locally available is viewed as a priority for sustainable development in a region. This study aimed to evaluate the efficacy and safety of Thai herbal formulation-6 (THF-6) in comparison with oral diclofenac in patients with moderate-to-severe osteoarthritis of the knee. METHODS: This randomized, double-blind, active-controlled, noninferiority trial randomly assigned patients with osteoarthritis of the knee to receive either THF-6 or diclofenac for four weeks. The primary outcome measure was the change from baseline in knee pain as measured by a 100 mm visual analog scale (VAS). Secondary outcome measures included knee stiffness, a stair climb test, the Knee Injury and Osteoarthritis Outcome Score, and safety parameters. Outcomes were assessed on a biweekly basis. Modified intention-to-treat (MITT) and perprotocol (PP) analyses were applied. RESULTS: A total of 200 patients were enrolled of whom 175 (87.5%) were included in the MITT analysis and 153 (76.5%) in the PP analysis. The mean change in VAS pain did not differ between the two groups, and the upper limit of the two-sided 95% confidence interval (CI) for comparison between the two groups was within the prespecified margin of 10 mm for noninferiority (MITT analysis: mean difference = 0.86, 95% CI = -4.39 to 6.10, p=0.748; PP analysis: mean difference = 1.98, 95% CI = -3.61 to 7.56, p=0.486). Significant improvement was observed in all the efficacy parameters in both groups. Dyspepsia was the most common adverse event: 23 patients in the THF-6 group and 28 in the diclofenac group (p=0.417). CONCLUSIONS: THF-6 offers an alternative to oral diclofenac for the short-term treatment of osteoarthritis of the knee. It was shown to be noninferior to oral diclofenac in relieving knee pain. This trial is registered with ChiCTR-IPR-15007213.

Acute and chronic oral toxicity assessment of longan sugar extracts derived from whole fruit and from fruit pulp in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Longan (Dimocarpus longan Lour.) is one of the most popular subtropical fruits. Various parts of longan, including seeds, pericarp and pulp, have long been used in traditional medicine in China, Thailand and other Asian countries. The pulp has high sugar, vitamin and mineral content as well as bioactive components. The seeds and pericarp have also been reported to contain beneficial polyphenolic compounds. Longan sugar extract from pulp (LGSP) is prepared as a conventional sugar product. Longan sugar extract from whole longan fruit (LGSW) is also offered as a health food and as a medicinal product. AIM OF THE STUDY: The objective of this study was to identify and compare potential health hazards of both LGSW and LGSP by testing for acute and chronic oral toxicity in rats. MATERIALS AND METHODS: In acute toxicity testing, an oral dose (20 g/kg) of either LGSW or LGSP was administered to groups of rats. Mortality and clinical signs of toxicity were observed for 24 h, and then daily for a total of 14 days. In the chronic toxicity test, either LGSW (1, 2.5 and 5 g/kg/day) or LGSP (5 g/kg/day) was administered orally for a period of 180 days. After that treatment period, the rats in the satellite groups which received the highest doses of either LGSW or LGSP were observed for an additional 28 days. The rats then underwent clinical observation, body and organ weight measurement, hematological and biochemical analyses, and histopathological examination. RESULTS: In the acute toxicity study, the oral administration of LGSP or LGSW in either pellet or syrup formulations did not cause mortality or any pathological abnormalities. In the chronic toxicity study, neither LGSW nor LGSP resulted in death or in any changes in behavior of the rats. All hematological and serum biochemical values of both the LGSW- and LGSP-treated groups were within the normal ranges. No histopathological abnormalities of any internal organs were observed. CONCLUSION: The safety of longan sugar extract made from whole fruit (pulp, seeds and pericarb) is comparable to that of longan sugar extract made from pulp alone.

Pyranonaphthoquinone and anthraquinone derivatives from Ventilago harmandiana and their potent anti-inflammatory activity.

The chemical study on the heartwoods extract of Ventilago harmandiana (Rhamnaceae) resulted in the isolation of ten previously undescribed pyranonaphthoquinones (ventilanones A-J), an undescribed anthraquinone (ventilanone K), together with eight known anthraquinone derivatives. Their structures were elucidated by extensive analysis of their spectroscopic data. The absolute configuration of ventilanone A was established from single crystal X-ray crystallographic analysis of its p-bromobenzenesulfonate ester derivative using Cu Kα radiation. The absolute configurations of the other related compounds were identified by comparison of their ECD data with those of ventilanone A and related known compounds. Cytotoxic and anti-inflammatory activities of some of the isolated compounds were evaluated. Ventilanone A and ventilanone C exhibited moderate cytotoxicity against P-388 cell line. Ventilanone D exhibited significant anti-inflammatory activity while ventilanone A and ventilanone C showed moderate activity.

Anti-inflammatory effect of trans-4-methoxycinnamaldehyde from Etlingera pavieana in LPS-stimulated macrophages mediated through inactivation of NF-κB and JNK/c-Jun signaling pathways and in rat models of acute inflammation.

Trans-4-methoxycinnamaldehyde (MCD) was isolated from the rhizomes of Etlingera pavieana (Pierre ex Gagnep.) R.M.Sm. MCD shows anti-inflammatory effects. However, the molecular mechanism underlying its anti-inflammatory action has not been described. In this study, we investigated this mechanism in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and found MCD significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in a concentration-dependent manner. MCD could decrease LPS- and Pam3CSK4- induced the expressions of both iNOS and COX-2. The phosphorylation of inhibitory κB (IκB) and translocation of nuclear factor-κB (NF-κB) p65 subunit into the nucleus were also inhibited by MCD. Moreover, MCD suppressed LPS-induced phosphorylation of JNK except for ERK and p38 mitogen-activated protein kinases (MAPKs). Moreover, MCD significantly reduced ethyl phenylpropiolate-induced ear edema and carrageenan-induced paw edema in rat models. These findings indicated MCD has anti-inflammatory activity by inhibiting the production of NO and PGE2 by blocking NF-κB and JNK/c-Jun signaling pathways. Collectively, these data suggest that MCD could be developed as a novel therapeutic agent for inflammatory disorders.

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.

Gastroprotective activity of the rhizome ethanol extract of Zingiber simaoense Y. Y. Qian in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Zingiber simaoense Y. Y. Qian belongs to the Zingiberaceae family. Its rhizome has been used in Thai folk medicine to relieve gastric disorders; however, scientific evidence of its pharmacological activities has not yet been revealed. AIM OF THE STUDY: This study was designed to validate the gastroprotective activity and to identify possible mechanisms of gastroprotection of Z. simaoense rhizome ethanol extract (ZSE) in rats. MATERIALS AND METHODS: The gastroprotective effect of ZSE was tested using models of gastric ulcers induced by acidified ethanol, indomethacin, and restraint water immersion stress. Models for determination of gastric wall mucus secretion and plasma malondialdehyde levels as well as pylorus ligation were used to explore the mechanisms of action. RESULTS: After oral administration by intragastric gavage, ZSE 7.5, 15, and 30mg/kg or cimetidine 100mg/kg significantly inhibited the formation of gastric ulcer in all gastric ulcer models. The gastric wall mucus amount was significantly higher than that of the ulcer control group, plasma malondialdehyde levels were normalized, and gastric secretion was partly inhibited by pretreatment with ZSE. CONCLUSIONS: This study demonstrates the gastroprotective activity of ZSE in rats. The mechanisms of action of ZSE may depend on its ability to maintain the integrity of gastric wall mucus through the protection of gastric mucus, and/or by increasing the gastric mucus synthesis and secretion through prostaglandin synthesis. Moreover, the antioxidant activity of ZSE may also contribute to its mechanism of gastroprotection.

Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study.

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (Cmax), time to reach peak concentration (Tmax), area under the plasma concentration-time curve (AUC), and half-life (t1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects.

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.

Cytotoxic Effect of Coscinium fenestratum on Human Head and Neck Cancer Cell Line (HN31).

Coscinium fenestratum is widely used as a medicinal plant in many Asian countries. This study aimed to investigate the cytotoxic effect of a crude water extract of C. fenestratum (CF extract) compared to 5-fluorouracil (5-FU) on human HN31 cell line, a metastatic squamous cell carcinoma of the pharynx. The results revealed that cell morphology visualized under inverted light microscopy was changed from flat with a polygonal appearance to round appearance after CF extract application. The cell viability assay (MTT test) showed that the concentration producing 50% growth inhibition (IC50) at 48-hour incubation of CF extract on HN31 was 0.12 mg/mL, while the IC50 of 5-FU was 6.6 mg/mL, indicating that CF extract has a higher potency. However, combining various concentrations of 5-FU and CF extract at IC50 did not show synergistic effect. The CF extract dose dependently increased cell apoptosis determined by Annexin-V and propidium iodide staining. It decreased the phosphorylation of p38 MAPK and pAkt, while it increased the tumor suppressor protein p53. In conclusion, the cytotoxicity of CF extract was associated with the modulation of p38 MAPK, pAkt, and p53 signal molecules, leading to inhibiting cell survival and increasing apoptosis. No synergistic effects of CF extract and 5-FU were observed.

Investigation of anti-inflammatory, antinociceptive and antipyretic activities of Stahlianthus involucratus rhizome ethanol extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Stahlianthus involucratus (Zingiberaceae) has long been used in traditional medicine to treat inflammation, pain, and fever. However, no pharmacological study of this plant has been reported to confirm these activities. The aim of this study was to investigate the anti-inflammatory, antinociceptive and antipyretic activities of Stahlianthus involucratus rhizome ethanol extract (SiE) in animal models. MATERIALS AND METHODS: Anti-inflammatory activity of SiE was investigated in rats using ethyl phenylpropiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid (AA)-induced hind paw edema, and cotton pellet-induced granuloma formation models. Acetic acid-induced writhing response in mice and tail-flick test in rats as well as yeast-induced hyperthermia in rats were used to investigate the antinociceptive and antipyretic activities, respectively. RESULTS: SiE significantly inhibited EPP-induced ear edema, carrageenan- and AA-induced hind paw edema. Its inhibitory effect in carrageenan-induced hind paw edema seemed to be in a dose-dependent manner. In cotton pellet-induced granuloma formation, SiE showed suppressive effects on granuloma formation but not on body weight gain and dry thymus weight. It could normalize serum alkaline phosphatase activity to nearly normal level. SiE also possessed a significant inhibitory effect, which seemed to be dose-dependent, on acetic acid-induced writhing response, whereas only at the highest dose of SiE could significantly increase test reaction time at all time-points in tail-flick test. However, no antipyretic activity was observed. CONCLUSIONS: These results suggest that SiE possesses anti-inflammatory and antinociceptive, but not antipyretic, activities. This study therefore rationalizes the traditional use of SiE for the treatment of inflammation and pain.