Enhancement of oxidative response and cytokine production by yam mucopolysaccharide in murine peritoneal macrophage

Yam (Dioscorea batatas) mucopolysaccharide (YMP) was examined for the ability to induce secretory and cellular responses in murine peritoneal macrophages. When macrophages were treated with various doses (10-100 microg/ml) of YMP for 48 h, a significant cytotoxicity against B 16 cells was observed. YMP also increased the myeloperoxidase activity and the production of H(2)O(2), O(2)(-), nitric oxide (NO) and tumor necrosis factor (TNF-alpha). However, there was a little alteration on the production of IFN-gamma. These results indicate that reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI) and TNF-alpha are likely major mediators of cytotoxic activity of YMP-treated macrophages.     

Antitumor activity of Dioscorea bulbifera L. rhizome in vivo

Antitumor activities of water extract (fraction A), ethanol extract (fraction B), ethyl acetate extract (fraction C), non-ethyl acetate extract (fraction D) and compound diosbulbin B isolated from Dioscorea bulbifera L. (DB) were investigated in vivo in this present study. The results showed that fractions B and C both decreased tumor weight in S180 and H22 tumor cells bearing mice, while fractions A and D had no such effect. Furthermore, fraction C altered the weight of spleen and thymus, and the amounts of total leukocytes, lymphocytes and neutrophils in tumor-bearing mice. Further results showed that compound diosbulbin B demonstrated anti-tumor effects in the dose-dependent manner at the dosage of 2 to 16 mg/kg without significant toxicity in vivo. Furthermore, on the basis of chemical analysis of the above extracts by high-performance liquid chromatography (HPLC) with a diode array detector (DAD), diosbulbin B was found to be the major antitumor bioactive component of DB. These results suggest that DB has potential anti-tumor effects which may be related to influencing the immune system for the first time, and the compound diosbulbin B is the major antitumor component of DB.     

Antiinflammatory activity of Polygala japonica extract

The antiinflammatory activity of the aqueous extract of Polygala japonica (AEPJ) was investigated in mice and rats to find the pharmacological basis for its ethnomedical use. The extract produced a significant inhibition of peritoneal and cutaneous vascular permeability induced by acetic acid and histamine, respectively and ear swelling induced by picryl chloride in mice at the dose of 25.0 mg/kg. Moreover, the extract markedly inhibited footpad edema induced by histamine in rats, and decreased prostaglandin E(2) (PGE(2)) content in carrageenan-induced air-pouch at doses of 12.5 and 6.25 mg/kg respectively.     

Antinociceptive effect and acute toxicity of the Hyptis suaveolens leaves aqueous extract on mice

The aqueous extract of Hyptis suaveolens leaves was studied for their antinociceptive property in chemical and thermal models of nociception in mice. Oral administration of the aqueous extract (100, 200, and 400 mg/kg) dose-dependently reduced the number of writhings induced by acetic acid, decreased the licking activity of the early phase in formalin test and increased the reaction time in hot-plate test. The antinociceptive effect was significantly antagonized by naloxone (3 mg/kg; i.p.). Preliminary acute toxicity study showed that no animal death with doses up to 5 g/kg (p.o.).     

Passiflora alata and Passiflora edulis spray-dried aqueous extracts inhibit inflammation in mouse model of pleurisy

The aqueous leaves extracts of Passiflora alata (100-300 mg/kg, i.p.) and Passiflora edulis (100-1000 mg/kg, i.p.) possess a significant antiinflammatory activity on carrageenan-induced pleurisy in mice. Treatment with the extracts inhibited leukocyte migration and reduced the formation of exudate. Moreover, a significant inhibition of myeloperoxidase and adenosine-deaminase activities was observed at the doses tested (100 or 250 mg/kg, i.p.). At the same doses, a significant decrease of serum C-reactive protein was observed.     

Antiinflammatory activity of Sambucus ebulus hexane extracts

Hexane extracts of aerial parts (flowered browes), leaves and roots of Sambucus ebulus were investigated for their antiinflammatory activity in rats. Aerial parts and roots extracts produced statistically significant and dose dependent inhibition of edema induced by carrageenan at all doses when compared to the control groups. On the contrary, hexane extract of leaves did not show any activity up to 600 mg/kg i.p. The highest activity was showed in the aerial parts and roots that at 600 mg/kg i.p. inhibited inflammation by ca. 80% (78% for diclofenac at 100 mg /kg i.p.). No extracts exhibit toxicity when injected up to 2 g/ kg intraperitoneally in mice.     

Anti-anaphylactic effect of Euphorbia hirta

The Euphorbia hirta ethanolic extract (EH A001) was found to possess a prominent anti-anaphylactic activity. A preventive effect of EH-A001 given by oral route at dose from 100 to 1000 mg/kg was observed against compound 48/80-induced systemic anaphylaxis. At the same range of dose, EH-A001 inhibited passive cutaneous anaphylaxis (PCA) in rat and active paw anaphylaxis in mice. A suppressive effect of EH-A001 was observed on the release of TNF-alpha and IL-6 from anti-DNP-HSA activated rat peritoneal mast cells.     

Antidiarrhoeal activity of Cyperus rotundus

The methanol extract of Cyperus rotundus rhizome, given orally at the doses of 250 and 500 mg/kg b.w., showed significant antidiarrhoeal activity in castor oil induced diarrhoea in mice. Among the fractions, tested at 250 mg/kg, the petroleum ether fraction (PEF) and residual methanol fraction (RMF) were found to retain the activity, the latter being more active as compared to the control. The ethyl acetate fraction (EAF) did not show any antidiarrhoeal activity.     

Effect of Mitragyna speciosa aqueous extract on ethanol withdrawal symptoms in mice

Administration of the aqueous extract of Mitragyna speciosa at a dose of 300 mg/kg significantly inhibited ethanol withdrawal-induced behaviors that included rearing, displacement and head weaving. The results also showed that at doses of 100, 300 and 500 mg/kg M. speciosa showed antidepressant activity without effect on the spontaneous motor activity.     

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

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

Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide Krestin,a Trametes versicolor mushroom extract

Woody fungi and yeast preparations show promise in cancer treatment by activating anti-tumor immune responses. Macrophages (J774A.1) were treated with PSK, Reishi extract, scleroglucan or vehicle control. Pre-incubation with TLR4 blocking antibody inhibited TNF-alpha secretion by both J774A.1 cells and primary splenocytes but had inconclusive effect on scleroglucan-induced secretion of TNF-alpha. PSK induced TNF-alpha and IL-6 secretion by wild type but not by TLR4-deficient peritoneal macrophages. We conclude that constituents from PSK act as ligands for TLR4 receptors leading to induction of TNF-alpha and IL-6 inflammatory cytokines. Receptor-mediated differences may be due to structural differences in beta glucans or non-glucan constituents.     

Evaluation of central nervous system effects of iso-6-cassine isolated from Senna spectabilis var. excelsa (Schrad) in mice

The depressant and anticonvulsant activities of iso-6-cassine (ISO) from Senna spectabilis (0.5, 1.0 and 1.5 mg/kg) injected by oral route in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to 30 days after the administration and at dose of 1.5 mg/kg, it reduced the remaining time of animals on Rota-rod apparatus. Additionally, ISO at doses tested was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole and picrotoxin. These results suggest possible depressant and anticonvulsant activities in mice that need further investigation.     

Taiwanin A targets non-steroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma

Taiwanin A (α,β-bis(piperonylidene)-γ-butyrolactone) is extracted from Taiwania cryptomerioides. Taiwanin A is extracted from tree bark and exhibits antitumor activity in breast, liver, and lung cancer cell lines. The objective of this study was to demonstrate the cytotoxicity of Taiwanin A against tumor cells by increasing the expression of non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1). NAG-1 has been reported to exhibit antitumor and proapoptotic activities, suggesting potential use in cancer therapy. Inhibiting NAG-1 mRNA expression in A549 reduced the cytotoxicity caused by Taiwanin A. Furthermore, the c-Jun-N-terminal kinase/Ste20-related protein proline/alanine-rich kinase (JNK/SPAK) pathway played a key role in the influence of NAG-1 on cell viability, whereas the addition of the JNK pathway inhibitor SP600125 resulted in an inhibitory effect on NAG-1 and recovery of Taiwanin-A-treated cells. A xenograft tumor model demonstrated that Taiwanin A dose-dependently significantly decreases tumor-mediated growth in nude mice by increasing the NAG-1 expression accompanying tumor apoptosis. These data supported the hypothesis that Taiwanin A inhibits lung carcinoma growth by increasing NAG-1 expression through the JNK pathway both in vivo and in vitro. This result can contribute to a compound design for increasing cytotoxicity activity in the future.     

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

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

Effect of alcoholic extract of Ayurvedic herb Tinospora cordifolia on the proliferation and myeloid differentiation of bone marrow precursor cells in a tumor-bearing host

The present study investigates the effect of in vivo administration of alcoholic extract of Tinospora cordifolia whole plant (ALTC) on the proliferation and myeloid differentiation of bone marrow hematopoietic precursor cells in mice bearing a transplantable T cell lymphoma of spontaneous origin designated as Dalton's lymphoma (DL). BMC obtained from ALTC administered DL-bearing mice showed an enhanced BMC proliferation and colony forming ability in vitro in response to L929 conditioned medium as a source of colony stimulating factor (CSF). The number of granulocyte-macrophages colony (CFU-GM) was predominantly higher in the cultures of BMC obtained from ALTC administered mice as compared to mice injected with PBS alone. An increase in the count of bone marrow derived macrophages (BMDM) from ALTC administered mice was also observed along with an increase in the count of tumor associated macrophages. The BMDM obtained from ALTC administered mice showed an enhanced response to signal of LPS for activation to produce IL-1 and TNF. This study indicates that the T. cordifolia can influence the myeloid differentiation of bone marrow progenitor cells and the recruitment of macrophages in response to tumor growth in situ.     

Ocotea quixos Lam. essential oil: In vitro and in vivo investigation on its anti-inflammatory properties

Here we investigated the anti-inflammatory properties of Ocotea quixos essential oil and of its main components, trans-cinnamaldehyde and methyl cinnamate, in in vitro and in vivo models. Ocotea essential oil and trans-cinnamaldehyde but not methyl cinnamate significantly reduced LPS-induced NO release from J774 macrophages at non-toxic concentrations, inhibited LPS-induced COX-2 expression and increased forskolin-induced cAMP production. The essential oil (30–100 mg/kg os) and trans-cinnamaldehyde (10 mg/kg os) in carrageenan-induced rat paw edema showed anti-inflammatory effect without damaging gastric mucosa. In conclusion we provide the first evidence of a significant anti-inflammatory gastro-sparing activity of O.quixos essential oil.     

Anti-inflammatory activity of patchouli alcohol isolated from Pogostemonis Herba in animal models

Pogostemonis Herba has long been used in traditional Chinese medicine for the treatment of inflammatory disorders. Patchouli alcohol (PA), a tricyclic sesquiterpene isolated from Pogostemonis Herba, is known to possess a variety of pharmacological activities. The present study aimed to investigate the in vivo anti-inflammatory effect of PA using two common inflammatory animal models i.e., xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. The degree of edema in both inflammatory animals, as well as the protein and mRNA expression of some inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E₂ (PGE₂) and nitric oxide (NO) in the hind paw of carrageenan-treated rats were measured. Results showed that PA (10–40 mg/kg) significantly inhibited the ear edema induced by xylene in mice and the paw edema induced by carrageenan in rats. In addition, treatment with PA (10–40 mg/kg) also dose-dependently decreased the production of TNF-α, IL-1β, PGE₂ and NO in the hind paw of carrageenan-treated rats. Furthermore, PA treatment also suppressed the mRNA expression of TNF-α, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hind paw of carrageenan-treated rats. These results suggest that PA possesses potent anti-inflammatory activity, which may be mediated, at least in part, by down-regulating the mRNA expression of a panel of inflammatory mediators including TNF-α, IL-1β, iNOS and COX-2.     

Anti-inflammatory activity of Butea monosperma flowers

Methanolic extract of Butea monosperma flowers (MEBM) was studied for anti-inflammatory activity against carrageenin induced paw edema and cotton pellet granuloma in albino rats. In carrageenin induced paw edema, MEBM at oral doses of 600 mg/kg and 800 mg/kg, dose-dependently inhibited the paw edema. In cotton pellet induced granuloma, MEBM at the same doses was found to significantly inhibit granuloma tissue formation, including significant reduction in levels of serum lysosomal enzymes (SGOT, SGPT and ALP) and lipid peroxides as compared to control.     

Type 2 antidiabetic activity of bergenin from the roots of Caesalpinia digyna Rottler

Bergenin, a major constituent of Caesalpinia digyna Rottler (Leguminosae) was isolated from its roots and was characterized by comparing its melting point and spectroscopic data (IR, (1)H, (13)C, Mass Spectra) with standard bergenin. Isolated bergenin was then evaluated for antidiabetic (Type 2) activity in streptozotocin (STZ)-nicotinamide induced diabetic rats. Bergenin was administered at doses of 2.5, 5, and 10 mg/kg; p.o. to normal rats which were subjected to oral glucose tolerance test (OGTT). Bergenin at same dose level was given to diabetic rats and fasting blood glucose level was estimated on 0th, 7th and 14th day of treatment while plasma lipids, antioxidant enzymes and liver glycogen level in diabetic rats were estimated on 14th day of treatment followed by histopathological studies of pancreas. Bergenin at 10mg/kg; p.o. was found to reduce blood glucose level significantly in OGTT (P<0.01) while it showed a significant reduction in fasting blood glucose level in diabetic rats at same dose level only on 14th day of treatment. Bergenin in all dose levels reversed plasma lipid (reduced elevated TC, LDL-C and increased HDL-C level) profile to normal values except TG. However, bergenin showed no significant effect on liver glycogen at all dose level. The decrease in lipid peroxides and increase in superoxide dismutase (SOD) and catalase (CAT) in liver illustrated the antioxidant potential of bergenin. Histopathological studies demonstrated the regenerative effect of bergenin on pancreatic β cells. Hence, bergenin isolated from C. digyna possesses significant antidiabetic, hypolipidemic and antioxidant activity in Type 2 diabetic rats.     

Impact of Pueraria candollei var. mirifica and its potent phytoestrogen miroestrol on expression of bone-specific genes in ovariectomized mice

Miroestrol (MR) is a highly active phytoestrogen isolated from tuberous root of Pueraria candollei var. mirifica (PM). Modulatory effects of PM and MR on osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) mRNAs which are bone-specific genes were investigated in ovariectomized female ICR mice. After ovariectomy, expression of OPG mRNA was suppressed but that of RANKL was induced. Estradiol benzoate (E2) recovered OPG expression to the level comparable to the sham while that of RANKL was suppressed in ovariectomized mice. PM crude extract (PME) significantly down-regulated the expression of RANKL mRNA with no change in the OPG level whereas MR elevated the expression of OPG mRNA with lowering level of RANKL mRNA, resulting in the increased OPG/RANKL ratio, and consequently lead to lowering progression of osteoporosis at molecular level. These findings revealed potential of PME and MR on bone loss prevention via increasing the ratio of OPG to RANKL (osteoformation/osteoresorption) in liver of ovariectomized mice. Therefore, using PME and MR as alternative hormone replacement therapy of E2 might be beneficial recommended due to advantageous on regulation of osteoporosis related genes.