Kalopanaxsaponin B Ameliorates TNBS-Induced Colitis in Mice.

The stem-bark of Kalopanax pictus (KP, family Araliaceae), of which main constituent is kalopanaxsaponin B, has been used for asthma, rhinitis, and arthritis in Chinese traditional medicine. To clarify anticolitic effect of KP, we examined anti-inflammatory effect of KP extract and kalopanaxsaponin B in lipopolysaccharide (LPS)-stimulated peritoneal macrophage and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice. Of KP extracts, KP BuOH-soluble fraction most potently inhibited LPS-induced IL-1β, IL-6 and TNF-α expression, as well as NF-κB activation.

Lactobacillus casei HY7213 ameliorates cyclophosphamide-induced immunosuppression in mice by activating NK, cytotoxic T cells and macrophages.

Lactic acid bacteria (LAB) have recently attracted considerable attention as treatment options for immune diseases, the incidence of which has been increasing worldwide. The ability of tumor necrosis factor-α producing LAB isolated from cheese to inhibit NF-κB activation in lipopolysaccharide (LPS)-stimulated peritoneal macrophages was investigated. Among the tested LAB, Lactobacillus casei HY7213 inhibited NF-κB activation most potently.

Inhibitory effect of echinocystic acid on 12-O-tetradecanoylphorbol-13-acetate-induced dermatitis in mice.

The rhizome of Codonopsis lanceolata (family Campanulaceae), which contains lancemaside A as a main constituent, is frequently used in the traditional Chinese medicine for the treatment of inflammatory diseases. Lancemaside A exhibits anti-inflammatory effect in vitro and in vivo. However, orally administered lancemaside A is metabolized to echinocystic acid by the intestinal microflora and the metabolite is absorbed into the blood.

Lactobacillus plantarum HY7712 ameliorates cyclophosphamide-induced immunosuppression in mice.

Lactic acid bacteria (LAB) in fermented foods have attracted considerable attention recently as treatment options for immune diseases, the incidence of which has been increasing worldwide. The ability of 500 strains of LAB, isolated from kimchi, to induce TNF--α production in peritoneal macrophages was investigated. Lactobacillus plantarum HY7712 most strongly induced TNF--α production as well as NF-κB activation.

Synthesis, characterization and Akt phosphorylation inhibitory activity of cyclopentanecarboxylate-substituted alkylphosphocholines.

Akt is activated in most human cancers and contributes to cell growth, proliferation and cellular survival pathway. Accordingly, it is an attractive target for anticancer therapy. A series of novel alkylphosphocholines, incorporating cyclopentanecarboxylate in the phospholipid head group with trans and cis orientations, were synthesized and evaluated for their Akt phosphorylation inhibitory activities and cytotoxicities against human cancer cell lines, A549, MCF-7 and KATO III.

Echinocystic acid, a metabolite of lancemaside A, inhibits TNBS-induced colitis in mice.

The rhizome of Codonopsis lanceolata (CL, family Campanulaceae), of which the main constituent is lancemaside A, has been used for cough and bronchitis in traditional Chinese medicine. To evaluate anti-colitic effect of CL, we examined anti-inflammatory effect of CL extracts, lancemaside A and its metabolites in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice. Among CL extracts, CL BuOH extract inhibited LPS-induced IL-1β, IL-6 and TNF-α expression, as well as NF-κB activation most potently.

Pleckstrin homology domain of Akt kinase: a proof of principle for highly specific and effective non-enzymatic anti-cancer target.

While pharmacological inhibition of Akt kinase has been regarded as a promising anti-cancer strategy, most of the Akt inhibitors that have been developed are enzymatic inhibitors that target the kinase active site of Akt. Another key cellular regulatory event for Akt activation is the translocation of Akt kinase to the cell membrane from the cytoplasm, which is accomplished through the pleckstrin homology (PH) domain of Akt. However, compounds specifically interacting with the PH domain of Akt to inhibit Akt activation are currently limited.

Kalopanaxsaponin B inhibits LPS-induced inflammation by inhibiting IRAK1 Kinase.

The stem bark of Kalopanax pictus Nakai (KP, family Araliaceae), of which main constituent is kalopanaxsaponin B, has been used for inflammation in Chinese traditional medicine. We isolated kalopanaxsaponin B from KP and investigated its anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and on LPS-stimulated systemic inflammation in male ICR mice. Kalopanaxsaponin B inhibited the expression of TNF-α, IL-1β, iNOS and COX-2 in LPS-stimulated peritoneal macrophages.

High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway.

Background & Aims: While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet.

Methods: C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high-fat (60 kcal % fat) diet (HFD) for 8 weeks.

Lancemaside A isolated from Codonopsis lanceolata and its metabolite echinocystic acid ameliorate scopolamine-induced memory and learning deficits in mice.

The rhizome of Codonopsis lanceolata (family Campanulaceae), which contains lancemaside A as a main constituent, has been used as herbal medicine to treat inflammation, insomnia, and hypomnesia. Lancemaside A and echinocystic acid, which is its metabolite by intestinal microflora, potently inhibited acetylcholinesterase activity in a dose-dependent manner, with IC₅₀ value 13.6 μM and 12.

Antibiotics attenuate anti-scratching behavioral effect of ginsenoside Re in mice.

Ethnopharmacological Relevance: The root of Panax ginseng CA Meyer (ginseng) has been used for diabetes, cancer, stress and allergic diseases in the traditional Chinese medicine.

Aim Of The Study: To understand the role of intestinal microflora in the pharmacological effect of ginsenoside Re, which is a main constituent of ginseng, we investigated its anti-scratching behavioral effect in the mice treated with or without antibiotics.

Materials And Methods: Ginsenoside Re was orally administered to the mice treated with antibiotics (cefadroxil, oxytetracycline and erythromycin mixture (COE), streptomycin or/and tetracycline) and then investigated the relationship between ginsenoside Re-metabolizing β-glucosidase and α-rhamnosidase activities of intestinal microflora and its antiscratching behavioral effect.

Echinocystic acid ameliorates lung inflammation in mice and alveolar macrophages by inhibiting the binding of LPS to TLR4 in NF-κB and MAPK pathways.

Orally administered lancemaside A, which is isolated from Codonopsis lanceolata (family Campanulaceae), showed anti-colitic effect in mice. However, its metabolite echinocystic acid was absorbed into the blood. Therefore, its anti-inflammatory effects were investigated in lipopolysaccharide (LPS)-stimulated alveolar macrophages in vitro and acute lung injury in vivo.

Synthesis and biological evaluation of cyclopentane-linked alkyl phosphocholines as potential anticancer agents that act by inhibiting Akt phosphorylation.

Three new series of novel alkylphosphocholine (APC) derivatives containing a cyclopentane ring near the phosphocholine head group were synthesized. In the first set of analogues, the phosphocholine head group was attached to the secondary alcohol of trans-2-(hydroxymethyl)cyclopentanol, whereas in the second and third sets of analogues, the phosphocholine head group was linked to the primary alcohol of trans- and cis-2-(hydroxymethyl)cyclopentanol, respectively. Of the compounds synthesized, compound 6d most potently inhibited Akt phosphorylation with an IC(50) value of 3.

Ginsenoside Rg5 ameliorates lung inflammation in mice by inhibiting the binding of LPS to toll-like receptor-4 on macrophages.

Heating and steaming processes have been applied to various natural medicines for either enhancing or altering their pharmacological activities, and the chemical compositions of the active components. While ginsenoside Rb1, which is the major constituent of raw ginseng, has been studied extensively for its anti-inflammatory effect, the biological activity of ginsenoside Rg5, a major constituent of steamed ginseng, remains to be explored. Here, we isolated Rg5 and examined anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated macrophages and on LPS-induced lung inflammation.

Soyasaponin Ab ameliorates colitis by inhibiting the binding of lipopolysaccharide (LPS) to Toll-like receptor (TLR)4 on macrophages.

Many clinical studies have shown that daily intake of soybean [ Glycine max (L.) Merr., Fabacease] or its foods may reduce the risk of osteoporosis, heart attack, hyperlipidemia, coronary heart disease, cardiovascular and chronic renal diseases, and cancers, including prostate, colon, and breast cancers.

Kalopanaxsaponins A and B isolated from Kalopanax pictus ameliorate memory deficits in mice.

The stem-bark of Kalopanax pictus (KP, family Araliaceae), which contains triterpenoid saponins, has been shown to exhibit anticarcinogenic, antiinflammatory, antirheumatoid and antidiabetic activities. In a preliminary study, a KP methanol extract demonstrated acetylcholinesterase activity in vitro and memory enhancement in scopolamine-treated mice. Therefore, we isolated acetylcholinesterase inhibitors, kalopanaxsaponins A and B, from a KP butanol (BuOH) fraction, measured acetylcholinesterase activity in vitro, and investigated their memory-enhancing effects in a passive avoidance test, Y-maze test and Morris water maze test.

Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation--the key step of inflammation.

In the preliminary study, ginsenoside Rb1, a main constituent of the root of Panax ginseng (family Araliaceae), and its metabolite compound K inhibited a key factor of inflammation, nuclear transcription factor κB (NF-κB) activation, in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. When ginsenoside Rb1 or compound K were orally administered to 2,4,6-trinitrobenzene sulfuric acid (TNBS)-induced colitic mice, these agents inhibited colon shortening, macroscopic score, and colonic thickening. Furthermore, treatment with ginsenoside Rb1 or compound K at 20mg/kg inhibited colonic myeloperoxidase activity by 84% and 88%, respectively, as compared with TNBS alone (p<0.

Gypenoside TN-2 ameliorates scopolamine-induced learning deficit in mice.

Ethnopharmacological Relevance: Gynostemma pentaphyllum (Thunb.) Makino (GP, family Cucurbitaceae), which contains dammarane saponins as its main constituents, is used in China, Japan, and Korea as a traditional medicine to treat cancer, obesity, arteriosclerosis, asthma and senility.

Aim Of The Study: To investigate the memory-enhancing effects of GP, Gypenoside TN-2 (TN-2) was isolated by activity-guided fractionation and administered to scopolamine-induced memory-deficient mice.

Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice.

The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity.

Kalopanaxsaponin A ameliorates experimental colitis in mice by inhibiting IRAK-1 activation in the NF-κB and MAPK pathways.

Background And Purpose: Kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus (family Araliaceae), potently inhibited nuclear factor-kappa B (NF-κB) activation in lipopolysaccharide (LPS)-stimulated peritoneal macrophages during a screening programme for anti-colitis agents from natural products. Its anti-inflammatory mechanism remains unknown. Therefore, we investigated its anti-inflammatory effects in lipopolysaccharide (LPS)- or peptidoglycan-stimulated murine peritoneal macrophages and trinitrobenzene sulphonic acid (TNBS)-induced colitic mice.

Tanshinones isolated from the rhizome of Salvia miltiorrhiza inhibit passive cutaneous anaphylaxis reaction in mice.

Ethnopharmacological Relevance: The rhizome of Salvia miltiorrhiza Bunge (SM, family Labiatae), which contains tanshinones as main constituents, has been used as a cardiovascular and anti-inflammatory agent in Chinese medicine.

Aim Of The Study: This study aimed to elucidate anti-allergic effects of the root of Salvia miltiorrhiza Bunge (SM, family Labiatae) and its main constituents, tanshinones, against passive cutaneous anaphylaxis (PCA) reaction.

Materials And Methods: PCA reaction was induced by IgE-antigen complex (IAC) in ICR mice.

Lancemaside A inhibits lipopolysaccharide-induced inflammation by targeting LPS/TLR4 complex.

In our previous study, lancemaside A isolated from Codonopsis lanceolata (family Campanulaceae) ameliorated colitis in mice. In this study, the anti-inflammatory effects of lancemaside A was investigated in lipopolysaccharide (LPS)-stimulated mice and their peritoneal macrophage cells. Lancemaside A suppressed the production of pro-inflammatory cytokines, TNF-α and IL-1β, in vitro and in vivo.

A sensitive liquid chromatography-electrospray tandem mass spectrometric method for lancemaside A and its metabolites in plasma and a pharmacokinetic study in mice.

A high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method employing electrospray ionization (ESI) has been developed for simultaneous determination of lancemaside A (3-O-beta-D-glucuronopyranosyl-3beta, 16alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl ester) and its metabolites in mouse plasma. When lancemaside A (60 mg/kg) was orally administered to mice, echinocystic acid was detected in the blood. T(max) and C(max) of the echinocystic acid were 6.

Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice.

Aim: To explore whether intestinal microflora plays a role in anti-pruritic activity of baicalin, a main constituent of the rhizome of Scutellaria baicalensis (SB).

Methods: Baicalin was anaerobically incubated with human fecal microflora, and its metabolites, baicalein and oroxylin A, were isolated. The inhibitory effect of baicalin and its metabolites was accessed in histamine- or compound 48/80-induced scratching behavior in mice.

Liquid chromatography/mass spectrometry-based structural analysis of soyasaponin Ab metabolites by human fecal microflora.

Soyasaponin Ab, a major constituent of soybean by human intestinal microflora, was anaerobically incubated with fecal suspensions from ten individuals for 48 h and its metabolites were measured by LC-MS/MS analysis. Ten metabolites were detected. The spectra of the parental constituent soyasaponin Ab showed a peak at m/z 1435 [M-H](-) ion and those of its nine metabolites showed peaks at m/z 1310.