Meroterpenoids with unknown skeletons from the leaves of Psidium guajava including one anti-inflammatory and anticoagulant compound: psidial F.

Four unknown meroterpenoids named as psidials D-G (1-4) together with 5 known compounds (5-9) had been obtained from the leaves of Psidium guajava. Their absolute structures were elucidated by spectral and calculated methods. Psidials DF (1-3) represented unknown carbon skeleton of the 3,5-diformylbenzyl phloroglucinol-coupled sesquiterpenoid. The possible biosynthetic pathway for 1-3 was postulated. In the bioactivity assay, psidial F (3) was found to possess anti-inflammatory and anticoagulant activities.

Perilla Leaf Extract Attenuates Asthma Airway Inflammation by Blocking the Syk Pathway.

Perilla frutescens (L.) Britton is a classic herbal plant used widely against asthma in China. But its mechanism of beneficial effect remains undermined. In the study, the antiallergic asthma effects of Perilla leaf extract (PLE) were investigated, and the underlying mechanism was also explored. Results showed that PLE treatment significantly attenuated airway inflammation in OVA-induced asthma mice, by ameliorating lung pathological changes, inhibiting recruitment of inflammatory cells in lung tissues and bronchoalveolar lavage fluid (BALF), decreasing the production of inflammatory cytokines in the BALF, and reducing the level of immunoglobulin in serum. PLE treatment suppressed inflammatory response in antigen-induced rat basophilic leukemia 2H3 (RBL-2H3) cells as well as in OVA-induced human peripheral blood mononuclear cells (PBMCs). Furthermore, PLE markedly inhibited the expression and phosphorylation of Syk, NF-κB, PKC, and cPLA2 both in vivo and in vitro. By cotreating with inhibitors (BAY61-3606, Rottlerin, BAY11-7082, and arachidonyl trifluoromethyl ketone) in vitro, results revealed that PLE's antiallergic inflammatory effects were associated with the inhibition of Syk and its downstream signals NF-κB, PKC, and cPLA2. Collectively, the present results suggested that PLE could attenuate allergic inflammation, and its mechanism might be partly mediated through inhibiting the Syk pathway.

Perilla Leaf Extract (PLE) Attenuates COPD Airway Inflammation via the TLR4/Syk/PKC/NF-κB Pathway In Vivo and In Vitro.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by persistent airflow limitation but still lacking effective treatments. Perilla frutescens (L.) Britt., an important traditional medicinal plant with excellent antioxidant and anti-inflammatory properties, is widely used for the treatment of respiratory disease in China. However, its protective activity and mechanism against COPD airway inflammation have not been fully studied. Here, the anti-inflammatory effects of the PLE were investigated, and its underlying mechanisms were then elucidated. The presented results suggested a notable effect of the PLE on airway inflammation of COPD, by significantly ameliorating inflammatory cell infiltration in lung tissue, lessening leukocytes (lymphocytes, neutrophils, and macrophages) and inflammatory mediators (interleukin 4 (IL-4), IL-6, IL-17A, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α)) in the bronchoalveolar lavage fluid (BALF) of cigarette smoke (CS)/lipopolysaccharide (LPS)-induced COPD mice in vivo and inhibiting the production of inflammatory factors (nitric oxide (NO), IL-6, and TNF-α) and intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells in vitro. For further extent, PLE treatment significantly suppressed the expression and phosphorylation of TLR4, Syk, PKC, and NF-κB p65 in vivo and their mRNA in vitro. Subsequently, by co-treating with their inhibitors in vitro, its potential mechanism via TLR4/Syk/PKC/NF-κB p65 signals was disclosed. In summary, the obtained results indicated a noteworthy effective activity of the PLE on COPD inflammation, and partly, the TLR4/Syk/PKC/NF-κB p65 axis might be the potential mechanism.

Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk.

BACKGROUND: Perilla frutescens (L.) Britt., a classic medicinal plant, has been demonstrated to have anti-inflammatory and anti-allergic effects in asthma. Perilla leaves extract (PLE) exerted significant therapeutic effect against allergic asthma inflammation through Syk inhibition. But the active chemical ingredients from PLE are complex and unclear, it is difficult to fully elucidate its pharmacological mechanisms. METHODS: A method was established for rapid screening and characterization of active ingredients from PLE that targeted Syk, with which three potential active ingredients were identified. By using OVA-induced allergic asthma mouse model in vivo, OVA-induced human PBMCs inflammation model and DNP-IgE/BSA-induced RBL-2H3 cells model in vitro, the effects and mechanisms of PLE and its active components were evaluated. RESULTS: Using Syk-affinity screening method, roseoside (RosS), vicenin-2 (Vic-2) and rosmarinic acid (RosA) were identified from PLE. In vitro, PLE and its ingredients showed significant inhibitory activities against Syk, with their mixture (Mix, prepared by RosS, Vic-2 and RosA in accordance with their ratio in Syk-conjugated beads bound fraction) showing a stronger inhibitory activity. RosS, Vic-2 and RosA also showed significant effects on allergic asthma, and a synergistic effect of Mix was observed. Moreover, treatment with PLE, RosS, Vic-2, RosA, and Mix significantly inhibited the expression and phosphorylation of Syk, PKC, NF-κB p65, and cPLA2 in allergic mice lung tissue and in RBL-2H3 cells. CONCLUSION: PLE may alleviate allergic airway inflammation partly through the multiple components synergistic targeting on Syk and its downstream inflammatory pathway.

Beneficial Effects of Qingzixiaoban Granule on Henoch-Schönlein Purpura Nephritis Mice through Inhibiting Immune Complex Deposition and Th2 Immunodeviation.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is the principal cause of morbidity and mortality in Henoch-Schönlein purpura (HSP). However, there is no absolute consensus for the best management of severe HSPN till now. Qingzixiaoban Granule (QZXB GR), a traditional Chinese medicine formula, has been applied to treat HSP in clinical in China. However, the therapeutic effects and potential mechanism of QZXB GR on HSPN is still unknown. METHODS: A Gliadin plus Indian Ink-induced HSPN mice model was established. Renal histopathologic changes and the subcutaneous hemorrhage on left legs were assessed. Hematuria and proteinuria were determined using hemocytometer and bicinchoninic acid assay, respectively. The serum circular immune complex and interleukin-6 were quantified by ELISA. Using blood biochemical analyzer, the renal biochemical parameters, including serum total protein, albumin, creatinine, and blood urea nitrogen, were measured. The deposition of immune complex in renal tissues and the lymphocyte subsets in peripheral blood and spleen was investigated by immunohistochemistry and flow cytometry. RESULTS: QZXB GR treatment significantly ameliorated renal injury in HSPN mice, by attenuating renal histopathological changes, reducing subcutaneous hemorrhage, decreasing proteinuria/hematuria, regulating renal biochemical parameters, and inhibiting the release of serum interleukin-6. Furthermore, QZXB GR treatment significantly decreased the level of serum circular immune complex, decreased immune complex IgA and IgG deposition in renal tissue, and suppressed Th2 immunodeviation. CONCLUSION: QZXB GR could prevent renal injury in HSPN mice, and its renoprotective mechanism might be exerted partly through suppressing immune complexes deposition and Th2 immune deviation.

Structural characterization and immunological activity of polysaccharides from the tuber of Bletilla striata.

Two water-soluble polysaccharides, BSP-1 and BSP-2, were extracted and purified from the tuber of Bletilla striata. The molecular weights of BSP-1 and BSP-2 were 83.54 kDa and 12.60 kDa, respectively. The composition and proportion of BSP-1 and BSP-2 were mannose and glucose in molar ratios of 4.0:1.0 and 3.0:1.0 respectively. The two polysaccharides had a linear backbone, consisting mainly of repeating ß­1,4­linked d­mannosyl residues and ß­1,4­linked d­glucosyl residues. BSP-1 exhibited immunomodulatory effects by increasing the thymus and spleen indices of immunocompromised model mice.

New triterpenoid saponins from the leaves of Ilex chinensis.

Eight new triterpenoid saponins, including four ursane-type saponins, ilexchinenosides J-M (1-4), and four oleanane-type saponins, ilexchinenosides N-Q (5-8), along with three known triterpenoid saponins (9-11) were isolated from the leaves of Ilex chinensis Sims. Their structures were established by 1D, 2D NMR and MS spectroscopic analyses and through comparisons with known compounds. Moreover, compounds 1, 3, 5, 7-9 and 11 exhibited significant levels of hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in in vitro assays while compound 10 had moderately inhibitory effects on the NO production of lipopolysaccharide (LPS)-induced murine macrophages.

Diterpenoids and lignans from the leaves of Tripterygium wilfordii.

Three new diterpenoids (1-3) and three new esterifying lignans (4-6) were isolated from the leaves of Tripterygium wilfordii. The structures of these compounds were elucidated on the basis of spectroscopic techniques (UV, IR, NMR, HRESIMS, and ECD method). At 10 µmol/L, compounds 4-6 showed moderate inhibitory effects on nitric oxide production in LPS-induced macrophages with inhibitory rate >80%.

3-Hydroxy-3-methylglutaryl flavone glycosides from the leaves of Turpinia arguta.

Three new 3-hydroxy-3-methylglutaryl (HMG) flavone 7-O-diglycosides, argutosides A-C (1-3); two new flavone 7-O-triglycosides, argutosides D-E (4-5); and one known apigenin 7-O-triglycoside (6), were isolated from the leaves of Turpinia arguta. The structures of these compounds were elucidated by spectroscopic and chemical techniques. The NO inhibitory activities of compounds 1-6 were evaluated using lipopolysaccharide-induced RAW264.7 cells. Only compound 2 showed a moderate inhibitory effect on NO production with an IC50 value of 25.74µM. Compounds 1-6 were not cytotoxic to RAW264.7 cells at 10µM.

Ginsenoside Rg1 protects against transient focal cerebral ischemic injury and suppresses its systemic metabolic changes in cerabral injury rats.

Ginsenoside Rg1 (GR), a major bioactive compound of traditional Chinese medicine, such as Panax ginseng or Radix Notoginseng, has been shown to exert neuroprotective effects against ischemic stroke. However, pharmacokinetic studies have suggested that GR could not be efficiently transported through the blood-brain barrier. The mechanism by which GR attenuates cerebral ischemic injury in vivo remains largely unknown. Therefore, this study explored potential neuro-protective effects of GR through its systemic metabolic regulating mechanism by using mass spectrometry-based metabolomic profiling. Rats with middle cerebral artery occlusion (MCAO) were treated with GR intravenously. Their metabolic profiles in serum were measured by gas chromatography coupled with mass spectrometry on 1 and 3 days after MCAO. GR exhibited a potent neuro-protective effect by significantly decreasing the neurological scores and infarct volume in the MCAO rats. Moreover, 18 differential metabolites were tentatively identified, all of which appeared to correlate well with these disease indices. Our findings suggested that GR carries a therapeutic potential in stroke possibly through a feed-back mechanism by regulating systematic metabolic mediation.

Bioactive Sesquiterpenes and Lignans from the Fruits of Xanthium sibiricum.

Seven new sesquiterpenes (1, 3-8), a new sesquiterpene natural product (2), and two new lignans (9 and 10), together with 15 known compounds, were isolated from the fruits of Xanthium sibiricum. The structures of the new compounds were established by NMR spectroscopic analysis, ECD calculations, and Mo2(OAc)4-induced circular dichroism, with the structures of 1 and 4 confirmed by single-crystal X-ray diffraction. Compound 1 is the first example of a 3/5/6/5 tetracyclic eudesmane sesquiterpene lactone formed at C-6 and C-7. In turn, compound 4 is the first example of a natural xanthane tetranorsesquiterpene, while compounds 5-8 are the first xanthane trinorsesquiterpenes found to date. Compounds 8, 11-15, 17, and 24 exhibited indirect anti-inflammatory activity by suppressing the lipopolysaccharide-induced proinflammatory factors in BV2 microglial cells, with IC50 values between 1.6 and 8.5 µM. Furthermore, compounds 13 and 17 exhibited anti-inflammatory activity against ear edema in mice produced by croton oil, with inhibition rates of 46.9% and 37.7%, respectively. Compounds 8, 11, 12, 23, and 24 exhibited potent activity against influenza A virus (A/FM/1/47, H1N1) with IC50 values between 3.7 and 8.4 µM.

Methylophiopogonanone A Protects against Cerebral Ischemia/Reperfusion Injury and Attenuates Blood-Brain Barrier Disruption In Vitro.

Methylophiopogonanone A (MO-A), an active homoisoflavonoid of the Chinese herb Ophiopogon japonicus which has been shown to have protective effects on cerebral ischemia/reperfusion (I/R) injury, has been demonstrated to have anti-inflammatory and anti-oxidative properties. However, little is known about its role in cerebral I/R injury. Therefore, in this study, by using a middle cerebral artery occlusion (MCAO) and reperfusion rat model, the effect of MO-A on cerebral I/R injury was examined. The results showed that MO-A treatment reduced infarct volume and brain edema, improved neurological deficit scores, reversed animal body weight decreases, and increased animal survival time in the stroke groups. Western blotting showed that MO-A suppressed MMP-9, but restored the expression of claudin-3 and claudin-5. Furthermore, transmission electron microscopy were monitored to determine the blood-brain barrier (BBB) alterations in vitro. The results showed that MO-A markedly attenuated BBB damage in vitro. Additionally, MO-A inhibited ROS production in ECs and MMP-9 release in differentiated THP-1 cells in vitro, and suppressed ICAM-1 and VCAM-1 expression in ECs and leukocyte/EC adhesion. In conclusion, our data indicate that MO-A has therapeutic potential against cerebral I/R injury through its ability to attenuate BBB disruption by regulating the expression of MMP-9 and tight junction proteins.

Anti-inflammatory Hydrolyzable Tannins from Myricaria bracteata.

Twelve hydrolyzable tannins were obtained from the twigs of Myricaria bracteata, including two new hellinoyl-type dimers, bracteatinins D1 (1) and D2 (2); a new hellinoyl-type trimer, bracteatinin T1 (3); two known monomers, nilotinin M4 (4) and 1,3-di-O-galloyl-4,6-O-(aS)-hexahydroxydiphenoyl-ß-d-glucose (5); six known dimers, tamarixinin A (6), nilotinin D8 (7), hirtellins A (10), B (9), and E (8), and isohirtellin C (11); and a known trimer, hirtellin T3 (12). The structures of the tannins were elucidated by spectroscopic data analysis and comparisons to known tannins. All compounds were evaluated as free radical scavengers using 1,1-diphenyl-2-picrylhydrazyl and hydroxy radicals and compared to the activity of BHT and Trolox. Compound 6 showed a significant anti-inflammatory effect on croton oil-induced ear edema in mice (200 mg/kg, inhibition rate 69.8%) and on collagen-induced arthritis in DBA/1 mice (20 mg/kg, inhibition rate 46.0% at day 57).

New triterpenoid saponins from the aerial parts of Comastomapedunculatum.

Three new saikosaponin analogs, comastomasaponins I-K (1-3), were isolated from the aerial portions of Comastomapedunculatum. The structures of these compounds were elucidated on the basis of spectroscopic data analysis, and their nitric oxide production inhibitory activity was evaluated invitro.

FLLL31, a derivative of curcumin, attenuates airway inflammation in a multi-allergen challenged mouse model.

Signal transducer and activator of transcription protein 3 (STAT3), one of the major regulators of inflammation, plays multiple roles in cellular transcription, differentiation, proliferation, and survival in human diseases. Dysregulation of STAT3 is related to the severe airway inflammation associated with asthma. FLLL31 is a newly developed compound based on the herbal medicine curcumin, which specifically suppresses the activation of STAT3. However, the function of FLLL31 on inflammatory diseases, especially on the regulation of airway inflammation, has not been fully studied. In our prior investigations, we developed a mouse model that was challenged with a mixture of DRA allergens (including house dust mite, ragweed, and Aspergillums species) to mimic the severe airway inflammation observed in human patients. In this study, we performed a series of experiments on the inflammatory regulation activities of FLLL31 in both in vitro cultured cells and our in vivo DRA-challenged mouse model. Our results show that FLLL31 exhibits anti-inflammatory effects on macrophage activation, lymphocyte differentiation, and pro-inflammatory factor production. Importantly, FLLL31 significantly inhibited airway inflammation and recruitment of inflammatory cells in the DRA-challenged mouse model. Based on these results, we conclude that FLLL31 is a potential therapeutic agent that can be used against severe airway inflammation diseases.

Historical perspective of traditional indigenous medical practices: the current renaissance and conservation of herbal resources.

In recent years, increasing numbers of people have been choosing herbal medicines or products to improve their health conditions, either alone or in combination with others. Herbs are staging a comeback and herbal "renaissance" occurs all over the world. According to the World Health Organization, 75% of the world's populations are using herbs for basic healthcare needs. Since the dawn of mankind, in fact, the use of herbs/plants has offered an effective medicine for the treatment of illnesses. Moreover, many conventional/pharmaceutical drugs are derived directly from both nature and traditional remedies distributed around the world. Up to now, the practice of herbal medicine entails the use of more than 53,000 species, and a number of these are facing the threat of extinction due to overexploitation. This paper aims to provide a review of the history and status quo of Chinese, Indian, and Arabic herbal medicines in terms of their significant contribution to the health promotion in present-day over-populated and aging societies. Attention will be focused on the depletion of plant resources on earth in meeting the increasing demand for herbs.

Effect of Tianshengyuan-1 (TSY-1) on telomerase activity and hematopoietic recovery - in vitro, ex vivo, and in vivo studies.

Aplastic anemia is a heterogeneous disorder of bone marrow failure syndrome. Accumulating evidence indicates that both acquired and congenital aplastic anemia is linked to telomerase activity and telomere length. Chinese herbal medicine Tianshengyuan-1 (TSY-1), a liquid extraction of multiple Chinese herbs, appears to stimulate hematopoiesis in patients with bone marrow deficiencies; however, the exact mechanism of action remains unclear. In this study, we investigated the effect of TSY-1 on telomere length and telomerase activity. We first investigated the effects of TSY on in vitro cultured cell lines including CD34+ hepatic stem cells and CD4+/CD8- Jurkat cells. An immune-mediated murine aplastic anemia model and human samples, including peripheral blood samples of 4 healthy donors and bone marrow hematopoietic cells from 4 patients with hypocellular myelodysplastic syndrome (MDS), were also used to test the efficacy of TSY on hematopoiesis, telomerase activity and telomere length. Our results indicated that TSY-1 increased the telomerase activity and telomere length in a dose-response manner in vitro, in vivo, and in human samples including 3 of 4 healthy individuals and 3 of 4 bone marrow samples from MDS patients. In immune-mediated murine aplastic anemia model, TSY-1 activity on Telomere length was parallel to the significant increasing of the RBC, hemoglobin, hematocrit, and platelet count in peripheral blood, increasing of CD34+ cell count and hematopoiesis, and decreasing of fatty infiltration in bone marrow samples. Our study demonstrated that TSY-1 may exert its effects by modulating telomerase activity of hematopoietic cells. Further studies are warranted to explore the precise molecular mechanisms of how TSY-1 regulates telomerase activity and telomere length, and also to test the TSY-1 in randomized control trials.

Bioactive sesquiterpene polyol esters from the leaves of Tripterygium wilfordii.

Tripterygium wilfordii, a member of Celastraceae family, has been used as a traditional plant insecticide and a medicinal plant. Phytochemical investigation of the leaves of T. wilfordii has resulted in the isolation of eight sesquiterpene polyol esters triptersinines M-T (1-8) and one sesquiterpene pyridine alkaloid (9). The structures of the compounds were elucidated on the basis of spectroscopic data analyses, including UV, IR, MS, and NMR experiments. The inhibitory effects on nitric oxide production in LPS-induced macrophages of 1-9 were also evaluated.

Five new compounds from Rhododendron mariae Hance.

Five new compounds (-)-(7R,8S,7'R,8'S)-4,9,4',9'-tetrahydroxy-3,3'-dimethoxy-7,7'-epoxylignan 9-O-ß-d-xylopyranoside (1), (-)-(7'R,8'S)-5'-methoxyl(dimeric coniferyl acetate) (2), (+)-(1R,2S)-1,2-bis(4-hydroxy-3-methoxyphenyl)-3-acetyl-1,3-propanediol (3), (-)-3-((2R,3R)-2-ethoxy-3-(hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl)propan-1-ol (4), and (+)-3-((2S,3S)-2-ethoxy-3-(hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl)propan-1-ol (5), together with 12 known compounds, were isolated from an ethanol extract of the dried stems of Rhododendron mariae Hance. Their structures were elucidated by NMR, HR-MS, CD, ORD experiments and chemical methods. Compounds 2, 3, 6, and 17 exhibited significant inhibitory effects on the nitric oxide production in lipopolysaccharide activated C57BL6/J mouse macrophages.