Rosmarinic acid Ameliorates neuronal regeneration in the bridging silicone rubber conduits of the sciatic nerve in taxol-treated rats.

Background and aim: Taxol modulates local inflammatory conditions in peripheral nerves, which may impair their regeneration and recovery when injured. This study aimed to determine the effects of rosmarinic acid (RA, a polyphenol constituent of many culinary herbs) on the regeneration of the sciatic nerves in the bridging conduits. Experimental procedure: In the cell study, RA decreased nuclear factor (NF)-κB activity induced by taxol in a dose dependency. In the animal model, taxol-treated rats were divided into 3 groups (n = 10/group): taxol (2 mg/kg body weight for 4 times) and taxol + RA (3 times/week for 4 weeks at 20 and 40 mg/kg body weight) groups. Macrophage infiltration, calcitonin gene-related peptide (CGRP) expression levels, neuronal connectivity, animal behavior, and neuronal electrophysiology were evaluated. Results and conclusion: At the end of 4 weeks, macrophage density, CGRP expression level, and axon number significantly increased in the RA group compared with the taxol group. The RA administration unaffected heat, cold plate licking latencies, and motor coordination. Moreover, the 40 mg/kg RA group had significantly larger nerve conduction velocity and less latency compared to the taxol group. This study suggested that RA could ameliorate local inflammatory conditions to augment the recovery of regenerating nerves by accelerating their regrowth and improving electrophysiological function in taxol-treated peripheral nerve injury repaired with the silicone rubber conduit.

Screening and rational identification of a novel angiotensin-converting enzyme C-domain inhibitory peptide from Fabaceae food peptide library.

Angiotensin-converting enzyme (ACE), consisting of N-domain and C-domain, is a key regulator of blood pressure. The use of cACE-specific inhibitors helps minimize side effects in clinical applications. Legumes are a good source of proteins containing ACE inhibitory peptides; however, no studies have reported the identification of cACE-specific inhibitory peptides from Fabaceae. In this study, thermal hydrolysates from seeds, sprouts, pods, seedlings, and flowers of legumes were analyzed. Flowers of legumes exhibited a C-domain-preference ACE inhibition and anti-hypertensive effect in rats. Screening the legume peptide library identified a novel cACE inhibitory peptide, SJ-1. This study reported the first identification of cACE inhibitory peptide from Fabaceae foods. SJ-1, identified from the legume flowers, interacted with active site residues of cACE, leading to the inhibition of ACE activity, downregulation of bradykinin levels, and reduction of blood pressure. These findings also suggested the potential of legume proteins as a source of cACE inhibitory peptides.

Analysis of target organs of Houttuynia cordata: A study on the anti-inflammatory effect of upper respiratory system.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (HC) is a traditional anti-pyretic herb that is classified as the lung meridian in traditional Chinese medicine. However, no articles have explored the main organs responsible for the anti-inflammatory activities of HC. AIM OF THE STUDY: The aim of the study was to investigate the meridian tropism theory of HC in lipopolysaccharide (LPS)-induced pyretic mice, as well as to identify the underlying mechanisms. MATERIALS AND METHODS: Transgenic mice carrying the luciferase gene driven by nuclear factor-κB (NF-κB) were intraperitoneally injected with LPS and orally administered standardized concentrated HC aqueous extract. The phytochemicals present in the HC extract were analyzed using high-performance liquid chromatography. In vivo and ex vivo luminescent imaging from transgenic mice was used to investigate the meridian tropism theory and anti-inflammatory effects of HC. Microarray analysis of gene expression patterns was used to elucidate the therapeutic mechanisms of HC. RESULTS: HC extract was found to contain phenolic acids, such as protocatechuic acid (4.52%) and chlorogenic acid (8.12%), as well as flavonoids like rutin (2.05%) and quercitrin (7.73%). The bioluminescent intensities induced by LPS in the heart, liver, respiratory system, and kidney were significantly suppressed by HC, while the maximal decrease (about 90% reduction) of induced luminescent intensity was observed in the upper respiratory tract. These data suggested that upper respiratory system might be the target for HC anti-inflammatory abilities. HC affected the processes involved in innate immunity, such as chemokine-mediated signaling pathway, inflammatory response, chemotaxis, neutrophil chemotaxis, and cellular response to interleukin-1 (IL-1). Moreover, HC significantly reduced the proportions of p65-stained cells and the amount of IL-1ß in trachea tissues. CONCLUSION: Bioluminescent imaging coupled with gene expression profile was used to demonstrate the organ selectivity, anti-inflammatory effects, and therapeutic mechanisms of HC. Our data demonstrated for the first time that HC displayed lung meridian-guiding effects and exhibited great anti-inflammatory potential in the upper respiratory tract. The NF-κB and IL-1ß pathways were associated with the anti-inflammatory mechanism of HC against LPS-provoked airway inflammation. Moreover, chlorogenic acid and quercitrin might be involved in the anti-inflammatory properties of HC.

Rosmarinic acid ameliorated psoriatic skin inflammation in mice through the novel inhibition of the interleukin-17A/interleukin-17A receptor interaction.

The interaction between interleukin-17A (IL-17A) and IL-17A receptor (IL-17RA) is a crucial target of psoriasis. Several natural compounds from foods or herbs have displayed efficacies on the amelioration of psoriasis. However, the anti-psoriatic mechanisms are mostly through the common anti-inflammatory effects and rarely via the blockage of the IL-17A/IL-17RA interaction. In this study, the IL-17A/IL-17RA-targeting effects of phenylpropanoids, a large class of secondary metabolites in plants, were analyzed. By screening 17 phenylpropanoids, we found that top four compounds with IL-17A/IL-17RA-blocking abilities were rosmarinic acid, eugenol, syringic acid, and gallic acid, with inhibitory concentrations at 50% of 2.14 ± 0.35 mM, 6.35 ± 0.1 mM, 4.79 ± 0.2 mM, and >10 mM, respectively. The oral administration of rosmarinic acid ameliorated redness and scaling on the dorsal skin of imiquimod-induced psoriatic mice in a dose-dependent manner. Rosmarinic acid suppressed the production of IL-23 and IL-17A and the infiltration of granulocyte subsets in skin tissues. Docking analysis showed that rosmarinic acid docked into IL-17A/IL-17RA interaction regions and exhibited hydrogen bonding with Arg-61, Glu-68, Arg-100, and Ser-118 of IL-17A, which are located in the epitope regions recognized by IL-17A neutralizing antibodies Fab6785 and Fab6468. In conclusion, this is the first study reporting that rosmarinic acid is an IL-17A-targeting agent that ameliorates psoriatic skin inflammation in mice via blocking the IL-17A/IL-17RA interaction.

The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy.

Diabetic nephropathy is an inflammatory immune disorder accompanying diabetes. A trypsin inhibitor of Momordica charantia, mcIRBP, is an abundant 68 amino acid residue protein that interacts with the insulin receptor. Here the long-term effects of mcIRBP on the improvement of diabetic nephropathy were determined. Type 2 diabetic mice (db/db) were given mcIRBP administered orally for 12 consecutive weeks. Histological changes relating to the kidney were evaluated using Periodic Acid Schiff and Sirius Red staining. The mcIRBP-affected gene expression profile in the kidney was determined using RNA-Seq. The renoprotective mechanism of mcIRBP was elucidated based on ex vivo imaging and immunohistochemistry staining. Data showed that the administration of mcIRBP significantly decreased fasting blood glucose and glycated hemoglobin A1c (HbA1c) levels by 61% and 27.92%, respectively, suggesting that mcIRBP exhibited HbA1c-lowering abilities in diabetic mice. RNA sequencing (RNA-Seq) analysis showed that the majority of the mcIRBP-affected biological pathways were associated with inflammation and immunity, and the nuclear factor-κB (NF-κB) signaling pathway was significantly affected by mcIRBP. Ex vivo imaging showed that mcIRBP significantly decreased NF-κB-driven bioluminescence in the kidney by 46 ± 23%. The levels of the renal function indices, Evans blue dye content, fibrosis lesions, and cytokine expression were significantly decreased by mcIRBP, suggesting that mcIRBP improved vascular leakage and the pathological and inflammatory characteristics of diabetic nephropathy. This is the first study reporting that, in addition to blood glucose regulation, mcIRBP can act as a novel renoprotective and anti-inflammatory polypeptide, thereby improving diabetic nephropathy in db/db mice. In addition, this study suggested that there was a potential medicinal use of mcIRBP for the management of diabetes and its complications.

Correction: The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy.

Correction for 'The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy' by Pei-Yung Liao et al., Food Funct., 2022, DOI: 10.1039/d1fo03620c.

A gastro-resistant peptide from Momordica charantia improves diabetic nephropathy in db/db mice via its novel reno-protective and anti-inflammatory activities.

Diabetic nephropathy (DN), a principal diabetic microvascular complication, is a chronic inflammatory immune disorder. A gastro-resistant peptide mcIRBP-9 from Momordica charantia has shown modulation of blood glucose homeostasis in diabetic mice. Here we conducted a long-term experiment to evaluate the therapeutic effects and mechanisms of mcIRBP-9 on DN. Type 2 diabetic mice (db/db mice) were orally given mcIRBP-9 once daily for 12 consecutive weeks. The amelioration of DN was evaluated by renal function indexes, vascular leakage, and pathological lesions. Possible effective mechanisms of mcIRBP-9 on DN were analyzed by gene expression profiles. A pharmacokinetic study in rats was carried out to evaluate the oral bioavailability of mcIRBP-9. Our data showed that mcIRBP-9 was able to enter systemic circulation in rats after oral administration. In comparison with mock, long-term administration of mcIRBP-9 significantly decreased blood glucose (572.25 ± 1.55 mg dL-1vs. 213.50 ± 163.39 mg dL-1) and HbA1c levels (13.58 ± 0.30% vs. 8.23 ± 2.98%) and improved the survival rate (85.7% vs. 100%) in diabetic mice. mcIRBP-9 ameliorated DN by reducing renal vascular leakage and histopathological changes. mcIRBP-9 altered the pathways involved in inflammatory and immune responses, and the nuclear factor-κB played a central role in the regulation of mcIRBP-9-affected pathways. Moreover, mcIRBP-9 improved the inflammatory characteristic of DN in diabetic and non-diabetic mice. In conclusion, mcIRBP-9 displayed a novel anti-inflammatory activity and exhibited a reno-protective ability in addition to controlling the blood glucose and HbA1c levels. These findings suggested the role of mcIRBP-9 from M. charantia as a nutraceutical agent for diabetes and subsequent DN.

Novel serotonin-boosting effect of incense smoke from Kynam agarwood in mice: The involvement of multiple neuroactive pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Stress is a state of feeling that inhibits one from responding properly in the face of a threat. Agarwood smoke has been used in traditional medicine as a sedative anti-anxious, and anti-restless therapy. Its scent emitted from heat induces people to enter a stable state; however, the underlying molecular effect is still unclear. AIM OF THE STUDY: This study analyzed novel biological events and gene expression signatures induced by agarwood incense smoke in mice. MATERIALS AND METHODS: Incense smoke was produced by heating at 150 °C for 30 min in a headspace autosampler oven. We treated mice with exposure to incense smoke from Kynam agarwood for 45 min/day for 7 consecutive days. After a 7-day inhalation period, the potent agarwood smoke affected-indicators in serum were measured, and the RNA profiles of the mouse brains were analyzed by microarray to elucidate the biological events induced by agarwood incense smoke. RESULTS: Chemical profile analysis showed that the major component in the incense smoke of Kynam was 2-(2-phenylethyl) chromone (26.82%). Incense smoke from Kynam induced mice to enter a stable state and increased the levels of serotonin in sera. The emotion-related pathways, including dopaminergic synapse, serotonergic synapse, GABAergic synapse, long-term depression and neuroactive ligand-receptor interaction, were significantly affected by incense smoke. Moreover, the expression of Crhr2 and Chrnd genes, involved with neuroactive ligand-receptor interaction pathway, was upregulated by incense smoke. CONCLUSIONS: By a newly-established incense smoke exposure system, we first identified that anti-anxious and anti-depressant effects of agarwood incense smoke were likely associated with the increase of serotonin levels and multiple neuroactive pathways in mice.

The protective effect of quercetin on retinal inflammation in mice: the involvement of tumor necrosis factor/nuclear factor-κB signaling pathways.

Quercetin is a natural flavonoid that occurs in fruits and vegetables. Retinal inflammation is an important cause of vision loss. This study was aimed to analyze the effects of oral administration of quercetin on retinal inflammation. Transgenic mice, carrying nuclear factor-κB (NF-κB)-driven luciferase genes, were injected with 1 mg per kg body weight of lipopolysaccharide (LPS). Various amounts (1, 10, and 100 mg per kg body weight) of quercetin were orally given to mice. LPS-induced retinal inflammation was evaluated by bioluminescence imaging and histological examination 4 hours later. RNA-Seq analysis of gene expression profiles was performed to explain the mechanisms of quercetin on eye inflammation. Our data showed that LPS enhanced luminescent signals on ocular tissues, while LPS-induced luminescence intensities were significantly suppressed by quercetin by 73.61 ± 21.74%. LPS significantly increased the thickness of retinal tissues by 1.52 ± 0.37 fold, in comparison with the mock, while quercetin reduced the LPS-induced retinal thickness and decreased the accumulation of infiltrating granulocytes. Biological pathway analysis showed that tumor necrosis factor (TNF), cytokine, and NF-κB signaling pathways were involved in the anti-inflammatory mechanisms of quercetin. Immunohistochemical staining further showed that quercetin reduced the activation of NF-κB, the expression of interleukin-1ß and TNF-α, and the infiltration of granulocytes in retinal tissues. In conclusion, this is the first study reporting the effects and mechanisms of orally administered quercetin against LPS-induced retinal inflammation in mice. Due to its safety, our study suggested that supplementation of quercetin has beneficial effects on the eyes.

Anti-hypertensive and angiotensin-converting enzyme inhibitory effects of Radix Astragali and its bioactive peptide AM-1.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypertension is one of the common chronic health problems in the world. Astragalus membranaceus root (AM), also known as Huangqi, is a popular medicinal herb traditionally used to reinforce vital energy and modulate hypertension. AIM OF THE STUDY: This study was to reveal the anti-hypertensive activities and mechanisms of AM in spontaneously hypertensive rats (SHRs). Moreover, the presence of bioactive components in AM was further identified. MATERIALS AND METHODS: We analyzed the effects of aqueous extract of AM (AME) on the regulation of blood pressure and angiotensin converting enzyme (ACE), the major target of anti-hypertensive drugs. Proteomic, bioinformatics, and docking analyses were performed to identify the anti-hypertensive bioactive peptides in AME. RESULTS: Our data showed that AME inhibited ACE activities in a dose-dependent manner, with an IC50 of 1.85 ± 0.01 µg/ml. In comparison with mock, oral administration of AME reduced systolic blood pressure (SBP) levels in SHRs, and the level of SBP was decreased by 22.33 ± 3.61 mmHg at 200 mg/kg AME. Proteomic analysis identified that an abundant 152-amino-acid putative protein kinase fragment accounted for approximately 11.7% of protein spots in AME. AM-1 (LVPPHA), a gastrointestinal enzyme-resistant peptide cleaved from putative protein kinase fragment, inhibited ACE activities, with an IC50 value of 414.88 ± 41.88 µM. Moreover, oral administration of AM-1 significantly decreased SBP levels by 42 ± 2.65 mmHg at 10 µmol/kg. Docking analysis further showed that AM-1 docked into the active site channel of ACE and interacted with Ala-354 in the active site pocket of ACE. CONCLUSIONS: the ACE inhibitory effect of AM and the presence of ACE inhibitory phytopeptide in AME supported the ethnomedical use of AM on hypertension.

A Potential Herbal Adjuvant Combined With a Peptide-Based Vaccine Acts Against HPV-Related Tumors Through Enhancing Effector and Memory T-Cell Immune Responses.

Viral infection is associated with many types of tumorigenesis, including human papillomavirus (HPV)-induced cervical cancer. The induction of a specific T-cell response against virus-infected cells is desired to develop an efficient therapeutic approach for virus-associated cancer. Chinese herbal medicine (CHM) has a long history in the treatment of cancer patients in Asian countries. Hedyotis diffusa Willd (Bai Hua She She Cao, BHSSC) is frequently used clinically and has been shown to inhibit tumor growth in vitro. However, in vivo data demonstrating the antitumor efficacy of BHSSC are still lacking. We showed that BHSSC induces murine and human antigen-presenting cell (APC) activation via the MAPK signaling pathway and enhances antigen presentation in bone marrow-derived dendritic cells (BMDCs) in vitro. Furthermore, we identified that treatment with BHSSC leads to improved specific effector and memory T-cell responses in vivo. Variant peptide-based vaccines combined with BHSSC improved antitumor activity in preventive, therapeutic, and recurrent HPV-related tumor models. Furthermore, we showed that rutin, one of the ingredients in BHSSC, induces a strong specific immune response against HPV-related tumors in vivo. In summary, we demonstrated that BHSSC extract and its active compound, rutin, can be used as adjuvants in peptide-based vaccines to increase immunogenicity and to bypass the requirement of a conditional adjuvant.

Regulation effect and mechanism of Sheng-Hua-Tang on female reproductive system: From experimental transcriptomic analysis to clinical applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-Hua-Tang (SHT) is commonly used to treat female illnesses, especially postpartum conditioning. However, its effects and mechanisms on female reproductive system remain unclear. The aim of the present study was to investigate the effect of SHT on female brain-ovary-uterus axis from bench to clinic. MATERIALS AND METHODS: Mice were administrated SHT (200 mg/kg) orally for seven consecutive days. Brain, ovary, and uterus tissues were then collected for microarray analysis. A nationwide database analysis and a pilot randomized, open-label clinical trial were further applied to evaluate the clinical application and effects of SHT on postpartum women. RESULTS: Microarray analysis showed that oral administration of SHT induced a cascade reaction of gene expression, with 17, 883, and 1592 genes were significantly regulated by SHT in brain, ovary, and uterus, respectively. Population-based analysis of one million subjects in Taiwan's National Health Insurance Research Database between 1997 and 2013 showed that SHT was commonly used in menstrual disorders in female population, especially dysmenorrhea, abnormal uterine bleeding, and variation of menstrual cycle. Clinical trial on postpartum women showed that oral administration SHT for one week alleviated uterine contraction pain and breast swelling pain. Furthermore, Mmp2, Mmp3, Mmp9, Mmp11, Mmp15, Oxtr, Plrl, and Tph2 gene expression affected by SHT in mice were correlated with clinical effects of SHT in human subjects. CONCLUSION: This report provided the scientific evidences of mechanisms and clinical efficacies of SHT. Moreover, our findings might afford insights for clinical doctors in terms of SHT prescription.

Antihypertensive Effects of Corn Silk Extract and Its Novel Bioactive Constituent in Spontaneously Hypertensive Rats: The Involvement of Angiotensin-Converting Enzyme Inhibition.

Corn silk tea has been used in folk medicine for anti-hypertensive healthcare. Angiotensin-converting enzyme (ACE) plays a crucial role on the homeostasis of blood pressure. However, effects of corn silk tea on ACE activity and the presence of ACE inhibitory constituents in corn silk are still unknown. Here we applied proteomics and bioinformatics approaches to identify corn silk bioactive peptides (CSBps) that target ACE from the boiling water extract of corn silk (CSE). CSE significantly reduced systolic blood pressure (SBP) levels in spontaneously hypertensive rats and inhibited the ACE activity. By proteomics coupled with bioinformatics analyses, we identified a novel ACE inhibitory peptide CSBp5 in CSE. CSBp5 significantly inhibited the ACE activity and decreased SBP levels in a dose-dependent manner. Docking analysis showed that CSBp5 occupied the substrate-binding channel of ACE and interacted with ACE via hydrogen bonds. In conclusion, we identified that CSE exhibited anti-hypertensive effects in SHRs via the inhibition of ACE, the target of most anti-hypertensive drugs. In addition, an ACE inhibitory phytopeptide CSBp5 that decreased SBP levels in rats was newly identified. Our findings supported the ethnomedical use of corn silk tea on hypertension. Moreover, the identification of ACE inhibitory phytopeptide in corn silk further strengthened our findings.

Ferulic acid altered IL-17A/IL-17RA interaction and protected against imiquimod-induced psoriasis-like skin injury in mice.

Ferulic acid (FA), a phenolic phytochemical, is commonly found in grains, vegetables, and fruits. Interleukin-17A (IL-17A) and IL-17 receptor A (IL-17RA) interaction is one of important therapeutic targets for psoriasis. Here we analyzed the FA effects on IL-17A/IL-17RA interaction and psoriasis-like skin injury induced by imiquimod (IMQ). IL-17A-blocking assay and docking analysis showed that FA interacted with Trp-67, Gln-94, and Glu-95 residues of IL-17A via hydrogen bonds and consequently abolished the binding of IL-17RA to IL-17A. Mice were topically given with IMQ and orally given with various amounts of FA for 14 consecutive days. FA attenuated IMQ-induced psoriasis-like skin lesions in a dose-dependent manner, and the epidermal thickness of mice treated with 100 mg/kg FA was reduced by 53.48 ±â€¯4.44% in comparison with sham. Global analysis of differentially expressed genes showed that IMQ and FA significantly affected immune response, metabolism, and mitogen-activated protein kinase signaling pathways. Immunohistochemical staining showed that FA inhibited the infiltration and the cytokine secretion of Th17 cell, dendritic cell, and granulocyte subsets in psoriatic skin tissues. In conclusion, we newly identified that oral administration of FA protected against IMQ-induced psoriatic skin injury in mice. Moreover, its protection was associated with the interference of IL-17A/IL-17RA interaction.

Adjunctive Chinese herbal medicine therapy for nasopharyngeal carcinoma: Clinical evidence and experimental validation.

BACKGROUND: To investigate the benefits of adjunctive Chinese herbal medicine (CHM) for patients with nasopharyngeal carcinoma (NPC). METHODS: We included all patients diagnosed with NPC during 1997-2009 and followed until 2011 in Taiwan. We used 1:1 frequency matching by age, sex, comorbidity, conventional treatment, and index year to compare the CHM users and non-CHM users (n = 2542 each). The prescribed CHM was further investigated with regard to its cytotoxicity. RESULTS: Compared with non-CHM users, adjunctive CHM users had a lower hazard ratio of mortality risk, and a better survival probability. Gan-Lu-Yin (GLY) was the most commonly prescribed CHM, and it reduced cell viability, inhibited tumor proliferation, and induced apoptosis through the poly (ADP-ribose) polymerase and caspase-3-dependent pathway in human NPC TW01 cells. Oral administration of GLY retarded NPC-TW01 tumor growth in the xenograft nude mouse model. CONCLUSION: Real-world data and laboratory experiments implied that adjunctive CHM might be beneficial for NPC patients.

Chemical Profiles of Incense Smoke Ingredients from Agarwood by Headspace Gas Chromatography-Tandem Mass Spectrometry.

Agarwood, the resinous wood in the heartwood of Aquilaria trees, has been used as incense in traditional Chinese medicine for its sedative, aphrodisiac, carminative, and anti-emetic effects. Grading of agarwood is usually based on its physical properties. Therefore, it is important to develop analytic methods for judgment and grading of agarwood. Here, we created a headspace (HS) preheating system that is combined with gas chromatography-mass spectrometry (HS GC-MS) to analyze the chemical constituents in the incense smoke produced by agarwood. Incense smoke generated in the HS preheating system was injected directly to GC-MS for analysis. A total of 40 compounds were identified in the incense smoke produced by Kynam agarwood, the best agarwood in the world. About half of the compounds are aromatics and sesquiterpenes. By analyzing chemical constituents in the incense smoke produced by Vietnamese, Lao, and Cambodian varieties of agarwood, we found that butyl hexadecanoate, butyl octadecanoate, bis(2-ethylhexyl) 1,2-benzenedicarboxylate, and squalene were common in the aforementioned four varieties of agarwoods. 2-(2-Phenylethyl) chromone derivatives were identified only in the incense smoke produced by Kynam agarwood, and were the major ingredient (27.23%) in the same. In conclusion, this is the first study that analyzes chemical profiles of incense smoke produced by agarwood using HS GC-MS. Our data showed that 2-(2-phenylethyl) chromone derivatives could be used to assess quality of agarwoods. Moreover, HS GC/MS may be a useful tool for grading quality of agarwood.

Vanillin-Ameliorated Development of Azoxymethane/Dextran Sodium Sulfate-Induced Murine Colorectal Cancer: The Involvement of Proteasome/Nuclear Factor-κB/Mitogen-Activated Protein Kinase Pathways.

Vanillin is a natural dietary flavoring widely used in the food industry. Colorectal cancer (CRC) is one of the common malignancies in the world. Chronic intestinal inflammation is a risk factor for the development of CRC. We have previously found that vanillin improves and prevents colitis in mice. Here we evaluated the inhibitory activities of vanillin on a mouse model of colitis-induced CRC. Mice were challenged intraperitoneally with azoxymethane (AOM) and orally with dextran sodium sulfate (DSS). Various dosages of vanillin were orally administered for 13 consecutive weeks. Vanillin alleviated the development of tumors in AOM/DSS-induced mice. The total number of tumors in 100 mg/kg vanillin group was significantly reduced by 57.14 ± 7.67%, compared with sham group. Gene expression analysis showed that vanillin downregulated the expression levels of proteasome genes in colon tissues. Moreover, vanillin at 10 mM significantly suppressed proteasome activities in HCT-116 cells by 41.27 ± 0.41%. Furthermore, vanillin diminished the phosphorylation of mitogen-activated protein kinases (MAPKs) and reduced the number of p65-positive cells, proliferating cells, and granulocytes in colon tissues with statistical significance. In conclusion, our data suggested that vanillin was a bioactive compound that ameliorated the development of AOM/DSS-induced colon cancer in mice. Moreover, the amelioration of vanillin might be associated with the downregulation of proteasome, nuclear factor-κB, and MAPK pathways.

Radix Paeoniae Rubra stimulates osteoclast differentiation by activation of the NF-κB and mitogen-activated protein kinase pathways.

BACKGROUND: Radix Paeoniae Rubra (RPR), a traditional Chinese herb, has anti-inflammatory and immuno-regulatory properties. This study explored the effects of RPR on stimulation of osteoclast differentiation in RAW264.7 cells and peripheral blood mononuclear cells (PBMC)s. METHODS: The mature osteoclasts were measured by bone resorption assays and TRAP staining. JNK, ERK, p38 and NF-κB inhibitors were used applied in order to verify their contribution in RPR-induced osteoclast differentiation. The NF-κB and MAPK pathways were evaluated by western blotting, RT-PCR and luciferase assay. RESULTS: RPR induced osteoclast differentiation in a dose-dependent manner and induced the resorption activity of osteoclasts differentiation of RAW264.7 cells and PBMCs. Western blotting showed that RPR treatment induced phosphorylation of JNK, ERK, and p38 in RAW 264.7 cells. Treatment of JNK, ERK, and p38 MAP kinase inhibitors verified the contribution of JNK, ERK and p38. RPR treatment induced c-Fos and NFATc1 protein expression; NF-κB inhibitor treatment and luciferase assay verified the contribution of the NF-κB pathway. CONCLUSIONS: This study demonstrated the interesting effect, in which RPR stimulated osteoclast differentiation in murine RAW264.7 cells and human monocytes.

Gallic Acid Induces Apoptosis in Human Gastric Adenocarcinoma Cells.

BACKGROUND/AIM: Gastric cancer is one of the most common malignant cancers with a poor prognosis and high mortality rate worldwide. Current treatment of gastric cancer includes surgery and chemotherapy as the main modalities, but the potentially severe side-effects of chemotherapy present a considerable challenge. Gallic acid is a trihydroxybenzoic acid found to exert an anticancer effect against a variety of cancer cells. The purpose of this study was to determine the anti-cancer activity of Galla chinensis and its main component gallic acid on human gastric adenocarcinoma cells. MATERIALS AND METHODS: MTT assay and cell death ELISA were used to determine the apoptotic effect of Gallic Chinensis and gallic acid on human gastric adenocarcinoma cells. To determine the pathway and relevant components by which gallic acid-induced apoptosis is mediated through, cells were transfected with siRNA (Fas, FasL, DR5, p53) using Lipofectamine 2000. Reults: Gallic Chinensis and gallic acid induced apoptosis of human gastric adenocarcinoma cells. Gallic acid induced up-regulation of Fas, FasL, and DR5 expression in AGS cells. Transfection of cells with Fas, FasL, or DR5 siRNA reduced gallic acid-induced cell death. In addition, p53 was shown to be involved in gallic acid-mediated Fas, FasL, and DR5 expression as well as cell apoptosis in AGS cells. CONCLUSION: These results suggest that gallic acid has a potential role in the treatment of gastric cancer.

Angelica sinensis Exerts Angiogenic and Anti-apoptotic Effects Against Cerebral Ischemia-Reperfusion Injury by Activating p38MAPK/HIF-1[Formula: see text]/VEGF-A Signaling in Rats.

This study evaluated the effects of Angelica sinensis extract [Dang Gui (DG)] administered before 60[Formula: see text]min of middle cerebral artery occlusion followed by 3[Formula: see text]d of reperfusion and investigated the involvement of mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor (HIF)-1[Formula: see text] signaling in the cortical ischemic penumbra. DG was intraperitoneally administered at a dose of 0.25[Formula: see text]g/kg (DG-0.25g), 0.5[Formula: see text]g/kg (DG-0.5g), or 1[Formula: see text]g/kg (DG-1g) 30[Formula: see text]min before the onset of cerebral ischemia. Our study results revealed that DG-0.5g and DG-1g pretreatment effectively attenuated cerebral infarct and improved neurological deficits. DG-0.5g and DG-1g pretreatment significantly downregulated glial fibrillary acidic protein (GFAP), cytochrome c, and cleaved caspase-3 expression and upregulated phospho-p38 MAPK (p-p38 MAPK)/p38 MAPK, phospho-cAMP response element-binding protein (p-CREB)/CREB, cytosolic and mitochondrial phospho-Bad (p-Bad)/Bad ratios, and HIF-1[Formula: see text], vascular endothelial growth factor-A (VEGF-A), phospho-90 kDa ribosomal S6 kinase (p-p90RSK), and von Willebrand factor (vWF) expression in the cortical ischemic penumbra. Pretreatment with SB203580, a p38 MAPK inhibitor, dramatically abrogated the upregulating effects of DG-1g on p-p38 MAPK/p38 MAPK, p-CREB/CREB, and p-Bad/Bad ratios and HIF-1[Formula: see text], VEGF-A, and vWF expression and the downregulating effects of DG-1g on GFAP, cytochrome c, cleaved caspase-3, and cerebral infarction. DG-0.5g and DG-1g pretreatment provided neuroprotective effects against astrocyte-mediated cerebral infarction by activating angiogenic and anti-apoptotic signaling. Moreover, the angiogenic and anti-apoptotic effects of DG pretreatment can be attributed to the activation of p38 MAPK/HIF-1[Formula: see text]/VEGF-A/vWF signaling and p38 MAPK/HIF-1[Formula: see text]/VEGF-A/p-Bad-related regulation of cytochrome c/caspase-3 signaling, respectively, in the cortical ischemic penumbra 3[Formula: see text]d after reperfusion.