Volatile profiling coupled with multivariate analysis, antiproliferative and anti-inflammatory activities of rhizome essential oil of four Hedychium species from India.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hedychium of family Zingiberaceae comprises several perennial rhizomatous species widely used in perfumery and traditional folk medicine to treat diseases related to asthma, diarrhoea, nausea, stomach disorders, inflammation and tumours. Several species of Hedychium have remained under-explored with respect to their chemical composition and biological activities. AIM OF THE STUDY: The current research aimed to explore the chemical composition and evaluate the antiproliferative and anti-inflammatory activities of rhizome essential oil from four Hedychium species (H. coccineum, H. gardnerianum, H. greenii and H. griffithianum). MATERIALS AND METHODS: Compound identification was accomplished using a Clarus 580 gas chromatography system in conjunction with mass spectrometry (GC-MS). The multivariate data statistics using chemometrics (PCA, PLS-DA, sPLS-DA) and cluster analysis (Dendrogram, Heat maps, K-means) were used to compare the similarity and relationship among Hedychium metabolomes. MTT assay was employed to visualize the antiproliferative property against MCF7, HepG2 and PC3 cancerous cell lines. The toxicity of essential oils was determined using 3T3-L1 non-tumorigenic/normal cells. Lipopolysaccharide (LPS)-induced RAW 264.7 cells were used to investigate the anti-inflammatory properties of Hedychium essential oils by measuring the production of nitric oxide (NO) using the Griess reagent method. Furthermore, the levels of prostaglandin (PGE2) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) was assessed using the ELISA technique. RESULTS: In total, 82 compounds were identified in four targeted species of Hedychium from which 1,8-cineole (52.71%), ß-pinene (32.83%), α-pinene (19.62%), humulene epoxide II (19.86%) and humulene epoxide I (19.10%) were the major constituents. Monoterpenes (8.5-59.9%) and sesquiterpenes (2.87-54.11%) were the two class of compounds, found as the most prevalent in the extracted essential oils. The multivariate analysis classified the four Hedychium species into three different clusters. Hedychium essential oils exhibited potent antiproliferative activity against MCF7, HepG2 and PC3 cancer cell lines with IC50 values less than 150 µg/mL where H. gardnerianum exhibited the highest selective cytotoxicity against human breast and prostate adenocarcinoma cells with an IC50 value of 44.04 ± 1.07 µg/mL and 56.11 ± 1.44 µg/mL, respectively. The essential oils on normal (3T3-L1) cells displayed no toxicity with higher IC50 values thereby concluding as safe to use for normal human health without causing any side effects. Besides, the essential oils at 100 µg/mL concentration revealed remarkable anti-inflammatory activity in LPS-activated RAW 264.7 murine macrophages by inhibiting the production of inflammatory mediators, with H. greenii exhibiting the maximum anti-inflammation response by significantly suppressing the levels of NO (84%), PGE2 (87%), TNF-α (94.3%), IL-6 (95%) and IL-1ß (85%) as compared to LPS treated group. CONCLUSION: The present findings revealed that the Hedychium species traditionally used in therapeutics could be a potential source of active compounds with antiproliferative and anti-inflammatory properties.

1-Tetracosanol isolated from the leaves of Eupatorium glandulosum, accelerates wound healing by expressing inflammatory cytokines and matrix metalloproteinase.

ETHNOPHARMACOLOGICAL RELEVANCE: The leave paste of the plant, Eupatorium glandulosum H. B & K, has been traditionally used to treat cuts and wounds by the tribal community of the Nilgiris district of Tamilnadu, India. AIM OF THE STUDY: The present study was carried out to investigate the wound healing potential of this plant extract and the compound, 1-Tetracosanol, isolated from the ethyl acetate fraction. MATERIALS AND METHODS: An in vitro study was designed to compare the viability, migration and apoptosis of the fresh methanolic extract fractions and 1-Tetracosanol using mouse fibroblast NIH3T3 cell lines and human keratinocytes HaCaT cell lines, respectively. 1-Tetracosanol was evaluated for its viability, migration, qPCR analysis, in silico, in vitro and in vivo. RESULTS: 1-Tetracosanol at the concentration of 800, 1600, 3200 µM has significant wound closure of 99% at 24 h. The compound when screened in silico against various wound healing markers, TNF-α, IL-12, IL-18, GM-CSF and MMP-9, revealed high binding energy of -5, 4.9 and -6.4 kcal/mol for TNF-α, IL-18 and MMP-9, respectively. Gene expression and the release of cytokines increased at an early stage of the wound repair. 1-Tetracosanol, at 2% gel showed 97.35 ± 2.06% wound closure at 21st day. CONCLUSION: 1-Tetracosanol is a good lead for drug development targeted towards wound healing activity and work in this direction is in progress.

Phytochemical characterization and anti-inflammatory activity of a water extract of Gentiana purpurea roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana purpurea was one of the most important medicinal plants in Norway during the 18th and 19th centuries, and the roots were used against different types of gastrointestinal and airway diseases. AIM OF THE STUDY: To explore the content of bioactive compounds in a water extract from the roots, a preparation commonly used in traditional medicine in Norway, to assess the anti-inflammatory potential, and furthermore to quantify the major bitter compounds in both roots and leaves. MATERIALS AND METHODS: G. purpurea roots were boiled in water, the water extract applied on a Diaion HP20 column and further fractionated with Sephadex LH20, reverse phase C18 and normal phase silica gel to obtain the low molecular compounds. 1D NMR, 2D NMR, and ESI-MS were used for structure elucidation. HPLC-DAD analysis was used for quantification. The inhibition of TNF-α secretion in ConA stimulated peripheral blood mononuclear cells (PBMCs) was investigated. RESULTS: Eleven compounds were isolated and identified from the hot water extract of G. purpurea roots. Gentiopicrin, amarogentin, erythrocentaurin and gentiogenal showed dose-dependent inhibition of TNF-α secretion. Gentiopicrin is the major secondary metabolite in the roots, while sweroside dominates in the leaves. CONCLUSIONS: The present work gives a comprehensive overview of the major low-molecular weight compounds in the water extracts of G. purpurea, including metabolites produced during the decoction process, and show new anti-inflammatory activities for the native bitter compounds as well as the metabolites produced during preparation of the crude drug.

Investigation of the potential curative effects of Gui-Zhi-Jia-Ge-Gen decoction on wind-cold type of common cold using multidimensional analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Gui-Zhi-Jia-Ge-Gen decoction (GJGD) is a classical Chinese medicine prescription that has been widely used in clinical practice for centuries. In recent times, TCM has received considerable attention for its potential efficacy in treating a wind-cold type of common cold. However, the effect of the Gui-Zhi-Jia-Ge-Gen decoction on the wind-cold type of common cold is still not fully understood, which presents challenges for both quality control, research and development. Furthermore, the identification of potential pharmacodynamic ingredients (PPIs) is important for developing quality control procedures for industrial and large-scale production. AIM OF THE STUDY: The aim of this study was to investigate the potential curative effect of Gui-Zhi-Jia-Ge-Gen decoction on wind-type of common cold using multidimensional qualitative analysis that combined water-decoction spectrums, in vivo plasma spectrums, and molecular docking to identify key constituents of GJGD. MATERIALS AND METHODS: Water-based GJGDs were formulated according to the clinical usage documented in ancient medical texts. Ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS) was combined with computer-aided modeling screening to identify GJGD PPIs in rats following oral administration. Molecular docking experiments were carried out to predict the binding affinity of the PPIs to tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin-1ß (IL-1ß). Finally, the active ingredients of GJGD were further validated through pharmacodynamic experiments by assessing their efficacy in treating a wind-cold type of common cold in rats. RESULTS: A total of 61 compounds were identified in the GJGD, 8 of which were detected in rat blood samples, providing stronger evidence for PPIs. Molecular docking also confirmed that these 8 compounds had a better affinity for TNF-α, IL-6, and IL-1ß. In animal studies, various doses of the GJGD groups and the positive control groups caused significant elevations (P < 0.05) in the levels of white blood cell count and lymphocyte ratio and caused a significant decrease (P < 0.05) in the monocyte ratio and neutrophilic granulocyte ratio compared to the model group. Organ indexes of the GJGD treated groups were higher than the model group (P < 0.05). Significant neutrophil infiltration, hemorrhage, compensatory vacuole, and interstitium proliferation were observed in the lung tissue of the model group. However, the lung tissues of the various dose groups that received GJGD showed a near normal appearance, except for slight thickening, interstitium proliferation, and compensatory vacuole in some areas. The GJGD was found to be effective against a cold-wind type of common cold, which is in accordance with molecular docking studies suggesting that GJGD may be effective against a cold-wind type of common cold. Finally, based on multidimensional analysis, 8 potential compounds in GJGD were identified as PPIs (puerarin, 3'-hydroxy puerarin, 3'- methoxy puerarin, daidzin, cinnamic acid, paeoniflorin, liquiritin, and glycyrrhizic acid). CONCLUSION: The present study combined water decoction spectral analysis, molecular docking, and in vivo blood plasma spectrum analysis to develop a multidimensional qualitative approach for the development of GJGD and to assess its effectiveness in a wind type of common cold in Sprague Dawley rats. Meanwhile, 8 compounds in the GJGD were identified as PPIs in this study, which may be useful in developing quality standards for complex TCM prescriptions.

Digested Human Colostrum Reduces Interleukin-8 Production in Induced Human Intestinal Epithelial Cells.

Little is known about the impact of human colostrum on infant intestinal health following digestion. The aim of this study was to compare the effect of digested versus undigested human colostrum on inflammation and cytotoxicity in human intestinal epithelial cells (Caco2BBe) stimulated with lipopolysaccharides (LPS) or tumor necrosis factor (TNF). Colostrum samples (days 2-8 postpartum) from ten mothers of preterm infant were applied. Caco2BBe cells were pretreated by digested or undigested colostrum before stimulation with LPS or TNF. The inflammatory response was determined by measuring the production of interleukin-8 (IL-8) from cells using enzyme linked immunosorbent assay (ELISA). Cytotoxicity was examined by measuring the release of lactate dehydrogenase (LDH) from the cells. Digested colostrum significantly reduced IL-8 production under LPS and TNF stimulation compared with undigested colostrum. Individual colostrum samples exhibited wide variance in the ability to suppress IL-8 production and cytotoxicity in Caco2BBe cells. In vitro-digested human colostrum suppressed an inflammatory response more than undigested human colostrum in an induced intestinal cell culture model.

Ananas comosus (L) Merrill (pineapple) fruit peel extract demonstrates antimalarial, anti-nociceptive and anti-inflammatory activities in experimental models.

ETHNOPHARMACOLOGY RELEVANCE: Pineapple (Ananas comosus) peel is a major waste in pineapple canning industry and it is reported to be used in ethnomedicine as a component of herbal remedies for malarial management. This study aimed to evaluate the antimalarial, antinociceptive and anti-inflammatory properties of Ananas comosus peel extract (PEAC). METHODS: Ananas comosus peel was extracted with 80% methanol. PEAC (100, 200 and 400 mg/kg) was investigated for antimalarial effect using Peter's 4-day suppressive test (4-DST) model in mice. Antinociceptive activity of PEAC was investigated in hot plate, acetic acid-induced writhing and formalin tests in mice. The anti-inflammatory activity was evaluated using the lipopolysaccharides-induced sickness behavior in mice and carrageenan-induced air pouch in rats' models. RESULTS: PEAC could not significantly (p > 0.05) suppressed parasitemia level at 7-day post-infection in 4-DST. PEAC (400 mg/kg) mildly prolongs survival of infected mice up till day 21. PEAC demonstrated significant (p < 0.05) antinociceptive activity by increasing latency to jump on the hot plate, reduced number of writhings in acetic acid test and reduced paw licking time in 2nd phase of formalin test. PEAC significantly reduced anxiogenic and depressive-like symptoms of sickness behavior in LPS-injected mice. PEAC demonstrated significant anti-inflammatory activity in carrageenan-induced air pouch experiment by reducing exudates formation, inflammatory cell counts, and nitrite, tumor necrosis factor-alpha and interleukin-6 levels. CONCLUSION: Ananas comosus peel extract demonstrated mild antimalarial activity but significant anti-nociceptive and anti-inflammatory properties probably mediated via inhibition of pro-inflammatory mediators.

Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. AIM OF THE STUDY: To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. MATERIALS AND METHODS: Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. RESULTS: Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1ß, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.

Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats: an in silico and in vivo evidence of GABAergic action and cytokine inhibition.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg i.p.)- induced neuropathic pain in Wistar rats.Methods: Docking simulation studies were done on the three-dimensional (3D) structure of the GABAA and PPAR γ receptor for the binding of EA as well as punicalagin docking studies on TNF-α, and IL-6. The Present Study conceptualized a test battery to evaluate the behavioral, biochemical and histological changes.Results: Vincristine -induced significant cold allodynia, mechanical hyperalgesia, and functional deficit on 12th and 21st days. It also increased in the levels of TNF-α (Tumor necrosis factor-α), IL-6 (Interleukin-6), and MPO (Myeloperoxidase). Administration of PFE (100 and 300 mg/kg, p.o.), EA (50 mg/kg), and gabapentin (100 mg/kg) attenuated Vincristine-induced behavioral and biochemical changes significantly (P < .05). PFE showed better antinociceptive activity to EA. The histopathological evaluation also revealed the protective effects of PFE. Pretreatment of bicuculline (selective antagonist of GABAA receptors) reversed antinociceptive action of PFE, but administration of γ aminobutyric acid potentiated the action of PFE. PPAR-γ antagonist BADGE did not modify the effect of PFE. Docking results revealed that EA properly positioned into GABA and PPARγ binding site and acts as a partial agonist. Docking score of Punicalagin found to be - 9.02 kcal/mol and - 8.32 kcal/mol on IL-6 and TNFα respectively.Discussion: Conclusively, the attenuating effect of PFE may be attributed to the GABAergic system, cytokine inhibition, and anti-inflammatory activities.

Photobiomodulation inhibits inflammation in the temporomandibular joint of rats.

Photobiomodulation (PBM) has been applied as a non-invasive technique for treating temporomandibular joint symptoms, especially on painful condition's relief, however the anti-inflammatory mechanism underlying the effect of PBM remains uncertain. This study aims to evaluate the mechanisms of action of PBM (808 nm) in a carrageenan-induced inflammation on temporomandibular joint (TMJ) of rats. In this study male Wistar rats were pre-treated with irradiation of a low-power diode laser for 15 s on TMJ (infra-red 808 nm, 100 mW, 50 J/cm2 and 1.5 J) 15 min prior an injection in the temporomandibular joint of carrageenan (100 µg/TMJ). 1 h after the TMJ treatments, the rats were terminally anesthetized for joint cavity wash and periarticular tissues collect. Samples analysis demonstrated that PBM inhibit leukocytes chemotaxis in the TMJ and significantly reduces amounts of TNF-α, IL-1ß and CINC-1. In addition, Western blotting analysis demonstrated that PBM significantly decreased the protein levels of P2X3 and P2X7 receptors in the periarticular tissues. On the other hand, PBM was able to increase protein level of IL-10 (anti-inflammatory cytokine). In summary, it is possible to suggest that PBM inhibit inflammatory chemotaxis, modulation the balance of the pro- and anti-inflammatory characteristics of inflammatory cells.

Pain-relieving effects of Lawsonia inermis on neuropathic pain induced by chronic constriction injury.

The aim of this study was to determine the role of Lawsonia inermis (L. inermis) extract in the chronic constriction injury (CCI)-induced neuropathic pain. Following CCI surgery, L. inermis extract (250 mg/kg and 500 mg/kg) and gabapentin (100 mg/kg) were administered intraperitoneally for 14 consecutive days. Heat hyperalgesia and allodynia were assessed by radiant heat, aceton drop, and von frey filament tests, respectively. Rat pain behaviors were evaluated on -1sh, 3rd, 5th, 7th, 10th and 14th days post CCI surgery. At the end of the study, the spinal levels of malondialdehyde (MDA), total thiol, IL1-ß, and TNF-α were estimated. Treatment of L. inermis extract reversed the decreased level of thiol and the elevation of MDA level in the spinal cord of CCI rats. Besides, L. inermis extract treatment decreased the elevation of inflammatory markers including IL1-ß, and TNF-α in the spinal cord of CCI rats. These results indicated that L. inermis has potential neuroprotective effects against CCI induced neuropathic pain due to its anti-oxidant, and anti-inflammatory effects.

Apelin-13 attenuates spatial memory impairment by anti-oxidative, anti-apoptosis, and anti-inflammatory mechanism against ethanol neurotoxicity in the neonatal rat hippocampus.

It has been shown that alcohol consumption by pregnant women can have detrimental effects on the developing fetus and lead to fetal alcohol spectrum disorders (FASD). Exposure to alcohol in rat pups during this period causes long-term changes in the structure of the animal's hippocampus, leading to impaired hippocampal-related brain functions such as navigation tasks and spatial memory. Apelin-13, a principal neuropeptide with inhibitory effects on neuroinflammation and brain oxidative stress production, has beneficial properties on memory impairment and neuronal injury. The protective effects of apelin-13 have been evaluated on ethanol-related neurotoxicity in the hippocampus of rat pups. Rat pups from 2 until 10 postnatal day, similar to the third trimester of pregnancy in humans, were intubated total daily dose of ethanol (5/27 g/kg/day). Immediately after intubation, 25 and 50 µg/ kg of apelin-13 was injected subcutaneously. By using Morris water maze task, the hippocampus- dependent memory and spatial learning were evaluated 36 days after birth. Then, Immunohistochemical staining was done to determine the levels of GFAP and caspase-3. ELISA assay was also performed to measure both TNF-α and antioxidant enzymes levels. The current study demonstrates that administration of apelin-13 attenuates spatial memory impairment significantly (P < 0.001). After ethanol neurotoxicity, apelin-13 could also increase the catalase level (P < 0.001), activity of total superoxide dismutase as well as glutathione concentration noticeably (P < 0.05). Other impacts of it could be mentioned as attenuating TNF-α production and also preventing lipid peroxidation (P < 0.001). In addition, the results showed that the level of GFAP as a neuroinflammation factor and the number of active caspase-3 positive cells can be decreased by apelin-13 (P < 0.01). Regarding the protective effects of apelin-13 against ethanol-induced neurotoxicity, it is a promising therapeutic choice for FASD; but more studies are needed.

Tumor necrosis factor-alpha is associated with mineral bone disorder and growth impairment in children with chronic kidney disease.

BACKGROUND: Mineral and bone disorder (MBD) and growth impairment are common complications of pediatric chronic kidney disease (CKD). Chronic inflammation detrimentally affects bone health and statural growth in non-CKD settings, but the impact of inflammation on CKD-MBD and growth in pediatric CKD remains poorly understood. This study assessed associations between inflammatory cytokines with biomarkers of CKD-MBD and statural growth in pediatric CKD. METHODS: This is a cross-sectional study of children with predialysis CKD stages II-V. Cytokines (IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, interferon-γ), bone alkaline phosphatase (BAP), and procollagen type 1 N-terminal propeptide (P1NP) were measured at the same time as standard CKD-MBD biomarkers. Associations between cytokines, CKD-MBD biomarkers, and height z-score were assessed using linear regression analysis. RESULTS: Among 63 children, 52.4% had stage 3 CKD, 76.2% non-glomerular CKD etiology, and 21% short stature. TNF-α was the only cytokine associated with parathyroid hormone (PTH) independent of glomerular filtration rate. After stratification by low, medium, and high TNF-α tertiles, significant differences in PTH, serum phosphorus, alkaline phosphatase, BAP, P1NP, and height z-score were found. In a multivariate analysis, TNF-α positively associated with phosphorus, PTH, and alkaline phosphatase and inversely associated with height z-score, independent of kidney function, age, sex, and active vitamin D analogue use. CONCLUSIONS: TNF-α is positively associated with biomarkers of CKD-MBD and inversely associated with height z-score, indicating that inflammation likely contributes to the development of CKD-MBD and growth impairment in pediatric CKD. Prospective studies to definitively assess causative effects of inflammation on bone health and growth in children with CKD are warranted.

Early radiation-induced oral pain signaling responses are reduced with pentoxifylline treatment.

Radiation-induced acute oral mucositis is associated with inflammation and pain. In other realms of pain research, nociceptors are known to be activated by inflammatory cytokines; for example, tumor necrosis factor alpha (TNF-α) can activate transient receptor potential ion channels on sensory neurons. But there is an unclear relationship between inflammatory cytokines and molecular mediators of pain in radiation-induced mucositis (RIM) and radiation-associated pain (RAP). In this prospective, analytical, experimental pilot study, a common drug (pentoxifylline [PTX]) was used with the goal of inhibiting TNF-α signaling in mice that underwent lingual irradiation to induce severe acute oral RIM/RAP. Body weight and glossitis scores were recorded daily. Eye wiping behaviors were assayed as a surrogate measure of oral discomfort (which is possible due to cross-sensitization of the mandibular and ophthalmic branches of the trigeminal nerve). Quantitative real-time reverse transcription polymerase chain reaction was performed on irradiated tongue tissue to measure changes in expression of TNF-α, its receptor, nuclear factor kappa-light-chain-enhancer of activated B cells, transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential vanilloid type 4 (TRPV4). Responsiveness of afferent sensory trigeminal neurons to TNF-α, a TRPV1 agonist (capsaicin), and a partial TRPV4 agonist (histamine) was measured via calcium imaging. Although PTX treatment did not reduce glossitis severity or mitigate weight loss in mice with RIM/RAP, it did inhibit the upregulation of TNF-α's receptor that normally accompanies RIM, and it also reduced neuronal responsiveness to each of the aforementioned chemical stimuli. These results provide provisional evidence that inhibition of TNF-α signaling with PTX treatment may serve as a useful tool for reducing pain in head and neck cancer patients.

Anti-Obesity and Antidiabetic Effects of Nelumbinis Semen Powder in High-Fat Diet-Induced Obese C57BL/6 Mice.

Nelumbinis Semen (NS, the seeds of Nelumbo nucifera) extract is a traditional Korean medicine with anti-oxidant activity. The present study examined the anti-obesity and antidiabetic effects of NS powder in high-fat diet (HFD)-induced obese C57BL/6 mice. Mice (n = 8/group) were fed a normal diet (CON), HFD, HFD containing 5% NS powder (HFD-NS5%), or HFD containing 10% NS powder (HFD-NS10%) for 12 weeks. Food intake was relatively higher in groups HFD-NS5% and HFD-NS10%, while the food efficiency ratio was highest in group HFD (p < 0.05). HFD-NS5% reduced the body weight (-39.1%) and fat weight (-26.6%), including epididymal fat and perirenal fat, and lowered the serum triglyceride levels (-20.6%) compared with HFD. Groups HFD-NS5% and HFD-NS10% showed hepatoprotective properties, reducing the serum ALT levels (p < 0.05) and fat globules (size and number) in the liver compared with group HFD. HFD-NS5% and HFD-NS10% regulated the blood glucose, improved the glucose intolerance, and showed a 12.5% and 15.0% reduction in the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT), and a 26.8% and 47.3% improvement in homeostatic model assessment insulin resistance (HOMA-IR), respectively, compared with HFD (p < 0.05). Regarding the expressions of genes related to anti-obesity and antidiabetes, there was a 1.7- and 1.3-fold increase in PPAR-α protein expression, 1.4- and 1.6-fold increase in PPAR-γ protein expression, and 0.7- and 0.6-fold decrease in TNF-α protein expression, respectively, following HFD-NS5% and HFD-NS10% treatments, compared with HFD, and GLUT4 protein expression increased relative to CON (p < 0.05). These results comprehensively provide the fundamental data for NS powder's functional and health-promoting benefits associated with anti-obesity and antidiabetes.

Chemical profiling and anti-psoriatic activity of marine sponge (Dysidea avara) in induced imiquimod-psoriasis-skin model.

Since Marine sponge Dysidea avara is regarded as a source of anti-inflammatory compounds, we decided to evaluate its potential anti-psoriatic activity in a psoriasis Imiquimod-induced in the mouse model. Psoriatic mice were treated with three different methanolic extracts of Dysidea avara compared with betamethasone-treated mice in in- vivo studies. Clinical skin severity was assessed with the psoriasis area index (PASI), whilst ELISA detected the expression of TNF-α, IL-17A, and IL-22. Dysidea avara activity was studied by employing GC-MS (to distinguish compounds), HPTLC (for skin permeation and accumulation), and SEA DOCK to predict single compound potential anti-inflammatory activity. After 7 days of treatment, mice treated with Dysidea avara displayed a dose-dependent, statistically significant improvement compared to controls (p< 0.001). In line with the clinical results, ELISA revealed a statistically significant decrease in IL-22, IL-17A, and TNF-α after treatment; the same SEA DOCK analysis suggests a possible anti-psoriatic activity of the extracts.

Febuxostat mitigates concanavalin A-induced acute liver injury via modulation of MCP-1, IL-1ß, TNF-α, neutrophil infiltration, and apoptosis in mice.

AIM: Liver plays a crucial role in innate immunity reactions. This role predisposes the liver to innate-mediated liver injury when uncontrolled inflammation occurs. In this study, the effect of febuxostat administration on acute liver injury induced by concanavalin A (Con A) injection into mouse eye orbital sinus was studied. MATERIALS AND METHODS: Two doses of febuxostat (10 and 20 mg/kg, orally) were administered either 1 h before or 30 min after the administration of Con A. Febuxostat at a low dose (10 mg/kg) before and after Con A modulated the elevation of serum ALT, liver uric acid, liver myeloperoxidase (MPO), and interleukin-1ß (IL-1ß) induced by Con A. The same dose of febuxostat before Con A also decreased serum total bilirubin and neutrophil infiltration, as evidenced by flow cytometry and histopathological analysis. KEY FINDINGS: Febuxostat at a high dose (20 mg/kg) significantly improved serum ALT, AST, albumin, total bilirubin, liver uric acid, MPO, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), IL-1ß, and neutrophil infiltration induced by Con A administration. The results of histopathological examination of liver cells paralleled the observed biochemical improvements. Hepatocyte apoptosis as evidenced by immunohistochemical examination of cleaved caspase-3 was markedly decreased in the febuxostat protection and treatment groups, in a dose-dependent manner SIGNIFICANCE: These results indicate that febuxostat, especially at the higher dose, may be an effective inhibitor of immune reactions evoked by Con A administration.

Plasmodium chabaudi-infected mice spleen response to synthesized silver nanoparticles from Indigofera oblongifolia extract.

Malaria is a worldwide serious-threatening infectious disease caused by Plasmodium and the parasite resistance to antimalarial drugs has confirmed a significant obstacle to novel therapeutic antimalarial drugs. In this article, we assessed the antioxidant and anti-inflammatory activity of nanoparticles prepared from Indigofera oblongifolia extract (AgNPs) against the infection with Plasmodium chabaudi caused in mice spleen. AgNPs could significantly suppress the parasitaemia caused by the parasite to approximately 98% on day 7 postinfection with P. chabaudi and could improve the histopathological induced spleen damage. Also, AgNPs were able to increase the capsule thickness of the infected mice spleen. In addition, the AgNPs functioned as an antioxidant agent that affects the change in glutathione, nitric oxide and catalase levels in the spleen. Moreover spleen IL1ß, IL-6 and TNF-α-mRNA expression was regulated by AgNPs administration to the infected mice. These results indicated the anti-oxidant and the anti-inflammatory protective role of AgNPs against P. chabaudi-induced spleen injury.

Evidence for the involvement of IL-1ß and TNF-α in anti-inflammatory effect and antioxidative stress profile of the standardized dried extract from Miconia albicans Sw. (Triana) Leaves (Melastomataceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Miconia albicans (Melastomataceae), commonly known in Brazil as "canela-de-velho", is used in folk medicine for treating rheumatoid arthritis and reducing pain and inflammation. THE AIM OF THE CURRENT WORK WAS: to provide data on physicochemical characterization of the drug plant and dried extract from M. albicans leaves, as well as investigate the anti-inflammatory effect and antioxidant stress profile from the standardized dried extract of this species employing different model systems. MATERIALS AND METHODS: plant material (dried crushed leaves) was extracted by turboextraction using 50% ethanol (v/v). Different pharmacological techniques were performed to establish quality control parameters of the plant drug, and dried extract of M. albicans (DEMA) was chemically characterized by HPLC-PDA to selection of the chemical marker. Total phenolic and flavonoid contents were determined by the Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. Antioxidant potential of the DEMA was investigated by employing different in vitro antioxidant assays, including DPPH and ABTS radical scavenging assays, ferric reducing antioxidant assay, NO scavenging assay, metal ion (Fe2+) chelating activity and antioxidant capacity by inhibition of lipid peroxidation (TBARS). Finally, anti-inflammatory activity of the DEMA was evaluated using two models of acute inflammation: carrageenan induced inflammation and mechanical hyperalgesia. RESULTS AND DISCUSSION: M. albicans leaves, after drying in forced air circulation chamber at ±40 °C for 48 h and crushing in knife mill, presented a moisture content below the maximum allowed for plant drugs (6.4%). The powder of M. albicans was classified as moderately coarse and total ash content was found to be 6.27%. Preliminary phytochemical screening of DEMA revealed the presence of flavonoids, tannins, saponins, leucoanthocyanins and steroids. DEMA had significant higher total phenolic (551.3 mg gallic acid equivalent/g of dried extract) and flavonoid contents (367.19 mg catechin equivalent/g of dried extract). Two major compounds (λ = 340 nm) were identified in DEMA by HPLC-PDA: the flavonoids rutin and quercetin. Rutin content, selected as chemical marker, was determined and found to be 1.16 mg/g dried extract (r = 0.9941). Regarding to antioxidant activity, our results revealed the DEMA exhibited good antioxidant activity on different models. M. albicans treatment also reduced the levels of TNF-α e IL-1ß and consequently inflammatory nociception and edema caused by carrageenan injection. Based on previous studies and our results, is possible to suggest a positive correlation between the flavonoids rutin and quercetin and the antioxidant and anti-inflammatory capacities. CONCLUSION: Together, these data suggest that M. albicans has the possibility of use in conditions such as arthritis or other joint pain, even needing other work to better consolidate this profile.

Inhalation of Tetrandrine-hydroxypropyl-ß-cyclodextrin Inclusion Complexes for Pulmonary Fibrosis Treatment.

Pulmonary fibrosis (PF) is a kind of interstitial lung disease with the features of progressive and often fatal dyspnea. Tetrandrine (TET) is the major active constituent of Chinese herbal Stephania tetrandra S. Moore, which has already applied clinically to treat rheumatism, lung cancer, and silicosis. In this work, a tetrandrine-hydroxypropyl-ß-cyclodextrin inclusion compound (TET-HP-ß-CD) was developed for the treatment of pulmonary fibrosis via inhalation administration. TET-HP-ß-CD was prepared by the freeze-drying method and identified using the cascade impactor, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectrum (FT-IR). A bleomycin-induced pulmonary fibrosis rat model was used to assess the effects of inhaled TET and TET-HP-ß-CD. Animal survival, hydroxyproline content in the lungs, and lung histology were detected. The results showed that inhalation of TET-HP-ß-CD alleviated inflammation and fibrosis, limited the accumulation of hydroxyproline in the lungs, regulated protein expression in PF development, and improved postoperative survival. Moreover, nebulized delivery of TET-HP-ß-CD accumulated chiefly in the lungs and limited systemic distribution compared with intravenous administration. The present results indicated that inhalation of TET-HP-ß-CD is an attractive candidate for the treatment of pulmonary fibrosis.

Fructus mume Protects Against Cigarette Smoke Induced Chronic Cough Guinea Pig.

Fructus mume was recorded in the Chinese Pharmacopoeia and traditional Chinese medical books for chronic cough, but the effect and related constituents are still unknown. Thus, we investigated the protect effects and the relevant constituents of F. mume in a guinea pig model with chronic cough induced by cigarette smoke (CS). The organic acids and polysaccharides in F. mume were detected by high performance liquid chromatography, gel permeation chromatography, and gas chromatography-mass spectrometry. The guinea pigs were orally administrated with vehicle or the water extract of Fructus mume (FW) during the 14 days of CS exposure. Citric acid induced coughs were automatically measured by Buxco system. The differential cells in bronchoalveolar lavage fluid (BALF) and histopathological changes in lung tissue were assessed by hematoxylin and eosin staining. The tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) levels in lung tissue were detected via enzyme-linked immunosorbent assay. The mucus productions in tracheas were determined with Alcian blue-periodic acid Schiff staining. The results suggested relatively high concentration of citric acid, chlorogenic acid, and neochlorogenic acid in F. mume, and high proportion of galactose and glucose and lower molecular weight of polysaccharides. Administration of FW significantly reduced the cough frequency, decreased inflammatory cells in BALF and lung tissue, and attenuated the thickening of airway epithelium and submucosa compared with CS-exposure group. Moreover, the overproduction of TNF-α and IL-8 in lung tissues, and mucus in central airways of CS-induced guinea pigs was markedly inhibited by FW. The extract could also protect against CS exposure-induced chronic cough in guinea pigs by reducing coughs, airways inflammation, and mucus overproduction.