Therapeutic effect of Brucea javanica oil emulsion on experimental Crohn's disease in rats: Involvement of TLR4/ NF-κB signaling pathway.

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.

Ameliorative effect of supercritical fluid extract of Chrysanthemum indicum Linnén against D-galactose induced brain and liver injury in senescent mice via suppression of oxidative stress, inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum Linne (C. indicum), a healthy food and folk medicine in China for thousands of years, has been reported to exert heat-clearing and detoxifying effects and extensively applied to treat various symptoms such as inflammation diseases, hepatitis and headache. AIM OF THIS STUDY: The purpose of the present study was to investigate the protective effect of the supercritical carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) on D-galactose-induced brain and liver damage during aging process and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with CISCFE (100, 150 and 300 mg/kg) after injection with D-galactose. 24 h after the last administration, the blood samples, whole brain and liver tissues were collected for biochemical analysis, histological examination and western blot analysis. The body weight, spleen and thymus indexes, alanine transaminase (ALT), aspartate transaminase (AST), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) in brain and liver, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and necrosis factor-α (TNF-α) were detected. Besides, the expressions of Bax, Bcl-2 and cleaved caspase-3 were determined by western blot assay. RESULTS: The results indicated that CISCFE effectively increased the suppressed body weight, attenuated the decline of thymus and spleen indexes, and reduced the elevated levels of ALT and AST induced by D-gal. Furthermore, CISCFE might notably alleviate D-gal-induced abnormal alterations in structure and function of brain and liver dose-dependently via renewing normal antioxidant enzymes activities (SOD, CAT, GSH-Px), reducing MDA accumulation, decreasing inflammatory cytokines productions (IL-1ß, IL-6, TNF-α), as well as attenuating the increase of Bax/Bcl-2 ratio and cleaved caspase-3 activation in the liver and brain. CONCLUSIONS: Taken together, our present results suggested that CISCFE treatment could effectively mitigate the D-gal-induced hepatic and cerebral injury, and the underlying mechanism might be tightly related to the decreased oxidative stress, inflammation and apoptosis, indicating CISCFE might be an alternative and promising agent for the treatment of aging and age-associated brain and liver diseases.

Self-nanoemulsifying drug delivery system of bruceine D: a new approach for anti-ulcerative colitis.

BACKGROUND: Bruceine D (BD) is a major bioactive component isolated from the traditional Chinese medicinal plant Brucea javanica which has been widely utilized to treat dysentery (also known as ulcerative colitis [UC]). METHODS: To improve the water solubility and absolute bioavailability of BD, we developed a self-nanoemulsifying drug delivery system (SNEDDS) composing of MCT (oil), Solutol HS-15 (surfactant), propylene glycol (co-surfactant) and BD. The physicochemical properties and pharmacokinetics of BD-SNEDDS were characterized, and its anti-UC activity and potential mechanism were evaluated in TNBS-induced UC rat model. RESULTS: The prepared nanoemulsion has multiple beneficial aspects including small mean droplet size, low polydispersity index (PDI), high zeta potential (ZP) and excellent stability. Transmission electron microscopy showed that nanoemulsion droplets contained uniform shape and size of globules. Pharmacokinetic studies demonstrated that BD-SNEDDS exhibited enhanced pharmacokinetic parameters as compared with BD-suspension. Moreover, BD-SNEDDS significantly restored the colon length and body weight, reduced disease activity index (DAI) and colon pathology, decreased histological scores, diminished oxidative stress, and suppressed TLR4, MyD88, TRAF6, NF-κB p65 protein expressions in TNBS-induced UC rat model. CONCLUSION: These results demonstrated that BD-SNEDDS exhibited highly improved oral bioavailability and advanced anti-UC efficacy. In conclusion, our current results provided a foundation for further research of BD-SNEDDS as a potential complementary therapeutic agent for UC treatment.

Polydatin Protects Rat Liver against Ethanol-Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 Pathway.

Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target gene haem oxygenase-1 (HO-1). Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) via downregulating toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

Protective Effects of Li-Fei-Xiao-Yan Prescription on Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Oxidative Stress and the TLR4/NF-κB Pathway.

Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responses via decreasing the expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment with LFXY significantly prevented LPS-induced TLR4 expression and NF-κB (p65) phosphorylation. Overall, the present study suggests that LFXY protected mice from acute lung injury induced by LPS via inhibition of TLR4/NF-κB p65 activation and upregulation of antioxidative enzymes and it may be a potential preventive and therapeutic agent for ALI in the clinical setting.

Anti-inflammatory effects of Brucea javanica oil emulsion by suppressing NF-κB activation on dextran sulfate sodium-induced ulcerative colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Brucea javanica is an important traditional medicinal herb used for the treatment of dysentery, malaria, inflammation and cancer in southeast Asia for many years. However, the anti-inflammatory mechanism of Brucea javanica in the treatment of dysentery (also known as ulcerative colitis, UC) has not been fully illuminated. Brucea javanica oil emulsion (BJOE) is the major active and most common application form of Brucea javanica oil (BJO), which has a variety of pharmacological activities. The aim of this study was to investigate the potential anti-inflammatory effect of BJOE and possible mechanism of action on dextran sulfate sodium (DSS)-induced UC in mice. MATERIALS AND METHODS: The components of BJOE were determined by gas chromatography-mass spectrometry (GC-MS). Balb/C mice with dextran sulfate sodium (DSS, 30mg/mL) induced colitis were treated with BJOE (0.5, 1 and 2g/kg) and two positive drugs (sulfasalazine, SASP, 200mg/kg; and azathioprine, AZA, 13mg/kg) once daily by gavage for 7 days. Mice in normal control group and DSS group were orally given the same volume of distilled water and soybean lecithin suspension (0.15g/kg) respectively. The effects of BJOE on DSS-induced UC were assessed by determination of body weight loss, disease activity index (DAI), colon length, histological analysis, as well as levels of pro-inflammatory cytokines. The mRNA expression of MPO, iNOS and COX-2 in colon tissues was detected by qRT-PCR. In addition, NF-κB p65, p-p65 and IκB-α, p-IκBα protein expression levels in colon tissues were investigated using Western blotting. RESULTS: The major components of BJOE were found to be oleic acid (62.68%) and linoleic acid (19.53%) as detected by GC-MS. Our results indicated that BJOE, SASP and AZA showed beneficial effect on DSS-induced colitis in mice, and significantly reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, decreased histological scores, and decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-8, IL-17 and IFN-γ) as compared with the DSS group. In addition, the mRNA expression of MPO, iNOS and COX-2 induced by DSS treatment was remarkably inhibited by BJOE, SASP or AZA treatments. Furthermore, when compared with DSS-treated mice, the activation of NF-κB was significantly inhibited by AZA and BJOE treatment. CONCLUSIONS: Our study shows that BJOE possessed appreciable anti-inflammatory effect against murine experimental UC induced by DSS. The protective mechanism of BJOE may involve inhibition of NF-κB signal transduction pathways and subsequent down-regulation of inflammatory mediators. These findings suggest that BJOE might be an efficacious and promising therapeutic approach for the treatment of UC. Our investigation might also provide experimental evidence for the traditional application of Brucea javanica in the treatment of dysentery and might add new dimension to the clinical indications for BJOE.

Protective Effect of Super-Critical Carbon Dioxide Fluid Extract from Flowers and Buds of Chrysanthemum indicum Linnén Against Ultraviolet-Induced Photo-Aging in Mice.

It is known that solar ultraviolet (UV) radiation to human skin causes photo-aging, including increases in skin thickness and wrinkle formation and reduction in skin elasticity. UV radiation induces damage to skin mainly by superfluous reactive oxygen species and chronic low-grade inflammation, which eventually up-regulate the expression of matrix metalloproteinases (MMPs). In this study, the super-critical carbon dioxide extract from flowers and buds of Chrysanthemum indicum Linnén (CISCFE), which has been reported to possess free radical scavenging and anti-inflammatory properties, was investigated for its photo-protective effect by topical application on the skin of mice. Moreover, CISCFE effectively suppressed the UV-induced increase in skin thickness and wrinkle grading in a dose-dependent manner, which was correlated with the inhibition of loss of collagen fiber content and epidermal thickening. Furthermore, we observed that CISCFE could obviously decrease UV-induced skin inflammation by inhibiting the production of inflammatory cytokines (interleukin-1ß [IL-1ß, IL-6, IL-10, tumor necrosis factor-α), alleviate the abnormal changes of anti-oxidative indicators (superoxide dismutase, catalase, and glutathione peroxidase), and down-regulate the levels of MMP-1 and MMP-3. The results indicated that CISCFE was a novel photo-protective agent from natural resources against UV irradiation.

Prevention of UV radiation-induced cutaneous photoaging in mice by topical administration of patchouli oil.

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin has been widely used in traditional Chinese medicine for the treatment of many diseases, including skin disorders. In the skin beauty and care prescriptions, Pogostemon cablin is one of the top ten frequently used traditional Chinese medicines. AIM OF THE STUDY: The present study was aimed to investigate the protective effects of the essential oil of Pogostemon cablin (patchouli oil, PO) against UV-induced skin photoaging in mice. MATERIALS AND METHODS: To ensure the quality of PO, the chemical compositions of PO were identified, and the content of its chemical marker patchouli alcohol was determined, which was around 28.2% (g/g) in PO. During the experiment period, the dorsal depilated skin of mice was treated with PO for two hours prior to UV irradiation. Then the protective effects of PO on UV-induced skin photoaging were determined by macroscopic and histological evaluations, skin elastic test, collagen content determination and biochemical assays of malondiaidehyde (MDA) content, activities of anti-oxidative indicators including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). RESULTS: Compared to UV exposure groups, present results showed that topical administration of PO, especially at dose of 6mg/mouse and 9mg/mouse, significantly inhibited the increase in skin wrinkle formation, alleviated the reduction in skin elasticity and increased the collagen content by about 21.9% and 26.3%, respectively. We also found that application of 6-9mg/mouse PO could not only decrease the epidermal thickness by about 32.6%, but also prevent the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, the content of MDA was decreased by almost 26.5% and activities of SOD, GSH-Px and CAT were significantly up-regulated after the treatment of PO. CONCLUSION: Results of present study revealed that PO was capable of maintaining skin structural integrity caused by UV irradiation and it was useful in preventing photoaging. These protective effects of PO were possibly due to its anti-oxidative property. Therefore, we suggested that PO should be viewed as a potential therapeutic agent for preventing photoaging.

Relieving visceral hyperalgesia effect of Kangtai capsule and its potential mechanisms via modulating the 5-HT and NO level in vivo.

Kangtai capsule (KT) is one type of traditional Chinese medicine preparation derived from the proved recipe, which was frequently applied as an effective clinical treatment of IBS. However, there still lack the reasonable and all-round analytical approach and the scientific studies on its underlying mechanisms. Therefore, our study aimed to develop the novel method for evaluating its quality as well as to interpret the potential mechanisms. In our study, high performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of KT. The neonatal maternal separation (NMS) on Sprague-Dawley pups was employed to evaluate the therapeutic effect of KT by virtue of various parameters including visceral hyperalgesia, serum nitric oxide (NO) level, and tissue 5-hydroxytryptamine (5-HT) level. Consequently, a chromatographic condition, which was carried at 30°C with a flow rate of 0.5 ml/min on AQUA 3µ C18 column with mobile phase of acetonitrile and water-phosphoric acid (100:0.1, v/v), was established to give a common fingerprint chromatography under 254 nm with a similarity index of 0.963 within ten batches of KT samples. On the NMS model, KT markedly elevated the pain threshold of NMS rats. Furthermore, KT at three doses significantly decreased 5-HT content from distal colon of visceral hyperalgesia rats induced by NMS, while the significant decrease of 5-HT content in serum was only observed in the group with KT at high dose. However, compared with that in NMS rats without KT, there was no apparent difference of 5-HT level from brain issue in the rats with various doses. Besides, KT could substantially elevate the concentration of NO in the serum. The results showed our study developed the simple, rapid, accurate, reproducible qualitative and quantitative analysis by HPLC fingerprint for the quality control for KT. Data from the pharmacological investigation suggested that the curative effect of KT to the visceral hypersensitivity may be concerned with the level of 5-HT and NO in vivo, promising its potential in irritable bowel syndrome treatment.

[Effect compound decoction on notoginsenosides in Panax notoginseng].

OBJECTIVE: To explore the effect of compound decoction on notoginsenosides in Panax notoginseng. METHOD: Notoginsenoside R1, Rg1, Re, Rb1 and pH were used as the parameters to investigate the changes on the content of notoginsenosides in different compound extractions by heating for two hours and their correlation with pH. RESULT: When the pH values of solution of P. notoginseng with Fructus ligustri, P. notoginseng with Eupolyphaga seu steleophaga, P. notoginseng with Pheretima asiatica, and Zhitangjiang Fang (free of Hirudo) were rept higher than 5.7, the reserved rate (RR) of notoginsenside were higher than 90%; When the pH values of decoetion of P. notoginseng with Salvia miltiorrhiza, P. notoginseng with Paeonia lactiflora, P. notoginseng with Platycodon grandiflorum, P. notoginseng with Arctium lappa were kept 4.5-5.5, their RR of notoginsenside were 60% - 85%; When the pH values of the decotction of P. notoginseng with Hirudo nipponica was decreased to 3.4, its RR of of notoginsenside was 38.4%; When the pH values of Zhitangjiang Fang extraction was regulated by 0.1% NaOH solution to pH 6. 3, and the RR of notoginsenside increased to 97%. CONCLUSION: The pH of other Chinese herbal medicines extraction with P. notoginseng compound is a critical effect on the stability and yields of notoginsensides.