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J Ethnopharmacol [journal]
- Hugan Qingzhi medication ameliorates hepatic steatosis by activating AMPK and PPARα pathways in L02 cells and HepG2 cells. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Apr 12.
Hugan Qingzhi tablet (HQT), a lipid- lowering traditional Chinese medicine formula, has been used for the prevention and treatment of nonalcoholic fatty liver (NAFLD).This study was realized to evaluate the effects of HQT-medicated serum on hepatic steatosis using in vitro experiments with cells and explore the relevant mechanisms with method of serum pharmacology.A model of hepatic steatosis in the L02 and HepG2 cells was induced by free fatty acid (FFA). The components in the HQT-medicated serum were assayed by high-performance liquid chromatography. Intracellular lipid droplets were detected by Oil Red O staining, and their ultrastructure was examined by transmission electron microscope. The biochemical parameters, including triglyceride (TG), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total antioxidant capacity (T-AOC), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH), were measured with commercial kits. Furthermore, the expression of adiponectin, AMP-activated protein kinase (AMPK) phosphorylation, sterol regulatory element-binding protein 1 (SREBP-1), peroxisome proliferator activated receptor-α (PPARα), carnitine palmitoyltransferase 1 (CPT-1), and acetyl-CoA oxidase 1 (ACOX1) was analyzed by Western blot and/or quantitative reverse transcription- polymerase chain reaction (qRT-PCR).Moderate- and high-dose HQT-medicated serum reduced (P<0.05 or P<0.01) the accumulation of lipid droplets and the cellular TG content in L02 and HepG2 cells. They caused significant reductions (P<0.01) in LDH, AST, ALT and MDA and significant increase (P<0.05 or P<0.01) in T-AOC in the culture medium. They also caused increase (P<0.05 or P<0.01) in GSH level and SOD activity in FFA-induced steatotic L-02 and HepG2 cells. Furthermore, Moderate- and high-dose HQT-medicated serum enhanced (P<0.01) adiponectin expression in a concentration-dependent manner and increased (P<0.05 or P<0.01) the phosphorylation of AMPK and the expression of PPARα, CPT-1, and ACOX1, and reduced (P<0.05 or P<0.01) the expression of SREBP-1.The results suggested that HQT-medicated serum exerts a preventive effect against hepatic steatosis, and the potential mechanism might be activation of AMPK and PPARα pathways.
- Sub-acute toxicity of the chloroformic extract of Rapanea melanophloeos (L.) Mez in rats. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Apr 12.
Cape beech (Rapanea melanophloeos) is an important medicinal plant that is widely used in most of Africa. Currently, little toxicological information is available on its safety following prolonged use.In this study, we sought to evaluate the oral sub-acute toxicity of R. melanophloeos stem bark chloroformic extract using Sprague Dawley rats.Six-week old rats were orally administered with the extract at dosage levels of 100mg/kg, 300mg/kg and 1000mg/kg for 28 days. Clinical signs, hematological and clinical chemistry parameters were monitored, while organ weights and organ pathology were evaluated at the end of the study.The extract caused a significant reduction in bodyweight at 1000mg/kg. The hematological profiles of animals at this dose showed an increase in the erythrocyte count and the hematocrit that were accompanied by decreases in the mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Biochemical parameters were not altered in a dose-related manner when compared to the controls. There were time associated alterations on both hematological and biochemical parameters, but pathological examination did not reveal any treatment related changes in any of the organs.Our results demonstrate that the chloroformic stem bark extract of R. melanophloeos may be of no toxicological concern at dosage levels up to 1000mg/kg. Rapanea melanophloeos can therefore be used confidently in African traditional medicine at these or lower dosage levels.
- ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Apr 12.
Korean Red Ginseng (KRG) is one of representative traditional herbal medicines prepared from Panax ginseng Meyer (Araliaceae) in Korea. It has been reported that KRG exhibits a lot of different biological actions such as anti-aging, anti-fatigue, anti-stress, anti-atherosclerosis, anti-diabetic, anti-cancer, and anti-inflammatory activities.Although systematic studies have investigated how KRG is able to ameliorate various inflammatory diseases, its molecular inhibitory mechanisms had not been carried out prior to this study.In order to investigate these mechanisms, we evaluated the effects of a water extract of Korean Red Ginseng (KRG-WE) on the in vitro inflammatory responses of activated RAW264.7 cells, and on in vivo gastritis and peritonitis models by analyzing the activation events of inflammation-inducing transcription factors and their upstream kinases.KRG-WE reduced the production of nitric oxide (NO), protected cells against NO-induced apoptosis, suppressed mRNA levels of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and interferon (IFN)-β, ameliorated EtOH/HCl-induced gastritis, and downregulated peritoneal exudate-derived NO production from lipopolysaccharide (LPS)-injected mice. The inhibition of these inflammatory responses by KRG-WE was regulated through the suppression of p38, c-Jun N-terminal kinase (JNK), and TANK-binding kinase 1 (TBK1) and by subsequent inhibition of activating transcription factor (ATF)-2, cAMP response element-binding protein (CREB), and IRF-3 activation. Of ginsensides included in this extract, interestingly, G-Rc showed the highest inhibitory potency on IRF-3-mediated luciferase activity.These results strongly suggest that the anti-inflammatory activities of KRG-WE could be due to its inhibition of the p38/JNK/TBK1 activation pathway.
- Evaluation of antiinflammatory properties of Ocimum sanctum in human monocytic (THP-1) cells. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Apr 11.
Ocimum sanctum (OS), commonly known as Holy basil/Tulsi, has been traditionally used to treat cardiovascular diseases (CVD) and manage general cardiac health.The present study is designed to evaluate the antiinflammatory effect of O. sanctum and its phenolic compound and eugenol (EUG) in human monocytic (THP-1) cells and validate its traditional use for treating cardiovascular diseases.The phytochemical analysis of alcoholic and water extracts of OS-dry leaves (OSAE and OSWE) was done using LC-QTOF-MS. A phenolic compound, EUG was quantified in both OSAE and OSWE by LC-MS technique using mass hunter work station software quantitative analysis system. The effect of both OSAE, OSWE, pure compound EUG and positive control imatinib (IMT) was investigated in THP-1 cells by studying the following markers: lipopolysaccharide (LPS) induced tumour necrosis factor alpha (TNF-α) secretion by ELISA, gene expression of inflammatory markers (TNF-α, IL-6, MIP-1α and MCP-1) by real time PCR and translocation of nuclear factor kappa B (NF-κB) by confocol microscopy. Furthermore, the effect of the extracts, EUG and IMT was studied on phorbol-12-myristate-13-acetate (PMA) induced monocyte to macrophage differentiation and gene expression of CD14, TLR2 and TLR4.The LC-MS analysis of OSAE and OSWE revealed for the presence of several bioactive compounds including eugenol. Quantitative analysis revealed that OSAE and OSWE had EUG of 12ng/mg dwt and 19ng/mg dwt respectively. OSAE, OSWE (1mg dwt/mL) pure compound EUG (60µg/mL) and positive control IMT (20µg/mL) showed marked inhibition on LPS induced TNF-α secretion by THP-1 cells. At the selected concentration, the plant extracts, EUG and IMT inhibited gene expression of cytokines and chemokines (IL-6, TNF-α, MIP-1α, MCP-1) and translocation of NF-κB-p65 to the nuclei. In addition, they showed significant inhibition on PMA induced monocyte to macrophage differentiation and the gene expression of CD14, TLR2 and TLR4 markers.The result of the present study validated traditional use of O. sanctum for treating cardiovascular disease for the first time by testing antiinflammatory activity of O. sanctum in acute inflammatory model, LPS induced THP-1 cells. The plant extracts showed significant antiinflammatory activity, however, further to be evaluated using chronic inflammatory animal models like diabetic or apolipoprotein E-deficent mice to make it evidence based medicine. The phenolic compound eugenol (60µg/mL) showed significant antiinflammatory activity. However the amount of eugenol present in 1mg of OSAE and OSWE (12ng/mg and 19ng/mg dwt respectively) used for cell based assays was very low. It suggests that several other metabolites along with eugenol are responsible for the efficacy of the extracts.
- Hydnocarpus: An Ethnopharmacological, Phytochemical and Pharmacological Review. [REVIEW]
- J Ethnopharmacol 2014 Apr 11.
The genus Hydnocarpus (Flacourtiaceae) includes forty species that are spread across the globe. In the Indian System of Medicine, Hydnocarpus pentandrus (Buch.-Ham.) Oken. is primarily used for treating leprosy and other skin disorders. It is known as "Chaulmoogra" and is also used to treat other indications including constipation, inflammation, blood disorders, and worm infestations. Various species of Hydnocarpus are also used in traditional medicine in China, Thailand, Malaysia, and Myanmar for several skin disorders.To assess the therapeutic potential of species from the Hydnocarpus genus and to determine future avenues for research.All relevant scientific literature published up to the end of December 2013 was retrieved via a library and electronic search (SciFinder, PubMed, ScienceDirect, and Google Scholar). Manual searches of traditional books like to ancient classics, including Vaidya Yoga Ratnavali, Siddha Materia Medica, and contemporary references including The Ayurvedic Pharmacopoeia of India and The Ayurveda Formulary, were also performed.Seed oil from species of the Hydnocarpus genus is used for medicinal purposes, predominantly for various skin disorders. This oil is reported to contain a characteristic class of compounds known as cyclopentenyl fatty acids. Furthermore, seeds of this genus are reported to contain triglycerides of fatty acids, sterols, flavonoids, and flavonolignans. Hydnocarpin, a flavonolignan, is reported to potentiate antimicrobial and anticancer activity. The extracts and compounds isolated from this plant show a wide spectrum of pharmacological properties, including antibacterial, antileprotic, antitubercular, antipsoriatic, antirheumatic, hypolipidemic, antidiabetic, anticancer, anti-inflammatory, and antioxidant activities. The antileprotic activity is postulated to be due to the cyclopentenyl fatty acids present in the seed oil.Flavonolignans have an interesting chemical motif, and hydnocarpin and its congeners should be investigated for their activities and the mechanism underlying these activities. Multi-drug-resistant microbes are on the increase, and the possible inhibitory effect of these compounds when used with current antimicrobials should also be evaluated. Furthermore, unique cyclopentenyl fatty acids should also be investigated to understand the exact mechanism of action underlying antileprotic activity. Additional in depth phytochemical investigations of seed oil and extracts are required to tap the true potential of species from the Hydnocarpus genus.
- Effects of deer velvet extract from Formosan sika deer on the embryonic development and anti-oxidative enzymes mRNA expression in mouse embryos. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Apr 11.
The deer velvet or its extracts has been widely used in clinic. It has been used in promoting reproductive performances and treating of oxidation and aging process.The aim of this study is to investigate the effects of velvet extract from Formosan sika deer (Formosan sika deer; Cervus nippon taiouanus, FSD) velvet on mouse embryonic development and anti-oxidant ability in vitro.Mouse 4-cells embryos were divided into sixteen groups for 72h in vitro incubation. The embryonic development stages and morphology were evaluated every 12h in experimental period. The quantitative real time PCR was used to measure the CuZn-SOD, GPx and CAT mRNA expression of the blastocysts.The 4-cells embryos of hydrogen peroxide (HP) groups did not continue developing after oxidant stress challenged. The blastocyst developmental rate (90.0∼90.4%, P>0.05) and normal morphological rate (84.4∼85.1%, P>0.05) of the 1 and 2% DV extract groups were similar to that in the control group (90.7 and 88.8%, respectively). The embryos challenged by HP (5, 10 and 25μM) and subsequently incubated in mHTF medium with 1 and 2% of deer velvet (DV) extracts were able to continue development, the blastocyst developmental rate of those groups were similar to that in the control group. The relative mRNA expression of the focused anti-oxidative enzymes in the mouse embryos did not significantly differ among the designed DV treatment groups (P>0.05).The FSD velvet extract in adequate concentration could promote anti-oxidative enzymes mRNA expression followed the challenge of hydrogen peroxide, relieve the mouse embryo under oxidative stress, and maintain the blastocyst developmental ability in vitro.
- Clerodendrum serratum (L.) Moon.- A Review on Traditional Uses, Phytochemistry and Pharmacological Activities. [REVIEW]
- J Ethnopharmacol 2014 Apr 10.
Clerodendrum serratum (L.) Moon. (Verbenaceae) is an important medicinal plant growing in the tropical and warm temperate regions like Africa, Southern Asia; Malaysia and distributed throughout in forests of India and Srilanka. It is traditionally valued and reported for treating pain, inflammation, rheumatism, respiratory disorders, fever and malarial fever in India with a long history.To provide a comprehensive overview of the traditional and ethno medicinal uses, phytochemistry and biological activities of C. serratum with clinical and toxicity data and possibly make recommendations for further research.All relevant worldwide accepted databases were searched for the terms "Clerodendrum", "Clerodendrum serratum", "Bharangi" and "Cheruthekku" along with the other literature from Indian classical texts and pharmacopoeias. There was no specific timeline set for the search. The accessible literatures available on C. serratum were collected via electronic search using Pubmed, Scopus, Science Direct and traditional books reports on ethnopharmacology and traditional medicines.C. serratum has played an important role in Indian system of medicine. In addition to the common local use in respiratory diseases, other ethnomedicinal uses include treatment of pain, inflammation, rheumatism and fever especially malarial fever. Scientific studies on extracts and formulations revealed anti-asthmatic, mast cell stabilization and anti-allergic effects of roots of C. serratum. Reported data on pharmacological activities also includes hepatoprotective, anti-oxidant, anti-inflammatory and anticancer potential of the drug. Saponins (terpenoids and steroids), flavonoids and phenolics isolated from roots have been the focus of phytochemical investigations as the biological activity has been ascribed to the saponins, which are known to possess anti-inflammatory and anti-cancer activity. Isolated bioactives from roots like icosahydropicenic acid and ursolic acid have been claimed to offer anti-allergic and hepatoprotective activity.Therapeutic potential of roots and leaves of C. serratum has been demonstrated in the conditions like asthma, allergy, fever, inflammation and liver disorders attributed to the presence of various flavonoids, phenolics and saponins present in the drug. Many ethnobotanical claims have been confirmed through modern in-vitro and in-vivo pharmacological studies of different extracts and isolates from plant; however, additional studies on the biomarkers are needed to establish mechanism of action and to validate the traditional use of this drug in clinical practices after proper safety assessment.
- Gochnatia polymorpha ssp. floccosa: Bioprospecting of an anti-inflammatory phytotherapy for use during pregnancy. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Apr 9.
Gochnatia polymorpha ssp. floccosa is used in folk medicine to treat inflammation and infections. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly consumed medications during pregnancy in women with inflammatory diseases. However, the relationship between the use of NSAIDs and the risk of miscarriage and birth defects and/or benefits is not fully understood. Thus, an investigation regarding the use of G. polymorpha during gestation is of relevance for developing safe anti-inflammatory drugs for use during pregnancy.The pregnant females were randomly divided into 5 groups. Control Group received a hydroalcoholic solution (1.2%), via gavage, for at least 15 days prior to mating and throughout the gestational period. The Pre-treatment Group received G. polymorpha ethanol extract (GPEE), via gavage, at a dose of 100mg/kg body weight (b.w.) for at least 15 days prior to mating and up to the appearance of the vaginal plug. The Organogenesis Group received GPEE at a dose of 100mg/kg (b.w.), via gavage, on the 5-15th gestacional day. The Pregnancy Group received GPEE at a dose of 100mg/kg (b.w.), via gavage, throughout the gestational period (from the 1st to the 18th day of pregnancy). The Pre+Pregnancy Group received GPEE at a dose of 100mg/kg (b.w.), via gavage, for at least 15 days prior to mating and throughout the entire gestational period. The clinical signals of maternal toxicity and teratogenesis were evaluated. Additional assays to evaluate chronic inflammation, antigenotoxicity and immunomodolatory activity were performed.The results indicated that GPEE does not interfere with reproductive performance or embryo-fetal development but does correlate with reduced weight and fetal length. The extract was not teratogenic or mutagenic or an immunomodulator. However, GPEE did exhibit effective anti-inflammatory activity. Based on this study, it can be inferred that GPEE is an important, safe anti-inflammatory agent for use during pregnancy according to the experimental design we utilized, which opens up possibilities for the bioprospecting of a new anti-inflammatory phytotherapy for use during pregnancy.
- Therapeutic effect of Soshiho-tang, a traditional herbal formula, on liver fibrosis or cirrhosis in animal models: A systematic review and meta-analysis. [REVIEW]
- J Ethnopharmacol 2014 Apr 13.
Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis at the end stage. Soshiho-tang (SST) has been used to improve liver fibrosis/cirrhosis by ameliorating fibrosis-specific markers. This study aimed to assess the efficacy of SST on liver fibrosis/cirrhosis through a systematic review of the literature and meta-analysis using animal models.Studies of SST treatment in liver fibrosis/cirrhosis-induced animal models were searched by electronic data bases. The quality of the studies included was assessed and the efficacy of SST was evaluated based on markers from liver tissues and serum.Among the 838 studies identified in the literature search, 20 studies that met the inclusion criteria were included in the analysis. SST significantly reduced the elevated levels of fibrosis markers, such as the degree of fibrosis, hydroxyproline, hyaluronic acid, transforming growth factor-β1, and procollagen III in liver tissues, and aspartate aminotransferase, alanine aminotransferase, procollagen III, tissue inhibitor of metalloproteinase-1, and type IV collagen in the serum.SST was effective in decreasing pathologically increased markers in animal models of liver fibrosis/cirrhosis. A larger-scale of animals, well-designed animal study is expected to improve the methodological quality, heterogeneity, and potential biases of the meta-analysis.
- Anti-inflammatory effects of Bryophyllum pinnatum (Lam.) Oken ethanol extract in acute and chronic cutaneous inflammation. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Apr 9.
Bryophyllum pinnatum (Lam.) Oken (Crassulaceae), popularly known in Brazil as "folha-da-fortuna", is a plant species used in folk medicine for the external and internal treatment of inflammation, infection, wound, burn, boil, ulcers and gastritis, and several other diseases.The present study aimed to perform the chemical characterization and the evaluation of the topical anti-inflammatory effect of the ethanol extract of Bryophyllum pinnatum leaves (EEBP) in acute and chronic mice ear edema models induced by different irritant agents.The EEBP chemical characterization was performed by HPLC-UV DAD. Ear edema on Swiss mice was induced by the topical application of Croton oil (single and multiple applications), arachidonic acid, phenol, capsaicin and ethyl phenylpropiolate (EPP). The topical anti-inflammatory effect of EEBP was evaluated by measuring the ear weight (acute inflammation models) and thickness (chronic inflammation model). Histopathological analyses of ear tissue samples sensitized with Croton oil (single and multiple applications) were also performed.The flavonoids rutin, quercetin, luteolin and luteolin7-O-β-D-glucoside were detected in EEBP. Topical application of EEBP significantly (P<0.001) inhibited the ear edema induced by Croton oil single application (inhibition of 57%), arachidonic acid (inhibition of 67%), phenol (inhibition of 80%), capsaicin (inhibition of 72%), EPP (inhibition of 75%) and Croton oil multiple application (55% after 9 days). Histopathological analyses confirmed the topical anti-inflammatory effect of EEBP since it was observed reduction of edema, epidermal hyperplasia, inflammatory cells infiltration and vasodilatation.The results suggest that EEBP is effective as a topical anti-inflammatory agent in acute and chronic inflammatory processes possibly due to inhibition of arachidonic acid pathway, which justify the traditional use of B. pinnatum as a remedy for skin disorders.