In vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. against chemically and immunologically induced liver injuries in mice

Aim of the study

This study aimed to evaluate in vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. (AEAA), which has been used for the treatment of liver disorders in Traditional Uighur Medicine.

Materials and methods

Qualitative and quantitative phytochemical analysis of the AEAA was performed by means of thin layer chromatography and spectrophometric assays. Aqueous extract (50, 100 or 200 mg/kg body weight/day) was administered orally to experimental mice. Liver injury was induced chemically, by a single CCl₄ administration (0.1% in olive oil, 10 ml/kg, i.v.), or immunologically, by injection of endotoxin (LPS, 10 μg, i.v.) in BCG-primed mice. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in mouse sera, as well as superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) in mouse liver tissues were measured. The biochemical observations were supplemented by histopathological examination.

Results

Obtained results demonstrated that the pretreatment with AEAA significantly (P < 0.001) and dose-dependently prevented chemically or immunologically induced increase in serum levels of hepatic enzymes. Furthermore, AEAA significantly (P < 0.05) reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes SOD and GPx towards normal levels. In the BCG/LPS model, increase of the levels of important pro-inflammatory mediators TNF-α and IL-1 was significantly (P < 0.01) suppressed by AEAA pretreatment. Histopathology of the liver tissue showed that AEAA attenuated the hepatocellular necrosis and led to reduction of inflammatory cells infiltration. Phytochemical analyses revealed the presence of sesquiterpene lactones, flavonoids, phenolic acids and tannins in the AEAA.

Conclusions

The results of this study strongly indicate the protective efect of AEAA against acute liver injury which may be attributed to its antioxidative and/or immunomodulatory activity, and thereby scientifically support its traditional use.     

Myrsine seguinii ethanolic extract and its active component quercetin inhibit macrophage activation and peritonitis induced by LPS by targeting to Syk/Src/IRAK-1

Ethnopharmacological relevance

Myrsine seguinii H. LÉVEILLÉ (syn. Rapanea neriifolia) (Myrsinaceae) is a medicinal plants traditionally used in Myanmar to treat infectious and inflammatory diseases. Since none of reports have systematically demonstrated the anti-inflammatory activity of this plant, we aimed to mechanistically understand the regulatory roles of the plant in inflammatory responses using the ethanolic extract of Myrsine seguinii (Ms-EE).

Materials and methods

Activated macrophages and peritonitis symptoms induced by lipopolysaccharide (LPS) were employed. HPLC analysis was used to identify active components. To characterize direct target enzymes, kinase assay was established.

Results

Ms-EE inhibited the production of nitric oxide (NO) and prostaglandin (PG)E₂ in RAW264.7 cells and peritoneal macrophages stimulated by LPS. This extract suppressed the mRNA expression of the inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 genes by down-regulating the activation of nuclear factor (NF)-κB and activator protein (AP-1). Interestingly, it was found that Ms-EE can directly suppress the enzyme activities of Syk, Src, and interleukin-1 receptor-associated kinase-1 (IRAK-1). Similarly, orally administered Ms-EE inhibited the phosphorylation of Src and Syk in peritoneal exudate-derived cells prepared from peritonitis. Finally, HPLC analysis clearly demonstrated that quercetin is a major active component with suppressing activity on the release of inflammatory mediators (NO and PGE₂), and the enzyme activities of Src, Syk, and IRAK-1.

Conclusion

Ms-EE containing quercetin negatively modulates macrophage-mediated in vitro inflammatory responses and LPS-induced peritonitis by blocking the Src/Syk/NF-κB and IRAK-1/AP-1 pathways, which contributes to its major ethnopharmacological use as an anti-inflammatory herbal medicine.     

Methanol extract of Hopea odorata suppresses inflammatory responses via the direct inhibition of multiple kinases

Ethnopharmacological relevance

Hopea odorata Roxb. (Dipterocarpaceae) is a representative Thai ethnopharmacological herbal plant used in the treatment of various inflammation-related diseases. In spite of its traditional use, systematic studies of its anti-inflammatory action have not been performed.

Materials and methods

The inhibitory activities of a Hopea odorata methanol extract (Ho-ME) on the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin E₂ (PGE₂) in RAW264.7 cells and peritoneal macrophages were investigated. The effects of Ho-ME on the gastritis symptoms induced by HCl/EtOH and on ear oedemas induced by arachidonic acid were also examined. Furthermore, to identify the immunopharmacological targets of this extract, nuclear fractionation, a reporter gene assay, immunoprecipitation, immunoblot analysis, and a kinase assay were employed.

Results

Ho-ME strongly inhibited the release of NO, PGE₂, and TNF-α in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ho-ME also clearly suppressed the gene expression of pro-inflammatory cytokines and chemokines, such as interferon (IFN)-β, interleukin (IL)-12, and monocyte chemotactic protein-1 (MCP-1). By analysing the inhibited target molecules, Syk and Src were found to be suppressed in the inhibition of nuclear factor (NF)-κB pathway. In addition, the observed downregulation of activator protein (AP)-1 and cAMP response element-binding (CREB) was due to the direct inhibition of interleukin-1 receptor-associated kinase (IRAK)1 and IRAK4, which was also linked to the suppression of c-Jun N-terminal kinase (JNK) and p38. In agreement with the in vitro observations, this extract also ameliorated the inflammatory symptoms in EtOH/HCl-induced gastritis and arachidonic acid-induced ear oedemas in mice.

Conclusion

Ho-ME has potential as a functional herbal remedy targeting Syk- and Src-mediated anti-inflammatory mechanisms. Future pre-clinical studies will be needed to investigate this possibility.     

Syk and Src are major pharmacological targets of a Cerbera manghas methanol extract with kaempferol-based anti-inflammatory activity

Ethnopharmacological relevance

Cerbera manghas L. (Apocynaceae), a semi-mangrove medicinal plant distributed throughout tropical and subtropical countries, is traditionally known to possess analgesic, anti-inflammatory, anti-convulsant, cardiotonic, and hypotensive activity. In vitro and in vivo anti-inflammatory activities of a methanol extract of the leaves of Cerbera manghas and the underlying molecular mechanisms were investigated to validate the ethnopharmacological use of this plant.

Materials and methods

The effect of Cerbera manghas methanol extract (Cm-ME) on the production of inflammatory mediators and the induction of HCl/EtOH-treated gastritis was explored using macrophages, HEK293 cells, and ICR mice. The molecular targets of this extract and potential active components in Cm-ME were also investigated.

Results

Cm-ME inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS)-treated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. This extract also suppressed the expression of NO synthase (iNOS) and cyclooxygenase (COX)-2. NF-κB-mediated enhancement of luciferase activity, nuclear translocation of p50 and p65, and phosphorylation of IκBα were markedly reduced by Cm-ME treatment. Direct enzyme assays, reporter gene assays, and immunoprecipitation analysis of kinases revealed Syk and Src as immunopharmacological targets of Cm-ME. Moreover, this extract strongly ameliorated the gastric symptoms induced by HCl/EtOH treatment of mice. Finally, HPLC analysis and pharmacological tests identified kaempferol as an active component of the extract with Src/Syk inhibitory activities.

Conclusion

Inhibition of Syk/Src and the NF-κB pathway by kaempferol could play a key role in the anti-inflammatory pharmacological action of Cerbera manghas.     

Management of diabetic complications: A chemical constituents based approach

Ethnopharmacological relevance

Long term hyperglycemia leads to development of complications associated with diabetes. Diabetic complications are now a global health problem without effective therapeutic approach. Hyperglycemia and oxidative stress are important components for the development of diabetic complications. Over the past few decades, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets and less toxic side effects. This review aims to assess the current available knowledge of medicinal herbs for attenuation and management of diabetic complications and their underlying mechanisms.

Material and methods

Bibliographic investigation was carried out by scrutinizing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases (SCOPUS, PUBMED, SCIELO, NISCAIR, Google Scholar) to retrieve available published literature. The inclusion criteria for the selection of plants were based upon all medicinal herbs and their active compounds with attributed potentials in relieving diabetic complications. Moreover, plants which have potential effect in ameliorating oxidative stress in diabetic animals have been included.

Results

Overall, 238 articles were reviewed for plant literature and out of the reviewed literature, 127 articles were selected for the study. Various medicinal plants/plant extracts containing flavonoids, alkaloids, phenolic compounds, terpenoids, saponins and phytosterol type chemical constituents were found to be effective in the management of diabetic complications. This effect might be attributed to amelioration of persistent hyperglycemia, oxidative stress and modulation of various metabolic pathways involved in the pathogenesis of diabetic complications.

Conclusion

Screening chemical candidate from herbal medicine might be a promising approach for new drug discovery to treat the diabetic complications. There is still a dire need to explore the mechanism of action of various plant extracts and their toxicity profile and to determine their role in therapy of diabetic complications. Moreover, a perfect rodent model which completely mimics human diabetic complications should be developed.     

Behavioral recovery following sub-chronic paeoniflorin administration in the striatal 6-OHDA lesion rodent model of Parkinson's disease

In the present studies, the effect of paeoniflorin (PF), one of the main compounds extracted from Paeoniae radix, in alleviating the neurological impairment following unilateral striatal 6-hydroxydopamine (6-OHDA) lesion was examined in Sprague-Dawley rats. Sub-chronic PF (2.5, 5 and 10 mg/kg, s.c., twice daily for 11 days) administration dose-dependently reduced apomorphine (APO)-induced rotation, suggesting that PF had an ameliorative effect on the 6-OHDA-induced neurological impairment. Notably, PF had no direct action on dopamine D(1) receptor or dopamine D(2) receptor indicated by the competitive binding experiments. These results suggest that PF, an active component of Paeoniae radix, might provide an opportunity to introduce a non-dopaminergic management of Parkinson's disease.     

Combination use of ferulic acid,ligustrazine and tetrahydropalmatine inhibits the growth of ectopic endometrial tissue: A multi-target therapy for endometriosis rats

Ethnopharmacological relevance

Ferulic acid (FA), ligustrazine (LZ) and tetrahydropalmatine (THP) are separately isolated from Chinese Angelica, Szechwan Lovage Rhizome and Rhizoma in the Jiawei-Foshou-San formula, a popular traditional Chinese medicine for irregular menses. It has been reported that the combination use of FA+LZ+THP has similar effect on endometriosis, but the underlying mechanisms are unclear. This study was to investigate the combination effects and mechanisms of FA+LZ+THP on endometriosis rats.

Materials and methods

Fifty endometriosis rats were intragastricly treated with FA+LZ+THP for 4 wk. The volume of ectopic endometrial tissue was measured to evaluate the effects. Then the changes in hypothalamic–pituitary–ovarian axis and ERE pathway were indicated by the levels of E₂, GnRH, FSH and LH, and the expressions of ER, HSP90 and COX-2, respectively. In addition, peritoneal macrophages of each rat were cultured in vitro and treated with (FA+LZ+THP)-medicated serum for 24 h. The proliferation and phagocytosis abilities, the levels of IL-1β and TNF-α, and the expression of IκBα were then measured for the changes of peritoneal macrophage activities.

Results

Combination use of FA+LZ+THP diminished the volume of the ectopic endometrial tissues (P<0.05 or P<0.01). It also decreased the E₂ level, suppressed the expression of GnRH, FSH and LH, and decreased the protein expression of ER, HSP90 and COX-2 (all P<0.05 or P<0.01). The phagocytosis ability of peritoneal macrophage was enhanced by (FA+LZ+THP)-medicated serum (P<0.05) with no change of proliferation (P>0.05). Moreover, IL-1β and TNF-α were downregulated (both P<0.05 or P<0.01) and IκBα was upregulated by the (FA+LZ+THP)-medicated serum (P<0.01).

Conclusions

The combination use of FA, LZ and THP could inhibit the growth of ectopic endometrial tissue in endometriosis rats. It might be related to the down-regulation of hypothalamic–pituitary–ovarian axis, the amelioration in ERE pathway and the improvement of peritoneal macrophage activities.     

Compatibility art of traditional Chinese medicine: From the perspective of herb pairs

Ethnopharmacological relevance

Over the past decades, research of traditional Chinese medicine (TCM) mainly focused on developing potential candidates from Chinese medicinal herbs, while the wisdom of applying these traditional herbs has not been paid as much attention as it deserves. As is well-known, multi-herb therapy is one of the most important characteristics of TCM, but the modernization drive of this conventional wisdom has faced many obstacles due to its unimaginable complexity. Herb pairs, the most fundamental and the simplest form of multi-herb formulae, are a centralized representative of Chinese herbal compatibility. In light of their simplicity and the basic characteristics of complex formulae, herb pairs are of great importance in the studies of herb compatibility.

Materials and methods

A systematic search of herb pair related research was carried out using multiple online literature databases, books and monographs published in the past 20 years.

Results

A comprehensive introduction to the compatibility of TCM, the position of herb pairs in TCM and the progresses of several famous herb pairs were provided in this review. Furthermore, the clinical study and the future research trends of herb pairs were also discussed.

Conclusions

Herb pairs have played, and may continue to play a key role in full investigation of general herb compatibility for their indispensable position in TCM. Much more research is needed for the standardization, safety evaluation, and mechanism exploration of herb pairs.     

Phyllanthus amarus: ethnomedicinal uses, phytochemistry and pharmacology: a review

Ethnopharmacological relevance

Phyllanthus amarus Schum. &; Thonn. belongs to the family Euphorbiaceae is a small herb well known for its medicinal properties and widely used worldwide. P. amarus is an important plant of Indian Ayurvedic system of medicine which is used in the problems of stomach, genitourinary system, liver, kidney and spleen. It is bitter, astringent, stomachic, diuretic, febrifuge and antiseptic. The whole plant is used in gonorrhea, menorrhagia and other genital affections. It is useful in gastropathy, diarrhoea, dysentery, intermittent fevers, ophthalmopathy, scabies, ulcers and wounds.

Materials and methods

The present review covers a literature across from 1980 to 2011. Some information collected from traditional Ayurvedic texts and published literature on ethanomedicinal uses of Phyllanthus amarus in different countries worldwide.

Results

Phytochemical studies have shown the presence of many valuable compounds such as lignans, flavonoids, hydrolysable tannins (ellagitannins), polyphenols, triterpenes, sterols and alkaloids. The extracts and the compounds isolated from P. amarus show a wide spectrum of pharmacological activities including antiviral, antibacterial, antiplasmodial, anti-inflammatory, antimalarial, antimicrobial, anticancer, antidiabetic, hypolipidemic, antioxidant, hepatoprotective nephroprotective and diurectic properties.

Conclusion

The present review summarizes information concerning the morphology, ecology, ethnopharmacology, phytochemistry, biological activities, clinical applications and toxicological reports of P. amarus. This review aims at gathering the research work undertaken till date on this plant in order to provide sufficient baseline information for future works and commercial exploitation.     

In vitro and in vivo anti-inflammatory effect of Rhodomyrtus tomentosa methanol extract

Ethnopharmacological relevance

Rhodomyrtus tomentosa (Aiton) Hassk. is a representative Thai medicinal plant traditionally used in South Asian countries to relieve various inflammatory symptoms. However, no systematic studies on its anti-inflammatory activity and mechanisms have been reported.

Materials and methods

The effect of the methanol extract from the leaves of this plant (Rt-ME) on the production of inflammatory mediators [nitric oxide (NO) and prostaglandin E₂ (PGE₂)] and the molecular mechanism of Rt-ME-mediated inhibition, including target enzymes, were studied with RAW264.7, peritoneal macrophage, and HEK293 cells. Additionally, the in vivo anti-inflammatory activity of this extract was evaluated with mouse gastritis and colitis models.

Results

Rt-ME clearly inhibited the production of NO and PGE₂ in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. According to RT-PCR, immunoblotting and immunoprecipitation analyses and a kinase assay with mRNA, whole cell extract, and nucleus lysates from RAW264.7 cells and mice, it was revealed that Rt-ME was capable of suppressing the activation of both nuclear factor (NF)-κB and activator protein (AP)-1 pathways by directly targeting Syk/Src and IRAK1/IRAK4.

Conclusion

Rt-ME could have anti-inflammatory properties by suppressing Syk/Src/NF-kB and IRAK1/IRAK4/AP-1 pathways and will be further developed as a herbal remedy for preventive and/or curative purposes in various inflammatory diseases.     

A review of Omics research in acupuncture: the relevance and future prospects for understanding the nature of meridians and acupoints

Relevance

Acupuncture is an intrinsic part of traditional Chinese medicine. The current understanding of the acupuncture meridian system, acupoints and the potential utilizing Omics technologies are summarized in this review.

Material and methods

A systematic search for acupuncture involving Omics technologies was carried out using multiple online literature databases. The records retrieved were from the full collections of each database dated to September 2011. Data produced from functional genomic technologies were extracted from the collected acupuncture/moxibustion studies and subjected to evaluation. Analyses and comments were summarized on the advances in experimental research in acupuncture/moxibustion-related studies, and the future for strategies and approaches in the era of functional genomics highlighted.

Results

An overview of articles indicated that several diseases or symptoms with evidence of effectiveness had been piloted for using functional genomic technologies, such as Parkinson's disease, allergic disorders, pain, and spinal cord injury, most of which are chronic “difficult diseases”. High-throughput genomic and proteomic profiling of gene expression in tissues has been able to identify potential candidates for the effects of acupuncture and provide valuable information toward understanding the possible mechanisms of the therapy. However, without further holistic and sophisticated analyses in the context of metabolomics and systems biology, the current attempts and the foreseeable developments appear to be insufficient to produce firm conclusions. Noticeably, the recent rapid advances in functional molecular imaging targeting specific metabolites have shown great promise and if combined with other post-genomic technologies, could be extremely helpful for the acupuncture studies in human subjects.

Conclusion

This review suggest that disease-oriented studies using the approach of multi-indexed high-throughput technologies and systems biology analyses will be a preferred strategy for future acupuncture/moxibustion research.