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Dipterocarpus alatus has been used for the treatment of infectious skin diseases and ulcerative wounds in Thai traditional medicine. A major pathogen in human superficial skin infections is methicillin-resistant Staphylococcus aureus (MRSA). This study determined the wound healing, antibacterial, and anti-inflammatory activities of D. alatus twig emulgel against MRSA-infected mouse superficial skin wounds. Ethyl acetate-methanol crude extract of D. alatus twig was incorporated into emulgel at concentrations of 20 and 40 mg/g (D20 and D40) and its activity was compared to tetracycline emulgel (160 µg/g, Tetra). MRSA-infected superficial wounds demonstrated decreased skin barrier strength, increased transepidermal water loss (TEWL), and mast cell accumulation. Expression of toll-like receptor 2 (TLR-2), NF-κß, TNFα, IL-1ß, IL-6 and IL-10 genes were induced after MRSA infection. Daily application of 100 µL of D20 or D40 for 9 days restored skin barrier strength and TEWL while reducing mast cell and MRSA numbers compared to the non-treated group (MRSA-NT). The wounds treated with D20 and D40 were entirely healed on day 9. Expression of TLR-2 and cytokine-related genes NF-κß, TNFα, IL-1ß, IL-6 and IL-10 were normalized by treatment with either D20 or D40. Therefore, emulgel containing 20 to 40 mg/g ethyl acetate-methanol crude D. alatus twig extract is a good candidate for development as a topical formulation for MRSA-infected ulcerated wounds.

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<b>Background and Objective:</b> Ulcerative colitis (UC) is inflammation of the large intestine with ulceration but can also cause extraintestinal manifestations (EIM) by damaging surrounding organs such as the liver. <i>Garcinia mangostana</i> (GM) pericarp and α-mangostin (MGS) have been reported to have anti-inflammatory activity. This study evaluated the effects of GM pericarp extract and MGS on the expression of hepatic cytochrome P450 (CYP) enzymes as an EIM of UC. <b>Materials and Methods:</b> Male ICR mice were orally administered GM pericarp extract (40, 200 and 1000 mg/kg/day), MGS (30 mg/kg/day) or sulfasalazine (SUL) (100 mg/kg/day) daily for 7 days. On days 4-7, UC was induced by dextran sulfate sodium (DSS 40 kDa, 6 g/kg/day). Profiles of CYP mRNA expression were determined by RT/qPCR. Alkoxyresorufin <i>O</i>-dealkylation (including ethoxy-, methoxy-, pentoxy- and benzyloxy-resorufin), aniline hydroxylation and erythromycin <i>N</i>-demethylation CYP responsive activities were also examined. <b>Results:</b> The DSS-induced UC mice showed suppressed expression<i> </i>of <i>Cyp1a1</i>, <i>Cyp1a2</i>, <i>Cyp2b9/10</i>, <i>Cyp2e1</i>, <i>Cyp2c29</i>, <i>Cyp2d9</i>, <i>Cyp3a11</i> and <i>Cyp3a13</i> mRNAs. The GM pericarp extract and MGS restored expression of all investigated CYPs and their responsive enzyme activities in DSS-induced UC mice to levels comparable to the control and parallel to the effects of the anti-inflammatory control SUL. <b>Conclusion:</b> The GM is a promising therapy to restore UC-modified hepatic CYP profiles.

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ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is an inflammatory disorder of the colon. Garcinia mangostana Linn. (GM) has been traditionally used for its anti-inflammatory and antioxidant activities. AIM OF THE STUDY: The effects of GM and its bioactive constituent α-mangostin on dextran sulfate sodium (DSS)-induced UC in mice were investigated. MATERIALS AND METHODS: Adult ICR mice (n = 63) were pretreated with ethanolic GM extract at 40, 200, and 1000 mg/kg/day (GM40, GM200, and GM1000), α-mangostin at 30 mg/kg/day, or sulfasalazine at 100 mg/kg/day (SA) for 7 consecutive days. On days 4-7, UC was induced in the mice by the oral administration of DSS (40 kDa, 6 g/kg/day), while control mice received distilled water. The UC disease activity index (DAI) and histological changes were recorded. The activities of myeloperoxidase, catalase, and superoxide dismutase, and the levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) were determined. The mRNA expression of inflammatory related genes including proinflammatory cytokine Tnf-α, Toll-like receptor (Tlr-2), adhesion molecules (Icam-1 and Vcam-1), and monocyte chemoattractant protein (Mcp-1) were evaluated. RESULTS: Treatment with GM or α-mangostin decreased the UC DAI and protected against colon shortening and spleen and kidney enlargement. GM and α-mangostin prevented histological damage, reduced mast cell infiltration in the colon, and decreased myeloperoxidase activity. GM and α-mangostin increased catalase and superoxide dismutase activity and decreased ROS, NO, and MDA production. GM downregulated mRNA expression of Tnf-α, Tlr-2, Icam-1, Vcam-1, and Mcp-1. CONCLUSIONS: GM and α-mangostin attenuated the severity of DSS-induced UC via anti-inflammatory and antioxidant effects. Therefore, GM is a promising candidate for development into a novel therapeutic agent for UC.

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Garcinia mangostana (mangosteen) pericarp has antibacterial effects; however, information regarding its anti-inflammatory activity in vivo is limited. The anti-inflammatory effect of G. mangostana pericarp extract against methicillin-resistant Staphylococcus aureus (MRSA)-induced superficial skin infection was investigated in mice using a tape stripping model. G. mangostana pericarp ethanolic extract (GME) and its constituent, α-mangostin, were topically administered to mice with MRSA-induced superficial skin infection. MRSA-infected wounds treated with GME were completely healed on the 10th day of the study and the number of MRSA-colonies decreased from the first day of the study, whereas α-mangostin-treated wounds never completely healed with higher numbers of MRSA colonies. The epidermis of GME-treated wounds had nearly completely regenerated, with no inflammatory cell infiltration. In contrast, α-mangostin-treated wounds exhibited neutrophil infiltration and accumulation of mast cells. MRSA-infected wounds without treatment showed high expression of TNF-α, IL-6, IL-1ß, and TLR-2 genes. In contrast, GME decreased mRNA levels, restoring expression of those genes to normal levels. Notably, α-mangostin did not down-regulate the expression of pro-inflammatory cytokines to the same extent as GME. Hence, GME is a promising alternative MRSA treatment because of its antibacterial, anti-inflammatory, and wound healing effects.

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Ulcerative colitis (UC) is an idiopathic relapsing inflammatory disease. Although the etiology of UC remains unclear, it could be characterized by inflammation of the intestinal mucosa, starting from the rectum and potentially involving the entire colon. The immune response and inflammatory pathway of UC have shown that tissue damage is driven by dynamic and complexes of cells and cytokines. Various types of cells, including antigen-presenting cells (dendritic cells and macrophages), T helper cells, regulatory T cells, and natural killer T cells, play a crucial role in UC pathogenesis by regulation, suppression, and maintenance of inflammation. Moreover, cytokine networks become an important part due to their signaling function, which is indispensable for cell communication. Pro-inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1, IL-6, IL-9, IL-13, and IL-33] play significant roles in upregulation, while anti-inflammatory cytokines (transforming growth factor-ß, IL-10, and IL-37) play significant roles in downregulation of disease progression. The pathogenesis of UC consists of immuno-inflammatory pathways related to the multiple components of the intestine, including the epithelial barrier, commensal microflora, antigen recognition, dysregulation of immunological responses, leukocyte recruitment, and genetic factors. The understanding of immuno-inflammatory pathways of UC might lead to the development of a specific therapy and/or a novel treatment that could be more efficient.

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CONTEXT: Garcinia mangostana Linn. (Guttiferae) (GM) pericarp has been shown to exhibit good in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA); however, there is currently no available information regarding its in vivo antibacterial activity. OBJECTIVE: To examine in vivo antibacterial activity of G. mangostana extract against MRSA. MATERIALS AND METHODS: GM pericarp was extracted by ethanol (GM-EtOH) and methanol (GM-MeOH). The crude extracts were examined for in vitro antibacterial activity against MRSA using broth microdilution assay. The in vivo antibacterial activity of 10% GM-EtOH against MRSA was determined in a tape stripping mouse model of superficial skin infection for 9 days by evaluating transepidermal water loss (TEWL) and performing colony counts from cultured swabs. RESULTS: GM-EtOH showed greater in vitro activity against MRSA than GM-MeOH in broth microdilution assay with minimum inhibitory concentration 17 versus 20 µg/mL and minimum bactericidal concentration 30 versus 35 µg/mL, respectively. The GM-EtOH (13.20 ± 0.49%) contained α-mangostin more than the GM-MeOH (9.83 ± 0.30%). In the tape stripping mouse model, 10% GM-EtOH reduced the number of MRSA colonies (0-1) recovered from infected wounds (>100 colonies) on the first day of treatment, restored TEWL to normal levels on the fourth day, and had completely healed the wounds by day 9. CONCLUSION: GM-EtOH showed promising in vivo antibacterial activity against MRSA in a superficial skin infection model in mice. It is of interest to develop a topical formulation of GM-EtOH to further study its potential as a novel antibacterial agent.

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BACKGROUND/AIM: Plumbago indica (PI) L. and its active constituent, plumbagin, has been traditionally claimed for several pharmacological activities; however, there is little information regarding their toxicity. The present study aims to examine the effects of plumbagin and PI extract (PI) on hepatic histomorphology and antioxidative system in mice. MATERIALS AND METHODS: Adult male intelligent character recognition mice were intragastrically administered plumbagin (1, 5, and 15 mg/kg/day) or PI (20, 200, and 1,000 mg/kg/day) consecutively for 14 days. Hepatic histomorphology was examined. Plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and the ratio of reduced to oxidized glutathione (GSH/GSSG) were determined. RESULTS: Plumbagin and PI concentration-dependently induced hepatic injury based on histopathological changes via imbalance of antioxidative system. Plumbagin and PI significantly increased plasma ALT and AST levels, hepatic lipid peroxidation, and GPx activity but significantly decreased hepatic SOD and CAT activities. The GSH/GSSG ratio was significantly reduced by plumbagin. CONCLUSION: Plumbagin and PI caused hepatotoxic effects in the mice by unbalancing of the redox defense system. Therefore, plumbagin and PI-containing supplements should be used cautiously, especially when consumed in high quantities or for long periods.