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Purpose: Mucositis is a major complication associated with chemotherapy and radiation therapy for cancer. Mechanisms of developing mucosal damage from both chemotherapy and radiotherapy are thought to be an inflammatory process. It has been known that many herbs have an anti-inflammatory effect. This study was aimed to evaluate the anti-inflammatory effect of Scutellaria baicalensis extract (S) in vitro and in vivo using Wistar rat with methotrexate (MTX)-induced enteritis or radiation-induced proctitis. Materials and Methods: For in vitro study, RAW 264.7 cells were grown in DMEM containing 0.1% FBS for 24 hours. To evaluate the effect of S on production of inflammatory cytokines induced by radiation, RAW cells were treated with two different concentrations (0.5 and 1 mg/mL) of S for 24 hours and then irradiated with one of two different doses (three-culture soup 48 hours' incubation after irradiation) and measured levels of inflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1) with ELISA. We investigated whether S affected the transcription of the various proinflammatory genes. Cells were untreated or treated with S for 30 minutes before exposure to 100 ng/mL lipopolysaccharide (LPS). At the indicated time points following LPS stimulation, cells were harvested. Total RNA was isolated and RT-PCR was carried out using 1 µg of total RNA. To evaluate the possible mechanisms responsible for the anti-inflammatory effects of S in LPS-stimulated RAW cells, the levels of phosphorylation of Erk and p38 were measured and nuclear extracts were analyzed for measurement of levels of NF-κB p65 present in nuclei. In an in vivo study, we used 6- to 8-week-old female Wistar rat. Rats for MTX-induced enteritis were orally administrated once a day with three different concentrations (5, 10, and 15 mg/kg) of S and saline for total 12 days from 1 week before MTX injection and then injected with MTX (2.5 mg/kg, subcutaneously) for 3 days to induce intestinal mucositis. The histologic severity of gut damage from MTX treatment on day 5 was assessed semiquantitatively. For the radiation proctitis model, rats received radiation with a single dose of 17.5 Gy to the rectum. They were fed daily with S 15 mg/kg/d or saline for 7 days prior to radiation and continued for 10 days after irradiation. Rats were sacrificed on the tenth day and sixth week after irradiation for histologic grading of acute and chronic changes, respectively. Results: In an in vitro study, after irradiation with 3 and 6 Gy, all of the IL-β, IL-6, TNF-α and MCP-1 levels were increased in proportion to radiation dose. A dose-dependent reduction of these values was observed after treatment of S. Treatment with 25 and 50 µg/mL of S suppressed mRNA level of IL-1 and iNOS in LPS-stimulated RAW cells. In contrast, S was not capable to suppress LPS-induced IL-6, Cox-2, and TNF-α transcription. Treatment with S inhibited the ERK pathway stimulated by LPS in RAW cells, possibly leading to inhibiting the inflammation. Furthermore, S decreased slightly the NF-κB retention within nucleus of the LPS-stimulated RAW cells. There was no significant effect to reduce the inflammatory severity in both jejunum-ileum of rats treated with MTX and irradiated rectal mucosa. Conclusions: This study shows that S has an anti-inflammatory effect in vitro. The main mechanism of the anti-inflammatory effect of S was by attenuating activity of Erk and inhibiting NF-κB-mediated transcription. However, the amount of S used in this study could not reduce the mucosal damage by MTX or radiation in animal model. We are in the process of studying with different dose levels of S or with combined herbal remedies on the same animal model. [ABSTRACT FROM AUTHOR] |
