Millingtonia hortensis L.f. ethanol extract exerts in vivo and in vitro anti-inflammatory activities through inhibition of Syk kinase in NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Millingtonia hortensis L.f., commonly known as tree jasmine or Indian cork tree, is native to South Asia and Southeast Asia. Traditionally, its stem bark, leaves, and roots are employed for pulmonary, gastrointestinal, and antimicrobial purposes, while the flowers are used in treating asthma and sinusitis. AIM OF THE STUDY: The underlying anti-inflammatory mechanisms of M. hortensis remain relatively unexplored. Therefore, we studied the anti-inflammatory effects of M. hortensis and the molecular mechanisms of its ethanol extracts (Mh-EE) both in vitro and in vivo. MATERIALS AND METHODS: Nitric oxide (NO) production was assessed using Griess reagent, while cell viability of RAW264.7 cell and HEK293T cells were determined via the MTT assay. Constituent analysis of Mh-EE using GC/MS-MS and HPLC, and mRNA expression of inflammatory cytokines was measured through PCR and RT-PCR. Protein levels were analyzed using western blotting. The thermal stability of Mh-EE was evaluated by CESTA. Lastly, a gastritis in vivo model was induced by HCl/EtOH, and protein expression levels were measured using western blotting. RESULTS: Mh-EE significantly reduced NO production in LPS-induced RAW264.7 cells without substantially affecting cell viability. Additionally, Mh-EE decreased the expression of proinflammatory factors, such as iNOS, IL-1ß and COX2. Furthermore, Mh-EE downregulated TLR4 expression, altered MyD88 recruitment, and suppressed phosphorylation of Syk, IKKα, IκBα and AKT. Simultaneously, Mh-EE also attenuated NF-κB signaling in HCl/EtOH-induced mice. CONCLUSIONS: Mh-EE exerts anti-inflammatory effects by suppressing p-Syk in the NF-κB pathway, and it has potential as a novel treatment agent for inflammatory diseases.

Anti-apoptotic, anti-inflammatory, and anti-melanogenic effects of the ethanol extract of Picrasma quassioides (D. Don) Benn.

ETHNOPHARMACOLOGICAL RELEVANCE: Picrasma quassioides (D. Don) Benn is a vascular plant belonging to the genus Picrasma of Simaroubaceae family and grows in Korea, China, India, Taiwan, and Japan. Picrasma quassioides extract has been reported to have anti-inflammatory, anti-bacterial, and anti-cancer properties. Moreover, this plant has been also traditionally used to alleviate symptoms of eczema, atopic dermatitis, psoriasis, scabies, and boils in skin. AIM OF THE STUDY: The Pq-EE has been reported in Chinese pharmacopoeia for its pharmacological effects on skin. However, the detailed mechanism on alleviating skin conditions is not understood. Hence, we investigated the skin improvement potential of Pq-EE against skin damage. MATERIALS AND METHODS: We used the human keratinocyte cell line (HaCaT) and mouse melanoma cell line (B16F10) to study the effects of Pq-EE on the epidermis. Additionally, in vitro antioxidant assays were performed using a solution that included either metal ions or free radicals. RESULTS: In colorimetric antioxidant assays, Pq-EE inhibited free radicals in a dose-dependent manner. The Pq-EE did not affect cell viability and promoted cell survival under UVB exposure conditions in the MTT assay. The Pq-EE downregulated the mRNA levels of apoptotic factors. Moreover, MMP1 and inflammatory cytokine iNOS mRNA levels decreased with Pq-EE treatment. With regard to protein levels, caspases and cleaved caspases were more powerfully inhibited by Pq-EE than UVB-irritated conditions. p53 and Bax also decreased with Pq-EE treatment. The melanin contents and secretion were decreased at nontoxic concentrations of Pq-EE. The pigmentation pathway genes also were inhibited by treatment with Pq-EE. CONCLUSIONS: In summary, we suggest the cell protective potential of Pq-EE against UVB and ROS, indicating its use in UV-protective cosmeceutical materials.

Pilot study of stereotactic body radiotherapy for huge hepatocellular carcinoma unsuitable for other therapies.

AIMS: To determine the feasibility and efficacy of stereotactic body radiotherapy (SBRT) for huge hepatocellular carcinoma unsuitable for other therapies. METHODS: Six patients with very large hepatocellular carcinomas (>10 cm) unsuitable for surgical resection or that failed to respond to transcatheter arterial chemoembolization (TACE) were treated by SBRT. Doses ranged from 32 Gy to 40 Gy in four fractions. Survival, response, and toxicities were evaluated. RESULTS: After a median follow-up of 25.9 months (range 8.1-56 months), three patients had died and three were alive. Overall, treatment was well tolerated and no dose-limiting toxicity or radiation-induced liver disease was observed. The median survival was 10 months (range 3-56 months) and the median progression-free duration was 6 months (range, 2-21 months). Partial response was achieved by four patients, stable disease by one, and one patient had disease progression. One patient with a partial response who underwent lobectomy after SBRT was alive 56 months post-SBRT. CONCLUSION: This study suggests that SBRT can be delivered safely at 32-40 Gy in four fractions to huge hepatocellular carcinoma. Furthermore, combinations of SBRT with other modalities such as surgery or TACE might prolong survival.