Objective: To evaluate the anti-arthritic effect of aqueous and methanolic extracts of Distemonanthus benthamianus. Methods: Monoarthritis was induced by an injection of 0.3 mL zymosan A (0.9% NaCl, v/v) in the right posterior knee joints of rats. Then, joint diameter and pain threshold were determined. Polyarthritis was induced by an intracaudal injection of complete Freund’s adjuvant and rats were treated from day 14 post 1st complete Freund’s adjuvant injection until 28 day. The clinical, hematological, biochemical and oxidative stress parameters were evaluated. In addition, histological analysis of the knee joint was perfomed in both tests. Results: The aqueous and methanolic extracts of Distemonanthus benthamianus at a dose of 500 mg/kg ameliorated zymosan A-induced monoarthritis, as evidenced by reduced joint diameter, increased pain threshold, as well as improved joint architecture. In addition, both extracts of Distemonanthus benthamianus markedly increased body weight and pain threshold, while reducing paw edema in polyarthritic rats. They also led to a marked decrease in platelets and white blood cells (P<0.05), as well as a significant increase in red blood cells, hemoglobin and hematocrit (P<0.05). The aqueous and methanolic extracts of Distemonanthus benthamianus significantly reduced alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activities, while increasing serum protein levels (P<0.05) with no significant variation in creatinine level. Moreover, both extracts increased catalase and glutathione activities (P<0.05), and inhibited malondialdehyde and nitric oxide production (P<0.01 and P<0.001) in the liver and kidneys. Histological analysis of the joints showed that both extracts triggered tissue reparation. Conclusions: Distemonanthus benthamianus could be used as a potential candidate in the treatment of rheumatoid arthritis.

Objective: To explore the anti-inflammatory and antioxidant effects of caraway on atopic dermatitis (AD) in mice. Methods: AD was induced in two stages, including sensitization and challenge with the application of 2,4 dinitrochlorobenzene 2% and 0.2%, respectively. Clinical symptoms and histological analysis of the skin were assessed. The effects of caraway on oxidant/antioxidant parameters as well as Th1- and Th2-related cytokines were also evaluated. Results: Caraway reduced the severity of dermatitis in AD-induced mice, as evidenced by significant inhibition of Th2-related cytokines (IL-4 and IL-13) and increased Th1-related cytokine (IFN-γ). Additionally, treatment with caraway significantly increased superoxide dismutase and catalase activity and decreased the malondialdehyde level in the serum of AD mice. Furthermore, caraway inhibited the differentiation of Th2 cells while favoring Th1 cell differentiation in the spleen via regulating their master transcription factors GATA3 and T-bet. Conclusions: Caraway could improve AD autoimmune responses and could be considered a potential candidate to treat AD disease.

Objective: To elucidate the potential anti-inflammatory mechanisms of Rhamnus crenata leaf extracts using RAW264.7 cells. Methods: We used 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay to measure cell viability. Nitric oxide (NO) production was measured using Griess reagent. Western blotting and RT-PCR assays were carried out for analyzing the protein and gene expressions of pro-inflammatory mediators, respectively. Moreover, PD98059 (ERK1/2 inhibitor), SB203580 (p38 inhibitor), SP600125 (JNK inhibitor), and BAY11-7082 (NF-κB inhibitor) were used to evaluate the anti-inflammatory mechanism of Rhamnus crenata leaf extract. Results: Rhamnus crenata leaf extracts significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, IL-1β, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Rhamnus crenata leaf extracts also suppressed LPS-induced degradation of IκB-α and nuclear accumulation of p65, which resulted in the inhibition of NF-κB activation in RAW264.7 cells. Additionally, the extracts attenuated the phosphorylation of p38, ERK1/2, and JNK in LPS-stimulated RAW264.7 cells. Moreover, HO-1 expression induced by Rhamnus crenata leaf extracts was significantly downregulated by SB230580, PD98059, SP600125 and BAY11-7082. Conclusions: Rhamnus crenata leaf extract may upregulate HO-1 expression through inhibition of p38, ERK1/2, and NF-κB activation, which may contribute to the anti-inflammatory activity of the extracts. Rhamnus crenata leaf extracts may have great potential for the development of anti-inflammatory drugs to treat acute and chronic inflammatory diseases.

Objective: To evaluate the effect of erianin on the viability, migration, and invasion of KB cells and elucidate its underlying mechanisms. Methods: Cell Counting Kit-8, colony formation, wound healing, and Transwell assays were used to determine the proliferation, migration, and invasion of oral cancer KB cells. Furthermore, malondialdehyde (MDA) and glutathione (GSH) levels were determined. Fluorescent probes were used to detect changes in intracellular reactive oxygen species and iron ions. Additionally, the expressions of ferroptosis-related proteins, NF-E2-related factor 2 (Nrf2), ferritin heavy chain 1 (FTH1), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4) were analyzed by Western blotting assays. Results: Erianin induced ferroptosis and inhibited the proliferation, migration, and invasion of KB cells. Moreover, erianin decreased GSH level, increased MDA level, elevated intracellular ROS and Fe²⁺ contents, and downregulated the expression of the ferroptosis-related proteins Nrf2, HO-1, GPX4, and FTH1 in KB cells. These effects of erianin were effectively reversed by a ferroptosis inhibitor, ferrostatin-1. Conclusions: Erianin inhibits the proliferation, migration, and invasion of oral cancer cells and induces ferroptosis via the Nrf2/HO-1/GPX4 signaling pathway. Therefore, erianin may be a potential candidate for the treatment of oral cancer.

Objective: To evaluate the effects of phenolic acids (caffeic, ferulic, and coumaric acids) and flavones (luteolin and apigenin) on the proliferation and melanogenesis in murine melanoma B16-F10 cells. Methods: Cell proliferation was determined after 24 and 48 hours of incubation using MTT assay. The effects of these tested compounds on cell cycle progression were analyzed by flow cytometry. Moreover, the melanin content and tyrosinase activity were measured spectrophotometrically at 475 nm. Results: Luteolin and apigenin exhibited significant anti-proliferative activity against B16-F10 cells, while caffeic, ferulic, and coumaric acids induced slight inhibition after 24 and 48 hours of incubation. The tested compounds disturbed cell cycle progression of B16-F10, by a subsequent decrease in G₁ and arrested cycle progression in either G₁/S or G₂/M phase. Furthermore, apigenin provoked an increase in melanin content of B16-F10 cells. In contrast, luteolin, caffeic, ferulic and coumaric acids induced a decrease in melanin content of B16-F10 cells by inhibiting tyrosinase activity. Conclusions: These active polyphenols may be used as skin whitening agents or natural tanning agents to treat skin pigmentation disorders.