Investigation of the effect of phlomisoside F on complete Freund's adjuvant-induced arthritis.

Phlomis younghusbandii Mukerjee (Labiatae) has been reported to be effective in the treatment of rheumatoid arthritis (RA). In the present study, the anti-inflammatory and anti-arthritic effects of phlomisoside F (PF), isolated from P. younghusbandii Mukerjee (Labiatae), were investigated in male Wistar rats subjected to carrageen-induced paw edema and complete Freund's adjuvant (CFA)-induced arthritis. Arthritis scores were evaluated by a 5-point ordinal scale (scores 0-4). Expression levels of TNF-α, IL-1ß, IL-6, IL-10, COX-2 and 5-LOX were determined via ELISA and western blot assays. Subsequent to establishing the edema and arthritis models, oral administration of PF (5, 10 and 20 mg/kg) significantly inhibited mean edema rate, compared with the control group in carrageenan-induced paw edema assay. In addition, administration of PF (5, 10 and 20 mg/kg/day) for 28 days markedly exhibited an anti-arthritic activity by offsetting the body weight loss, inhibiting the paw edema, reducing the arthritis scores and the indices of thymus and spleen, inhibiting the expression levels of TNF-α, IL-1ß, IL-6, COX-2 and 5-LOX, and increasing the expression of IL-10, when compared with the respective control group in CFA-induced arthritis assay. In conclusion, PF is a valuable anti-arthritic constituent of P. younghusbandii, and the present study results suggest that this herb may be used in the treatment of RA.

Anti-inflammatory activity of phlomisoside F isolated from Phlomis younghusbandii Mukerjee.

This study was designed to investigate the anti-inflammatory effect of phlomisoside F (PMF) isolated from Phlomis younghusbandii and to explore the possible pharmacological mechanisms. Anti-inflammatory effects of PMF were evaluated by using carrageenan-induced rat paw edema test, dimethylbenzen-induced ear edema test, acetic acid-induced vascular permeability and cotton pellet granuloma test. Furthermore, the releases of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) were determined by ELISA. To explore the potential mechanisms, expressions of iNOS and COX-2 were determined by quantitative real-time PCR and western blotting assays. In addition, the expressions of nuclear p65, cytosolic p65, IκB, p38, p-p38, p-ERK1/2, ERK1/2, JNK and p-JNK were determined by western blotting assay. Our results indicated that PMF administered orally could not only significantly decrease rat paw edema in rats and ear edema in mice, but also reduce the vascular permeability in mice and granuloma weights in rats. In vitro, the releases of LPS-induced pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) and enzymes (iNOS and COX-2) were decreased significantly by PMF treatment in RAW 264.7 cells. In addition, the LPS-induced up-regulations of nuclear p65, p38, p-p38, p-ERK1/2, JNK and p-JNK proteins in RAW 264.7 cells significantly decreased by PMF, and expressions of cytosolic p65 and IκB were obviously up-regulated after treatment with PMF. In conclusion, we suggested that the PMF is a promising potential anti-inflammatory drug, and PMF could down-regulate expressions of pro-inflammatory cytokines and mediators by inhibiting the NF-κB/MAPK pathways.

Protective effect of phenylethanoid glycosides extracted from phlomis younghusbandii on acute high altitude pulmonary edema in rats / 解放军医学杂志

Objective To investigate the protective effect of phenylethanoid glycosides (PhGCs) extracted from Phlomis younghusbandii on acute high altitude pulmonary edema (HAPE) in rats. MethodsSeventy male Wistar rats were randomly divided into 7 groups (10 each): normoxia control group (NG, distilled water), normoxia+PhGCs group (NG+PhGCs, 400mg/ kg), hypoxia model group (HG, distilled water), dexamethasone (Dex, 4mg/kg), and three groups of PhGCs in high (PhGCs-H, 400mg/kg), middle (PhGCs-M, 200mg/kg) and low (PhGCs-L, 50mg/kg) dosage. PhGCs extracted from Phlomis younghusbandii were administered prophylactically to rats for 3 days, and HAPE was induced by the hypobaric hypoxia exposure for 72 hours in an animal decompression chamber with the chamber pressure of 267mmHg to simulate an altitude of 8000m. The water content of rat lung tissue was determined with wet/dry specific gravity method, and histopathologic changes were observed with HE staining. The enzymatic activities of SOD and GSH, and the contents of MDA in lung tissue were determined with spectrophotometry, and the contents of IL-1β, TNF-α in serum and lung tissue were determined with ELISA. ResultsCompared with NG group, no obvious difference was found in the water content of rat lung tissue in NG+PhGCs group, but the water content increased obviously in HG group (P<0.05). Compared with NG group, lung tissue congestion and edema were found in HG group, with a heavy inflammatory cell infiltration, widening of alveolar interval, and thickening of alveolar wall were found. The enzymatic activities of SOD and GSH were notablely depressed, and the contents of MDA in lung tissue, and the contents of IL-1β and TNF-α in serum and lung tissue remarkably increased (P<0.05). Compared with HG group, the water content of rat lung tissue in each PhGCs group decreased obviously. Inflammatory cells infiltration, widening of alveolar interval, and thickening of alveolar wall, the enzymatic activity of SOD and GSH increased, and the contents of IL-1β, TNF-α and MDA decreased significantly in PhGCs groups (P<0.05). Conclusion PhGCs extracted from Phlomis younghusbandii may alleviate the oxidative stress and inflammatory response of acute lung injury induced by acute hypoxia. PhGC showed a protective effect against acute HAPE in a rat model.

Improving Effect of Phenylethanoid Glycosides from Tibetan Medicine Phlomis younghusbandii on Rats with Acute High-altitude Cerebral Edema / 中国药房

OBJECTIVE:To investigate the improving effect of phenylethanoid glycosides (PhGCs) from Tibetan medicine Phlomis younghusbandii on rats with acute high-altitude cerebral edema. METHODS:60 Wistar rats were randomly divided into a normoxia control group (isometric sterile water for injection),a hypoxia model group (isometric sterile water for injection),a dexamethasone group(4 mg/kg),and three groups of PhGCs at high(400 mg/kg),middle(200 mg/kg)and low(50 mg/kg)dos-es,with 10 rats in each group. The rats were given drugs,ig,6 d before the establishment of models. On the 4th day of administra-tion,ig,the rats in all groups except the normoxia blank group were placed in a simulated 8 000 m altitude plateau environment for 72 h hypoxic exposure to establish the rat models of high-altitude cerebral edema. Following HE stain,the pathological changes in rats’brain tissues were observed under the light microscope. Dry-wet proportion method was used to determine the water con-tents in rats’brain. The content of MDA and the activities of SOD and GSH in rats’brain tissues were detected. Enzyme-linked im-munosorbent assay was adopted to determine the contents of IL-1β and TNF-α in rats’serum and brain tissues. RESULTS:Com-pared to the rats in the normoxia control group,those in the hypoxia model group showed obvious brain edema,and thickened lacu-nas around cells and vessels and inflammatory cell infiltration, higher water contents and MDA and weaker activities of SOD and GSH in brain,and higher contents of IL-1β and TNF-α in serum and brain tissues. There were statistically significances (P<0.01 or P<0.05). Compared to the rats in the hypoxia model group,those in the groups of PhGCs at high,middleand low dosages demonstrated less inflammatory cell infiltration and lower water contents in brain tissues,in which the groups of PhGCs at high and middle dosages demonstrated lower content of MDA and stronger activities of SOD and GSH in brain tissues, and lower contents of IL-1β and TNF-α in serum and brain tissues. There were statistically significances (P<0.01 or P<0.05). CONCLUSIONS:PhGCs can obviously alleviate the acute cerebral injury in rats which is caused by acute hypoxia and has im-provement effect to some degree on the rats with acute high-altitude cerebral edema.