Angiogenic and MMPs modulatory effects of icariin improved cutaneous wound healing in rats.

Icariin is a flavonoid from plant belonging to the genus Epimedium, commonly known as Horny goat weed or Yin Yang Huo. The compound possesses multiple biological activities which are associated with the modulation of many signalling pathways, like NF-κB, Erk-p38-JNK, and release of various cytokines and growth factors. The present study determined wound healing potential of icariin in male Wistar rats. Icariin ointment (0%, 0.004%, 0.02%, 0.1% and 0.5%), was applied daily (b.i.d.) for 14 days on ≈ 400 mm2 cutaneous wound in different groups of rats. On day 14 post-wounding, 0.1% and 0.5% icariin treatment significantly (P < 0.01 and P < 0.001, respectively) increased wound contraction, as compared to control. Western blots revealed upregulation of IL-10 and downregulation of NF-κB and TNF-α. Increased expression of CD-31 showed abundance of microvessels in healing tissues after treatment with icariin. The MMP-2 and MMP-9 activities were reduced in icariin treated groups. Masson's trichrome staining revealed relatively better completion of re-epithelisation as well as increased deposition of well organised collagen fibres in the healing tissues compared to control. It is concluded that icariin has potential to accelerate cutaneous wound healing in rats.

Diarylheptanoids from Alnus nepalensis attenuates LPS-induced inflammation in macrophages and endotoxic shock in mice.

Diarylheptanoids, a group of plant secondary metabolites are increasingly recognized as potential therapeutic agents. The aim of study was to ascertain the anti-inflammatory profile of diarylheptanoids from Alnus nepalensis against lipopolysaccharide (LPS)-induced inflammation in macrophages and endotoxic shock in mice. Extracts prepared from dried leaves of A. nepalensis using standard solvents were tested against LPS-induced inflammation in macrophages. Among all, butanol extract (ANB) has shown most significant inhibition of pro-inflammatory cytokines without any cytotoxicity. HPLC analysis of ANB showed the presence of diarylheptanoids. The diarylheptanoids were further isolated and tested in-vitro for anti-inflammatory activity. Treatment of isolated diarylheptanoids (HOG, ORE and PLS) was able to reduce the production and mRNA level of pro-inflammatory cytokines (TNF-α and IL-6). Furthermore, we demonstrated that it inhibited the expression of NF-kB protein in LPS-induced inflammation in macrophages. In-vivo efficacy and safety profile of ANB revealed that oral treatment of ANB was able to improve the survival rate, and inhibited the production of pro-inflammatory cytokines in serum, attenuated vital organ injury in a dose dependent manner without any toxic effect at higher dose in mice. The results suggest that diarylheptanoids from A. nepalensis can be considered as potential therapeutic candidates for the management of inflammation related diseases.

Effect of alcoholic extract of Entada pursaetha DC on monosodium iodoacetate-induced osteoarthritis pain in rats.

BACKGROUND & OBJECTIVES: Osteoarthritis (OA) is a degenerative disease characterized by joint pain and progressive loss of articular cartilage. Entada pursaetha has been traditionally used in the treatment of inflammatory disease, liver ailment, etc. In this study we investigated suppressive effect of ethanolic extract of E. pursaetha (EPE) on monosodium iodoacetate (MIA)-induced osteoarthritis pain and disease progression by histopathological changes in joints in a rat model. METHODS: OA was induced in right knee of rat by intra-articular injection of 3 mg of MIA and characterized by pathological progression of disease and pain of affected joint. Spontaneous movements, mechanical, thermal and cold sensitivity were monitored at days 0 (before drug and MIA injection), 7, 14 and 21 of MIA administration. EPE (30, 100 and 300 mg/kg), vehicle or etoricoxib (10 mg/ kg; reference drug) were administered daily for 21 days by oral route. RESULTS: EPE at various doses significantly reduced mechanical, heat, cold hyperalgesia and increased the horizontal and vertical movements in intra-articular MIA injected rats. EPE prevented the damage to cartilage structure and reduced the cellular abnormalities. Articular cartilage of rats treated with EPE at 300 mg/kg group was almost normal with well-developed smooth surface and chondrocytes were distributed individually or arranged in column. INTERPRETATION & CONCLUSIONS: The present findings showed that the EPE was not only able to mitigate pain and hyperalgesia but also inhibited MIA-induced cartilage degeneration in vivo. EPE may have the potential to become therapeutic modality in the treatment of osteoarthritis. However, further studies need to be done to confirm these findings in other models and clinical trials.

Betulinic acid negates oxidative lung injury in surgical sepsis model.

BACKGROUND: Sepsis commonly progresses to acute lung injury and is associated with high morbidity and mortality. Septic acute lung injury is characterized by severe oxidative stress response, remained refractory to present therapies, and new therapies need to be developed to improve further clinical outcomes. We determined the effect of betulinic acid (BA) on oxidative lung injury in mice using cecal ligation and puncture (CLP) model. MATERIALS AND METHODS: Five groups of mice (six in each group) received three pretreatments at 24-h interval before surgery. Surgery was done 1 h after last dosing. Sham and CLP control group mice received vehicle. BA was administered to other three groups of mice at 3, 10, and 30 mg/kg dose. Lung and plasma samples were collected for analysis by sacrificing the mice at 18 h of surgery. RESULTS: Compared with sham, CLP significantly increased total protein, nitrite, malondialdehyde, isoprostane, superoxide, protein carbonyl, oxidative stress index, inducible nitric oxide synthase protein, and histopathologic changes and reduced the superoxide dismutase, catalase activity, and total thiol levels in lungs and plasma, which were restored by BA pretreatment. CONCLUSIONS: BA pretreatment decreased the levels of oxidants, increased the levels of antioxidants in lungs and plasma thereby reducing the oxidative lung injury in CLP mice. Additionally, BA was found to scavenge the superoxide and nitric oxide radical in vitro. Thus, BA is suggested to be effective in treatment of oxidative lung injury in sepsis.