brucine and Edema

Brucine (BRU) is a natural product derived from nux-vomica seeds. It is commonly used as an anti-inflammatory and anti-nociceptive drug to relieve arthritis and traumatic pain. Nevertheless, its use is significantly limited by its low aqueous solubility, as well as the gastrointestinal problems and systemic toxicity that may occur following oral administration. The goal of this study, therefore, was to formulate and evaluate a nanoemulgel formulation of BRU for enhanced topical anti-inflammatory and anti-nociceptive activities. Different formulations were developed (BRU gel, emulgel and nanoemulgel) using 1% w/w NaCMC as a gelling agent. The formulated preparations were assessed for their physical appearance, spreadability, viscosity, particle size, in vitro drug release and ex vivo permeation studies. In addition, the carrageenan-induced rat hind paw edema method was adopted to scrutinize the anti-inflammatory activity, while the hot plate method and acetic acid-induced writhing test were used to assess the anti-nociceptive activity of different formulations in male BALB/c mice. The formulated BRU-loaded preparations showed good physical characteristics. Cumulative drug release from BRU-loaded nanoemulgel was remarkably higher than that of the other formulations. Ex vivo drug permeation of the nanoemulgel formulation across rat skin showed enhanced drug permeation and higher transdermal flux as compared to BRU-loaded gel or emulgel. Most importantly, the carrageenan-induced rat hind paw edema model verified the efficient anti-inflammatory potential of BRU-loaded nanoemulgel. In addition, BRU-loaded nanoemulgel exhibited significant protective effects against thermal stimulation in the hot plate test and remarkably inhibited acetic acid-induced abdominal writhing in mice. Furthermore, a skin irritation test indicated that BRU-loaded nanoemulgel elicited neither edema nor erythema upon application to rat skin. Collectively, our results suggest that myrrh oil-based nanoemulgel might represent a promising delivery vehicle for potentiating the anti-inflammatory and anti-nociceptive actions of brucine.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Edema; Male; Mice; Mice, Inbred BALB C; Rats; Skin Absorption; Strychnine

The seeds of

Topics: Administration, Cutaneous; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Cell Line; Cell Proliferation; Cell Survival; Cells, Cultured; Dinoprostone; Disease Models, Animal; Drug Delivery Systems; Edema; Formaldehyde; Gels; Humans; Macrophages; Male; Mice; Pain; Phytotherapy; Rats, Wistar; Strychnine; Strychnos nux-vomica; Synoviocytes

To further understand the purpose of the traditional processing method of the seeds of Strychnos nux-vomica L. (Loganiaceae) as well as analgesic and anti-inflammatory activities of brucine and brucine N-oxide extracted from this medicinal plant, various pain and inflammatory models were employed in the present study to investigate their pharmacological profiles. Both brucine and brucine N-oxide revealed significant protective effects against thermic and chemical stimuli in hot-plate test and writhing test. However, on different phases they exerted analgesic activities in formalin test. Brucine N-oxide showed stronger inhibitory effect than brucine in carrageenan-induced rat paw edema, both of them significantly inhibited the release of prostaglandin E2 in inflammatory tissue, reduced acetic acid-induced vascular permeability and the content of 6-keto-PGF1a in Freund's complete adjuvant (FCA) induced arthritis rat's blood plasma. In addition, brucine and brucine N-oxide were shown to reduce the content of 5-hydroxytryptamine (5-HT) in FCA-induced arthritis rat's blood plasma, while increase the content of 5-hydroxytryindole-3-acetic acid (5-HIAA) accordingly. These results suggest that central and peripheral mechanism are involved in the pain modulation and anti-inflammation effects of brucine and brucine N-oxide, biochemical mechanisms of brucine and brucine N-oxide are different even though they are similar in chemical structure.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Capillary Permeability; Cyclic N-Oxides; Disease Models, Animal; Edema; Female; Male; Mice; Mice, Inbred ICR; Pain; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds; Serotonin; Strychnine; Strychnos nux-vomica