Anti-inflammatory, healing and antiophidic potential of Jatropha mollissima (Pohl) Baill. (Euphorbiaceae): From popular use to pharmaceutical formulation in gel.

Jatropha mollissima (Pohl) Baill. (Euphorbiaceae) is widely used in traditional medicine to treat inflammatory disorders. So, a topical gel containing the hydroethanolic extract of its leaves was developed and evaluated for its anti-inflammatory, wound healing, and antiophidic properties in mice. First, the chemical profile of different parts of the plant was characterized by liquid chromatography coupled to mass spectrometry (LC-MS) using molecular networking. In the leaf extract, 11 compounds were characterized, with a particular emphasis on the identification of flavonoids. The gel efficiently inhibited carrageenan-induced paw edema, as well as acute and chronic croton oil-induced ear edema models, thereby reducing inflammatory and oxidative parameters in inflamed tissues. Besides anti-inflammatory activity, the herbal gel showed significant wound healing activity. The edematogenic, hemorrhagic and dermonecrotic activities induced by Bothrops jararaca snake venom were effectively inhibited by the treatment with J. mollissima gel. The association with the herbal gel improved in up to 90% the efficacy of commercial snake antivenom in reduce venom-induced edema. Additionally, while antivenom was not able to inhibit venom-induced dermonecrosis, treatment with herbal gel reduced in 55% the dermonocrotic halo produced. These results demonstrate the pharmacological potential of the herbal gel containing J. mollissima extract, which could be a strong candidate for the development of herbal products that can be used to complement the current antivenom therapy against snake venom local toxicity.

Development of an effective and safe topical anti-inflammatory gel containing Jatropha gossypiifolia leaf extract: Results from a pre-clinical trial in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha gossypiifolia L. (Euphorbiaceae) is a medicinal plant widely used in traditional medicine as an anti-inflammatory remedy. The topical use of the leaves and/or aerial parts of this plant as anti-inflammatory, analgesic, wound healing and anti-infective in several skin diseases is a common practice in many countries. The use of baths or dressings with this vegetal species is frequently reported in folk medicine. AIM OF THE STUDY: To evaluate the topical anti-inflammatory of aqueous extract from leaves of J. gossypiifolia and to develop a safe and effective herbal gel with anti-inflammatory potential. MATERIAL AND METHODS: First, the topical acute anti-inflammatory activity of J. gossypiifolia extract was evaluated in ear edema induced by single application of croton oil in mice. Then, a polaxamer-based gel containing J. gossypiifolia extract was developed, physicochemically characterized and evaluated in the same model of inflammation to assess whether the extract incorporation in gel would affect its anti-inflammatory potential. The best formulation was then assayed in ear edema induced by multiple applications of croton oil in mice, to evaluate its chronic anti-inflammatory potential. Inflammatory parameters evaluated included edema, nitrite concentration, mieloperoxidase (MPO) activity and oxidative damage in lipids and proteins. Finally, dermal irritation/corrosion test in mice was performed to access the safeness of the developed gel. Phytochemical characterization of J. gossypiifolia extract was performed by high performance liquid chromatography with diode array detector (HPLC-DAD) analysis. RESULTS: J. gossypiifolia showed significant acute anti-inflammatory activity in ear edema model, and this activity was significantly increased when equivalent amounts of extract was applied incorporated in the developed polaxamer gels. The gels containing different amounts of extract reduced significantly the levels of edema, nitrite and MPO enzyme in mice ears, with intensity similar to the anti-inflammatory standard drug dexamethasone. The gel containing 1.0% of extract was further evaluated and also showed significant anti-inflammatory activity in chronic inflammation test, reducing significantly ear edema, lipid peroxidation and depletion of reduced glutathione, similarly to dexamethasone. Placebo formulation as well as gel containing extract showed pH compatible to that of human skin and exhibited absence of signs of toxicity in mice, indicating the safeness of the developed product for topical use. HPLC analysis confirmed the presence of C-glycosylflavonoids (orientin, isoorientin, vitexin and isovitexin) as the major compounds of J. gossypiifolia aqueous leaf extract. CONCLUSIONS: The results demonstrate the potentiality of J. gossypiifolia gel as a promising safe and effective topical anti-inflammatory agent for treatment of cutaneous inflammatory diseases.

Inhibition of local effects induced by Bothrops erythromelas snake venom: Assessment of the effectiveness of Brazilian polyvalent bothropic antivenom and aqueous leaf extract of Jatropha gossypiifolia.

Bothrops erythromelas is a snake of medical importance responsible for most of the venomous incidents in Northeastern Brazil. However, this species is not included in the pool of venoms that are used in the Brazilian polyvalent bothropic antivenom (BAv) production. Furthermore, it is well known that antivenom therapy has limited efficacy against venom-induced local effects, making the search for complementary alternatives to treat snakebites an important task. Jatropha gossypiifolia is a medicinal plant widely indicated in folk medicine as an antidote for snakebites, whose effectiveness against Bothrops jararaca venom (BjV) has been previously demonstrated in mice. In this context, this study assessed the effectiveness of the aqueous extract (AE) of this plant and of the BAv against local effects induced by B. erythromelas venom (BeV). Inhibition of BeV-induced edematogenic and hemorrhagic local effects was assayed in mice in pre-treatment (treatment prior to BeV injection) and post-treatment (treatment post-envenomation) protocols. Inhibition of proteolytic, phospholipase A2 (PLA2) and hyaluronidase enzymatic activities of BeV were evaluated in vitro. BAv cross-reactivity and estimation of antibody titers against BeV and BjV were assessed by Ouchterlony double diffusion test. The results show that in pre-treatment protocol AE and BAv presented very similar effects (about 70% of inhibition for edematogenic and 40% for hemorrhagic activities). However, BAv poorly inhibited edema and hemorrhage in post-envenomation protocol, whilst, in contrast, AE was significantly active even when used after BeV injection. AE was able to inhibit all the tested enzymatic activities of BeV, while BAv was active only against hyaluronidase activity, which could justify the low effectiveness of BAv against BeV-induced local effects in vivo. Ouchterlony's test showed positive cross-reactivity against BeV, but the antibody titers were slightly higher against BjV. Together, these data indicate that despite the presence of immunological cross-reactivity, Brazilian polyvalent bothropic antivenom presented low inhibitory potential against biological and enzymatic effects of BeV, illustrating the need for new strategies in the production of antivenom with broad neutralizing potential in the treatment of Bothrops spp. envenomation throughout the country. Together, the results highlight the antiophidic potential of J. gossypiifolia, suggesting that it can be considered a potential adjuvant in the treatment of bothropic envenomation local effects.

Inhibition of local effects induced by Bothrops erythromelas snake venom: assessment of the effectiveness of Brazilian polyvalent bothropic antivenom and aqueous leaf extract of Jatropha gossypiifolia

Bothrops erythromelas is a snake of medical importance responsible for most of the venomous incidents in Northeastern Brazil. However, this species is not included in the pool of venoms that are used in the Brazilian polyvalent bothropic antivenom (BAv) production. Furthermore, it is well known that anti venom therapy has limited efficacy against venom-induced local effects, making the search for complementary alternatives to treat snakebites an important task. Jatropha gossypiifolia is a medicinal plant widely indicated in folk medicine as an antidote for snakebites, whose effectiveness against Bothrops jararaca venom (BjV) has been previously demonstrated in mice. In this context, this study assessed the effectiveness of the aqueous extract (AE) of this plant and of the BAv against local effects induced by B. erythromelas venom (BeV). Inhibition of BeV-induced edematogenic and hemorrhagic local effects was assayed in mice in pre-treatment (treatment prior to BeV injection) and post-treatment (treatment post-envenomation) protocols. Inhibition of proteolytic, phospholipase A(2) (PLA(2)) and hyaluronidase enzymatic activities of BeV were evaluated in vitro. BAv cross-reactivity and estimation of antibody titers against BeV and BjV were assessed by Ouchterlony double diffusion test. The results show that in pretreatment protocol AE and BAv presented very similar effects (about 70% of inhibition for edematogenic and 40% for hemorrhagic activities). However, BAv poorly inhibited edema and hemorrhage in post-envenomation protocol, whilst, in contrast, AE was significantly active even when used after BeV injection. AE was able to inhibit all the tested enzymatic activities of BeV, while BAv was active only against hyaluronidase activity, which could justify the low effectiveness of BAv against BeV-induced local effects in vivo. Ouchterlony's test showed positive cross-reactivity against BeV, but the antibody titers were slightly higher against BjV. Together, these data indicate that despite the presence of immunological cross-reactivity, Brazilian polyvalent bothropic antivenom presented low inhibitory potential against biological and enzymatic effects of BeV, illustrating the need for new strategies in the production of antivenom with broad neutralizing potential in the treatment of Bothrops spp. envenomation throughout the country. Together, the results highlight the antiophidic potential off. gossypiifolia, suggesting that it can be considered a potential adjuvant in the treatment of bothropic envenomation local effects.