Anti-biofilm and anti-inflammatory active diterpene isolated from the fruit of Xylopia benthamii R.E.Fr.

Xylopia benthamii (Annonaceae) is a plant with limited phytochemical and pharmacological evidence. Thus, using LC-MS/MS, we performed exploratory analyses of the fruit extract of X. benthamii, resulting in the tentative identification of alkaloids (1-7) and diterpenes (8-13). Through the application of chromatography techniques with the extract of X. benthamii, two kaurane diterpenes were isolated, xylopinic acid (9) and ent-15-oxo-kaur-16-en-19-oic acid (11). Their structures were established using spectroscopy (NMR 1D/2D) and mass spectrometry. The isolated compounds were submitted to anti-biofilm analysis against Acinetobacter baumannii, anti-neuroinflammatory and cytotoxic activity in BV-2 cells. Compound 11 (201.75 µM) inhibited 35% of bacterial biofilm formation and high anti-inflammatory activity in BV-2 (IC50 = 0.78 µM). In conclusion, the results demonstrated that compound 11 was characterized for the first time with pharmacological potential in the development of new alternatives for studies with neuroinflammatory diseases.

Plant-Derived Toxin Inhibitors as Potential Candidates to Complement Antivenom Treatment in Snakebite Envenomations.

Snakebite envenomations (SBEs) are a neglected medical condition of global importance that mainly affect the tropical and subtropical regions. Clinical manifestations include pain, edema, hemorrhage, tissue necrosis, and neurotoxic signs, and may evolve to functional loss of the affected limb, acute renal and/or respiratory failure, and even death. The standard treatment for snake envenomations is antivenom, which is produced from the hyperimmunization of animals with snake toxins. The inhibition of the effects of SBEs using natural or synthetic compounds has been suggested as a complementary treatment particularly before admission to hospital for antivenom treatment, since these alternative molecules are also able to inhibit toxins. Biodiversity-derived molecules, namely those extracted from medicinal plants, are promising sources of toxin inhibitors that can minimize the deleterious consequences of SBEs. In this review, we systematically synthesize the literature on plant metabolites that can be used as toxin-inhibiting agents, as well as present the potential mechanisms of action of molecules derived from natural sources. These findings aim to further our understanding of the potential of natural products and provide new lead compounds as auxiliary therapies for SBEs.

Essential Oil from Bark of Aniba parviflora (Meisn.) Mez (Lauraceae) Reduces HepG2 Cell Proliferation and Inhibits Tumor Development in a Xenograft Model.

Aniba parviflora (Meisn.) Mez (Lauraceae) is an aromatic plant of the Amazon rainforest, which has a tremendous commercial value in the perfumery industry; it is popularly used as flavoring sachets and aromatic baths. In Brazilian folk medicine, A. parviflora is used to treat victims of snakebites. Herein, we analyzed the chemical composition of A. parviflora bark essential oil (EO) and its effect on the growth of human hepatocellular carcinoma HepG2 cells in vitro and in vivo. EO was obtained by hydrodistillation and characterized by GC-MS and GC-FID. The main constituents of EO were linalool (16.3±3.15), α-humulene (14.5±2.41 %), δ-cadinene (10.2±1.09 %), α-copaene (9.51±1.12 %) and germacrene B (7.58±2.15 %). Initially, EO's cytotoxic effect was evaluated against five cancer cell lines (HepG2, MCF-7, HCT116, HL-60 and B16-F10) and one non-cancerous one (MRC-5), using the Alamar blue method after 72 h of treatment. The calculated IC50 values were 9.05, 22.04, >50, 15.36, 17.57, and 30.46 µg/mL, respectively. The best selectivity was for HepG2 cells with a selective index of 3.4. DNA Fragmentation and cell cycle distribution were quantified in HepG2 cells by flow cytometry after a treatment period of 24 and 48 h. The effect of EO on tumor development in vivo was evaluated in a xenograft model using C.B-17 SCID mice engrafted with HepG2 cells. In vivo tumor growth inhibition of HepG2 xenograft at the doses of 40 and 80 mg/kg were 12.1 and 62.4 %, respectively.