Flindissone, a Limonoid Isolated from Trichilia prieuriana, Is an LXR Agonist.

In this study, the ability of six limonoids from Trichilia prieuriana (Meliaceae) to activate the liver X receptor (LXR) was assessed. One of these limonoids, flindissone, was shown to activate LXR by reporter-gene assays. Flindissone is a ring-intact limonoid, structurally similar to sterol-like LXR ligands. In endogenous cellular settings, flindissone showed an activity profile that is characteristic of LXR agonists. It induced cholesterol efflux in THP-1 macrophages by increasing the cholesterol transporter ABCA1 and ABCG1 gene expression. In HepG2 cells, flindissone induced the expression of IDOL, an LXR-target gene that is associated with the downregulation of the LDL receptor. However, unlike synthetic and similarly to sterol-based LXR agonists, flindissone did not induce the expression of the SREBP1c gene, a major transcription factor regulating de novo lipogenesis. Additionally, flindissone also appeared to be able to inhibit post-translational activation of SREBP1c. The results presented here reveal a natural product as a new LXR agonist and point to an additional property of T. prieuriana and other plant extracts containing flindissone.

Vismione B Interferes with Trypanosoma cruzi Infection of Vero Cells and Human Stem Cell-Derived Cardiomyocytes.

Traditional African medicine is a source of new molecules that might be useful in modern therapeutics. We tested ten limonoids, six quinones, one xanthone, one alkaloid, and one cycloartane, isolated from four Cameroonian medicinal plants, and one plant-associated endophytic fungus, against Trypanosoma cruzi, the etiological agent of Chagas disease (CD). Vero cells, or human-induced pluripotent stem cells (hiPSC)-derived cardiomyocytes (hiPSC-CM) were infected with T. cruzi trypomastigotes (discrete typing unit types I or II). Infection took place in the presence of drugs, or 24 hours before drug treatment. Forty-eight hours after infection, infection rates and parasite multiplication were evaluated by Giemsa stain. Cell metabolism was measured to determine functional integrity. In Vero cells, several individual molecules significantly affected T. cruzi infection and multiplication with no, or minor, effects on cell viability. Reduced infection rates and multiplication by the quinone vismione B was superior to the commonly used therapeutic benznidazole (BNZ). The vismione B concentration inhibiting 50% of T. cruzi infection (IC50) was 1.3 µM. When drug was applied after infection, anti-Trypanosoma effects of vismione B [10 µM) were significantly stronger than effects of BNZ (23 µM). Furthermore, in hiPSC-CM cultures, infection and multiplication rates in the presence of vismione B (10 µM) were significantly lower than in BNZ (11.5 µM), without showing signs of cytotoxicity. Our data indicate that vismione B is more potent against T. cruzi infection and multiplication than BNZ, with stronger effects on established infection. Vismione B, therefore, might become a promising lead molecule for treatment development for CD.

Cytotoxicity, antimicrobial and antioxidant activity of eight compounds isolated from Entada abyssinica (Fabaceae).

BACKGROUND: Entada abyssinica is a plant traditionally used against gastrointestinal bacterial infections. Eight compounds including three flavonoids, three terpenoids, a monoglyceride and a phenolic compound isolated from E. abyssinica were investigated for their cytotoxicity, antibacterial and antioxidant activity. RESULTS: Compounds 7 and 2 had remarkable activity against Salmonella typhimurium with the lowest respective minimum inhibitory concentration (MIC) values of 1.56 and 3.12 µg/mL. The antioxidant assay gave IC50 values varied from 0.48 to 2.87 µg/mL in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, from 2.53 to 17.04 µg/mL in the 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) assay and from 1.43 to 103.98 µg/mL in the FRAP assay. Compounds had relatively low cytotoxicity (LC50 values ranging from 22.42 to 80.55 µg/mL) towards Vero cells. Ursolic acid had the most potent cytotoxicity against THP-1 and RAW 264.7 cells with LC50 values of 9.62 and 4.56 µg/mL respectively, and selectivity index values of 7.32 and 15.44 respectively. CONCLUSION: Our findings suggest that among the terpenoid and flavonoid compounds studied, entadanin (compound 7) possess tremendous antibacterial activity against S. typhimurium and could be developed for the treatment of bacterial diseases.