Anticancer Activity and Molecular Targets of Piper cernuum Substances in Oral Squamous Cell Carcinoma Models.

Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, with high morbidity and mortality rates. The development of new drugs to treat OSCC is paramount. Piper plant species have shown many biological activities. In the present study, we show that dichloromethane partition of Piper cernuum (PCLd) is nontoxic in chronic treatment in mice, reduces the amount of atypia in tongues of chemically induced OSCC, and significantly increases animal survival. To identify the main active compounds, chromatographic purification of PCLd was performed, where fractions 09.07 and 14.05 were the most active and selective. These fractions promoted cell death by apoptosis characterized by phosphatidyl serine exposition, DNA fragmentation, and activation of effector caspase-3/7 and were nonhemolytic. LC-DAD-MS/MS analysis did not propose matching spectra for the 09.07 fraction, suggesting compounds not yet known. However, aporphine alkaloids were annotated in fraction 14.05, which are being described for the first time in P. cernuum and corroborate the observed cytotoxic activity. Putative molecular targets were determined for these alkaloids, in silico, where the androgen receptor (AR), CHK1, CK2, DYRK1A, EHMT2, LXRß, and VEGFR2 were the most relevant. The results obtained from P. cernuum fractions point to promising compounds as new preclinical anticancer candidates.

Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation.

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl-), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.

Isolation of a larvicidal compound from Piper solmsianum C.DC. (Piperaceae).

The Aedes aegypti mosquito is one of the major vectors of arboviruses. These diseases have re-emerged and the insecticides used nowadays are toxic to mammals and environment and have only been effective in the short-term. In this context, natural products are an alternative. The genus Piper has many active compounds against arthropods, including neolignans. The present study evaluated the larvicidal potential of the n-hexanic extract of Piper solmsianum and eupomatenoid-6, identified by GC-MS and NMR techniques, from this extract against Ae. aegypti. The crude extract (100 µg/mL) killed 80% and 98.3% of larvae in the first and third day, respectively. Eupomatenoid-6 exhibited LD50 of 19.33 µM and LD90 of 28.68 µM and was then assayed in human fibroblast cells (MRC5), showing an IC50 of 39.30 µM with estimated LD50 of 42.26 mmol/kg. Our results indicate eupomatenoid-6 as a potent insecticide with relatively low toxicity for mammals.

Local ecological knowledge and its relationship with biodiversity conservation among two Quilombola groups living in the Atlantic Rainforest, Brazil.

Information on the knowledge, uses, and abundance of natural resources in local communities can provide insight on conservation status and conservation strategies in these locations. The aim of this research was to evaluate the uses, knowledge and conservation status of plants in two Quilombolas (descendants of slaves of African origin) communities in the Atlantic rainforest of Brazil, São Sebastião da Boa Vista (SSBV) and São Bento (SB). We used a combination of ethnobotanical and ecological survey methods to ask: 1) What ethnobotanical knowledge do the communities hold? 2) What native species are most valuable to them? 3) What is the conservation status of the native species used? Thirteen local experts described the names and uses of 212 species in SSBV (105 native species) and 221 in SB (96 native species). Shannon Wiener diversity and Pielou's Equitability indices of ethnobotanical knowledge of species were very high (5.27/0.96 and 5.28/0.96, respectively). Species with the highest cultural significance and use-value indexes in SSBV were Dalbergia hortensis (26/2.14), Eremanthus erythropappus (6.88/1), and Tibouchina granulosa (6.02/1); while Piptadenia gonoacantha (3.32/1), Sparattosperma leucanthum (3.32/1) and Cecropia glaziovii (3.32/0.67) were the highest in SB. Thirty-three native species ranked in the highest conservation priority category at SSBV and 31 at SB. D. hortensis was noteworthy because of its extremely high cultural importance at SSBV, and its categorization as a conservation priority in both communities. This information can be used towards generating sustainable use and conservation plans that are appropriate for the local communities.

An Overview of Neolignans of the Genus Piper L.: Isolation Methods and Biological Activities.

BACKGROUND: The genus Piper L. has the shikimic acid pathway predominantly expressed, biosynthesizing many cinnamic acid derivatives (CAD). OBJECTIVE: Neolignans comprise an important class of CAD that exhibit a wide range of pharmacological properties such as antibacterial, antitumor, insecticidal, anti-inflammatory, antioxidant, smooth muscle relaxant, neuroprotective, antiprotozoal and against platelet aggregation factor. These substances have been extracted and isolated from Piper species using different technics. RESULTS: The present review aims to summarize extraction and isolation methods and biological activities of the different types of neolignans covering the period from 1968 to January 2016.