Natural Compounds Purified from the Leaves of Aristotelia chilensis: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on NaV Channels.

Aristotelia chilensis or "maqui" is a tree native to Chile used in the folk medicine of the Mapuche people as an anti-inflammatory agent for the treatment of digestive ailments, fever, and skin lesions. Maqui fruits are black berries which are considered a "superfruit" with notable potential health benefits, promoted to be an antioxidant, cardioprotective, and anti-inflammatory. Maqui leaves contain non-iridoid monoterpene indole alkaloids which have previously been shown to act on nicotinic acetylcholine receptors, potassium channels, and calcium channels. Here, we isolated a new alkaloid from maqui leaves, now called makomakinol, together with the known alkaloids aristoteline, hobartine, and 3-formylindole. Moreover, the polyphenols quercetine, ethyl caffeate, and the terpenes, dihydro-ß-ionone and terpin hydrate, were also obtained. In light of the reported analgesic and anti-nociceptive properties of A. chilensis, in particular a crude mixture of alkaloids containing aristoteline and hobartinol (PMID 21585384), we therefore evaluated the activity of aristoteline and hobartine on NaV1.8, a key NaV isoform involved in nociception, using automated whole-cell patch-clamp electrophysiology. Aristoteline and hobartine both inhibited Nav1.8 with an IC50 of 68 ± 3 µM and 54 ± 1 µM, respectively. Hobartine caused a hyperpolarizing shift of the voltage-dependence of the activation, whereas aristoteline did not change the voltage-dependence of the activation or inactivation. The inhibitory activity of these alkaloids on NaV channels may contribute to the reported analgesic properties of Aristotelia chilensis used by the Mapuche people.

The Potential Role of Epigallocatechin-3-Gallate (EGCG) in Breast Cancer Treatment.

Breast cancer is one of the most diagnosed cancers worldwide, with an incidence of 47.8%. Its treatment includes surgery, radiotherapy, chemotherapy, and antibodies giving a mortality of 13.6%. Breast tumor development is driven by a variety of signaling pathways with high heterogeneity of surface receptors, which makes treatment difficult. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol isolated as the main component in green tea; it has shown multiple beneficial effects in breast cancer, controlling proliferation, invasion, apoptosis, inflammation, and demethylation of DNA. These properties were proved in vitro and in vivo together with synergistic effects in combination with traditional chemotherapy, increasing the effectiveness of the treatment. This review focuses on the effects of EGCG on the functional capabilities acquired by breast tumor cells during its multistep development, the molecular and signal pathways involved, the synergistic effects in combination with current drugs, and how nanomaterials can improve its bioavailability on breast cancer treatment.

The potential role of Epigallocatechin-3-Gallate (EGCG) in breast cancer treatment

Breast cancer is one of the most diagnosed cancers worldwide, with an incidence of 47.8%. Its treatment includes surgery, radiotherapy, chemotherapy, and antibodies giving a mortality of 13.6%. Breast tumor development is driven by a variety of signaling pathways with high heterogeneity of surface receptors, which makes treatment difficult. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol isolated as the main component in green tea; it has shown multiple beneficial effects in breast cancer, controlling proliferation, invasion, apoptosis, inflammation, and demethylation of DNA. These properties were proved in vitro and in vivo together with synergistic effects in combination with traditional chemotherapy, increasing the effectiveness of the treatment. This review focuses on the effects of EGCG on the functional capabilities acquired by breast tumor cells during its multistep development, the molecular and signal pathways involved, the synergistic effects in combination with current drugs, and how nanomaterials can improve its bioavailability on breast cancer treatment.

Therapeutic Effects of Cannabinoids and Their Applications in COVID-19 Treatment.

Cannabis sativa is one of the first medicinal plants used by humans. Its medical use remains controversial because it is a psychotropic drug whose use has been banned. Recently, however, some countries have approved its use, including for recreational and medical purposes, and have allowed the scientific study of its compounds. Cannabis is characterized by the production of special types of natural products called phytocannabinoids that are synthesized exclusively by this genus. Phytocannabinoids and endocannabinoids are chemically different, but both pharmacologically modulate CB1, CB2, GRP55, GRP119 and TRPV1 receptor activities, involving activities such as memory, sleep, mood, appetite and motor regulation, pain sensation, neuroinflammation, neurogenesis and apoptosis. Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids with greater pharmacological potential, including anti-inflammatory, neuroprotective and anticonvulsant activities. Cannabidiol is showing promising results for the treatment of COVID-19, due to its capability of acting on the unleashed cytokine storm, on the proteins necessary for both virus entry and replication and on the neurological consequences of patients who have been infected by the virus. Here, we summarize the latest knowledge regarding the advantages of using cannabinoids in the treatment of COVID-19.

Ginkgolides and Huperzine A for complementary treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual deterioration of cognitive function, memory, and inability to perform daily, social, or occupational activities. Its etiology is associated with the accumulation of ß-amyloid peptides, phosphorylated tau protein, and neuroinflammatory and oxidative processes in the brain. Currently, there is no successful pharmacological treatment for AD. The few approved drugs are mainly aimed at treating the symptoms; however, due to the increasing discovery of etiopathological factors, there are great efforts to find new multifunctional molecules to slow down the course of this neurodegenerative disease. The commercial Ginkgo biloba formulation EGb 761® and Huperzine A, an alkaloid present in the plant Huperzia serrata, have shown in clinical trials to possess cholinergic and neuroprotective activities, including improvement in cognition, activities of daily living, and neuropsychiatric symptoms in AD patients. The purpose of this review is to expose the positive results of intervention with EGb 761® and Huperzine in patients with mild to moderate AD in the last 10 years, highlighting the pharmacological functions that justify their use in AD therapy.

Curcuma as an adjuvant in colorectal cancer treatment.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and mostly affects men. Around 20% of its incidence is by familiar disposition due to hereditary syndromes. The CRC treatment involves surgery and chemotherapy; however, the side effects of treatments and the fast emergence of drug resistance evidence the necessity to find more effective drugs. Curcumin is the main polyphenol pigment present in Curcuma longa, a plant widely used as healthy food with antioxidant properties. Curcumin has synergistic effects with antineoplastics such as 5-fluorouracil and oxaliplatin, as well anti-inflammatory drugs by inhibiting cyclooxygenase-2 and the Nuclear factor kappa B. Furthermore, curcumin shows anticancer properties by inhibition of the Wnt/ß-catenin, Hedgehog, Notch, and the phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways implicated in the progression of CRC. However, the consumption of pure curcumin is less suitable, as the absorption is poor, and the metabolism and excretion are high. Pharmacological formulations and essential oils of the plant improve the curcumin absorption, resulting in therapeutical dosages. Despite the evidence obtained in vitro and in vivo, clinical studies have not yet confirmed the therapeutic potential of curcumin against CRC. Here we reviewed the last scientific information that supports the consumption of curcumin as an adjuvant for CRC therapy.

Polyhydroxyalkanoates production from methane emissions in Sphagnum mosses: Assessing the effect of temperature and phosphorus limitation.

The isolation of highly efficient methanotrophic communities is crucial for the optimization of methane bioconversion into products with a high market value such as polyhydroxyalkanoates (PHA). The research here presented aimed at enriching a methanotrophic consortium from two different inocula (Sphagnum peat moss (Sp) and Sphagnum and activated sludge (M)) able to accumulate PHA while efficiently oxidizing CH4. Moreover, the effect of the temperature and phosphorus limitation on the biodegradation rate of CH4 and the PHA accumulation potential was investigated. Higher CH4 degradation rates were obtained under P availability at increasing temperature (25, 30 and 37 °C). The biomass enriched from the mixed inoculum always exhibited a superior biodegradation performance regardless of the temperature (a maximum value of 84.3 ±â€¯8.4 mg CH4 h-1 g biomass-1 was recorded at 37 °C). The results of the PHB production showed that phosphorus limitation is required to promote PHB accumulation, the highest PHB content being observed with the Sphagnum inoculum at 25 °C (13.6 ±â€¯5.6%). The differential specialization of the microbial communities depending on the enrichment temperature supported the key role of this parameter on the results obtained. In all cases after the completion of the enrichment process and of the P limitation tests, Methylocystis, a type II methanotroph known for its ability to accumulate PHA, was the genus that became dominant (reaching percentages from 16 to 46% depending on the enrichment temperature). Thus, the results here obtained demonstrated for the first time the relevance of the temperature used for the enrichment of the methanotrophic bacteria to boost PHA production yields under P limiting condition, highlighting the importance of optimizing culture conditions to improve the cost-efficiency of bioprocesses based on using methane as the primary feedstock for the PHA industrial market.

Anoxic denitrification of BTEX: Biodegradation kinetics and pollutant interactions.

Anoxic mineralization of BTEX represents a promising alternative for their abatement from O2-deprived emissions. However, the kinetics of anoxic BTEX biodegradation and the interactions underlying the treatment of BTEX mixtures are still unknown. An activated sludge inoculum was used for the anoxic abatement of single, dual and quaternary BTEX mixtures, being acclimated prior performing the biodegradation kinetic tests. The Monod model and a Modified Gompertz model were then used for the estimation of the biodegradation kinetic parameters. Results showed that both toluene and ethylbenzene are readily biodegradable under anoxic conditions, whereas the accumulation of toxic metabolites resulted in partial xylene and benzene degradation when present both as single components or in mixtures. Moreover, the supplementation of an additional pollutant always resulted in an inhibitory competition, with xylene inducing the highest degree of inhibition. The Modified Gompertz model provided an accurate fitting for the experimental data for single and dual substrate experiments, satisfactorily representing the antagonistic pollutant interactions. Finally, microbial analysis suggested that the degradation of the most biodegradable compounds required a lower microbial specialization and diversity, while the presence of the recalcitrant compounds resulted in the selection of a specific group of microorganisms.

Comparative assessment of a biofilter, a biotrickling filter and a hollow fiber membrane bioreactor for odor treatment in wastewater treatment plants.

A low abatement efficiency for the hydrophobic fraction of odorous emissions and a high footprint are often pointed out as the major drawbacks of conventional biotechnologies for odor treatment. In this work, two conventional biotechnologies (a compost-based biofilter, BF, and a biotrickling filter, BTF), and a hollow-fiber membrane bioreactor (HF-MBR) were comparatively evaluated in terms of odor abatement potential and pressure drop (ΔP) at empty bed residence times (EBRTs) ranging from 4 to 84 s, during the treatment of methyl-mercaptan, toluene, alpha-pinene and hexane at trace level concentrations (0.75-4.9 mg m(-3)). High removal efficiencies (RE > 90% regardless of the air pollutant) were recorded in the BF at EBRTs ≥ 8 s, although the high ΔP across the packed bed limited its cost-effective operation to EBRTs > 19 s. A complete methyl-mercaptan, toluene and alpha-pinene removal was recorded in the BTF at EBRTs ≥ 4 s and ΔP lower than 33 mmH2O (∼611 Pa mbed(-1)), whereas slightly lower REs were observed for hexane (∼88%). The HF-MBR completely removed methyl-mercaptan and toluene at all EBRTs tested, but exhibited an unstable alpha-pinene removal performance as a result of biomass accumulation and a low hexane abatement efficiency. Thus, a periodical membrane-cleaning procedure was required to ensure a steady abatement performance. Finally, a high bacterial diversity was observed in the three bioreactors in spite of the low carbon source spectrum present in the air emission.

Biological anoxic treatment of O2-free VOC emissions from the petrochemical industry: a proof of concept study.

An innovative biofiltration technology based on anoxic biodegradation was proposed in this work for the treatment of inert VOC-laden emissions from the petrochemical industry. Anoxic biofiltration does not require conventional O2 supply to mineralize VOCs, which increases process safety and allows for the reuse of the residual gas for inertization purposes in plant. The potential of this technology was evaluated in a biotrickling filter using toluene as a model VOC at loads of 3, 5, 12 and 34 g m(-3)h(-1) (corresponding to empty bed residence times of 16, 8, 4 and 1.3 min) with a maximum elimination capacity of ∼3 g m(-3)h(-1). However, significant differences in the nature and number of metabolites accumulated at each toluene load tested were observed, o- and p-cresol being detected only at 34 g m(-3)h(-1), while benzyl alcohol, benzaldehyde and phenol were detected at lower loads. A complete toluene removal was maintained after increasing the inlet toluene concentration from 0.5 to 1 g m(-3) (which entailed a loading rate increase from 3 to 6 g m(-3)h(-1)), indicating that the system was limited by mass transfer rather than by biological activity. A high bacterial diversity was observed, the predominant phyla being Actinobacteria and Proteobacteria.