Development of Jelly Loaded with Nanogel Containing Natural L-Dopa from Mucuna pruriens Seed Extract for Neuroprotection in Parkinson's Disease.

The first line therapy of patients with Parkinson's disease, a neurodegenerative disorder caused by the degeneration of dopaminergic neurons, is levodopa (L-dopa) given orally. Recently, the presence of natural L-dopa in the seed of Mucuna pruriens, a tropical legume in the Fabaceae family, was reported and it showed superior efficiency compared with synthetic L-dopa. Therefore, this study aimed to examine the phytochemical compounds, particularly for natural L-dopa, in M. pruriens seed extract and subsequently prepare a nanogel containing the extract prior to incorporation into a jelly formulation for use as a functional food in elderly patients with Parkinson's disease. The results show that M. pruriens seed extract contains phenolic compounds, flavonoids, tannins, alkaloids, terpenoids, and saponins. The quantitative analysis performed by the HPLC method revealed that spray-dried M. pruriens seed extract contained 5.59 ± 0.21% L-dopa. M. pruriens seed extract possesses a ferric-reducing antioxidant power and shows free-radical scavenging activity, determined by DPPH and ABTS methods, suggesting a distinctive antioxidant ability of the extract. M. pruriens seed extract at 10 ng/mL did not show cytotoxicity against a neuronal cell line (SH-SY5Y cells), kidney cells (HEK293 cells), or Caco-2 cells. Nanogel of M. pruriens seed extract prepared by ionic gelation had the hydrodynamic diameter, polydispersity index and zeta potential value of 384.53 ± 11.24 nm, 0.38 ± 0.05, and -11.23 ± 1.15 mV, respectively. The transepithelial transport of L-dopa in M. pruriens seed-extract nanogel through Caco-2 cells was measured. Nanogel containing M. pruriens seed extract at the concentration of 10 ng/mL exhibited neuroprotective activity. A jelly formulation containing M. pruriens seed-extract nanogel was successfully developed. The prepared jelly exhibited the acceptable physical and microbiological stabilities upon 6 months of the stability test. The half-life of natural L-dopa in jelly were 3.2, 0.9, and 0.6 years for storage conditions at 4, 30, and 40 °C, respectively, indicating the thermal degradation of natural L-dopa. The prepared jelly containing natural L-dopa from M. pruriens seed extract with the prominent antioxidant activity is a promising option for elderly patients suffering from Parkinson's disease.

A novel diterpene agent isolated from Microbispora hainanensis strain CSR-4 and its in vitro and in silico inhibition effects on acetylcholine esterase enzyme.

An actinomycete strain CSR-4 was isolated from the rhizosphere soil of Zingiber montanum. Taxonomic characterization revealed strain CSR-4 was a member of the genus Microbispora. Whole-genome sequence analysis exhibited the highest average nucleotide identity (ANI) value (95.34%) and digital DNA-DNA hybridization (DDH) value (74.7%) between strain CSR-4 and the closest relative M. hainanensis DSM 45428T, which was in line with the assignment to same species. In addition, a new diterpene compound, 2α-hydroxy-8(14), 15-pimaradien-17, 18-dioic acid, and nine known compounds were isolated from the ethyl acetate crude extract of fermentation broth. Interestingly, a new diterpene displayed the suppressive effect on the recombinant human acetylcholinesterase (rhAChE) enzymes (IC50 96.87 ± 2.31 µg/ml). In silico studies based on molecular docking and molecular dynamics (MD) simulations were performed to predict a binding mode of the new compound into the binding pocket of the rhAChE enzyme and revealed that some amino acids in the peripheral anions site (PAS), anionic subsite, oxyanion site and catalytic active site (CAS) of the rhAChE have interacted with the compound. Therefore, our new compound could be proposed as a potential active human AChE inhibitor. Moreover, the new compound can protect significantly the neuron cells (% neuron viability = 88.56 ± 5.19%) from oxidative stress induced by serum deprivation method at 1 ng/ml without both neurotoxicities on murine P19-derived neuron cells and cytotoxicity against Vero cells.

Physicochemical properties and anti-Propionibacterium acnes activity of film-forming solutions containing alpha-mangostin-rich extract.

The objective of this study was to study the effect of formulation compositions on physicochemical properties and anti-Propionibacterium acnes activity of film-forming solutions containing alpha-mangostin-rich extract (AM). Film-forming solution bases and film-forming solutions containing AM were prepared by using Eudragit RL PO or Klucel LF or combinations of them as film-forming polymers. Rheological properties, pH values of the solutions, and mechanical properties of the dry films were investigated. An optimized formulation was selected and evaluated for the film surface, in vitro AM release, an anti-P. acnes activity, and potential for being a skin irritant. It was found that mechanical properties of the dry films were affected by total polymer contents, ratios of Klucel LF/Eudragit RL PO, AM, and contents of triethyl citrate. The film-forming solutions containing AM had pH values around 7.0. Their flow curves exhibited Newtonian flow behaviors. The optimized formulation provided films possessing smooth and nonporous surfaces. These films showed greater anti-P. acnes activity than their base films without toxicity to skin fibroblasts. Furthermore, AM released from the film matrix obeyed Higuchi's equation. In conclusion, the film-forming solutions containing AM had potential for treatment of acne vulgaris caused by P. acnes. However, further in vivo study is necessary to determine their efficacy and safety for using in patients suffering from acne vulgaris.

Temperature is the key to altitudinal variation of phenolics in Arnica montana L. cv. ARBO.

Plants in alpine habitats are exposed to many environmental stresses, in particular temperature and radiation extremes. Recent field experiments on Arnica montana L. cv. ARBO indicated pronounced altitudinal variation in plant phenolics. Ortho-diphenolics increased with altitude compared to other phenolic compounds, resulting in an increase in antioxidative capacity of the tissues involved. Factors causing these variations were investigated by climate chamber (CC) experiments focusing on temperature and ultraviolet (UV)-B radiation. Plants of A. montana L. cv. ARBO were grown in CCs under realistic climatic and radiation regimes. Key factors temperature and UV-B radiation were altered between different groups of plants. Subsequently, flowering heads were analyzed by HPLC for their contents of flavonoids and caffeic acid derivatives. Surprisingly, increased UV-B radiation did not trigger any change in phenolic metabolites in Arnica. In contrast, a pronounced increase in the ratio of B-ring ortho-diphenolic (quercetin) compared to B-ring monophenolic (kaempferol) flavonols resulted from a decrease in temperature by 5 degrees C in the applied climate regime. In conclusion, enhanced UV-B radiation is probably not the key factor triggering shifts in the phenolic composition in Arnica grown at higher altitudes but rather temperature, which decreases with altitude.