Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.

Background: The objective of this meta-analysis was to review clinical trials of the combination of Pycnogenol ® and L-arginine (PAL) in the treatment of erectile dysfunction in men and to observe the effect of PAL combined therapy on sexual function in patients with erectile dysfunction (ED), and we hope to provide more choices of drugs for treating patients with ED. Methods and analysis: The study was constructed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched seven databases from inception to 15 February 2023, for a comprehensive search of clinical trials using relevant keywords. Continuous variables in this meta-analysis were calculated using the mean difference and 95% confidence interval. All relevant statistical analyses were performed using RevMan v. 5.4 software. Results: Three studies with 184 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. The results of the current meta-analysis showed that there were significant differences in the international index of erectile function scores (erectile domain), intercourse satisfaction scores, orgasmic function scores, overall satisfaction scores, and sexual desire scores between the combination treatment group and the control group. There was no significant difference in improving the testosterone levels between the two groups. Conclusion: These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED. This study will provide clinicians with more options for treating patients with ED. More randomized controlled trials are needed in the future to further demonstrate the effect of combination therapy on sexual function in patients with ED. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprosperoUnique, Identifier: CRD42023411781.

Unification of medicines and excipients: The roles of natural excipients for promoting drug delivery.

INTRODUCTION: Drug delivery systems (DDSs) formed by natural active compounds be instrumental in developing new green excipients and novel DDS from natural active compounds (NACs). 'Unification of medicines and excipients'(UME), the special inherent nature of the natural active compounds, provides the inspiration and conduction to achieve this goal. AREAS COVERED: This review summarizes the typical types of NACs from herbal medicine, such as saponins, flavonoids, polysaccharides, etc. that act as excipients and their main application in DDS. The comparison of the drug delivery systems formed by NACs and common materials and the primary formation mechanisms of these NACs are also introduced to provide a deepened understanding of their performance in DDS. EXPERT OPINION: Many natural bioactive compounds, such as saponins, polysaccharides, etc. have been used in DDS. Diversity of structure and pharmacological effects of NACs turn out the unique advantages in improving the performance of DDSs like targeting ability, adhesion, encapsulation efficiency(EE), etc. and enhancing the bioavailability of loaded drugs.

Sulfite as the substrate of C-sulfonate metabolism of α, ß-unsaturated carbonyl containing andrographolide: analysis of sulfite in rats' intestinal tract and the reaction kinetics of andrographolide with sulfite.

One-sixth of the currently known natural products contain α, ß-unsaturated carbonyl groups. Our previous studies reported a rare C-sulfonate metabolic pathway. Sulfonate groups were linked to the ß-carbon of α, ß-unsaturated carbonyl-based natural compounds through this pathway. However, the mechanism of this type of metabolism is still not fully understood, especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition. In this work, the enzyme-mediated and non-enzymatic pathways were studied. First, the sulfite content in rat intestine was determined by LC-MS/MS. The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383 µg·g-1, whereas the amount of sulfite in rat feed was lower than the lower limit of quantitation (20 µg·g-1). Second, the reaction kinetics of sulfite-andrographolide reactions in phosphate buffer solutions (pH 6-8) was studied. The half-lives of andrographolide ranged from minutes to hours. This was suggested that the C-sulfonate reaction of andrographolide was very fast. Third, the C-sulfonate metabolites of andrographolide were both detected when andrographolide and L-cysteine-S-conjugate andrographolide were incubated with the rat small intestine contents or sulfite, indicating that the sulfite amount in rat intestine contents was high enough to react with andrographolide, which assisted a significant portion of andrographolide metabolism. Finally, the comparison of andrographolide metabolite profiles among liver homogenate (with NADPH), liver S9 (with NADPH), small intestine contents homogenate (with no NADPH), and sulfite solution incubations showed that the C-sulfonate metabolites were predominantly generated in the intestinal tract by non-enzymatic pathway. In summary, sulfite can serve as a substrate for C-sulfonate metabolism, and these results identified non-enzymatically nucleophilic addition as the potential mechanism for C-sulfonate metabolism of compounds containing α, ß-unsaturated carbonyl moiety.

New pathway ameliorating ulcerative colitis: focus on Roseburia intestinalis and the gut-brain axis.

BACKGROUND: The community of gut microbes is a key factor controlling the intestinal barrier that communicates with the nervous system through the gut-brain axis. Based on our clinical data showing that populations of Roseburia intestinalis are dramatically decreased in the gut of patients with ulcerative colitis, we studied the efficacy of a strain belonging to this species in the context of colitis and stress using animal models. METHODS: Dextran sulfate sodium was used to induce colitis in rats, which then underwent an enema with R. intestinalis as a treatment. The disease activity index, fecal changes and body weight of rats were recorded to evaluate colitis, while histological and immunohistochemical analyses were carried out to examine colon function, and 16S rRNA sequencing was performed to evaluate the gut microbiota change. Behavioral assays and immunohistochemical staining of brain were performed to assess the effect of R. intestinalis on the gut-brain axis. RESULTS: Colitis-related symptoms in rats were significantly relieved after R. intestinalis enema, and the stool traits and colon length of rats were significantly recovered after treatment. The gut epithelial integrity and intestinal barrier were restored in treated rats, as evidenced by the higher expression of Zo-1 in colon tissues, accompanied by the restoration of gut microbiota. Meanwhile, depressive-like behaviors of rats were reduced after treatment, and laboratory experiments on neuronal cells also showed that IL-6, IL-7 and 5-HT were downregulated by R. intestinalis treatment in both serum and brain tissue, while Iba-1 expression was reduced in treated rats. CONCLUSIONS: The administration of R. intestinalis contributes to restoration of the gut microbiota, promoting colon repair and the recovery of gastrointestinal function. These alterations are accompanied by the relief of depressive-like behaviors through a process modulated by the neuronal network and the regulation of inflammation by the gut-brain axis.

Evaluation of the chemical qualities and microstructural changes of Lentinula edodes caused by airborne ultrasonic treatment combined with microwave vacuum drying.

This study analyzed a new drying method using airborne ultrasound combined with microwave vacuum to study its effect on the quality characteristics and microstructure of dehydrated L. edodes. Ultrasonic treatment resulted in many micropores in the product, forming the sponge effect caused by ultrasonic waves, which can promote the rapid evaporation of water in the product. Samples of Lentinula edodes individuals were dried using four methods: hot air drying (HAD), microwave vacuum drying (MVD), microwave vacuum drying after ultrasonic pretreatment (US+MVD) and airborne ultrasonic treatment combined with microwave vacuum drying (USMVD). The results showed that USMVD can reduced the loss of total sugar, total phenol, and total antioxidants in L. edodes, and increased the relative content of ergosterol, sulfur compounds, and free amino acids (p < 0.05). Scanning electron microscope observation revealed that USMVD resulted in a uniform reticular porous structure, which could better maintain desirable levels of nutrients. Therefore, USMVD can produce high quality products. PRACTICAL APPLICATION: Airborne ultrasonic waves combined with MVD provides an innovative drying method for mushrooms, which has not been studied at present. The mixed drying method has great potential in maintaining product quality. It provides a theoretical basis for studying drying technology in the future.

Sonchus oleraceus Linn protects against LPS-induced sepsis and inhibits inflammatory responses in RAW264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Sonchus oleraceus Linn (SOL) belongs to family of Asteraceae, is a traditional medicinal plant, which has been used to treat tumor, inflammatory diseases, infection and so on in Chinese folk culture. AIM OF THE STUDY: This work investigated the influence of aqueous ethanol extract of whole plant of SOL and contribution of its main components on inflammation METHODS AND RESULTS: Oral administration of SOL (10 mg/kg) to mice reduced the expression of inflammatory cytokines including IL-6, IL-1ß, and TNF-α, in the LPS-induced sepsis mouse model. Major phenolics in SOL were isolated and determined by HPLC. Results indicate that SOL at the concentration range from 25 to 100 µg/mL and its main components, chlorogenic acid, caffeic acid (25-100 µM) significantly reduced the pro-inflammatory cytokine IL-1ß, IL-6, TNF-α, attenuated iNOS and COX-2 expression in LPS-stimulated Macrophages. In addition, western blot analysis showed SOL suppressed inducible nitric oxide synthase (iNOS) protein expression and the phosphorylation of extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK). CONCLUSION: The underlying mechanism of anti-inflammation might be in according with the inhibition of MAPKs activation as well as down regulation of iNOS and cyclooxygenase-2 (COX-2).

Rheological properties, molecular distribution, and microstructure of Fortunella margarita (Lour.) swingle polysaccharides.

Fortunella margarita polysaccharides (FMPS) are one of the main bioactive components of F. margarita. The activity is related to their rheological properties and structure. The objective of this study was to investigate the relationship between rheological properties, molecular distribution, and microstructure of crude FMPS (C-FMPS) and purified FMPS (P-FMPS). The results showed that both of solutions were shear-thinning pseudoplastic fluids with flow properties in line with the Power Law model. The pseudoplasticity of P-FMPS was stronger compared to C-FMPS. Additionally, the molecular weight and polydispersity of P-FMPS were greater, whereas the molecular radius was less compared to C-FMPS. The surface of C-FMPS was rough and dense whereas P-FMPS displayed a smooth network structure by environment scanning electron microscopy. According to confocal laser scanning microscopy, C-FMPS dispersed in the medium without connected network, whereas the network of P-FMPS was unevenly distributed in the medium and the shape was compact and smooth. The molecular distribution and microstructure of P-FMPS were attributed to the purification process while rearrangement and aggregation of polysaccharide molecules took place, which resulted in the significant difference of rheological properties between C-FMPS and P-FMPS.

Extraction optimization, structure and antioxidant activities of Fortunella margarita Swingle polysaccharides.

The objective of this study was to maximize the yield of polysaccharides extracted from Fortunella margarita Swingle (FMPS) and investigate the relationship between the structure and antioxidant activities. The optimal conditions for ultrasonic-assisted extraction (UAE) of FMPS were ultrasonic power 171W, extraction temperature 50°C, water volume to raw material weight (W/M) ratio 32 ml/g and extraction time 87 min. Under these conditions, the yield of FMPS was 4.15±0.11% (w/w), which was increased by 129.28% compared to hot water extraction. FMPS3, the main fraction of FMPS, was isolated by DEAE Sepharose CL-6B column chromatography. According to size-exclusion chromatography, multi-angle laser light-scattering and refractive index (SEC-MALLS-RI), the molecular weight (Mw), polydispersity index (Mw/Mn) and root-mean-square turning radius (Rg) of FMPS3 were 4.58×10(5) (±2.02%) Da, 1.08 (±1.23%), 28.13 (±1.73%) nm, respectively. FMPS3, linked mainly by ß-glycosidic bonds, consisted of galactose, galacturonic acid, glucose, mannose and rhamnose as shown by HPLC, FT-IR, 1H NMR and 13C NMR. Furthermore, FMPS3 displayed strong scavenging ability against hydroxyl, superoxide and DPPH radicals. The activity was affected by the monosaccharide composition, molecular weight and proportion of ß-glycosidic bonds and was a result of a combination of multiple structural factors. FMPS3 is potentially a novel natural antioxidant agent.

Optimization of ultrasonic-assisted extraction of pomegranate (Punica granatum L.) seed oil.

The effectiveness of ultrasonic-assisted extraction (UAE) of pomegranate seed oil (PSO) was evaluated using a variety of solvents. Petroleum ether was the most effective for oil extraction, followed by n-hexane, ethyl acetate, diethyl ether, acetone, and isopropanol. Several variables, such as ultrasonic power, extraction temperature, extraction time, and the ratio of solvent volume and seed weight (S/S ratio) were studied for optimization using response surface methodology (RSM). The highest oil yield, 25.11% (w/w), was obtained using petroleum ether under optimal conditions for ultrasonic power, extraction temperature, extraction time, and S/S ratio at 140 W, 40 °C, 36 min, and 10 ml/g, respectively. The PSO yield extracted by UAE was significantly higher than by using Soxhlet extraction (SE; 20.50%) and supercriti cal fluid extraction (SFE; 15.72%). The fatty acid compositions were significantly different among the PSO extracted by Soxhlet extraction, SFE, and UAE, with punicic acid (>65%) being the most dominant using UAE.

Optimization of microwave vacuum drying of lotus (Nelumbo nucifera Gaertn.) seeds by response surface methodology.

Drying is the main process used to treat lotus seeds for storage. In this study, response surface methodology was used to optimize processing methods for microwave vacuum (MWV) drying of lotus seeds and to create a desirable product. A central composite design with three important factors: microwave output power (2.0-4.0 kW), vacuum degree (-0.070 to -0.090 MPa) and on/off ratio (68/52 s to 99/21 s) was used to study the response variables of drying time, shrinkage ratio, rehydration ratio and whiteness index. The optimum conditions for MWV drying of lotus seeds were determined to obtain a minimal drying time, minimal shrinkage ratio, maximum rehydration ratio and maximum whiteness index. The optimum drying conditions were found to be: microwave output power 3.2 kW, vacuum degree -0.083 MPa and on/off ratio 94/26 s. Under these optimal conditions, drying time, shrinkage ratio, rehydration ratio and whiteness index were found to be 10 min, 37.66%, 157.1% and 68.83, respectively.

Improvement of coenzyme Q10 production: mutagenesis induced by high hydrostatic pressure treatment and optimization of fermentation conditions.

Coenzyme Q10 (CoQ10, ubiquinone), a potent antioxidative dietary supplement, was produced by submerged fermentation using Agrobacterium tumefaciens instead of chemical synthesis or solvent extraction. Agrobacterium tumefaciens 1.2554 was subjected to mutagenesis using a series of treatments including high hydrostatic pressure (HHP) treatment, UV irradiation, and diethyl sulfate (DES) treatment to obtain mutant strains showing higher CoQ10 production than wild-type strains. A mutant strain PK38 with four genetic markers was isolated: the specific CoQ10 content of the mutant strain increased by 52.83% compared with the original strain. Effects of carbon and nitrogen sources on CoQ10 production with PK38 were studied. Sucrose at concentration of 30 g/l was tested as the best carbon source, and yeast extract at concentration of 30 g/l supplemented with 10 g/l of ammonium sulfate was identified to be the most favorable for CoQ10 production using PK38. Fed-batch culture strategy was then used for increasing production of CoQ10 in 5-l fermentor. Using the exponential feeding fed-batch culture of sucrose, cell growth and CoQ10 formation were significantly improved. With this strategy, the final cell biomass, CoQ10 production, and specific CoQ10 production increased by 126.11, 173.12, and 22.76%, respectively, compared to those of batch culture.

Tobacco biomass hydrolysate enhances coenzyme Q10 production using photosynthetic Rhodospirillum rubrum.

Coenzyme Q10 (CoQ10), a potent antioxidative dietary supplement, was produced using a photosynthetic bacteria Rhodospirillum rubrum ATCC 25852 by submerged fermentation supplemented with tobacco biomass hydrolysate (TBH) in comparison with media supplemented with hydrolysates prepared with alfalfa (ABH) or spinach (SBH). Growth medium supplemented with 20% (v/v) TBH was found favorable with regard to cell density and CoQ10 concentration. The stimulation effects on cell growth (shortened lag phase, accelerated exponential growth, and elevated final cell concentration) and CoQ10 production (enhanced specific CoQ10 content per unit cell weight) could be attributed to the presence of solanesol, the precursor of CoQ10, in the tobacco biomass. The final yield of CoQ10 reached 20.16 mg/l in the fermentation medium supplemented with 20% TBH.