Influence of Lactobacillus rhamnosus Supplementation on the Glycaemic Index, Lipid Profile, and Microbiome of Healthy Elderly Subjects: A Preliminary Randomized Clinical Trial.

Aging is a time-dependent complex biological process of organisms with gradual deterioration of the anatomical and physiological functions. The role of gut microbiota is inevitable in the aging process. Probiotic interventions improve gut homeostasis and support healthy aging by enhancing beneficial species and microbial biodiversity in older adults. The present preliminary clinical trial delves into the impact of an 8-week Lactobacillus rhamnosus intervention (10 × 109 CFU per day) on the glycaemic index, lipid profile, and microbiome of elderly subjects. Body weight, body fat, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein (LDL) are assessed at baseline (Week 0) and after treatment (Week 8) in placebo and probiotic groups. Gaussian regression analysis highlights a significant improvement in LDL cholesterol in the probiotic group (p = 0.045). Microbiome analysis reveals numeric changes in taxonomic abundance at various levels. At the phylum level, Proteobacteria increases its relative frequency (RF) from 14.79 ± 5.58 at baseline to 23.46 ± 8.02 at 8 weeks, though statistically insignificant (p = 0.100). Compared to the placebo group, probiotic supplementations significantly increased the proteobacteria abundance. Genus-level analysis indicates changes in the abundance of several microbes, including Escherichia-Shigella, Akkermansia, and Bacteroides, but only Butyricimonas showed a statistically significant level of reduction in its abundance. Probiotic supplementations significantly altered the Escherichia-Shigella and Sutterella abundance compared to the placebo group. At the species level, Bacteroides vulgatus substantially increases after probiotic treatment (p = 0.021). Alpha and beta diversity assessments depict subtle shifts in microbial composition. The study has limitations, including a small sample size, short study duration, single-strain probiotic use, and lack of long-term follow-up. Despite these constraints, the study provides valuable preliminary insights into the multifaceted impact of L. rhamnosus on elderly subjects. Further detailed studies are required to define the beneficial effect of L. rhamnosus on the health status of elderly subjects.

Optimization and Transfollicular Delivery of Finasteride-Loaded Proniosomes for Hair Growth Stimulation in C57BL/6Mlac Mice.

The study aimed to develop the finasteride-loaded proniosome (FLP) to enhance the transfollicular delivery of finasteride (FN). The response surface methodology (RSM) combined with central composite design (CCD) with three independent variables (FN concentrations, total lipid content, and cholesterol content) was used to optimize the FLP preparation. The particles size, zeta potential, entrapment efficiency, and drug loading capacity of the FLP were analyzed. The transfollicular delivery of the optimum formulation was investigated in vitro. In vivo hair growth stimulation study was performed on C57BL/6Mlac mice dorsal areas. The Draize primary skin irritation test for erythema and edema was performed in the New Zealand white rabbit skin. The optimum FLP consists of 5.0 mM of FN, 10.1 mM of total lipid content, and 50.0% of the cholesterol in the total lipid. The prepared proniosome delivered the FN significantly (p < 0.05), compared to the naked finasteride solution in a dose- and time-dependent manner. The FLP treatment significantly increases the number and size of hair follicles in a dose-dependent manner. The efficiency of 1% FLP was comparable to the 2% minoxidil solution. The FLP exhibited no skin irritation after 72 h. Therefore, the results demonstrated that the FLP could stimulate hair growth via a transfollicular delivery system.

Improvement of Biophysical Skin Parameters of Topically Applied Fermented Soybean Extract-Loaded Niosomes with No Systemic Toxicity in Ovariectomized Rats.

Despite the known beneficial impacts of estrogen used as hormone replacement therapy to ameliorate signs of skin aging in postmenopausal women, its compliance rates are low. A significant amount of estrogen may be absorbed into the blood circulation and can lead to systemic actions. Soy isoflavone exhibits biological activities similar to synthetic estrogen because it is a heterocyclic phenolic compound. The disadvantage of most topical ingredients based on isoflavone is that they contain biologically inactive glycoside forms, which must be converted to a readily absorbed aglycone for the topical application. The purposes of this study were to develop niosomes-loaded Aspergillus oryzae-fermented soybean extract (FSE) to enhance skin absorption with proven systemic side effect compared to estrogen application. Skin hydration and viscoelasticity of 75 days post-ovariectomized (OVX) Wistar rats following 84-day topical treatment with various tested gel formulations containing fermented soybean extract (FSE) were evaluated. The tested formulations were gel + FSE nanoniosomes, gel + FSE microniosomes, gel + FSE (200 µg FSE/9 cm2/rat), gel + blank nanoniosomes (a negative control), and gel + 17ß-estradiol (E2) nanoniosomes (a positive control, 20 µg E2/9 cm2/rat). Changes in vaginal cornifications and weights of uteri, livers, and kidneys in the OVX rats and signs of primary skin irritation in the rabbits were evaluated for their toxicities. Results showed that FSE-loaded nanoniosomes improved the skin hydration and viscoelasticity better than gel + FSE microniosomes and gel + FSE, respectively, but lower than those of gel + E2 nanoniosomes (p < 0.05). Unlike all gel + E2 nanoniosomes, the FSE formulations showed no changes in vaginal cells and weights of uteri, livers, and kidneys and no signs of skin irritation. In conclusion, The FSE niosome-based gels should be promising candidates for delivering phytoestrogens against signs of skin aging with no systemic toxicities.

Effects of Litsea cubeba (Lour.) Persoon Essential Oil Aromatherapy on Mood States and Salivary Cortisol Levels in Healthy Volunteers.

Aromatherapy is one of the complementary therapies to improve health. The aromatic essential oils have been used in the treatment procedure through inhalation of essential oil vapor, massage, and herbal bathing. Litsea species are generally used in traditional medicine, and Litsea cubeba (Lour.) Persoon is a potent fumigant plant, used in cosmetics and foods as essence. The chemical composition of the essential oil of different parts of L. cubeba has been found to be varied. L. cubeba essential oil (LEO) is known for the treatment of cognition-associated discomforts. The current study assessed the impact of inhalation of LEO on mood states and salivary cortisol levels of healthy people. Fifteen healthy volunteers were involved in the study. The Profile of Mood States (POMS) Questionnaire and ELISA methods were employed to determine the mood states and salivary cortisol level, respectively. (-)-ß-pinene, ß-citral, cis- and trans-citral, citronellal, limonene, linalool, and 6-methyl-5-hepten-2-one were detected in LEO by GC-MS analysis. The heart rate and blood pressure were not affected significantly during LEO exposure. The inhalation of LEO significantly improved the total mood disturbance and reduced the confusion among the healthy human subjects. LEO inhalation reduced the salivary cortisol level at a notable level. The results of the current study warrant further studies on the beneficial effect of LEO aromatherapy in healthy and diseased subjects to uncover the therapeutic nature of the L. cubeba plant.

Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation.

The aim of this study was to develop lipid-based nanoparticles that entrapped a high concentration of capsaicin (0.25%) from a capsicum oleoresin extract. The solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were strategically fabricated to entrap capsaicin without a hazardous solvent. Optimized nanosize lipid particles with high capsaicin entrapment and loading capacity were achieved from pair-wise comparison of the solid lipid mixtures consisting of fatty esters and fatty alcohols, representing small and large crystal-structure molecules combined with a compatible liquid lipid and surfactants (crystallinity index = 3%). This report was focused on selectively captured capsaicin from oleoresin in amorphous chili extract-loaded NLCs with 85.27% ± 0.12% entrapment efficiency (EE) and 8.53% ± 0.01% loading capacity (LC). The particle size, polydispersity index, and zeta potential of chili extract-loaded NLCs were 148.50 ± 2.94 nm, 0.12 ± 0.03, and -29.58 ± 1.37 mV, respectively. The favorable zero-order kinetics that prolonged capsaicin release and the significantly faster transdermal penetration of the NLC attributed to the reduction in skin irritation of the concentrated capsaicin NLCs, as illustrated by the in vitro EpiDermTM three-dimensional human skin irritation test and hen's egg test chorioallantoic membrane assay (HET-CAM).

Dermal targeting of Centella asiatica extract using hyaluronic acid surface modified niosomes.

The work aimed to develop Centella asiatica extract-loaded niosomes (CAE-Nio) and surface modified niosomes by hyaluronic acid (CAE-Nio-HA) to enhance transdermal penetration. Niosome formulations were prepared by film hydration method using Tween 60 and Span 60 as nonionic surfactants, cholesterol and various CAE contents. Various HA concentrations were investigated to obtain optimized CAE-Nio enhancing further skin penetration. Results showed that niosomes prepared from Tween 60 yielded suitable CAE encapsulated niosomes with mean particle size and zeta-potential of 155 nm and -15 mV, respectively. The niosomes exhibited high encapsulation efficiency (%EE) and drug loading capacity (%DL) of 71-77% and 3-7%, respectively. Incorporating HA to niosome decreased %DL and caused larger particle size and increased zeta-potential in a dose dependent manner while %EE remained unaffected. The sustained-release behaviour of CAE from all niosomes was under a diffusion controlled mechanism. Asiaticoside, a relatively polar compound from CAE-Nio-HA could penetrate through the stratum corneum and dermis in a larger amount than from CAE-Nio and CAE solution. CAE-Nio-HA formulations showed good stability under low temperature (4 °C and 25 °C) for periods longer than 4 months. In conclusion, the developed Nio-HA is a promising delivery system for asiaticoside to enhanced dermal absorption, permeation and accumulation in viable epidermis and dermis layers. This system can also be applied to other hydrophilic natural active compounds.

Determination of the Marker Diarylheptanoid Phytoestrogens in Curcuma comosa Rhizomes and Selected Herbal Medicinal Products by HPLC-DAD.

A method for quantification of diarylheptanoids in Curcuma comosa rhizomes and selected pharmaceutical preparations was established by using HPLC-diode array detector (DAD). The chromatographic separation of three diarylheptanoids [(3S)-1-(3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol (1), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (2), and (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (3)] was performed on a Luna C18 analytical column using gradient elution with 0.5% acetic acid in water and acetonitrile with a flow rate of 1 mL/min and a column temperature of 35°C. The calibration curves for the analytes showed good linearity (R2>0.999), high precision (relative standard deviation (RSD) <2%) and acceptable recovery (98.35-103.90%, RSD <2%). The limit of detection (LOD) and limit of quantification (LOQ) were 0.06-0.22 and 0.18-0.69 µg/mL, respectively. The results of all validated parameters were within the limits according to the International Conference on Harmonization (ICH) Guidelines. The established method was successfully applied for qualitative and quantitative determination of the three constituents in different samples of C. comosa and some commercial products in capsules. The simplicity, rapidity, and reliability of the method could be useful for the fingerprint analysis and standardization of diarylheptanoids, which are responsible for the estrogenic activity in raw materials and herbal medicinal products of C. comosa.

5α-reductase inhibition and hair growth promotion of some Thai plants traditionally used for hair treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Many Thai traditional herbs have been used for hundreds of years for hair treatment and nourishment, including hair loss. However, scientific evidence about their mechanisms of action has not yet been elucidated. AIMS OF THE STUDY: The purpose of this research is to define the possible mechanisms involved in hair loss treatment of the selected plants by determining the 5α-reductase enzyme inhibition and hair growth promoting activities, and the relationship between these two activities. MATERIALS AND METHODS: Seventeen Thai plants traditionally used for hair treatment were selected. The plants were dried, ground and extracted by maceration with ethyl alcohol. These extracts were further tested for 5α-reductase inhibition using enzymes from rat livers. Hair growth promoting activity was tested in C57BL/6 mice. RESULTS: Carthamus tinctorius L. was the most potent 5α-reductase inhibitor, with a finasteride equivalent 5α-reductase inhibitory activity (FEA) value of 24.30±1.64 mg finasteride equivalent per 1g crude extract. Phyllanthus emblica L. was the second most potent inhibitor, with FEA of 18.99±0.40. Rhinacanthus nasutus (L.) Kurz. was the least potent 5α-reductase inhibitor (FEA 10.69±0.96). Carthamus tinctorius also was the most potent hair growth promoter in C57BL/6 mice. There were strong relationships between 5α-reductase inhibitory activity and hair growth promoting activity (r=0.719), and between 5α-reductase inhibitory activity and hair follicle count (r=0.766). CONCLUSIONS: Ethanolic extract of Carthamus tinctorius was the most potent 5α-reductase inhibitor and hair growth promoter. This discovery may lead to the development of new alternative medicines for hair loss prevention and treatment.

Myotoxicity studies of O/W-in situ forming microparticle systems.

The objective of this study was to investigate the myotoxicity potential of the solvents used in the preparation of polymer solutions and O/W-in situ forming microparticle (ISM) systems. The acute myotoxicity studies of the tested solvents, emulsions of the solvents, polymer solutions as well as the O/W-ISM formulations with varying phase ratios were investigated using the in vitro isolated rodent skeletal muscle model by measuring the cumulative creatine kinase (CK) efflux. Phenytoin and isotonic sodium chloride solution served as positive and negative controls, respectively. Results from the in vitro myotoxicity studies suggested that the investigated five partially water miscible solvents caused muscle damage in the following rank order: benzyl alcohol>triethyl citrate>triacetin>propylene carbonate>ethyl acetate. Myotoxicity of ethyl acetate was found to be comparable to that of the isotonic sodium chloride solution. Emulsions of the undiluted solvents and an aqueous 0.5% Pluronic F 68 solution (ratio 1:4) could dramatically reduce the myotoxicities to 24-65%. The myotoxicity of O/W-ISM was less than those of the polymer solutions and the undiluted solvents. The cumulative CK level from the muscle treated with the O/W-ISM with phase ratio 1:4 was comparable to those from the negative controls. Area under the CK plasma curve from Sprague-Dawley rats was used to evaluate the in vivo myotoxicity following an intramuscular injection of the formulations. The in vivo myotoxicity data was well correlated with the in vitro myotoxicity data and confirmed the good muscle compatibility of the O/W-ISM formulations.