Efficacy and Tolerability of a Scutellaria lateriflora L. and Cistus × incanus L.-Based Chewing Gum on the Symptoms of Gingivitis: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Preclinical studies have shown that the combination of Cistus × incanus L. and Scutellaria lateriflora L. extracts exerts beneficial effects on oral health against gingivitis. Thus, this study aimed to assess the tolerability of a chewing gum and its efficacy on gingivitis in a double-blind, placebo-controlled clinical trial. Enrolled subjects (n = 60, 18-70 years) were randomized to receive two chewing gums or a placebo daily for 3 months. At baseline (t0) and monthly (t1, t2, and t3) timepoints, the Quantitative Gingival Bleeding Index (QGBI), the Modified Gingival Index (MGI), and the Oral Health 15 items (OH-15)] were employed to assess potential improvements in gingivitis. Pain was self-quantified via the Visual Analogue Scale (VAS), and the Clinical Global Impression Scale for Severity of illness (CGI-S) helped in evaluating the oral general conditions. This study is listed on the ISRCTN registry. At t3, the QGBI, MGI, OH-15, VAS, and CGI-S values decreased in the treated but not in the placebo group (ß = 0.6 ± 0.1, t176 = 3.680, p < 0.001; ß = 0.87 ± 0.21, t115 = 4.263, p < 0.001; ß = 5.3 ± 2.5, t172 = 2.086, p = 0.038; ß = 3.16 ± 0.51, t88 = 6.253, p < 0.001; and ß = 1.09 ± 0.32, t83 = 3.419, p < 0.001, respectively). A significant improvement in gingival health occurred after a 3-month intervention with the chewing gums containing S. lateriflora and C. incanus extracts.

Exploring the Therapeutic Potential of Royal Jelly in Metabolic Disorders and Gastrointestinal Diseases.

Metabolic disorders, encompassing diabetes mellitus, cardiovascular diseases, gastrointestinal disorders, etc., pose a substantial global health threat, with rising morbidity and mortality rates. Addressing these disorders is crucial, as conventional drugs often come with high costs and adverse effects. This review explores the potential of royal jelly (RJ), a natural bee product rich in bioactive components, as an alternative strategy for managing metabolic diseases. RJ exhibits diverse therapeutic properties, including antimicrobial, estrogen-like, anti-inflammatory, hypotensive, anticancer, and antioxidant effects. This review's focus is on investigating how RJ and its components impact conditions like diabetes mellitus, cardiovascular disease, and gastrointestinal illnesses. Evidence suggests that RJ serves as a complementary treatment for various health issues, notably demonstrating cholesterol- and glucose-lowering effects in diabetic rats. Specific RJ-derived metabolites, such as 10-hydroxy-2-decenoic acid (10-HDA), also known as the "Queen bee acid," show promise in reducing insulin resistance and hyperglycemia. Recent research highlights RJ's role in modulating immune responses, enhancing anti-inflammatory cytokines, and suppressing key inflammatory mediators. Despite these promising findings, further research is needed to comprehensively understand the mechanisms underlying RJ's therapeutic effects.

In Vitro Assessment of Cortisol Release Inhibition, Bioaccessibility and Bioavailability of a Chemically Characterized Scutellaria lateriflora L. Hydroethanolic Extract.

Excess cortisol release is associated with numerous health concerns, including psychiatric issues (i.e., anxiety, insomnia, and depression) and nonpsychiatric issues (i.e., osteoporosis). The aim of this study was to assess the in vitro inhibition of cortisol release, bioaccessibility, and bioavailability exerted by a chemically characterized Scutellaria lateriflora L. extract (SLE). The treatment of H295R cells with SLE at increasing, noncytotoxic, concentrations (5-30 ng/mL) showed significant inhibition of cortisol release ranging from 58 to 91%. The in vitro simulated gastric, duodenal, and gastroduodenal digestions, induced statistically significant reductions (p < 0.0001) in the bioactive polyphenolic compounds that most represented SLE. Bioavailability studies on duodenal digested SLE, using Caco-2 cells grown on transwell inserts and a parallel artificial membrane permeability assay, indicated oroxylin A glucuronide and oroxylin A were the only bioactive compounds able to cross the Caco-2 cell membrane and the artificial lipid membrane, respectively. The results suggest possible applications of SLE as a food supplement ingredient against cortisol-mediated stress response and the use of gastroresistant oral dosage forms to partially prevent the degradation of SLE bioactive compounds. In vivo studies and clinical trials remain necessary to draw a conclusion on the efficacy and tolerability of this plant extract.

Petroselinum crispum (Mill.) Fuss (Parsley): An Updated Review of the Traditional Uses, Phytochemistry, and Pharmacology.

Petroselinum crispum (Mill.) Fuss (parsley) is a popular medicinal plant widely used in different traditional medicines all over the world. This paper provides an updated review on the traditional use, phytochemistry, and pharmacological activities of parsley. Parsley contains volatile compounds such as terpenes and terpenoids in the essential oil, as well as phenolic compounds in the plant extract. Parsley is traditionally used as a diuretic, liver and stomach tonic, and for urolithiasis and indigestion. Pharmacological investigations also confirm several biological activities of parsley including hepatoprotective, nephroprotective, antiurolithiatic, neuroprotective, cardioprotective, and antineoplastic effects in animal and cell-based studies. Parsley has currently demonstrated several pharmacological activities in preclinical studies; however, there is a big lack in clinical evidence. Considering parsley as a possible valuable medicinal food, future clinical trials are recommended to evaluate the clinical efficacy and safety of the plant in different health conditions.

Efficacy of digestive enzyme supplementation in functional dyspepsia: A monocentric, randomized, double-blind, placebo-controlled, clinical trial.

Functional dyspepsia is a form of dyspepsia lacking in clear causes following clinical assessment. Dyspepsia is characterized by episodic or persistent abdominal pain or discomfort of the upper gastrointestinal (GI) tract. Its onset has been linked with a deficiency or dysfunction of digestive enzymes. Thus, consumption of digestive multi-enzymatic preparations may be effectively used for the reduction of symptoms. The aim of this study is to assess the effectiveness and tolerability of the supplementation of a normal diet with a multi-enzyme blend obtained from fungal fermentation, in a randomized, placebo-controlled, double-blind, clinical trial. Enrolled subjects (n = 120, male: 63, female: 57), aged 18-59 years, were randomized (allocation ratio 1:1) to receive either 2 capsules per day of the food supplement (containing 200 mg of the multi-enzyme blend/capsule) or placebo, for 2 months. The primary outcome of the study (i.e., improvements in quality of life) was evaluated by the Nepean Dyspepsia Index-SF (NDI-SF) questionnaire, while the secondary outcomes (i.e., severity of pain and the quality of sleep) were assessed through the Visual Analogue Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) questionnaire. The results showed an improvement in NDI-SF1, NDI-SF2-5, VAS, and PSQI scores in subjects treated with the multi-enzyme blend, indicating an improvement in quality of life and of sleep, and a decreased severity of pain, following the supplementation with digestive enzymes, without side effects. In conclusion, treatment with digestive enzymes was found to be effective in the reduction of functional dyspepsia symptoms and in the improvement of sleep quality, and is well-tolerated.

Anthocyanins as Immunomodulatory Dietary Supplements: A Nutraceutical Perspective and Micro-/Nano-Strategies for Enhanced Bioavailability.

Anthocyanins (ACNs) have attracted considerable attention for their potential to modulate the immune system. Research has revealed their antioxidant and anti-inflammatory properties, which play a crucial role in immune regulation by influencing key immune cells, such as lymphocytes, macrophages, and dendritic cells. Moreover, ACNs contribute towards maintaining a balance between proinflammatory and anti-inflammatory cytokines, thus promoting immune health. Beyond their direct effects on immune cells, ACNs significantly impact gut health and the microbiota, essential factors in immune regulation. Emerging evidence suggests that they positively influence the composition of the gut microbiome, enhancing their immunomodulatory effects. Furthermore, these compounds synergize with other bioactive substances, such as vitamins and minerals, further enhancing their potential as immune-supporting dietary supplements. However, detailed clinical studies must fully validate these findings and determine safe dosages across varied populations. Incorporating these natural compounds into functional foods or supplements could revolutionize the management of immune-related conditions. Personalized nutrition and healthcare strategies may be developed to enhance overall well-being and immune resilience by fully understanding the mechanisms underlying the actions of their components. Recent advancements in delivery methods have focused on improving the bioavailability and effectiveness of ACNs, providing promising avenues for future applications.

Polyphenol-enriched Desmodium elegans DC. ameliorate scopolamine-induced amnesia in animal model of Alzheimer's disease: In Vitro, In Vivo and In Silico approaches.

The current study aims to quantify HPLC-DAD polyphenolics in the crude extracts of Desmodium elegans, evaluating its cholinesterase inhibitory, antioxidant, molecular docking and protective effects against scopolamine-induced amnesia in mice. A total of 16 compounds were identified which include gallic acid (239 mg g-1), p-hydroxybenzoic acid (11.2 mg g-1), coumaric acid (10.0 mg g-1), chlorogenic acid (10.88 mg g-1), caffeic acid (13.9 mg g-1), p-coumaroylhexose (41.2 mg g-1), 3-O-caffeoylquinic acid (22.4 mg g-1), 4-O-caffeoylquinic acid (6.16 mg g-1), (+)-catechin (71.34 mg g-1), (-)-catechin (211.79 mg g-1), quercetin-3-O-glucuronide (17.9 mg g-1), kaempferol-7-O-glucuronide (13.2 mg g-1), kaempferol-7-O-rutinoside (53.67 mg g-1), quercetin-3-rutinoside (12.4 mg g-1), isorhamnetin-7-O-glucuronide (17.6 mg g-1) and isorhamnetin-3-O-rutinoside (15.0 mg g-1). In a DPPH free radical scavenging assay, the chloroform fraction showed the highest antioxidant activity, with an IC50 value of 31.43 µg mL-1. In an AChE inhibitory assay, the methanolic and chloroform fractions showed high inhibitory activities causing 89% and 86.5% inhibitions with IC50 values of 62.34 and 47.32 µg mL-1 respectively. In a BChE inhibition assay, the chloroform fraction exhibited 84.36% inhibition with IC50 values of 45.98 µg mL-1. Furthermore, molecular docking studies revealed that quercetin-3-rutinoside and quercetin-3-O-glucuronide fit perfectly in the active sites of AChE and BChE respectively. Overall, the polyphenols identified exhibited good efficacy, which is likely as a result of the compounds' electron-donating hydroxyl groups (-OH) and electron cloud density. The administration of methanolic extract improved cognitive performance and demonstrated anxiolytic behavior among tested animals.

Combination of Chemically Characterized Pomegranate Extract and Hydrophilic Vitamins against Prolonged Fatigue: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Prolonged fatigue is associated with non-pathological causes and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve™) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue severity scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stress conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months of supplementation in healthy subjects with mild prolonged fatigue.

Beneficial Effects of Astragalus membranaceus (Fisch.) Bunge Extract in Controlling Inflammatory Response and Preventing Asthma Features.

Astragalus membranaceus (Fisch.) Bunge root is used as herbal medicine for its immunomodulating activities in Chinese medicine. Recently, beneficial properties of A. membranaceus on allergic diseases have been proposed. Here we investigated the role of a commercial extract of A. membranaceus, standardized to 16% polysaccharides, in regulating the immune-inflammatory response in vitro and in vivo and its therapeutic application in asthma. A. membranaceus extract inhibited prostaglandin E2 and leukotriene C4 production in stimulated J774 and peritoneal macrophages, respectively. The extract also reduced interlukin-1ß, tumor necrosis factor-α, and nitrite production, affecting inducible nitric oxide synthase expression. In vivo experiments confirmed the anti-inflammatory properties of A. membranaceus, as evident by a reduction in zymosan-induced peritoneal cellular infiltration and pro-inflammatory mediator production. The efficacy of A. membranaceus extract in modulating the immune response was confirmed in a model of allergic airway inflammation. Extracts improve lung function by inhibiting airway hyperresponsiveness, airway remodeling, and fibrosis. Its anti-asthmatic effects were further sustained by inhibition of the sensitization process, as indicated by a reduction of ovalbumin-induced IgE levels and the mounting of a Th2 immune response. In conclusion, our data demonstrate the anti-inflammatory properties of the commercial extract of A. membranaceus and its beneficial effects on asthma feature development.

Chemical and Nutritional Profiling of the Seaweed Dictyota dichotoma and Evaluation of Its Antioxidant, Antimicrobial and Hypoglycemic Potentials.

Seaweed has been known to possess beneficial effects forhuman health due to the presence of functional bioactive components. The n-butanol and ethyl acetate extracts of Dictyota dichotoma showed ash (31.78%), crude fat (18.93%), crude protein (14.5%), and carbohydrate (12.35%) contents. About 19 compounds were identified in the n-butanol extract, primarily undecane, cetylic acid, hexadecenoic acid, Z-11-, lageracetal, dodecane, and tridecane, whereas 25 compounds were identified in the ethyl acetate extract, mainly tetradecanoic, hexadecenoic acid, Z-11-, undecane, and myristic acid. FT-IR spectroscopy confirmed the presence of carboxylic acid, phenols, aromatics, ethers, amides, sulfonates, and ketones. Moreover, total phenolic contents (TPC) and total flavonoid contents (TFC) in ethyl acetate extract were 2.56 and 2.51 mg GAE/g and in n-butanol extract were 2.11 and 2.25 mg QE/g, respectively. Ethyl acetate and n-butanol extracts at a high concentration of 100 mg mL-1 showed 66.64 and 56.56 % inhibition of DPPH, respectively. Antimicrobial activity revealed that Candida albicans was the most susceptible microorganism, followed by Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, whereas Pseudomonas aeruginosa showed the least inhibition at all concentrations. The in vivo hypoglycemic study revealed that both extracts exhibited concentration-dependent hypoglycemic activities. In conclusion, this macroalgae exhibited antioxidant, antimicrobial, and hypoglycemic potentials.

In Vitro Antimicrobial and Antibiofilm Properties and Bioaccessibility after Oral Digestion of Chemically Characterized Extracts Obtained from Cistus × incanus L., Scutellaria lateriflora L., and Their Combination.

Periodontal diseases are oral inflammatory diseases ranging from gingivitis to chronic periodontitis. Porphyromonas gingivalis is one of the major pathogens responsible for severe and chronic periodontitis. Plant extracts with antimicrobial activity could be considered possible alternatives to chlorhexidine, an antiseptic substance used in oral hygiene thatcan cause bacteria resistance. Here, two commercial extracts obtained from Cistus × incanus L. and Scutellaria lateriflora L. were chemically characterized usingUltra-High-Performance Liquid Chromatography (UHPLC) coupled with a Q-Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. The extracts were studied for their bioaccessibility after simulated in vitro oral digestion, their antimicrobial activity against P. gingivalis, their protective effects against cellular invasion by P. gingivalis, and their antibiofilm activity. The extracts were found to contain very complex mixtures of polyphenols, which were quite stable after in vitro simulated oral digestion and demonstrated mild, dose-dependent inhibitory activity against P. gingivalis growth. This activity increased with the combination of the two extracts. Moreover, the combination of the extracts induced a reduction in P. gingivalis HaCaT invasiveness, and the reduction in biofilm came to around 80%. In conclusion, a combination of C. incanus and S. lateriflora showed promising effects useful in the treatment of gingivitis.

Arctium lappa (Burdock): Insights from ethnopharmacology potential, chemical constituents, clinical studies, pharmacological utility and nanomedicine.

Arctium lappa L. is a medicinal edible homologous plant, commonly known as burdock or bardana, which belongs to the Asteraceae family. It is widely distributed throughout Northern Asia, Europe, and North America and has been utilized for hundreds of years. The roots, fruits, seeds, and leaves of A. lappa have been extensively used in traditional Chinese Medicine (TCM). A. lappa has attracted a great deal of attention due to its possession of highly recognized bioactive metabolites with significant therapeutic potential. Numerous pharmacological effects have been demonstrated in vitro and in vivo by A. lappa and its bioactive metabolites, including antimicrobial, anti-obesity, antioxidant, anticancer, anti-inflammatory, anti-diabetic, anti-allergic, antiviral, gastroprotective, hepatoprotective, and neuroprotective activities. Additionally, A. lappa has demonstrated considerable clinical efficacies and valuable applications in nanomedicine. Collectively, this review covers the properties of A. lappa and its bioactive metabolites, ethnopharmacology aspects, pharmacological effects, clinical trials, and applications in the field of nanomedicine. Hence, a significant attention should be paid to clinical trials and industrial applications of this plant with particular emphasis, on drug discovery and nanotechnology.

In Vitro Bioaccessibility and Anti-Inflammatory Activity of a Chemically Characterized Allium cepa L. Extract Rich in Quercetin Derivatives Optimized by the Design of Experiments.

Allium cepa L. is a highly consumed garden crop rich in biologically active phenolic and organosulfur compounds. This study aimed to assess the in vitro bioaccessibility and anti-inflammatory effect of a chemically characterized A. cepa extract rich in quercetin and its derivatives. Different varieties of A. cepa were studied; based on the highest total phenolic content, the "Golden" variety was selected. Its extracts, obtained from the tunicate bulb, tunic, and bulb, were subjected to determination of quercetin and its derivatives with LC-MS analysis and based on the highest total quercetin content, the tunic extract was utilized for further experiments. The extraction method was optimized through a design of experiment (DoE) method via full factorial design, which showed that 40% ethanol and 1 g tunic/20 mL solvent are the best extraction conditions. HPLC analysis of the optimized tunic extract identified 14 flavonols, including 10 quercetin derivatives. As far as in vitro bioaccessibility was concerned, the increases in some quercetin derivatives following the gastro-duodenal digestion process support the bioaccessibility of these bioactive compounds. Moreover, the extract significantly inhibited the production of PGE2 in stimulated J774 cell lines, while no effects of the tunic extract were observed against the release of IL-1ß, TNF-α, and nitrites. The study provided insights into the optimized extraction conditions to obtain an A. cepa tunic extract rich in bioavailable quercetin derivatives with significant anti-inflammatory effects against PGE2.

Efficacy of a food supplement based on S-adenosyl methionine and probiotic strains in subjects with subthreshold depression and mild-to-moderate depression: A monocentric, randomized, cross-over, double-blind, placebo-controlled clinical trial.

Depression is one of the most serious chronic psychiatric disorders affecting people worldwide. Subthreshold depression (SD) is a form of subclinical depression with increased risk of major depressive disorder (MDD). Patients diagnosed with SD may not be eligible for antidepressant drugs and, particularly in the case of MDD, these antidepressants may have adverse effects which outweigh their therapeutic effects, leading to discontinuation of therapy. Food supplements could provide an alternative strategy. The aim of this study is to demonstrate the efficacy of a food supplement based on a combination of S-adenosyl methionine (SAMe, 200 mg/day) and probiotics (Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175, 3 ×109 CFU/day) in reducing depression symptoms in a monocentric, randomised, double-blind, placebo-controlled, cross-over clinical trial. 80 Subjects were recruited and offered the food supplement or placebo daily for three months, according to a cross-over clinical trial design, followed by a six-week follow-up period. The efficacy of the food supplement was measured by means of the "Hamilton Depression Rating Scale" (HAM-D) and "Patient Health Questionnaire-9" (PHQ-9), using a mixed analysis of variance model, with random intercept, for statistical analysis. The food supplement showed a significant decrease of PHQ-9 and HAM-D scores resulting in reduced SD and MDD symptoms as compared to placebo. In conclusion, the daily intake of the food supplement based on SAMe and probiotic strains for a period of three months is effective in improving the quality of life of SD subjects who are not eligible for antidepressant therapies, and patients suffering from mild-to-moderate depression who are not sensitive or cannot tolerate conventional drugs.

Insights into the Role of Natural Products in the Control of the Honey Bee Gut Parasite (Nosema spp.).

The honey bee is an important economic insect due to its role in pollinating many agricultural plants. Unfortunately, bees are susceptible to many pathogens, including pests, parasites, bacteria, and viruses, most of which exert a destructive impact on thousands of colonies. The occurrence of resistance to the therapeutic substances used against these organisms is rising, and the residue from these chemicals may accumulate in honey bee products, subsequently affecting the human health. There is current advice to avoid the use of antibiotics, antifungals, antivirals, and other drugs in bees, and therefore, it is necessary to develop alternative strategies for the treatment of bee diseases. In this context, the impact of nosema diseases (nosemosis) on bee health and the negative insults of existing drugs are discussed. Moreover, attempts to combat nosema through the use of alternative compounds, including essential oils, plant extracts, and microbes in vitro and in vivo, are documented.

Postprandial Glycemic and Insulinemic Response by a Brewer's Spent Grain Extract-Based Food Supplement in Subjects with Slightly Impaired Glucose Tolerance: A Monocentric, Randomized, Cross-Over, Double-Blind, Placebo-Controlled Clinical Trial.

Dietary fiber exerts beneficial effects on human health reducing the risk factors of metabolic related diseases such as hyperglycemia, insulin resistance, and hypercholesterolemia. The aim of this study is to demonstrate the efficacy of a food supplement based on brewer's spent grain (BSG) extract in the reduction of postprandial glycemia and insulinemia in normoglycemic subjects. BSG was chemically characterized, revealing the presence of resistant starch (14.64 g/100 g), arabinoxylans (7.50 g/100 g), ß-glucans (1.92 g/100 g) and other soluble fibers (6.43 g/100 g), and bioaccessible ferulic acid (91.3 mg/100 g). For the clinical study, 40 normoglycemic subjects were randomized into two groups, 1 and 2 (n = 20), for a cross-over clinical design and received either BSG extract-based food supplement or placebo. Postprandial blood glucose values were significantly lower than corresponding values in the placebo group after 90 and 120 min, while at the baseline and in the first 60 min, the two glycemic curves overlapped substantially. This improved clinical outcome was corroborated by significant reductions in postprandial insulinemia. None of the subjects reported adverse effects. This study showed that the tested BSG extract-based food supplement improves glucose metabolism and insulinemic response in normoglycemic subjects with at most a mild insulin resistance.

Kaempferol and atherosclerosis: From mechanism to medicine.

Natural products possess pleiotropic cardiovascular protective effects owing to their anti-oxidation, anti-inflammation and anti-thrombotic properties. Kaempferol, (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), is a kind of naturally occurring flavonoid existing in many common fruits and vegetables (e.g., onions, broccoli, strawberries and grapes) and particularly in traditional Chinese medicine as exemplified by Ginkgo biloba. Epidemiological, preclinical and clinical studies have revealed an inverse association between the consumption of kaempferol-containing foods and medicines and the risk of developing cardiovascular diseases. Numerous translational studies in experimental animal models and cultured cells have demonstrated a wide range of pharmacological activities of kaempferol. In this article, we reviewed the antioxidant, anti-inflammatory and cardio-protective activities of kaempferol and elucidated the potential molecular basis of the therapeutic capacity of kaempferol by focusing on its anti-atherosclerotic effects. Overall, the review presents the health benefits of kaempferol-containing plants and medicines and reflects on the potential of kaempferol as a possible drug candidate to prevent and treat atherosclerosis, the underlying pathology of most cardiovascular diseases.

The Efficacy of S-Adenosyl Methionine and Probiotic Supplementation on Depression: A Synergistic Approach.

Depression is a common and serious health issue affecting around 280 million people around the world. Suicidal ideation more frequently occurs in people with moderate to severe depression. Psychotherapy and pharmacological drugs are the mainstay of available treatment options for depressive disorders. However, pharmacological options do not offer complete cure, especially in moderate to severe depression, and are often seen with a range of adverse events. S-adenosyl methionine (SAMe) supplementation has been widely studied, and an impressive collection of literature published over the last few decades suggests its antidepressant efficacy. Probiotics have gained significant attention due to their wide array of clinical uses, and multiple studies have explored the link between probiotic species and mood disorders. Gut dysbiosis is one of the risk factors in depression by inducing systemic inflammation accompanied by an imbalance in neurotransmitter production. Thus, concomitant administration of probiotics may be an effective treatment strategy in patients with depressed mood, particularly in resistant cases, as these can aid in dysbiosis, possibly resulting in the attenuation of systemic inflammatory processes and the improvement of the therapeutic efficacy of SAMe. The current review highlights the therapeutic roles of SAMe and probiotics in depression, their mechanistic targets, and their possible synergistic effects and may help in the development of food supplements consisting of a combination of SAMe and probiotics with new dosage forms that may improve their bioavailability.

Total flavonoids from the dried root of Tetrastigma hemsleyanum Diels et Gilg inhibit colorectal cancer growth through PI3K/AKT/mTOR signaling pathway.

The dried root of Tetrastigma hemsleyanum Diels et Gilg is used as a traditional Chinese medicine in southern China, as a folk remedy for carcinomas and gastrointestinal diseases. The total flavonoids of T. hemsleyanum (THTF) provide its main bioactive constituents. However, the mechanisms underlying its potential activity on colorectal cancer are still unknown. Here, we investigated the antitumor effect of THTF on colorectal cancer in vitro and in vivo. It was found that THTF inhibited HCT-116 and HT-29 cell growth, with an IC50 of 105.60 and 140.80 µg/mL, respectively. THTF suppressed clonogenicity and promoted apoptosis in HCT-116. In vivo, THTF (120 mg/kg) delayed tumor growth in HCT-116 xenografts without influencing on body weight, organ pathology and indexes, and blood routine level. Mechanistically, THTF inhibited the expression of PI3K, AKT, and mTOR at the protein level and transcriptional levels. Molecular docking indicated eight compounds in THTF (kaempferol 3-rutinoside, rutinum, isoquercitrin, L-epicatechin, quercetin, astragalin, kaempferol 3-sambubioside, and catechin) strongly bound with amino acid sites of PI3K and mTOR proteins, indicating a high affinity. The results suggest that THTF delayed colorectal tumor growth by inhibiting the PI3K/AKT/mTOR pathway and might be a potential candidate for colorectal cancer prevention.