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Distribution of bloating. Bloating during the run-in period (V1), the first two weeks (V2_1) and the last two weeks (V2_2) of intake phase (Placebo p = 0.0733, Perilla p = 0.0003; Repeated measures ANOVA).

Distribution of bloating. Bloating during the run-in period (V1), the first two weeks (V2_1) and the last two weeks (V2_2) of intake phase (Placebo p = 0.0733, Perilla p = 0.0003; Repeated measures ANOVA).

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Gastrointestinal (GI) discomfort, e.g. bloating or rumbling, is a common symptom in otherwise healthy adults. Approximately 20% of the population, particularly women suffer from gastrointestinal discomfort and this affects quality of life. Recent studies discovered a link between the body and mind, called the gut-brain axis. Psychosocial factors, s...

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... passage of gas, GI rumbling, feeling of fullness and abdominal discom- fort improved significantly over time (repeated measures ANOVA) from the run-in phase until the end of supple- mentation phase in the Perilla group (bloating: -0.44 ± 0.56, p = 0.0003; passage of gas: -0.30 ± 0.66, p = 0.0264; GI rum- bling: -0.55 ± 0.87, p = 0.0014; feeling of fullness: -0.36 ± 0.72, p = 0.0152; abdominal discomfort: -0.54 ± 0.75, p = 0.004), whereas in the placebo group only abdominal dis- comfort was significantly improved (-0.31 ± 0.55, p = 0.0345) (Table 3). Figures 3 and 4 are showing the course of effect on bloating and abdominal discomfort over time, ex- emplarily. The placebo effects were only measurable after 4 weeks of intake, whereas the Perilla extract effects were measurable already in the first part of intervention and were even strengthened with ongoing supplementation. ...
Context 2
... the subgroup of women, the reduction of GI symp- toms by supplementation of Perilla extract appeared even more pronounced. All five GI symptoms decreased signifi- cantly over time within the perilla group (repeated mea- sures ANOVA) (bloating: -0.51 ± 0.57, p = 0.0002; passage of gas: -0.34 ± 0.60, p = 0.0272; GI rumbling: -0.74 ± 0.85, p = 0.0002; feeling of fullness: -0.45 ± 0.73, p = 0.0062; ab- dominal discomfort: -0.63 ± 0.79, p = 0.0004), whereas in the placebo group none of the symptoms decreased sig- nificantly over time (see also Table 4).The benefit of perilla in comparison to placebo in the subgroup of women was seen by trend for the following GI symptoms: bloating (95%CI -0.031 to 0.79, p = 0.069) (Figure 3), GI rumbling (95%CI -0.080 to 0.95, p = 0.095) and abdominal discom- fort (95%CI -0.0314 to 0.83, p = 0.068) (Figure 4). In women, the summary score out of all 5 GI symptoms showed significant reduction in the Perilla group (-0.54 ± 0.61, p = 0.0001). ...

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... Although these effects resulted from the analysis of in vitro and in vivo studies, there were few clinical trials that outlined significant therapeutic effects for human subjects. Attenuation of age-related cognitive decline, antiallergic, antioxidant, prokinetic, and antispasmodic effects are among the proven therapeutic proprieties of Perilla frutescens in these studies [24][25][26][27][28][29]. ...
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(1) Background: Chronic renal disorders (CRD) are associated with significant comorbidities and necessitate complex therapeutic management. As time passed, Perilla frutescens (PF) became a promising therapeutic option for CRD. The aim of this systematic review and meta-analysis was to outline the therapeutic effects of PF extracts on various models of immunoglobulin a (IgA) nephropathy; (2) Methods: Medline, Embase, and Cochrane databases were used to find relevant studies. All prospective interventional studies that evaluated the effect of PF extract versus placebo on rat models of chronic renal disorders were assessed according to the international guidelines; (3) Results: Our search yielded 23 unique records, out of which only five were included in the analysis. Our results showed that administration of PF extracts led to a statistically significant reduction in proteinuria and PCNA levels in rats that received high doses of the extract as well as in the PCNA level and DNA synthesis in rats that received low doses of the extract. The evaluated outcomes benefited from a low degree of heterogeneity; (4) Conclusions: Some of the evaluated outcomes were significantly reduced by both high and low doses of extracts from Perilla frutescens. Further studies are needed to determine the exact effect over IgA nephropathy in human subjects.
... These actions make Perilla frutescens a perfect alternative therapeutic agent for gastrointestinal discomfort, as demonstrated in a double-blind, randomized, placebo-controlled parallel study by Buchwald-Werner et al., which enrolled 50 adult patients with gastrointestinal symptoms, such as cramps and constipation. The study found that Perilla frutescens extract significantly improved all gastrointestinal symptoms over time during the intervention stage [104]. A recent literature review by Thumann et al. outlined that human gut bacteria are able to metabolize rosmarinic acid and that it may have impacts on the gut microbiome, possibly acting as a prebiotic [105]. ...
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(1) Background: Perilla frutescens (L.) Britt. is an important pharmaceutical crop that remains a focus point for researchers worldwide due to its complex phytochemical constituents, medicinal effects, and nutraceutical properties. The literature data are based on animal and cell culture studies, so the clinical evidence for the therapeutic effects is poorly outlined. The aim of this review was to provide an updated and thorough understanding of Perilla frutescens applications in clinical practice using data derived from human studies, and to outline the potential directions and perspectives for further studies on this crop. (2) Methods: Medline, Embase, and Cochrane databases were used to find relevant studies. All interventional studies that evaluated the effect of Perilla frutescens in human subjects were assessed. (3) Results: The main perspectives that can be contoured from the presented literature evaluation are an important clinical effect of Perilla frutescens extracts on allergic rhinoconjuctivitis, especially in young populations, a potent hypolipemiant effect that, in conjunction with increased serum biological antioxidant potential, determines significant improvements in cognitive function and a wide variety of miscellaneous clinical effects that need further exploration. (4) Conclusions: Supplementary research is needed in order to demonstrate the therapeutic effects of Perilla frutescens in controlled clinical settings.
... Apigenin reduced the IL-17A secretion and increased the anti-inflammatory cytokine IL-10. These reports suggest that P. frutescens polyphenols are potential therapeutical phyto-medications to manage IBS and increasing the QOL scores [136][137][138]. ...
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Irritable bowel syndrome (IBS) is a well diagnosed disease, thoroughly attributed to series of symptoms criteria that embrace a broad range of abdominal complainers. Such criteria help to diagnosis the disease and can guide controlled clinical trials to seek new therapeutic agents. Accordingly, a verity of mechanisms and pathophysiological conditions including inflammation, oxidative stress, lipid peroxidation and different life styles are involved in IBS. Predictably, diverse therapeutic approaches are available and prescribed by clinicians due to major manifestations (i.e., diarrhea-predominance, constipation-predominance, abdominal pain and visceral hypersensitivity), psychological disturbances, and patient preferences between herbal treatments versus pharmacological therapies, dietary or microbiological approaches. Herein, we gathered the latest scientific data between 1973 and 2019 from databases such as PubMed, Google Scholar, Scopus and Cochrane library on relevant studies concerning beneficial effects of herbal treatments for IBS, in particular polyphenols. This is concluded that polyphenols might be applicable for preventing IBS and improving the IBS symptoms, mainly through suppressing the inflammatory signaling pathways, which nowadays are known as novel platform for the IBS management. Graphical abstract Graphical abstract
... Assuming alpha equaled to 5% and a power of 80%, the sample size was estimated with a difference in PAC-SYM of 4.08 units between groups, and a standard deviation (SD) of 6.36 units. The above assumptions were based on prior studies with probiotic 29 and plant extract 30 interventions that used the PAC-SYM score to assess symptoms. Accounting for premature withdrawal, 100 participants were forecasted for randomization, with 50 participants in each group. ...
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Aim: To investigate the clinical efficacy of a multi-strain probiotic product on bowel habits and microbial profile in subjects with functional constipation. Methods: This study (clinicaltrials.gov NCT02418507) was randomized, double-blind, placebo-controlled and parallel-arm. Ninety-four otherwise healthy adults with symptoms of functional constipation, aged 18 to 65 years, were randomized as part of the intention to treat population. Participants received placebo or the probiotic product (1.5x1010 CFU/day), consisting of L. acidophilus DDS-1, B. animalis subsp. lactis UABla-12, B. longum UABl-14 and B. bifidum UABb-10 over four weeks. Outcomes included the patient assessment of constipation-symptom (PAC-SYM) questionnaire, stool frequency and consistency, microbial profile and strain recovery. Results: There were no significant between group differences in the PAC-SYM score (P>0.05), despite significant within group differences (P<0.001) over the study. Subjects in the probiotic group demonstrated a faster normalization of stool frequency and consistency, with most subjects achieving a normalized profile after one week. Probiotic group fecal samples exhibited higher relative abundance of Ruminococcaceae (P=0.0047), including the Ruminococcus genus, and lower relative abundance of Erysipelotrichaceae (P=0.0172) at endpoint as compared to baseline. Placebo group samples showed similar abundance profiles over the study, with the exception of Clostridiaceae, which was lower at the study endpoint (P=0.0033). Among treated subjects, all four probiotic strains were significantly more abundant after intervention. Conclusions: No significant differences were observed in symptomology, with both groups showing a greater than 20% improvement. However, the probiotic helped modulate bowel function earlier than placebo, with a corresponding shift to a more fibrolytic microbiota. This article is protected by copyright. All rights reserved.
... In most instances, it is challenging to show beneficial gut health effects within a target population of healthy individuals [14]. Therefore, most, if not all trials enrol specific patient groups in gut-health studies. ...
... Validated 'quality of life questionnaires' are also considered to provide supportive evidence for claims on GI discomfort. Therefore, we have made use of previously validated questionnaires in order to investigate the effects on symptoms of GI dysfunction, stool frequency/ consistency and constipation-associated quality of life [14,33] (see further below). ...
... To assess this, the volunteers were asked to document daily (during the 2-week run-in phase and 6-week intervention phase) their GI symptoms as well as the frequency and consistency of their stools. For assessment of GI symptoms, the volunteers were asked to grade daily in the evening the average severity over the previous 24 h on a 5-point scale from 0 (absent) to 4 (very severe) the following five items: Bloating/Distension, Passage of gas, GI Rumbling, Feeling of fullness and Abdominal discomfort (this instrument has been described and used by Buchwald-Werner and colleagues (2014) in a similar study [14]). A Daily Total Score (DTS) was also calculated by summing all items recorded each day. ...
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Background Constipation and symptoms of gastrointestinal discomfort such as bloating are common among otherwise healthy individuals, but with significant impact on quality of life. Despite the recognized contribution of the gut microbiome to this pathology, little is known about which group(s) of microorganism(s) are playing a role. A previous study performed in vitro suggests that EpiCor® fermentate has prebiotic-like properties, being able to favorably modulate the composition of the gut microbiome. Therefore, the aim of this study was to investigate the effects of EpiCor fermentate in a population with symptoms of gastrointestinal discomfort and reduced bowel movements and to evaluate its effect at the level of the gut microbiome. Methods This pilot study was performed according to a randomized, double-blind, placebo-controlled parallel design. Eighty subjects with symptoms of gastrointestinal discomfort and constipation were allocated to one of two trial arms (placebo or EpiCor fermentate). Randomization was done in a stratified manner according to symptom severity, resulting in two subgroups of patients: severe and moderate. Daily records of gastrointestinal symptoms were assessed on a 5-point scale, and also stool frequency and consistency were documented during a 2-week run-in and a 6-week intervention phases. Averages over two-week intervals were calculated. Constipation-associated quality of life and general perceived stress were assessed at baseline and after 3 and 6 weeks of intervention. Fecal samples were also collected at these same time points. Results EpiCor fermentate led to a significant improvement of symptoms such as bloating/distension (p = 0.033 and p = 0.024 after 2 and 4 weeks of intervention, respectively), feeling of fullness (p = 0.004 and p = 0.023 after 2 and 4 weeks of intervention, respectively) and general daily scores (p = 0.046 after 2 weeks of intervention) in the moderate subgroup. A significant improvement in stool consistency was observed for the total population (p = 0.023 after 2 weeks of intervention) as well as for the severe subgroup (p = 0.046 after 2 weeks of intervention), and a nearly significant increase in stool frequency was detected for the total cohort (p = 0.083 and p = 0.090 after 2 and 4 weeks of intervention, respectively). These effects were accompanied by an improvement in constipation-associated quality of life and general perceived stress, particularly in the moderate subgroup. Members of the families Bacteroidaceae and Prevotellaceae, two groups of bacteria that have been previously reported to be deficient in constipated patients, were found to increase with EpiCor fermentate in the severe subgroup. In the moderate subgroup, a significant increase in Akkermansia muciniphila was observed. Conclusions Despite the relatively low dose administered (500 mg/day), particularly when comparing to the high recommended doses for prebiotic fibers, EpiCor fermentate was able to modulate the composition of the gut microbiome, resulting in improvement of constipation-associated symptoms. Conversely, the reported increase in bowel movements may have altered the gut microbial community by increasing those groups of bacteria that are better adapted to a faster gastrointestinal transit time. Trial registration NCT03051399 at ClinicalTrials.gov. Retrospectively registered. Registration date: 13 February 2017. Electronic supplementary material The online version of this article (10.1186/s12906-017-1948-0) contains supplementary material, which is available to authorized users.
... PE extract (150 mg, twice a day, p.o.) has been reported to improve gastrointestinal discomfort in a double-blind, randomized, placebo-controlled study (Buchwald-Werner et al., 2014). PE contains many polyphenols and some of them have strong anti-inflammatory and antioxidant effects (Zhou et al., 2014). ...
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Perilla frutescens is a culinary and medicinal herb which has a strong anti-inflammatory and antioxidative effects. In the present study, we investigated the effects of Perilla frutescens extract (PE) against dextran sulfate sodium (DSS)-induced mouse colitis, an animal model that mimics human inflammatory bowel disease (IBD). Five-week-old male ICR mice were treated with a daily dose of PE (20 or 100 mg/kg, p.o.) for 1 week, followed by administration of 3% DSS in double distilled drinking water and PE by gavage for another week. DSS-induced colitis was characterized by body weight loss, colon length shortening, diarrhea and bloody stool, and these symptoms were significantly ameliorated by PE treatment. PE administration suppressed DSS-induced expression of proinflammatory enzymes, including cyclooxygenase-2 and inducible nitric oxide synthase as well as cyclin D1, in a dose-dependent fashion. Nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) are major transcriptional regulators of inflammatory signaling. PE administration significantly inhibited the activation of both NF-κB and STAT3 induced by DSS, while it elevated the accumulation of Nrf2 and heme oxygenase-1 in the colon. In another experiment, treatment of CCD841CoN human normal colon epithelial cells with PE (10 mg/ml) resulted in the attenuation of the tumor necrosis factor-α-induced expression/activation of mediators of proinflammatory signaling. The above results indicate that PE has a preventive potential for use in the management of IBD.
... In addition, methanol extracts from P. frutescens leaves showed anti-allergy, anti-inflammatory [6], and anti-cancer [7] activities. Water extracts from P. frutescens leaves improved gastrointestinal discomfort [8] and suppressed tumor necrosis factor-alpha production in mice [9]. ...
... After HPLC analysis and assay-based purification of the mutant, we showed that the enhanced anti-inflammatory activity was due to a 10-fold increase in IK content in the leaves compared with the wild-type [10]. There have been many reports regarding extraction from perilla using organic solvents [3][4][5][6][7][8][9], SC-CO 2 [16,17], and microwave-assisted techniques [18]. In this study, we focused on the SC-CO 2 method, because the mutant P. frutescens has a high content of IK, a kind of oil component, and the SC-CO 2 method had never been used for obtaining extract from perilla leaves. ...
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In this study, we aimed to compare supercritical carbon dioxide extraction and ethanol extraction for isoegomaketone (IK) content in perilla leaf extracts and to identify the optimal method. We measured the IK concentration using HPLC and inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells from the extracts. The IK concentration was 10-fold higher in perilla leaf extracts by supercritical carbon dioxide extraction (SFE) compared with that in perilla leaf extracts by ethanol extraction (EE). When the extracts were treated in LPS-induced RAW 264.7 cells at 25 μg/mL, the SFE inhibited the expression of inflammatory mediators such as nitric oxide (NO), monocyte chemoattractant protein-1 (MCP-1), interleutkin-6 (IL-6), interferon-β (IFN-β), and inducible nitric oxide synthase (iNOS) to a much greater extent compared with EE. Taken together, supercritical carbon dioxide extraction is considered the optimal process for obtaining high IK content and anti-inflammatory activities in leaf extracts from the P. frutescens Britt. radiation mutant.
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In recent years there has been growing interest in the use of nutraceuticals and biotics in both pediatric and adult clinical practice. The overlapping and often ambiguous symptoms of both functional and organic gastrointestinal disorders have led to a search for alternative therapeutic approaches that avoid the use of synthetic or chemical treatments. However, while nutraceuticals and natural supplements are widely used, their health benefits are often not supported by adequate scientific evidence, and an unregulated use of nutraceuticals can be potentially harmful. The correct use of nutraceuticals, prebiotics, and probiotics can optimize the results of drug therapy in some cases and reduce the risk of side effects. This review aims to provide clinicians with guidance on the use of complementary therapies for pediatric gastrointestinal symptoms and disorders, highlighting the scarcity of studies on the kinetics and dynamics of nutraceuticals and biotics. While it is generally difficult to associate their intakes with adverse events due to the often-coexisting pharmacological treatments, it is essential to avoid the abandonment of traditional drugs with proven efficacy in the treatment of single diseases. Overall, the use of nutraceuticals, prebiotics, and probiotics in pediatric gastroenterological practice requires caution and medical supervision. Further research is needed to determine the effects of alternative therapies on pediatric gastrointestinal symptoms and disorders, and to ensure their safe and effective use in the clinical practice.
Article
Background: In Western countries functional dyspepsia (FD) has a prevalence of 10-20% among adults and although many drugs are currently available for use within clinical practice, FD remains an important challenge for physicians. Recently, food supplements that are ginger-based, along with other botanicals, have been proposed to be a possible natural alternative to pharmaceutical drugs to empirically counteract the symptoms of FD. Methods: We have therefore retrospectively analyzed the efficacy and safety profiles of a nutraceutical containing, in addition to a highly standardized ginger root extract, a multi-fractionated botanical obtained from Perilla frutescens leaf containing an innovative bouquet of compounds, including hydrophilic polyphenols and the lipophilic terpenoid perilla ketone. Results: The results of our single-group study, obtained from patients with a diagnosis of FD who were treated with the perilla/ginger nutraceutical, demonstrated a good efficacy profile, with a significant reduction observed in nearly all evaluated symptoms (epigastric pain, heartburn, gastric reflux, nausea, borborygmi, early satiety, diarrhea/constipation) starting from the first week of treatment that was further improved after 2 weeks. The treatment was well tolerated with very mild side effects (flatulence, meteorism, gastric burning, difficulty in falling asleep) lasting 3-4 days, which disappeared without stopping the treatment. Conclusions: Despite all the limitations of our pragmatic study, we believe that the perilla and ginger supplement we have used can be considered a valid tool for an empirical approach to treating patients with FD, especially when a non-conventional drug treatment is preferable to the patient and considered suitable by the physician.
Article
Beta‐amyloid (Aβ) aggregates are a major cause of Alzheimer's disease (AD), and the inhibition of Aβ aggregation is a good therapeutic target against AD. Thus, the effects of Perilla extract (4–100 µg/mL) on the aggregation of Aβ (20 µM) monomers and disaggregation of pre‐aggregated Aβ aggregates were determined. The Perilla methanol extract and its hexane fraction significantly reduced Aβ aggregation determined by a Theoflavin T fluorescence assay (IC50 = 24.5 and 19.8 µg/mL, respectively) and confirmed by Western blot analysis with native gels. The inhibition of Aβ aggregation by hexane fraction of Perilla extract (20 and 100 µg/mL) rescued the PC12 cells from Aβ aggregate‐induced toxicity to the levels of DMSO‐treated control groups. Furthermore, hexane fraction efficiently disaggregated the preformed Aβ aggregates (IC50 = 10.2 µg/mL). Perilla frutescens var. acuta leaves exhibited anti‐amyloidogenic effects against Aβ aggregation and disaggregation. Practical application These results suggest that P. frutescens var. acuta has the potential to be developed as a preventive and therapeutic agent.