Perilla Frutescens Extract Research Articles

Unlocking the antibacterial activity and mechanisms of ε-poly-l-Lysine and perilla combination against Pseudomonas fluorescens: Insights from non-targeted metabolomic analyses

Perilla frutescens extract has been acknowledged for its robust antibacterial properties, while ε-Poly-Lysine (ε-PL) stands as a naturally occurring food preservative. However, their combined antibacterial activity and mechanisms has not been fully understood. Therefore, the aim of this study was to elucidate the combined antibacterial activity of the ε-PL/Perilla combination against Pseudomonas fluorescens. The findings unveiled a significant antibacterial efficacy of ε-PL and perilla against P. fluorescens, respectively. Upon treatment with ε-PL and perilla, a decline in membrane potential (MP) was observed. These alterations were further accompanied by reductions in nucleic acid content, metabolic activity, and respiratory chain dehydrogenase activity. And by morphological observation, it was found that the cells treated with perilla or ε-PL were severely broken. The metabolomic analysis following treatment with ε-PL and perilla unveiled substantial shifts in a multitude of metabolites. Multivariate statistical analysis showed that ε-PL and perilla hindered nucleotide metabolism and interfered with carbohydrate, amino acid, and lipid metabolism, impacting cell wall biosynthesis, cell membrane structure, and genetic material expression, leading to growth inhibition and bacterial demise. Collectively, these outcomes provide fresh insights into the intricate mechanisms underlying the inhibitory action of ε-PL and perilla against P. fluorescens.

Assessing the Antioxidant Properties, In Vitro Cytotoxicity and Antitumoral Effects of Polyphenol-Rich Perilla leaves Extracts.

(1) Background: This study aimed to outline the antioxidant, antitumoral, and cytotoxic proprieties of various types of Perilla frutescens extracts obtained from the leaves of the species. (2) Methods: We determined total polyphenols, flavonoids and anthocyanins contents, as well as the in vitro antioxidant, antitumoral, and cytotoxic actions in three types of ethanolic extracts (E1, E2, E3) and in three types of acetone: ethanol extracts (A1, A2, A3) of Perilla frutescens according to standardized procedures. (3) Results: We found that Perilla frutescens ethanolic extracts had the highest total phenol and anthocyanins concentrations. The flavonoids concentration was not statistically different between the extracts. The iron chelating capacity, hydroxyl radical scavenging capacity, superoxide anion radical scavenging capacity, and lipoxygenase inhibition capacity showed a significant increase with higher concentrations of Perilla frutescens extracts, particularly the ethanolic extracts. Perillyl alcohol had greater cytotoxic capacity in the MG-63 cell line and E1 extract showed similar significant cytotoxic effects in the A431 cell line. (4) Conclusions: Both ethanolic and acetone-ethanol extracts from Perilla frutescens exhibited important antioxidant and antitumoral actions in vitro, which proportionally increased with concentration. The cytotoxic threshold determined in this study for various types of extracts could help determine the best dosage with the maximum antioxidant and antitumoral potential. Our results could serve as a basis for further studies that will investigate the cytotoxic effects of Perilla frutescens variants on various types of cancer cell lines.

Separation and Purification of Plant Extracts by Removal of Chlorophyll, Xanthophylls and Pigments using Mineral Adsorbents in Liquid Chromatography (CLS)

This study focused on the purification of plant extracts, with the help of adsorption chromatography (liquid chromatography with a solid stationary phase - CLS) so that the purified plant extracts lead to obtaining bioactive compounds in a pure state or with advanced purity. The studied extracts can be divide into categories as follows: a) The purification of extracts from perilla frutescens b) The purification of extracts from rosmarinus officinalis c) The purification of extracts from artemisia annua (peliniță) For the perilla frutescens extract, dried leaves, the purification aimed at obtaining pure crystals of ursolic acid and the physico-chemical analysis of the plant extracts before and after extraction, to determine the loss of the important compounds of the plant, due to their retention in the adsorbent layer. For the rosemary and wormwood (artemisia annua) extracts, dry leaves, the purification aimed at obtaining pure crystals of bioactive compounds (ursolic acid, artemisinin) and their gravimetric dosing to determine the bioactive compound content of the original plant. Mineral adsorbents and combinations of mineral adsorbents in the form of adsorbent mixtures have been used. Glass liquid columns of various sizes were used. For each experiment, the working times (saturation-activation time, elution and column washing time) were noted. All experiments were performed with the adsorption chromatography procedure, with gravity flow column (in adsorption chromatography with gravity flow column), without using Sephadex LH-20 macroporous resins as a stationary phase.

The Effects of Perilla frutescens Extracts on IgA Nephropathy: A Systematic Review and Meta-Analysis.

(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.

Applications of Perilla frutescens Extracts in Clinical Practice

(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.

Purple perilla frutescens extracts containing α-asarone inhibit inflammatory atheroma formation and promote hepatic HDL cholesterol uptake in dyslipidemic apoE-deficient mice.

Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

The Attenuation of TNF-α-mediated Inflammatory Responses in Human Lung Adenocarcinoma Cell Line by Perilla Seed and Seed Meal Extract

Abstract Thai perilla (Perilla frutescens) extracts, which contain a substantial quantity of bioactive substances including phenolics and flavonoids, have shown marked anti-inflammatory activities in several investigated models. In the present study, the effect of perilla seed extract (PSE) and seed meal extract (PSME) on TNF-α-induced inflammatory response in human lung adenocarcinoma A549 cells was investigated. The total phenolic and flavonoid contents in PSME was lower than PSE. Markedly, rosmarinic acid was identified as the main constituent in both extracts. However, the DPPH and ABTS assays indicated that the antioxidant capacity of PSME was equal to PSE. Moreover, the iron-binding activity of PSE and PSME were exhibited by complex formation with Fe3+-NTA, indicating that the extracts may inhibit hydroxyl radical production via Fenton reaction. In vitro cytotoxicity analysis showed that both PSE or PSME co-treated with TNF-α, at 24 h exposure, were not toxic to the A549 cells. Interestingly, PSE and PSME dramatically exhibited an anti-inflammatory activity by inhibiting the mRNA expression of pro-inflammatory cytokines, IL-1β, IL-6, IL-8, and TNF-α, but did not influence iNOS and COX-2 mRNA expressions. Moreover, both extracts significantly reduced reactive oxygen species (ROS) production in TNF-α-induced A549 cells. The findings presented in this paper suggest that PSE and PSME could mitigate TNF-α-mediated inflammatory responses via limiting pro-inflammatory cytokine expressions and decreasing ROS production. Thus, perilla seed and seed meal, the by-product of a perilla seed oil cold-pressed extraction process, could be developed as food supplements or functional foods for the prevention of inflammation-induced lung carcinogenesis development. Keywords: Human lung adenocarcinoma cell line, Inflammation, Perilla seed, Perilla seed meal, Tumor necrosis factor-alpha (TNF-α)

Development and validation of a green and sustainable procedure for the preparation of Perilla frutescens extracts

A procedure combining supercritical CO2 and ultrasound-assisted (USC-CO2) extraction was developed to obtain rosmarinic acid (RA)-rich extracts from Perilla frutescens. Based on extraction yields and efficiencies, USC-CO2 was considered the best extraction method among the methods studied for obtaining RA from P. frutescens. The constant extraction rate period and the falling extraction rate period for USC-CO2 extraction of P. frutescens were 45 and 96 min long, respectively, and they were significantly shorter than those of traditional SC-CO2 (TSC-CO2) extraction. Furthermore, mass transfer coefficients were derived using the Sovová model for the fluid and solid phases from USC-CO2 extraction, with values of 9.752 × 10−3 and 4.203 × 10−3 min−1, respectively, which were obviously higher than those for TSC-CO2 extraction. Consequently, the theoretical solubilities of RA in the supercritical solvents used in dynamic USC-CO2 and TSC-CO2 extractions were estimated and found to be well correlated using three density-based models.

Affinity measurement of ligands in Perilla frutescens extract towards α-glucosidase using affinity-based ultrafiltration-high-performance liquid chromatography

It is a time-consuming and challenging task for affinity measurement of drug lead compounds from a plant extract because of its chemical complexity. In this research, a strategy of ultrafiltration-high-performance liquid chromatography (HPLC) was developed to directly measure dissociation constant (Kd) of compounds from natural product extract to target protein, and the Kd measurement of α-glucosidase ligands from the ethyl acetate fraction of Perilla frutescens (L.) Britt. (PFEA) was performed. The recovery value, binding degree, and signal-to-noise ratio of α-glucosidase ligands from PFEA were first determined according to the ultrafiltration-HPLC results; the Kd values were then calculated using proposed equilibrium. Finally, oleanolic acid (4) and apigenin (8) from PFEA were determined as the high affinity ligands for α-glucosidase, and their Kds were calculated as 44.9 μM and 88.5 μM, respectively, which agreed with the isothermal titration calorimetry analysis, kinetic analysis, and computer simulation of molecular docking. These results suggested that the proposed strategy is a simple and convenient method for the direct Kd determination of compounds from natural product extract without using any internal calibrants or internal standards.

Effect of Ethanol Extracts from DefattedPerilla frutescenson LPS-induced Inflammation in Mouse BV2 Microglial Cells

To evaluate the antioxidant and anti-neuroinflammatory effects of defatted Perilla frutescens extract (DPE) in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Cell viabilities were estimated by MTT assay. LPS-stimulated BV-2 microglia were used to study the expression and production of inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), Cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE₂). Pretreatment with DPE prior to LPS treatment significantly inhibited excessive production of NO (10, 25, 50, 75, and 100 μg/mL) in a dose-dependent manner, and was associated with down regulation of expression of iNOS and COX-2. DPE also suppressed the LPSinduced increase in PGE₂ level (10, 25, 50, 75, and 100 μg/mL) in BV-2 cells. Therefore, DPE can be considered as a useful therapeutic and preventive approach for the treatment of several neurodegenerative diseases.

The promotion of hair regrowth by topical application of a Perilla frutescens extract through increased cell viability and antagonism of testosterone and dihydrotestosterone.

This study investigated the potential hair regrowth effects associated with a plant extract of Perilla frutescens, which was selected due to its putative hair regrowth activity. Extracts were prepared from dried P. frutescens suspended in distilled water, where the resultant aqueous suspension was fractionated sequentially using hexane, ethyl acetate, n-butanol, and distilled water. We observed that the n-butanol fraction resulted in the highest hair regrowth activity. The n-butanol soluble fraction of P. frutescens extract (BFPE) was further separated using AB-8 macroporous resin and silica gel chromatography to obtain rosmarinic acid (RA), which demonstrated effective hair growth regeneration potential. BFPE also showed in vivo anti-androgenic activity following the use of a hair growth assay in testosterone-sensitive male C57Bl/6NCrSlc mice. Furthermore, the effects of cell viability promotion were investigated following an in vitro analysis in primary hair follicle fibroblast cells (PHFCs) treated with RA. The results suggested that RA was the active compound in P. frutescens that triggers hair growth, and RA could be a potential therapeutic agent for the promotion of hair growth and prevention of androgenetic alopecia (AGA).

Perilla frutescens Extracts Protects against Dextran Sulfate Sodium-Induced Murine Colitis: NF-κB, STAT3, and Nrf2 as Putative Targets.

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.

Staurosporine에 의해 분화된 망막신경절세포에서 산화 스트레스 유도 세포사멸에 대한 차조기 추출물의 보호 효능

본 연구에서는 산화적 스트레스로 유도한 시신경 세포사멸에 대한 차조기 물 추출물(PFE)의 효과를 확인하였다. Staurosporine으로 분화된 ssdRGC-5 세포에 buthionine과 glutamate(B/G)로 산화적 스트레스를 유도하였으며, LDH release assay, MTT reduction assay를 통하여 PFE가 농도의존적으로 B/G에 의한 세포사멸을 억제함을 관찰하였다. 세포사멸의 기전을 연구하기 위해 caspase 활성, 세포 내 ROS 생성량, 세포고사 관련 단백질 발현을 관찰한 결과, B/G에 의해 증가한 ROS 생성량, caspase 활성을 PFE가 억제하였고, 세포질로 방출된 cytochrome c와 미토콘드리아로 이동한 Bax도 감소함을 확인하였다. 이상의 결과로부터 차조기는 산화적 스트레스로 유도된 시신경 세포사멸 과정에서 항산화 효과와 미토콘드리아성 세포사멸을 완화함으로써 세포 보호 작용을 나타냄을 확인하였다.

Rapid High Performance Liquid Chromatography Determination and Optimization of Extraction Parameters of the α-Asarone Isolated from Perilla frutescens L.

Response surface methodology (RSM), based on a central composite design, was used to determine the best liquid-to-raw material ratio (10:3–15 mL/g), extraction time (1–3 h), and ethanol concentration (50%–100%) for maximum content of α-asarone from Perilla frutescens (PF) extract. Experimental values of α-asarone were 9.51–46.36 mg/g; the results fitted a second-order quadratic polynomial model and correlated with the proposed model (R2 > 0.9354). The best conditions were obtained with extraction time of 1.76 h, liquid-to-raw material ratio of 10:13.5 mL/g, and ethanol concentration of 90.37%. Under these conditions, the model predicted extraction content of 40.56 mg/g, while experimental PF content of α-asarone was 43.84 mg/g dried plant. Optimized conditions determined for maximum content of α-asarone were similar to the experimental range. Experimental values agreed with those predicted, thus validating and indicating suitability of both the model and the RSM approach for optimizing extraction conditions. In addition, a reliable, reproducible and accurate method for the quantitative determination of α-asarone by High Performance Liquid Chromatography (HPLC) analysis was developed with limit of detection (LOD), limit of quantitation (LOQ) values of 0.10 and 0.29 µg/mL and excellent linearity (R2 > 0.9999).

Competitive binding experiments can reduce the false positive results of affinity-based ultrafiltration-HPLC: A case study for identification of potent xanthine oxidase inhibitors from Perilla frutescens extract.

The purpose of this study was to assess the possibility of using competitive binding experiments with ultrafiltration-HPLC analysis to identify potent xanthine oxidase (XO) inhibitors from the Perilla frutescens extract as an attempt to reduce the number of false positive results. To isolate the enzyme-ligand complex from unbound compounds, the P. frutescens extract was either incubated in the absence of XO, in the presence of XO, or with the active site blocked XO before the ultrafiltration was performed. Allopurinaol was used as the XO active site blocker. The unbound compounds were subjected to HPLC analysis. The degree of total binding (TBD) and degree of specific binding (SBD) of each compound were calculated using the peak areas. TBD represents the binding affinities of compounds from the P. frutescens extract for the XO binding site. SBD represents the XO competitive binding between allopurinol and ligands from the extract samples. Two criteria were applied to select putative targets that could help avoid false positives. These include TBD>30% and SBD>10%. Using that approach, kaempferol-3-O-rutinoside, rosmarinic acid, methyl-rosmarinic acid, apigenin, and 4',5,7-trimethoxyflavone were identified, from total 11 compounds, as potent XO inhibitors. Finally, apigenin, 4',5,7-trimethoxyflavone, and luteolin were XO inhibitors verified through an XO inhibition assay and structural simulation of the complex. These results showed that the newly developed strategy has the advantage that the number of targets identified via ultrafiltration-HPLC can be narrowed from many false positives. However, not all false positives can be eliminated with this approach. Some potent inhibitors might also be excluded with the use of this method. The limitations of this method are also discussed herein.

Effect of Perilla frutescens Extracts on Porcine Jejunal Epithelial Cells.

Green-leaved Perilla frutescens extracts were investigated on their effect on cell proliferation of the porcine jejunal epithelial cell line, IPEC-J2, as well as on the gene expression of cell cycle or cancer-related genes. Some extracted compounds were, however, susceptible to degradation in cell culture medium, whereas others were found to be stable during the entire experimental time. Control experiments also included the assessment of H2 O2 generation in cell culture medium caused by oxidation of natural extract compounds, which was proved to be absent at low extract concentrations. A fast and significant inhibition of cell growth at low physiological extract concentrations could be observed. This finding, along with an immediate downregulation of 67 kDa laminin receptor and cyclin D1 expression, can be accounted to the presence of Perilla frutescens extract. Copyright © 2016 John Wiley & Sons, Ltd.

HPLC method development for the online-coupling of chromatographic Perilla frutescens extract separation with xanthine oxidase enzymatic assay

Enzyme-regulatory effects of compounds contained in complex mixtures can be unveiled by coupling a continuous-flow enzyme assay to a chromatographic separation. A temperature-elevated separation was developed and the performance was tested using Perilla frutescens plant extracts of various polarity (water, methanol, ethanol/water). Owning to the need of maintaining sufficient enzymatic activity, only low organic solvent concentrations can be added to the mobile phase. Hence, to broaden the spectrum of eluting compounds, two different organic solvents and various contents were tested. The chromatographic performance and elution was further improved by the application of a moderate temperature gradient to the column. By taking the effect of eluent composition as well as calculated logD values and molecular structure of known extract compounds into account, unknown features were tentatively assigned. The method used allowed the successful observation of an enzymatic inhibition caused by P. frutescens extract.

Purple perilla extracts with α-asarone enhance cholesterol efflux from oxidized LDL-exposed macrophages.

The cellular accumulation of cholesterol is critical in the development and progression of atherosclerosis. ATP-binding cassette (ABC) transporters play an essential role in mediating the efflux of excess cholesterol. In the current study, we investigated whether purple Perilla frutescens extracts (PPE) at a non-toxic concentration of 1–10 μg/ml stimulate the induction of the ABC transporters, ABCA1 and ABCG1, and cholesterol efflux from lipid-laden J774A.1 murine macrophages exposed to 50 ng/ml oxidized low-density lipoprotein (LDL). Purple perilla, an annual herb in the mint family and its constituents, have been reported to exhibit antioxidant and cytostatic activity, as well as to exert anti-allergic effects. Our results revealed that treatment with oxidized LDL for 24 h led to the accumulation of lipid droplets in the macrophages. PPE suppressed the oxidized LDL-induced foam cell formation by blocking the induction of scavenger receptor B1. However, PPE promoted the induction of the ABC transporters, ABCA1 and ABCG1, and subsequently accelerated cholesterol efflux from the lipid-loaded macrophages. The liver X receptor (LXR) agonist, TO-091317, and the peroxisome proliferator-activated receptor (PPAR) agonist, pioglitazone, increased ABCA1 expression and treatment with 10 μg/ml PPE further enhanced this effect. PPE did not induce LXRα and PPARγ expression per se, but enhanced their expression in the macrophages exposed to oxidized LDL. α-asarone was isolated from PPE and characterized as a major component enhancing the induction of ABCA1 and ABCG1 in macrophages exposed to oxidized LDL. α-asarone, but not β-asarone was effective in attenuating foam cell formation and enhancing cholesterol efflux, revealing an isomeric difference in their activity. The results from the present study demonstrate that PPE promotes cholesterol efflux from macrophages by activating the interaction of PPARγ-LXRα-ABC transporters.

Perilla Extract improves gastrointestinal discomfort in a randomized placebo controlled double blind human pilot study

BackgroundGastrointestinal (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, such as e.g. daily stress may cause altered gut physiology leading to ileum contractions and consequently gastrointestinal symptoms. In vitro and ex vivo studies clearly showed that a Perilla frutescens extract combines prokinetic, antispasmodic and anti-inflammatory effects. The aim of the intervention was to investigate the effects of the proprietary Perilla extract on GI discomfort in healthy subjects with gastrointestinal discomfort and reduced bowel movements in comparison to a placebo product.MethodsThe pilot study was performed according to a double-blind, randomized, placebo-controlled parallel design. Fifty healthy subjects with gastrointestinal discomfort and reduced bowel movements, 30-70 years, documented their GI symptoms, stool frequency and consistency daily during a 2-week run-in phase and a 4-week intervention phase with Perilla frutescens extract or placebo. GI symptoms were assessed on a 5-point scale daily and average scores over 14 days intervals were calculated.ResultsAll GI symptoms were significantly improved over time by Perilla frutescens extract during the intervention phase (bloating: -0.44 ± 0.56, p = 0.0003; passage of gas: -0.30 ± 0.66, p = 0.0264; GI rumbling: -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 discomfort was significantly improved (-0.31 ± 0.55, p = 0.0345). In the subgroup of women results were strengthened and a subscore out of bloating and abdominal discomfort was significantly improved against placebo (95%CI 0.003 to 0.77; p = 0.048).ConclusionThe demonstrated effects of Perilla frutescens extract to improve GI complaints offer very promising results, taking into consideration the challenging set up of a nutritional human study with healthy subjects and in the area of digestive health, which is known for high placebo effects.Trial registration numberNCT01931930 at ClinicalTrials.gov, Registration date 23rd August 2013.

Purple Perilla frutescens extracts enhanced cholesterol efflux and inhibited ER stress in macrophages exposed to oxidized LDL (831.8)

There is growing evidence that excess lipids can stimulate endoplasmic reticulum (ER) stress in atherosclerosis. However, the pathophysiological importance and the underlying mechanisms of this phenomenon remain unknown. The current study tested that oxidized LDL promoted ER stress in macrophages, which was blocked by purple Perilla frutescens extracts (PPE). The ER stressor tunicamycin was employed as a positive control. Treating oxidized LDL for 24 h accumulated lipid droplets in macrophages and formed foam cells, evidenced by Oil red O staining. PPE suppressed foam cell formation, but enhanced ATP‐binding cassette (ABC) transporter A1 and G1, cholesterol efflux markers. Oxidized LDL as well as tunicamycin induced the ER stress markers of activating transcription factor 6 and this effect was blocked by 蠅5 μg/ml PPE, indicating that intracellular toxic lipids in macrophages initiated ER stress. PPE also down‐regulated the induction of the ER resident chaperone BiP/Grp78. The LXR ligand TO‐0131917 increased ABCA1 expression that was blunted by the ER stressor. Accordingly, an upstream mechanism that links toxic lipids to ER stress may entail the action of lipid chaperones through inhibition of LXR. Purple Perilla frutescens extract (PPE) is an annual herb of mint family, which has possessed against inflammation and cancer. Therefore, PPE enhanced cholesterol efflux and inhibited ER stress in macrophages exposed to lipotoxic signals associated with atherosclerosis.Grant Funding Source: Supported by Ministry for Food, Agriculture, Forestry and Fisheries and Brain Korea 21 plus