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Air pollution poses a significant global concern, notably impacting pregnancy outcomes through mechanisms such as DNA damage, oxidative stress, inflammation, and altered miRNA expression, all of which can adversely affect trophoblast functions. Cleistocalyx nervosum var. paniala, known for its abundance of anthocyanins with diverse biological activities including anti-mutagenic, antioxidant, and anti-inflammatory properties, is the focus of this study examining its effect on Particulate Matter 10 (PM10) soluble extract-induced trophoblast cell dysfunction via miRNA expression. The study involved the extraction of C. nervosum fruit using 70% ethanol, followed by fractionation with hexane, dichloromethane, and ethyl acetate. Subsequent testing for total phenolics, flavonoids, anthocyanins, and antioxidant activity revealed the ethyl acetate fraction (CN-EtOAcF) as possessing the highest phenolic and anthocyanin content along with potent antioxidant activity, prompting its selection for further investigation. In vitro studies on HTR-8/SVneo cells demonstrated that 5–10 µg/mL PM10 soluble extract exposure inhibited cell proliferation, migration, invasion, and induced apoptosis. However, pretreatment with 20–80 µg/mL CN-EtOAcF followed by 5 µg/mL PM10 soluble extract exposure exhibited protective effects against PM10 soluble extract-induced damage, including inflammation inhibition and intracellular ROS suppression. Notably, CN-EtOAcF down-regulated PM10-induced miR-146a-5p expression, with SOX5 identified as a potential target. Overall, CN-EtOAcF demonstrated the potential to protect against PM10-induced harm in trophoblast cells, suggesting its possible application in future therapeutic approaches. [ABSTRACT FROM AUTHOR]

An excessive inflammatory response of the gastrointestinal tract is recognized as one of the major contributors to ulcerative colitis (UC). Despite this, effective preventive approaches for UC remain limited. Rosmarinic acid (RA), an enriched fraction from Perilla frutescens, has been shown to exert beneficial effects on disease-related inflammatory disorders. However, RA-enriched perilla seed meal (RAPSM) and perilla seed (RAPS) extracts have not been investigated in dextran sulfate sodium (DSS)-induced UC in mice. RAPSM and RAPS were extracted using the solvent-partitioning method and analyzed with high-pressure liquid chromatography (HPLC). Mice with UC induced using 2.5% DSS for 7 days were pretreated with RAPSM and RAPS (50, 250, 500 mg/kg). Then, the clinical manifestation, colonic histopathology, and serum proinflammatory cytokines were determined. Indeed, DSS-induced UC mice exhibited colonic pathological defects including an impaired colon structure, colon length shortening, and increased serum proinflammatory cytokines. However, RAPSM and RAPS had a protective effect at all doses by attenuating colonic pathology in DSS-induced UC mice, potentially through the suppression of proinflammatory cytokines. Concentrations of 50 mg/kg of RAPSM and RAPS were sufficient to achieve a beneficial effect in UC mice. This suggests that RAPSM and RAPS have a preventive effect against DSS-induced UC, potentially through alleviating inflammatory responses and relieving severe inflammation in the colon. [ABSTRACT FROM AUTHOR]

Perilla frutescens is commonly used as an n-3-fatty acid source for people living in Northern Thailand. However, cultivated areas are limited because it apparently requires specific growth conditions. Our results suggested that perilla seeds grown at higher altitude in Maehongson province contained more α-linoleic acid (ALA) contents than seeds collected from Chiang Rai and Nan provinces. Furthermore, mass spectrometry, proteomic and gene expression analysis revealed that the increase of KASII and FAD3 proteins was associated with mRNA expression and ALA production. Predictive bioinformatics analysis demonstrated two important transcription factor binding sites, AP2 and B3, are responsible for kasII and fad3 genes, respectively. The AP2 and B3 transcription factor families were known to be responsible for abiotic stress such as drought and temperature changes. From our observation, geographical factors could possibly influence the expression of genes related to fatty acid production. Furthermore, plant responses to abiotic stress environments contribute to the increase of kasII and fad3 genes and their protein expression. However, responsive transcription factors will be further studied as well as other geographical influences for a proof of concept and also to improve growing methods in order to increase perilla productivity. [ABSTRACT FROM AUTHOR]

Gastric ulcers are a common problem in upper gastrointestinal tract (GI) disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most aggressive factors leading to inducing gastric ulcers. Natural products with lower toxicity and safety are currently sought as a potential source to minimize the effect of the gastric ulcers. Perilla frutescens or Nga-mon (in Thai) leaves are rich in rosmarinic acid (RA), which has antioxidant, anti-inflammatory, and anticancer effects. This study investigates the protective effect of ethanolic extract (EE) and aqueous fraction (AF) from Perilla frutescens leaves, which are rich in RA, on indomethacin- (IND-) induced gastric ulcer in a rat model. The EE at the doses of 50 and 500 mg/kg body weight, AF at the doses of 50, 250, and 500 mg/kg body weight, or famotidine (a standard drug) were administered for 14 days prior to ulcer induction. The ulceration was performed by intragastric administration of IND. Gross gastric ulcers and biological and histological parameters were examined. The pretreatment with AF had more significant effects than EE, including reduced ulcer index, decreased gastric secretion volume and decreased acidity, but it had an elevated gastric pH relative to the IND-induced gastric ulcer. In a histopathological study, the EE and AF decreased mucosal ulcer, inflammatory infiltration, and degenerative lining cells. The IND-induced expression of inflammatory mediators was significantly attenuated with EE and AF. The experiment also remarkably showed the preservation of mucus and apoptosis protection of EE and AF on a gastric mucosal ulcer. The findings demonstrated that the EE and AF of perilla leaves were capable of protecting the stomach against gastric ulcers induced by IND through anti-inflammatory and antiapoptotic mechanisms that should be further investigated. It is suggested that Perilla frutescens leaf could be a potential alternative source of RA as a therapeutic agent and food supplement for NSAID-induced gastric injuries. [ABSTRACT FROM AUTHOR]

Thai perilla (Perilla frutescens), also called Nga-mon, contains a substantial quantity of bioactive substances including phenolics and flavonoids. These phytochemicals have been linked to various bioactivities of P. frutescens such as in vitro and in vivo antiinflammatory, anti-oxidative and anti-cancer capacities. In this study we evaluated antiinvasive and anti-migratory activities of Thai perilla leaf extract (PLE) on human breast cancer cells, MDA-MB-231. Our results demonstrate that rosmarinic acid is the main constituent of PLE. In vitro cytotoxicity analysis shows that PLE, at 24-hr exposure, is not toxic to MDA-MB-231 cells. A Boyden chamber-based transmembrane assay shows that PLE at a non-toxic dose (12.5-50 µg/mL) dramatically exhibits an inhibitory effect on cell invasion and migration. Gelatin zymography shows that PLE at a concentration of 100-400 µg/mL dose-dependently decreases matrix metalloproteinase-9 (MMP-9) secretion (p < 0.05-0.001) and activity (p < 0.001). Our data indicate that PLE can inhibit breast cancer cell invasion and migration through the reduction in activity and availability of MMP-9. Our observations also suggest that rosmarinic acid in PLE may account for the anti-invasion and anti-migration activities. In particular, rosmarinic acid as a food-derived chemotherapeutic agent can potentially be used in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: In this study, the chemopreventive properties of Perilla frutescens leaf extract (PLE) on rat colon carcinogenesis were investigated during initiation and postinitiation stages. Rats were fed orally by 50 and 500 mg/kg bw of PLE continuously from 1 week before subcutaneously injection of 1,2‐dimethylhydrazine (DMH) until the end of experiment. PLE administration reduced the aberrant crypt foci (ACF) number in DMH‐treated rats through the inhibition of hepatic cytochrome P4502E1 (CYP2E1) and bacterial β‐glucuronidase activity in the colonic lumen. These events led to the reduction of DNA methylation in colonic epithelial cells. For the postinitiation model, rats were injected (s.c.) with DMH, followed by PLE administration until the end of experiment. PLE administration also reduced the ACF number in DMH‐induced rats, resulting from apoptosis induction and reduction of proliferation in colon crypt cells. These studies demonstrated that perilla leaf could inhibit ACF formation and progression in DMH‐initiated colon carcinogenesis in rats. Practical applications: This study revealed the inhibitory effect of PLE on chemical‐induced colon carcinogenesis in rats. Altogether, our data supported that PLE acts as a chemopreventive agent for colon cancer. Thus, PLE might be developed as food supplement or functional tea for colon cancer prevention. [ABSTRACT FROM AUTHOR]

Purpose: Multidrug resistance (MDR) is known as a problem limiting the success of therapy in patients treated long term with chemotherapeutic drugs. The drug resistance is mainly due to the overexpression of the 170 kDa P-glycoprotein (Pgp), which causes a reduction in drug accumulation in the cancer cells. In this study, novel chemical modulator(s) from bitter melon (Momordica charantia L.) extracts obtained from leaves, fruits and tendrils were tested for their abilities to modulate the function of Pgp and the MDR phenotype in the multidrug-resistant human cervical carcinoma KB-V1 cells (high Pgp expression) in comparison with wildtype drug-sensitive KB-3-1 cells (lacking Pgp). Methods: The KB-V1 and KB-3-1 cells were exposed to bitter melon extracts in the presence of various concentrations of vinblastine, and cytotoxicity was assessed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Relative resistance was calculated as the ratio of the IC50 value of the KB-V1 cells to the IC50 value of the KB-3-1 cells. Accumulation and efflux of vinblastine in KB-V1 and KB-3-1 cells were measured using a [³H]-vinblastine incorporation assay. Results: The leaf extracts increased the intracellular accumulation of [³H]-vinblastine in KB- V I cells in a dose-dependent manner, but extracts from the fruits and tendrils had no effect. By modulating Pgp-mediated vinblastine efflux, the leaf extracts decreased the [³H]-vinblastine efflux in KB-V1 cells in a dose- dependent manner, but not in KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with bitter melon leaf extracts increased their sensitivity to vinblastine, but similar treatment of KB-3-1 cells showed no modulating effect. The fruit and tendril extracts did not affect the MDR phenotype in either cell line. Conclusion: The leaf extracts from bitter melon were able to reverse the MDR phenotype, which is consistent with an increase in intracellular accumulation of the drug. The exact nature of the active components of bitter melon leaf extracts remains to be identified. [ABSTRACT FROM AUTHOR]

Perilla frutescens is an herb traditionally used to treat chronic diseases owing to its antioxidant and anti-inflammatory properties. This study aimed to determine the antioxidant and anti-inflammatory effects of perilla leaf extract (PLE) in TNF-α- treated A549 human lung carcinoma cell line. Perilla frutescens leaves were extracted with 70% ethanol, and the phenolic, flavonoid, and rosmarinic acid contents were determined. Cytotoxicity of PLE was assessed using the MTT assay. The antioxidant activity and intracellular ROS production in TNF-α-treated A549 cells were evaluated. Furthermore, mRNA expression of pro-inflammatory mediators was assessed by RT-qPCR. These results showed that PLE contained phenolic acid, flavonoids, and rosmarinic acid and had no cytotoxicity. PLE exhibits antioxidant activity through a reduction in intracellular ROS production in TNF-α-treated A549 cells. Moreover, PLE showed significantly decreased mRNA expression of IL-1β, IL-8, TNF-α and COX-2. Thus, PLE plays an important role as an antioxidant and anti-inflammatory agent for the prevention of ROS formation and inflammation in A549 cells. [ABSTRACT FROM AUTHOR]

Cancer is the primary cause of death worldwide, and conventional treatments are painful, complicated, and have negative effects on healthy cells. However, cancer immunotherapy has emerged as a promising alternative. Principle of cancer immunotherapy is the re-activation of T-cell to combat the tumor that presents the peptide antigen on major histocompatibility complex (MHC). Those peptide antigens are identified with the set of omics technology, proteomics, genomics, and bioinformatics, which referred to immunopeptidomics. Indeed, immunopeptidomics can identify the neoantigens that are very useful for cancer immunotherapies. This review explored the use of immunopeptidomics for various immunotherapies, i.e., peptide-based vaccines, immune checkpoint inhibitors, oncolytic viruses, and chimeric antigen receptor T-cell. We also discussed how the diversity of neoantigens allows for the discovery of novel antigenic peptides while post-translationally modified peptides diversify the overall peptides binding to MHC or so-called MHC ligandome. The development of immunopeptidomics is keeping up-to-date and very active, particularly for clinical application. Immunopeptidomics is expected to be fast, accurate and reliable for the application for cancer immunotherapies., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2024.)