Fermentation of medicinal herbs can be a significant technique to obtain bioactive compounds. Paeoniae Radix (PR) used in the present study is a well-known herbal medicine that exhibits anti-inflammatory and immunomodulatory activity. The aim of this study is to explore the possibility that a bioactive compound is newly generated in PR extract by fermentation with a plant-derived lactic acid bacteria Lactobacillus brevis 174A. We determined the anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The PR extract fermented with Lactobacillus brevis 174A markedly increased the total phenolic content, decreased intracellular ROS levels, inhibited the release of nitric oxide (NO). It also suppressed inflammatory cytokines IL-6, TNF-ɑ, while simultaneously downregulating the gene expressions of iNOS, IL-6, TNF-ɑ, and IL-1β compared to the unfermented PR extract. Furthermore, the bioactive compound newly generated from the fermentation was identified as pyrogallol. It inhibits the inflammatory responses in a dose-dependent manner suggesting that fermentation of the herbal extract used as a medium together with the plant-derived lactic acid bacterial strain may be a practical strategy to produce medicines and supplements for healthcare.

Functional foods or drinks prepared using lactic acid bacteria (LAB) have recently gained considerable attention because they can offer additional nutritional and health benefits. The present study aimed to develop functional drinks by the fermentation of buttermilk and soymilk preparations using the Pediococcus acidilactici BD16 (alaD⁺) strain expressing the L-alanine dehydrogenase enzyme. LAB fermentation was carried out for 24 h and its impact on the physicochemical and quality attributes of the fermented drinks was evaluated. Levels of total antioxidants, phenolics, flavonoids, and especially L-alanine enhanced significantly after LAB fermentation. Further, GC-MS-based metabolomic fingerprinting was performed to identify the presence of bioactive metabolites such as 1,2-benzenedicarboxylic acid, 1-dodecene, 2-aminononadecane, 3-octadecene, 4-octen-3-one, acetic acid, azanonane, benzaldehyde, benzoic acid, chloroacetic acid, colchicine, heptadecanenitrile, hexadecanal, quercetin, and triacontane, which could be accountable for the improvement of organoleptic attributes and health benefits of the drinks. Meanwhile, the levels of certain undesirable metabolites such as 1-pentadecene, 2-bromopropionic acid, 8-heptadecene, formic acid, and propionic acid, which impart bitterness, rancidity, and unpleasant odor to the fermented drinks, were reduced considerably after LAB fermentation. This study is probably the first of its kind that highlights the application of P. acidilactici BD16 (alaD⁺) as a starter culture candidate for the production of functional buttermilk and soymilk.

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by chronic inflammation of the gastrointestinal tract. IBD includes Crohn’s disease (CD) and ulcerative colitis (UC). CD can occur in any part of the gastrointestinal tract, whereas UC mainly occurs in the colon and rectum. We previously demonstrated that a novel exopolysaccharide (EPS) produced by a plant-derived bacterium, Lactobacillus paracasei IJH-SONE68, prevents and improves the inflammation in contact dermatitis model mice via oral administration. To evaluate the preventive effect of the EPS against other inflammatory diseases, in the present study, we employed dextran sulfate sodium (DSS)-induced UC model mice. The stool consistency, hematochezia, and colonic atrophy of the mice were improved by the orally administered EPS. We also evaluated the cytokine transcription. Overexpression of the mouse macrophage inflammatory protein 2 mRNA in the colon as a functional homolog of human interleukin-8 was decreased by the orally administered EPS. However, the expression of interleukin-10, which is known as an anti-inflammatory cytokine, was stimulated in the EPS-administrated group. Based on these results, we conclude that the IJH-SONE68-derived EPS is a promising lead material for the development of drugs useful in treating inflammatory diseases such as UC.

Allergic disease is one of the most important and common health problems worldwide. We have previously demonstrated that a fig leaf-derived lactic acid bacterium Lactobacillus (Lb.) paracasei IJH-SONE68 produces a novel exopolysaccharide (EPS). Furthermore, we have shown that the EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.36) promoting inflammatory reactions. To evaluate the anti-allergy and anti-inflammatory effects of the EPS, in the present study, we employed the picryl-chloride-induced delayed-type (type IV) allergy model mice, which is used to evaluate the contact dermatitis. Oral administration of the EPS was observed to reduce the ear swelling in the model mice. We also observed that the overexpression of ear interleukin-4 (T helper (Th) 2 cytokine) mRNA and the increase in serum immunoglobulin E (IgE) are repressed. However, the expression of interferon-γ (Th1 cytokine) was not accelerated in all of the allergen-challenged model mice. The improvement may be responsible for the Th2 downregulation rather than the Th1 upregulation. In addition, the symptom of immediate-type (type I) allergy model mice was improved by oral administration of the IJH-SONE68 cell (data not shown). We can conclude that the IJH-SONE68-derived EPS is useful to improve the type I and IV allergies including atopic dermatitis.

Cariogenic bacteria, such as Streptococcus (S.) mutans and S. sobrinus, produce insoluble and sticky glucans as a biofilm material. The present study demonstrates that a lactic acid bacterium (LAB) named BM53-1 produces a substance that inhibits the sticky glucan synthesis. The BM53-1 strain was isolated from a flower of Actinidia polygama and identified as Lactobacillus reuteri. The substance that inhibits sticky glucan synthesis does not exhibit antibacterial activity against S. mutans. The cariogenic S. mutans produces glucans under the control of three glucosyltransferase (GTF) enzymes, named GtfB, GtfC, and GtfD. Although GtfB and GtfC produce insoluble glucans, GtfD forms soluble glucans. Through quantitative reverse-transcriptional (qRT)-PCR analysis, it was revealed that the BM53-1-derived glucan-production inhibitor (GI) enhances the transcriptions of gtfB and gtfC genes 2- to 7-fold at the early stage of cultivation. However, that of gtfD was not enhanced in the presence of the GI, indicating that the glucan stickiness produced by S. mutans was significantly weaker in the presence of the GI. Our result demonstrates that Lb. reuteri BM53-1 is useful to prevent dental caries.

Pancreatic cancer is a highly malignant tumor that remains a significant global health burden. In this study, we demonstrated the anticancer potential of stevia leaf extract fermented with plant-derived Lactobacillus (L.) plantarum SN13T strain. Evaluation of antioxidant capacity (including DPPH and ABTS radical scavenging activities and H₂O₂-induced oxidative damage repair in HEK-293 cells), as well as cytotoxicity against pancreatic cancer cells (PANC-1) and non-cancerous human embryonic kidney (HEK-293), revealed that the fermented extract exhibited significantly enhanced antioxidant activity and cytotoxicity against PANC-1 cells while showing minimal toxicity to HEK-293 cells compared to the unfermented extract. Further, validation through clonogenic, migration, and wound-healing assays demonstrated that the fermented extract effectively inhibited the proliferation and migration of PANC-1 cells. The active compound in the fermented extract has been identified as chlorogenic acid methyl ester (CAME), with a concentration of 374.4 μg/mL. Flow cytometry analysis indicated that CAME significantly arrested PANC-1 cells in the G₀/G₁ phase and induced apoptosis. Furthermore, CAME upregulated the expression of pro-apoptotic genes Bax, Bad, Caspase-3/9, Cytochrome c, and E-cadherin, while downregulating the anti-apoptotic gene Bcl-2. These findings suggest that CAME exerts potent cytotoxic effects on PANC-1 cells by inhibiting cell proliferation and migration, arresting the cell cycle, and regulating apoptosis-related gene expression. In conclusion, stevia leaf extract fermented with L. plantarum SN13T, which contains CAME, may serve as a promising candidate for pancreatic cancer treatment.