Acne vulgaris (acne) is a common inflammatory skin disorder, and Propionibacterium acnes plays a major role in the development and progression of acne inflammation. Herbs possessing antimicrobial and anti-inflammatory activity have been applied as a medical option for centuries. In this study, we examined the suppressive effect of ethanolic oregano (Origanum vulgare) extract on live P. acnes-induced in vivo and in vitro inflammation. Following ethanol extraction of oregano leaves, four compounds with strong antioxidant activity, including rosmarinic acid, quercetin, apigenin, and carvacrol, were identified by high-performance liquid chromatography. Using the mouse ear edema model, we demonstrated that ethanol oregano extracts (EOE) significantly suppressed P. acnes-induced skin inflammation, as measured by ear thickness (32%) and biopsy weight (37%). In a separate study, using the co-culture of P. acnes and human THP-1 monocytes, EOE reduced the production of interleukin (IL)-8, IL-1β and tumor necrosis factor (TNF)-α up to 40%, 37%, and 18%, respectively, as well as the expression of these three pro-inflammatory mediators at the transcriptional level. Furthermore, EOE inhibited the translocation of nuclear factor-kappa B (NF-κB) into the nucleus possibly by inactivating toll-like receptor-2 (TLR2). The suppressive effect of EOE on live P. acnes-induced inflammatory responses could be due, in part, to the anti-inflammatory and antioxidant properties, but not the anti-microbial effect of EOE.

Polyphenols and flavonoids from non-fermented green tea and fully-fermented black tea exhibit antioxidant abilities that function as natural health foods for daily consumption. Nonetheless, evidence regarding prophylactic effects of purple shoot tea on immunomodulation remains scarce. We compared the immunomodulatory effects of different tea processes on oxidative stress and cytokine expressions in lipopolysaccharide (LPS)-stimulated macrophages. Major constituents of four tea products, Taiwan Tea Experiment Station No.12 (TTES No. 12) black and green tea and purple shoot black and purple shoot green tea (TB, TG, PB and PG, respectively), were analyzed to explore the prophylactic effects on expressions of free radicals, nitric oxide (NO), monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in LPS-activated RAW264.7 cell models. PG contained abundant levels of total polyphenols, flavonoids, condensed tannins and proanthocyanidins (371.28 ± 3.83; 86.37 ± 1.46; 234.67 ± 10.1; and 24.81 ± 0.75 mg/g, respectively) contributing to excellent free radical scavenging potency. In both the LPS-activated inflammation model and the prophylactic model, all tea extracts suppressed NO secretion in a dose-dependent manner, especially for PG. Intriguingly, most tea extracts enhanced expressions of IL-6 in LPS-stimulated macrophages, except PG. However, all teas disrupted downstream transduction of chemoattractant MCP-1 for immune cell trafficking. In the prophylactic model, all teas inhibited inflammatory responses by attenuating expressions of IL-6 and TNF-α in a dose-dependent manner, especially for TG and PG. Our prophylactic model demonstrated PG exerts robust effects on modulating LPS-induced cytokine expressions of MCP-1, IL-6 and TNF-α through scavenging free radicals and NO. In light of the prophylactic effects on LPS-related inflammation, PG effectively scavenges free radicals to modulate cytokine cascades that could serve as a functional beverage for immunomodulation.

Cutibacterium acnes (formerly Propionibacterium acnes) is one of the major bacterial species responsible for acne vulgaris. Numerous bioactive compounds from Momordica charantia Linn. var. abbreviata Ser. have been isolated and examined for many years. In this study, we evaluated the suppressive effect of two cucurbitane-type triterpenoids, 5β,19-epoxycucurbita-6,23-dien-3β,19,25-triol (Kuguacin R; KR) and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al (TCD) on live C. acnes-stimulated in vitro and in vivo inflammatory responses. Using human THP-1 monocytes, KR or TCD suppressed C. acnes-induced production of interleukin (IL)-1β, IL-6 and IL-8 at least above 56% or 45%, as well as gene expression of these three pro-inflammatory cytokines. However, a significantly strong inhibitory effect on production and expression of tumor necrosis factor (TNF)-α was not observed. Both cucurbitanes inhibited C. acnes-induced activation of the myeloid differentiation primary response 88 (MyD88) (up to 62%) and mitogen-activated protein kinases (MAPK) (at least 36%). Furthermore, TCD suppressed the expression of pro-caspase-1 and cleaved caspase-1 (p10). In a separate study, KR or TCD decreased C. acnes-stimulated mouse ear edema by ear thickness (20% or 14%), and reduced IL-1β-expressing leukocytes and neutrophils in mouse ears. We demonstrated that KR and TCD are potential anti-inflammatory agents for modulating C. acnes-induced inflammation in vitro and in vivo.

Background/Aim: Colorectal cancer (CRC) is the third most common cancer with a high mortality rate worldwide. Although gallic acid and hesperidin exert anticancer activity, synergistic effects of gallic acid and hesperidin against CRC remain elusive. This study aims to investigate the therapeutic mechanism of a novel combination of gallic acid and hesperidin against CRC cell growth, including cell viability, cell-cycle-associated proteins, spheroid formation, and stemness. Methods: Gallic acid and hesperidin derived from Hakka pomelo tea (HPT) were detected by colorimetric methods and high-performance liquid chromatography using ethyl acetate as an extraction medium. CRC cell lines (HT-29 and HCT-116) treated with the combined extract were investigated in our study for cell viability (trypan blue or soft agar colony formation assay), cell cycle (propidium iodide staining), cell-cycle-associated proteins (immunoblotting), and stem cell markers (immunohistochemistry staining). Results: Compared with other extraction methods, HPT extraction using an ethyl acetate medium exerts the most potent effect on inhibiting HT-29 cell growth in a dose-dependent manner. Furthermore, the treatment with combined extract had a higher inhibitory effect on CRC cell viability than gallic acid or hesperidin alone. The underlying mechanism was involved in G1-phase arrest and Cip1/p21 upregulation that could attenuate HCT-116 cell proliferation (Ki-67), stemness (CD-133), and spheroid growth in a 3D formation assay mimicking in vivo tumorigenesis. Conclusion: Gallic acid and hesperidin exert synergistic effects on cell growth, spheroids, and stemness of CRC and may serve as a potential chemopreventive agent. Further testing for the safety and effectiveness of the combined extract in large-scale randomized trials is required.