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Pulmonary inflammation is a characteristic of many lung diseases. Increased levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-8, have been correlated with lung inflammation. In this study, we used lipopolysaccharide (LPS) to induce iNOS, COX-2, and cytokines (TNF-α, IL-1β, and IL-8) productions in human lung epithelial cells (A-549). Leaf of Eriobotrya japonica (Pi-Pa-Ye, PPY), a traditional Chinese medicine for the treatment of pulmonary inflammatory diseases, was capable of suppressing LPS-induced cytokine productions in a dose-dependent manner. Moreover, the suppression of PPY on the cytokine productions resulted from the inhibition of inhibitory κB-α phosphorylation and nuclear factor-κB (NF-κB) activation. Analysis of the anti-inflammatory effects of ursolic acid and oleanolic acid, the triterpene compounds present in PPY, showed that ursolic acid significantly inhibited LPS-induced IL-8 production, NF-κB activation, and iNOS mRNA expression, whereas oleanolic acid did not have these effects. In conclusion, our findings suggested the potential mechanisms of PPY and its active component, ursolic acid, in the treatment of pulmonary inflammation.

The fruits of Cornus officinalis have been used in traditional oriental medicine for treatment of inner ear diseases, such as tinnitus and hearing loss. In the present study, we investigated the protective effect of C. officinalis on hydrogen peroxide-induced cytotoxicity in HEI-OC1 auditory cells. The results from bioassay-guided fractionation of methanol extract of C. officinalis fruits showed that ursolic acid is a major active component. Ursolic acid (0.05–2 μg/ml) had protective effect against the HEI-OC1 cell damage and reduced lipid peroxidation in a dose-dependent manner. In addition, pre-treatment with ursolic acid significantly attenuated the decrease of activities of catalase (CAT) and glutathione peroxidase (GPX), but superoxide dismutase (SOD) activity was not significantly affected by ursolic acid. These results indicate that ursolic acid protects hydrogen peroxide-induced HEI-OC1 cell damage through inhibition of lipid peroxidation and induction of antioxidant enzymes, CAT and GPX, and may be one of the active components responsible for these effects of C. officinalis fruits.

Hedyotis diffusa Willd. (Rubiaceae) is an important folk herb used to prevent and cure hepatitis and liver cancer in Taiwan. For differentiation of H. diffusa from counterfeits, macroscopic and microscopic characters of H. diffusa, H. corymbosa and H. tenelliflora were examined in this study. According to Trypan blue exclusion assay and Western blot analysis, H. diffusa had a significant inhibition of cell growth and induction of cell apoptosis in COLO 205 (colon cancer), Hep 3B (hepatocellular carcinoma) and H460 (lung cancer) cell lines. This study also used high-performance liquid chromatography (HPLC) to determine the quality control of H. diffusa. The HPLC data showed that ursolic and oleanolic acid are the components of the H. diffusa, consisting of approximately 4.66–4.80% and 1.86–1.96%, respectively. Our study also demonstrated that ursolic acid has significant anti-tumor activity in COLO 205, Hep 3B and H460 cancer cells.

Ursolic acid (UA), a pentacyclic triterpenoid, is known to exert antitumor activity in breast, lung, liver and colon cancers. Nonetheless, the underlying mechanism of ursolic acid in prostate cancer cells still remains unclear. In the present study, we report the chemotherapeutic effects of ursolic acid as assessed using in vitro and in vivo models. Treatment of human prostate cancer cells (LNCaP and PC-3) with UA inhibited the proliferation and induced apoptosis in both cell lines as characterized by the increased Annexin V-binding. The induction of apoptosis by UA was associated with a decrease in the levels of Bcl-2, Bcl-xl, survivin, and activated caspase-3. Treatment with UA also inhibited the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylation of Akt and mTOR signaling proteins. Further, administration of UA significantly inhibited the growth of LNCaP prostate tumor xenografts in athymic nude mice, which was associated with inhibition of cell proliferation, induction of apoptosis of tumor cells and decreased expression of PI3K downstream factors, such as p-Akt and p-mTOR in tumor xenograft tissues. Our study demonstrates that UA not only inhibits cell growth but also induces apoptosis through modulation of the PI3K/Akt/mTOR pathway in human prostate cancer cells. We suggest that UA may be a new chemotherapeutic candidate against prostate cancer.

The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).

Glycolysis is one of the key metabolic reprogramming characteristics of ovarian cancer. Ursolic Acid (UA), as a natural compound, exerts a beneficial regulatory effect on tumor metabolism. In this study, we have confirmed through RNA-seq analysis and a series of in vitro and in vivo functional experiments that UA significantly inhibits ovarian cancer cell proliferation, promotes tumor apoptosis, and reduces glycolysis levels. Additionally, it demonstrates synergistic therapeutic effects with cisplatin in both in vitro and in vivo experiments. Furthermore, at the molecular level, we found that UA inhibits glycolysis in ovarian cancer by binding to the transcription factor KLF5 and blocking the transcriptional expression of the downstream PI3K/AKT signaling pathway, thereby exerting its therapeutic effect. In conclusion, our research indicates that UA can inhibit the proliferation, apoptosis, and glycolysis levels of ovarian cancer cells through the KLF5/PI3K/AKT signaling axis. Our findings offer a new perspective on the therapeutic application of the natural compound UA in ovarian cancer and support its potential development as a candidate for chemotherapy.