Tuberculosis is a major infectious disease that globally causes the highest human mortality. From this aspect, this study was carried out to evaluate novel pharmacological activities/effects of artesunate and artemisinin causing anti-tubercular activity/effects against Mycobacterium tuberculosis (Mtb). The anti-Mtb activities/effects of artesunate and artemisinin were evaluated using different anti-Mtb indicator assays, such as the resazurin microtiter assay, the Mycobacteria Growth Indicator Tube (MGIT) 960 system assay, and the Ogawa slant medium assay, as well as in vivo tests. Artesunate showed selective anti-Mtb effects by strongly inhibiting the growth of Mtb compared to artemisinin, and consistently induced anti-Mtb activity/effects by effectively inhibiting Mtb in the MGIT 960 system and in Ogawa slant medium for 21 days with a single dose; its minimum inhibitory concentration was 300 µg/mL in in vitro testing. Furthermore, artesunate demonstrated an anti-tubercular effect/action with a daily dose of 3.5 mg/kg in an in vivo test for four weeks, which did not indicate or induce toxicity and side effects. These results demonstrate that artesunate effectively inhibits the growth and/or proliferation of Mtb through novel pharmacological activities/actions, as well as induces anti-Mtb activity. This study shows its potential as a potent candidate agent for developing new anti-tuberculosis drugs of an effective/safe next generation, and suggests novel insights into its effective use by repurposing existing drugs through new pharmacological activity/effects as one of the substantive alternatives for inhibiting tuberculosis.

This study was performed to investigate the mechanism of action of ursolic acid in terms of anti-Toxoplasma gondii effects, including immunomodulatory effects. We evaluated the anti-T. gondii effects of ursolic acid, and analyzed the production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines through co-cultured immune cells, as well as the expression of intracellular organelles of T. gondii. The subcellular organelles and granules of T. gondii, particularly rhoptry protein 18, microneme protein 8, and inner membrane complex sub-compartment protein 3, were markedly decreased when T. gondii was treated with ursolic acid, and their expressions were effectively inhibited. Furthermore, ursolic acid effectively increased the production of NO, ROS, interleukin (IL)-10, IL-12, granulocyte macrophage colony stimulating factor (GM-CSF), and interferon-β, while reducing the expression of IL-1β, IL-6, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) in T. gondii-infected immune cells. These results demonstrate that ursolic acid not only causes anti-T. gondii activity/action by effectively inhibiting the survival of T. gondii and the subcellular organelles of T. gondii, but also induces specific immunomodulatory effects in T. gondii-infected immune cells. Therefore, this study indicates that ursolic acid can be effectively utilized as a potential candidate agent for developing novel anti-toxoplasmosis drugs, and has immunomodulatory activity.

This study was carried out to evaluate the anti-parasitic effect of ursolic acid against Toxoplasma gondii (T. gondii) that induces toxoplasmosis, particularly in humans. The anti-parasitic effects of ursolic acid against T. gondii-infected cells and T. gondii were evaluated through different specific assays, including immunofluorescence staining and animal testing. Ursolic acid effectively inhibited the proliferation of T. gondii when compared with sulfadiazine, and consistently induced anti-T. gondii activity/effect. In particular, the formation of parasitophorous vacuole membrane (PVM) in host cells was markedly decreased after treating ursolic acid, which was effectively suppressed. Moreover, the survival rate of T. gondii was strongly inhibited in T. gondii group treated with ursolic acid, and then 50% inhibitory concentration (IC₅₀) against T. gondii was measured as 94.62 μg/mL. The T. gondii-infected mice treated with ursolic acid indicated the same survival rates and activity as the normal group. These results demonstrate that ursolic acid causes anti-T. gondii action and effect by strongly blocking the proliferation of T. gondii through the direct and the selective T. gondii-inhibitory ability as well as increases the survival of T. gondii-infected mice. This study shows that ursolic acid has the potential to be used as a promising anti-T. gondii candidate substance for developing effective anti-parasitic drugs.

Corni Fructus has traditionally been used as herbal medicine for the treatment of tuberculosis, asthma, hepatitis, and chronic nephritis in Korea, Japan, and China. This research was carried out to evaluate the proliferative-inhibitory effect of CF extracts against cancer cells and to identify the new pro-substance from medicinal plants. Among these herbal extracts extracted from KCF (Korean Corni Fructus), JCF (Japanese Corni Fructus) and CCF (Chinese Corni Fructus), KCF extracts strongly induced anti-proliferation of cancer cells in a dose-dependent manner compared with other extracts. Moreover, after treatment with CM/F3 (fraction 3 obtained from KCF extracts) for 24 h, A549 cells were evaluated by several indicators such as cell viability, LDH release, DNA fragmentation, nuclear condensation, and apoptotic proteins in vitro. CM/F3 showed the tumor-selective growth inhibitory activity in a dose- and time-dependent manner in A549 cells. Consistently, CM/F3 effectively induced the activation of bax, cytochrome-c, caspase-3, -8, -9, p53, and p21 causing apoptosis, and caused the suppression of Cdk2, pRb, and E2F1 related to cell arrest in A549 cells. These results demonstrate that CM/F3 caused not only anti-proliferation but also cell death involving cell arrest through interaction between apoptotic proteins and the upregulation of p53 in A549 cells.

We analyzed parasitic diseases diagnosed by tissue biopsy specimens at KyungHee Medical Center (KMC) from 1984 to 2005. The total number of parasite infection cases was 150 (0.07%) out of the total 211,859 biopsy specimens submitted for histopathological examinations. They consisted of 62 cysticercosis, 23 sparganosis, 16 paragonimiasis, 15 amebiasis, 11 anisakiasis, 11 clonorchiasis, 3 ascariasis, 2 scabies, 2 enterobiasis, 2 trichuriasis, 1 leishmaniasis, 1 taeniasis, and 1 thelaziasis. Out of 62 cysticercosis cases, 55 were detected in subcutaneous tissues or the central nerve system. Eighteen out of 23 sparganosis cases were involved in muscular and subcutaneous tissues. In most anisakiasis cases, the involved organ was the stomach. The lung and the pleura were the most common site of paragonimiasis. The incidence of parasitic diseases during the first 5 years (1984-1988) was the highest of all observed periods. After 1989, similar incidences were shown throughout the period. Whereas cysticercosis was diagnosed in 34 cases during 1984-1988, no case has been diagnosed since 2000. In the case of sparganosis, the chronological incidence was almost uniform throughout the period 1984-2005. Paragonimiasis showed a similar tendency to cysticercosis. In gender and age distribution of parasitic diseases, men showed higher incidence rates than females, and the age groups of the 40s or older indicated higher infection frequencies than other age groups. Therefore, these results are a significant report to appear the tendency of human parasitic disease diagnosed by tissue biopsy in association with parasitosis at KMC in Seoul.