Artemisia Capillaris leaves inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma.

BACKGROUND: Natural product is one of the most important sources of drugs used in pharmaceutical therapeutics. Artemisia capillaris has been traditionally used as a hepatoprotective and anti-inflammatory agent. In this study, we extracted an ethanol fraction (LAC117) from the dried leaves of Artemisia capillaris and identified its anticancer activity and mechanism of action against hepatocellular carcinoma (HCC). METHODS: Anti-proliferative effect of LAC117 was evaluated by MTT assay and BrdU assay. The apoptotic effect of LAC117 on the expression of cleaved PARP and cleaved caspase-3 was evaluated by Western blot and immunohistochemistry from in vivo mouse xenograft, respectively. RESULTS: We found that LAC117 strongly suppressed the growth and proliferation of human HCC cell lines (HepG2 and Huh7). Induction of apoptosis was evidenced by the increases of cleaved caspase-3 and PARP as well as TUNEL-positive cells. Additionally, the pro-apoptotic effect of LAC117 was observed by a decrease in the expression of the XIAP and an increase in cytochrome c releases via mitochondrial membrane potential. Moreover, it significantly inhibited PI3K/AKT pathway in HCC in vivo and in vitro. LAC117 suppressed tumor growth in an ex vivo model as well as in vivo mouse xenograft by inducing apoptosis and inhibiting tumor cell proliferation. CONCLUSIONS: The present study highlights that LAC117 could not only efficiently induce apoptosis, but also inhibit the growth of human HCC cells by blocking the PI3K/AKT signaling pathway, suggesting that LAC117 would be a potentially useful drug candidate against HCC.

Effects of peribulbar anesthesia (sub-Tenon injection of a local anesthetic) on akinesia of extraocular muscles, mydriasis, and intraoperative and postoperative analgesia in dogs undergoing phacoemulsification.

OBJECTIVE: To evaluate the effects of peribulbar anesthesia (sub-Tenon injection of lidocaine hydrochloride) on akinesia of extraocular muscles, mydriasis, and intraoperative and postoperative analgesia in dogs undergoing phacoemulsification. ANIMALS: 14 Beagles with ophthalmically normal eyes. PROCEDURES: A blinded randomized controlled trial was performed. Dogs were anesthetized and assigned to 2 treatments: concurrent sub-Tenon injection of 2% lidocaine hydrochloride solution (2 mL) and IV injection of saline (0.9% NaCl) solution (0.02 mL/kg; lidocaine group [n = 7]) or concurrent sub-Tenon injection of saline solution (2 mL) and IV injection of 0.2 mg of atracurium/kg (0.02 mL/kg; control group [7]). Pupils were dilated by topical application of a combined tropicamide and phenylephrine ophthalmic solution. Ten minutes after the injections, pupil diameter was measured and phacoemulsification was performed. End-tidal isoflurane concentration was used to evaluate intraoperative pain. Subjective pain scores were recorded during the postoperative period. RESULTS: Akinesia was induced and maintained throughout the surgery in all eyes. Mean ± SD pupil diameter was significantly greater in the lidocaine group (13.7 ± 0.7 mm) than in the control group (12.2 ± 0.8 mm). Isoflurane requirements were significantly lower in the lidocaine group than the control group. However, postoperative pain scores were not significantly different between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: Sub-Tenon injection of lidocaine was an effective method for inducing akinesia of extraocular muscles, mydriasis, and intraoperative analgesia for phacoemulsification in dogs. Therefore, this could be another option for surgical field exposure and pain management during phacoemulsification in dogs.

Differentiation of antlers from deer on different feeds using an NMR-based metabolomics approach.

Deer antler has been widely used as a dietary supplement for hundreds of years in Asian countries. The chemical composition of deer antlers strongly depends on the growth conditions of the deer, especially the feeds, but the effects of different feeds on deer antlers have not been studied. To expand our knowledge of the chemical constituents of deer antler and establish an efficient way of differentiating antlers obtained with different feeds, we applied an NMR-based metabolomics approach and OPLS-DA multivariate analysis. We show that the antlers from one species on two different feeds, made from grass or mulberry trees, can be reliably differentiated by our metabolomics approach. We identified chemical constituents of the deer antlers and the marker compounds that contribute to the difference between the feed groups. We also rigorously validated our differentiation approach by showing that it can correctly classify blind samples into their respective feed groups. Our approach is expected to help design feeds to produce antlers with more defined constituents, especially those with higher bioactivities.

Application of a 1H nuclear magnetic resonance (NMR) metabolomics approach combined with orthogonal projections to latent structure-discriminant analysis as an efficient tool for discriminating between Korean and Chinese herbal medicines.

Correct identification of the origins of herbal medical products is becoming increasingly important in tandem with the growing interest in alternative medicine. However, visual inspection of raw material is still the most widely used method, and newer scientific approaches are needed. To develop a more objective and efficient tool for discriminating herbal origins, particularly Korean and Chinese, we employed a nuclear magnetic resonance (NMR)-based metabolomics approach combined with an orthogonal projections to latent structure-discriminant analysis (OPLS-DA) multivariate analysis. We first analyzed the constituent metabolites of Scutellaria baicalensis through NMR studies. Subsequent holistic data analysis with OPLS-DA yielded a statistical model that could cleanly discriminate between the sample groups even in the presence of large structured noise. An analysis of the statistical total correlation spectroscopy (STOCSY) spectrum identified citric acid and arginine as the key discriminating metabolites for Korean and Chinese samples. As a validation of the discrimination model, we performed blind prediction tests of sample origins using an external test set. Our model correctly predicted the origins of all of the 11 test samples, demonstrating its robustness. We tested the wider applicability of the developed method with three additional herbal medicines from Korea and China and obtained very high prediction accuracy. The solid discriminatory power and statistical validity of our method suggest its general applicability for determining the origins of herbal medicines.

NMR-based metabolomics approach for the differentiation of ginseng (Panax ginseng) roots from different origins.

Agro-herbal materials vary in prices and qualities depending on the origin and age and the differentiation is both scientific and public health issue. Here, we describe a metabolomics approach used to discriminate ginseng roots from different sources. Six different types of ginseng roots from China and Korea were analyzed by NMR-based metabolomics. Chinese Dangsam showed prominent differences and was easily differentiated. The difference was mainly due to the large signals in the sugar region. We further analyzed the metabolomics results in subgroups. Jeonra (Korean), Choongcheong (Korean), and Chinese ginseng in subgroup 1 could be easily differentiated by the first two principal components. The loading plot for PC1 showed that the Jeonra and Chinese ginseng roots were mainly separated by sugar signals and methyl signals but that they were reverse-correlated. A diffusion-ordered spectroscopy (DOSY) analysis showed that the methyl signals are from high molecular weight compounds and that the sugar signals are either from oligosaccharides or ginsenosides. In subgroup 2, composed of Korean Choongcheong ginseng at different ages, we were able to see age-dependent transitions in the score plot. We believe our approach can be applied to detecting the adulteration of ginseng root powders and other herbal products from different origins.