Hypopigmenting activity of bisabolangelone isolated from Angelica koreana Maxim. in α-melanocyte stimulating hormone-activated B16 or melan-a cells.

Tyrosinase is a key enzyme in the biosynthetic pathway of melanin pigments. Abnormal accumulation of melanin pigments causes melasma, freckles, and senile lentigo, which can be substantially ameliorated by treatment with arbutin or other tyrosinase inhibitors. In this study, roots of Angelica koreana Maxim. (Umbelliferae) inhibited melanin production in α-melanocyte stimulating hormone ( α-MSH)-activated B16 melanoma cells or melan-a melanocytes. To elucidate the hypopigmenting principle of A. koreana, the plant extracts were subjected to bioassay-guided phytochemical analysis, resulting in the identification of bisabolangelone. Bisabolangelone dose-dependently inhibited α-MSH-induced melanin production in B16 or melan-a cells with IC(15) values of 9-17 µM. The positive control arbutin also inhibited melanin production in B16 cells with an IC(50) value of 317 µM. Bisabolangelone suppressed α-MSH-inducible protein levels of tyrosinase in B16 cells but could not significantly inhibit the catalytic activity of cell-free tyrosinase. Taken together, this study indicates that bisabolangelone is the primary hypopigmenting principle of A. koreana and may have pharmacological potential in the melanin-associated hyperpigmentation disorders.

Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus.

The effects of processed Aloe vera gel (PAG) on the course of established diet-induced non-insulin-dependent diabetes mellitus (NIDDM) were studied in C57BL/6J mice. NIDDM was induced in C57BL/6J mice by feeding them a high-fat diet. Mice exhibiting diet-induced obesity (DIO) with blood glucose levels above 180mg/dl were selected to examine the antidiabetic effects of PAG. Oral administration of PAG for 8 weeks reduced circulating blood glucose concentrations to a normal level in these DIO mice. In addition, the administration of PAG significantly decreased plasma insulin. The antidiabetic effects of PAG were also confirmed by intraperitoneal glucose tolerance testing. PAG appeared to lower blood glucose levels by decreasing insulin resistance. The administration of PAG also lowered triacylglyceride levels in liver and plasma. Histological examinations of periepididymal fat pad showed that PAG reduced the average size of adipocytes. These results demonstrate that the oral administration of PAG prevents the progression of NIDDM-related symptoms in high-fat diet-fed mice, and suggest that PAG could be useful for treating NIDDM.

Protective effect of a mixture of Aloe vera and Silybum marianum against carbon tetrachloride-induced acute hepatotoxicity and liver fibrosis.

The hepatoprotective effects of ACTIValoe N-931 complex, a mixture of Aloe vera and Silybum marianum, against acute and chronic carbon tetrachloride (CCl(4))-induced liver injuries were investigated. Acute hepatotoxicity was induced by intraperitoneal injection of CCl(4) (50 microl/kg), and ACTIValoe N-931 complex at 85, 170, and 340 mg/kg was administered orally 48, 24, and 2 h before and 6 h after injection of CCl(4). Hepatotoxicity was assessed 24 h after CCl(4) treatment. Liver fibrosis was induced by intraperitoneal injection of CCl(4) for 8 weeks (0.5 ml/kg, twice per week), and mice were treated with ACTIValoe N-931 complex at 85, 170, or 340 mg/kg once a day (p.o.). In both acute hepatotoxicity and liver fibrosis, serum aminotransferase levels and lipid peroxidation were increased and the hepatic glutathione content was decreased. These changes were prevented by ACTIValoe N-931 complex. The ACTIValoe N-931 complex attenuated the increase in tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), mRNA expressions in acute hepatotoxicity. In antifibrotic experiments, tissue inhibitor of metalloprotease-1 (TIMP-1) mRNA expression was attenuated by treatment with ACTIValoe N-931 complex. The ACTIValoe N-931 complex decreased the hepatic hydroxyproline content and the transforming growth factor-beta1 levels. Our results suggest that the ACTIValoe N-931 complex has hepatoprotective effects in both acute and chronic liver injuries induced by CCl(4).

Synergistic activation of monocytes by polysaccharides isolated from Salicornia herbacea and interferon-gamma.

The hot water extract of Salicornia herbacea, SHE, has recently been shown to have strong immunomodulatory activity. In the present study, we purified the polysaccharides, termed SHP, from SHE preparation and examined their immunomodulatory activity alone and in combination with interferon (IFN)-gamma. The combination of SHP and IFN-gamma synergistically inhibited the growth of the mouse monocytic cell line, RAW 264.7, inducing further differentiation to strongly adherent macrophages. The differentiation-inducing activity of SHP alone and in combination with IFN-gamma was confirmed by changes in the expression of differentiation antigens such as CD11b, CD18 and CD24. In addition, the combination of SHP and IFN-gamma synergistically activated RAW cells to produce cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta, and nitric oxide (NO). The synergistic activity of SHP was more prominent when SHP concentration was low. Increased production of TNF-alpha, IL-1 beta and NO was correlated with an increased level of their respective transcripts. These results confirm that Salicornia herbacea contains immunomodulatory polysaccharides that activate monocytes synergistically with small doses of IFN-gamma.

Identification of optimal molecular size of modified Aloe polysaccharides with maximum immunomodulatory activity.

Polysaccharides isolated from the gel of Aloe species have been known to have diverse biological activities, including immunomodulatory and antitumor activities. The molecular size-immunomodulatory activity relationship of modified Aloe polysaccharide (MAP) was examined in this study. Crude MAP (G2E1) was prepared from the gel of Aloe vera that was partially digested with cellulase. Proteins in crude MAP were removed by passage through a DEAE-Sephacel column, and then the protein-free MAP (G2E1D) was further separated into three fractions, G2E1DS3 molecular weight (MW > or = 400 KDa), G2E1DS2 (5 KDa < or = MW < or = 400 KDa), G2E1DS1 (MW < or = 5 KDa), by Sephacryl column chromatography and ultrafiltration. Immunomodulatory activities of MAP preparations were examined on a mouse macrophage cell line, RAW 264.7 cells, and in ICR strain of mouse implanted with sarcoma 180 cells. We found that polysaccharides between 400 and 5 KDa exhibit the most potent macrophage-activating activity as determined by increased cytokine production, nitric oxide release, expression of surface molecules, and phagocytic activity. In accordance with the in vitro activity, polysaccharides between 400 and 5 KDa also exhibited the most potent antitumor activity in vivo.