Evaluation of Environmental Factor Effects on the Polyphenol and Flavonoid Content in the Leaves of Chrysanthemum indicum L. and Its Habitat Suitability Prediction Mapping.

The leaves of Chrysanthemum indicum L. are known to have various bioactive compounds; however, industrial use is extremely limited. To overcome this situation by producing high-quality leaves with high bioactive content, this study examined the environmental factors affecting the phytochemical content and antioxidant activity using C. indicum leaves collected from 22 sites in Kochi Prefecture, Japan. Total phenolic and flavonoid content in the dry leaves ranged between 15.0 and 64.1 (mg gallic acid g-1) and 2.3 and 11.4 (mg quercetin g-1), while the antioxidant activity (EC50) of the 50% ethanol extracts ranged between 28.0 and 123.2 (µg mL-1) in 1,1-Diphenyl-2-picrylhydrazyl radical scavenging assay. Among the identified compounds, chlorogenic acid and 1,5-dicaffeoylquinic acid were the main constituents in C. indicum leaves. The antioxidant activity demonstrated a positive correlation with 1,5-dicaffeoylquinic acid (R2 = 0.62) and 3,5-dicaffeoylquinic acid (R2 = 0.77). The content of chlorogenic acid and dicaffeoylquinic acid isomers varied significantly according to the effects of exchangeable magnesium, cation exchange capacity, annual temperature, and precipitation, based on analysis of variance. The habitat suitability map using the geographical information system and the MaxEnt model predicted very high and high regions, comprising 3.2% and 10.1% of the total area, respectively. These findings could be used in future cultivation to produce high-quality leaves of C. indicum.

Turkish Plants, Including Quercetin and Oenothein B, Inhibit the HIV-1 Release and Accelerate Cell Apoptosis.

The introduction of combined anti-retroviral therapy (cART) in 1996, along with a continual breakthrough in anti-human immunodeficiency virus-1 (HIV-1) drugs, has improved the life expectancies of HIV-1-infected individuals. However, the incidence of drug-resistant viruses between individuals undergoing cART and treatment-naïve individuals is a common challenge. Therefore, there is a requirement to explore potential drug targets by considering various stages of the viral life cycle. For instance, the late stage, or viral release stage, remains uninvestigated extensively in antiviral drug discovery. In this study, we prepared a natural plant library and selected candidate plant extracts that inhibited HIV-1 release based on our laboratory-established screening system. The plant extracts from Epilobium hirsutum L. and Chamerion angustifolium (L.) Holub, belonging to the family Onagraceae, decreased HIV-1 release and accelerated the apoptosis in HIV-1-infected T cells but not uninfected T cells. A flavonol glycoside quercetin with oenothein B in Onagraceae reduced HIV-1 release in HIV-1-infected T cells. Moreover, extracts from Chamerion angustifolium (L.) Holub and Senna alexandrina Mill. inhibited the infectivity of progeny viruses. Together, these results suggest that C. angustifolium (L.) Holub contains quercetin with oenothein B that synergistically blocks viral replication and kills infected cells via an apoptotic pathway. Consequently, the plant extracts from the plant library of Turkey might be suitable candidates for developing novel anti-retroviral drugs that target the late phase of the HIV-1 life cycle.

Antileukemic Activity of Twig Components of Caucasian Beech in Turkey.

Despite the development of a range of anti-cancer agents, cancer diagnoses are still increasing in number, remaining a leading cause of death. Anticancer drug treatment is particularly important for leukemia. We screened Turkish plants and found the unique antileukemic activity of twig components in Turkish Caucasian beech, selectively inducing apoptosis in leukemia cells. This effect is unique among some kinds of beeches, presumably related to oxidative stress. This study would lead to effective use of discarded material, i.e., twig of beech, and a new anti-leukemic drug based on large tree.

The Importance of 11α-OH, 15-oxo, and 16-en Moieties of 11α-Hydroxy-15-oxo-kaur-16-en-19-oic Acid in Its Inhibitory Activity on Melanogenesis.

Cosmetic industries have an interest in exploring and developing materials that have the potential to regulate melanin synthesis in human skin. Although melanin protects the skin from ultraviolet irradiation, excess melanin can be undesirable, particularly on the face where spots or freckles are associated with an appearance of aging. In this study, we found that ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (11α-OH KA) in Pteris dispar Kunze strongly inhibited melanin synthesis by suppressing tyrosinase gene expression. The melanogenic transcription factor microphthalmia-associated transcription factor (MITF) is required for this suppression. However, 11α-OH KA did not modulate the expression level or activity of MITF. Structure-activity relationship analyses suggested that the 11α-OH, 15-oxo, and 16-en moieties of 11α-OH KA are essential for the suppression of melanin synthesis. On the other hand, the 19-COOH moiety is important for preventing cellular toxicity associated with 11α-OH KA and its related compounds. These results suggest that 11α-OH KA is an attractive target for potential use in the production of cosmetic items.

Construction of Prediction Models for the Transient Receptor Potential Vanilloid Subtype 1 (TRPV1)-Stimulating Activity of Ginger and Processed Ginger Based on LC-HRMS Data and PLS Regression Analyses.

To construct a model formula to evaluate the thermogenetic effect of ginger (Zingiber officinale Roscoe) from the ingredient information, we established transient receptor potential vanilloid subtype 1 (TRPV1)-stimulating activity prediction models by using a partial least-squares projections to latent structures (PLS) regression analysis in which the ingredient data from liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and the stimulating activity values for TRPV1 receptor were used as explanatory and objective variables, respectively. By optimizing the peak extraction condition of the LC-HRMS data and the data preprocessing parameters of the PLS regression analysis, we succeeded in the construction of a TRPV1-stimulating activity prediction model with high precision ability. We then searched for the components responsible for the TRPV1-stimulating activity by analyzing the loading plot and s-plot of the model, and we identified [6]-gingerol (1) and hexahydrocurcumin (3) as TRPV1-stimulating activity components.

Development of intron length polymorphism markers in genes encoding diketide-CoA synthase and curcumin synthase for discriminating Curcuma species.

Various Curcuma rhizomes have been used as medicines or spices in Asia since ancient times. It is very difficult to distinguish them morphologically, especially when they are boiled and dried, which causes misidentification leading to a loss of efficacy. We developed a method for discriminating Curcuma species by intron length polymorphism markers in genes encoding diketide-CoA synthase and curcumin synthase. This method could apply to identification of not only fresh plants but also samples of crude drugs or edible spices. By applying this method to Curcuma specimens and samples, and constructing a dendrogram based on these markers, seven Curcuma species were clearly distinguishable. Moreover, Curcuma longa specimens were geographically distinguishable. On the other hand, Curcuma kwangsiensis (gl type) specimens also showed intraspecies polymorphism, which may have occurred as a result of hybridization with other Curcuma species. The molecular method we developed is a potential tool for global classification of the genus Curcuma.

Callicarpa longissima extract, carnosol-rich, potently inhibits melanogenesis in B16F10 melanoma cells.

Cosmetic industries focus on developing materials and resources that regulate skin pigmentation. Melanin, the major pigment in human skin, protects the skin against damage from ultraviolet light. An ethanolic extract of the leaves of Callicarpa longissima inhibits melanin production in B16F10 mouse melanoma cells by suppressing microphthalmia-associated transcription factor (MITF) gene expression. Following purification and analysis using liquid chromatography-mass spectrometry (LC-MS), NMR, and biochemical assays, carnosol was determined to be responsible for the major inhibitory effect of the C. longissima extract on melanin production. Carnosol is an oxidative product of carnosic acid, whose presence in the extract was also confirmed by an authentic reference. The carnosol and carnosic acid content in the extract was approximately 16% (w/w). These results suggest that C. longissima is a novel, useful, and attractive source of skin-whitening agents.

Influence of genetic factors on the ephedrine alkaloid composition ratio of Ephedra plants.

We investigated the ephedrine alkaloid [(-)-ephedrine and (+)-pseudoephedrine] composition ratio of a crude Chinese herbal drug described in the Japanese Pharmacopoeia 'Ephedra herb (Chinese name: Mahuang)'. There were marked changes in the alkaloid composition ratio of wild plants in areas where both male and female clusters coexisted. However, in genetically homogeneous areas with the growth of male or female clusters alone, all of the coefficients of the regression lines were positive, but each gradient varied. This suggests that the alkaloid composition ratio has a clear tendency in each individual. Based on this, we cultivated individuals for vegetative propagation, and evaluated the alkaloid content ratio. Those propagated by separating the roots showed a specific tendency regardless of the cultivation area (Wakayama, Tanegashima). Those propagated by separating the herbaceous stem showed a specific tendency regardless of the soil or harvest time. In addition, we surveyed the (-)-ephedrine content ratio of 3- to 6-year-old strains. There was a high positive correlation coefficient between the previous and subsequent years. These findings suggest that the ephedrine alkaloid composition ratio of Ephedra herb depends on genetic factors, but not on environmental factors or the growth period.