Schisandrin B promotes hepatic differentiation from human umbilical cord mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (UC-MSCs)-derived hepatocyte-like cells (HLCs) have shown great promise in the treatment of liver diseases. However, most current induction protocols yield hepatocyte-like cells with limited function as compared with primary hepatocytes. Schisandrin B (Sch B) is one of the main components of Schisandra chinensis, which can prevent fibrosis progression and promote liver cell regeneration. Herein, we investigated the effects of Sch B on hepatic differentiation of UC-MSCs. We found that treatment with 10 µM Sch B from the second stage of the differentiation process increased hepatic marker levels and hepatic function. Additionally, RNA-seq analysis revealed that Sch B promoted hepatic differentiation via activating the JAK2/STAT3 pathway. When transplanted HLCs into mice with CCL4-induced liver fibrosis, Sch B-treated HLCs exhibited significant therapeutic effects. This study provides an optimized hepatic differentiation protocol for UC-MSCs based on Sch B, yielding functioning cells for liver disease treatment.

Chemical and biological characterization of vaccine adjuvant QS-21 produced via plant cell culture.

Many vaccines, including those using recombinant antigen subunits, rely on adjuvant(s) to enhance the efficacy of the host immune responses. Among the few adjuvants clinically approved, QS-21, a saponin-based immunomodulatory molecule isolated from the tree bark of Quillaja saponaria (QS) is used in complex formulations in approved effective vaccines. High demand of the QS raw material as well as manufacturing scalability limitation has been barriers here. We report for the first-time successful plant cell culture production of QS-21 having structural, chemical, and biologic, properties similar to the bark extracted product. These data ensure QS-21 and related saponins are broadly available and accessible to drug developers.

Soap application alters mosquito-host interactions.

To find nutrients, mosquitoes use volatile organic compounds (VOCs) emitted by plants and animal hosts. These resources overlap in their chemical composition, and an important layer of information resides in VOCs' relative abundance in the headspace of each resource. In addition, a large majority of the human species regularly uses personal care products such as soaps and perfumes, which add plant-related VOCs to their olfactory signature. Using headspace sampling and gas chromatography-mass spectrometry, we quantified how human odor is modified by soap application. We showed that soaps alter mosquito host selection, with some soaps increasing the attractiveness of the host and some soaps reducing it. Analytical methods revealed the main chemicals associated with these changes. These results provide proof-of-concept that data on host-soap valences can be reverse-engineered to produce chemical blends for artificial baits or mosquito repellents, and evince the impact of personal care products on host selection processes.

Phylobioactive hotspots in plant resources used to treat Chagas disease.

Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medica compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada, the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses.

Phytochemical composition and antioxidant activity of coconut cotyledon.

Coconut tree (Cocos nucifera L.), a perennial, monocot tree, belonging to the family Arecaceae, is distributed through the tropics. Bioactivities of coconut water, husk fiber, oil, flowers, spadix and mesocarp of coconut fruit are widely reported. However, there is no study on cotyledon of coconut. In this study, carbohydrates, proteins, lipids, phenols, flavonoids, tannins, alkaloids and antioxidants were quantified in hot and cold percolated extracts of coconut cotyledon. Further, the antioxidant activity was studied using 2,2-diphenyl-1-picrylhydrazyl (DPPH); ferric reducing antioxidant power (FRAP); ferric thiocyanate (FTC); thiobarbituric acid (TBA); nitric oxide (NO) radical scavenging and ß-carotene bleaching assays. Among the secondary metabolites, only cardiac glycosides were detected. Methanolic extraction by cold percolation extracted high content of secondary metabolites and exhibited significant antioxidant activity in DPPH, FRAP, NO and ß-carotene bleaching assays, with EC50 of 0.12, 6.43, 16.21 and 8.09 mg/ml respectively. The chloroform extracts recorded high lipid content and scavenged the radicals in FTC (EC50 13.31 mg/ml) and TBA (EC50 9.21 mg/ml) assays. The study recommends extraction of compounds using methanol through cold percolation. The cotyledon of coconut is found to be a potent nutritive source equivalent to the endosperm.

Cytotoxic effect of selected wild orchids on two different human cancer cell lines.

Majority of the orchid species are used in the traditional medicines for the treatment of several diseases. They are the sources of polysaccharides, phenanthrenes, bibenzyl derivatives, revesteral, stilbenoids and polyphenol compounds. This study explored the cytotoxic activity of seven wild orchid species and identification of medicinally active compounds. The extracts of orchid species were screened for cytotoxic effect on the human cervical cancer cells (HeLa) and human glioblastoma cells (U251) using an MTT assay. The medicinally active compounds of high cytotoxic extracts were identified by GC-MS resulting in many stilbenoids and phenolic derivatives. The extract of Dendrobium transparens (DTs) and Vanda cristata (VCw) showed high cytotoxic effect towards the HeLa and U251 cell lines (IC50 of DTs: 382.14 µg/ml and 75.84 µg/ml respectively and IC50 of VCw: 317.23 µg/ml and 163.66 µg/ml respectively). This study concludes that they could be used as cancer therapeutics.

The use of antimalarial plants as traditional treatment in Papua Island, Indonesia.

The residents of the Eastern part of Indonesia, specifically, Papua and West Papua provinces, are dependent on traditional medicines with the use of plants, which includes treating malaria. However, there are limited information on the diversity of medicinal plants in Papua Island. Hence, the Indonesian Ministry of Health put together a database of all the natural plant-based raw materials in Indonesia, to address part of the issues encountered as a result of the limited information on the diversity of plants. Based on this background, the aim of the research was to analyze the information on medicinal plants used by the traditional healers in Papua Island based on the results of research on medicinal plants and Jamu (RISTOJA), especially in treating malaria. Data were obtained through ethnomedicine research conducted in 2012 and 2017 involving 54 ethnicities in Papua. Based on the results, 72 species of medicinal plants from 67 genera and 40 families were used traditionally in treating malaria on Papua Island. The most common medicinal plants used as traditional antimalarial concoction are Alstonia scholaris (L.) R. Br., Carica papaya L., Andrographis paniculata (Burm. f.) Nees, and Physalis minima L. Similar to other ethnobotany research, the leaves were the most used plant parts in preparing the various traditional concoctions.

Neurobehavioral evaluation and phytochemical characterization of a series of argentine valerian species.

Folkloric or galenic preparations of valerian roots and rhizomes have been used as sedatives/anxiolytics and sleep inducers since ancient times. "Valerianas" are plants that naturally grow in our region. Although some of them are used in folk medicine, they lack scientific information. We performed a comparative study of the phytochemical composition and the potential in vivo effects of ethanolic extracts of argentine valerian species: Valeriana carnosa Sm., V. clarionifolia Phil. and V. macrorhiza Poepp. ex DC., from "Patagonia Argentina"; V. ferax (Griseb.) Höck and V. effusa Griseb., from the central part of our country, and V. officinalis (as the reference plant). All these plants were rich in phenolic compounds, evidenced the presence of ligands for the benzodiazepine binding site of the GABAA receptor and were able to induce sedation as assessed by loss-of-righting reflex assays (500 mg/kg, i.p.). Mice treated with V. macrorhiza, V. carnosa and V. ferax extracts showed reduced exploratory behaviors while V. clarionifolia produced anxiolytic-like activities (500 mg/kg, i.p.) in the Hole board test. Oral administrations (300 mg/kg and 600 mg/kg, p.o.) evidenced sedative effects for V. ferax and anxiolytic-like properties for V. macrorhiza, V. carnosa and V. clarionifolia extracts. Our native valerian species are active on the CNS, validating its folkloric use as anxiolytic/sedative and sleep enhancers.

Botanical preparation HX109 inhibits macrophage-mediated activation of prostate epithelial cells through the CCL4-STAT3 pathway: implication for the mechanism underlying HX109 suppression of prostate hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most frequently observed diseases in the elderly male population worldwide. A variety of factors such as aging, hormonal imbalance, chronic inflammation, and oxidative stress play an important role in its pathogenesis. We have previously shown that HX109, an ethanol extract prepared from 3 plants (Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera), alleviates prostate hyperplasia in the BPH rat model and suppresses AR signaling by upregulating Ca2+/CAMKKß and ATF3. In this study, we used macrophage cell lines to examine the effects of HX109 on inflammation, which is considered an important causative factor in BPH pathogenesis. In the co-culture system involving macrophage-prostate epithelial cells, HX109 inhibited macrophage-induced cell proliferation, migration and epithelial-mesenchymal transition (EMT) by inhibiting the expression of CCL4 and the phosphorylation of STAT3. Furthermore, HX109 inhibited the expression of inflammatory cytokines and the phosphorylation of p65 NF-κB in a concentration dependent manner. Taken together, our results suggested that HX109 could regulate macrophage activation and its crosstalk with prostate cells, thereby inhibiting BPH.

The effect of hawthorn flower and leaf extract (Crataegus Spp.) on cardiac hemostasis and oxidative parameters in Sprague Dawley rats.

Cardiovascular diseases are described as disorders of heart and vessels that involve stroke and coronary heart diseases. People in the Middle East converged to complementary medicine as an economic alternative to expensive healthcare services. Crataegus monogyna Jacq. (Lindm.) Rosacea is among the most commonly used herb for the treatment of declining cardiac performance, hypertension, and arrhythmias. Previously, we had shown that Crataegus Spp. (Hawthorn) extract increased the tendency of bleeding among patients undergoing coronary artery bypass grafting. Herein, the effects of Crataegus Spp. extract on oxidative stress, cardiac and hematological parameters were evaluated in Sprague Dawley rats. Male rats were randomly assigned into four groups. Group 1 served as control while groups 2-4 served as the experimental groups and were administered extract at doses of 100, 200, and 500 mg/kg. All the doses were given orally once/day and the treatment was continued for three weeks. Hawthorn treatment resulted in a significant decrease in the liver thiobarbituric acid reactive substances level in a dose-dependent manner compared to the control (1.258 (3, 24); P < 0.0001). We found a significant increase in the cardiac antithrombin III among hawthorn treated group compared to the control (4.18 (3, 24); P < 0.0001). On the other hand, hawthorn treatment decreased significantly the liver factor-X level (0.1341 (3, 22); P < 0.0001), while no significant changes were seen in soluble-platelet endothelial cell adhesion molecule-1 (P-value = 0.0599). In conclusions, hawthorn extract possesses an antioxidant effect and blood-thinning properties. Hence, we recommend attention when using this herbal extract with other anticoagulation and/or antiplatelet drugs or undergoing major cardiac surgery.

Antifungal activity and toxicity studies of flavanones isolated from Tessaria dodoneifolia aerial parts.

Tessaria dodoneifolia [Asteraceae] is traditionally employed in Northwestern Argentina for fungal infections treatment. We report the antifungal activity guided isolation and identification of substances from aerial parts of this species, both individually and in combination with fluconazole (FLU), against Candida albicans strains. Two antifungal flavanones were identified as naringenin (NAR) and pinocembrin (PIN). These compounds could individually inhibit the growth of C. albicans strains. Combinations of NAR and PIN with FLU were synergistic against the FLU resistant and sensitive C. albicans strains. Genotoxic and cytotoxic evaluations were also performed. NAR, PIN and their combinations with FLU did not have a genotoxic effect on Bacillus subtilis rec strains. Finally, these compounds did not show cytotoxicity at concentrations below 80 µg/mL.

Proton NMR and HR-LC/MS based phytochemical analysis of methanolic fraction of Alectra parasitica A. Rich. rhizomes.

INTRODUCTION: Alectra parasitica (Scrophulariaceae/Orobanchaceae) is a rarely occurring parasitic plant grows on roots of Vitex negundo L. (Verbenaceae). As per Indian system of medicine, Ayurveda, it can be used in treatment of various diseases. So far, this plant has not been explored phyto-chemically in detail. Non-small cell lung cancer (NSCLC) is mostly occurring type of lung cancer, which so far can be treated by chemotherapy approach including cisplatin. AIM: Present research work was aimed towards preparation of methanolic fraction of A. parasitica rhizomes; its phytochemical analysis by 1H-NMR and HR-LC/MS; evaluation of its anti-cancer property against NSCLC-A549 cell line. METHODS: For preparation of methanolic fraction (MF), A. parasitica rhizome powder was defatted; extracted with combination of water and alcohol (1:1); added with lead acetate and then sulphuric acid; fractionation of ethyl acetate fraction with methanol. After phytochemical analysis of MF by preliminary chemical testing, TLC, 1H-NMR and HR-LC/MS techniques, MF was screened for its anti - cancer property against NSCLC-A549 cell line by MTT assay. RESULTS: Detail phytochemical analysis reflected successful preparation of tannin-less MF of A. parasitica rhizomes. Different types of analytical techniques first time proved the proved the presence of various types of phytochemicals in this plant. On MTT assay, it was found that MF has anti-cancer property against NSCLC-A549 cell line with IC50 value, 306.51 µg/ml. CONCLUSION: MF contains different phytochemicals like iridoids, flavonoids, steroid glycosides and also strigalactones; which cumulatively exert anti-cancer effect on A549. Appearance of all these compounds is significant in chemotaxonomic surveillance of this rare plant and specially, strigalactones can be proved important in establishing their parasitism with host plant.

Anti-cancer mechanisms of linalool and 1,8-cineole in non-small cell lung cancer A549 cells.

Linalool and 1,8-cineole are plant-derived isoprenoids with anticancer activities in lung cancer cells, nevertheless, the cellular and molecular mechanisms of action remain poorly understood. The purpose of this study was to determine the anticancer mechanisms of action of linalool and 1,8-cineole in lung adenocarcinoma A549 cells. Linalool (0-2.0 mM) and 1,8-cineole (0-8.0 mM) inhibited cell proliferation by inducing G0/G1 and/or G2/M cell cycle arrest without affecting cell viability of normal lung WI-38 cells. None of the two monoterpenes were able to induce apoptosis, as observed by the lack of caspase-3 and caspase-9 activation, PARP cleavage, and DNA fragmentation. Linalool, but not 1,8-cineole, increased reactive oxygen species production and mitochondrial membrane potential depolarization. Reactive oxygen species were involved in cell growth inhibition and mitochondrial depolarization induced by linalool since the antioxidant N-acetyl-L-cysteine prevented both effects. Besides, linalool (2.0 mM) and 1,8-cineole (8.0 mM) inhibited A549 cell migration. The combination of each monoterpene with simvastatin increased the G0/G1 cell cycle arrest and sensitized cells to apoptosis compared with simvastatin alone. Our results showed that both monoterpenes might be promising anticancer agents with antiproliferative, anti-metastatic, and sensitizer properties for lung cancer therapy.