Novel Antiviral Efficacy of Hedyotis diffusa and Artemisia capillaris Extracts against Dengue Virus, Japanese Encephalitis Virus, and Zika Virus Infection and Immunoregulatory Cytokine Signatures

Currently, there are no specific therapeutics for flavivirus infections, including dengue virus (DENV) and Zika virus (ZIKV). In this study, we evaluated extracts from the plants Hedyotis diffusa (HD) and Artemisia capillaris (AC) to determine the antiviral activity against DENV, ZIKV, and Japanese encephalitis virus (JEV). HD and AC demonstrated inhibitory activity against JEV, ZIKV, and DENV replication and reduced viral RNA levels in a dose–responsive manner, with non-cytotoxic concentration ranging from 0.1 to 10 mg/mL. HD and AC had low cytotoxicity to Vero cells, with CC50 values of 33.7 ± 1.6 and 30.3 ± 1.7 mg/mL (mean ± SD), respectively. The anti-flavivirus activity of HD and AC was also consistent in human cell lines, including human glioblastoma (T98G), human chronic myeloid leukemia (K562), and human embryonic kidney (HEK-293T) cells. Viral-infected, HD-treated cells demonstrated downregulation of cytokines including CCR1, CCL26, CCL15, CCL5, IL21, and IL17C. In contrast, CCR1, CCL26, and AIMP1 were elevated following AC treatment in viral-infected cells. Overall, HD and AC plant extracts demonstrated flavivirus replication inhibitory activity, and together with immunoregulatory cytokine signatures, these results suggest that HD and AC possess bioactive compounds that may further be refined as promising candidates for clinical applications

The ethnopharmacological literature: An analysis of the scientific landscape

ETHNOPHARMACOLOGICAL RELEVANCE The research into bioactive natural products originating from medicinal plants, fungi and other organisms has a long history, accumulating abundant and diverse publications. However no quantitative literature analysis has been conducted. AIM OF THE STUDY Here we analyze the bibliometric data of ethnopharmacology literature and relate the semantic content to the publication and citation data so that the major research themes, contributors, and journals of different time periods could be identified and evaluated. MATERIALS AND METHODS Web of Science (WoS) was searched to identify relevant publications. The Analyze function of WoS and bibliometric software (VOSviewer) were utilized to perform the analyses. RESULTS Until the end of November 2018, 59,576 publications -linked to ‘ethnopharmacology’ indexed by WoS, published since 1958 in more than 5,600 journals, and contributed by over 20,600 institutions located in more than 200 countries/regions, were identified. The papers were published under four dominating WoS categories, namely pharmacology/pharmacy (34.4%), plant sciences (28.6%), medicinal chemistry (25.3%), and integrative complementary medicine (20.6%). India (14.6%) and China (13.2%) were dominating the publication space. The United States and Brazil also had more than 8.0% contribution each. The rest of the top ten countries/regions were mainly from Asia. There were around ten-fold more original articles (84.6%) than reviews (8.4%). CONCLUSIONS Ethnopharmacological research has a consistent focus on food and plant sciences, (bio)chemistry, complementary medicine and pharmacology, with a more limited scientific acceptance in the socio-cultural sciences. Dynamic global contributions have been shifting from developed countries to economically and scientifically emerging countries in Asia, South America and the Middle East. Research on recording medicinal plant species used by traditional medicine continues, but the evaluation of specific properties or treatment effects of extracts and compounds has increased enormously. Moreover increasing attention is paid to some widely distributed natural products, such as curcumin, quercetin, and rutin

Systematic evaluation of clinical and experimental evidence for the application of Chinese herbal medicines in the management of colorectal cancer

Worldwide, colorectal cancer (CRC) is the third most common cancer in men and the second in women. CRC is curable by surgical resection if it is diagnosed in early stage but requires more complex therapeutic approaches including chemotherapy at more advanced stages. Although overall patient survival is improving, survival rates for advanced CRC are poor and adverse events (AEs) associated with multi-drug combination chemotherapy can severely compromise quality of life in CRC sufferers. In China, integrative treatments which combine herbal medicines (HM) and chemotherapy are applied in hospital settings with the aim of enhancing the benefits of conventional treatments and alleviating the side effects of chemotherapy. Outside China, there is widespread use of HMs by cancer patients. However, the number of different HMs in use is large, they are often used in combination, and the evidence for their effects (if any) is limited. Hence, the primary objectives of this study were to: Evaluate the efficacy and safety of HMs in the clinical management of CRC; Identify potentially effective HMs and combinations of HMs that warrant further research; Investigate the actions and mechanisms of action of promising HMs in experimental models of CRC; and Determine directions for future research. The first stage of the project involved a comprehensive systematic review of randomised controlled trials (RCTs) that evaluated HMs in patients with CRC. Eighty-eight (88) RCTs were included (Chapter 4). The majority of studies were of integrative treatments for CRC. Meta-analyses found the addition of HM interventions to conventional chemotherapy provided benefits for tumour response, survival, alleviation of chemotherapy-related AEs and improved quality of life. This suggested that at least some of the included HMs improved clinical outcomes and warranted further study. However, the variety of HMs and chemotherapy regimens tested in the studies was considerable, participants were at different stages of the disease and there was potential for bias in the published studies (publication 1 Chen et al 2018). To further explore the effects of HMs, more focussed meta-analyses were conducted of RCTs that only enrolled people with advanced CRC and all employed FOLFOX4, which is the most commonly used regimen (Chapter 5, publication 5 Chen et al 2014). The result showed that even in advanced CRC patients, the addition of HMs to FOLFOX4 enhanced the tumour response rate by 9% based on data from 12 RCTs (880 participants) without statistical heterogeneity, and improved Quality of Life based on Karnofsky Performance Status. Importantly, there were significant reductions in severe (grade 3/4) chemotherapy-induced AEs for nausea & vomiting (9.5% reduction, 9 RCTs) and neutropenia (8.7% reduction, 10 RCTs) without heterogeneity. Both AEs are clinically important since they can lead to cessation of treatment which shortens overall survival. The HMs were composed of multiple ingredients, so the question was which of these ingredients made greater contributions to the overall effects detected in the pooled data in the meta-analyses? To approach this question, a larger meta-analysis pool was identified and a novel approach to sensitivity analyses was developed. The inclusion criteria for studies were broadened to encompass other oxaliplatin-based chemotherapies besides FOLFOX4, since these are known to have similar effects on tumour response and similar AE profiles. The resultant studies were all of Chinese HMs, most of which used orally administered formulae. Meta-analyses of the oral HM studies were conducted for tumour response rate (31 studies, 2,145 participants), nausea and vomiting (21 studies, 1,322 participants) and neutropenia (24 studies, 1,319 participants) (Chapter 6). In each case, there were significant improvements in the oral HM plus chemotherapy groups compared to the chemotherapy alone groups for all grades of the AE without important heterogeneity, based on large sample sizes. This lack of statistical heterogeneity combined with large sample sizes provided the opportunity for a series of sensitivity analyses aimed at determining which (if any) specific herbs, or combinations of herbs, improved the meta-analysis results of the pool of studies in which the herb was an ingredient. If a herb consistently improved the outcome, whenever it was included in a formula along with a variety of other herbs, it was considered a candidate for further research. The above meta-analyses and sensitivity analyses identified promising herbs for reducing chemotherapy-induced nausea and vomiting (publication 3 Chen et al 2016b) and chemotherapy-induced neutropenia (publication 2 Chen et al 2016c); and improving tumour response rate (publication 4 Chen et al 2016a). Of these outcomes, tumour response was selected as particularly relevant for further research. Of the three herbs identified as most likely to have contributed to improved tumour response (ku shen, chi shao and e zhu), one was selected for further research. This herb (ku shen) is always derived from the root of the plant Sophora flavescens, is well characterised, and some of its constituent compounds have been identified. Of these, the alkaloid matrine has been reported to have antitumour effects, so this was selected for a series of experiments. Matrine was tested in four human CRC cell lines: LS 174T, Caco-2, SW1116 and RKO (Chapter 7). Cell viability, measured using CCK-8 assays, showed that matrine inhibited proliferation of these cell-lines, time- and dose-dependently. Optical microscopy of cell morphology indicated cells underwent apoptosis rather than necrosis. Matrine was much less cytotoxic than oxaliplatin. Flow cytometry was used to measure DNA content for cell cycle analysis, and Annexin V-FITC/PI double staining was used to measure cellular apoptosis. The results showed that matrine induced cell cycle arrest at the G1 phase, and induced apoptosis in each cell-line in a time- and dose-dependent manner. To explore the likely molecular mechanisms of action of S. flavescens and its various constituent compounds, including matrine, a detailed review was conducted of published in vitro and in vivo studies in models of CRC (Chapter 8). This identified a number of intracellular signalling pathways, including WNT signalling, MAPK signalling, TGF-β signalling, and p53 signalling, as likely to be central to the anti-proliferative actions of this HM. In conclusion, matrine and other S. flavescens compounds show important bioactivities in CRC. Future studies in CRC cell-lines and in vivo models of CRC could investigate the effects of Sophora alkaloids and flavonoids on the protein components of the above pathways (Chapter 9)

Phytochemical Omics in Medicinal Plants

Medicinal plants are used to treat diseases and provide health benefits, and their applications are increasing around the world. A huge array of phytochemicals have been identified from medicinal plants, belonging to carotenoids, flavonoids, lignans, and phenolic acids, and so on, with a wide range of biological activities. In order to explore our knowledge of phytochemicals with the assistance of modern molecular tools and high-throughput technologies, this book collects recent innovative original research and review articles on subtopics of mechanistic insights into bioactivities, treatment of diseases, profiling, extraction and identification, and biotechnology

Molecular Mechanisms and Therapies of Colorectal Cancer

Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality, with 1.9 million incidence cases and 0.9 million deaths worldwide. The global number of new CRC cases is predicted to reach 3.2 million in 2040, based on the projection of aging, population growth, and human development.In clinics, despite advances of diagnosis and surgical procedures, 20% of the patients with CRC present with metastasis at the time of diagnosis, caused by residual tumor cells that have spread to distant organs prior to surgery, affecting the patient survival rate. Standard systemic chemotherapy, alternative therapies that target mechanisms involved in cancer progression and metastasis, immunotherapy, and combination therapies are the major CRC-treatment strategies. In the advanced stage of CRC the transforming growth factor-beta (TGF-β) plays an oncogenic role by promoting cancer cell proliferation, cancer cell self-renewal, epithelial-to-mesenchymal transition, invasion, tumor progression, metastatic spread, and immune escape. Furthermore, high levels of TGF-β1 confers poor prognosis and is associated with early recurrence after surgery, resistance to chemo- or immunotherapy, and shorter survival. Based on the body of experimental evidence indicating that TGF-β signaling has the potential to be a good therapeutic target in CRC, several anti-TGF-β drugs have been investigated in cancer clinical trials. Here, we presented a comprehensive collection of manuscripts regarding studies on targeting the TGF-β signaling in CRC to improve patient’s prognosis and personalized treatments

Natural Products for Cancer Prevention and Therapy

ca. 200 words; this text will present the book in all promotional forms (e.g. flyers). Please describe the book in straightforward and consumer-friendly terms. [This Special Issue book, “Natural Products for Cancer Prevention and Therapy”, is based on recent advances in natural products for cancer prevention and therapy. For this purpose, the authors of this book have been organizing a biennial international conference series. The first meeting (First International Conference on Natural Products for Cancer Prevention and Therapy) was held in Istanbul between 31 August and 2 September 2015, with the support and contribution of many valuable researchers in this field. The abstracts of the first conference were published in the Anticancer Drugs journal as a supplement. The second meeting, namely The Second International Conference on Natural Products for Cancer Prevention and Therapy, was held at Erciyes University, Kayseri, Turkey, between 8 and 11 November 2017. The abstracts of all of the presentations from the second meeting were published in the Special Issue of Proceedings by the MDPI publishing group. Furthermore, the conference report and the selected full-length papers based on the presentations at the meeting, as well as other papers based on natural products for cancer prevention and therapy, were published as a Special Issue of the Nutrients journal from MDPI. This Special Issue has contributions from various participants of the aforementioned conference, as well as other cancer and natural product researchers. These contributions include original research papers, authoritative and up-to-date reviews, and commentaries on the following topics and areas: •Natural products for the prevention and therapy of oncologic diseases •Mechanism of natural agents for anticancer and cancer preventive effects •In vitro, in vivo, and clinical studies related to natural agents and cancer • Combinatorial effects of phytochemicals and cancer chemotherapeutic drugs •Challenges and innovative approaches for anticancer drug development based on natural products •Emerging studies on anticancer phytochemicals

Bio-Functional Natural Products in Edible Resources for Human Health and Beauty

Natural products remain important repositories of promising therapeutic candidates due to their rich chemical and biological diversity. The Special Issue on "Bio-functional Natural Products in Edible Resources for Human Health and Beauty" is intended to offer biological active natural products from edible resources as candidates and/or leads for pharmaceuticals, dietary supplements, functional foods, cosmetics, and food additives, etc. The research fields of this Special Issue include natural products chemistry, phytochemistry, pharmacognosy, food chemistry, bioorganic chemistry, chemical biology, molecular biology, molecular pharmacology, and other related research fields of bioactive natural products obtained from the edible resources. This eBook contains 12 Reviews and Articles focusing on these research areas. I hope that this eBook will be of benefit to outstanding professionals in these research areas