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Phloroglucinol and derived compounds comprise a huge class of secondary metabolites widely distributed in plants and brown algae. A vast array of biological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer has been associated to this class of compounds. In this review, the available data on the antiviral and antibacterial capacity of phloroglucinols have been analyzed. Some of these compounds and derivatives show important antimicrobial properties

Background: Purified fractions from a Boswellia serrata Roxb. Ex. Colebr. (Burseraceae) extract (ETOH and DCM) contain biologically active compounds that are well known for having inflammation inhibitory properties. In this work, the purified fractions were tested in-vitro for LTC4, LTA4 and COX-2 activities using ELISA and qPCR was performed to determine gene regulation in human leukemia (HL-60) Cells. Two D-imaging tomography was performed to determine the anti-inflammatory activities of the fractions in BALB/c mouse model of lung inflammation. Objective: To evaluate anti-inflammatory activities of bioactive compounds of Boswellia serrata purified fractions. Methods: In-vitro MTT assay was performed in HL-60 cell lines for measuring the toxicity/ viability of the cells. ELISA tests were performed for evaluating LTA4, LTC4 and COX-2 activities. qPCR was performed to evaluate the expression of mRNA in HL-60 cells. In-vivo experiments were performed in OVA sensitized and challenged BALB/c mice at two doses of Boswellia serrata purified fraction containing 6% Boswellic acid of 50 and 100mg/kg body weight were given orally and the standard drug dexamethasone (DXA, 4 mg/kg body weight) and reduction in lung inflammation was assessed by using an IVIS Xenogen in-vivo fluorescence imaging system. Results: A purified fraction of Boswellia serrata ETOH extracts reduced leukotriene-C4-synthase activity by 52%, leuktotriene-A4-hydrolase activity by 22% and COX-2 activity by 99% with an IC50 of 12.5μg/ml. Intragastric administration of the purified fraction of Boswellia serrata at two doses of 50mg/kg b.w. and 100mg/kg b.w., respectively along with 2-3% HPMC resulted in a ~51% (P value Conclusion: The present study describes that Boswellia serrata ethanolic extracts purified fraction (ETOH-BS) possess significant anti-inflammatory activities in HL-60 and in BALB/c and further supports for its use as Ayurvedic medicines traditionally in the treatment of lung disorders including allergy and asthma.

The anthocyanin delphinidin is a natural compound found as water-soluble pigment in coloured fruits and berries. Anthocyanin-rich diets have been proposed to have bone protective effects in humans and mice, but the underlying mechanisms remain unclear. In this study, we used a medaka (Oryzias latipes) osteoporosis model to test the effects of delphinidin on bone cells in vivo. In this model, inducible transgenic expression of receptor-activator of NF-kβ ligand (Rankl) leads to ectopic formation of osteoclasts and excessive bone resorption, similar to the situation in human osteoporosis patients. Using live imaging in medaka bone reporter lines, we show that delphinidin significantly reduces the number of osteoclasts after Rankl induction and protects bone integrity in a dose-dependent manner. Our in vivo findings suggest that delphinidin primarily affects the de novo differentiation of macrophages into osteoclasts rather than the recruitment of macrophages to sites of bone resorption. For already existing osteoclasts, delphinidin treatment affected their morphology, leading to fewer protrusions and a more spherical shape. Apoptosis rates were not increased by delphinidin, suggesting that osteoclast numbers were reduced primarily by impaired differentiation from macrophage progenitors and reduced maintenance of pre-existing osteoclasts. Importantly, and in contrast to previously reported cell culture experiments, no effect of delphinidin on osteoblast differentiation and distribution was observed in medaka in vivo. Our study is the first report on the effects of delphinidin on bone cells in fish embryos, which are a unique model system for compound testing that is suitable for live imaging of bone cell behaviour in vivo.

Experimental and clinical studies suggest a positive impact of anthocyanins on bone health; however, the mechanisms of anthocyanins altering the differentiation and function of osteoblasts and osteoclasts are not fully understood. This work demonstrates that dietary anthocyanins and resveratrol increased proliferation of cultured human hFOB 1.19 osteoblasts. In addition, treatment of serum starvation of hFOB osteoblasts with anthocyanins and resveratrol at 1.0 μg/ml reduced apoptosis, the Bax/Bcl-2 ratio, p53, and HDAC1 expression, but increased SIRT1/3 and PGC1α mRNA expression, suggesting mitochondrial and epigenetic regulation. In Sp7/osterix:mCherry transgenic medaka, peonidin-3-O-glucoside and resveratrol increased osteoblast differentiation and increased the expression of Sp7/osterix. Cyanidin, peonidin-3-O-glucoside, and resveratrol also reduced RANKL-induced ectopic osteoclast formation and bone resorption in col10α1:nlGFP/rankl:HSE: CFP medaka in doses of 1–4 μg/ml. The results indicate that both cyanidin and peonidin-3-O-glucoside have anabolic effects on bone, increasing osteoblast proliferation and differentiation, mitochondrial biogenesis, and by altering the osteoblast epigenome. Cyanidin and peonidin-3-O-glucoside also reduced RANKL-induced bone resorption in a transgenic medaka model of bone resorption. Thus, peonidin-3-O-glucoside and cyanidin appear to both increase bone formation and reduce bone loss, suggesting that they be further investigated as potential treatments for osteoporosis and osteomalacia.

Background: Leukotrienes are powerful mediators of inflammation and interact with specific receptors in target cell membrane to initiate an inflammatory response. Thus, Leukotrienes (LTs) are considered to be potent mediators of inflammatory diseases including allergic rhinitis, inflammatory bowel disease and asthma. Leukotriene B4 and the series of cysteinyl leukotrienes (C4, D4, and E4) are metabolites of arachidonic acid metabolism that cause inflammation. The cysteinyl LTs are known to increase vascular permeability, bronco-constriction and mucus secretion. Objectives: To review the published data for leukotriene inhibitors of plant origin and the recent patents for leukotriene inhibitors, as well as their role in the management of inflammatory diseases. Methods: Published data for leukotrienes antagonists of plant origin were searched from 1938 to 2019, without language restrictions using relevant keywords in both free text and Medical Subject Headings (MeSH terms) format. Literature and patent searches in the field of leukotriene inhibitors were carried out by using numerous scientific databases including Science Direct, PubMed, MEDLINE, Google Patents, US Patents, US Patent Applications, Abstract of Japan, German Patents, European Patents, WIPO and NAPRALERT. Finally, data from these information resources were analyzed and reported in the present study. Results: Currently, numerous anti-histaminic medicines are available including chloropheneremine, brompheniramine, cetirizine, and clementine. Furthermore, specific leukotriene antagonists from allopathic medicines are also available including zileuton, montelukast, pranlukast and zafirlukast and are considered effective and safe medicines as compared to the first generation medicines. The present study reports leukotrienes antagonistic agents of natural products and certain recent patents that could be an alternative medicine in the management of inflammation in respiratory diseases. Conclusion: The present study highlights recent updates on the pharmacology and patents on leukotriene antagonists in the management of inflammation respiratory diseases.

Acori Tatarinowii Rhizome (ATR, the dried rhizome of Acorus tatarinowii Schott), a well-recognized traditional Chinese herbal medicine, is prescribed to treat neurological disorders. The essential oil is considered as the active fraction of ATR, and the neuroprotection of ATR essential oil (ATEO) is proven, including the protection against oxidative stress. However, the cellular mechanism of ATEO against oxidative stress has not been fully illustrated. In this study, to investigate the cellular mechanism of ATEO, the cytoprotective effect of ATEO against H2O2-induced injury was revealed in PC12 cells. ATEO treatment increased the viability of cells affected by H2O2-mediated injury, inhibited reactive oxygen species (ROS) accumulation, and induced the expression of several antioxidant proteins (SODs, GPx, and UCPs). The cytoprotective effect of ATEO was related to upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression, which was counteracted by PGC-1α specific knockdown. Using inhibitor of protein kinase A (PKA), we found that cAMP-response element binding protein (CREB) activation was involved in ATEO-induced PGC-1α expression. Taken together, we suggest that ATEO effectively prevents H2O2-induced cell injury possibly through the activation of CREB/PGC-1α signaling in PC12 cells. The results provide a molecular insight into the effect of ATEO on cytoprotection against oxidative stress.

Zhitao Ren,1 Qingping Lan,1 Yan Chen,1 Yuet Wa Judy Chan,1 Gail B Mahady,2 Simon Ming-Yuen Lee1 1State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 2Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Center for Traditional Medicine, University of Illinois at Chicago, Chicago, IL, USACorrespondence: Simon Ming-Yuen LeeInstitute of Chinese Medical Sciences, University of Macau, Avenide Da Universidade, Room 7003, N22 Building, Taipa, Macau, People’s Republic of ChinaTel +853-88224695Email simonlee@umac.moObjective: Toevaluate the effect LMHFV on body weight gain, NAFLD and muscle strength and explore effect in mitochondrial biogenesis, AMPKα and p38 pathways.Methods: Vibration platform used in this study provides specific whole-body cyclic mechanical stimulation at low magnitude (0.3 g) and high frequency (50 Hz). Diabetic mice (8– 9 mice per group) (C57BL/KsJ-m+/+Leprdb) were randomly divided into untreated group (no vibration) and two vibration groups. Lean mice (8 mice) were used as non-diabetic control for both groups. Two diabetic vibration groups received LMHFV every day for 20 min/day and 40 min/day separately.Results: After 8weeks of treatment, results showed that body weight, liver weight, fat pad weight, glucose level and insulin level were lower in vibration group when compared with the untreated group. The ratio of fat in liver was significantly decreased after vibration treatment. Muscle strength was significantly increased after vibration. Mitochondrial biogenesis-related gene expression was increased in soleus, gastrocnemius and liver. AMPKα mRNA expression level was increased in soleus and gastrocnemius after vibration treatment. p38 and AMPKα mRNA expression level and protein expression level in liver were enhanced with vibration treatment. Moreover, phosphorylation of p38 and AMPKα was enhanced in liver.Conclusion: LMHFV applied in our study decreases body weight gain and improves muscle strength and NAFLD in diabetic mice which were partly through improving mitochondrial biogenesis by enhancing p38 and AMPKα pathway.Keywords: type 2 diabetes mellitus, low-magnitude high-frequency vibration, mitochondrial biogenesis, AMPKα, p38

Introduction: In previous work, we have shown the synergistic effects of combinations of vitamins A, D2, and D3 in reducing the proliferation of HCT-116 colon cancer cells. This combination also induced apoptosis and altered gene expression patterns as determined by transcriptomic profiling. Aims: The aims of this study were to investigate the effects of vitamins A and D in HCT-116 Crl:NU(NCr)-Foxn1nu mouse xenographs. Also, to determine potential mechanisms of action using miRNA-seq and correlated these data with results from RNA-seq.Methods: HCT-116 colon cancer cells were cultured and used for the xenograph study. Crl:NU(NCr)-Male Foxn1nu mice were injected subcutaneously with HCT-116-cells (1 X 106 in 100 µl 50% Matrigel and Sterile PBS), and after 7 days, were treated with vitamin A and D in feed for 21 days. The mice were imaged on day 28, sacrificed and the tumors were excised and measured. RNA was isolated from the HCT-116 cells and tumors, and RNA-seq and miRNA-seq were performed.Results: There was a concentration-dependent reduction in the HCT-116 colon cancer cell viability after treatment with vitamin A and D combinations. In Crl:NU(NCr)-Foxn1nu mice injected with HCT-116 colon tumor cells, treatment with vitamin A (25,000 IU) and vitamin D (4,000 IU) or vitamin A (35,000 IU) and vitamin D (5,000 IU) for 21 days significantly reduced tumor growth by ~38% and ~58%, respectively (p < 0.001). In the HCT-116 cells and excised tumors, treatment upregulated the expression of Bim, Bax, p53, and PTEN, and downregulated AXIN2, ID2 and DDX20 mRNAs, all well-known pro-apoptotic proteins, tumor suppressors, and molecules involved in the epithelial-mesenchymal transition. Ingenuity Pathway Analysis of miRNA-seq paired with RNA-seq showed correlations between miRNAs expression and expression of these genes. For example, miRNA-mRNA correlation pairing showed that treatment downregulated miR-30c-3p and miR-125b-3p which was associated with upregulated TP53. Upregulation of the tumor suppressor PTEN was associated with the downregulation of eleven miRNAs, including oncogenic miR17 and miR21.Conclusion: The results suggest that the combinations of vitamins A and D reduced the HCT-116 tumor burden in mice and altered the expression of miRNAs directly associated with genes in the apoptosis, tumor suppression, and epithelial-mesenchymal transition pathways. The data supports the hypothesis that vitamin A and D combinations impact multiple cancer signaling pathways and thus may be more effective in the treatment and prevention of cancer, as well as reducing cancer metastasis. Keywords: apoptosis, cholcalciferol, colon cancer, DDX20, epithelial-mesenchymal transition, ergocalciferol, p53, RNA-seq, miRNA-seq, PTEN, synergism, transcriptome

Oral diseases are considered the most common noncommunicable diseases and are related to serious local and systemic disorders. Oral pathogens can grow and spread in the oral mucosae and frequently in biomaterials (e.g., dentures or prostheses) under polymicrobial biofilms, leading to several disorders such as dental caries and periodontal disease. Biofilms harbor a complex array of interacting microbes, increasingly unapproachable to antimicrobials and with dynamic processes key to disease pathogenicity, which partially explain the gradual loss of response towards conventional therapeutic regimens. New drugs (synthesized and natural) and other therapies that have revealed promising results for the treatment or control of these mixed biofilms are presented and discussed here. A structured search of bibliographic databases was applied to include recent research. There are several promising new approaches in the treatment of Candida spp.–Streptococcus mutans oral mixed biofilms that could be clinically applied in the near future. These findings confirm the importance of developing effective therapies for oral Candida–bacterial infections. C.F.R. would like to acknowledge the UID/EQU/00511/2019 Project—Laboratory of Process Engineering, Environment, Biotechnology and Energy (LEPABE), financed by national funds through FCT/MCTES (PIDDAC). N.M. would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020—Northern Regional Operational Program” (NORTE-01-0145-FEDER-000012).

Ocimum tenuiflorum (tulsi) is used traditionally in India for management of asthma, common cough, mild upper respiratory infection, and various metabolic and mental disorders. The pharmacological activities of tulsi are attributed to a wide range of phytochemical constituents present in the plant extracts. It is suggested that tulsi is beneficial in the treatment of both metabolic and neurological disorders. The review in this chapter summarizes the experimental research that supports the utilization of tulsi for the management of metabolic and mental stress. Based on the available animal experiments and clinical data, it is attempted to correlate these biological activities and their potential clinical implications. The discussion of the clinical implications may be beneficial in deciding alternative therapies for the control of metabolic and mental disorders.

Purified fractions from a Boswellia serrata Roxb. Ex. Colebr. (Burseraceae) extract (ETOH and DCM) contain biologically active compounds that are well known for having inflammation inhibitory properties. In this work, the purified fractions were tested in-vitro for LTCTo evaluate anti-inflammatory activities of bioactive compounds of Boswellia serrata purified fractions.In-vitro MTT assay was performed in HL-60 cell lines for measuring the toxicity/ viability of the cells. ELISA tests were performed for evaluating LTAA purified fraction of Boswellia serrata ETOH extracts reduced leukotriene-CThe present study describes that Boswellia serrata ethanolic extracts purified fraction (ETOH-BS) possess significant anti-inflammatory activities in HL-60 and in BALB/c and further supports for its use as Ayurvedic medicines traditionally in the treatment of lung disorders including allergy and asthma.

Integrated systems biology approaches suggest that combinations of nutrients may be more effective against cancer due to the large number of signaling pathways associated with cancer initiation and promotion. In a previous work, we have reported that combinations of vitamins A (as all trans-retinoic acid, ATRA), D2, and D3 act synergistically to induce apoptosis in colon and gastric cancer cells. In this work, we use whole-genome transcriptomic profiling to detect gene expression changes using RNA-seq to more comprehensively investigate the biological pathways affected by the combination of vitamin D2, D3 and ATRA. HCT-116 colon cancer cells were harvested, RNA was isolated and RNA-seq libraries were prepared using a Universal Plus mRNASeq kit. Sequencing was carried out on NovaSeq 6000. General quality-control metrics were obtained using FastQC and raw reads were aligned to human reference genome hg38 using STAR and BWA MEM. ENSEMBL genes were quantified using FeatureCounts, and differential expression statistics were computed using EdgeR. Specific gene expression was validated using qPCR. Transcriptomic analysis showed that of 26,313 genes analyzed, the expression of 8,402 genes was significantly altered (4030 up-regulated and 4373 down-regulated, FDR+1 and an FDR

The development of effective and less toxic antimicrobial agents is required for the treatment of respiratory tract infections. This study was carried out to evaluate the phytochemical and antibacterial activities of Anogeissus leiocarpus (DC.) (Guill. & Perr.) and Terminalia glaucescens (Planch. ex Benth.) against non-tuberculous mycobacteria species. The methanol, dichloromethane and aqueous extracts were screened against five (5) non-tuberculosis mycobacteria (NTM) species by agar diffusion method. Minimum inhibitory concentration (MIC) was determined by agar dilution method while bactericidal studies were done by viable count technique. The methanol and aqueous extracts were active against all the test organisms with zones of inhibition ranging from 10±0.0 to 25±0.5 mm. The MIC and MBC range from 0.3125 to 2.5 and 1.25 to 10 mg/mL, respectively. Bactericidal activities of aqueous extracts against Mycobacterium smegmatis ATCC 19420 revealed a drastic dose-dependent decline in the surviving population after 6 h of exposure accompanied by a total (100%) kill after 24 h of exposure. The antimicrobial activities demonstrated by these plants suggest the presence of therapeutically important antimycobacterial compounds and thus justify as well as support the use of these medicinal plants for the treatment of respiratory tract infections. Key words: Anogeissus leiocarpus (DC.) (Guill. & Perr.), Terminalia glaucescens (Planch. ex Benth.), antibacterial, nontuberculous mycobacteria species, bactericidal, in vitro.

In traditional Chinese medicine, Ganoderma (Ganodermataceae), a genus of medicinal mushrooms, has been employed as an herbal medicine for more than 2000 years. This chapter reviews some of the anticancer research published for Ganoderma, and its bioactive chemical constituents in detail. Of all the Ganoderma species only two, G. lucidum (W. Curtis: Fr.) P. Karst and G. sinense J.D. Zhao, L.W. Hsu, and X.Q. Zhang, have been extensively investigated. Both species contain polysaccharides and triterpenes and are reported to have antitumor effects in both cell culture and animal models. Overall, the scientific and medical literature suggests that G. lucidum extracts have an excellent potential in cancer therapy, but further clinical studies are needed to assure that the effects observed in animal studies are valid in humans. Other issues include quality control/assurance; however, new methodologies including chemometrics and biochemometrics may overcome these issues as they correlate chemistry with biological effects.

Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.

Icaritin, a prenylflavonoid isolated from Herbal Epimedii, is well known for its osteoplastic and anti-tumour activities. Here, we examined the cardioprotective actions of icaritin on cardiac H9c2 cells under oxidative stress conditions induced by treatment with tert-butylhydroperoxide (t-BHP). Icaritin at a concentration range between 1 and 4 µM effectively increased cell viability and decreased lactate dehydrogenase (LDH) leakage and reactive oxygen species (ROS) release in t-BHP treated cells, reflecting its ability to reduce t-BHP-induced cell injury. Icaritin also protected cell membrane integrity by preventing the collapse of the mitochondrial membrane potential. In addition, pretreatment of NF-E2-related factor 2 (Nrf2) siRNA and Akt inhibitor abolished the cardioprotective effect of icaritin. Furthermore, Nrf2 siRNA transfection interfered with the effect of icaritin on the inhibition of Ca2+ overload, whereas Akt inhibitor reduced icaritin-induced haemo-oxygenase-1 (HO-1) expression. Collectively, these results suggest that icaritin exerted its cardioprotective effect through the Akt/Nrf2/HO-1 and calcium signalling pathways.

Context: Pimenta dioica (L.) Merr. (Myrtaceae) is used in Costa Rican traditional medicine for women’s health. Our previous work showed that P. dioica extracts were oestrogenic. Objectives: This work identifies phytochemicals from P. dioica that are responsible for the plant’s oestrogen-like activities. Materials and methods: P. dioica leaves were collected in Costa Rica in 2005. Fractions resulting from chromatographic separation of a methanol extract were tested at 50 μg/mL in a competitive oestrogen receptor-binding assay. Active compounds were isolated by HPLC and identified by NMR and MS. Pure compounds were tested at 1 μM in the oestrogen-responsive SEAP reporter gene assay. The effects on cell viability, cytotoxicity and apoptosis were investigated in breast cancer (MCF-7 and SK-BR3) and gastric cancer (AGS and NCI-N87) cell lines using the ApoTox-Glo and Caspase-Glo assays and qPCR. Results: Quercitrin and three new chromones, including a 2-phenoxychromone, 6,8-di-C-methylcapillarisin (1) were isolated and identified. Compound 1 caused a 6.2-fold increase in SEAP expression at 1 μM (p

Sarcopenia is caused by the progressive loss of skeletal muscle mass (myopenia) and strength (dynapenia) over decades, and is a significant cause of frailty and disability in the elderly. However, sarcopenia has also been observed in younger patients, including those with inflammatory diseases, physical disabilities, malnutrition, and cachexia. Malnutrition and alterations in the muscle anabolic response to nutritional stimuli have been identified as potentially preventable factors that may significantly contribute to sarcopenia. Currently, resistance training and proper nutrition are the most important ways to prevent sarcopenia in the elderly; however, other nutritional interventions include supplementation with amino acids, creatine, protein powders, vitamin D3, and food supplements. Newer data suggest that dark fruit extracts and anthocyanins may also assist in muscle building by reducing myoblast apoptosis.

Over the past 20 years, Central America (CA) has made considerable progress in improving the health status of its populations. However, in some countries, the overall health status remains below average with poor outcomes concentrated geographically among the poor and Indigenous populations. Although Indigenous people make up the second largest population in CA, these populations have less access to healthcare, and funding for initiatives to improve maternal health is scarce. In many communities across CA, women continue to rely heavily on plant-based medicines for health and well-being, and yet there is a paucity of information regarding the safety and efficacy of these therapies. Sourced from available academic, governmental, and gray literature, in both English and Spanish, this chapter reviews maternal health issues among the Indigenous, Ladino, and other ethnic women of CA, evaluates the role of traditional medicine practices and their influence on maternal health outcomes, and reviews the existing scientific evidence supporting the use of traditional (i.e., plant-based) medicines for pregnancy-related health conditions.

Similar to their US counterparts, Costa Rican women enter menopause at ∼50 years of age, have similar symptoms, including hot flashes and night sweats, as well as an overall negative attitude toward the menopausal transition. One study of rural women in Monteverde reported that women knew little about the menopausal transition, as the subject was not discussed. Similar to other Latin American women, the use of hormone therapy by Costa Rican women is low and instead they use alternative therapies, including massage, dietary changes and herbal medicines. A wide variety of herbal therapies are used, and some of these herbs have estrogenic activities in vitro. However, clinical data on the safety and efficacy of any of these treatments is lacking. Recently, a disturbing increase in the incidence of human papilloma virus infections in menopausal women has been reported, due in part to more sexual freedom after menopause. Fortunately, the strain of HPV infecting these women is not associated with cervical cancer. Overall, there is a significant lack of scientific and medical research on menopausal women in Costa Rica. Considering the aging population, the high use of herbal medicines by menopausal women and the lack of clinical studies on these treatments, future research should focus on gaining a better understanding of menopause in this population. Furthermore, new educational programs for these women and the health professionals who serve them are necessary, as well as investigations of the safety and efficacy of the herbal supplements women use to manage their menopausal symptoms.

Allium ascalonicum Linn. and Gladiolus psittacinus Hook., are two important plants cultivated across the world for their nutritional as well as medicinal values. In the quest for a more natural bioactive substance to check the rising incidence of antimicrobial resistance amongst pathogens, these two plants were in this study, screened for activity against five common pathogens; namely, Staphylococcus aure- us ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 35657, and Candida albicans ATCC 90029. Phytochemical screening carried out on the extracts showed the presence of secondary metabolites like saponins, cardiac glycoside, alkaloids and flavonoids in both plant samples but only Allium ascalonicum yielded essential oil, while carbohydrate and tannins were detected in Gladiolus psittacinus. While the crude extracts of Gladiolus psittacinus did not show any inhibitory potential against any of the tested organisms, three pathogens were susceptible to Allium ascalonicum, with minimum inhibitory concentration (MIC) of 100 mg/mL. Bactericidal kinetics studies on the three pathogens showed that within the exposure time of 4 hours, the organisms were killed (69% and 95% at 2 × MIC and 4 × MIC, respectively) , a result which compared well with the positive control Gentamicin. The result of this study while agreeing with earlier reports on the non-activity of Gladiolus corms against Candida albicans contradicts the same report on the activity of the crude extract of this plant against Pseudomonas aeruginosa. The significant inhibitory potential of the crude methanolic extract of Alli- um ascalonicum against food borne pathogens such as Staphylococcus aureus, Escherichia coli and nosocomial pathogen such as Klebsiella pneumoniae, suggests that it can be explored as a natural alternative to chemical preservatives in food industries, and in the formulation of drugs against nosocomial infections .

Background: Vitamin D was first hypothesized to play a role in cancer chemoprevention in 1980 when it was observed that there was a higher rate of colon cancer in the Northern USA as compared with populations living in the South. While cholecalciferol (vitamin D3) has been tested in many cancer-cell lines, published results for ergocalciferol (vitamin D2) are lacking for most epithelial cell cancers, and combination studies of both D2 and D3 and vitamin A (retinoic acid) are lacking in general. The goal of the study was to investigate the effects of vitamins D2, D3, and A, alone and in combination on the growth of all gastric and colon cancer cell lines in vitro. Methods: Colon (SW480 and HCT-116) and gastric (AGS and NCI-N87) cell lines were treated with varying concentrations of D2, D3 and all-trans retinoic acid (ATRA) and combinations thereof. Cell viability and cytotoxicity were measured using the CellTiter-Glo® 2.0 assay, while caspase activities and cytotoxicity were determined using the Caspase-Glo® 3/7, Caspase 8, ApoTox-Glo™ Triplex assays. Autophagy was determined using the CYTO-ID® Autophagy Detection Kit 2.0. Gene expression studies were performed using qPCR. Results: Both vitamin D2 and D3 inhibited the growth of all cell lines tested, with IC 50 ranging from 19-56 μM. However, when combined (1:1), the IC 50 for the combination of D2 and D3 was significantly reduced to a range of 5-6.0 μM indicating synergism. ATRA also inhibited the growth of all cell lines tested with an IC 50 range of 2.6 to 5.6 μM. When ATRA was combined with D2 and D3, the IC 50 s were significantly reduced to 0.65 to 1.4 μM, further indicating synergistic effects. In the gastric and colon cancer cell lines, the combination induced apoptosis via caspase 3/7 and 8, increased the Bax/Bcl-2 ratio, while in the SW480 colon cancer line, the combination also induced autophagy. Conclusion: Our data demonstrated that vitamins D2, D3 and ATRA inhibit the proliferation of colon and gastric cancer cells. The combinations of D2+D3 or ATRA+D2+D3 had synergistic effects or additive effects on all cell lines tested, increased Bax expression and the Bax/Bcl-2 ratio, and increased caspase 3/7 and 8 activities to favor apoptosis. In SW480 colon cancer cells the combination also induced autophagy. This data suggest that combinations of vitamins A and D have synergistic effects in colon and gastric cancers, and considering the potential clinical implications, further research is justified. Key words: apoptosis, autophagy cholcalciferol, ergocalciferol, gastric cancer, colon cancer, caspase, synergism

Osteoporosis and osteopenia impact more than 54 million Americans, resulting in significant morbidity and mortality. Alterations in bone remodeling are the hallmarks for osteoporosis, and thus the development of novel treatments that will prevent or treat bone diseases would be clinically significant, and improve the quality of life for these patients. Bone remodeling involves the removal of old bone by osteoclasts and the formation of new bone by osteoblasts. This process is tightly coupled, and is essential for the maintenance of bone strength and integrity. Since the osteoclast is the only cell capable of bone resorption, the development of drugs to treat bone disorders has primarily focused on reducing osteoclast differentiation, maturation, and bone resorption mechanisms, and there are few treatments that actually increase bone formation. Evidence from observational, experimental, and clinical studies demonstrate a positive link between naturally occurring compounds and improved indices of bone health. While many natural extracts and compounds are reported to have beneficial effects on bone, only resveratrol, sulforaphane, specific phenolic acids and anthocyanins, have been shown to both increase bone formation and reduce resorption through their effects on the bone epigenome. Each of these compounds alters specific aspects of the bone epigenome to improve osteoblast differentiation, reduce osteoblast apoptosis, improve bone mineralization, and reduce osteoclast differentiation and function. This review focuses on these specific natural compounds and their epigenetic regulation of bone remodeling.

The purpose of this chapter is to review some of the most common drug interactions with food and beverages. By acting on gastric motility, pH, and drug metabolism, food and beverages can have a variety of effects on the absorption and metabolism of prescription drugs, as well as vitamins and minerals. The clinical significance of these interactions ranges from mild to moderate concern to the possibility of significant reductions in drug action, as is seen with garlic and saquinavir, or an increase in serious adverse events, as is seen with cranberry and warfarin. For interactions that affect drug metabolism through cytochrome P450 isoenzymes such as grapefruit juice, there is wide variability from one patient to another and the risk of dangerous interactions may present in only a few. With the advent of pharmacogenomics, our understanding and perhaps profiling of patients for the gene expression of metabolic enzymes may identify patients most at risk for both beverage–drug and drug–drug interactions.

Tuberculosis is a highly infectious disease declared a global health emergency by the World Health Organization, with approximately one third of the world's population being latently infected with Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation phase. Unfortunately, the appearance of multi drug-resistant tuberculosis, mainly due to low adherence to prescribed therapies or inefficient healthcare structures, requires at least 20 months of treatment with second-line, more toxic and less efficient drugs, i.e., capreomycin, kanamycin, amikacin and fluoroquinolones. Therefore, there exists an urgent need for discovery and development of new drugs to reduce the global burden of this disease, including the multi-drug-resistant tuberculosis. To this end, many plant species, as well as marine organisms and fungi have been and continue to be used in various traditional healing systems around the world to treat tuberculosis, thus representing a nearly unlimited source of active ingredients. Besides their antimycobacterial activity, natural products can be useful in adjuvant therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their adverse effects and to reverse mycobacterial multi-drug resistance due to the genetic plasticity and environmental adaptability of Mycobacterium. However, even if some natural products have still been investigated in preclinical and clinical studies, the validation of their efficacy and safety as antituberculosis agents is far from being reached, and, therefore, according to an evidence-based approach, more high-level randomized clinical trials are urgently needed.

Disclosures None. SUMMARY Background and Aims: The use of herbs and dietary supplements (HDS) alone or concomitantly with medications can potentially increase the risk of adverse events experienced by the patients. This review aims to evaluate the documented HDS-drug interactions and contraindications. Methods: A structured literature review was conducted on PubMed, EMBASE, Cochrane Library, tertiary literature and Internet. Results: While 85 primary literatures, six books and two web sites were reviewed for a total of 1,491 unique pairs of HDS-drug interactions, 213 HDS entities and 509 medications were involved. HDS products containing St. John’s Wort, magnesium, calcium, iron, ginkgo had the greatest number of documented interactions with medications. Warfarin, insulin, aspirin, digoxin, and ticlopidine had the greatest number of reported interactions with HDS. Medications affecting the central nervous system or cardiovascular system had more documented interactions with HDS. Of the 882 HDS-drug interactions being described its mechanism and severity, 42.3% were due to altered pharmacokinetics and 240 were described as major interactions. Of the 152 identified HDS contraindications, the most frequent involved gastrointestinal (16.4%), neurological (14.5%), and renal ⁄ genitourinary diseases (12.5%). Flaxseed, echinacea, and yohimbe had the largest number of documented contraindications. Conclusions: Although HDSdrug interactions and contraindications primarily concerned a relatively small subset of commonly used medications and HDS entities, this review provides the summary to identify patients, HDS products, and medications that are more susceptible to HDS-drug interactions and contraindications. The findings would facilitate the health-care professionals to communicate these documented interactions and contraindications to their patients and ⁄ or caregivers thereby preventing serious adverse events and improving desired therapeutic outcomes.

Helicobacter pylori is a Gram-negative bacillus that is associated with the development of gastritis and peptic ulcer disease (PUD). In Nigeria, leaf extracts of Eucalyptus torelliana F. Muell. are used in traditional medicine to treat PUD and other gastrointestinal ailments. The additive and synergistic effects of E. torelliana leaf extracts, in combination with clarithromycin, were investigated using two types of H. pylori strains (ATCC 43629, ATCC 43579) and four clinical isolates of H. pylori (Ed, A2, G1-1, 5514) in the checkerboard assay and the fractional inhibitory concentration (FIC) index. A time-kill study was also performed on the strain ATCC 43579. The results showed that the E. torelliana extract inhibited the growth of all H. pylori strains, and the addition of one of the isolated active compounds, namely compound 2 (a substituted pyrenyl ester) enhanced the activity of clarithromycin. The minimum inhibitory concentration values of clarithromycin and the botanical compound were reduced twofold (from 0.125 to 0.0625 µg/mL and > 100 to 50 µg/mL respectively). A 100% reduction in CFU/mL of H. pylori ATCC 43579 was observed with the combination of 0.25 µg/mL clarithromycin and 100 µg/mL and 200 µg/mL compound 2 after 3 h of exposure. The results of the investigation showed that the combination of botanical compounds and antibiotics may be beneficial in the treatment of H. pylori infections.

Eucalyptus camaldulensis Dehnh. (Myrtaceae) and Eucalyptus torelliana F. Muell are used in Nigerian traditional medicine for the treatment of cough associated with tuberculosis (TB) and other respiratory infections.Hexane, chloroform, methanol extracts, and isolated compounds of E. camaldulensis and E. torelliana were screened for activity against Mycobacterium tuberculosis H37Rv (MtbH37Rv) to authenticate the traditional use of these plants.The microplate alamar blue assay (MABA) method was used to investigate the anti-M. tuberculosis activities. Bioassay-guided fractionation of the hexane extract of E. torelliana leaf was performed, and isolated compounds were characterized by MS, 1D- and 2D-NMR.The extracts inhibited the growth of MtbH37Rv [minimum inhibitory concentration (MIC) 4-64 µg/mL]. Spectroscopic characterization led to the identification of two compounds, hydroxymyristic acid methylester (1) and a substituted pyrenyl ester, a sterol (2). Compounds 1 and 2 had MIC of 49.45 and 46.99 µg/mL; IC(50)100 and 38.21 µg/mL; selectivity index (SI)2.02 and 0.81, respectively, and a minimum bactericidal concentration (MBC) of 62.50 µg/mL.The anti-TB activities of these plants on M. tuberculosis H37Rv support their use in traditional medicine for the treatment of coughs associated with TB and reveals the presence of anti-Mtb active compounds in the plants. These findings not only demonstrate a new potential area of therapeutic value of E. camaldulensis and E. torelliana, but also illustrate the role of esters as anti-Mtb active principles in ethnobotanical preparations and as lead compounds in the development of new and effective anti-Mtb drugs.

The Dietary Supplements Information Expert Committee (DSI-EC) of the United States Pharmacopeial Convention (USP) reviews the safety of dietary supplements and dietary supplement ingredients for the purpose of determining whether they should be admitted as quality monographs into the United States Pharmacopeia and National Formulary (USP-NF). The United States Food and Drug Administration (FDA) has enforcement authority to pursue a misbranding action in those instances where a dietary supplement product indicates that it conforms to USP standards but fails to so conform. Recently DSI-EC undertook a safety evaluation of spirulina, a widely used dietary ingredient. DSI-EC reviewed information from human clinical trials, animal studies, and regulatory and pharmacopeial sources and analyzed 31 adverse event reports regarding spirulina to assess potential health concerns. At the conclusion of this review, DSI-EC assigned a Class A safety rating for Spirulina maxima and S. platensis, thereby permitting the admission of quality monographs for these dietary supplement ingredients in USP-NF. DSI-EC continually monitors reports concerning the safety of dietary supplements and dietary supplement ingredients for which USP dietary supplement monographs are developed. The DSI-EC may revisit the safety classification of spirulina as new information on this dietary ingredient becomes available.