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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: To evaluate 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 8 weeks 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

Green tea [Camellia sinensis (L.) Kuntze] is the fourth most commonly used dietary supplement in the US. Recently, regulatory agencies in France and Spain suspended market authorization of a weight-loss product containing green tea extract because of hepatotoxicity concerns. This was followed by publication of adverse event case reports involving green tea products. In response, the US Pharmacopeia (USP) Dietary Supplement Information Expert Committee (DSI EC) systematically reviewed the safety information for green tea products in order to re-evaluate the current safety class to which these products are assigned. DSI EC searched PubMed (January 1966-June 2007) and EMBASE (January 1988-June 2007) for clinical case reports and animal pharmacological or toxicological information. Reports were also obtained from a diverse range of other sources, including published reviews, the US FDA MedWatch programme, USP's MEDMARX adverse event reporting system, the Australian Therapeutic Goods Administration, the UK Medicines and Healthcare products Regulatory Agency, and Health Canada's Canadian Adverse Drug Reaction Monitoring Program. Case reports pertaining to liver damage were evaluated according to the Naranjo causality algorithm scale. In addition, the Committee analysed information concerning historical use, regulatory status, and current extent of use of green tea products. A total of 216 case reports on green tea products were analysed, including 34 reports concerning liver damage. Twenty-seven reports pertaining to liver damage were categorized as possible causality and seven as probable causality. Clinical pharmacokinetic and animal toxicological information indicated that consumption of green tea concentrated extracts on an empty stomach is more likely to lead to adverse effects than consumption in the fed state. Based on this safety review, the DSI EC determined that when dietary supplement products containing green tea extracts are used and formulated appropriately the Committee is unaware of significant safety issues that would prohibit monograph development, provided a caution statement is included in the labelling section. Following this decision, USP's DSI ECs may develop monographs for green tea extracts, and USP may offer its verification programmes related to that dietary ingredient. [ABSTRACT FROM AUTHOR]

The present study explored symptoms, attitudes and treatments surrounding women's health and menopause among the Q'eqchi Maya of the eastern tropical lowlands of Guatemala. Data were obtained through participant observation, semi-structured interviews, focus groups and plant walks with 50 Q'eqchi community members from the state of Izabal, Municipality of Livingston, including five midwives, five traditional male healers and eight postmenopausal women. Results indicate that the Q'eqchi Maya of Livingston possess their own cultural perceptions of women's health which affect attitudes, symptoms and treatment choices during the menopausal transition. Since discussions of menstruation and menopause are considered cultural taboos among the Q'eqchi, many women mentioned experiencing excessive preoccupation when unanticipated and unfamiliar symptoms occurred. Furthermore, many women suffered from additional hardship when their spouse misinterpreted menopausal symptoms (vaginal dryness, sexual disinterest) as infidelity. Seven of the eight postmenopausal women interviewed indicated experiencing one or more symptoms during the menopausal transition, including headaches, anxiety, muscular pain, depression, and hot flashes. These results differ from the lack of symptomatology reported in previous studies in Mexico, but are in line with the result of menopausal research conducted among other Maya groups from the highlands of Guatemala. Although the Q'eqchi did not use a specific term for 'hot flash', three Q'eqchi women used the expression 'baja presion' or a 'lowering of blood pressure' to explain symptoms of profuse sweating followed by chills, heart palpitations, and emotional instability. The Q'eqchi Maya mentioned a number of herbal remedies to treat menopausal symptoms. Further research on these botanical treatments is needed in order to ascertain their safety and efficacy for continued use. [ABSTRACT FROM AUTHOR]

Results from clinical trials demonstrate that standardized leaf extracts of Ginkgo biloba (SGB extract) reduce the symptoms of age-associated memory impairment and dementia, including Alzheimer's disease, and may be of benefit in treating intermittent claudication. In addition, preliminary results suggest that SGB extract may be useful in preventing and treating cardiovascular disease (CVD), particularly ischemic cardiac syndrome. Since many patients with cardiovascular disease are already taking anticoagulants and antiplatelet drugs, self-medication with SGB extract is not recommended without the advice of their physician. Although SGB extracts look promising for preventing and treating CVD, well-controlled clinical trials are needed before clinical recommendations can be made. Copyright © 2002 by Aspen Publishers, Inc. [ABSTRACT FROM AUTHOR]

Investigation on the medical ethnobotany of the Q'eqchi Maya of Livingston, Izabal, Guatemala, was undertaken in order to explore Q'eqchi perceptions, attitudes, and treatment choices related to women's health. Through participant observation and interviews a total of 48 medicinal plants used to treat conditions related to pregnancy, childbirth, menstruation, and menopause were collected and identified followed by the evaluation of 20 species in bioassays relevant to women's health. Results of field interviews indicate that Q'eqchi cultural perceptions affect women's health experiences while laboratory results (estrogen receptor and serotonin receptor binding assays) provide a scientific correlation between empirical medicinal plant use among the Q'eqchi and the pharmacological basis for their administration. These data can contribute to Guatemala's national effort to promote a complementary relationship between traditional Maya medicine and public health services and can serve as a basis for further pharmacology and phytochemistry on Q'eqchi medicinal plants for the treatment of women's health conditions. [ABSTRACT FROM AUTHOR]

Background: Unlike plant phytochemicals, little has been done to explore the metabolites from phyllosphere bacterial flora, some of which enabled them to survive interspecific competition through amensalism. This study evaluated the antimicrobial activity of metabolites from Phyllospheric Bacteria (PB) isolated from Funtumia elastica (FE), against selected bacterial and fungal pathogens. Phenotypic and molecular methods were used to identify the isolated phyllo-microbiota., Methods: The PB were aseptically isolated by sonication. Their metabolites were obtained from the fresh overnight culture of the organisms. The cell-free supernatants containing the metabolites were used for antimicrobial assays against the pathogens. The DNA of the bacterial isolates were isolated using a NIMR-BIOTECH DNA extraction kit, while their 16S rRNA was amplified with the primer: 799F 5'-AACACGGATTA GATACC-3', 1193R 5'- ACGTCATCCCCACCTTCC-3', using SolisFast* Master Mix, (Solis Biodyne-Estonia). The BLAST of the sequence was done from the NCBI Gen-bank. The PB strains identified were submitted to NCBI and accession numbers were assigned to them., Results: The phyllosphere of FE yielded 21 bacterial isolates: 7 Gram-positives and 14 Gram-negatives. The metabolites from these isolates showed varying degrees of bioactivity against Staphylococcus aureus (ATCC29213), Escherichia coli (ATCC 25922) Klebsiella pneumoniae (ATCC 35659); Trychophyton rubrum , Candida albicans and Microsporum canis. Fifteen bioactive isolates sequenced yielded four genera, Enterobacter ( E. hormaechei 98.44%), Bacillus ( B. cereus 100%), Pontoea ( P. dispersa 99.72%), Staphylococcus ( S. arlettae 99.72%)., Conclusion: Bacteria from FE phyllosphere, produced metabolites antagonistic ( cidal ) to some human pathogens. This has great potential for possible drug discovery., (Copyright© 2024 Avicenna Research Institute.)

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 in vitro . Phloroglucinols have been shown to be effective against viruses, such as human immunodeficiency virus (HIV), herpes or enterovirus, and preliminary data through docking analysis suggest that they can be effective against SARS-CoV-19. Also, some phloroglucinols derivatives have shown antibacterial effects against diverse bacteria strains, including Bacillus subtilis and Staphylococcus aureus , and (semi)synthetic development of novel compounds have led to phloroglucinols with a significantly increased biological activity. However, therapeutic use of these compounds is hindered by the absence of in vivo studies and scarcity of information on their mechanisms of action, and hence further research efforts are required. On the basis of this consideration, our work aims to gather data regarding the efficacy of natural-occurring and synthetic phloroglucinol derivatives as antiviral and antibacterial agents against human pathogens, which have been published during the last three decades. The recollection of results reported in this review represents a valuable source of updated information that will potentially help researchers in the development of novel antimicrobial agents.

High-throughput RNA-sequencing can determine the impact of nutrients and their combinations on gene transcription levels in osteocytes, and clarify the biological pathways associated with their impact on bone tissues. Previously, we reported that resveratrol (RES) and peonidin-3- O -glucoside (POG) increased osteoblastogenesis, as well as reduced osteoclastogenesis in transgenic teleost fish models. Here, we perform whole-genome transcriptomic profiling of osteoblasts treated with POG or RES to provide a comprehensive understanding of alterations in gene expression and the molecular mechanisms involved. Cultured human fetal osteoblastic hFOB 1.19 cells were treated with the test compounds, and then RNA was used to prepare RNA-seq libraries, that were sequenced using a NovaSeq 6000. Treatment with POG or RES increased osteoblast proliferation and reduced apoptosis. Transcriptomic profiling showed that of the 29,762 genes investigated, 3177 were differentially expressed (1481 upregulated, 1696 downregulated, FDR ≤ 0.05) in POG-treated osteoblasts. In the RES-treated osteoblasts, 2288 genes were differentially expressed (DGEs, 1068 upregulated, 1220 downregulated, FDR ≤ 0.05). Ingenuity ® Pathway Analysis (IPA) of DGEs from RES or POG-treated osteoblasts revealed significant downregulation of the apoptosis, osteoarthritis and HIF1α canonical pathways, and a significant reduction in Rankl mRNA expression. The data suggest that RES and POG have both anabolic and anticlastogenic effects.

Like China, Mexico has a traditional system of medicine dating back almost 5000 years that incorporates the healing practices of pre-Columbian civilizations, including the Maya and Aztec. Mexican Traditional Medicine (MTM) women depend on MTM practices and herbal medicines for their primary healthcare needs as limited access and high costs of Western medicine is a significant problem. The aims of this work were to determine the medicinal plants more commonly used in MTM for women's reproductive health issues and assess the clinical data supporting their use. Data from multiple sources was compiled and information on plants commonly used by women in Mexico MTM for the treatment of fertility and menstruation issues, pregnancy, and menopause was analyzed. Analysis of the data show that 185 species of plants representing > 60 families were used for a wide range of reproductive health issues. Some of these plants have been used in MTM for fertility regulation in women of which 35 species were used as emmenagogues and abortifacients. Approximate 40 species were used for the symptoms of premenstrual syndrome, heavy menstrual bleeding, and dysmenorrhea. In terms of pregnancy, 35 species were used for postpartum care and to facilitate breastfeeding, 16 species were used as oxytocic agents to induce labor and speed birth, and six plant species were used to prevent miscarriage. Fourteen plant species were reported to treat infertility or promote fertility, and seven species were used to treat uterine prolapse. Three plants species were reported to treat menopause and two plants were used for osteoporosis. Analysis of the clinical data for commonly used medicinal plants showed some clinical support for the use of these plants in MTM. In Mexico, women use medicinal plants for almost every aspect of reproductive health. While some plants have clinical data, most medicinal plants used in MTM have no safety or efficacy data available and could serve as the basis of future investigations., (© 2023. The Author(s).)

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., (© 2021 John Wiley & Sons Ltd.)

The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For example, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided., Competing Interests: The authors declare that the paper was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ayatollahi, Sharifi-Rad, Tsouh Fokou, Mahady, Ansar Rasul Suleria, Krishna Kapuganti, Gadhave, Giri, Garg, Sharma, Ribeiro, Rodrigues, Reiner, Taheri and Cruz-Martins.)

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 LTC 4 , LTA 4 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 LTA 4 , LTC 4 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-C 4 -synthase activity by 52%, leuktotriene-A 4 -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 <0.01) reduction in OVA induced lung inflammation in BALB/c mice as observed by imaging tomography. Treatment of the OVA challenged mice with standard drug dexamethasone (DXA) reduced inflammation by ~66% with significant value (P<0.0001)., 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright © 2020. Published by Elsevier Inc.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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 < 0.05). This activity was blocked by the ER antagonist ICI 182,780. Compound 2 caused a 6.0-fold increase in SEAP, inhibited the growth of MCF-7, AGS and NCI-N87 cells (IC 50 54.27, 38.13 and 51.22 μg/mL, respectively), and induced apoptosis via caspase 8 and increased the Bax/Bcl-2 mRNA ratio in MCF-7 cells. Compound 3 was anti-oestrogenic in MCF-7 cells., Discussion and Conclusions: Compounds from P. dioica have oestrogenic, anti-oestrogenic and cytotoxic effects that may explain the ethnomedical use of this plant.

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., Competing Interests: The authors declare no conflict of interest.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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 20months 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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause., Methods: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using flow cytometry. In vitro, the effects of AST on cultured GCs were investigated using the MTT proliferation assay and western blot assays., Results: Aged rats had significantly higher GC apoptosis as compared with young female rats. Treatment of aged rats with AST (all three doses; p < 0.01) or Progynova (p < 0.01) significantly reduced GC apoptosis as compared with the aged controls. The proportions of total apoptotic GCs was 25.70%, 86.65%, 47.04%, 27.02%, 42.09% and 56.42% in the normal, aged, 17β-estradiol (E₂), high dose AST, medium dose AST, and low dose AST-treated groups, respectively. Significant increases of serum E₂ and P₄ levels, as well as altered levels of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. In cultured rat GCs, AST stimulated GC proliferation, E₂ and progesterone (P₄) secretion, reduced apoptosis, reduced the level of the pro-apoptotic protein Bcl-2 (p < 0.01), but had no effect on BAX., Conclusions: AST enhanced ovarian function in aged female rats by increasing E₂ and P₄ levels, and reducing ovarian GC apoptosis via a mechanism involving Bcl-2. These data demonstrate a new pharmacological activity for AST, as well as a novel mechanism of action, and further suggest that AST may be a new therapeutic agent for the management of menopausal symptoms.

Ethnopharmacological Relevance: In Central America, most Maya women use ethnomedicines for all aspects of their reproductive cycle including menstruation, pregnancy and menopause. However, very few of these plants have been documented, collected and tested in appropriate pharmacological assays to determine possible safety and efficacy. The aim of this work was to provide an overview of information on the ethnomedical uses, ethnopharmacology, chemistry and pharmacological research for medicinal plants used for women's reproductive health in Guatemala, with a special emphasis on the Q'eqchi Maya of the Lake Izabal region, to demonstrate therapeutic potential and support future research in the field., Materials and Methods: Reviews of the ethnobotanical, ethnomedical and ethnopharmacological literature were performed for 30 plants collected in the Lake Izabal region of Guatemala and used by the Q'eqchi Maya for treatment of reproductive health issues were performed up to and including July 2015 using multiple databases, library searches for abstracts, books, dissertations, and websites., Results and Conclusions: Review of the published research confirms that many of the plants used by Q'eqchi Maya women for the management of reproductive health issues have pharmacological activities, including analgesic, anti-inflammatory, estrogenic, progestagenic and/or serotonergic effects, that support the use of these plants and provide plausible mechanisms of action for their traditional uses. Furthermore, a new serotonin agonist, 9, 10-methylenedioxy-5, 6-Z-fadyenolide was isolated, thereby demonstrating an untapped potential for drug discovery. However, to date much of the pharmacological assays have been in vitro only, and few in vivo studies have been performed. Considering the large percentage of the Maya population in Guatemala that use traditional medicines, there remains a significant lack of pharmacological and toxicological data for these plants. Future research should focus on the safety and efficacy of medicinal plants using in vivo preclinical studies and clinical trials, as well as chemical analysis. Since medicinal plants from the Piperaceae are most commonly used as traditional medicines by the Q'eqchi Maya women, and new bioactive compounds have been identified from Piper species, investigations of commonly used plants from this family would be an appropriate place to start. Data generated from such studies would contribute to Guatemala's national effort to promote a complementary relationship between traditional Maya medicine and public health services., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The effect of Menoprogen (MPG) on ovarian granulosa cell (GC) apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma E2 levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM) analysis of isolated GCs from MPG-treated aged rats showed reductions in the G0/G1 ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases E2 production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms.

Objective: Menoprogen (MPG), a traditional Chinese medicine formula for menopause, improves menopausal symptoms; however, its mechanism remains unknown. Previous studies have shown that MPG is not directly estrogenic; thus, the goal of this study was to investigate the effects of MPG on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) levels in an aged female rat model of menopause., Methods: In a six-arm study, 14-month-old female Sprague-Dawley rats (n = 8 per arm) were randomly divided into the following groups: untreated aged, 17β-estradiol-treated aged (estradiol [E2]), and three arms with increasing doses of MPG (162, 324, or 648 mg/kg/d). The sixth arm contained 4-month-old female Sprague-Dawley rats as a normal comparison group. Four weeks after MPG or E2 administration, animals were killed after blood draws, and ovarian tissues were excised. Levels of E2 and progesterone (P4) were determined by radioimmunoassay. Serum and ovarian tissue levels of IGF-1, IGFBP-1, and IGF-1 receptor were determined by enzyme-linked immunosorbent assay., Results: Compared with the normal group, aged rats had significantly reduced serum levels of E2, P4, and IGF-1, and increased serum and ovarian tissue levels of IGFBP-1. MPG restored serum IGF-1 and IGFBP-1 levels and down-regulated ovarian levels of IGFBP-1, which were closely related to increases in E2 and P4 levels in aged rats. No significant differences in either IGF-1 or IGFBP-1 were observed between the three doses of MPG., Conclusions: MPG exerts a direct in vivo effect on aged female rats by positively regulating serum and ovarian IGF-1 and IGFBP-1 levels.

Background: The risks attributed to drug-herb interactions, even when known, are often ignored or underestimated, especially for those involving anti-clotting drugs and Chinese medicines. The aim of this study was to structurally search and evaluate the existing evidence-based data associated with potential drug interactions between anticoagulant/antiplatelet drugs and Chinese herbal medicines (CHMs) and evaluate the documented mechanisms, consequences, and/or severity of interactions., Methodology and Findings: Information related to anticoagulant/antiplatelet drug-CHM interactions was retrieved from eight interaction-based textbooks, four web resources and available primary biomedical literature. The primary literature searches were conducted in English and/or Chinese from January 2000 through December 2011 using the secondary databases (e.g., PubMed, Airiti Library, China Journal full-text database). The search terms included the corresponding medical subject headings and key words. Herbs or natural products not used as a single entity CHM or in Chinese Medicinal Prescriptions were excluded from further review. The corresponding mechanisms and severity ratings of interactions were retrieved using MicroMedex®, Lexicomp® and Natural Medicines Comprehensive Database®. Finally, we found 90 single entity CHMs contributed to 306 documented drug-CHM interactions. A total of 194 (63.4%) interactions were verified for its evidence describing possible mechanisms and severity. Of them, 155 interactions (79.9%) were attributable to pharmacodynamic interactions, and almost all were rated as moderate to severe interactions. The major consequences of these interactions were increased bleeding risks due to the additive anticoagulant or antiplatelet effects of the CHMs, specifically danshen, dong quai, ginger, ginkgo, licorice, and turmeric., Conclusions/significance: Conventional anticoagulants and antiplatelet drugs were documented to have harmful interactions with some commonly used single entity CHMs. For those patients who are taking conventional anti-clotting medications with CHMs for cardiovascular or cerebrovascular diseases, the potential risks of increased bleeding due to drug-CHM interactions should not be ignored.

The botanical status in EU, USA, and Thailand is different owing to the regulatory status, the progress of science, and the influence of culture and society. In the EU, botanicals are positioned as herbal medicinal products and food supplements, in the US they are regulated as dietary supplements but often used as traditional medicines, and in Thailand, they are regulated and used as traditional medicines. Information for some of the most popular botanicals from each country is included in this review.

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 HDS-drug 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., (© 2012 Blackwell Publishing Ltd.)

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., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Astragali Radix has been used widely for the treatment of cardiovascular and cerebrovascular diseases, and to enhance endurance and stamina in traditional Chinese medicine (TCM) for over 2000 years. The polysaccharide constituents of Astragali Radix (ARP) are considered as one of the major constituents contributing to the multiple pharmacological effects of this medicinal plant. The purpose of the study is to evaluate the vascular regenerative activities of ARPs in a chemically-induced blood vessel loss model in zebrafish., Methods: Blood vessel loss was induced in both Tg(fli-1a:EGFP)y1 and Tg(fli-1a:nEGFP)y7 embryos by administration of 300 nM VEGFR tyrosine kinase inhibitor II (VRI) for 3 h at 24 hpf (hour post-fertilization). Then, the blood vessel damaged zebrafish were treated with ARPs for 21 h and 45 h after VRI withdrawal. Morphological changes in intersegmental vessels (ISVs) of zebrafish larvae were observed under the fluorescence microscope and measured quantitatively. The rescue effect of ARPs in the zebrafish models was validated by measuring the relative mRNA expressions of Kdrl, Kdr and Flt-1 using real-time PCR., Results: Two polysaccharide fractions, P4 (50000 D < molecular weight & diameter < 0.1 μm) and P5 (molecular diameter > 0.1 μm), isolated from Astragali Radix by ultrafiltration, produced a significant and dose-dependent recovery in VRI-induced blood vessel loss in zebrafish. Furthermore, the down-regulation of Flk-1 and Flt-1 mRNA expression induced by VRI was reversed by treatment with P4., Conclusion: The present study demonstrates that P4 isolated from Astragali Radix reduces VRI-induced blood vessel loss in zebrafish. These findings support the hypothesis that polysaccharides are one of the active constituents in Astragali Radix, contributing to its beneficial effect on treatment of diseases associated with a deficiency in angiogenesis.

Context: 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., Objective: 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., Materials and Methods: 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., Results: 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., Discussion and Conclusions: 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.

Flavonoids isolated from Herba Epimedii such as icaritin, icariin and epimedin C have been suggested as potential bone anabolic compounds. However, the "specific localized effects" of these flavonoids in bone, in vivo, and the metabolism of these flavonoids in zebrafish larvae have never been demonstrated. In this study, we used multiple methods including in vivo imaging, drug metabolites profiling, transcriptomic and proteomic approaches to determine the mechanisms involved in the distribution and metabolism of the flavonoids in zebrafish larvae by measuring the fluorescence emission, in vivo, of icaritin and its glycoside derivatives. The fluorescence emission mechanism of icaritin in vitro was identified by spectrophotometric analysis, and the fluorescent property of icaritin was used as a probe to visualize the metabolism and distribution of icaritin and its glycoside derivatives in zebrafish larvae. Phase I and phase II metabolism of icaritin and its derivatives were identified in zebrafish by mass spectrometry. The combined transcriptomics and proteomics demonstrate a high degree of conservation of phase I and phase II drug metabolic enzymes between zebrafish larvae and mammals. Icaritin and its glycoside derivatives were demonstrated using combined approaches of in vivo imaging, drug metabolites identification, and transcriptomic and proteomic profiling to illustrate phase I and phase II metabolism of the flavonoids and their distribution in bone of zebrafish larvae. This study provides a new methodological model for use of the zebrafish larvae to examine drug metabolism.