Mulberry leaves and their potential effects against cardiometabolic risks: a review of chemical compositions,biological properties and clinical efficacy

Context: Cardiometabolic risks are regarded as the crucial factors associated with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Regarding an increased attention to medicinal plants in the current healthcare system, the effects of mulberry (Morus spp., Moraceae) leaves on cardiometabolic risks have been consecutively considered in scientific research.

Objective: The present review compiles and summarizes the chemical compositions, biological properties and clinical efficacy of mulberry leaves that are related to the amelioration of cardiometabolic risks.

Methods: Published English literature from the PubMed, Science Direct and Google Scholar databases was searched by using ‘mulberry leaves’ ‘Morus spp.’, ‘hyperglycemia’, ‘hyperlipidemia’, ‘obesity’, ‘hypertension’, ‘oxidative stress’, ‘atherosclerosis’ and ‘cardiovascular diseases’ as the keywords. The relevant articles published over the past two decades were identified and reviewed.

Results: Mulberry leaves contain numerous chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the prominent functional compounds. Preclinical and clinical studies showed that mulberry leaves possessed various beneficial effects against cardiometabolic risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity, antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and cardioprotective effects.

Conclusions: Mulberry leaves could be a promising therapeutic option for modulating cardiometabolic risks. However, further investigations should be performed to substantiate the potential of mulberry leaves in practical uses.     

The anti-inflammatory activity of licorice,a widely used Chinese herb

Context: Increasing incidence and impact of inflammatory diseases have encouraged the search of new pharmacological strategies to face them. Licorice has been used to treat inflammatory diseases since ancient times in China.

Objective: To summarize the current knowledge on anti-inflammatory properties and mechanisms of compounds isolated from licorice, to introduce the traditional use, modern clinical trials and officially approved drugs, to evaluate the safety and to obtain new insights for further research of licorice.

Methods: PubMed, Web of Science, Science Direct and ResearchGate were information sources for the search terms ‘licorice’, ‘licorice metabolites’, ‘anti-inflammatory’, ‘triterpenoids’, ‘flavonoids’ and their combinations, mainly from year 2010 to 2016 without language restriction. Studies were selected from Science Citation Index journals, in vitro studies with Jadad score less than 2 points and in vivo and clinical studies with experimental flaws were excluded.

Results: Two hundred and ninety-five papers were searched and 93 papers were reviewed. Licorice extract, 3 triterpenes and 13 flavonoids exhibit evident anti-inflammatory properties mainly by decreasing TNF, MMPs, PGE2 and free radicals, which also explained its traditional applications in stimulating digestive system functions, eliminating phlegm, relieving coughing, nourishing qi and alleviating pain in TCM. Five hundred and fifty-four drugs containing licorice have been approved by CFDA. The side effect may due to the cortical hormone like action.

Conclusion: Licorice and its natural compounds have demonstrated anti-inflammatory activities. More pharmacokinetic studies using different models with different dosages should be carried out, and the maximum tolerated dose is also critical for clinical use of licorice extract and purified compounds.     

Taurine reduces blue light-induced retinal neuronal cell apoptosis in vitro

Background: The massive uptake of organic compatible osmolytes is a self-protective response to multiple stressors.

Objective: This study aimed to determine the protective effects of the osmolyte taurine against blue light-induced apoptosis in retinal neuronal cells in vitro.

Methods: Real-time PCR was used to measure osmolyte transport. Radioimmunoassays were performed to measure osmolyte uptake. Cell Counting Kit-8 assays were conducted to measure cellular viability. Flow cytometry analysis was used to measure apoptosis.

Results: Compared with normotonic stress, hypertonic stress-induced uptake of osmolytes, including betaine, myoinositol, and taurine, into the retinal neuronal cells. Blue light increased osmolyte transporter mRNA expression together with osmolyte uptake. Furthermore, taurine significantly suppressed blue light-induced retinal neuronal cell apoptosis.

Conclusion: The compatible osmolyte taurine may have an important role in cell resistance to blue light and cell survival.     

Inhibitors of α-glucosidase and α-amylase from Cyperus rotundus

Context: A methanol extract of Cyperus rotundus L. (Cyperaceae) rhizomes showed inhibitory activity against α-glucosidase and α-amylase, two enzymes involve in carbohydrate digestion.

Objective: Identification of compounds from C. rotundus rhizomes responsible for the inhibition of α-glucosidase and α-amylase.

Materials and methods: Compounds were identified by a phytochemical investigation using combined chromatographic and spectroscopic methods. α-glucosidase and α-amylase inhibitory activities were evaluated by in vitro enzyme inhibition assays.

Results: A new (2RS,3SR)-3,4′,5,6,7,8-hexahydroxyflavane (1), together with three known stilbene dimers cassigarol E (2), scirpusin A (3) and B (4) were isolated. Compound 2 inhibited both α-glucosidase and α-amylase activities while the flavane 1 only showed effect on α-amylase, and compounds 3 and 4 were active on α-glucosidase. All four compounds showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity.

Discussion: The inhibitory activities against α-amylase and α-glucosidase of the C. rotundus rhizomes were reported for the first time. Stilbene dimers are considered as potent inhibitors of α-glucosidase and promising antihyperglycemic agents.

Conclusion: The isolated compounds may contribute to the antidiabetic property of C. rotundus.     

A review on phytochemical and pharmacological properties of Litsea coreana

Context: Litsea coreana H. Lév. (Lauraceae) is used as an ethnic herb or beverage in China. Substantial studies indicate that it contains a variety of compounds and shows diverse bioactivities with no toxicity.

Objective: This review analyzes and summarizes the ethnopharmacological applications, phytochemistry, and pharmacological activities and molecular mechanisms of L. coreana.

Methods: Related literature (from 1998 to 2016) was obtained and compiled via searching databases including Scopus, Web of Science, Google Scholar, CNKI and PubMed. Keywords (Litsea coreana, hawk tea, eagle tea and laoying cha) were used to select the articles.

Results: Studies indicate that L. coreana contains characteristic polysaccharides, polyphenols, essential oils, and numerious flavonoids, which exhibit remarkable bioactivities, such as hepatoprotection, hyperglycaemia, anti-inflammation, antioxidation and antibacterial, through multiple molecular mechanisms.

Conclusion: This paper provides a systematic review on the phytochemicals and pharmacological activities of L. coreana which should be useful for further study and application of this medicinal herb.     

Meta-analysis of the efficacy of the fentanyl iontophoretic transdermal system versus intravenous patient-controlled analgesia in postoperative pain management

Objective: This meta-analysis was conducted to analyze and compare the efficacy outcomes associated with the fentanyl iontophoretic transdermal system (ITS) and morphine intravenous (IV) patient-controlled analgesia (PCA) in the management of postoperative pain.

Research design and methods: This meta-analysis assessed the efficacy of the fentanyl ITS versus morphine IV PCA using data from four randomized, active-controlled trials (n = 1271 fentanyl ITS and 1298 morphine IV PCA patients). Main outcome measures were patient global assessment (PGA) of the method of pain control at 24 h.

Results: Fentanyl ITS and morphine IV PCA did not significantly differ regarding ‘good’ and ‘excellent’ ratings on the PGA of the method of pain control at 24 h (odds ratio = 0.95, p = 0.66), however, fentanyl ITS was superior in terms of ‘excellent’ PGA ratings at that time point (odds ratio = 1.53, p < 0.0001). No significant differences were found in weighted mean pain intensity scores at 24, 48 and 72 h.

Conclusions: In this meta-analysis, fentanyl ITS was as efficacious as morphine IV PCA and may offer additional benefits as demonstrated by its ‘excellent’ PGA ratings.     

Updates on the treatment of gout,including a review of updated treatment guidelines and use of small molecule therapies for difficult-to-treat gout and gout flares

Introduction: Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues.

Areas covered: In this article, we describe the role of currently available drug therapies for managing acute gout flares and used in reducing serum urate levels. Further, we explore the role of novel small molecular therapies and biologic agents in the treatment of refractory or severe gout symptoms. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-June 2017) was conducted utilizing the key words ‘gout’, ‘interleukin-1 inhibitors’, ‘acute gout’, ‘gout treatment’, ‘urate lowering therapies’, ‘hyperuricemia’, ‘colchicine’, ‘pegloticase’, ‘lesinurad’, ‘xanthine oxidase’, ‘xanthine oxidase inhibitors’, ‘allopurinol’, ‘febuxostat’, ‘uricosurics’, ‘probenecid’, and ‘benzbromarone’. All published articles regarding therapeutic management of gout and hyperuricemia were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed.

Expert opinion: Numerous therapies are currently available to managing acute gout flares and for lowering serum urate levels; advances in the understanding of the pathophysiology of this disorder has led to the emergence of targeted therapies and novel biologic preparations currently in development which may improve the clinical management of severe or refractory cases of disease that fail to respond to traditional therapies.     

Double-blind placebo-controlled study of bepotastine besilate in pediatric patients with perennial allergic rhinitis

Background: Although second-generation antihistamines, such as bepotastine besilate, are recommended as a first-line treatment option for adult perennial allergic rhinitis (PAR), few non-sedating second-generation antihistamines are safe for children.

Objective: A double-blind, placebo-controlled, comparative study of 473 pediatric PAR patients (7 – 15 years old) to determine the superiority and safety of bepotastine besilate (10 mg twice daily) relative to placebo for improved total and individual nasal symptom scores compared with baseline.

Research design and methods: Subjects were randomized to placebo (n = 233) or bepotastine besilate (n = 240, 10 mg orally twice daily for 2 weeks). Interference of daily life by PAR was assessed by measuring change in individual nasal symptom scores from baseline.

Results: Bepotastine besilate was superior to placebo in terms of total nasal symptom scores, with improved overall nasal symptoms of PAR compared with baseline values. Subgroup analyses demonstrated bepotastine besilate was effective irrespective of age, sex or body weight. No clinically significant adverse drug reactions often observed with first-generation antihistamines were reported and no difference in adverse events between groups was observed.

Conclusions: Bepotastine besilate is effective and safe for pediatric PAR patients aged 7 – 15 years, and has a significant clinical impact on PAR. Clinical trial registration: ClinicalTrials.gov identifier: NCT01861522 (https://clinicaltrials.gov/ct2/show/NCT01861522).     

Safety considerations surrounding use of treatment options for nausea and vomiting in pregnancy

Introduction: Nausea and vomiting of pregnancy (NVP) is the most prevalent medical condition during gestation, affecting up to 85% of pregnant women. Many of them hesitate to use medications due to perceived fetal risks.

Areas covered: There are two main aspects to medication safety in NVP: The fetal safety of drugs used to treat NVP symptoms, and the risks of untreated NVP.

While mild and moderate NVP are not associated with major increase in fetal or maternal risks, and may render protective fetal effects, they have major impact on the quality of life of the mother. In contrast, severe NVP and hyperemesis gravidarum (HG) are associated with increased maternal and fetal risks, from in utero growth restriction to developmental delay.

For the doxylamine/pyridoxine combination, H1blockers and metoclopramide there are large studies documenting fetal safety. There are also large reassuring studies on the fetal safety of ondansetron, but they are contrasted by some studies claiming increased fetal risk.

Expert opinion: Fetal safety of the doxylamine/pyridoxine combination, H1blockers and for metoclopramide has been documented. Reassuring studies on the fetal safety of ondansetron, are contrasted by some studies claiming increased teratogenicity. More studies are needed to quantify fetal risks of HG.     

Echinacea biotechnology: advances,commercialization and future considerations

Context: Plants of the genus Echinacea (Asteraceae) are among the most popular herbal supplements on the market today. Recent studies indicate there are potential new applications and emerging markets for this natural health product (NHP).

Objective: This review aims to synthesize recent developments in Echinacea biotechnology and to identify promising applications for these advances in the industry.

Methods: A comprehensive survey of peer-reviewed publications was carried out, focusing on Echinacea biotechnology and impacts on phytochemistry. This article primarily covers research findings since 2007 and builds on earlier reviews on the biotechnology of Echinacea.

Results: Bioreactors, genetic engineering and controlled biotic or abiotic elicitation have the potential to significantly improve the yield, consistency and overall quality of Echinacea products. Using these technologies, a variety of new applications for Echinacea can be realized, such as the use of seed oil and antimicrobial and immune boosting feed additives for livestock.

Conclusions: New applications can take advantage of the well-established popularity of Echinacea as a NHP. Echinacea presents a myriad of potential health benefits, including anti-inflammatory, anxiolytic and antibiotic activities that have yet to be fully translated into new applications. The distinct chemistry and bioactivity of different Echinacea species and organs, moreover, can lead to interesting and diverse commercial opportunities.     

Monoterpenoids from the whole herb of Veronicastrum axillare

Context: Veronicastrum axillare (Sieb. et Zucc.) Yamazaki (Scrophulariaceae) embraces varieties of bioactivities such as anti-inflammatory, anti-pyresis and detoxification activity, while little is known of the phytochemical components of this medicinal plant.

Objective: To isolate and identify bioactive constituents from the whole herb of V. axillare.

Materials and methods: Ethanol extract of the whole herb of V. axillare was subjected to successive column chromatography. Chemical structures of the compounds were elucidated by detailed spectroscopic analyses on the basis of NMR, IR and HR-MS data.

Results: A new monoterpenoid, axillacetal A (1) and a known analogue, tarumal (2), were isolated from the whole herb of V. axillare. The structure of tarumal (2) was also revised according to our NMR data.

Discussion and conclusion: This is the first report on the isolation and authentication of novel chemical constituents from V. axillare.     

Dosing strategies to optimize currently available anti-MRSA treatment options (Part 2: PO options)

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen in both outpatient and inpatient settings. Research to optimize the dosing of these agents is needed to slow the development of antimicrobial resistance and to decrease the likelihood of clinical failure.

Areas covered: This review summarizes the available data for orally administered antimicrobials routinely used as monotherapy for MRSA infections. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 – Present) search was performed to identify relevant literature for this review.

Expert commentary: There is a vast divide in the amount of pharmacokinetic/pharmacodynamic data to guide dosing decisions for older MRSA agents compared with the oxazolidenones.

Five-year view: Additional retrospective data will become available for the older MRSA agents in severe MRSA infections.     

The influence of excipients on physical and pharmaceutical properties of oral lyophilisates containing a pregabalin-acetaminophen combination

Objectives: The purpose of the study was to investigate and characterize the oral lyophilisates containing the pregabalin-acetaminophen drug combination and as xcipients mannitol with microcrystalline cellulose or hydroxypropyl methylcellulose, in order to conclude upon drug-excipient interactions and their stability implications, impact of excipients on drug release and on the physicochemical and mechanical properties of the pharmaceutical formulations.

Methods: The oral tablets were made by using a Christ freeze-dryer alpha 2–4-LSC lyophilizer, and evaluated for stability, drug-excipient compatibility and homogeneity of the prepared pharmaceutical formulations. The formulations were evaluated for in vivo absorption in rabbits by histopathological exams.

Results: FTIR and thermogravimetric analyses, DLS technique, SEM and NIR-CI studies confirmed the compatibility between compounds. From the determined physical and biochemical parameters of the formulations it was established that they are stable, homogeneous, and meet the conditions for orally disintegrating tablets.

Conclusion: In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the ‘codrug’ complex, which do not affect the release of the bioactive compounds.     

Overcoming platinum resistance in ovarian cancer treatment: from clinical practice to emerging chemical therapies

Introduction: The objective of this review is to summarize results from clinical trials that tested cytotoxic drugs and target strategies for the treatment of platinum resistant (PR) recurrent ovarian cancer (ROC) with particular attention to Phase III and ongoing trials.

Areas covered: Since platinum free interval (PFI) represents the most important predictive factor for response to platinum re-treatment in ROC, non-platinum regimens are conventionally considered the most appropriate approaches.

Impressive progress has been made in recent decades, resulting in the identification of most effective cytotoxic agents and in the development of new target strategies.

However, the efficacy of most of these drugs for the treatment of PR disease is still limited.

Expert opinion: The most favorable benefit for the treatment of PR disease, has been described by the AURELIA trial that showed a 3.3 months increase in progression free survival (PFS) when bevacizumab was combined with non-platinum single agent chemotherapy in bevacizumab-naïve patients.

Nevertheless, the use of novel agents is associated to important costs for just little gains in survival.

Thus, in our opinion the economic evaluation, such as the incorporation of quality of life into the clinical studies is crucial for the development of future trials for PR-ROC.     

Survey to determine the efficacy and safety of guideline-based pharmacological therapy for chronic obstructive pulmonary disease patients not previously receiving maintenance treatment

Objective: To investigate the potential beneficial effects of guideline-based pharmacological therapy on pulmonary function and quality of life (QOL) in Japanese chronic obstructive pulmonary disease (COPD) patients without prior treatment.

Research design and methods: Multicenter survey, open-label study of 49 Japanese COPD patients aged ≥ 40 years; outpatients with >10 pack years of smoking history; ratio of forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) < 70%; predicted FEV₁ < 80%; treated with bronchodilators and/or inhaled corticosteroids as maintenance therapy until week 48.

Main outcome measures: The primary endpoint was change in pulmonary function (trough FEV₁, trough FVC); secondary endpoints were QOL and physical activity at 48 weeks after initiation of therapy.

Results: Airway reversibility was confirmed in untreated patients. Significant changes over time were not observed for FEV₁ and FVC, indicating lung function at initiation of treatment was maintained during the observation period. COPD assessment test scores showed statistical and clinical improvements. Cough, sputum, breathlessness, and shortness of breath were significantly improved.

Conclusions: Lung function and QOL of untreated Japanese COPD patients improved and improvements were maintained by performing a therapeutic intervention that conformed to published guidelines.     

Inducible nitric oxide synthase as a target for osteoarthritis treatment

Introduction: Inducible nitric oxide synthase (iNOS) is the enzyme responsible for the production of nitric oxide (NO), a major proinflammatory and destructive mediator in osteoarthritis (OA).

Areas covered: This is a comprehensive review of the recent literature on the involvement of iNOS in osteoarthritis and its potential to be used as a target for OA treatment. Evidence from in vitro, in vivo and human studies was systematically collected using medical search engines. Preclinical studies have focused on the effect of direct and indirect iNOS inhibitors in both animal and human tissues. Apart from direct inhibitors, common pharmacological agents, herbal and dietary medicines as well as hyperbaric oxygen, low level laser and low intensity pulsed ultrasound have been shown to exhibit a chondroprotective effect by inhibiting the expression of iNOS.

Expert opinion: Data support the further investigation of iNOS inhibitors for the treatment of OA in human studies and clinical trials. Indirect iNOS inhibitors such as interleukin 1 inhibitors also need to be studied in greater detail. Finally, human studies need to be conducted on the herbal and dietary medicines and on the non-invasive, non-pharmacological treatments.     

Impact of bodyweight/body mass index on the effectiveness of emergency contraception with levonorgestrel: a pooled-analysis of three randomized controlled trials

Objective:

A pooled analysis of two randomized controlled trials (RCTs) suggested that increased bodyweight and body mass index (BMI) may be associated with a greater probability of pregnancy. To address this issue we investigated whether higher bodyweight and/or BMI negatively impacted the risk of pregnancy in women receiving LNG-EC (levonorgestrel – emergency contraception) after unprotected sexual intercourse in a pooled analysis of three large multinational RCTs conducted by the World Health Organization (WHO).

Methods:

A pooled analysis of three double-blind, multinational RCTs conducted by the WHO to investigate the efficacy of LNG-EC in the general population. All analyses were done on the per-protocol set (PPS) which included 5812 women who received LNG-EC within 72 hours following unprotected sexual intercourse. The analysis was based on logistic regression, with pregnancy as the outcome. BMI and weight were represented in the same model.

Results:

A total of 56 pregnancies were available for analysis in the PPS. Increasing bodyweight and BMI were not correlated with an increased risk of pregnancy in the studied population. A limitation of this study is that despite the large study population in the pooled analysis there were relatively small numbers of women in the high-BMI and high-bodyweight subgroups.

Conclusion:

LNG-EC is effective for preventing pregnancy after unprotected intercourse or contraceptive failure and no evidence was found to support the hypothesis of a loss of EC efficacy in subjects with high BMI or bodyweight. Therefore, access to LNG-EC should not be limited only to women of lower bodyweight or BMI.     

Taurine prevents ultraviolet B induced apoptosis in retinal ganglion cells

Background: Compatible osmolytes accumulation is an active resistance response in retina under ultraviolet (UV) radiation and hypertonicity conditions.

Objective: The purpose of this research is to investigate the protective role of taurine on retina under UVB radiation.

Methods: Osmolytes transporters were measured by quantitative realtime PCR. Osmolytes uptake was estimated by radioimmunoassay. Cell viability was calculated by MTT assay. Cell apoptosis was measured by flow cytometry analysis.

Results: Hypertonicity accelerated osmolytes uptake into retinal ganglion cells (RGCs) including taurine, betadine, and myoinositol. UVB radiation increased osmolytes transporter expression and osmolytes uptake. In addition, osmolyte taurine remarkably prevented UVB radiation induced cell apoptosis in RGCs.

Conclusions: The effect of compatible osmolyte taurine on cell survival rate may play an important role in cell resistance and adaption to UVB exposure.     

The bioactivity of Hedysarum coronarium extracts on skin enzymes and cells correlates with phenolic content

Context: The search for bioactive compounds from botanical sources is attracting much interest. However, differences in chemical composition may occur within the same species depending on different geographical origins.

Objectives: We evaluated the properties on skin enzymes and cells of extracts from sulla legume crop Hedysarum coronarium L. (Fabaceae), collected at two Italian sites near Pisa and Ventimiglia, for possible dermatological and cosmetic applications.

Material and methods: Plant aerial portions were extracted in MTBE/ethyl acetate/acetone, obtaining two extracts named Pisa sulla extract (PSE) and Ventimiglia sulla extract (VSE). Extracts were subjected to chemical characterization, LC-MS/MS analysis and biological assays.

Results: PSE showed stronger antiradical scavenging and higher phenolic and flavonoid contents with respect to VSE. LC-MS/MS analysis revealed similar composition for the two extracts, but PSE was richer in condensed tannins and flavonoids, principally rhoifolin, quercetin, naringenin and derivatives. PSE induced stronger inhibition on collagenase and elastase by in vitro enzyme assays, possibly due to higher levels of condensed tannins and quercetin. ELISA bioassay on human dermal fibroblasts revealed stronger PSE induction of collagen production. Determination of glycerol release from adipocytes disclosed stronger stimulation of lipolysis by PSE, allegedly ascribed to higher charge of quercetin and derivatives. In summary, the higher richness in phenolics of PSE is strictly related to stronger bioactivity.

Discussion and conclusions: Data indicate that aerial H. coronarium material is suitable for the development of dermatological and cosmeceutical products, but the geographical origin is an important factor for maximally exploiting the biological properties of this species.