Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of Clinical Trials in the Past 20 years

Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.

Building a Barrier: The Influence of Different Wax Fractions on the Water Transpiration Barrier of Leaf Cuticles

Waxes are critical in limiting non-stomatal water loss in higher terrestrial plants by making up the limiting barrier for water diffusion across cuticles. Using a differential extraction protocol, we investigated the influence of various wax fractions on the cuticular transpiration barrier. Triterpenoids (TRPs) and very long-chain aliphatics (VLCAs) were selectively extracted from isolated adaxial leaf cuticles using methanol (MeOH) followed by chloroform (TCM). The water permeabilities of the native and the solvent-treated cuticles were measured gravimetrically. Seven plant species (Camellia sinensis, Ficus elastica, Hedera helix, Ilex aquifolium, Nerium oleander, Vinca minor, and Zamioculcas zamiifolia) with highly varying wax compositions ranging from nearly pure VLCA- to TRP-dominated waxes were selected. After TRP removal with MeOH, water permeability did not or only slightly increase. The subsequent VLCA extraction with TCM led to increases in cuticular water permeabilities by up to two orders of magnitude. These effects were consistent across all species investigated, providing direct evidence that the cuticular transpiration barrier is mainly composed of VLCA. In contrast, TRPs play no or only a minor role in controlling water loss.

Study of wound healing in rat skin treated with extract of Hedera helix, L / Estudo da cura de feridas na pele de rato tratada com extrato de Hedera helix, L

The Hera (Hedera helix L) is part of the ARALIACEAE family, is included in the group of plants that produce saponins, has antifungal action, is hypocholesterolemic, has anti-inflammatory activity, is expectorant, antispasmodic and purifying. It was evaluated, by histological studies, the wound healing action of the extract of Hera leaves on skin wounds, as well as changes in the epithelial tissue and wound healing period. 75 Wistar rats were used and divided into five groups, according to the treatment: negative control (PBS), Hera 10 mg/ml, Hera 30 mg/ml, Hera 50 mg/ml and the positive control (Nebacetin). The animals were anesthetized and undergone through a cut of 4 cm in the dorsal region, exposing their muscle fascias. Right after, daily, the suitable substance to each group was applied in the lesion. After periods of 3, 7, 14, 21 days after the surgery, the animals were killed to collect fragments of the lesion. The material was prepared in stained slides with HE and toluidine blue for histologic analysis. The results showed that at day 14 of treatment, the animals under effect of 30 mg/ml and 50 mg/ml of Hera extract did not present edema. It was also observed a reduction in vascular congestion in the Hera of 30 mg/ml, Hera 50 mg/ml and Nebacetin groups compared to the other groups analyzed. All groups treated with Hera extract showed a reduction of inflammatory cells in day 14 post-lesion, besides the increase of fibroblast this period, showing acceleration in the chronicity of the lesion. Regarding the number of mast cells, a significant increase in the early lesion, in the 3 and 7 days periods was observed, in Hera 50 mg/ml and 30 mg/ml groups, respectively. According to the results, the Hera extract, especially at concentrations of 30 mg/ml and 50 mg/ml accelerated the healing process; based on the decreased permanence period of the edema and congestion of the vessels, as well as changes in the number of cells related to inflammation of lesions.

Particulate Matter (PM) Adsorption and Leaf Characteristics of Ornamental Sweet Potato (Ipomoea batatas L.) Cultivars and Two Common Indoor Plants (Hedera helix L. and Epipremnum aureum Lindl. & Andre)

Particulate matter (PM) is a serious threat to human health, climate, and ecosystems. Furthermore, owing to the combined influence of indoor and outdoor particles, indoor PM can pose a greater threat than urban PM. Plants can help to reduce PM pollution by acting as biofilters. Plants with different leaf characteristics have varying capacities to capture PM. However, the PM mitigation effects of plants and their primary factors are unclear. In this study, we investigated the PM adsorption and leaf characteristics of five ornamental sweet potato (Ipomea batatas L.) cultivars and two common indoor plants (Hedera helix L. and Epipremnum aureum Lindl. & Andre) exposed to approximately 300 μg m−3 of fly ash particles to assess the factors influencing PM adsorption on leaves and to understand the effects of PM pollution on the leaf characteristics of plants. We analyzed the correlation between PM adsorption and photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (Tr), leaf area (LA), leaf width/length ratio (W/L), stomatal density (SD), and stomatal pore size (SP). A Pearson’s correlation analysis and a principal component analysis (PCA) were used to evaluate the effects of different leaf characteristics on PM adsorption. The analysis indicated that leaf gas exchange factors, such as Pn and Tr, and morphological factors, such as W/L and LA, were the primary parameters influencing PM adsorption in all cultivars and species tested. Pn, Tr, and W/L showed a positive correlation with PM accumulation, whereas LA was negatively correlated.

Morphological and Chemical Evaluations of Leaf Surface on Particulate Matter2.5 (PM2.5) Removal in a Botanical Plant-Based Biofilter System

Particulate matter has been increasing worldwide causing air pollution and serious health hazards. Owing to increased time spent indoors and lifestyle changes, assessing indoor air quality has become crucial. This study investigated the effect of watering and drought and illumination conditions (constant light, light/dark cycle, and constant dark) on particulate matter2.5 (PM2.5) removal and surface characterization of leaf in a botanical plant-based biofilter system. Using Ardisia japonica and Hedera helix as experimental plants in the plant-based biofilter system, PM2.5, volatile organic carbon, and CO2, as the evaluators of indoor air quality, were estimated using a sensor. Morphological and chemical changes of the leaf surface (i.e., roughness and wax) associated with PM2.5 removal were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The highest PM2.5 removal efficiency, stomata closure, high leaf roughness, and wax layer were observed under drought with constant light condition. Consequently, PM2.5 removal was attributed to the combined effect of leaf roughness and wax by adsorption rather than stomatal uptake. These results suggest that operating conditions of indoor plant-based biofilter system such as watering (or drought) and illumination may be applied as a potential strategy for enhancing PM2.5 removal.

ISSR markers and morphometry determine genetic diversity and population structure in Hedera helix L.

Hedera helix L. is an invasive, but medicinally important plant. In Iran, there is no available study on the H. helix population to reveal the genetic diversity and population structure. Fifty-six individual plants belonging to nine geographical populations were collected in four provinces of Iran. High genetic diversity, polymorphisms, and a Shannon diversity index of 0.269 were detected in Mazandaran, Kandovan (Population 3). Analysis of the molecular variance indicated 40% of total genetic variation of the whole population was present in the subpopulation. A high genetic similarity (0.922) between plant Populations 5 (Kermanshah; Islamabad) and 6 (Kermanshah; Paveh) was noted. On the other hand, a low genetic similarity was observed between plant Populations 1 (Tehran; Darband) and 8 (Ardabil; Hur). The Mantel test revealed a correlation between the genetic and geographical distances. Furthermore, it demonstrated the isolation mechanism responsible for the population structure in the H. helix plant populations. The principal component analysis explained the majority of the variation in the morphological characteristics. Three components explained 87% of the variation, and the first component explained 60% of the variation. For instance, the leaf morphology showed a correlation of > 0.7 between leaf morphological and floral characters. The plant leaves and quantitative flower characteristics separated the plant populations according to the differences in length. The current results have implications for plant conservation and management.

Possibilities of phyto preparations in treatment of patients with acute cough

Patients with complaints of coughing make up a significant percentage of doctors in various specialties. Cough is not an independent disease, in most clinical cases it is a symptom of a respiratory disease. In acute respiratory pathology, the cough is usually short-lived and stops after the eradication of the infectious agent and the relief of inflammatory changes. It is important therapeutically to provide a reduction in the duration and relief of cough, as well as the prevention of complications. An effective symptomatic agent in the treatment of coughs of various origins, including inflammatory diseases of the respiratory tract, are herbal preparations. The fairly widespread use of phytopreparations in clinical practice is due to their high safety, physiological action, availability and effectiveness. The pharmacological action of these drugs in respiratory infections is manifested by antiinflammatory, cytoprotective, antiviral and antioxidant effects, multifactorial improvement of mucociliary cleansing processes. One of these phytopreparations is a monocomponent syrup with expectorant, mucolytic and antispasmodic. The therapeutic effect of drug is explained by the presence in the composition of triterpene glycosides (saponins) from the leaves of Hedera helix . The effectiveness and safety of drug is proved by a sufficient volume of clinical studies and observations. Literature data show that Hedera helix leaf preparations significantly reduce the severity of acute respiratory infections of the upper respiratory tract.Virtually none of the patients had severe side effects. Allergic reactions were recorded in less than 0.5% of cases, with no mention of a severe allergic reaction of the anaphylaxis type. Thus, the drug of plant origin in the form of drops can be successfully used in patients with symptoms of acute respiratory diseases.

Zinc uptake and distribution in ivy (Hedera helix L.) leaves

Detached leaves of ivy (Hedera helix L.) were used as a model for the study of zinc uptake and transport in vascular plants. By the uptake via the surface of fully immersed leaves in 25 % Hoagland nutrient media (HM) spiked with 65ZnCl2 (50 μmol/dm3 ZnCl2), concentration in leaves 4.98 μg Zn/g (dry wt.), i. e. 2.6 μg Zn/dm2 leaf area after 7d exposition were obtained. By the uptake via immersed stalks of not immersed (transpiring) leaves concentrations up to 370 μg Zn/g (dry wt.) were obtained. When Zn enters into detached leaves via the surface of immersed leaf blades, zinc is uniformly distributed in leaf blades and leaf stalks. When zinc enters detached leaves via immersed stalks of non-immersed transpiring leaves, only small part of zinc is transported to leaf blades and the prevailing part remains in leaf stalks. Stalks act as a trap, able to prevent other leaf tissues against inhibitory effects of high Zn concentrations. Mineral nutrient salts in solutions mobilize Zn trapped in leaf stalks and facilitate Zn transport by transpiration stream to leaf blades, what means that Zn in stalks is bound in ion-exchageable forms.