Safety assessment of natural products in Malaysia: current practices, challenges, and new strategies.

The belief that natural products are inherently safe is a primary reason for consumers to choose traditional medicines and herbal supplements for health maintenance and disease prevention. Unfortunately, some natural products on the market have been found to contain toxic compounds, such as heavy metals and microbes, as well as banned ingredients such as aristolochic acids. It shows that the existing regulatory system is inadequate and highlights the importance of thorough safety evaluations. In Malaysia, the National Pharmaceutical Regulatory Agency is responsible for the regulatory control of medicinal products and cosmetics, including natural products. For registration purpose, the safety of natural products is primarily determined through the review of documents, including monographs, research articles and scientific reports. One of the main factors hampering safety evaluations of natural products is the lack of toxicological data from animal studies. However, international regulatory agencies such as the European Food Safety Authority and the United States Food and Drug Administration are beginning to accept data obtained using alternative strategies such as non-animal predictive toxicological tools. Our paper discusses the use of state-of-the-art techniques, including chemometrics, in silico modelling and omics technologies and their applications to the safety assessments of natural products.

Cosmos caudatus extract/fractions reduce smooth muscle cells migration and invasion in vitro : A potential benefit of suppressing atherosclerosis.

HIGHLIGHTS: Cosmos caudatus Ethanolic extract fractionation by n-butanol produced a phenolics-saponin rich fraction.Cosmos caudatus butanol fraction was the most potent in all antioxidant and MTT assays.High concentrations of all fractions increased cells migration and invasion in vitro.Butanol fraction intermediate concentration maximally inhibited VSMC migration and invasion.Mild concentrations of crude and butanol fractions showed the best invasion inhibition index. BACKGROUND: Cosmos caudatus Kunth is a medicinal herb used traditionally in Latin America and South East Asia to retard aging, rigidify bones and for several cardiovascular uses. OBJECTIVE: Is to assess C. caudatus extract/fractions' antioxidant and vascular smooth muscle cells (VSMC) migration and invasion inhibition capacity in vitro. METHODS: Cosmos caudatus shoots were extracted by cold maceration in 50% ethanol to produce crude (CEE), and then the extract was fractionated to butanol (Bu.F), and aqueous fractions (Aq.f). Phenolics and saponins were quantified in extract and fractions by colorimetric methods and their antioxidant capacity was assayed in four different tests. Cytotoxic effect and safety level concentrations were determined for the fractions by using MTT assay. Migration and invasion inhibitory potential were measured in vitro at three different concentrations equivalent to (IC10, IC25, and IC50). Finally, invasion inhibitory index was calculated to obtain the best fraction(s) that show(s) the highest ratio of cell invasion inhibition to the total cell migration inhibition. RESULTS: Butanol fraction yield was the lowest; nevertheless, its phytochemical contents, antioxidant activities as well as its potency were the highest. Unlike other fractions, Bu.F was strongly correlated with all antioxidant assays experimented. In addition, it has the highest inhibitory effect at IC25 against VSMCs migration and invasion that accounts for 53.93% and 59.94% respectively. Unexpectedly, Bu.F and CEE at IC10 displayed the highest invasion inhibitory index (approx. 68%). CONCLUSION: Butanol fraction of C. caudatus offers a potentiality for the discovery of new leads for preventing atherosclerosis.

Comparative effectiveness of pharmacologic and nonpharmacologic interventions for orthodontic pain relief at peak pain intensity: A Bayesian network meta-analysis.

INTRODUCTION: The objective of this network meta-analysis was to synthesize the evidence of the comparative effectiveness for various interventions used for orthodontic pain relief during peak pain intensity. METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched to December 31, 2014, to identify relevant studies. Additional studies were found by hand searching of journals and reference lists. Unpublished articles were also searched. Eligible studies were randomized controlled trials evaluating the effectiveness of pharmacologic or nonpharmacologic interventions for pain relief after placement of separators or an initial aligning archwire. A covariate-adjusted arm-based 3-level hierarchical Bayesian random-effects model was used for this network meta-analysis. RESULTS: Twenty-four randomized controlled trials (2273 participants; 997 male, 1276 female; mean age, 18.2 years; SD, 4.4 years) were included in this network meta-analysis. A total of 26 interventions were identified and classified into 6 classes based on their mechanism of action. Compared with placebo-class, nonsteroidal anti-inflammatory drug analgesics and lasers were the most effective intervention classes with a shared median rank of 2 (95% credible interval [CrI], 1-3), followed by "other" analgesics (median rank, 3; 95% CrI, 1-4), behavior therapy (median rank, 4; 95% CrI, 3-6), and miscellaneous (median rank, 5; 95% CrI 3-6). The most effective individual interventions in the nonsteroidal anti-inflammatory drug analgesics and lasers classes were etoricoxib (median rank, 1; 95% CrI, 1-3) and gallium-arsenide superpulsed lasers (median rank, 3; 95% CrI, 1-13), respectively. Assessment of transitivity and consistency assumption showed no threat to the network meta-analysis estimates. There was no evidence of significant publication bias. Heterogeneity was mild to moderate (tau-square, 0.044; 95% CrI, 0.040-0.055). CONCLUSIONS: The results show that analgesics and lasers are effective in the management of orthodontic pain at its peak intensity. Further research is required to improve the quality of evidence, especially for analgesic interventions.