Efficacy and Safety of Centella Asiatica (L.) Urb. on Wrinkles: A Systematic Review of Published Data and Network Meta-Analysis.

Centella asiatica has many applications in cosmetics, including wrinkle treatments, but its effectiveness remains to be clarified. This systematic review study aimed to demonstrate the efficacy and safety of C. asiatica for reducing facial wrinkles. PubMed, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of clinical trials, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Thai Library Integrated System, and Thai university database/journals were searched until May 2019. Five double-blinded randomised controlled trials, including 172 Asian females, were included. Endpoints were wrinkling measured by visual score, image analysis, and participant satisfaction. Two placebo-controlled studies applied gel/creams containing C. asiatica or asiaticoside for 12 w to periorbital skin. Two studies applied tretinoin or Pueraria mirifica contralaterally and by network meta-analysis C. asiatica appeared more effective than P. mirifica but possibly less than tretinoin. Asiaticoside applied as a lipstick for 8 w reduced lip wrinkling. Skin hydration was markedly raised by C. asiatica but not tretinoin. One study reported 10 adverse events for C. asiatica and 35 for tretinoin. Cochrane risk of bias was generally low, reporting was weak, and lack of C. asiatica standardization prevents general application. From the reported data, it is possible to conclude that C. asiatica improved lip and periocular wrinkles, and may replace retinoids if its long-term safety is established and C. asiatica is standardized.

Sesquiterpene-Enriched Extract of Curcuma aeruginosa Roxb. Retards Axillary Hair Growth: A Randomised, Placebo-Controlled, Double-Blind Study.

BACKGROUND: Sesquiterpenes in Curcuma aeruginosa Roxb. inhibit steroid 5α-reductase and dihydrotestosterone production, and reverse androgenic alopecia. This study sought to show that a high sesquiterpene C. aeruginosa extract (CA-ext) retards axillary hair growth in women. METHODS: Thirty women (age 20-52 years) were recruited into a 12-week, double-blind, placebo-controlled intervention for CA-ext treatment, where they were randomly allocated to a left or right armpit group. At weekly intervals, axillary hair length was measured videometrically, the hair was shaved, and lotion was applied (to the contralateral axilla) twice daily via roll-on applicators containing either CA-ext or placebo. The primary endpoint of the study was hair growth. RESULTS: Participants showed 22% (range 8-56%, p < 0.0001) reduced axillary hair growth with CA-ext compared to placebo, albeit delayed by 6 weeks. Participants were satisfied with the treatment and no apparent adverse effects were reported. The quantities of lotion used for each axilla were identical between test and placebo throughout the trial for each participant. Participants reported having shorter and finer armpit hair with the test lotion but disliked its smell, even though it was perfumed. The "free of irritation" description gained the highest questionnaire ratings. CONCLUSION: CA-ext in lotion is an efficacious inhibitor of axillary hair growth, the preparation was well accepted and matched the effectiveness of finasteride. Thus, with some refinement, it should provide an alternative pharmacological treatment for unwanted androgenic hair.

Bacopa monnieri extract increases rat coronary flow and protects against myocardial ischemia/reperfusion injury.

BACKGROUND: This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points. METHODS: In normal isolated rat hearts, coronary flow, left ventricular developed pressure, heart rate, and functional recovery were measured using the Langendorff preparation. Hearts were perfused with either (i) Krebs-Henseleit (normal) solution, (control), or with 30, 100 µg/ml B. monnieri ethanolic extract (30 min), or (ii) with normal solution or extract for 10 min preceding no-perfusion ischemia (30 min) followed by reperfusion (30 min) with normal solution. Infarct volumes were measured by triphenyltetrazolium staining. L-type Ca2+-currents (ICa, L) were measured by whole-cell patching in HL-1 cells, a mouse atrial cardiomyocyte cell line. Cytotoxicity of B. monnieri was assessed in rat isolated ventricular myocytes by trypan blue exclusion. RESULTS: In normally perfused hearts, B. monnieri increased coronary flow by 63 ± 13% (30 µg/ml) and 216 ± 21% (100 µg/ml), compared to control (5 ± 3%) (n = 8-10, p < 0.001). B. monnieri treatment preceding ischemia/reperfusion improved left ventricular developed pressure by 84 ± 10% (30 µg/ml), 82 ± 10% (100 µg/ml) and 52 ± 6% (control) compared to pre- ischemia/reperfusion. Similarly, functional recovery showed a sustained increase. Moreover, B. monnieri (100 µg/ml) reduced the percentage of infarct size from 51 ± 2% (control) to 25 ± 2% (n = 6-8, p < 0.0001). B. monnieri (100 µg/ml) reduced ICa, L by 63 ± 4% in HL-1 cells. Ventricular myocyte survival decreased at higher concentrations (50-1000 µg/ml) B. monnieri. CONCLUSIONS: B. monnieri improves myocardial function following ischemia/reperfusion injury through recovery of coronary blood flow, contractile force and decrease in infarct size. Thus this may lead to a novel cardioprotectant strategy.

Depression and adherence to treatment in diabetic children and adolescents: a systematic review and meta-analysis of observational studies.

UNLABELLED: Depression compromises diabetes treatment in juveniles, and this study aimed to identify influential targets most likely to improve adherence to treatment and glycemic control. Prospective observational studies investigating associations between depression and treatment adherence in juveniles with type 1 diabetes were extracted from MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane Central. Nineteen studies comprising 2,935 juveniles met our criteria. Median effect sizes between depression and treatment adherence were 0.22 (interquartile range (IQR), 0.16­0.35) by patient and 0.13 (IQR, 0.12­0.24) caregiver report. Corresponding values for depression/glycemic control were 0.16 (IQR, 0.09­ 0.23) and 0.08 (IQR, 0.04­0.14), respectively. Effect sizes varied with study design, publication year and assessment tools: CES-D yielded a higher effect size than other assessment tools for depression, where associations for depression and either adherence or glycemic control was investigated. Several behaviours influenced adherence and glycemic control. CONCLUSION: This study showed moderate associations between depression and poor treatment adherence. Targeting behaviour and social environments, however, may ultimately provide more cost-effective health gains than targeting depressive symptoms.

Short isoforms of the cold receptor TRPM8 inhibit channel gating by mimicking heat action rather than chemical inhibitors.

Transient receptor potential (TRP) channels couple various environmental factors to changes in membrane potential, calcium influx, and cell signaling. They also integrate multiple stimuli through their typically polymodal activation. Thus, although the TRPM8 channel has been extensively investigated as the major neuronal cold sensor, it is also regulated by various chemicals, as well as by several short channel isoforms. Mechanistic understanding of such complex regulation is facilitated by quantitative single-channel analysis. We have recently proposed a single-channel mechanism of TRPM8 regulation by voltage and temperature. Using this gating mechanism, we now investigate TRPM8 inhibition in cell-attached patches using HEK293 cells expressing TRPM8 alone or coexpressed with its short sM8-6 isoform. This is compared with inhibition by the chemicals N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC) and clotrimazole or by elevated temperature. We found that within the seven-state single-channel gating mechanism, inhibition of TRPM8 by short sM8-6 isoforms closely resembles inhibition by increased temperature. In contrast, inhibition by BCTC and that by clotrimazole share a different set of common features.

Virulence factors and quorum sensing as targets of new therapeutic options by plant-derived compounds against bacterial infections caused by human and animal pathogens.

The emergence of antibiotic-resistant bacteria and hospital-acquired bacterial infection has become rampant due to antibiotic overuse. Virulence factors are secondary to bacterial growth and are important in their pathogenesis, and therefore, new antimicrobial therapies to inhibit bacterial virulence factors are becoming important strategies against antibiotic resistance. Here, we focus on anti-virulence factors that act through anti-quorum sensing and the subsequent clearance of bacteria by antimicrobial compounds, especially active herbal extracts. These quorum sensing systems are based on toxins, biofilms, and efflux pumps, and bioactive compounds isolated from medicinal plants can treat bacterial virulence pathologies. Ideally, bacterial virulence factors are secondary growth factors of bacteria. Hence, inhibition of bacterial virulence factors could reduce bacterial pathogenesis. Furthermore, anti-virulence factors from herbal compounds can be developed as novel treatments for bacterial infection. Therefore, this narrative review aims to discuss bacterial virulence factors acting through quorum sensing systems that are preserved as targets for treating bacterial infection by plant-derived compounds.

Bovine omphalocele: errors in embryonic development, veterinarian importance, and the way forward.

Omphalocele is an embryonic developmental error presented as a neonatal visceral umbilical herniation. Epidemiological and embryological studies are reviewed that revise our understanding of midgut development and defects in cattle. Google Scholar and PubMed were searched for omphalocele, exomphalos, calves, calf, cattle, epidemiology, genetics, disease presentation, and omphalocele treatments of bovine neonates. Omphalocele contains small intestine and sometimes liver and/or pyloric abomasum. This condition may arise from inadequately expanded abdominal cavity, herniated midgut entrapment, or inappropriate umbilical ring growth. Full-term neonates are otherwise healthy but comorbidities may be present. Limited epidemiological evidence suggests neonates, commonly female, of dairy dams have much higher omphalocele prevalence than humans but with fewer co-morbidities. Genetic or environmental influences may present at low incidences, especially with co-defects, while also epigenetics operate in metabolically challenged dairy cattle. Calf survival after surgical repair was commonly good if damage to eviscerated tissue was minimal and surgery prompt. Inadequate follow-ups prevented assessment of their commercial value. We also revised understanding of embryonic midgut development. There is little useful epidemiological information on bovine omphaloceles. To address this, we suggest: (i) Observations on omphaloceles should report herd and dam histories, abdominal disposition of contents, and comorbidities. (ii) Cases of surgical restitution must report full histories and thoroughly explore post-surgical follow-ups to assess animal commercial viability. There is a need for very large-scale multi-centre prospective observational studies on cattle health and productivity that should include omphaloceles.

A Thai Traditional Triple-Fruit Formulation "Phikud Tri-Phon" May Provide Fat Loss and Nutritional Benefits.

Obesity and overweight have serious health outcomes. "Phikud Tri-Phon" (PTP) is a traditional Thai medicine comprising three dried fruits from Aegle marmelos L., Morinda citrifolia L., and Coriandrum sativum L. Whether this medicine impacts on metabolic disease is unclear. This study aimed to investigate the phenolic and flavonoid contents of PTP and each of its herbal components, and further assess their antioxidant and anti-adipogenetic activities. Oil-red O staining was measured for lipid accumulation in 3T3-L1 adipocytes. The chemical profiles of PTP and each herbal extract were determined by LC-ESI-QTOF-MS/MS. Our results show that the total phenolic and flavonoid contents of PTP water extract were 22.35-108.42 mg of gallic acid equivalents and PTP ethanolic extract was 1.19-0.93 mg of quercetin equivalents and the DPPH scavenging capacity assay of PTP ethanolic extract (1 mg/mL) was 92.45 ± 6.58 (Trolox equivalent)/g. The PTP extracts and individual herbs had inhibitory adipogenesis activity, which reduced lipid accumulation by approximately 31% in PTP water extract and 22% in PTP ethanolic extract compared with control cells. These results provided insights into the traditional preparation method of using boiling water as a vehicle for PTP. In conclusion, PTP has antioxidant and anti-adipogenesis potential, indicating it is a promising ingredient in functional food and herbal health products.

Phenanthrene-enriched extract from Eulophia macrobulbon using subcritical dimethyl ether for phosphodiesterase-5A1 inhibition.

Eulophia macrobulbon (E.C.Parish & Rchb.f.) Hook.f. contains a natural PDE5A1 inhibitor, phenanthrene, 1-(4'-hydroxybenzyl)-4,8- dimethoxyphenanthrene-2,7-diol (HDP), a potential agent for the treatment of erectile dysfunction. The aim of this study was to improve the extraction efficiency of HDP from E. macrobulbon by using a more environmentally friendly extraction method, subcritical liquid dimethyl ether extraction (sDME), instead of classical solvent extraction (CSE) and ultrasound-assisted extraction (UAE). The efficiency and quality of the extracts obtained were evaluated using the following criteria: %process yield; solvent amount; extraction time; temperature; %HDP content by LC-MS, bioactivity as inhibition of phosphodiesterase-5A1 (PDE5A1) by radio-enzymatic assay; and chemical profiles by LC-QTOF-MS. sDME provided the highest content of HDP in the extract at 4.47%, much higher than the use of ethanol (0.4-0.5%), ethyl acetate (1.2-1.7%), or dichloromethane (0.7-1.4%). The process yield for sDME (1.5-2.7%) was similar to or lower than the other solvents (0.9-17%), but as long as the process yield is not prohibitively low, the concentration is a more important measure for clinical use. The optimal conditions for sDME extraction were: Extraction time, 40 min; 200% water as co-solvent; sample-to-solvent ratio of 1:8; temperature, 35 °C. Phenanthrene aglycone and glycoside derivatives were the major constituents of the sDME extracts and lesser amounts of phenolic compounds and sugars. The inhibition of PDE5A1 by sDME (IC50 0.67 ± 0.22 µg/ml) was tenfold more potent than ethanolic extract and other extraction methods, suggesting a high probability of clinical efficacy. Thus, sDME was a more efficient, faster, solvent-saving and environmentally friendly extraction method and more selective for phenanthrene when extracted from E. macrobulbon.

Detecting Ca2+ sparks on stationary and varying baselines.

Studies concerning the physiological significance of Ca(2+) sparks often depend on the detection and measurement of large populations of events in noisy microscopy images. Automated detection methods have been developed to quickly and objectively distinguish potential sparks from noise artifacts. However, previously described algorithms are not suited to the reliable detection of sparks in images where the local baseline fluorescence and noise properties can vary significantly, and risk introducing additional bias when applied to such data sets. Here, we describe a new, conceptually straightforward approach to spark detection in linescans that addresses this issue by combining variance stabilization with local baseline subtraction. We also show that in addition to greatly increasing the range of images in which sparks can be automatically detected, the use of a more accurate noise model enables our algorithm to achieve similar detection sensitivities with fewer false positives than previous approaches when applied both to synthetic and experimental data sets. We propose, therefore, that it might be a useful tool for improving the reliability and objectivity of spark analysis in general, and describe how it might be further optimized for specific applications.

Efficacy of an Anti-Cellulite Herbal Emgel: A Randomized Clinical Trial.

Cellulite describes unsightly skin overlying subcutaneous fat around thighs and buttocks of post-pubescent females. A herbal 'emgel' containing volatile oils and extracts of A traditional Thai herbal compress was tested in a double-blind, placebo-controlled trial with 18 women aged 20-50 year with severe cellulite. Appearance of cellulite (primary outcome), thigh circumferences, skin firmness, and cutaneous blood flow (secondary outcomes) were assessed at baseline, 2, 4, 8 and 12 weeks with a 2-week follow-up. Herbal emgel applied onto the thigh skin twice daily reduced cellulite severity scores in every time point. The score was reduced from 13.4 ± 0.3 (baseline) to 12.1 ± 0.3 (week 2) and 9.9 ± 0.6 (week 12). All secondary outcomes improved with both placebo and herbal emgels suggesting that ingredients in the base-formulation might be responsible. Querying of participants, analysis of their diaries, and physical monthly inspections found no adverse events. The herbal emgel safely improved the appearance of cellulite, while the base emgel may play a role for other endpoints. Further studies on the active constituents and their mechanism of action are needed to further explore these factors.

Diabetes downregulates large-conductance Ca2+-activated potassium beta 1 channel subunit in retinal arteriolar smooth muscle.

Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased retinal arteriolar tone during diabetes remain unclear. Normally, local Ca(2+) release events (Ca(2+)-sparks), trigger the activation of large-conductance Ca(2+)-activated K(+)(BK)-channels which hyperpolarize and relax vascular smooth muscle cells, thereby causing vasodilatation. In the present study, we examined BK channel function in retinal vascular smooth muscle cells from streptozotocin-induced diabetic rats. The BK channel inhibitor, Penitrem A, constricted nondiabetic retinal arterioles (pressurized to 70mmHg) by 28%. The BK current evoked by caffeine was dramatically reduced in retinal arterioles from diabetic animals even though caffeine-evoked [Ca(2+)](i) release was unaffected. Spontaneous BK currents were smaller in diabetic cells, but the amplitude of Ca(2+)-sparks was larger. The amplitudes of BK currents elicited by depolarizing voltage steps were similar in control and diabetic arterioles and mRNA expression of the pore-forming BKalpha subunit was unchanged. The Ca(2+)-sensitivity of single BK channels from diabetic retinal vascular smooth muscle cells was markedly reduced. The BKbeta1 subunit confers Ca(2+)-sensitivity to BK channel complexes and both transcript and protein levels for BKbeta1 were appreciably lower in diabetic retinal arterioles. The mean open times and the sensitivity of BK channels to tamoxifen were decreased in diabetic cells, consistent with a downregulation of BKbeta1 subunits. The potency of blockade by Pen A was lower for BK channels from diabetic animals. Thus, changes in the molecular composition of BK channels could account for retinal hypoperfusion in early diabetes, an idea having wider implications for the pathogenesis of diabetic hypertension.

Discovery of Natural Steroid 5 Alpha-Reductase Inhibitors.

Human steroid 5 alpha-reductases (S5αRs) and NADPH irreversibly reduce testosterone to the more potent dihydrotestosterone (DHT). S5αR inhibitors are useful treatments for DHT-dependent diseases, including benign prostatic hyperplasia, androgenic alopecia and hair growth, and acne. There are three S5αR isozymes, and there is a need for safer and more isozyme selective inhibitors than finasteride and dutasteride currently licensed. In this study, we review the methods used to screen for S5αR inhibitory activity and describe studies that characterize the ability of herbal preparations and their constituents to inhibit S5αRs. We identified enormous variations between studies in IC50s for finasteride and dutasteride used as standards. Accordingly, we make several recommendations: Stable isozyme specific transfection systems need creating a standardized enzyme/microsome preparation and all three isozymes, as well as androgen receptor binding, should be tested; agreed reaction conditions, especially the substrate concentrations, and separation/quantitation method optimized for high throughput screening; systematic screening of herbal compounds and most extensive use of leads to develop more potent and isozyme specific inhibitors.

Pharmacokinetics of mitragynine, a major analgesic alkaloid in kratom (Mitragyna speciosa): A systematic review.

BACKGROUND AND OBJECTIVE: Kratom (Mitragyna speciosa) is a tropical tree found in southern Thailand and northern states of the Malay Peninsula. Kratom is commercially available and used as an alternative to treat opioid withdrawal. Mitragynine is the major indole alkaloid found in kratom leaves. This review aimed to summarize available pharmacokinetic information about mitragynine. METHODS: PubMed, Scopus, and Web of Science were systematically searched from their inceptions to June 2018. All types of pharmacokinetic studies of mitragynine were included for further systematic review. RESULTS: Seventeen articles were reviewed. Mitragynine is a lipophilic weak base passively transported across the intestinal wall and blood brain barrier. 85-95% is bound to plasma protein and extensively metabolized by phase I and particularly phase II enzymes. Actions on CYP enzymes are unlikely to impact drug metabolism at concentrations likely to exist in kratom-consuming humans. In rats and humans, mitragynine is rapidly absorbed after orally administration (Tmax˜1.5 h, Cmax˜0.3-1.8 µM). Vd was 37-90 L/kg; t1/2 was 3-9 hr; mostly excreted as metabolites in urine. Bioavailability was estimated as 21%. It also rapidly penetrated and redistributed in brain. A quality assessment tool tailored for pharmacokinetic studies was also created which rated some studies of lower value. CONCLUSION: Rudimentary pharmacokinetics of mitragynine was described in this systematic review. However, the discovered studies provided scant information on the role of metabolism and redistribution into tissues nor the rate of excretion.

Modification of smooth muscle Ca2+-sparks by tetracaine: evidence for sequential RyR activation.

Spontaneous Ca(2+)-sparks were imaged using confocal line scans of fluo-4 loaded myocytes in retinal arterioles. Tetracaine produced concentration-dependent decreases in spark frequency, and modified the spatiotemporal characteristics of residual sparks. Tetracaine (10 microM) reduced the rate of rise but prolonged the average rise time so that average spark amplitude was unaltered. The mean half-time of spark decay was also unaffected, suggesting that spark termination, although delayed, remained well synchronized. Sparks spread transversely across the myocytes in these vessels, and the speed of spread within individual sparks was slowed by approximately 60% in 10 microM tetracaine, as expected if the spark was propagated across the cell but the average P(o) for RyRs was reduced. Staining of isolated vessels with BODIPY-ryanodine and di-4-ANEPPS showed that RyRs were located both peripherally, adjacent to the plasma membrane, and in transverse extensions of the SR from one side of the cell to the other. Immuno-labelling of retinal flat mounts demonstrated the presence RyR(2) in arteriole smooth muscle but not RyR(1). We conclude that Ca(2+)-sparks in smooth muscle can result from sequential activation of RyRs distributed over an area of several microm(2), rather than from tightly clustered channels as in striated muscle.

Hospital admissions associated with medication non-adherence: a systematic review of prospective observational studies.

BACKGROUND: Medication non-adherence in ambulatory care has received substantial attention in the literature, but less so as it affects acute care. Accordingly, we aimed to estimate the frequency with which non-adherence to medication contributes to hospital admissions. METHODS: We searched the Cochrane Library, EMBASE, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts and PubMed (until December 2017) to identify prospective observational studies that examined prevalence rates of hospital admissions associated with medication non-adherence. A quality assessment was performed using an expanded Crombie checklist. Data extraction covered patterns, circumstances, and patient and other key characteristics of non-adherence. Pooled estimates were obtained using a random-effect model. RESULTS: Of 24 included studies, 8 were undertaken in North America, 7 from Europe, 6 from Asia and 3 from Australia. Most studies (79%) were rated as low risk of bias. All but three studies used combination measures to detect non-adherence, but approaches to assess preventability varied considerably. Across the studies, there was high heterogeneity among prevalence estimates (χ2=548, df 23, p<0.001, I2=95.8%). The median prevalence rate of hospital admissions associated with non-adherence was 4.29% (IQR 3.22%-7.49%), with prevalence rates ranging from 0.72% to 10.79%. By definition, almost all of these admissions were considered preventable. The underlying causes contributing to these admissions included medication cost and side effects, and non-adherence most often involved cardiovascular medicines. CONCLUSIONS: Hospital admissions associated with non-adherence to medication are a common problem. This systematic review highlights important targets for intervention. Greater attention could be focused on adherence to medication during the hospital stay as part of an enhanced medication reconciliation process. Standardisation in study methods and definitions is needed to allow future comparisons among settings; future studies should also encompass emerging economies.

Cellulite Reduction by Modified Thai Herbal Compresses; A Randomized Double-Blind Trial.

Cellulite remains an obstinate clinical and cosmetic problem. In this study, we adapted the Thai traditional noninvasive treatment formulated with 5 additional herbals to improve blood flow, edema, and lipolysis, thereby augmenting cellulite treatment. This was a double-blind, randomized placebo-controlled paired trial. Twenty-one women (20-55 years) having cellulite (grade ≥2) were treated with steamed placebo or herbal compresses randomly assigned to one or other thigh twice weekly for 8 weeks with 2 weeks washout. Cellulite reduction was assessed from standardized photographs by 3 blinded evaluators at baseline and every 2 weeks; also assessed were thigh circumferences and cutaneous skin-fold thicknesses, trial diaries, and participant feedback. After 8 weeks, herbal compress treatment reduced Nürnberger-Müller cellulite scores from 12.6 ± 2.0 to 9.9 ± 2.4 compared with 12.5 ± 2.1 to 12.1 ± 2.0 (means ± SEM) for contralateral placebo-treated thighs ( P < .0001; effect size [ES] = 1.16, confidence interval [CI] = 0.48-1.83). Thigh circumferences diminished by 2.2 ± 0.9 cm (herbal) and 1.4 ± 0.7 cm (placebo) (ES = 0.96, CI = 0.30-1.61) and correspondingly skin-folds by 5.6 ± 2.2 and 2.4 ± 1.3 mm (ES = 1.72, CI = 0.99-2.45). No adverse actions were reported, and there were no dropouts, no missing data, and 100% adherence. Herbal compresses were efficacious against cellulite and thigh sizes. The herbal formula might be adapted to other delivery options, and rationally added herbals may increase effectiveness of traditional therapies and more sustainable actions.

Isolation of Retinal Arterioles for Ex Vivo Cell Physiology Studies.

The retina is a highly metabolically active tissue that requires a substantial blood supply. The retinal circulation supports the inner retina, while the choroidal vessels supply the photoreceptors. Alterations in retinal perfusion contribute to numerous sight-threatening disorders, including diabetic retinopathy, glaucoma and retinal branch vein occlusions. Understanding the molecular mechanisms involved in the control of blood flow through the retina and how these are altered during ocular disease could lead to the identification of new targets for the treatment of these conditions. Retinal arterioles are the main resistance vessels of the retina, and consequently, play a key role in regulating retinal hemodynamics through changes in luminal diameter. In recent years, we have developed methods for isolating arterioles from the rat retina which are suitable for a wide range of applications including cell physiology studies. This preparation has already begun to yield new insights into how blood flow is controlled in the retina and has allowed us to identify some of the key changes that occur during ocular disease. In this article, we describe methods for the isolation of rat retinal arterioles and include protocols for their use in patch-clamp electrophysiology, calcium imaging and pressure myography studies. These vessels are also amenable for use in PCR-, western blotting- and immunohistochemistry-based studies.

Efficacy and safety of "Yahom" as a traditional Thai herbal therapy: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Yahom is a traditional Thai medicine used to treat syncope and abdominal discomfort. AIM OF THE STUDY: This study aimed to systematically review all available evidence which purports to support these claims. MATERIAL AND METHODS: The systematic review accorded with the Cochrane Collaboration framework and PRISMA reporting. Databases including MEDLINE, Excerpta Medica Database (EMBASE), Cochrane library database, and Google Scholar were searched by keywords, Yahom and Ya-hom. Pharmacological and toxicity data from non-animal and animal studies were included. RESULTS: Twenty-four articles: 2 on in vitro cell lines or bacteria, 3 in vitro cell-free, 5 in vitro animal, 13 in vivo and 1 human mainly reported (A) Cardiovascular effects (i) transient hypotension (0.2-0.8g/kg, intravenous injection (i.v.)), increased cerebral blood flow (2g/kg, single oral) and vascular dilatation/relaxation (ii) elevated blood pressure (BP) (0.2-0.8g/kg, i.v. or 2-4g/kg oral) and vasocontraction. Single Yahom doses (3g) given to healthy volunteers had no effect on cutaneous blood flow, ECG or systolic BP although marginally increased diastolic BP was claimed. (B) Yahom (2-4g/kg) completely inhibited gastric acid secretion evoked by gastric secretagogues. (C) Toxicity: Chronic oral doses of selected Yahoms to rodents (0.001-1g/kg) supports its status as generally regarded as safe. CONCLUSIONS: Most studies supported declared objectives relating to perceived Yahom actions, but lacked background demonstrating clinical efficacy, and mechanistic data that would validate conclusions. Our study suggests that research into traditional medicinal herbs needs underpinning by appropriate clinical interventions and pharmacovigilance, thereby optimising efficacy and minimizing toxicity by combining traditional wisdom and modern testing.

Curcuma aeruginosa Roxb. essential oil slows hair-growth and lightens skin in axillae; a randomised, double blinded trial.

BACKGROUND: Androgenic hair-growth contributes to secondary gender characteristics but can be troublesome in women. Inhibiting axillary hair-growth via 5-α-reductases using the Thai medicinal plant, Curcuma aeruginosa Roxb. is an attractive treatment strategy. HYPOTHESIS/PURPOSE: C. aeruginosa essential oil (CA-oil) formulated as a lotion is an efficacious and safe inhibitor of axillary hair growth. STUDY DESIGN: This trial was a single center, randomized, double-blind, placebo controlled 10 weeks, intervention in 60 women (18-23 years) and 2 weeks washout with axillary hair length was the primary end-point. METHODS: Bioactive-enriched essential oil of C. aeruginosa was formulated with a base lotion. All participants were pre-challenged with lotions by 4-h patch irritation tests to exclude skin reactions. Participants were randomly allocated to use either 1 or 5%w/w CA-oil lotion on one axilla and base-lotion (placebo) to the other for 10 weeks followed by placebo in both axillae for 2 weeks. Every week, the axillae were photographed to measure hair lengths, shaved, and roll-on applicators containing appropriate lotion replaced. Also, skin melanin by spectrophotometry and hair density were measured. RESULTS: From weeks 5-11 of trial, 1 and 5%w/w CA-oil retarded growth by 13 ± 1.5% and 16 ± 0.9% respectively, while placebo was ineffective. CA-oil had no influence on hair density. Both concentrations of CA-oil rapidly and equally effectively brightened skin within 3 weeks which persisted 2 weeks after treatment ceased while placebo darkened the skin. Adherence appeared good as judged by consistency of lotion consumption and between axillae. Participants were satisfied with the treatment and reported reduced hairiness, freedom from any discomforts, but product odour attracted some negative comment. No adverse reactions ascribed to CA-oil were detected or reported. CONCLUSION: This study points to a safe and efficacious dual action on retarding hair-growth and skin lightening by CA-oil.