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Fulltext Factors Contributing to Exacerbating Vulnerabilities in Global Clinical Trials

da Silva RE, Amato AA, Guilhem DB, de Carvalho MR, Lima EDC, Novaes MRCG

Front Pharmacol, 2017;8:999.
PMID: 29403381 DOI: 10.3389/fphar.2017.00999

Background: Although policies and guidelines make use of the concept of vulnerability, few define it. The European Union's directive for clinical trials does not include explanations for or the reasoning behind the designation of certain groups as vulnerable. Emerging economies from lower middle-income countries have, in recent years, had the largest average annual growth rate, as well as increase, in number of clinical trials registered in the US government's database. Nevertheless, careful supervision of research activities has to be ensured. Objective: To describe and analyze the features of the clinical trials involving vulnerable populations in various countries classified by development status and geographic region. Methods: Retrospective study that involved analysis of data obtained from the International Clinical Trials Registry Platform (ICTRP) database between 01/2014 and 12/2014 from countries with (i) highest trial densities during 2005 to 2012, (ii) highest average growth rate in clinical trials, and (iii) greatest trial capabilities. Results: Statistical analysis of this study showed that patients incapable of giving consent personally are 11.4 times more likely to be vulnerable patients than patients who are capable, and that patients in upper-middle-income countries are 1.7 times more likely to be vulnerable patients than patients from high-income countries when participating in global clinical trials. Malaysia (21%), Egypt (20%), Turkey (19%), Israel (18%), and Brazil (17%) had the highest percentages of vulnerable populations involving children. Conclusions: Although the inability to provide consent personally was a factor associated with vulnerability, arbitrary criteria may have been considered when classifying the populations of clinical trials as vulnerable. The EU Clinical Trials Register should provide guidance regarding exactly what aspects or factors should be taken into account to frame given populations as vulnerable, because vulnerability is not applicable to all risk situations.
Fulltext Adolescent kratom exposure affects cognitive behaviours and brain metabolite profiles in Sprague-Dawley rats

Zul Aznal AN, Mohamad Nor Hazalin NA, Hassan Z, Mat NH, Chear NJ, Teh LK, et al.

Front Pharmacol, 2022;13:1057423.
PMID: 36518677 DOI: 10.3389/fphar.2022.1057423

Adolescence is a critical developmental period during which exposure to psychoactive substances like kratom (Mitragyna speciosa) can cause long-lasting deleterious effects. Here, we evaluated the effects of mitragynine, the main alkaloid of kratom, and lyophilised kratom decoction (LKD) on cognitive behaviours and brain metabolite profiles in adolescent rats. Male Sprague-Dawley rats (Postnatal day, PND31) were given vehicle, morphine (5 mg/kg), mitragynine (3, 10, or 30 mg/kg), or LKD (equivalent dose of 30 mg/kg mitragynine) for 15 consecutive days. Later, a battery of behavioural testing was conducted, brain was extracted and metabolomic analysis was performed using LCMS-QTOF. The results showed that mitragynine did not affect the recognition memory in the novel object recognition task. In the social interaction task, morphine, mitragynine, and LKD caused a marked deficit in social behaviour, while in Morris water maze task, mitragynine and LKD only affected reference memory. Metabolomic analysis revealed distinct metabolite profiles of animals with different treatments. Several pathways that may be involved in the effects of kratom exposure include arachidonic acid, pantothenate and CoA, and tryptophan pathways, with several potential biomarkers identified. These findings suggest that adolescent kratom exposure can cause cognitive behavioural deficits that may be associated with changes in the brain metabolite profiles.
Fulltext Differential Patterns of Adherence to Opioid Therapy in Opioid Naïve and Opioid Existing Patients With Different Age Groups

Zin CS, Taufek NH, Ahmad MM

Front Pharmacol, 2019;10:1286.
PMID: 31736760 DOI: 10.3389/fphar.2019.01286

Limited data are available on the adherence to opioid therapy and the influence of different patient groups on adherence. This study examined the patterns of adherence in opioid naïve and opioid existing patients with varying age and gender. This retrospective cohort study was conducted using the prescription databases in tertiary hospital settings in Malaysia from 2010 to 2016. Adult patients aged ≥18 years, receiving at least two opioid prescriptions, were included and stratified into the opioid naïve and existing patient groups. Adherence to opioid therapy was measured using the proportion of days covered (PDC), which was derived by dividing the total number of days covered with any opioids by the number of days in the follow-up period. Generalized linear modeling was used to assess factors associated with PDC. A total of 10,569 patients with 36,650 prescription episodes were included in the study. Of these, 91.7% (n = 9,696) were opioid naïve patients and 8.3% (n = 873) were opioid existing patients. The median PDC was 35.5% (interquartile range (IQR) 10.3-78.7%) and 26.8% (IQR 8.8-69.5%) for opioid naïve and opioid existing patients, respectively. A higher opioid daily dose (coefficient 0.010, confidence interval (CI) 0.009, 0.012 p < 0.0001) and increasing age (coefficient 0.002, CI 0.001, 0.003 p < 0.0001) were associated with higher levels of PDC, while lower PDC values were associated with male subjects (coefficient -0.0041, CI -0.072, -0.010 p = 0.009) and existing opioid patients (coefficient -0.134, CI -0.191, -0.077 p < 0.0001). The suboptimal adherence to opioid medications was commonly observed among patients with non-cancer pain, and the opioid existing patients were less adherent compared to opioid naïve patients. Increasing age and a higher daily opioid dose were factors associated with higher levels of adherence, while male and opioid existing patients were potential determinants for lower levels of adherence to opioid medications.
Fulltext Analgesic Activity, Chemical Profiling and Computational Study on Chrysopogon aciculatus

Zihad SMNK, Bhowmick N, Uddin SJ, Sifat N, Rahman MS, Rouf R, et al.

Front Pharmacol, 2018;9:1164.
PMID: 30374304 DOI: 10.3389/fphar.2018.01164

Present study was undertaken to evaluate the analgesic activity of the ethanol extract of Chrysopogon aciculatus. In addition to bioassays in mice, chemical profiling was done by LC-MS and GC-MS to identify phytochemicals, which were further docked on the catalytic site of COX-2 enzymes with a view to suggest the possible role of such phytoconstituents in the observed analgesic activity. Analgesic activity of C. aciculatus was evaluated by acetic acid induced writhing reflex method and hot plate technique. Phytochemical profiling was conducted using liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS). In docking studies, homology model of human COX-2 enzyme was prepared using Easy Modeler 4.0 and the identified phytoconstituents were docked using Autodock Vina. Preliminary acute toxicity test of the ethanol extract of C. aciculatus showed no sign of mortality at the highest dose of 4,000 mg/kg. The whole plant extract significantly (p < 0.05) inhibited acetic acid induced writhing in mice at the doses of 500 and 750 mg/kg. The extract delayed the response time in hot plate test in a dose dependent manner. LC-MS analysis of the plant extract revealed the presence of aciculatin, nudaphantin and 5α,8α-epidioxyergosta-6,22-diene-3β-ol. Three compounds namely citronellylisobutyrate; 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one and nudaphantin were identified in the n-hexane fraction by GC-MS. Among these compounds, six were found to be interacting with the binding site for arachidonic acid in COX-2 enzyme. Present study strongly supports the traditional use of C. aciculatus in the management of pain. In conclusion, compounds (tricin, campesterol, gamma oryzanol, and citronellyl isobutyrate) showing promising binding affinity in docking studies, along with previously known anti-inflammatory compound aciculatin can be held responsible for the observed activity.
Fulltext Efficacy of Forsythia suspensa (Thunb.) Vahl on mouse and rat models of inflammation-related diseases: a meta-analysis

Zhou C, Xia Q, Hamezah HS, Fan Z, Tong X, Han R

Front Pharmacol, 2024;15:1288584.
PMID: 38500762 DOI: 10.3389/fphar.2024.1288584

Objective: To evaluate the efficacy of the fruits of the medicinal plant Forsythia suspensa (Thunb.) Vahl (FS), in treating inflammation-associated diseases through a meta-analysis of animal models, and also probe deeply into the signaling pathways underlying the progression of inflammation. Materials and methods: All data analyses were performed using Review Manager 5.3 and the results are presented as flow diagrams, risk-of-bias summaries, forest plots, and funnel plots. Summary estimates were calculated using a random- or fixed-effect model, depending on the value of I2. Results: Of the 710 records identified in the initial search, 11 were selected for the final meta-analysis. Each study extracted data from the model and treatment groups for analysis, and the results showed that FS alleviated the inflammatory cytokine levels in serum; oxidant indicator: reactive oxygen species; enzymes of liver function; endotoxin and regulatory cells in blood; and improved the antioxidant enzyme superoxide dismutase. Conclusion: FS effectively reversed the change in acute or chronic inflammation indicators in animal models, and the regulation of multiple channel proteins in inflammatory signaling pathways suggests that FS is a good potential drug for inflammatory disease drug therapy.
Fulltext Editorial: Model-informed drug development and evidence-based translational pharmacology

Zhao J, Zhu X, Tan S, Chen C, Kaddoumi A, Guo XL, et al.

Front Pharmacol, 2022;13:1086551.
PMID: 36578539 DOI: 10.3389/fphar.2022.1086551
Fulltext Endogenous Antioxidant and LOX-Mediated Systems Contribute to the Hepatoprotective Activity of Aqueous Partition of Methanol Extract ofMuntingia calaburaL. Leaves against Paracetamol Intoxication

Zakaria ZA, Mahmood ND, Mamat SS, Nasir N, Omar MH

Front Pharmacol, 2017;8:982.
PMID: 29497375 DOI: 10.3389/fphar.2017.00982

Methanol extract ofMuntingia calaburaL. (family Muntingiaceae) leaf has been reported to exert various pharmacological activities including hepatoprotection. The present study was carried out to identify the most effective hepatoprotective partition derived from the extract and to determine the mechanisms of action involved. The extract was partitioned using solvents with different polarity to yield petroleum ether (PEMC), ethyl acetate (EAMC), and aqueous (AQMC) extracts. Each extract, at 250 mg/kg, was subjected to the paracetamol (PCM)-induced hepatotoxic assay and several parameters such as liver weight, liver/body weight ratio, serum liver enzymes' level, and histopathological examinations were determined. Each partition was also tested for their antioxidant and anti-inflammatory potentials. The most effective extract (AQMC) was prepared in additional dose of 50 and 500 mg/kg, and then subjected to the same liver toxicity test in addition to the endogenous antioxidant enzymes assay. Moreover, AQMC was also subjected to the phytochemical screening and HPLC analysis. Overall, from the results obtained: AQMC exerted significant (p< 0.05): (i) antioxidant activity when assessed using the DPPH, SOD and ORAC assays with high TPC detected; (ii) anti-inflammatory activity via LOX, but not XO pathway; (iii) hepatoprotective activity indicated by its ability to reverse the effect of PCM on the liver weight and liver/body weight ratio, the level of serum liver enzymes (ALT, AST, and ALP), and activity of several endogenous antioxidant enzymes (SOD and CAT). Phytochemicals analyses demonstrated the presence of several flavonoid-based bioactive compounds such as gallic acid and quercetin, which were reported to possess hepatoprotective activity. In conclusion, AQMC exerts hepatoprotective activity against the PCM-induced toxicity possibly by having a remarkable antioxidant potential and ability to activate the endogenous antioxidant system possibly via the synergistic action of its phytoconstituents.
Fulltext Immunomodulatory Effects and Mechanisms of Curcuma Species and Their Bioactive Compounds: A Review

Yuandani, Jantan I, Rohani AS, Sumantri IB

Front Pharmacol, 2021;12:643119.
PMID: 33995049 DOI: 10.3389/fphar.2021.643119

Curcuma species (family: Zingiberaceae) are widely utilized in traditional medicine to treat diverse immune-related disorders. There have been many scientific studies on their immunomodulating effects to support their ethnopharmacological uses. In this review, the efficacy of six Curcuma species, namely, C. longa L., C. zanthorrhiza Roxb., C. mangga Valeton & Zijp, C. aeruginosa Roxb. C. zedoaria (Christm.) Roscoe, and C. amada Roxb., and their bioactive metabolites to modulate the immune system, their mechanistic effects, and their potential to be developed into effective and safe immunomodulatory agents are highlighted. Literature search has been carried out extensively to gather significant findings on immunomodulating activities of these plants. The immunomodulatory effects of Curcuma species were critically analyzed, and future research strategies and appropriate perspectives on the plants as source of new immunomodulators were discussed. Most of the pharmacological investigations to evaluate their immunomodulatory effects were in vivo and in vitro experiments on the crude extracts of the plants. The extracts were not chemically characterized or standardized. Of all the Curcuma species investigated, the immunomodulatory effects of C. longa were the most studied. Most of the bioactive metabolites responsible for the immunomodulating activities were not determined, and mechanistic studies to understand the underlying mechanisms were scanty. There are limited clinical studies to confirm their efficacy in human. Of all the bioactive metabolites, only curcumin is undergoing extensive clinical trials based on its anti-inflammatory properties and main use as an adjuvant for the treatment of cancer. More in-depth studies to understand the underlying mechanisms using experimental in vivo animal models of immune-related disorders and elaborate bioavailability, preclinical pharmacokinetics, and toxicity studies are required before clinical trials can be pursued for development into immunomodulatory agents.
Fulltext Immunomodulatory effects and mechanisms of the extracts and secondary compounds of Zingiber and Alpinia species: a review

Yuandani, Jantan I, Haque MA, Rohani AS, Nugraha SE, Salim E, et al.

Front Pharmacol, 2023;14:1222195.
PMID: 37533631 DOI: 10.3389/fphar.2023.1222195

Zingiber and Alpinia species (family: Zingiberaceae) are popularly used in food as spices and flavoring agents and in ethnomedicine to heal numerous diseases, including immune-related disorders. However, their ethnomedicinal uses have not been sufficiently supported by scientific investigations. Numerous studies on the modulating effects of plants and their bioactive compounds on the different steps of the immune system have been documented. This review aimed to highlight up-to-date research findings and critically analyze the modulatory effects and mechanisms of the extracts and secondary compounds of several Zingiber and Alpinia species, namely, Zingiber officinale Roscoe, Z. cassumunar Roxb., Z. zerumbet (L.) Roscoe ex Sm., Alpinia galanga Linn., A. conchigera Griff, A. katsumadai Hayata, A. oxyphylla Miq., A. officinarum Hance, A. zerumbet (Pers.) Burtt. et Smith, and A. purpurata (Viell.) K. Schum. on the immune system, particularly via the inflammation-related signaling pathways. The immunomodulating activities of the crude extracts of the plants have been reported, but the constituents contributing to the activities have mostly not been identified. Among the extracts, Z. officinale extracts were the most investigated for their in vitro, in vivo, and clinical effects on the immune system. Among the bioactive metabolites, 6-, 8-, and 10-gingerols, 6-shogaol, and zerumbone from Zingiber species and cardamomin, 1'-acetoxychavicol acetate, yakuchinone, rutin, 1,8-cineole, and lectin from Alpinia species have demonstrated strong immunomodulating effects. More experimental studies using cell and animal models of immune-related disorders are necessary to further understand the underlying mechanisms, together with elaborate preclinical pharmacokinetics, pharmacodynamics, bioavailability, and toxicity studies. Many of these extracts and secondary metabolites are potential candidates for clinical development in immunomodulating agents or functional foods to prevent and treat chronic inflammatory disorders.
Fulltext Cost-Effectiveness of Zoledronic Acid Versus Oral Alendronate for Postmenopausal Osteoporotic Women in China

You R, Zhang Y, Wu DB, Liu J, Qian X, Luo N, et al.

Front Pharmacol, 2020;11:456.
PMID: 32425768 DOI: 10.3389/fphar.2020.00456

Objective: This study aims to estimate the cost-effectiveness of yearly intravenous zoledronic acid treatment versus weekly oral alendronate for postmenopausal osteoporotic women in China.
Methods: We used a Markov microsimulation model to compare the cost-effectiveness of zoledronic acid with alendronate in Chinese postmenopausal osteoporotic women with no fracture history at various ages of therapy initiation from health care payer perspective.
Results: The incremental cost-effectiveness ratios (ICERs) for the zoledronic acid versus alendronate were $23,581/QALY at age 65 years, $17,367/QALY at age 70 years, $14,714/QALY at age 75 years, and $12,169/QALY at age 80 years, respectively. In deterministic sensitivity analyses, the study demonstrated that the two most impactful parameters were the annual cost of zoledronic acid and the relative risk of hip fracture with zoledronic acid. In probabilistic sensitivity analyses, the probabilities of zoledronic acid being cost-effective compared with alendronate were 70-100% at a willingness-to-pay of $29,340 per QALY.
Conclusions: Among postmenopausal osteoporotic women in China, zoledronic acid therapy is cost-effective at all ages examined from health care payer perspective, compared with weekly oral alendronate. In addition, alendronate treatment is shown to be dominant for patients at ages 65 and 70 with full persistence. This study will help clinicians and policymakers make better decisions about the relative economic value of osteoporosis treatments in China.
Fulltext The Effectiveness and Safety of Topical Capsaicin in Postherpetic Neuralgia: A Systematic Review and Meta-analysis

Yong YL, Tan LT, Ming LC, Chan KG, Lee LH, Goh BH, et al.

Front Pharmacol, 2016;7:538.
PMID: 28119613 DOI: 10.3389/fphar.2016.00538

In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehicle-controlled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman(®) version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of p-values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia.
Potential Residual Contaminants in Edible Bird's Nest

Yeo BH, Tang TK, Wong SF, Tan CP, Wang Y, Cheong LZ, et al.

Front Pharmacol, 2021;12:631136.
PMID: 33833681 DOI: 10.3389/fphar.2021.631136

Edible bird's nest (EBN) is recognized as a nourishing food among Chinese people. The efficacy of EBN was stated in the records of traditional Chinese medicine and its activities have been reported in many researches. Malaysia is the second largest exporter of EBNs in the world, after Indonesia. For many years, EBN trade to China was not regulated until August 2011, when a safety alert was triggered for the consumption of EBNs. China banned the import of EBNs from Malaysia and Indonesia due to high level of nitrite. Since then, the Malaysia government has formulated Malaysia Standards for swiftlet farming (MS 2273:2012), edible bird's nest processing plant design and management (MS 2333:2010), and edible bird's nest product quality (MS 2334:2011) to enable the industry to meet the specified standards for the export to China. On the other hand, Indonesia's EBN industry formulated a standard operating procedure (SOP) for exportation to China. Both countries can export EBNs to China by complying with the standards and SOPs. EBN contaminants may include but not limited to nitrite, heavy metals, excessive minerals, fungi, bacteria, and mites. The possible source of contaminants may come from the swiftlet farms and the swiftlets or introduced during processing, storage, and transportation of EBNs, or adulterants. Swiftlet house design and management, and EBN processing affect the bird's nest color. Degradation of its optical quality has an impact on the selling price, and color changes are tied together with nitrite level. In this review, the current and future prospects of EBNs in Malaysia and Indonesia in terms of their quality, and the research on the contaminants and their effects on EBN color changes are discussed.
Fulltext Editorial: Experimental and computational aspects of bioactive proteins from animal venoms: an insight into pharmacological properties and drug discovery

Yap MKK, Modahl CM, Hall SR

Front Pharmacol, 2024;15:1380193.
PMID: 38434707 DOI: 10.3389/fphar.2024.1380193
Fulltext Inhibition of Protein Glycation by Tiger Milk Mushroom [Lignosus rhinocerus(Cooke) Ryvarden] and Search for Potential Anti-diabetic Activity-Related Metabolic Pathways by Genomic and Transcriptomic Data Mining

Yap HY, Tan NH, Ng ST, Tan CS, Fung SY

Front Pharmacol, 2018;9:103.
PMID: 29491836 DOI: 10.3389/fphar.2018.00103

Naturally occurring anti-glycation compounds have drawn much interest in recent years as they show potential in reducing or preventing the risk of chronic complications for diabetic patients. In this study, annotation of the genome-transcriptome data from tiger milk mushroom (Lignosus rhinocerus, syn.Lignosus rhinocerotis) to PlantCyc enzymes database identified transcripts that are related to anti-diabetic properties, and these include genes that are involved in carotenoid and abscisic acid biosynthesis as well as genes that code for glyoxalase I, catalase-peroxidases, and superoxide dismutases. The existence of these genes suggests thatL. rhinocerusmay contain bioactive compound(s) with anti-glycation properties that can be exploited for management of diabetic complications. A medium-molecular-weight (MMW) fraction which was obtained from a combination of cold water extraction and Sephadex®G-50 (fine) gel filtration chromatography ofL. rhinocerussclerotia powder was demonstrated to exhibit potent anti-glycation activity. The fraction specifically inhibited the formation of N𝜀-(carboxymethyl)lysine, pentosidine, and other advanced glycation end-product (AGE) structures in a human serum albumin-glucose system, with an IC50value of 0.001 mg/ml, almost 520 times lower than that of the positive control, aminoguanidine hydrochloride (IC50= 0.52 mg/ml). Its ability to suppress protein glycation may be partly associated with its strong superoxide anion radical scavenging activity (10.16 ± 0.12 mmol TE/g). Our results suggest that the MMW fraction ofL. rhinocerusshows potential to be developed into a potent glycation inhibitor for preventing AGE-mediated diabetic complications.
Fulltext Crosstalk Between Signaling Pathways Involved in the Regulation of Airway Smooth Muscle Cell Hyperplasia

Yap HM, Israf DA, Harith HH, Tham CL, Sulaiman MR

Front Pharmacol, 2019;10:1148.
PMID: 31649532 DOI: 10.3389/fphar.2019.01148

Increased ASM mass, primarily due to ASM hyperplasia, has been recognized as a hallmark of airway remodeling in asthma. Increased ASM mass is the major contributor to the airway narrowing, thus worsening the bronchoconstriction in response to stimuli. Inflammatory mediators and growth factors released during inflammation induce increased ASM mass surrounding airway wall via increased ASM proliferation, diminished ASM apoptosis and increased ASM migration. Several major pathways, such as MAPKs, PI3K/AKT, JAK2/STAT3 and Rho kinase, have been reported to regulate these cellular activities in ASM and were reported to be interrelated at certain points. This article aims to provide an overview of the signaling pathways/molecules involved in ASM hyperplasia as well as the mapping of the interplay/crosstalk between these major pathways in mediating ASM hyperplasia. A more comprehensive understanding of the complexity of cellular signaling in ASM cells will enable more specific and safer drug development in the control of asthma.
Fulltext Role of Traditional Chinese Medicine in the Management of Viral Pneumonia

Xi S, Li Y, Yue L, Gong Y, Qian L, Liang T, et al.

Front Pharmacol, 2020;11:582322.
PMID: 33192523 DOI: 10.3389/fphar.2020.582322

Viral pneumonia is one kind of acute respiratory tract infection caused by the virus. There have been many outbreaks of viral pneumonia with high contagiousness and mortality both in China and abroad, such as the great influenza in 1918, the severe acute respiratory syndrome (SARS) coronavirus in 2003, the Influenza A (H1N1) virus in 2009, and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 2012 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. These outbreaks and/or pandemic have significant impact on human life, social behaviors, and economic development. Moreover, no specific drug has been developed for these viruses. Traditional Chinese medicine (TCM) plays an important role in the treatment of viral pneumonia during these outbreaks especially in SARS and SARS-CoV-2 because studies suggest that TCM formulations may target several aspects of the disease and may have lesser side effects than manufactured pharmaceuticals. In recent years, a lot of clinicians and researchers have made a series of in-depth explorations and investigations on the treatment of viral pneumonia with TCM, which have understood TCM therapeutic mechanisms more specifically and clearly. But critical analysis of this research in addition to further studies are needed to assess the potential of TCM in the treatment of viral pneumonia.
Fulltext Anticancer Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin Delivery

Wu YS, Ngai SC, Goh BH, Chan KG, Lee LH, Chuah LH

Front Pharmacol, 2017;8:761.
PMID: 29123482 DOI: 10.3389/fphar.2017.00761

Surfactin, a cyclic lipopeptide biosurfactant produced by various strains of Bacillus genus, has been shown to induce cytotoxicity against many cancer types, such as Ehrlich ascites, breast and colon cancers, leukemia and hepatoma. Surfactin treatment can inhibit cancer progression by growth inhibition, cell cycle arrest, apoptosis, and metastasis arrest. Owing to the potent effect of surfactin on cancer cells, numerous studies have recently investigated the mechanisms that underlie its anticancer activity. The amphiphilic nature of surfactin allows its easy incorporation nano-formulations, such as polymeric nanoparticles, micelles, microemulsions, liposomes, to name a few. The use of nano-formulations offers the advantage of optimizing surfactin delivery for an improved anticancer therapy. This review focuses on the current knowledge of surfactin properties and biosynthesis; anticancer activity against different cancer models and the underlying mechanisms involved; as well as the potential application of nano-formulations for optimal surfactin delivery.
Fulltext Economic evaluation of combination therapy versus monotherapy for treatment of benign prostatic hyperplasia in Hong Kong

Wu DB, Yee CH, Ng CF, Lee SWH, Chaiyakunapruk N, Chang YS, et al.

Front Pharmacol, 2018;9:1078.
PMID: 30386234 DOI: 10.3389/fphar.2018.01078

Background: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) is a common condition affecting men. Studies have shown that the prevalence of LUTS/BPH increases with age, which will cause considerable economic burden to the healthcare system and society. The aim of the present study was to evaluate the long term cost effectiveness of dutasteride and tamsulosin therapy compared to tamsulosin alone in men with BPH in Hong Kong. Methods: A Markov decision model was constructed to estimate the economic impact from a healthcare payers' perspective, which only included direct costs. Analyses were conducted for a 4-year time frame. Results: When compared to tamsulosin alone, combination therapy was more expensive but also more effective in preventing complications and reduced the need for surgery. Over life-time projection suggest that combination therapy will be cost-effective if the willingness-to pay threshold of USD 20,000. Conclusion: Findings of this study found that combination therapy of tamsulosin and dutasteride was more cost-effective compared to tamsulosin alone across a wide range of scenario.
Fulltext The Skeletal-Protecting Action and Mechanisms of Action for Mood-Stabilizing Drug Lithium Chloride: Current Evidence and Future Potential Research Areas

Wong SK, Chin KY, Ima-Nirwana S

Front Pharmacol, 2020;11:430.
PMID: 32317977 DOI: 10.3389/fphar.2020.00430

Lithium, the lightest natural-occurring alkali metal with an atomic number of three, stabilizes the mood to prevent episodes of acute manic and depression. Multiple lines of evidence point to lithium as an anti-suicidal, anti-viral, anti-cancer, immunomodulatory, neuroprotective and osteoprotective agent. This review article provides a comprehensive review of studies investigating the bone-enhancing effects of lithium and its possible underlying molecular mechanisms. Most of the animal experimental studies reported the beneficial effects of lithium in defective bones but not in healthy bones. In humans, the effects of lithium on bones remain heterogeneous. Mechanistically, lithium promotes osteoblastic activities by activating canonical Wingless (Wnt)/beta (β)-catenin, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and bone morphogenetic protein-2 (BMP-2) transduction pathways but suppresses osteoclastic activities by inhibiting the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and calcium signaling cascades. In conclusion, lithium confers protection to the skeleton but its clinical utility awaits further validation from human clinical trials.
Fulltext Vitamin E As a Potential Interventional Treatment for Metabolic Syndrome: Evidence from Animal and Human Studies

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Front Pharmacol, 2017;8:444.
PMID: 28725195 DOI: 10.3389/fphar.2017.00444

A constellation of medical conditions inclusive of central obesity, hyperglycemia, hypertension, and dyslipidemia is known as metabolic syndrome (MetS). The safest option in curtailing the progression of MetS is through maintaining a healthy lifestyle, which by itself, is a long-term commitment entailing much determination. A combination of pharmacological and non-pharmacological approach, as well as lifestyle modification is a more holistic alternative in the management of MetS. Vitamin E has been revealed to possess anti-oxidative, anti-inflammatory, anti-obesity, anti-hyperglycemic, anti-hypertensive and anti-hypercholesterolemic properties. The pathways regulated by vitamin E are critical in the development of MetS and its components. Therefore, we postulate that vitamin E may exert some health benefits on MetS patients. This review intends to summarize the evidence in animal and human studies on the effects of vitamin E and articulate the contrasting potential of tocopherol (TF) and tocotrienol (T3) in preventing the medical conditions associated with MetS. As a conclusion, this review suggests that vitamin E may be a promising agent for attenuating MetS.

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