A Comprehensive Research Review of Herbal Textual Research, Phytochemistry, Pharmacology, Traditional Uses, Clinical Application, Safety Evaluation, and Quality Control of Trollius chinensis Bunge.

Trollius chinensis Bunge (TCB) is a perennial plant of the Ranunculaceae family with medicinal and edible values. It is widely distributed and commonly used in various regions, including Asia, Europe, and North America. The main chemical components of TCB include alkaloids, flavonoids, phenolic acids, and volatile oil compounds. TCB is renowned for its anti-inflammatory, heat-clearing, detoxifying, and eyesight-improving properties. Its dried flowers are commonly used as a traditional Chinese medicine indicated for the treatment of upper respiratory tract infections, chronic tonsillitis, pharyngitis, influenza, and bronchitis. Modern pharmacology has demonstrated the anti-cancer, anti-inflammatory, antihypertensive, and antioxidant effects of TCB. This study presents a comprehensive overview of various aspects of TCB, including herbal textual research, botany, phytochemistry, pharmacology, traditional uses, clinical application, and quality control, aiming to provide new ideas on the scientific application of TCB as well as the integration of modern research with traditional medicinal uses.

Novel Hyaluronic Acid ethosomes based gel formulation for topical use with reduced toxicity, better skin permeation, deposition, and improved pharmacodynamics.

Hyaluronic Acid (HA) has been applied as an anti-ageing molecule in the form of topical products. Current topical commercial formulations of HA face the limitations of very small and stagnant skin permeation, thereby demanding enduring administration of the formulation to sustain its action. In this study, Lipid-based nanocarriers in the form of ethosomes were formulated in a 1% w/w HA strength and were extensively evaluated in vitro, ex-vivo, and in vivo parameters along with a comparison to it's commercial counterpart. The optimised ethosomes-based HA gel formulation revealed required pH (6.9 ± 0.2), small globule size (1024 ± 9 nm), zeta potential of -6.39 ± 0.2 mV, and 98 ± 1.1% HA content. The ex vivo skin permeation and deposition potenwere conferred on synthetic membrane Strat-M, Human cadaver skin, mice skin, rat skin, and pig skin, and both parameters were found to be much higher in comparison to the commercial topical formulation. Skin deposition capacity of the optimised HA formulation was further confirmed by Scan Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) and it was observed that the developed ethosomal gel formulation got deposited more on the treated skin. The in vivo anti-ageing effect of optimised ethosomal gel on rats was found to be greater when compared to commercial formulation of HA and the developed carrier-based system proved to deliver the HA molecule in very small amounts into the systemic circulation. The results endorse the ethosomal carrier-based formulation of HA as a attractive technique for better local bioavailability of HA.

Berberine loaded nanostructured lipid carrier for Alzheimer's disease: Design, statistical optimization and enhanced in vivo performance.

Berberine, an isoquinoline alkaloid, is reported for the treatment of Alzheimer's disease. Despite having substantial therapeutic potential, it exhibits poor absorption, low oral bioavailability and limited penetration in the brain. In this study, berberine-loaded nanostructured lipid carriers (Berb-NLCs) were developed by melt-emulsification and ultrasonication using Geleol, Miglyol 812 N, Solutol HS 15 as a solid lipid, liquid lipid and surfactant, respectively. The Berb-NLC formulation was statistically optimized by a 32 factorial design in which the effect of surfactant and berberine concentration was assessed on particle size and entrapment efficiency of Berb-NLCs. Optimized Berb-NLCs (Trial-5) exhibited particle size of 186 nm, polydispersity index of 0.108, the zeta potential of -36.86 mV and 88% entrapment efficiency. The in vitro release of berberine from Batch-B5 was 82% in phosphate buffer at the end of 24 h. The comparative results of pharmacodynamic studies involving behavioral assessment by locomotor activity, passive avoidance test, elevated plus maze test and spatial memory assessment by Morris water maze demonstrated improved behavioral parameters in vivo by Berb-NLCs compared to pure berberine in Albino Wistar rats. Thus, berberine-loaded nanostructured lipid carriers have the potential of brain targeting and were effective in an animal model of Alzheimer's disease.

Use of medicinal plants for headache, and their potential implication in medication-overuse headache: Evidence from a population-based study in Nepal.

BACKGROUND: In Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause. METHODS: We used data from a cross-sectional, nationwide population-based study, which enquired into headache and use of medicinal plants and allopathic medications. We searched the literature for pharmacodynamic actions of the medicinal plants. RESULTS: Of 2100 participants, 1794 (85.4%) reported headache in the preceding year; 161 (7.7%) reported headache on ≥15 days/month, of whom 28 (17.4%) had used medicinal plants and 117 (72.7%) allopathic medication(s). Of 46 with probable medication-overuse headache, 87.0% (40/46) were using allopathic medication(s) and 13.0% (6/46) medicinal plants, a ratio of 6.7:1, higher than the overall ratio among those with headache of 4.9:1 (912/185). Of 60 plant species identified, 49 were pharmacodynamically active on the central nervous system, with various effects of likely relevance in medication-overuse headache causation. CONCLUSIONS: MPs are potentially a cause of medication-overuse headache, and not to be seen as innocent in this regard. Numbers presumptively affected in Nepal are low but not negligible. This pioneering project provides a starting point for further research to provide needed guidance on use of medicinal plants for headache.

[Off label uses of tigecycline]. / Les utilisations hors-autorisation de mise sur le marché de la tigécycline.

INTRODUCTION: Tigecycline is a relatively new antibiotic that have very limited valid indications. When no other alternative is available, this drug is widely used off label with promising results. The objective of this study is to summarize the different off label uses of tigecycline so that we can decide when and how to prescribe it in the absence of guidelines. MATERIAL AND METHODS: This study a revue of the literature collecting all the articles concerning the off label uses of tigecycline. RESULTS: Tigecycline was widely prescribed, off label, to treat infections with controversial results. Randomised clinical trials were conducted to evaluate its use to treat pneumonia. The results for this indication have a respectable level of evidence. For the other indications, the data collected was insufficient to support tigecycline prescription. In fact, different protocols were used which makes it hard to evaluate the efficacy and to conclude to the best treatment regimen. A tendency to prescribe high doses of the molecule was noted in different studies. When prescribed off label, tigecycline prescriptions were associated with a higher mortality and incidence of side effects. CONCLUSION: The tigecycline remains a valid option for the treatment of infections dues to multi-resistant bacteria especially when other alternatives are scarce or in cases of renal failure.

Self-emulsifying drug delivery system for enhanced solubility of asenapine maleate: design, characterization, in vitro, ex vivo and in vivo appraisal.

Self-emulsifying drug delivery systems (SES) were developed to improve oral bioavailability of asenapine maleate (ASM), an antipsychotic drug with challenging amphiphobic nature and extensive pre-systemic metabolism. ASM-SES was prepared by choosing the proportion of oil, surfactant, co-surfactant from constructed phase diagram. The in vitro and ex vivo evaluation was done. In vivo evaluation was done through pharmacokinetic and pharmacodynamic studies. Role of lymphatic absorption was studied by lymphatic absorption inhibition study. A formulation consisting of 9.9%, 59.4%, 29.7% and 1% of oil, surfactant, co-surfactant, and drug respectively was considered as optimized formulation. After various evaluation test, the globule size and zeta potential for optimized formulation (SES4) were found to be 137.9 nm and -28.8 mV respectively. A maximum of 99.64 ± 0.16% of ASM was released from SES4 in 60 minutes of time. The flux (ex vivo study) increased by 2.33 folds, which prove the enhanced release and permeation of ASM when loaded into SES. The animals administered with SES4 showed higher activity and good pharmacodynamic response than the control and ASM-Suspension, which may be due to the greater availability of the drug. The maximum pharmacodynamic response was observed at the tmax determined by Pharmacokinetic studies. The bioavailability increased by 1.64 folds with 16.55 ± 3.11% as extend of lymphatic absorption (r = 0.9732). Good in vitro in vivo correlation was observed. ASM-SES is a novel approach to effectively deliver ASM and improve the oral bioavailability.

Superior efficacy of the antifungal agent ciclopirox olamine over gemcitabine in pancreatic cancer models.

Ciclopirox olamine (CPX) is an antifungal agent that has recently demonstrated promising anti-neoplastic activity against hematologic and solid tumors. Here, we evaluated CPX compared with gemcitabine alone as well as their combination in human pancreatic cancer cell lines; BxPC-3, Panc-1, and MIA PaCa-2 and in humanized xenograft mouse models. We also examined the preclinical pharmacodynamic activity of CPX. CPX caused a pronounced decrease in cell proliferation and clonogenic growth potential. These inhibitory effects were accompanied by induction of reactive oxygen species (ROS), which were strongly associated with reduced Bcl-xL and survivin levels and activation of a panel of caspases, especially caspase-3, and finally resulted in apoptotic death. CPX-induced apoptosis was associated with reduced pEGFR (Y1068) and pAkt (Ser473) protein levels. Additionally, decreased proliferation was observed in CPX-treated xenografts tumors, demonstrating unique tumor regression and a profound survival benefit. Finally, we showed that CPX significantly abrogated gemcitabine-induced ROS levels in pancreatic tissues. These pre-clinical results have verified the superior antitumor efficacy of CPX over gemcitabine alone, while their combination is even more effective, providing the rationale for further clinical testing of CPX plus gemcitabine in pancreatic cancer patients.

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity.

Quality by Design approach for an in situ gelling microemulsion of Lorazepam via intranasal route.

The present study illustrates the application of the concept of Quality by Design for development, optimization and evaluation of Lorazepam loaded microemulsion containing ion responsive In situ gelator gellan gum and carbopol 934. A novel approach involving interactions between surfactant and polymer was employed to achieve controlled drug release and reduced mucociliary clearance. Microemulsion formulated using preliminary solubility study and pseudo ternary phase diagrams showed significantly improved solubilization capacity of Lorazepam with 54.31±6.07nm droplets size. The effect of oil to surfactant/cosurfactant ratio and concentration of gelling agent on the drug release and viscosity of microemulsion gel (MEG) was evaluated using a 32 full factorial design. The gel of optimized formulation (MEG1) showed a drug release up to 6h of 97.32±1.35% of total drug loaded. The change in shear-dependent viscosity for different formulations on interaction with Simulated Nasal Fluid depicts the crucial role of surfactant-polymer interactions on the gelation properties along with calcium ions binding on the polymer chains. It is proposed that the surfactant-polymer interactions in the form of a stoichiometric hydrogen bonding between oxyethylene and carboxylic groups of the polymers used, provides exceptional ME stability and adhesion properties. Compared with the marketed formulation, optimized MEG showed improved pharmacodynamic activity. Ex vivo diffusion studies revealed significantly higher release for MEG compared to microemulsion and drug solution. MEG showed higher flux and permeation across goat nasal mucosa. According to the study, it could be concluded that formulation would successfully provide the rapid onset of action, and decrease the mucociliary clearance due to formation of in situ gelling mucoadhesive system.

Pharmacokinetic and therapeutic efficacy of intrapulmonary administration of zoledronate for the prevention of bone destruction in rheumatoid arthritis.

Zoledronate, a third-generation nitrogen-containing bisphosphonate, is a new therapeutic agent for the prevention of joint destruction in rheumatoid arthritis (RA). Due to the poor oral absorption of zoledronate, the intravenous route has been the preferred method of administration. To evaluate whether the lung is a promising alternative route of zoledronate administration for the prevention of joint destruction in RA, we examined the pharmacokinetics, safety and therapeutic potential of zoledronate after intrapulmonary administration. The bioavailability of zoledronate was 55% after intrapulmonary administration in rats. In a collagen-induced RA mouse model, an intrapulmonary administration of zoledronate given 7 d before the 2nd collagen immunization effectively suppressed bone loss and joint destruction to a level similar to that achieved with intravenous injection at 21 d after the 2nd collagen immunization. Zoledronate only slightly affected lactate dehydrogenase activity in bronchoalveolar lavage fluid 4 h after intrapulmonary administration of the therapeutic dose in rats. Moreover, zoledronate only slightly changed the plasma level of creatinine after intrapulmonary administration while creatinine significantly increased after intravenous injection of zoledronate in mice. These results indicate that the lung is a promising alternative route of zoledronate administration for the treatment and prevention of joint destruction in RA.

In vitro and in vivo assessment of piroxicam incorporated Aloe vera transgel.

BACKGROUND: The aim of the study was to develop piroxicam-Aloe vera gel (PAG) formulation and make a pharmacodynamic evaluation of the formulation. MATERIALS AND METHODS: The gel was prepared by using carbopol 934 as gelling agent and methyl paraben as a preservative in an Aloe vera gel base. The formulated gel was also evaluated for physicochemical parameters like pH, viscosity, drug content, and in vitro diffusion assessment. Pharmacodynamic activity of the formulation was evaluated in Wistar albino rats. The formulated gel was compared with that of similar marketed gel (commercial piroxicam gel (CPG)) against the same parameters. RESULTS: From in vitro studies, an effective drug release from PAG was observed to be 68.17% when compared with that of the CPG (62.71%) at 180 min indicating better drug release from the gel formulated in this study. Percentage inhibition of edema was greater for the preparation of PAG (29.57 mean percent inhibition after 60 min) compared to marketed gel which exhibited 18.3% after 60 min. CONCLUSION: It was concluded from the results that the Aloe vera gel acts as an effective gel base to prepare piroxicam gel with high drug loading capacity and improved anti-inflammatory effect. From the statistical analysis the formulation of PAG showed better release than the CPG at p < 0.05 level of significance.