Azelaic acid and Melaleuca alternifolia essential oil co-loaded vesicular carrier for combinational therapy of acne

Aim: Azelaic acid (AzA), a comedolytic, antibacterial, anti-inflammatory anti-melanogenic agent, prescribed against acne vulgaris is safe on skin. Its combination with another widely used anti-acne agent, tea tree oil (EO) whose delivery is limited by volatility, instability and lipophilicity constraints was attempted. Method: Solvent injection was used to prepare AzA-EO integrated ethosomes. Result: Ethosomes were transformed into carbopol hydrogel, which exhibited pseudo-plastic properties with appreciable firmness, work of shear, stickiness and work of adhesion. The hydrogel showed better permeation and retention characteristics vis-a-vis commercial formulation (AzidermTM), when evaluated in Wistar rat skin. Further, ethosome hydrogel composite was better tolerated with no side effects. Conclusion: The findings suggests that the aforementioned strategy could be a potential treatment used for acne management. </jats:p

Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne.

Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index  90%), and negative zeta potential (-1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris

Polo-like kinase Cdc5 drives exit from pachytene during budding yeast meiosis

In budding yeast, exit from the pachytene stage of meiosis requires the mid-meiosis transcription factor Ndt80, which promotes expression of ∼200 genes. Ndt80 is required for meiotic function of polo-like kinase (PLK, Cdc5) and cyclin-dependent kinase (CDK), two cell cycle kinases previously implicated in pachytene exit. We show that ongoing CDK activity is dispensable for two events that accompany exit from pachytene: crossover formation and synaptonemal complex breakdown. In contrast, CDC5 expression in ndt80Δ mutants efficiently promotes both events. Thus, Cdc5 is the only member of the Ndt80 transcriptome required for this critical step in meiotic progression

Isolation and characterization of salt-tolerant bacteria with plant growth-promoting activities from saline agricultural fields of Haryana, India

Abstract Background Soil salinity has been one of the biggest hurdles in achieving better crop yield and quality. Plant growth-promoting rhizobacteria (PGPR) are the symbiotic heterogeneous bacteria that play an important role in the recycling of plant nutrients through phytostimulation and phytoremediation. In this study, bacterial isolates were isolated from salt-polluted soil of Jhajjar and Panipat districts of Haryana, India. The potential salt-tolerant bacteria were screened for their PGPR activities such as phosphate solubilization, hydrogen cyanide (HCN), indole acetic acid (IAA) and ammonia production. The molecular characterization of potent isolates with salt tolerance and PGPR activity was done by 16S rDNA sequencing. Results Eighteen soil samples from saline soils of Haryana state were screened for salt-tolerant bacteria. The bacterial isolates were analyzed for salt tolerance ranging from 2 to 10%. Thirteen isolates were found salt tolerant at varied salt concentrations. Isolates HB6P2 and HB6J2 showed maximum tolerance to salts at 10% followed by HB4A1, HB4N3 and HB8P1. All the salt-tolerant bacterial isolates showed HCN production with maximum production by HB6J2. Phosphate solubilization was demonstrated by three isolates viz., HB4N3, HB6P2 and HB6J2. IAA production was maximum in HB4A1 (15.89) and HB6P2 (14.01) and least in HB4N3 (8.91). Ammonia production was maximum in HB6P2 (12.3) and least in HB8P1 (6.2). Three isolates HB6J2, HB8P1 and HB4N3 with significant salt tolerance, and PGPR ability were identified through sequencing of amplified 16SrRNA gene and were found to be Bacillus paramycoides, Bacillus amyloliquefaciens and Bacillus pumilus, respectively. Conclusions The salt-tolerant plant growth-promoting rhizobacteria (PGPR) isolated from saline soil can be used to overcome the detrimental effects of salt stress on plants, with beneficial effects of physiological functions of plants such as growth and yield, and overcome disease resistance. Therefore, application of microbial inoculants to alleviate stresses and enhance yield in plants could be a low cost and environmental friendly option for the management of saline soil for better crop productivity

Comparative evaluation of antimicrobial and antioxidant potential of ethanolic extract and its fractions of bark and leaves of Terminalia arjuna from north-western Himalayas, India

The present study was aimed to evaluate the antimicrobial and antioxidant potential of ethanolic extract and its different solvent fractions (chloroform, ethyl acetate, n-butanol and aqueous fraction) of bark and leaves of Terminalia arjuna. The antimicrobial activity was determined by disc diffusion and minimum inhibitory concentration (MIC) methods against six bacterial stains. The antioxidant activity was evaluated by using DPPH, FRAP and Nitric oxide (NO) scavenging assay. The total phenolics and flavonoid content were found to be higher in n-butanolic fraction of bark (294.6 ± 8.1 mg/g GAE and 168.6 ± 12.3 mg/g RE, respectively) and leaves (203.7 ± 7.0 mg/g GAE and 144.8 ± 11.1 mg/g RE, respectively). The maximum antimicrobial activity was shown by n-butanolic fraction of bark and leaves. The zone of inhibition of 15.0 ± 0.7 mm, 15.5 ± 0.7 mm, 15.0 ± 1.5 mm, 15.5 ± 0.7 mm, 15.0 ± 0.7 mm, 15.0 ± 0.7 mm was observed against Bacillus subtilis, Staphylococcus aureus, Eschericia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhi respectively. In case of leaves extract, zone of inhibition of 13.5 ± 0.7 mm, 16.5 ± 0.7 mm, 14.0 ± 0.5 mm, 15.0 ± 0.5 mm, 13.5 ± 0.7 mm, 14.0 ± 0.7 mm was observed against B. subtilis, S. aureus, E. coli, K. pneumoniae, P. aeruginosa, S. typhi, respectively. The n-butanol fraction of bark [IC50-4.1 μg/ml (DPPH), 21.0 μM (FRAP), 3.3 μg/ml (NO)] and leaves [IC50-4.8 μg/ml (DPPH), 28.9 μM (FRAP), 3.2 μg/ml (NO)] showed more antioxidant potential as compared to that of crude ethanolic extract, ethyl acetate fraction, chloroform fraction, aqueous fraction and even ascorbic acid. These results clearly indicated comparative antioxidant potential and antimicrobial activity in extracts of bark and leaves of T. arjuna

A Review of Medicinal Plants of the Himalayas with Anti-Proliferative Activity for the Treatment of Various Cancers

Cancer is a serious and significantly progressive disease. Next to cardiovascular disease, cancer has become the most common cause of mortality in the entire world. Several factors, such as environmental factors, habitual activities, genetic factors, etc., are responsible for cancer. Many cancer patients seek alternative and/or complementary treatments because of the high death rate linked with cancer and the adverse side effects of chemotherapy and radiation therapy. Traditional medicine has a long history that begins with the hunt for botanicals to heal various diseases, including cancer. In the traditional medicinal system, several plants used to treat diseases have many bioactive compounds with curative capability, thereby also helping in disease prevention. Plants also significantly contributed to the modern pharmaceutical industry throughout the world. In the present review, we have listed 33 medicinal plants with active and significant anticancer activity, as well as their anticancer compounds. This article will provide a basic set of information for researchers interested in developing a safe and nontoxic active medicinal plant-based treatment for cancer. The research will give a scientific foundation for the traditional usage of these medicinal herbs to treat cancer

Multitarget Potential of Phytochemicals from Traditional Medicinal Tree, <i>Terminalia arjuna</i> (Roxb. ex DC.) Wight & Arnot as Potential Medicaments for Cardiovascular Disease: An In-Silico Approach

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Terminalia arjuna (Roxb. ex DC.) Wight & Arnot of the Combretaceae family is one of the most frequently approved and utilized medicinal trees in the traditional medicinal system, which was used for the treatment of a variety of diseases, including cardiovascular disorders. The present study aims to identify phytochemicals from T. arjuna, that do not exhibit any toxicity and have significant cardioprotective activity using an in-silico technique. Four different cardiovascular proteins, namely human angiotensin receptor (PDB ID: 4YAY), P38 mitogen-activated protein kinase (MAPK, PDB ID: 4DLI), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-Co A) reductase (PDB ID: 1HW9), and human C-reactive protein (PDB ID: 1B09), were used as target proteins to identify potential inhibitors using a virtual screening of the phytochemicals in T. arjuna revealed casuarinin as a potential inhibitor of all selected target proteins with strong binding energy. Furthermore, MD simulations for a 100 ns time scale also revealed that most of the key protein contacts of all target proteins were retained throughout the simulation trajectories. Binding free energy calculations using the MM-GBSA approach also support a strong inhibitory effect of casuarinin on target proteins. Casuarinin’s effective binding to these proteins lays the groundwork for the development of broad-spectrum drugs as well as the understanding of the underlying mechanism against cardiovascular diseases through in vivo and clinical studies

Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne

AbstractAzelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index &lt; 0.7), nano-range (~357.4 ± 2% nm), transmittance (&gt; 90%), and negative zeta potential (−1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris. Graphical abstract</jats:p