3D bioprinting of multifunctional alginate dialdehyde (ADA)-gelatin (GEL) (ADA-GEL) hydrogels incorporating ferulic acid.

The present work explores the 3D extrusion printing of ferulic acid (FA)-containing alginate dialdehyde (ADA)-gelatin (GEL) scaffolds with a wide spectrum of biophysical and pharmacological properties. The tailored addition of FA (≤0.2 %) increases the crosslinking between FA and GEL in the presence of calcium chloride (CaCl2) and microbial transglutaminase, as confirmed using trinitrobenzenesulfonic acid (TNBS) assay. In agreement with an increase in crosslinking density, a higher viscosity of ADA-GEL with FA incorporation was achieved, leading to better printability. Importantly, FA release, enzymatic degradation and swelling were progressively reduced with an increase in FA loading to ADA-GEL, over 28 days. Similar positive impact on antibacterial properties with S. epidermidis strains as well as antioxidant properties were recorded. Intriguingly, FA incorporated ADA-GEL supported murine pre-osteoblast proliferation with reduced osteosarcoma cell proliferation over 7 days in culture, implicating potential anticancer property. Most importantly, FA-incorporated and cell-encapsulated ADA-GEL can be extrusion printed to shape fidelity-compliant multilayer scaffolds, which also support pre-osteoblast cells over 7 days in culture. Taken together, the present study has confirmed the significant potential of 3D bioprinting of ADA-GEL-FA ink to obtain structurally stable scaffolds with a broad spectrum of biophysical and therapeutically significant properties, for bone tissue engineering applications.

Revisiting the Multifaceted Therapeutic Potential of Withaferin A (WA), a Novel Steroidal Lactone, W-ferinAmax Ashwagandha, from Withania Somnifera (L) Dunal.

Withania somnifera (L.) Dunal, abundant in the Indian subcontinent as Ashwagandha or winter cherry, is a herb of unprecedented therapeutic value. The number of ailments for which crude Ashwagandha extract can be used as a preventive or curative is practically limitless; and this explains why its use has been in vogue in ancient Ayurveda since at-least about four thousand years. The therapeutic potential of Ashwagandha mainly owes from its reservoir of alkaloids (isopelletierine, anaferine), steroidal lactones (withanolides) and saponins with an extra acyl group (sitoindoside VII and VIII). Withaferin A is an exceptionally potent withanolide which is found in high concentrations in W. somnifera plant extracts. The high reactivity of Withaferin A owes to the presence of a C-28 ergostane network with multiple sites of unsaturation and differential oxygenation. It interacts with the effectors of multiple signaling pathways involved in inflammatory response, oxidative stress response, cell cycle regulation and synaptic transmission and has been found to be significantly effective in inducing programmed cell death in cancer cells, restoring cognitive health, managing diabetes, alleviating metabolic disorders, and rejuvenating the overall body homeostasis. Additionally, recent studies suggest that Withaferin A (WA) has the potential to prevent viral endocytosis by sequestering TMPRSS2, the host transmembrane protease, without altering ACE-2 expression. The scope of performing subtle structural modifications in this multi-ring compound is believed to further expand its pharmacotherapeutic horizon. Very recently, a novel, heavy metal and pesticide free formulation of Ashwagandha whole herb extract, with a significant amount of WA, termed W-ferinAmax Ashwagandha, has been developed. The present review attempts to fathom the present and future of this wonder molecule with comprehensive discussion on its therapeutic potential, safety and toxicity.Key teaching pointsWithania somnifera (L.) Dunal is a medicinal plant with versatile therapeutic values.The therapeutic potential of the plant owes to the presence of withanolides such as Withaferin A.Withaferin A is a C-28 ergostane based triterpenoid with multiple reactive sites of therapeutic potential.It is effective against a broad spectrum of ailments including neurodegenerative disorders, cancer, inflammatory and oxidative stress disorders and it also promotes cardiovascular and sexual health.W-ferinAmax Ashwagandha, is a heavy metal and pesticide free Ashwagandha whole herb extract based formulation with significant amount of Withaferin A.

Modulatory Properties of Aloe secundiflora's Methanolic Extracts on Targeted Genes in Colorectal Cancer Management.

Colon tumors have a very complicated and poorly understood pathogenesis. Plant-based organic compounds might provide a novel source for cancer treatment with a sufficient novel mode of action. The objective of this study was to analyze and evaluate the efficacy of Aloe secundiflora's (AS) methanolic extracts on the expression of CASPS9, 5-LOX, Bcl2, Bcl-xL, and COX-2 in colorectal cancer (CRC) management. Caco-2 cell lines were used in the experimental study. In the serial exhaustive extraction (SEE) method, methanol was utilized as the extraction solvent. Upon treatment of CASPS9 with the methanolic extracts, the expression of the genes was progressively upregulated, thus, dose-dependently increasing the rate of apoptosis. On the other hand, the expressions of 5-LOX, Bcl2, and Bcl-xL were variably downregulated in a dose-dependent manner. This is a unique novel study that evaluated the effects of AS methanolic extracts in vitro on CRC cell lines using different dosage concentrations. We, therefore, recommend the utilization of AS and the application of methanol as the extraction solvent of choice for maximum modulatory benefits in CRC management. In addition, we suggest research on the specific metabolites in AS involved in the modulatory pathways that suppress the development of CRC and potential metastases.

Mikania micrantha Kunth: An Ethnopharmacological Treasure Trove of Therapeutic Potential.

Mikania micrantha is utilized as a therapeutic for the treatment of various human ailments including insect bites, rashes and itches of skin, chicken pox, healing of sores and wounds, colds and fever, nausea, jaundice, rheumatism, and respiratory ailments. This study aimed at summarizing the traditional uses, phytochemical profile, and biological activities of M. micrantha based on obtainable information screened from different databases. An up-to-date search was performed on M. micrantha in PubMed, Science Direct, clinicaltrials.gov, and Google Scholar databases with specific keywords. No language restrictions were imposed. Published articles, theses, seminar/conference papers, abstracts, and books on ethnobotany, phytochemistry and pharmacological evidence were considered. Based on the inclusion criteria, this study includes 53 published records from the above-mentioned databases. The results suggest that fresh leaves and whole plant are frequently used in folk medicine. The plant contains more than 150 different phytochemicals under the following groups: essential oils, phenolics and flavonoids, terpenes, terpene lactones, glycosides, and sulfated flavonoids. It contains carbohydrates and micronutrients including vitamins and major and trace minerals. M. micrantha possesses antioxidant, anti-inflammatory, anti-microbial, anti-dermatophytic, anti-protozoal, anthelmintic, cytotoxic, anxiolytic, anti-diabetic, lipid-lowering and antidiabetic, spasmolytic, memory-enhancing, wound-healing, anti-aging, and thrombolytic activities. No clinical studies have been reported to date. M. micrantha might be one of the potential sources of phytotherapeutic compounds against diverse ailments in humans. Studies are required to confirm its safety profile in experimental animals prior to initiating clinical trials. Moreover, adequate investigation is also crucial to clarify exact mechanism of action for each biological effect.

Regulatory activities of Warbugia ugandensis ethanolic extracts on colorectal cancer-specific genome expression dose-dependently.

The evaluation of natural biomass sources is a promising strategy in accelerating the development of novel anti-cancer medications. Our study aimed to evaluate the activity of W. ugandensis ethanolic roots and stems extracts on the expression of five targeted genes (COX-2, CASPS-9, Bcl-xL, Bcl2 and 5-LOX) in colorectal cancer (CRC) cell lines (Caco-2). Plant extracts were obtained using serial exhaustive extraction and dissolved in Dimethyl sulfoxide appropriately for bioassay. Caco-2 cell lines were passaged, treated with plant extracts at varying concentrations and their RNA's isolated for evaluation. Our unique study reports on W. ugandensis as efficient natural inhibitors of CRC growth, by directly linking its phytoconstituents to; downregulation of COX-2, 5-LOX, Bcl-xL, Bcl2 and upregulation of CASPS9 genes dose-dependently. We present W. ugandensis ethanolic roots and stems extracts as promising natural inhibitors for CRC carcinogenesis and recommend in vivo and subsequent clinical trials, with substantial clinical effects postulated. We further suggest studies on identification and characterization of the specific metabolites in W. ugandensis involved in the modulatory mechanisms, resulting to inhibition of CRC growth and possible metastases.

3D-Printed Multifunctional Hydrogels with Phytotherapeutic Properties: Development of Essential Oil-Incorporated ALG-XAN Hydrogels for Wound Healing Applications.

This study aimed to develop three-dimensional (3D)-printed hydrogels containing phytotherapeutic agents as multifunctional wound dressings. In this regard, 3D-printed sodium alginate (ALG)-xanthan gum (XAN) hydrogels incorporated with different clove essential oil (CLV) concentrations were produced by the extrusion-based 3D-printing technology. Rheology measurements, filament fusion, and filament collapse analyses indicated that XAN's blending overcame the challenges associated with ALG's printability and shape fidelity. Attenuated total reflection-Fourier-transform infrared (ATR-FTIR) spectra and total phenolic content assay confirmed the presence of CLV in the 3D-printed hydrogels. Additionally, the releasing profile showed that CLV exhibited long-term release for up to 28 days. Furthermore, the incorporation of CLV increased 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging while reducing the S. aureus and E. coli relative bacterial viability; thereby, the CLV incorporation enhanced the 3D-printed ALG-XAN hydrogel antioxidant and antibacterial activity. In addition, anti-inflammatory activity was assessed using Raw 264.7 macrophage-like cells, and the results demonstrated that CLV reduced nitric oxide (NO) concentration in medium, indicating a potential anti-inflammatory effect. Moreover, in vitro cytotoxicity results showed that the incorporation of CLV has no toxic effect on NHDF cells, whereas the proliferation of NHDF cells exhibited a dose-dependent response. In conclusion, the present study shows not only the development of a new ALG-XAN biomaterial ink but also the potential benefit of natural phytotherapeutics incorporated into 3D-printed hydrogels as a multifunctional wound dressing.

Effect of Vapor-Phase Oregano Essential Oil on Resistant Candida Species Biofilms: Mechanisms of Action.

Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases. The increasing incidence of drug-resistant Candida strains and the limited therapeutic options make the discovery of effective alternative therapies fundamental. Essential oils (EOs) have been suggested as a promising alternative, and interestingly, vapor-phase essential oils (VP-EOs) present more advantages than their direct application. Thus, this study aims to evaluate the effect of oregano VP-EO (VP-OEO) on biofilms of antifungal-resistant vaginal isolates of Candida species (Candida albicans and Candida glabrata) and determine its mode of action. CFU, membrane integrity, and metabolic activity were evaluated. Furthermore, a reconstituted vaginal epithelium was used to mimic vaginal conditions and evaluate the effect of VP-OEO on Candida species infection, analyzed by DNA quantification, microscopy, and lactate dehydrogenase activity. The results revealed high VP-OEO antifungal activity. There was a significant reduction (>4 log CFU) in Candida species biofilms. Furthermore, the results show that the mechanisms of action of VP-OEO are related to membrane integrity and metabolic activity. The epithelium model confirms the effectiveness of VP-OEO. This study suggests that VP-EO can be considered a first approach for the development of an alternative form of VVC treatment. IMPORTANCE This work presents a new approach to the application of essential oils, exposure to the vapor phase, which can be considered a first approach for the development of a complementary or alternative form of vulvovaginal candidiasis (VVC) treatment. VVC is a significant infection caused by Candida species and remains a common disease that affects millions of women every year. The great difficulty in treating VVC and the extremely limited effective therapeutic options make the development of alternative treatments crucial. In this scope, this study aims to contribute to the development of effective, inexpensive, and nontoxic strategies for the prevention and treatment of this infectious disease, based on natural products. Moreover, this new approach has several advantages for women, such as lower costs, easy access, an easier mode of application, avoidance of skin contact, and, therefore, fewer negative impacts on women's health.

Action of crude ethanol extract of Hymenaea martiana leaf, gallic acid, and polypyrrole (PPy) against Aeromonas hydrophila.

Pisciculture represents one of the industries with the fastest growth rates worldwide. However, it presents obstacles to its development, such as bacteriosis, which is conventionally treated with antibiotics. The indiscriminate and inappropriate use of antibiotics can lead to bacterial resistance, thus alternatives to the use of antibiotics have been researched. The study aimed to analyze the potential of crude ethanol extract (CEE) from Hymenaea martiana leaf, gallic acid (GA), and polypyrrole (PPy) against Aeromonas hydrophila. Tests were performed to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compounds individually and in synergy (checkerboard) against A. hydrophila and in silico tests between the compounds evaluated. The CEE of H. martiana leaf and PPy were effective against A. hydrophila with MBC results of 3125 µg/mL for the CEE of H. martiana and 125 µg/mL for PPy. Evaluating the GA, a MIC and MBC of 125 µg/mL was obtained. In the interaction tests (checkerboard, using PPy/CEE and PPy/GA), there was a significant reduction in individual introductions. Thus, for the PPy/CEE tests, we had a reduction of MIC/MBC to 1.95 and 781.25 µg/mL, and for the synergy tests between PPy/GA to 7.8125 and 31.125 µg/mL, respectively. The synergy tests are encouraging, and it is possible to verify a decrease of up to 98% in the introduction of PPy, 75% in CEE for H. martiana and 75.1% for GA, when compared to their individual tests. The tests with GA are encouraging due to GA's effectiveness as an antimicrobial agent and high synergy with polypyrrole, both in vitro results and molecular docking experiments showed the actions at the same activation site in A. hydrophila. In vivo tests evaluating isolated components of CEE from H. martiana in synergy with PPy should be performed, to verify the quality of the interactions and the improvement of the immune responses of the animals. It was evidenced that gallic acid, a substance isolated from the extract, tends to have more promising results. This is relevant since the industry has been developing these compounds for different uses, thus providing easier access to the product. Thus, the present study indicates an efficient alternative in the use of bioactive compounds as substitutes for conventional antimicrobials.

The chromatographic constitution of andiroba oil and his healing effects, compared to the LLLT outcomes, in oral mucositis induced in golden Syrian hamsters: a new treatment option.

The oral mucositis is a mucosal alteration that usually arises from oncological treatments, such as chemotherapy, and it is characterized as an inflammatory process. The aim of this study is to demonstrate the chromatographic constitution of Andiroba oil, comparing and evaluating Andiroba oil and laser scarring efficiency in treatments of oral mucositis in hamsters. These animals were submitted to 5-Fluorouracil. A total of 122 animals were used, randomized and divided into the following groups: (a) positive control; (b) laser associated to andiroba oil; (c) laser; (d) andiroba oil; (e) negative control; (f) cyclophosphamide (genotoxicity control). The induction of oral mucositis occurred by the administration of intraperitoneal Fluorouracila (60 mg/kg) and trauma to the mucosa. The laser protocol was performed once a day and the andiroba oil applied 3 times a day (1,5 ml/day). The mucosae were photographed and removed for clinical and histopathological analysis on day 4, 8, 12 and 15. The analysis was based in OM severity, in specific scoring for the clinical and histopathological aspect. Toxicity was evaluated on day 15 using comet assay and it was performed by variant DNA damage parameters. The data were analysed using analysis of variance (ANOVA) Tukey post-test and Kruskal-Wallis Dunn post-test. The "andiroba oil" and "laser" groups presented better results when compared to the control groups and the treatment associations. The andiroba oil presented the best scarring results, even considering its efficiency proximity to the laser treatment. Andiroba and laser, separately, did not present genotoxicity, however their association evidences damage to DNA.

A influência do acompanhamento farmacoterapêutico na adesão à terapia com Morosil / La influencia del seguimiento farmacoterapéutico sobre la adherencia a la terapia con Morosil / The influence of pharmacotherapeutic follow-up on adherence to Morosil therapy

Após proibição de substâncias utilizadas no emagrecimento, pela ANVISA, notou-se uma crescente procura pelo Morosil. Objetivou realizar o acompanhamento farmacoterapêutico a usuários de Morosil, inseridos em uma prática de atenção farmacêutica, quanto a adesão terapêutica e satisfação do cliente. O procedimento foi realizado no período de maio a julho de 2017. Os dados foram coletados por meio dos questionários: Método Dáder de Acompanhamento Farmacoterapêutico, Morisky Medication Adherence Scale e Pharmacy Services Questionnaire, adaptados. A amostra foi constituída de 35 indivíduos: 97,1% feminino, 100% insatisfeitos com seu peso. Avaliados, 60% pré-obesos e 40% obesos. Observou-se condições de saúde associada, distúrbios endócrinos/hormonais (34,2%), psiquicos (22,8%) e cardiovasculares (14,2%), 96,8% fazem uso de polimedicação. A adesão terapêutica foi de 100% e 93,3% classificaram os cuidados farmacêuticos como ótimo. Não se constatou interação medicamentosa com Morosil. O acompanhamento farmacoterapêutico permitiu: manutenção dos objetivos terapêuticos, promoção da saúde do paciente e reconhecimento profissional do farmacêutico. (AU)

Después de la prohibición de determinadas sustancias utilizadas en la pérdida de peso por parte de ANVISA, hubo una creciente demanda de Morosil. Objetivo: realizar un seguimiento farmacoterapéutico a los usuarios de Morosil, insertados en una práctica asistencial farmacéutica, en cuanto a adherencia terapéutica y satisfacción del cliente. El estudio se realizó de mayo a julio de 2017. Los datos se recolectaron mediante cuestionarios: Método de seguimiento farmacoterapéutico de Dáder, Escala de adherencia a la medicación de Morisky y Cuestionario de servicios de farmacia, adaptado. La muestra estuvo conformada por 35 individuos: 97,1% mujeres, 100% insatisfechas con su peso. Un 60% de los participantes eran preobesos y un 40% obesos. Se observaron problemas de salud asociados, trastornos endocrinos/hormonales (34,2%), psiquiátricos (22,8%) y cardiovasculares (14,2%). El 96,8% estaban polimedicados. La adherencia terapéutica fue del 100% y 93,3% calificó la atención farmacéutica como excelente. No hubo interacción farmacológica con Morosil. El seguimiento farmacoterapéutico permitió el mantenimiento de los objetivos terapéuticos, la promoción de la salud del paciente y el reconocimiento profesional del farmacéutico. (AU)

After the ban on substances used in slimming, by ANVISA, there has been a growing demand for Morosil. This study aimed to carry out pharmacotherapeutic follow-up to Morosil users, inserted in a pharmaceutical care practice, regarding therapeutic adherence and customer satisfaction. The procedure was carried out from May to July 2017. The data were collected through the questionnaires: Dáder Method of Pharmacotherapeutic Follow-up Morisky Medication Adherence Scale and Pharmacy Services Questionnaire, adapted. The sample consisted of 35 individuals: 97.1% female, 100% dissatisfied with their weight. Evaluated, 60% as pre-obese and 40% as obese. Associated health conditions, endocrine / hormonal disorders (34.2%), psychic (22.8%) and cardiovascular (14.2%) were observed, 96.8% use polymedication. Therapeutic adherence was 100% and 93.3% rated pharmaceutical care as excellent. There was no drug interaction with Morosil. The pharmacotherapeutic follow-up allowed: maintenance of the therapeutic objectives, promotion of the patient's health and professional recognition of the pharmacist. (AU)

Design and Optimization of a Natural Medicine from Copaifera reticulata Ducke for Skin Wound Care.

In this study, we developed a bioadhesive emulsion-filled gel containing a high amount of Copaifera reticulata Ducke oil-resin as a veterinary or human clinical proposal. The phytotherapeutic system had easy preparation, low cost, satisfactory healing ability, and fly repellency, making it a cost-effective clinical strategy for wound care and myiasis prevention. Mechanical, rheological, morphological, and physical stability assessments were performed. The results highlight the crosslinked nature of the gelling agent, with three-dimensional channel networks stabilizing the Copaifera reticulata Ducke oil-resin (CrD-Ore). The emulgel presented antimicrobial activity, satisfactory adhesion, hardness, cohesiveness, and viscosity profiles, ensuring the easy spreading of the formulation. Considering dermatological application, the oscillatory responses showed a viscoelastic performance that ensures emulgel retention at the action site, reducing the dosage frequencies. In Vivo evaluations were performed using a case report to treat ulcerative skin wounds aggravated by myiasis in calves and heifers, which demonstrated healing, anti-inflammatory, and repellent performance for the emulsion-filled gel. The emulgel preparation, which is low in cost, shows promise as a drug for wound therapy.

Vapor-Phase of Essential Oils as a Promising Solution to Prevent Candida Vaginal Biofilms Caused by Antifungal Resistant Strains.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a disease with high incidence, a huge impact on the quality of life and health of women, and which represents a great challenge to treat. The growing need to apply antifungal intensive therapies have contributed to an emergence of drug-resistant Candida strains. Thus, effective therapeutic options, to meet the antifungal-resistance challenge and to control high resilient biofilms, are urgently needed. This study aimed to investigate the antifungal activity of essentials oils (EOs) on drug-resistant Candida vaginal isolates. METHOD: Therefore, the antimicrobial effect of tea tree, niaouli, white thyme, and cajeput EOs on the planktonic growth of Candida isolates was initially evaluated by an agar disc diffusion method. Then, the vapor-phase effect of tea tree EO (VP-TTEO) on biofilm formation and on pre-formed biofilms was evaluated by crystal violet staining, XTT reduction assay, colony forming units' enumeration, and scanning electron microscopy. RESULTS: The results revealed high antifungal activity of EOs against drug-resistant Candida isolates. Additionally, the VP-TTEO showed a significant inhibitory effect on the biofilm formation of all tested isolates and was able to provoke an expressive reduction in mature Candida albicans biofilms. CONCLUSIONS: Overall, this study suggests that the VP-EO may be a promising solution that is able to prevent biofilm-related VVC caused by antifungal-resistant strains.

Green Synthesis-Mediated Nanoparticles and Their Curative Character Against Post COVID-19 Skin Diseases.

Purpose of Review: This article provides the explanatory manuscript regarding the SARS-Corona virus 2. Sub-titled as the history of single-stranded RNA, internal characters of COVID-19, resource, the life cycle of COVID-19, reservoir of the disease, secondary infections of COVID-19 and nano herbal remedy. Recent Findings: The skin is not the main target of the SARS-corona virus 2 infections but somehow directly or indirectly, it causes exacerbating eruptions on the skin. Recent research shows that curcumin-mediated synthesized AgNPs show its potential character in the entry of respiratory syncytial virus (RSV), blocks interaction with the viral surface, and damages the viral protein. In modern days, molecular docking studies fabricated copper iodide flower extract (CuI-FE) which shows tough inhibitory action against COVID-19. Many articles show green synthesis-mediated nanoparticles like silver, gold, zinc, copper, iron, titanium dioxide, selenium, and cadmium which possess high anti-viricidal activity. Summary: The anti-oxidant, anti-viral, anti-inflammatory, anti-hive rich plant-mediated nanoparticle synthesis might be an alternative betterment, cost-effective, and eco-friendly medication for the skin disease caused by SARS-corona virus 2 (the viral clinical signs are itchy, hives, rashes, papules, psoriasis, and inflammation) and (non-viral clinical signs-pressure urticaria, contact dermatitis, and acne) that occurred as the result of COVID-19.

Essential Oils as a Good Weapon against Drug-Resistant Candida auris.

Candida auris is a recently found Candida species, mainly associated with nosocomial outbreaks in intensive care hospital settings, and unlike other Candida species, it can be transmitted through person-to-person or by contact with surfaces. C. auris is described as resistant to first-line antifungals and, consequently, associated with high mortality. Nowadays, essential oils (EOs) are known to be effective against fungal and bacterial infections. This work aimed to evaluate the effect of four EOs (tea tree, niaouli, white thyme and cajeput) against C. auris. The EO's effect on C. auris planktonic growth was evaluated by the minimum inhibitory concentration determination and by the agar disc diffusion method. Then, the same effect was evaluated on biofilm by colony-forming units' enumeration. The results showed that EOs were able to inhibit the C. auris planktonic growth, with an MIC50 between 0.78 and 1.56% and halos of 20-21 mm for white thyme and tea tree and 13-14 mm for cajeput and niaouli. In addition, the EOs were also able to completely inhibit biofilm formation. Moreover, white thyme and cajeput completely eradicate pre-formed biofilms, while tea tree and niaouli significantly reduce it. Thus, this work demonstrates that EOs are a possible therapeutic alternative and a future perspective for the hard fight against C. auris.

Recombinant osmotin inclusion bodies from Calotropis procera produced in E. coli BL21(DE3) prevent acute inflammation in a mouse model of listeriosis.

BACKGROUND: The osmotin from the medicinal plant Calotropis procera (CpOsm) has characteristics similar to adiponectin, a human protein with immunoregulatory actions. PURPOSE: This study aimed to investigate whether recombinant osmotin inclusion bodies from C. procera (IB/rCpOsm) produced in E. coli BL21(DE3) can prevent infection-induced inflammation. A virulent strain of Listeria monocytogenes was used as an infection model. METHODS: Cells of E. coli BL21(DE3) carrying the plasmid pET303-CpOsm were used to express the recombinant osmotin, which accumulated at reasonable levels as inclusion bodies (IB/rCpOsm). IB/rCpOsm were purified from induced cells and SDS-polyacrylamide gel electrophoresis followed by mass spectrometry analyses confirmed the identity of the major protein band (23 kDa apparent molecular mass) as CpOsm. Peritoneal macrophages (pMØ) from Swiss mice were cultured with IB/rCpOsm (1 or 10 µg/ml) in 96-well plates and then infected with L. monocytogenes. IB/rCpOsm (0.1, 1 or 10 mg/kg) was also administered intravenously to Swiss mice, which were then infected intraperitoneally with L. monocytogenes. RESULTS: Pretreatment of the pMØ with IB/rCpOsm significantly increased cell viability after infection and reduced the intracellular bacterial load. The infiltration of neutrophils into the peritoneal cavity of mice pretreated with IB/rCpOsm at 10 mg/kg (but not 0.1 and 1 mg/kg) was reduced after infection. In these mice, the bacterial load was high in the peritoneal fluid and the liver, but histological damage was discrete. The treatments with IB/rCpOsm at 10 mg/kg significantly increased the expression of the anti-inflammatory cytokine IL-10. CONCLUSION: This study shows that recombinant osmotin inclusion bodies from C. procera were bioactive and prompted anti-inflammatory actions at therapeutic dosages in the L. monocytogenes infection model.

Phytotherapy for the Treatment of Glioblastoma: A Review.

Background: Phytotherapy; the study of extracts of natural origin in the treatment of disease, has scarcely been applied in the management of GBM. A body of literature exists studying in-vitro, the use of natural extracts against GBM cells. Given persisting poor prognoses, we evaluated, through systematic literature-review the therapeutic potential of naturally sourced extracts in-vivo. Methods: Using OVID, MEDLINE and EMBASE databases were searched with compound search term. Abstracts and full-texts were double-screened by independent reviewers. Results: Nine hundred and eighty-seven articles, excluding duplicated were screened, leading to the inclusion of 14. Amongst murine studies, Ashwagandha, Coptis Chinensis and Fructus Ligustri Lucidi in unprocessed forms, produced significant reductions in tumour volume. Amongst human studies, Perrilyl alcohol, derived from Lavender, reduced angiogenic cytokines in 31% of subjects, halted 6 month disease progression in 48.2% of subjects, and improved mean survival by 4.9 months in separate studies, respectively. Conclusion: Although cursory, current trends in literature demonstrate the value of inhaled Lavender extract in the treatment of GBM, offering tangible clinical benefit to patients receiving conventional treatments. Furthermore, the administration of 8, discrete extracts in mice to produce significant responses in survival and tumour volume, suggest there is further scope for study. Although additional safety tests are required, currently, phytotherapeutics are the crossover to clinical translation, and additional trials are warranted to expound upon thus far promising results.

Phytomelatonin: a potential phytotherapeutic intervention on COVID-19-exposed individuals.

Phytomelatonin is a pleiotropic molecule that originated in higher plants with many diverse actions and is primarily an antioxidant. The recent identification and advancement of phytomelatonin unraveled the potential of this modulatory molecule being considered a new plant hormone, suggesting its relevance in treating respiratory infections, including COVID-19. Besides, this molecule is also involved in multiple hormonal, physiological, and biological processes at different levels of cell organization and has been marked for its ability to cross the blood-brain barrier and prominent antioxidant effects, reducing mitochondrial electron leakage, up-regulating antioxidant enzymes, acting as a free radical scavenger, and interfering with pro-inflammatory signaling pathways as seen in mood swings, body temperature, sleep, cancer, cardiac rhythms, and immunological regulation modulators. However, due to its diversity, availability, affordability, convenience, and high safety profile, phytomelatonin has also been suggested as a natural adjuvant. This review discussed the origin, content in various plant species, processes of extraction, and detection and therapeutic potentials of phytomelatonin in treating COVID-19-exposed individuals.

3D printing of alginate dialdehyde-gelatin (ADA-GEL) hydrogels incorporating phytotherapeutic icariin loaded mesoporous SiO2-CaO nanoparticles for bone tissue engineering.

3D printing enables a better control over the microstructure of bone restoring constructs, addresses the challenges seen in the preparation of patient-specific bone scaffolds, and overcomes the bottlenecks that can appear in delivering drugs/growth factors promoting bone regeneration. Here, 3D printing is employed for the fabrication of an osteogenic construct made of hydrogel nanocomposites. Alginate dialdehyde-gelatin (ADA-GEL) hydrogel is reinforced by the incorporation of bioactive glass nanoparticles, i.e. mesoporous silica-calcia nanoparticles (MSNs), in two types of drug (icariin) loading. The composites hydrogel is printed as superhydrated composite constructs in a grid structure. The MSNs not only improve the mechanical stiffness of the constructs but also induce formation of an apatite layer when the construct is immersed in simulated body fluid (SBF), thereby promoting cell adhesion and proliferation. The nanocomposite constructs can hold and deliver icariin efficiently, regardless of its incorporation mode, either as loaded into the MSNs or freely distributed within the hydrogel. Biocompatibility tests showed that the hydrogel nanocomposites assure enhanced osteoblast proliferation, adhesion, and differentiation. Such optimum biological properties stem from the superior biocompatibility of ADA-GEL, the bioactivity of the MSNs, and the supportive effect of icariin in relation to cell proliferation and differentiation. Taken together, given the achieved structural and biological properties and effective drug delivery capability, the hydrogel nanocomposites show promising potential for bone tissue engineering.

O uso de fitoterápicos no tratamento do diabetes mellitus: uma revisão da literatura / Use of phytotherapes in the treatment of diabetes mellitus: a literature review / El uso de medicamentos a base de hierbas en el tratamiento de la diabetes mellitus: una revisión de la literatura

No Brasil, aproximadamente 9,1 milhões de pessoas são portadoras de diabetes mellitus, uma doença proveniente de falhas nos mecanismos metabólicos e que tem por consequência a hiperglicemia e várias outras complicações. Entre os programas ofertados pelo Sistema Único de Saúde para o seu controle, destaca-se a fitoterapia, que vem se mostrando bastante eficaz, conforme evidenciam os resultados de diferentes estudos. Por meio deste artigo de revisão, propõe-se conhecer e analisar a produção científica publicada acerca do uso de fitoterápicos e plantas medicinais no tratamento do diabetes mellitus. Para tal, optou-se pela realização de um estudo bibliográfico, em que foram analisadas publicações a partir de 1990. As plantas que obtiveram resultados positivos em diversos estudos foram as espécies: Bauhinia forficata (pata-de-vaca), Syzygium cumini (jamelão), Sphagneticola trilobata (insulina), Cissus sicyoides L (insulina vegetal), carqueja, tintura de mororó, Stevia rebaudiana, Chrysobalanus icaco Lin (abajeru), Myrcia multiflora (pedra-ume-caá) e epicarpo da romã. As evidências acerca dos benefícios proporcionados pelo uso das plantas medicinais corroboram a necessidade de investimento para sua utilização adequada e melhoria da qualidade de vida do paciente diabético.

In Brazil, approximately 9.1 million people live with diabetes mellitus (DM), a disease that results from failures in metabolic mechanisms and leads to hyperglycemia and several other complications. Among the programs provided by the Unified Health System for DM control, phytotherapy stands out as quite effective, as reported by different studies. Thus, this literature review proposes to examine and analyze the scientific production published on the use of herbal medicines and medicinal plants in treating diabetes mellitus. To this end, articles published starting from 1990 were analyzed. The plants Bauhinia forficata (cow's foot), Syzygium cumini (jamelão), Sphagneticola trilobata (insulin), Cissus sicyoides L (vegetable insulin), gorse, Mororó tincture, Stevia rebaudiana, Chrysobalanus icaco Lin (abajeru), Myrcia multiflora (rock-hume-caá), and pomegranate Epicarp obtained positive results in several studies. Evidence on the benefits provided by medicinal plants corroborates the need for investment aimed at proper phytotherapy and at improving the quality of life of diabetic patients.

En Brasil, aproximadamente 9,1 millones de personas tienen diabetes mellitus, una enfermedad causada por fallas en los mecanismos metabólicos y que resultan en hiperglucemia y varias otras complicaciones.  Entre los programas que ofrece el Sistema Único de Salud para su control, se destaca la fitoterapia, que ha demostrado ser bastante eficaz, como lo demuestran los resultados de diferentes estudios. A través de este artículo de revisión se propone conocer y analizar la producción científica publicada sobre el uso de hierbas y plantas medicinales en el tratamiento de la diabetes mellitus. Para ello, se decidió realizar un estudio bibliográfico, donde se analizaron publicaciones de 1990. Las plantas que obtuvieron resultados positivos en varios estudios fueron las especies: Bauhinia forficata (pata-de-vaca), Syzygium cumini (jamelão), Sphagneticola trilobata (insulina), Cissus sicyoides L (insulina vegetal), tojo, tintura de Mororó, Stevia rebaudiana, Chrysobalanus icaco Lin. (abajeru), Myrcia multiflora (Piedra-hume-caá) y Epicarpio de la granada. La evidencia sobre los beneficios que brinda el uso de plantas medicinales corrobora la necesidad de inversión para su adecuado uso y mejora de la calidad de vida del paciente diabético.