Nanotechnology-mediated delivery of resveratrol as promising strategy to improve therapeutic efficacy in triple negative breast cancer (TNBC): progress and promises.

INTRODUCTION: Triple-negative breast cancer (TNBC) presents unique challenges in diagnosis and treatment. Resveratrol exhibits potential as a therapeutic intervention against TNBC by regulating various pathways such as the PI3K/AKT, RAS/RAF/ERK, PKCδ, and AMPK, leading to apoptosis through ROS-mediated CHOP activationand the expression of DR4 and DR5. However, the clinical efficacy of resveratrol is limited due to its poor biopharmaceutical characteristics and low bioavailability at the tumor site. Nanotechnology offers a promising approach to improving the biopharmaceutical characteristics of resveratrol to achieve clinical efficacy in different cancers. The small dimension (<200 nm) of nanotechnology-mediated drug delivery system is helpful to improve the bioavailability, internalization into the TNBC cell, ligand-specific targeted delivery of loaded resveratrol to tumor site including reversal of MDR (multi-drug resistance) condition. AREAS COVERED: This manuscript provides a comprehensive discussion on the structure-activity relationship (SAR), underlying anticancer mechanism, evidence of anticancer activity in in-vitro/in-vivo investigations, and the significance of nanotechnology-mediated delivery of resveratrol in TNBC. EXPERT OPINION: Advanced nano-formulations of resveratrol such as oxidized mesoporous carbon nanoparticles, macrophage-derived vesicular system, functionalized gold nanoparticles, etc. have increased the accumulation of loaded therapeutics at the tumor-site, and avoid off-target drug release. In conclusion, nano-resveratrol as a strategy may provide improved tumor-specific image-guided treatment options for TNBC utilizing theranostic approach.

Flavonoids as promising anticancer therapeutics: Contemporary research, nanoantioxidant potential, and future scope.

Flavonoids are natural polyphenolic compounds considered safe, pleiotropic, and readily available molecules. It is widely distributed in various food products such as fruits and vegetables and beverages such as green tea, wine, and coca-based products. Many studies have reported the anticancer potential of flavonoids against different types of cancers, including solid tumors. The chemopreventive effect of flavonoids is attributed to various mechanisms, including modulation of autophagy, induction of cell cycle arrest, apoptosis, and antioxidant defense. Despite of significant anticancer activity of flavonoids, their clinical translation is limited due to their poor biopharmaceutical attributes (such as low aqueous solubility, limited permeability across the biological membranes (intestinal and blood-brain barrier), and stability issue in biological systems). A nanoparticulate system is an approach that is widely utilized to improve the biopharmaceutical performance and therapeutic efficacy of phytopharmaceuticals. The present review discusses the significant anticancer potential of promising flavonoids in different cancers and the utilization of nanoparticulate systems to improve their nanoantioxidant activity further to enhance the anticancer activity of loaded promising flavonoids. Although, various plant-derived secondary metabolites including flavonoids have been recommended for treating cancer, further vigilant research is warranted to prove their translational values.

Utilization of Nanotechnology to Improve Bone Health in Osteoporosis Exploiting Nigella sativa and Its Active Constituent Thymoquinone.

Osteoporosis, a chronic bone disorder, is one of the leading causes of fracture and morbidity risk. Numerous medicinally important herbs have been evaluated for their efficacy in improving bone mass density in exhaustive preclinical and limited clinical studies. Nigella sativa L. has been used as local folk medicine, and traditional healers have used it to manage various ailments. Its reported beneficial effects include controlling bone and joint diseases. The present manuscript aimed to provide a sound discussion on the pharmacological evidence of N. sativa and its active constituent, thymoquinone, for its utility in the effective management of osteoporosis. N. sativa is reported to possess anti-IL-1 and anti-TNF-α-mediated anti-inflammatory effects, leading to positive effects on bone turnover markers, such as alkaline phosphatase and tartrate-resistant acid phosphatase. It is reported to stimulate bone regeneration by prompting osteoblast proliferation, ossification, and decreasing osteoclast cells. Thymoquinone from N. sativa has exhibited an antioxidant effect on bone tissue by reducing the FeNTA-induced oxidative stress. The present manuscript highlights phytochemistry, pharmacological effect, and the important mechanistic perspective of N. sativa and its active constituents for the management of osteoporosis. Further, it also provides sound discussion on the utilization of a nanotechnology-mediated drug delivery approach as a promising strategy to improve the therapeutic performance of N. sativa and its active constituent, thymoquinone, in the effective management of osteoporosis.

How Internet Websites Portray Herbal Vitality Products Containing Eurycoma longifolia Jack: An Evaluation of the Quality and Risks of Online Information.

BACKGROUND: Tongkat Ali (TA) or Eurycoma longifolia is a herbal medicine (HM) plant traditionally used to treat sexual dysfunction and enhance libido in men. Websites containing information about HM are abundant. However, studies have shown that in general the quality of websites containing information on HM is low. The present study aims to assess the quality and risks of websites containing information about TA supplements and to identify the health claims for TA. METHODOLOGY: A cross-sectional study to evaluate the quality and risks of websites discussing TA supplements was conducted. Online marketing websites, research articles, news articles, personal opinions, and those restricted by password were excluded. The quality and risks of websites were assessed using a modified DISCERN tool and a set of risk assessment criteria, respectively. The health claims for TA were identified and analyzed using content analysis. RESULTS: Overall, 321 websites met the inclusion criteria and were further evaluated. The overall rating of the quality of the websites was low, with a mean score ± standard deviation of 1.07 ± 0.51. Most websites lacked information that there may be more than one possible treatment choice and did not discuss areas of uncertainty. However, 67.9% (218/321) of the websites received a risk score of zero. A minority of websites (5/321, 1.6%) discouraged the use of conventional medicines. The most common health claims for TA included in the websites related to the enhancement of testosterone level (121/321, 37.7%), treatment of malaria (112/321, 34.9%), and improvement in libido (108/321, 33.6%). CONCLUSIONS: Websites containing information about TA supplements generally have a low-quality rating based on a modified DISCERN tool despite having a low-risk score. Government agencies and healthcare professionals (HCPs) must be more proactive in the critique and dissemination of information relating to HM, and in ensuring the safe use of HM among the public and patients.

Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome.

Olive (Olea europaea Linn., Fam. Oleaceae) is commonly known as Zaytoon in Mediterranean region. Its fruits and oil are essential components of Mediterranean diets. Olive tree is a prevalent plant species and one of the important cultivated crops of Mediterranean region. Oleuropein is a phenolic constituents of olive, which, along with its related compounds, has been indicated to be majorly responsible for its beneficial effects. Oleuropein is a secoiridoid type of phenolic compound and consists of three structural subunits: hydroxytyrosol, elenolic acid, and a glucose molecule. It is also reported to be the chemotaxonomic marker of olive. The oleuropein is reported to possess a number of biological activities including action against dyslipidemia, antiobesity, antidiabetic, antioxidant, antiatherogenic, antihypertensive, antiinflammatory, and hepatoprotective actions. The scientific evidence supports the role of oleuropein as a potential agent against metabolic syndrome. The present review discusses chemistry of oleuropein along with potential role of oleuropein with reference to pathophysiology of metabolic syndrome.

Optimization of ultrasound-assisted extraction of charantin from Momordica charantia fruits using response surface methodology.

BACKGROUND: Momordica charantia Linn. (Cucurbitaceae) fruits are well known for their beneficial effects in diabetes that are often attributed to its bioactive component charantin. OBJECTIVE: The aim of the present study is to develop and optimize an efficient protocol for the extraction of charantin from M. charantia fruits. MATERIALS AND METHODS: Response surface methodology (RSM) was used for the optimization of ultrasound-assisted extraction (UAE) conditions. RSM was based on a three-level, three-variable Box-Behnken design (BBD), and the studied variables included solid to solvent ratio, extraction temperature, and extraction time. RESULTS: The optimal conditions predicted by the BBD were: UAE with methanol: Water (80:20, v/v) at 46°C for 120 min with solid to solvent ratio of 1:26 w/v, under which the yield of charantin was 3.18 mg/g. Confirmation trials under slightly adjusted conditions yielded 3.12 ± 0.14 mg/g of charantin on dry weight basis of fruits. The result of UAE was also compared with Soxhlet extraction method and UAE was found 2.74-fold more efficient than the Soxhlet extraction for extracting charantin. CONCLUSIONS: A facile UAE protocol for a high extraction yield of charantin was developed and validated.

Simultaneous Quantification of Gymnemic Acid as Gymnemagenin and Charantin as ß-Sitosterol Using Validated HPTLC Densitometric Method.

Gymnemic acid and charantin are well-established antidiabetic phytosterols found in Gymnema sylvestre and Momordica charantia, respectively. The fact that these plants are often used together in antidiabetic poly-herbal formulations lured us to develop an HPTLC densitometric method for the simultaneous quantification of their bioactive compounds. Indirect estimation of gymnemic acid as gymnemagenin and charantin as ß-sitosterol after hydrolysis has been proposed. Aluminum-backed silica gel 60 F254 plates (20 × 10 cm) were used as stationary phase and toluene-ethyl acetate-methanol-formic acid (60 : 20 : 15 : 5, v/v) as mobile phase. Developed chromatogram was scanned at 550 nm after derivatization with modified vanillin-sulfuric acid reagent. Regression analysis of the calibration data showed an excellent linear relationship between peak area versus concentration of the analytes. Linearity was found to be in the range of 500-2,500 and 100-500 ng/band for gymnemagenin and ß-sitosterol, respectively. The suitability of the developed HPTLC method for simultaneous estimation of analytes was established by validating it as per the ICH guidelines. The limits of detection and quantification for gymnemagenin were found to be ≈60 and ≈190 ng/band, and those for ß-sitosterol ≈30 and ≈90 ng/band, respectively. The developed method was found to be linear (r(2) = 0.9987 and 0.9943), precise (relative standard deviation <1.5 and <2% for intra- and interday precision) and accurate (mean recovery ranged between 98.43-101.44 and 98.68-100.20%) for gymnemagenin and ß-sitosterol, respectively. The proposed method was also found specific and robust for quantification of both the analytes and was successfully applied to herbal drugs and in-house herbal formulation without any interference.

Rapid preparative isolation of erythrocentaurin from Enicostemma littorale by medium-pressure liquid chromatography, its estimation by high-pressure thin-layer chromatography, and its α-amylase inhibitory activity.

Erythrocentaurin is a relatively simple natural product present among the members of Gentianaceae. A preparative method for the isolation of erythrocentaurin from the ethyl acetate fraction of Enicostemma littorale using medium-pressure liquid chromatography has been reported. The method consisted of a simple step gradient from 10 to 20% ethyl acetate in n-hexane. Using a 70 × 460 mm Si60 column, this method is capable of processing 20 g of material in <3 h (purity ≈ 97%). The recovery of erythrocentaurin was 87.77%. Estimation of erythrocentaurin in extracts and fractions based on high-pressure thin-layer chromatography was carried out on silica gel 60 F(254) plates with toluene/ethyl acetate/formic acid (80:18:2 v/v/v) as the mobile phase. The densitometric analysis was performed at 230 nm. A well-separated compact band of erythrocentaurin appeared at R(f )0.54 ± 0.04. The analytical method showed good linearity in the concentration range of 200-1500 ng/band with a correlation coefficient of 0.99417. The limits of detection and quantification were found to be ≈60 and ≈180 ng/band, respectively. Erythrocentaurin exhibited a concentration-dependent α-amylase inhibition (IC(50) 1.67 ± 0.28 mg/mL). The outcome of the study should be considered for pharmacokinetic and biotransformation studies involving E. littorale.