Gamma oryzanol niosomal gel for skin cancer: formulation and optimization using quality by design (QbD) approach

Skin cancer is fifth most diagnosed disease in human population due to ultraviolet radiation (UV) exposure. Gamma oryzanol (OZ) is a natural antioxidant, and it also has skin anti-aging properties. OZ is naturally found in rice bran oil. The main aim of the present work was to optimize OZ niosomal formulation using quality by design approach including one variable at a time and full factorial design. Niosomes were prepared by solvent injection method and characterized for size, polydispersity index, drug entrapment, and transmission electron microscopy. The optimized batch obtained at X1 [drug to span 60 molar ratio (1:5)], X2 [volume of hydration (75 mL)], and X3 [stirring speed (2500 rpm)] to Y1 [average vesicle size (196.6 nm)] and Y2 [entrapment efficiency (78.31%)] as dependent variables. The optimized OZ noisomes were formulated by niosomal gel to provide improved physicochemical stability upon topical application against UV. The niosomal gel was characterized using pH meter, viscometer, Draize test for skin irritancy, ex vivo permeation studies, and stability studies. Ex vivo permeation studies of OZ niosomal gel not only showed fourfold higher permeation but also exhibited better drug retention in dermal layers of skin as compared to OZ gel. Quality Target Product Profile of OZ niosomal formulation was generated. Risk analysis of optimized OZ gel suggested most critical quality attributes (CQAs) and critical process parameters (CPPs) to be characterized as low risk. Thus, γ-oryzanol niosomal gel for topical use can serve as a promising prophylactic treatment in skin cancer, and the developed prototype formulation can be further extended to future newly discovered drugs with similar characteristics. Graphical abstract

Diversity of Purple Rice (Oryza sativa L.) Landraces in Northern Thailand

Purple rice is a functional food with health benefits and industrial potentials. In northern Thailand, purple rice landraces are grown either as wetland or upland rice, in the lowlands and highlands, in small amounts along with the staple rice. This study examined diversity of 37 accessions of purple rice collected from farmers with InDel cytoplasm markers for subspecies differentiation, 16 SSRs markers for within and between accessions variation, and selected grain quality features, namely, anthocyanin, iron, zinc, and gamma oryzanol content, when grown together as wetland rice. Most of the purple rice, originally grown as upland rice in both the lowlands and highlands, were identified as tropical japonica, except the wetland accessions from the lowlands that almost all belonged to the indica group. A high degree of genetic differentiation was found between the upland and wetland ecotypes, but none between those from the lowlands and highlands. A highland origin of the purple upland rice populations in the lowlands, possibly with adaptation to the upland rice cultivation of the tropical japonica, is suggested by the close genetic affinity between the highland and lowland populations of the upland ecotype. Grown in a much smaller area than the staple unpigmented rice, purple rice landraces are also less diverse genetically. Identification of purple rice landrace populations with exceptional anthocyanin and gamma oryzanol contents demonstrates that purple rice landraces can be a source of agronomically useful traits, while being an important cultural heritage, and contributing to the genetic diversity of the local rice germplasm.

Gamma-oryzanol jako przykład kompleksu estrów fitosteroli i kwasu ferulowego o szerokiej aktywności biologicznej

Rośliny są naturalnymi laboratoriami, których wtórny metabolizm produkuje całe bogactwo związków chemicznych o ogromnym potencjale terapeutycznym. Olej ekstrahowany z otrębów ryżowych, stanowiących frakcję uboczną w procesie obróbki brązowego ryżu, obfituje w substancje biologicznie cenne. Jednym z głównych składników oleju ryżowego jest gamma-oryzanol stanowiący mieszaninę będących pochodnymi fitosteroli lub triterpenów oraz kwasu ferulowego. Substraty te charakteryzują się szeroką aktywnością biologiczną ściśle skorelowaną z ich właściwościami chemicznymi. Kluczowe w kontekście poprawy fizjologii i funkcjonowania organizmu są hipocholesterolemiczne oraz antyoksydacyjne właściwości tych związków. Z tego względu coraz więcej badań skupia się na wykorzystywaniu gamma-oryzanolu w terapiach wielu chorób przewlekłych, a nawet jako obiecującego, niefarmakologicznego środka leczniczego wspomagającego leczenie COVID-19 u osób cierpiących na nadwagę. W pracy scharakteryzowano strukturę chemiczną i działanie gamma-oryzanolu w oparciu o aktywność biologiczną estrów fitosteroli i kwasu ferulowego będących składnikami tej złożonej mieszaniny. Ponadto, opisano przykłady oddziaływania gamma oryzanolu na niektóre procesy fizjologiczne w organizmie człowieka i zwierząt.

Functional and Therapeutic Potential of γ-Oryzanol

This chapter summarizes the entire literature available on the nutritional value and diverse therapeutic potentials Gamma-oryzanol, a nutraceutical obtained from rice brain oil, composed of a mixture of γ - oryzanol, a mixture of ferulic acid esters of phytosterols and triterpenoids, cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, and campesteryl ferulate. In brief, the review covers the aspects such as the antioxidant mechanisms, effects on immune system, lipid disorders, diabetes, obesity and inflammation with the details of preclinical experiments, models and observations. Among the other highlights are the hepatoprotective, neuroprotective role in various neurological disorders such as Alzheimer’s, anxiety, Parkinson’s disease and wound healing effects. An overview of the sources, chemistry, physicochemical properties, pharmacokinetics and toxicity studies are also included.

Gamma-oryzanol reduces renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to high sugar-fat diet

Introduction: The receptor for AGEs (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface receptors expressed in many organs, among them, the kidneys. When activated, RAGE leads to a sequence of signaling that results in inflammation and oxidative stress, both involved in kidney disease pathogenesis. Gamma-oryzanol (γOz) comprises a mixture of ferulic acid (FA) esters and phytosterols (sterols and triterpene alcohols) mainly found in rice, with antioxidant and anti-inflammatory activities. Aim: To evaluate the effect of γOz to reduce renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to a high sugar-fat diet. Methods: Male Wistar rats (±187g) were randomly divided into two experimental groups: control (n = 7 animals) and high sugar-fat diet (HSF, n = 14 animals) for 20 weeks. After this period, when the presence of renal disease risk factors was detected in the HSF group (insulin resistance, dyslipidemia, increased systolic blood pressure and obesity), the HSF animals were divided to begin the treatment with γOz or continue receiving only HSF for 10 more weeks. Results: No effect of γOz on obesity and metabolic parameters was observed. However, kidney inflammation and oxidative stress decreased as soon as RAGE levels were reduced in HSF + γOz. Conclusion: It is possible to conclude that the gamma- oryzanol was effective in reducing inflammation and oxidative stress in the kidney by modulating the AGEs/RAGE axis.